Endocrinolo

. . . . . . . . . . . . . . . . . . .IIIIIIIIIIIIIIIMll•1t1111••....•11111•11111111N111• •11111U11•1• 1

Allam's internal medicine series

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ., • • • JI . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...

New edition,...............
...................................... 2018.

Dr. Mahmoud Allam MD

Edit. Moj:fulation &Aqiustment by :

Ahmed_Attg
2
 Dedication

Allah the all merciful, I beg thee to accept this effort for the soul of
my father He was your gift for me

3
 Table of contents
Scheme of any endocrinal disease 5

Pituitary Gland 6
• Acromegaly 8
• Gigantism & pit.dwarfism 13
• DD of dwarfism & short stature 15
• Hyper prolactinemia 17
• Diabetes insipidus 19
• SIADH 22
• Panhypopituitarism 23
• Pituitary & parasellar masses 27
Supra-renal gland 28
• Conn's syndrome 29
• Cushing syndrome 32
• Adreno-genital hyperplasia 37
• Pheochromocytoma 38
• Addison syndrome 40
• Acute addisonian crisis 43
Thyroid gland 45
• lry hyperthyroidism 47
• Myxedema 57
• Cretinism 61
• Goiter 62
• Thyroid neoplasm 64
• Thyroiditis 65
Parathyroid gland 66
• Hyperparathyroidism 68
• Hypocalcemia 73
Diabetes mellitus 77

• Om& ttt 78
• Complications 91
Collections (tumours) 111

Disorders of puperty 113

Hirsuitism 116
Gynecomastia & obesity 117
MEN 121
Osteoporosis , osteomalacia , 122
dyslipidemia 126

4
 SCHEME OF ANY ENDOCRINAL DISEASE
Introduction : physiology of hormone, Source, Action & Regulation.

Definition : Hyper/ Hypo of ( name of the hormone ) & the age of onset.

:Aetiology :_

In a case of ( 1-of the hormone level) In a case of (.J, of the hormone level)
or Hyperfunction of the gland or Hypo-function of the gland (4Ts)

• Hyperplasia • Trauma
• Adenoma • Tumor
• Iatragonic • TB
• Paramalignant • TTT (surgical)
• Other Causes • Other Causes

Clinical Picture :
( ~ or 1' ) the physiological function of the hormone according to the disease

Investigations :
1- Hormonal assessment :-

a- Static :- Serum level without any alternation.

b- Dynamic :- To check the changes at the hormonal level after :

• Stimulatory test:- for hypo function .

• Inhibitory test:- for Hyper function .
2- Hormonal effects:- e.g. ( effect of the hormone on metabolism).

3- Images :- for detection of the cause .

4- Other investigations :- according to the hormone

ifreatment :-,

• If Hyper : Symptomatic/ Surgical TTT

• If Hypo : Symptomatic / Replacement.

s
Pea sized gland in sella tursica at the base of the skull
a) weight .5 gram
b) the gland is connected to hypothalamus by portal circulation and pituitary stalk
c) it is formed of : two lobes separated by pituitary cleft
o Ant. lobe : connected to hypothalamus
Hypothalamus

by vascular connection. Optic

d,iasma l11fu11dibutum
o Post. lobe : connected to hypothalamus Posterior lobe
(neurohypophysis)
by neural connection.

Anterior ,
lobe •. ,

• Chromophobe cells : of unknown function.

'T-r:';;,: : Pars •, ~ -~
di;t \ a ~- i s
·

• Chromophil cells : Sphenoid sinus \ , ,,

1) Acidophil cells : Secrete the following

5ella turcica ~ ~ .. ~ .. ____
. . --
. .,,... .,...,,i,"'

- Prolactin hormone
- Growth hormone (GH)
2) Basophil cells : secrete the following.
- Gonadotrophins (FSH - LH)
- Thyroid Stimulating hormone TSH
- Adreno-cortico-tropic-hormone ACTH
- Melanocyte stimulating hormone MSH (not in humans)
- B-lipotropin (pigmenting hormone in humans)

Secretes 2 hormones :
- ADU (Anti-diuretic H.) : from the supraoptic nucleus in the hypothalamus.

- Oxytocin : from the paraventricular nucleus in the hypotamus.

6
Regulation of pituitary hormones :
Hypothalamic control
O Hypothalamus

The hypothalamus secretes the following :

• Releasing factors :
1. Thyrotropin releasing hormone (TRH)
2. Corticotropin Releasing hormone (CRH)
3. Growth hormone releasing 0 Pitooa,y

hormone( GHRH)
4. Gonadotrophin releasing hormone (GnRH)
5. MSH releasing hormone (MSH-RH) PAL ~

• Release inhibiting factors : O \0

Which -0- secretion of pituitary hormones

These factors are regulated by

Lactation
l"
a- CNS control: Stress, emotion.
b- Negative feedback : ( i T3 • .J, TSH i
Ctloodrooytes
Cortisol • .J, ACTH ) Linear &
o,gan growtll
Long feedback : from target organ to
hypothalamus.
Short feedback : From pituitary to hypothalamus

" Why be a man when you can be a success ? "

Bertold Brecht

7
 Increased GH secretion after fusion of epiphysis (after puperty)
Aetiology;
1- Acidophil adenoma (or hyperplasia).
2- Hypothalamic disorder: t GHRF or .J.. GH-Rlf.
3- MEN-1 (multiple endocrine neoplasia 1)
4- Rarely extra-pituitary causes: islet cell tumour

!Growth hormon~
It is a Polypeptide hormone activates liver & other tissues to secrete Insulin-like growth factor- 1.
(IGF - 1) previously named somatomedln C.
1) Action of GH : Mainly Metabolic action :-
- Carbohydrate : Diabetogenic (t gluconeogenesis & l uptake of glucose)
- Fat : lipolysis leading to f free fatty acids.
- Protein : anabolic t chondrogenesis, Osteogenesis, growth of muscles and viscera.
- Electrolytes: - Salt and water retention (fNa (Aldosterone like)
- tea (t intestinal absorption)
- fK & P04 (2ry tot protein synthesis).
N.& It's similar structurally to Prolactin & human placental somatomamotropin
2) Factors affecting (GH) regulations :
- Stimulatory factors :-
- Hypoglycemia (Insulin stimulatory test).
-Amino acids (arginin stimulatory test).
- Stress, exercise (hypothalamic effect) Central action.
- Estrogen, a - receptors, dopamine, GABA, Serotonin.
- Inhibitory factors : - glucose.

Clinical picture
1- In pituitary causes: manifestations of 1' ICT (headache. vomiting. blurred vision,
bitemboral hemianopia in large adenomas ......)
2- Manifestations of 1' level of the hormone (Metabolic+ Prolactin ,neurological and
pressure.

8
A) Metabolic action :
o CHO: DM in 30% of cases (relatively insulin resistant).
o Fat: - excess lipolysis with loss of SC fat & wrinkling of skin in forehead and face.
- excess grease sweating (signs of activity), due to hyperplasia & hypertrophy
of sweat and sebaceous glands.
o Protein: excess growth of Bones, Muscles &Viscera

o Electrolytes: Na retention leads to hypertension

( + hypertrophy of wall of BVs)

0 B.mle:
1. Acromegalic fades "Ape like"
o Big skull, prominent frontal sinuses, supraorbital
ridges, malar bones & mastoids.
o Enlarged nose, ears, lips & tongue (macroglossia,
with sleep apnea).
o Prognathism (prominent lower jaw) with separated
teeth.
o Hypertrophy of larynx with husky voice.
2. Feet & hands "spade like"
o enlarged with blunting of tips
o Frequent change of rings & shoes size .
3. Kyphosis : bone grows without cartilage.
4. Osteoarthrosis: with swollen joints & thick synovial membrane.

o Muscles:
- Earlyt in power
- later on decrease with muscle wasting ( decline stage).
o Viscera;
- Hepato-splenomegaly,
- cardiomegly & Heart Failure (due to hypertension & cardiomyopathy)
- enlargement of the gland.
- Colonic polyposis. (risk for devoloping malignancy)

9
B) Prolactin:

• damage of pituitary stalk or presence of mixed (GH & Prolactin) secreting tumor
• In males : gynecomastia & galactorrhea.
• In females : amenorrhea or menstrual disturbances. -
• Hypogonadism (Prolactin inhibits gonadotrophins).

C) neurological manifestations:
1. Emotional lability :- depression.
2. Peripheral neuritis: parasthesia of hands & feet) due to
• Interstitial neuropathy.
• Diabetic neuropathy.
• Carpal tunnel syndromes. Untreated carpal tunnel syndrome
(deu to median nerve compression by enlarged bone)

Don't forget

CAlt&E& r>F t>EAfM IN ACRr>MEGALf

1. Sleep apnea (respiratory).
2. Cardiovascular (Heart Failure).
3.DM.
4. Colonic polyps or cancer colon (usually
associated with skin tags)
--------------------------~
Investigations
1) Hormonal assessment :-
• Static: GH level: increased (N=l-5 ng/ml in adult - 20 ng/ml in children).

• Dynamic : - Glucose inhibitory test (IV glucose fails to decrease GH level).

• Insulin-like growth factor-1 (IGF-1): l level (more reliable than GH).

• Prolactin hormone level : hyperprolactenemia in 1/3 of cases.

2) Hormonal effect :-
• Increase glucose & FFA, hypercalcemia & hyperphosphatemia.

10
3) Images:- ( causes + effect)
- For cause :-X-ray, CT, MRI skull for tumor (wide or ruptured sella tursica).
- for Effect:- X-ray
• Skull:
- Thickening of cortex.
- Pneumanization of frontal air sinuses.
- Prominent external occipital protuberance.
- Big mastoid process.
- Prognathism and wide separation of teeth.
- wide or ruptured sella tursica.
• Hands
Periosteal thickening of phalanges + tufting of terminal
phalanges(mushroom shape or arrow head).
• Spine:
tAntero-posterior diameter of vertebrae, kyphosis &
osteoporosis.
NB : Measurement of thickness ofskin fold over dorsum of hands & lower part of triceps
(>3.5 mm at 25 y. or> 3 mm at 65 y. suggests acromegaiy)

4) Visual Acuity & visual field (For Bitemporal hemianopia due to compression by adenoma)

;J'reatment

1- Symptomatic treatment: Of OM , hypertension & hypogonadism.

2- Surgical excision of the tumor: it is the ideal treatment by transphenoidal
approach and in large tumors by transfrontal approach
3- Radiotherapy :
indicated in cases of
• GH is still elevated after surgery
• In cases of recurrence
• If complete excision of the tumor e=was not possible.

11
Types of Radiotraherapy

1- Conventional therapy of the sella : takes a long time to produce effect & aassociated
with depression of anterior pituitary function
2- Sreriostatic radiosurgery (Gamma knife) : More effective & works faster than
conventional radiotherapy but still needs months to years to work
4- Medical treatment (hormone antagonist):
Somatostatin analouges

Indications:
• In treating acromegaly in high surgical risk patients
• If surgery or radiotherapy failed to decrease GH
1- Octeriotide : produce shrinkage of tumor size in 50 % of patients
S/E: very expensive, Nausea, vomiting, steatorrhea, and requires long term course
2- Lanreotide & Pasireotide : newer analogues, more effective in suppressing GH

Growth hormone receptor antagonists :

Have been approaved e.g: Pegvisomant daily SQ (Somavert)

Dopamine agonist :

When Combined with somatostatin analogues they give synergetic effects

They are less effective than somatostatin analogues and need large
a. Bromocryptin (parlodel) : which ! GHRF in hypothalamus
(1.25 mg at bed time &lgradually to 15 mg/d).
b. CabergolinE : drug of choice - as Bromocryptin but few side effects.

Prepare the smile before you extend your hand to shake hands
"Ahmed Atta"'

12
 ~IGANTISMi
Definition: - Increased GH secretion before fusion of epiphysis (before puppetry)
'.Aetiology :-
• Hyperplasia of acidophil cells.
• Acidophil adenoma
Clinical picture

i. Generalized overgrowth of metaphysis of long bones leading to

disproportionate gigantism (span> height)+ ( lower segment>
upper segment).
ii. Later on features of acromegaly develops.
iii. End stage or decline stage :- weakness, fatigue due to pituitary insufficiency.

D.D OF TALL STATURE

Definition :- height above 97th percentile of normal people of the same age & sex.

Disease Bullt Others

Familial & racial Proportionate normal GH level
" most common "
Gigantism Disproportionate High GH level
Hypogonadism Disproportionate + hypogonadism (feminine)
Cerebral gigantism " Soto's in the 1st 5 years of life + MR + Big skull
syndrome" only
• normal GH level
Marfan's syndrome See later
Klienfilter syndrome ( XXV) Tall, slim and underweight ------------------
-------------------
Homocystenuria ----------------
----------------- MR + colored lens +
thrombosis+ homocystien
In urine
Hyperthyroidism
····-·-·-······· Manifestations of
hyperthyroidism
Sexual precocity
Early accelerated growth - later on _shorter stature

13
 )GH Deficiency "Pituitary Dwarfism"/
• GH deficiency can be isolated or associated with deficiencies of other pituitary
hormones
• The term (Hypo-pituitarism) refers to GH deficiency with deficiency of at least one other
Anterior pituitary hormone
• When hypopituitarism is associated with post. Pituitary hormone deficiency it is called
(Pan -Hypo-pituitarism).

!causes of GH Deficiency!

1. Idiopathic
IL Mutation of specific Gene
III. Congenital pituitart malformation
IV. lntracranial tumors near cella turcica e.g. cranipharyngioma
v. damage of pituitary by radiation, surgery, trauma or intracranial diseases
VI. Autoimmune hypophysisitis
VII. ischemic or hemorrhagic infarction (Sheehan$ or Apoplexy)

!C linical picture!

it is variable depending on age.

• In children :
o short stature for age and pupertal stage,
o may be accompanied by increased fat,
o high pitched voice and delayed physical maturation so that bone maturation
and puberty may be several years delayed .
• In adults:
o only changes in body composition , lipid metabolism , quality of life and
cardiovascular dysfunction

NB: Dwarfism + Hypogonadism = Infantilism

14
clinical syndromes associated with GH deficiency

syndrome Levi-Lorain syndrome Froehlich's syndrome Laurence-Moon-

Items 1ry deficiency of GH Bldel

Aetiology • End organ - Idiopathic

unresponsiveness • hypothalamo-
(African plgmles) pituitary tumor
(craniopharyngioma)
C/P 1. Proportionate Levi-Lorain + As Froehllch's +
dwarfism Skull deformity +
2. Childish features
3. Hypogonadism
4. some recent
......W'
- Hypothalamus:
Retinitis
pigmentosa

studies says that 1. Polyphagia,

those patients are 2, hypersomina.
resistant to cancer 3. Samboxa shape
andDM. obesity
· .! MR.
TTT -Hyman OH 20-45 mg I monthly-" Now replaced by recombinant GH"
• Ibvroxln,
• Gonadotrophin (for cyrptoorchldlsm):- before age of 9 years to
prevent testicular atrophy.

D.D OF DWARFISII
Definition:- height below the 3rd percentile of normal people of the same sex & age.
~etiology :-
A. Familial :- the commonest cause.
B. Genetic disorders :-
1. Mongolism (Down syndrome): Trisomy 21.
2. Turner's syndrome (XO): ovarian dysgenesis, lry amenorrhea, webbing of neck,
increase carrying angle, coartication of aorta.
3. Microcephaly.
4. Progeria: premature senility.

C. Endocrinal :-
1. GH deficiency : isolated GH deficiency, hypo or panhypopituitarism in children Or
syndromes as Levi-Lorain, Frohlich's & Laurence-Moon-Biedle syndromes.(see above)

15
 2. T4 deficiency : cretinism & juvenile myxedema.

3. 1' Sex hormones : precocious puberty (tall child short adult).

4. 1' Cortisol : Cushing syndrome or excess steroid treatment (Cortisol block the ability of
GH to produce somatomedin).
5. '1, Insulin : Juvenile DM • excess glucose • inhibit GH release .

D. Skeletal:-
i. congenital :-

1. Achondroplasia: short limbs & normal trunk.

2. Osteochondrodystrophy: limbs & trunk are short and deformed.
3. Osteogenesis imperfect: fragile bone, pathological fracture + malfusion &
dwarfism, joint dislocation, blue sclera, deafness due to otosclerosis.

ii. Acquired :-
1. Rickets.
2. Paget's disease.
3. Pott's disease.

E. Chronic severe illness during the childhood:-

1. CVS : rheumatic fever, congenital heart disease.

2. Lung: polycystic lung.

3. GIT : malabsorption, lipoid storage, parasitic infestation, malnutrition, liver cirrhosis.

4. Kidney : chronic nephritis.

16
J•llOI.Af~'flN DOllHONE
Physiology:- "production of milk"

a) Growth of ducts & alveoli of (estrogen & progesterone prepared female breast).
b) During Pregnancy :- Maintains corpus Luteum till placental formation.
c) GH like action.
,----- -- -- - - - -------- I
Regulations "factors affecting it's release" ,
I
itroJactia Stimulate• ,
I
: M'1mmary 1laab to
• Stimulatory : 4 s + others : Produce (Syatlaai•J milt.
I
- Stress - Sleep - Suckling - Serotonin I
I Oxytocia •timuJatea
I
I mammary ,ind• to Ooze
- Others: I
I
I (1{!leae) mill:.
- Opiates - VIP -TRH I---------------------
• Inhibitory :
- Dopamine
- Methsyrgide ( Serotonin Antagonist)
- Naloxone ( Opiate Antagonist).
~etiology;
• Physiologic causes: pregnancy, lactation, stress, sleep.

• Drugs:
a) Dopamine antagonists: phenothiazine, metoclopramide.
b) Dopamine depleting : methyl-dopa, reserpine.

c) Others: Estrogen -Opiates.

• Diseases:-
a) Pituitary tumors: acidophil adenoma causing Acromegaly & gynecomastia
b) Hypothalamus diseases (inhibits dopamine): granulomas, sarcoidosis.
c) Primary hypothyroidism : fTRH

d) Liver cirrhosis ( decreased metabolism)

e) CRF ( decreased clearance).

17
Clinical picture

❖ Hormone action:

o In d : impotence, infertility, gynecomastia & galactorrhea.

o In 9 : galactorrhea-amenorrhea (suppress GnRH).
o Infertility & osteoporosis (estrogen deficiency).
❖ Pressure manifestations:

in case of large adenoma which might lead to Panhypopituitirism.

Investigations

t) Hormonal assessment:-

• Serum Prolactin: > 300 ng /ml is diagnostic of pituitary adenoma.

(normally< 15 ng/ml in males and< 20 ng/ml in females)
2) Hormonal effect:- Thyroid functions for myxedema.

3) Images:- CT & MRI brain but useless in micro adenoma < 10 mm.

ifreatment : -
1. Surgical removal:

• transphenoidal or transcranial in large tumor with pressure symptoms or

failed medical treatment
2. Radiation : by proton or alpha particles
3. Drugs :- "Prolactin antagonist" i.e "Dopamine agonist"

a. Bromocryptin (parlodel) 10-15 mg/day.

b. Cabergoline: 250-1000 ug/week, fewer side effects.
c. Quinagolide: 50-150 ug/day.

4. Treatment of cause: e.g. myxedema.

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 '
Definition:•
Impaired water reabsorption by kidneys due to decrease ADH secretion by post. Pituitary
or impaired response of kidneys to ADH.

'.Aetiology & Types =

.~

1) Familial DI (DIDMOAD syndrome}

Wolfram syndrome: Hereditary DI, due to defects in osmo-receptors

• Diabetes insipidus (DI)

• Diabetes mellitus (OM)
• Optic Atrophy (OA)
• Deafness (D)
2) Neuorogenic or Central DI :-
Due to Damage ofhypothalamo-hypophyseal axis: (4Ts)
• Tumors (intra or suprasellar)
• Trauma: head injuries, after hypophysectomy.
• Granulomas: TB, sarcoidosis.
• after Treatment:- after hypophysectomy.

3) Nephrogenic DI:
a. Hereditary: X-linked disease, with renal tubules are insensitive to ADH.
b. Acquired diseases :

• Abnormal anatomy of nephrons :

- Sickle cell anemia (recurrent infarctions). - polycystic kidney
- infiltration (amyloidosis, myeloma) - pyelonephritis
• Renal tubular acidosis.
• Rapid clearance of medullary solutes : Diuretics and low protein diet

19
 • Decreased response to ADH: CRF, hypokalemia, hypercalcemia and bilateral urinary
tract obstruction
• Drugs : lithium, methoxyfluorane, and democlocycline.

4) DI of pregnancy:
Increased vasopressinase enzyme secretion from the placenta lead to ADH destruction

Clinical picture :
1-Hormonal effect:

• Polyurea: (>SO ml/Kg/day) and may be associated with:

- nocturia. - dehydration - weight loss

- low grade fever. - shock & encephalopathy may occur.

• Polyde psia.

• Hypovitaminosis : loss of water-soluble vitamins in urine.

2-Features of cause e.g. pituitary tumors • pressure manifestations.

Investigations :
Hormonal assessment:-

a) static : ADH level: -!,

b) dynamic:
1) Test hypothalamus "nicotine test" : (1-3 mg)
- Stimulates hypothalamus• fADH • oliguria.
- if hypothalamo hypophyseal axis lesion • ADH can't reach posterior
pituitary • -ve test.
2) Test Osmoreceptors (Hypertonic NaCL lV)
- Stimulates Osmoreceptors = oliguria.
- in familial DI • -ve test.
3) Test kidney "pitressin test":
- IM pitressin • causes oliguria.
- in Nephrogenic DI • -ve test

20
Definition :-
Impaired water reabsorption by kidneys due to decrease ADH secretion by post. Pituitary
or impaired response of kidneys to ADH.

:Aetiology- & Types :-

1) Familial DI (DIDMOAD syndrome}

Wolfram syndrome: Hereditary DI, due to defects in osmo-receptors

• Diabetes insipidus (DI)

• Diabetes mellitus (DM)
• Optic Atrophy (OA)
• Deafness (D)
2) Neuorogenic or Central DI:-
Due to Damage of hypothalamo-hypophyseal axis : (4Ts)
• Tumors (intra or suprasellar)
• Trauma: head injuries, after hypophysectomy.
• Granulomas: TB, sarcoidosis.
• after Treatment:- after hypophysectomy.

3) Nephrogenic DI:
a. Hereditary: X-linked disease, with renal tubules are insensitive to ADH.
b. Acquired diseases :

• Abnormal anatomy of nephrons :

- Sickle cell anemia (recurrent infarctions). - polycystic kidney
- infiltration (amyloidosis, myeloma) - pyelonephritis
• Renal tubular acidosis.
• Rapid clearance of medullary solutes : Diuretics and low protein diet

19
Hormonal effect:-
1. Urine:
- Polyurea - no pathological constituents - low urine osmolarity.
- Urine osmolarity doesn't increase after 8 hrs water deprivation.
2. Serum: (Opposite in urine) i osmolarity and serum Na level.
3. Images: (Skull X-ray, CT scan & MRI: exclude tumors).

Differential Diagnosis :
From other causes of Polyurea (urine volume> 1500 cc/day)-+ "see nephrology"

iTreatment :
1- Symptomatic treatment:

a- Diet: Excess fluids & vitamins with reduction of salts intake.

b- Avoid purines (coffee, tea).
2- Replacement therapy:-
• Pitressin tannate in oil : 3-5 Units -IM every other day
Side effects: pallor, angina, colic, bronchospasm, and uterine contraction

• Des-amino arginine vasopressin (DAVP):

- Minirine or desmopressine • Intranasal 10-20 ug /12-24 h.
- It has very low side effect compared to pitressin.

3-Drugs sensitize renal tubules to endogenous ADH:

• Chlorpropamide : ( side effect: hypoglycemia ).
• Carbamazepin : (Tegretol) .
• Thiazides diuretic: effective in Nephrogenic DI (paradoxical effect)

NB: Mechanism of action ofThiazides in DI is UnKnown But the most acceptable theory is due to
decrease in GFR & RBF

21
 Sheehan syndrome - simmond's disease

Causes: (Sheehan & Apoplexy+ 4 Ts+ others)

1. Sheehan syndrome "

Ischemic necrosis due to severe blood loss and hypovolemic shock during and after
childbirth ..... it depends on 2 factors :

1- Hypertrophy & hyperplasia of lactotrophes dutring pregnancy result in enlaged

ant.pituitary without corresponding increase in blood supply.
2- In severe hge, hypotension or shock especially in postpartum period, there is a drop
of blood supply

2. pituitary apoplexy"
• Acute He & infarction of pituitary
• Adenoma is usually present resulting in ischemia & subsequent necrosis.
• Usually there is sudden 1' in JCT with visual symptoms & Altered mental status
• Later hypopituitarism develops

3. 4 Ts:
- TTT : Hypophysectomy or pituitary irradiation.
- Tumor : chromophobe adenoma, supra sellar, end stage of acidophil adenoma.
- Traumatic : fracture base of skull.
- TB : Granulomas: TB, gumma, sarcoidosis, Histiocytosis, (Hand Schuller Christian
disease).
4. Others:
- Idiopathic : autoimmune.
- Congenital: - Kallmann's syndrome (isolated deficiency in gonadotrophins).
- Empty sella syndrome.

sella appears empty as it is filled with CSF which flattens the gland against the wall of the sella.
The patient is normal however he may develop pan-hypopituitarism
It may be congenital , primary or secondary to injurey
Typical patient is female 80%, obese 75% and hypertensive 30%

23
Clinical picture (Hormonal effect+ Pressure manifestations+ Hypothalamic S)

• The initial features are usually vague. GH is the initial hormone to decline then
gonadotrophins, TSH and ACTH
Hormonal effect:

1. lProlactin: failure to establish lactation after delivery (1st presentation).

2. l FSH/LH : - Amenorrhe - impotence
- loss oflibido - atrophy of breast & genitalia
- loss of pubic and axillary hair (but no hot flushes).

3. Thyroid deficiency due to l TSH:

a) Myxedema.
b) Hypothermic coma may occur on exposure to cold.

4. Adrenocortical insufficiency due to l ACTH:

-infection - Hypoglycemia

- Hypopituitary crisis: on exposure to stress.

- Present with acute abdomen like picture

5. Deficiency of GH: ( no obvious C/P in adults) skin wrinkling, weakness, wasting.

6. Coma: occurs terminally due to hypoglycemia, hypothermia or tumor pressure on RF.
Pressure manifestations: Headache and bi-temporal hemianopia.

Hypothalamic syndrome: as above + Diabetes insipidus.

Two differences from Addison disease:

• No pigmentation : Abscent ACTH + Pallor & Depigmented areas ( Abscent MSH &
Anemia)
• No marked hypotension

24
Investigations :

1 - Hormonal assessment :

1-
Low - FSH & LH + sex hormones
-TSH+T3&T4
- ACTH + corticosteroids

2- Combined insulin tolerance test:-

• Determine fasting blood sugar, then IV insulin is given then TRH & Gn-RH.
• Estimate every 1/2 hour blood sugar, GH, TSH, FSH, LH, prolactin & cortisol.
• Normally:- blood sugar should fall to 40% & level of all hormones should
increase 3 folds.
• Failure to do so indicates hypopituitarism.
2- hormonal effect: Hypoglycemia, normochromic anemia.

3- Images : (usually for cause detection)

1. X-ray sella tursica:

• .lntrasellar tumor:
• Ballooning of sella.
• Double floor in eccentric tumor.
• Destruction of dorsum sellae & posterior clenoid ± encroachment on sphenoid.
• Suprasellar tumor: - saucerisation of sella & calcification.
2. CT scan & MRI : the best in Sheehan syndrome, sella tursica is normal.

pifferential Diagnosis'
1) Primary hypogonadism: hypogonadism, gigantism, high FSH / LH.
2) Adrenal hypocorticism: skin pigmentation, high ACTH, marked hypotension.
3) Anorexia nervosa; normal hair & breasts, aggressive attitude, normal cortisol,
high GH (from hypoglycemia).
4) Pernicious anemia: see blood picture & serum B 12.
5) Thyroid myxoedema ..

25
il'reatment of Pan-Hypo-pituitarism
1- For coma: glucose and saline infusion + avoid cold weather or stress.

11- Hormone replacement:

1. Hydrocortisone: 25-75 mg/day (before thyroxin).
2. Thyroxin:
should follow cortisol with a gradual increasing dose (0.1 mg - 0.2 mg to avoid
adrenal failure).
3. Gonadal hormones:

- In d': methyl testosterone (25-50 mg /day.)

- In 9: oestradiol (0.02 mg/day for the first 21 days of each month.)

- GnRH for treatment of infertility.
4. Recently: purified pituitary hormone or hypothalamic RH.

Ill- Treatment of cause: e.g. removal of chromophobe adenoma.

26
 Pituitary and para-sellar masses
Types of msses :
1- Cysts : Rathke's pouh , Arachnoid , Dermoid or epidermoid cysts
2- Tumors : adenoma , Craniophryngioma , meningioma, Schwanoma , sarcoma or
metastatic tumors
3- Malformations and bamartomas : htypothalamic hamartoma
Clinical picture :
1- General effects :
• Headache
• Hydrocephalus , seizures , dementia , psychosis.
2- Local effects : resulting from compression or invasion of adjacent structures
• Optic chiasma : bitemporal hemianopia , scotoma and blindness
• Cavernous sinus : Invasion of 3rd, 4th, 5 th & 6th cranial nerves causing ptosis ,
diplopia, ophthalmoplegia and facial numbness
• Pituitary stalk: compression of portal vessels resulting in hyperprolactinemia
3- Hypothalamic effects
• Temperature dysregulation : hyper or hypo thermia
• Appetite disorder : obesity or anorexia .
• Thirst disorder : adipsia, compulsive water drinking or hypernatremia
• Sleep disorder : reversed sleep weak cycle
• Behavioral disorders : rage and hyperkinesis
• Autonomic dysfunction : Arrhythmia, loss of sphincter control
4- Hormonal derangement : functional adenoma (hormone excess state)

Investigations
1- Hormonal assessment for deficiency or excess level
2- Radiological evaluation: plain x-ray, CT, MRI,
Treatment
• Surgical ttt : is the usual choice for therapy
• Radiation is usually used as adjunctive therapy after surgery
• Medical therapy : dopamine agonist in prolactinoma, ketoconazole in cushing .....etc

27
 - Two glands, yellowish- brown in color . 40 gm

- Each is related to the medial part of the upper pole of the kidney On the crus of diaphragm
opposite the vertebral ends of 11th inter-space and the 12th rib

Diseases of

Supra-Renal
glands
capsu le
Adrenal cortex;

.--- "~-- ZonaglomerukJso

Functional Histology : __ ·.--· Zont.i krsdculotCl

Each gland is divided into: Medulla

1. Adrenal cortex : which includes 3 zones:

- Zona glomerulosa • secrete Aldosterone.
The Adrenal Gland
- Zona fasiculata • secrete Cortisol.
- Zona reticularis • secrete Androgens.

2.Adrenal medulla : - Secrets Catecholamines.

disorders of gland functions

Hyper-function Hypo-function
adrenal cortex Conn's syndrome : taldosterone
Cushing syndrome : fCortlsol
Adrenogenital hyperplasia : j androgen
adrenal medulla Pheochromocytoma

28
 Conn's Syndrome
Primary - hyperaldosteronism
Group of disorders in which there is excess production of aldosterone by zona glomerulosa
independent of renin angiotensin system stimulation
Physiology of aldosterone :
• Secreted by : Zona glomerulosa.
• It's function :
- Increases Na and water reabsorption.
- Increases K, and H secretion in:- DCT - Saliva - Sweat - Intestine.
Factors affecting it ( regulation ) :
It is a Stimulatory regulation :

• Renin - angiotensin system activation.

• Increased Kor Decreased Na.
• ACTH (only in stress).
• detected low blood pressure though stretch receptors lacated at the atria of
heart.

Regulation of aldosterone secretion b:)-' the renin-angiotensin-aldosterone (RAA) pathway.

Aldosterone helps regulate blood volume. blood pressure, and levels o f Na•, K... , and H+ in the blood.

0 Dehydration,
Ne• deficiency,
or hemorrhage

e Decrease in
blood volume B100<! p1'9Mta'9
lncreeees until

J
it returns to normal

• 0 Juxtaglomeru lar
cells of kidneys
_ t
Vaaoconatrlclion lnoreesedblood
of arterlOles volume
0 Increased renln

Liver e Adrenal

CD 1ncroas8d
..__ K•1n
extracellular
0 fluid

In kidneys, increased Na•

----•
Lungs (ACE ,. Angiotensin
Converti ng Enzym e)
and water reabsorpticm
Increased and Increased secretion of
• aldosterone K• and H+ ifllo urine

29
 etiology:
1. Adenoma of Zona glomerulosa.
2. Hyperplasia of Zona glomerulosa.
3. Para-malignant.

Clinical Picture: (3H + C/P of the cause.)

1. Hypertension : Mild Hypertension:- due to:
• Nephrogenic diabetes insipidus secondary to Hypokalemia.
• Renal escape phenomena (tblood volume -+t GFR-+ Polyurea).
2. Hypokalemia manifested by :-
a) muscle weakness: flaccidity up to paralysis.
b) GIT: l peristalsis, constipation up to paralytic ileus.
c) Cardiac: Arrhythmia and ECG changes (prolonged PR interval, depressed ST
segment, flat or inverted T wave and prominent U wave).

d) Kidney: Nephrogenic diabetes insipidus.

e) Glucose intolerance.
f) CNS : Finally coma.

3. i Hydrogen excretion "Alkalosis";

• which is exaggerated by intracellular shift of hydrogen with extracellular shift of K+
to compensate for K loss.
• Manifested as tetany due to decreased ionized calcium.
Investigations:-

1- Hormonal assessment:

Static
may be Selective adrenal vein sampling for
aldosterone.
- 't serum aldosterone level (N = 3-15 ng%).
- ! Serum rennin level (negative feedback).
Dynamic
by saline suppression test , if
- Aldosterone level ! after the test :
normal or +ve .
- Aldosterone level not affected : - ve .

2- Images: -Abdominal sonar, MRI, CTscan (For detection of the cause).

30
3- Hormonal effect:

n_cr_e_a_s_e_d_ _~ _Decreased
.....------+- _ _I_ I
Blood -Na+2 -Ph -K+
Urine T :i<_+ i - Na+2 -Ph 1

~---~I I
- IL - - - - - - ___________ J

Differential Diagnosis :
from Secondary hyperaldosteronism .

Primary hyperaldosteronism 2ry Hyperaldosteronism

Mild hypertension Not a must hypertensive
(except with RAS)
Mild or no oedema Marked oedema in liver, renal and HF
Hypokalemia can be corrected by K Hypokalemia cannot be corrected by K
intake
l Rennin t Rennin
Normal renal biopsy Hypertrophy of juxta-glomerular
apparatus.

reatrnent:
1. Symptomatic : - Diet: Increase Kand reduce Na in take .
2. Hormone antae;onism: - Spironolactone (200-600 mg/day).
- Triametrene or amiloride.
- Metyrapone (11-8 hydroxylase inhibitor).
3. Sur,:ical: -Removal of adenoma.

·-------------------------------------------·
l!'Y..!1YP.~!:.~~ft.9.~~~-~2n.i.!m.
The same as primary Hyperaldosteronism but with Marked Edema , High
serum renin & Dilutional Hyponatremia.
Caused By
1. Renal ischemia: - Renal artery stenosis (RAS).
- Malignant hypertension.
- Others : - HF- Nephrotic syndrome.
2. Barrter syndrome: - inherited defect in the thick limb of the loop of
Henle.(Hyperplasia ofJGA.)

L-------------------------------------------1
31
 Cushing Syndrome
t Cortisol
• cortisol is Secreted by: Zona fasiculata.

Physiology of Cortisol :
A- Metabolic :

• WO: Hyperglycemia
(anti-insulin:- increases gluconeogenesis and glycogenolysis).

• Lipids: lipolysis and redistribution of body fat to the trunk and the face from the
limbs.
• Proteins: Catabolic (proteolysis of collagen in :- - BVs wall • purpura. - SC tissue •
delay healing . - bone • pathological fructures . - muscles • muscle wasting.)
• Minerals: as aldosterone • i Na,! K ,! H+.
• Vitamins: Anti Vit-D effect (prevents renal activation).
B- Anti action: Adipose tissue
{promote the brea~down of lot)

• Anti-inflammatory.
Bone
• Anti-allergic. (rech.1~i
bone formadoo)

• Anti-stress. Pancreas ...._._,__

(oortlsolo:,unteracts
ln,ulln)
i _-"'
Cort•ISO I .I
• Anti-Vit. D.
C- Androgenic like action.
✓ ~

D- Bone Marrow :

• i RBCs & PMNLs

:l',:'~~n••~'
uptake by muscle)

• ! Lymphocytes & esinophils.

E- Others: -

• Potentiate the effect of catecholamines on BVs.

• GIT: reduces the protective gastric mucus secretion.
• Psychological effect
NB : Cortisol is stimulated by ACTH & inhibited by -ve Feed back mechanism.

32
 etiology of Cushing $ :
❖ ACTH dependent ; " Cushing disease "
• Pituitary basophil adenoma (65% microadenoma).
• Exogenous ACTH
• Para malignant: "ectopic secretion of ACTH":
eg. bronchogenic carcinoma - Carcinoid Syndrome

❖ Non ACTH dependant ; " Cushing syndrome "

- Adrenal adenoma or carcinoma.
Exogenous corticosteroids (Cushinoid).

Clinical Picture:
the patient is usually 30-40 years old ( sex: ~ >J )
1) Hormone effect:
o Metabolic; (5: Cho- Lipid- protein -minerals - Vitamins)
1- CHO: DM in 1/3 of cases (insulin resistant).
2- Lipids: Deposition of fat in:
• Buffalo hump (interscapular area)
• Trunkal obesity + thin limbs = Samboxa shaped
• Moon face, with fish mouth.
3- Proteins:
• Muscles • muscle wasting and proximal myopathy.
• Bone • Osteoporosis with bone aches and pathological fractures
• SC tissue • delayed wound healing, rupture of SC collagen fibers along with
mobilization of SC fat leads to reddish lines (striae rubra then alba).
• Blood vessels • Rupture of BVs leads to easy bruising and prolonged
bleeding time.
4- Minerals:
o Na and HzO retention • Hypertension and edema.
o Hypokalemia • (mention clinical picture).
o Alkalosis • Tetany.

33
 5- Vitamins:
Anti Vit D • Hypocalcaemia with osteomalacia or rickets " according to the age " .
Signs and symptoms of Cushing syndrome

Androe;enic manifestations:
- In d : Baldness and of! libido.

- In 9 : amenorrhea, hirsuitism, and acne.

Anti-inflammatory;
- ! immunity with increased liability for
infection with opportunistic organisms.
Abdominal weight g a i n -
Bone Marrow:
Stretch marks
- Polycythaemia "tRBCs" causing
plethoric face (RED MOON FACE), which
becomes cyanosed in cold weather.
Others:
• GIT • Peptic ulcer .
Common Symptoms of Cushin_g
• CNS • Psychiatric depression. ✓ Central obesity, Cervical fat pads
& Comedons"Acne"
✓ Urinry 'fr of free cortisol & glucose
2) C/P of the cause: ✓ Striae & Suppresed immunity
✓ Hypertension , hyperglycemia &
• Pituitary Cushing: hyperpigmentation &
Hirsutism
may be increased ICT. ✓ latragonic
• History of steroid intake: in Cushinoid. ✓ Neoplasm
✓ Glucose intolerance & Growth
• Carcinoid $ : in cases with Para malignant
retardation.
syndrome.
L------------------
NB : Cause of Death in Cushing$ is : infection & toxemia or CVS complications .

Investigations :

1 - Hocmongl g~s~$sm~ot ;
Static;-
• Serum Cortisol:- Initially there is loss of circadian rhythm followed by persistent
high level (N= 5-20 ug%).

34
 • Increased 24 Hrs urinary excretion of free Cortisol.
• Elevated 24 hrs urinary oxygenic steroid level (hormone end product).
D:yuamic:
• Dexamethzone suppression test (see below).
2- bsnmgogl eff~,t;
Increased Decreased
Metabollc S. glucose
Minerals S. Na - urinary:- K & Aciduria K - Alkalosis - Ca (Anti-Vit D ).
BM Erythrocytosis- PMN Esinopenia, lymphopenia.
leucocytosis

3- Image~; ( For detection of the cause)

• Abdominal Sonar • adenoma .

• Brain CT & MRI • pituitary adenoma .
• Chest CT Scan • lung tumors .

Dexamethzone suppression test

A-step 1:- low dose Dexamethzone : 0.5 mg/6 hrs for 48 Hrs
• Cortisol serum level measured before and at the end of the test
1• If suppressed : normal
2- lf not suppressed : It may be
• Pregnancy

NB : Nelson Syndrome
After bilateral Adrenectomy as a part of Ttt of pituitary cushing • loss of -ve feed back on
pituitary adenoma secreting ACTH • t size of tumor • t ICP & excess pigmentations.

35
 reatment:
1.Treatment of manifestations:
• Correction of hyperglycemia
(My need high doses of insulin).
• High protein diet.
• Fluid restriction and diuretics.
• K & Ca and Vitamins supplements.
• Avoid trauma and surgery.
• Proper treatment of infection.

2.Treatment of the cause:

A. Pituitary Cushing: B. Adrenal Cushing:
1. Surgical removal: followed by 1. Surgical removal : followed by ACTH to
ACTH supplementation. activate the other atrophic gland.
2. Irradiation :using yttrium-90. 2. medical adrenalectomy:
Metyrapc;me: 11 hydroxylase blocker .
3. Bilateral adrenalectomy :
3. Adrenal carcinoma : is inoperable due to
followed by external
corticosteroids supplementation metastasis.
to avoid Nelson $ .
4. Reduction of tumor size:
Bromocryptin, cyproheptadine.

Remember th.at picture.

Harrthmnlng
Hrsutism - - - - - -, .-;:.._- - - - - Psychosis

Acne -"'-- - - - - Cataracts

P lethora - - - M '!d exopnthalrnos

36
 Adreno-genital syndrome
❖ Aetlol09n : J. Cortisol secretion (AR. deficiency of Cortisol synthesis) will lead to
increased ACTH -+ secretion of androgenic steroids (androstendione, testosterone &
hydrogesterone) -+ virilizing syndrome.

❖ J;:llnlcal Picture :

• Pre-natal
In females : Pseudohermaphrodism (small vagina - big clitoris - big fused labia majora)

• Post-natal

Precocious puberty: • Virilism

• Macro-genito-mastia precox . • amenorrhea.
• Muscularization. • Breast
• deepening of voice.
• Atrophy
• fused eplphysis & dwarfism but with small
testicle and no spermatogenesis • dwarfism..

• After puberty
• In females :
• Secondary amenorrhea.
• Sterility.
• atrophy of external genitalia.
• enlarged clitoris.

❖ ln.~•J.tt1.11lon1;
1. tt ACTH.
2. t t 17-Hydroxy progesterone level.
3. Increased urinary pregnanteriol.

❖ Treatment:_ Glucocortecoid replacement.

37
 Pheochromocytoma

,--------I
1 Role of 10s
- Tumor of chromaffin tissue. (Cells that secrete catecholamines)
I ✓ 10% Malignant I
- 90% from adrenal medulla & 10% from other chromaffin tissue. I ✓ 10% Bilateral I
- 90% benign and 10% malignant. I ✓ 10% Ectopic I

- 10% is bilateral. ... _____ _

I ✓ 10% Multiple :

- 10% multiple tumors.

❖ Cllnlcal Picture :
Hormone effect : (t Catecholamines)

• Hypertension: at first paroxysmal then it is persistent (1 % of secondary causes of

•
hypertension, 0.5% of severe hypertension).
Papillary dilatation. (Blurred vision)
------------
I Common S~mgtoms of I
I Pheochromocytoma I
• Tachycardia, arrhythmia . I SPs I
• Anxiety. I ✓ Paroxismal rise in BP I
I ✓ Palpitations I
• Sweating, dyspnea & vomiting. I ✓ I
Perspiration
Complications: I I
✓ Pain in abdomed
_________ ...
I
✓ Papillay dilatation
I
I
• CNS: stroke secondary to hypertension .
• ~ : IHDs (coronary spasm+ HTN), cardiomyopathy (myo-necrosis).
• DM: due to insulin antagonism.
• Sudden death: due to arrhythmia.
Associations:
❖ Neurofibromatosis.
❖ MEN-II (multiple endocrine neoplasia 2) "see later"
❖ Hypertrophic Cardiomyopathy.
❖ Sturge Weber Syndrome: (CNS A-V malformation+ coetaneous angioma of the
face.)

38
 ❖ Von-Hipple Lindeau $:
1- CNS and retinal hemangioblstomas.
2- renal and pancreatic cysts.
3- hypernephroma.

Investigations:
1. Hormonal assessment:

• Static:
1- Serum catecholamines : ft .
2- Vallinyl mandelic acid (VMA): it in 24 acid" end product of catecholamines
metabolism." ~
. Not Used
• D
_ynam1c:
* Suppressor test: clonidine (a-blocker) 5mg IV
1. Normally: !of BP by 53/25 mmHg for 15 minutes"
2. It's -vein Pheochromocytoma • no! of Blood Pressure.

2. hormonal effect: ECG, ECHO and blood glucose level.

3. Images: "for detection of the cause"

• CT, MRI or sonography of abdomen : to detect adenoma .

• IVP : may show indentation of the upper pole of kidney
• Aortography : to show arterial supply of the tumor.
• Isotopic scan : by using Metaiodobenzyl guanidine (MIBG) .
reatment:
1- symptomatic III ;
• blocking the action of the hormone by :
phenoxybenzamine(Alpha): 20-40 mg/day followed by
Propranolol (Beta): 120-240 mg/day or combined a and B (labetolol).
Propranolol is not used Alone
2-Treatment of the cause; Surgical removal of the tumor.

39
 Addison's disease
etiology:
I- Primary Addison disease (80%):

• Autoimmune: the most common cause associated with other autoimmune

diseases e.g.: Type 1 DM, addisonian pernicious anemia, thyroiditis, vitiligo.
• Ill: One of the most common causes
• Iatra~nic :
Surgical : Adrenalectomy with neglected
replacement therapy.
Drugs : Ketoconazole, rifampicin
• Tumors & Infiltration:
Heamochromatosis, amyloidosis, and
sarcoidosis.
• AIDS; Secondary to CMV infection or due
Causes of Addison disease
✓ Autoimmune (90%)
✓ Degenerative (Amyloid/sarcoid..)
✓ Drugs: rifampicin & ketoconazole
✓ Infections: TB & HIV
✓ Secondary: ('1tACTH)
Hypopituitarism
✓ Others: Adrenal bleeding
✓ Neoplasia: secondary carcinoma

to treatment effect.
II- Secondary Addison disease (20%):
• Sheehan syndrome - Panhypopituitirism

Clinical Picture :
Hormonal effect:

1) Hypotension:
• Due to decreased cortisone & aldosterone-+ Hypovolemia (Na+ water loss)+ loss of
pressor response to catecholamines.
• Initially postural hypotension then persistent hypotension (BP<110).
2) Hypoglycemia:
• due to decreased cortisone -+ J. its anti insulin effect & May lead to hypoglycemic
coma without promontory symptoms.
3) Hypo power "Asthenia":
- !Cortisol-+ !glucose - lAldosterone -+ l Na - !.Androgen-+ l anabolic effect

40
4) Hyper pigmentation:-
• ACTH is released in the form of pro-opio-melano-cortin.
• In primary Addison disease there is excessive release of ACTH.
• Color: Slate colored (Grey-brown). Addison's disease

• Site : Skin
__ Hyperpigmeotailon
. ------
1- Exposed areas : face, neck
Low blood pres1ure
Weakness
2- Scars of operations after onset of the disease Adrenal glands
not produce
Weight las,
sufficient steroid
hormones
3- Already pigmented areas: e.g. areola and
nipple
- Adrem1t <rltla: l
- hir,.o~r;
4- Mucous membrane of the mouth and tongue - syncope;
- (Qnvul,11,ns;
- hypoglycemia;
-h)'por.atremia:
(diagnostic) - severe vomiting - - - Skin
and dlarrhta. I \lltlllgo

5- Palm creases.
S) Hyperkalemla:- ( write its manifestations J

6) GIT hyper mobility : Anorexia, nausea, vomiting, diarrhea and abdominal pain.

7) Infertility.

C/P of the cause : e.g. TB, or other autoimmune manifestations e.g. vitiligo.

Investigations :
1- Hormonal assessment:

Static:
• !! Cortisol level.
• U. Aldosterone serum level.
• !! Hormonal end products : urinary 17-oxygenic steroids & tetrahydroaldosterone.
• ACTH level : Can differentiate lry and 2ry.
High ACTH Low ACTH
Adrenal cause (Primary Addison) Pituitary cause (Secondary Addison)

• Adrenal antibodies. • CTskull.

• Abdominal CT and X-ray may show • Other hormones e.g. TSH, Prolactin.
calcification.
• Investigation for sarcoidosls.
Dynamic ; Stimulatory test : ACTH stimulation test "See below"

41
2- Hormonal effect:
Defective ii H

3- Images:- abdominal/brain/chest= Sonar, MRI, CT-scan to detect the cause.

D . Diagnosis :
1- Other causes of generalized pigmentation:

Racial or familial He"°amochromatosis - --- . Addison disease~

Sun exposure Pregnancy & Contraceptive pills Pituitary Cushing_J

2- Other causes of hypotension

3- Other causes of hypoglycemia and asthenia : e.g. malabsorption $, CRF, pellagra
4- Other causes of Hyperkalemia (mention: see nephrology book)
5- Primary from secondary Addison (mention)

reatment:
1, Symptomatic; J1ifil rich in CHO, Protein, Na with low K.
2. Hormone replacement ;
- Oral hydrocortisone: 20 mg in the morning & 10 mg at night.
- The dose should be increased in stress e.g. trauma, infection or surgery.
- Fludrocortisone: 0.1-0.2 mg/ day if BP is still low with Cortisol replacement.
3, Treatment ofthe cause ; e.g Heamochromatosis, & TB.

42
 Addisonian Crisis
Definition : one of the medical emergencies characterized by acute adrenal failure or
hypocortisism.
etiology:
1. Primarv causes:
Acute from the start:

• Meningococcal septicemia (Waterhouse•Friedrichsen syndrome).

• Sudden withdrawal of chronic steroid treatment.
• Hemorrhage in the gland:- after anticoagulant toxicity or in breech delivery.
• Thrombosis of adrenal veins as in purpura, burns, DIC or pregnancy.
Acute on top of chronic:

Patient with Addison disease exposed to stress e.g. trauma, infection, or

surgery without adequate hormone replacement.

2. Secondary causes:

• Pituitary apoplexy: hemorrhage in pituitary adenoma.

• Surgical removal: without replacement therapy.
• Panhypopituitirism: when treatment starts with Thyroxin before cortisone.

Clinical picture:

• Severe hypotension (shock= not corrected with saline or vasopressor).

• Hypoglycemia up to Coma.
• Severe weakness up to confusion.
• Skin desquamation.
• Severe nausea, vomiting and diarrhea with abdominal pain (acute abdomen).

Investigations:

As Addison disease after stabilization !

43
 reatment:
1. Symptomatic Ht:
fluids:
a- 1.5 L glucose .
b- 10% -1.5 L Saline (hypertonic saline) over 30-60 min.
2. Hormone replacement:

a- Hydrocortisone 200mg IV bolus • 100 mg/8hrs infusion.

b- Desoxycorticosteroid acetate 5-10 mg IM if shock is persistent.

3. Treatment of the cause e.g. infection.

'. ,.,...)'•.•.,•·.• •'•.• .·.' ,·. ,• ,~·. ,., ... , . '.,.., . ,.-...,.,··

..,

;. Other types of adrenal hypo function:

'":·.

1- Hyporeninimic: hypoaldosteronism:
Aetiology: Diabetic nephropathy, interstitial nephritis, obstructive
nephropathy.
,. 2- Hyperreninimic: hypoaldosteronism:
defect in z.glomerulosa-+ 1aldosterone .... trenin. ·.•.
..... J--~ <·(
¥

. ~ _., -.. ·.. ·...· .•..~ ...< . ,:·,, . ,/."•.. ,.'.~ ..•-;'•.. \. .(' :_.. -..•:"'.. :-' ..•.:-,;,.. '
-. '.I"•.•-: \;,t(-.. ,.~ .,<',, .·: ,._~. A.'-. :,.':-~".,,. -••. ,('."_,,'"._ .:.,:·,.:.... ,". ·-•••: ·-:,~,.-:

NB : Ca blocks Na channels in muscles & nerves • so it"' Ca & Na enterance to

Muscles • muscle twitches
Nerves • Paresthesia

44
 glg_n,,~
The Thyroid Gland
!Anatomy :I
- Formed of two lobes connected by an isthmus.
- Attached to the thyroid cartilage, and thus moves on
swallowing.

!Embryology :I
- arises from the base of the tongue
- Remnants can sometimes be found at the base of the tongue (Lingual thyroid) and along
the line of descent.
!Blood Supply:!

rich blood supply from superior and inferior thyroid arteries and others.

IHistolog~
- consists of follicles lined by cuboidal epithelioid cells.
- Inside the follicles there is colloid, which is an iodinated glycoprotein (thyroglobulin).
between which are parafollicular cells containing calcitonin secreting C cells.
~teps of thyroid synthesis :I 'r
~} .:
~i\ ........
• Trapping of iodine
• Binding of Tyrosine and iodine to form monoand di-
iodotyrosine.
• Coupling of two molecules of di-iodotyrosine to form

...... •.
T4 or mono and di-iodotyrosine for forming T3.
• Storage as thyroglobulin.
. .... •"
. •·-....
• Release after action of protease enzyme on Thyroglobulin.
• Circulating hormone is either free (active) or bound to thyroxin binding globulin, pre-
albumin and albumin.

45
Function of Thyroid Hormone.( Thyroxin) :

• 02 : 1' oxygen consumption and basal metabolic rate.

• CHO : 1' hypoglycemic effect even with glycogenolysis .

• Lipid : kholesterol Hypothalamus

• Protein : 1' catabolic effect.

• Vitamins : 1' Hepatic conversion of carotene to vitamin Pituitary

A. Tari•t tissues

Liver
• Catecholamines : 1' tissue Kldnay
Thyroid

Br•in
T4

responsiveness to catecholamines. He•rt

Mu.cle
I Bloodstream

• Development: Stimulates skeletal, T3

mental and sexual development. Liver

Factors affecting it "regulations " : stimulated

~ TRH (hypothalamus) • stimulates the release ofTSH (pituitary) • stimulates the release
of T3 & T4 (thyroid).
inhibited by : T3 has negative feedback effect on the pituitary and the hypothalamus.

Aetiology:
1. Primary : Graves' disease.
2. Secondary : toxic nodular gaiter.
3. Plummer's disease " not Plummer winson $ ": solitary toxic adenoma secreting T4.
4. TSH producing pituitary tumor (rare).
5. Ectopic thyroid tissue : e.g. choriocarcinoma.
6. Thyroiditis : Hashimoto "transient Thyrotoxicosis" viral" De Quervein disease".
7. Exogenous iodine" jod-Basedow phenomenon".
8. Iatrogenic : excess TSH, T4, amiodarone.

46
 1ry Thyrotoxicosis "Grave's disease"
Aetiology:
Autoimmune disorder as evidenced by:
a) Association with HLA B8, DR3.
b) TSI : Thyroid stimulating imrnunoglobulin act as TSH .
c) TRA :(TSH receptor antibody). "Recently"
d) autoimmune diseases association : thymic enlargement, splenomegaly,
lymhadenopathy, myasthenia gravies, SLE, pernicious anemia, and Addison's disease.
Clinical picture :
Graves' ~ Exophth~lmos
A. Jxpc gf PAlieot ; disease
symptoms
• ~: d' ratio is 8-1. - Goiter
Sweating -----.
................
• occur in middle age (30-50 y).
Headache
W@ightloss
Nervousness
E.motional
i. Polyphagia with loss of weight. in,tability

ii. Intolerance to hot weather.

iii. muscle weaknes progressively

iv. Hyperglycemia : due to ii glucose

absorption and insulin antagonism, but may be hypoglycemia as increasing BM Rs.
v. Polyurea may be present due to :
- Increase water intake (Polyphagia).
- Increase water production (metabolism)
- Increased renal blood flow.
~. GJgod;
• Thyroid gland diffusely enlarged & firm.
• Systolic bruit may be present due to increased vascularity.
• Examine also for retrosternal extension.
12, GQDQdgJ ; menstrual disturbance, infertility.

47
E, Gil; - Increased appetite with loss of weight.
- Diarrhea & even steatorrhea.
- Generalized lymphadenopathy & splenomegaly.
f, ~kin;
- Warm flushed (salmon pink)
- excess sweating (VD and hyper metabolism).
- Pigmentation is common but vitiligo occurs in 7% of cases.
- Hair : thin, with premature falling and graying.
- Nail : recession of nail bed base onycholysis "Plummer's nail".

Peri-tibial Myxedema : tender itchy swelling over the chin of tibia due to LATS .
It may be Accompanied by clubbing of fingers and Exophthalmos.

~' {;g[dlgxg1,ulgt 1x1ti:m;

1. Palpitation: is the commonest symptom due to
- Tachycardia (sleeping pulse> 100/ min).
- Hyper dynamic circulation.
-Arrhythmia.
- Neurosis.
2. Arrhythmia:
• any arrhythmia except heart block. The commonest is AF.
3. Hyper dynamic circulation:
due to high systole (forcible heart) & lowdiastole (arteriolar VD) leading to:
• water hammer pulse
• Big pulse volume
• functional systolic murmur & ending in high CO heart failure.

• Psychic : Restlessness, anxiety, insomnia & rarely mania occur.

• Organic:
- Fine tremors of outstretched hands & unsupported tongue.
- Myasthenia gravies (auto-immune disorder).

48
 - Thyrotoxic myopathy : 2 forms
- Chronic :-_involving proximal muscles.
- Acute:-_involving bulbar muscles.

I, ~ye gffectl20 "Qgbtbglmopgtby:" ;

• Non-Infiltrative : increased thyroxin leads to retraction of Muller'smuscle. (not

specific to Grave's) lead to the following signs:

• Stellwag's: Staring look+ Infrequent blinking.
• Dalrymple's : rim of sclera above cornea.
• Von Grafe's : lid lag on looking down" to wards
gravity ". Exophthalrnos and lid relractioo.

• Rosenbach's: fine tremors on closure of eye lids.

• Slight exophthalmos : retracted upper lid.

• Infiltrative : auto-antibody called Exophthalmos producing substance

(EPS) leads to infiltration with myxomatous tissue in retro bulbar space,

extraoccular muscle & lacrimal gland • lead to the following signs :
• Exophthalmos: unilateral or bi-lateral , may Uf¥f Id 1-alwo,,
"Jr
oe-· A'ff!'
d ~vO-:-'iOr Lmt~~
puoil
Ncwmol

occur before Thyrotoxicosis "ocular

Grave's".
• Injected conjunctiva.
• Swelling of eye lids & of lacrimal glands .
Bo'h !J, ." I'!(;,~ ~-:.s·1 fror, Ct-l'fie with
.,,£ib£ belaw ~ a[ rcunc th2i r'1
• External ophthalmoplegia : paresis of !Ce-ti

occulomotor muscles •
a. Mobius sign: lack of convergence due to weak medial recti .
b. Joffroy sign: Lack of forehead corrugation on looking upwards.
c. Ruler test is diagnostic.

NB. Malignant exophthalmos with papilledema & corneal ulcers may occur

49
Classification of eye changes in Graves disease
• 0 : no signs or symptoms
• 1 : only signs (lid lag & staring look) , no symptoms
• 2 : sof tissue involvement : (periorbital edema , redness & chemosis)
• 3 : proptosis
• 4: extra-occular muscle involvement
• 5 : corneal involvement
• 6 :slight loss (optic nerve involvement)

Investigations :

11 - Hormonal assessment~
1) Total T4 & T3 : increased (inaccurate) :
It's measures thyroxin which binds to thyroxin binding protein " TBP"
• T4 = 4-12 micro gm % I.l.=70-170 n gm%
• Disadvantage : affected by change in TBP :
- TBP J. in : LCF - nephrOtic - malnutrition - Thyrotoxicosis .
-TBP tin: estrogen (pregnancy, C. pills)-phenothiazine- myxedema.
2) Free T3 & T4: increased {accurate)

Measured by radioimmunoassay.

Normally: li : 1.6 ngm % - T3 : 0.4 ngm%.

3) TSH level :
Normally: 0.5 -5 mcµ/ml.
It increases in : primary hypothyroidism, TSH producing tumor.
It decreases in: secondary hyothroidism, thyrotoxicosis.
4) 13 resin uptake: Is High

• The T3RU test measures the level of proteins that carry thyroid hormone in the
blood.

50
 • Radioactive T3 is added to the patient serum where it is fixed to the binding sitesof
TBP not already saturated.
• The remaining unabsorbed radioactive T3 is then absorbed to a resin & the
radioactivity ofresin is measured, (Normally 25 - 35%)
5) Free thyroxin index T4 x T3 resin uptake : high > 11.5

It is now replaced by measurement of free T3 & T4.

6) T3 suppression test:
Measurement of radioactive iodine uptake (RIU) before & after giving T3. It is used to
diagnose mild hyperthyroidism.
7) Others (for the Cause):
1. Needle aspiration biopsy .
2. Thyroid antibodies .
-Thyroid receptor antibodies: TSI, LATS or LATSP (+vein Grave's).
- Thyroid microsomal antibodies: in Hashimoto's disease.

~- Hormonal effect:-!
• Increased : calcium - + glucose - Basal metabolic rate .
• decreased : cholesterol .

?- Images:-!
1. Thyroid ultrasound .
2. CT-scan.
3. Thyroid .fildill.: using 1131 or 99 mTc with Gamma camera
• Differentiate cold (malignant) from hot (benign) nodule.
• Differentiate Grave's (diffuse), toxic nodule & multinodular goiter
• Detect retro-sternal goiter or ectopic thyroid tissue.
4. Radioiodine uptake: increases in Thyrotoxicosis .

51
Differential Diagnosis :
Defferentiate lry from 2ry thyrotoxicosis

1ry 2ry Thyrotoxicosis

Thyrotoxicosis
1. Cause

2. Age of onset
3. Thyroid
4. CVS
5. CNS
6. Exophthalmos
7. Monosymptomatic
8. Treatment

1. T3-Toxicosis:
I
Cause: It may be due to excess conversion ofT4 to T3 in tissues.

C/P: It appears in old patient & its main features are cardiac (AF & HF) together with
severe muscles weakness, diarrhea, vitiligo of hands & feet.
lnvestigatio.ns: - T4 level & radioiodine uptake are normal.
- High T3 level is diagnostic.

2. Masked or apathetic Thyrotoxicosis:

Cause: due to depletion of catecholamine in long standing cases .

C/P : Occurs in old people where the general features of Thyrotoxicosis are
replaced by apathy, weakness, cool dry skin simulating myxedema.

3. Congenital Thyrotoxicosis: transmitted thyrotoxic mothers to babies (self limited).

4. Myasthenic form: associated myasthenia gravies with Thyrotoxicosis.

5. Monosymptomatic form: one of the manifestations is predominates e.g.

thyrocardia.

52
 TREATMENT OF TNYROTOXICOSIS :
IMedlcalm ~
• Indications :
1. Primary thyrotoxicosis.
2. Secondary thyrotoxicosis.
3. pre-operative preparation - inoperable.
4. Thyrotoxicosis with pregnancy.
5. For complications e.g. arrhythmia.
• Contraindications :
1. Retrosternal goiter or large one (TSH rise will increase pressure
symptoms and exophthalmos).
2. Suspicion of malignancy
• Methods & drugs :

1. Diet : Nutritious diet, proteins, vitamins.

2. Sedative & tranquilizers : diazepam, phenobarbitone

3. B-blockers :
Propranolol (inderal) : relieve systemic effects mediated by sympathetic over
tonus e.g. arrhythmia.
• Dose: 40 mg t.d.s. • Side effects(see cardiology).

4. Anti-thyroid drugs : Interfere with binding of Iodine with Tyrosine :

al Thiouracils:
Had in addition the ability to inhibit conversion of T4 to T3 in tissues
• Methyl-thiouracil: 200 mg tds then reduce dose after 4-6 weeks to 100 mg tds.
- Propyl-thiouracil: 100 mg tds then reduce dose after 4-6 weeks to 50 mg tds.
b) Carbimazol (Neomercazol):
· Dose : 20 mg tds to be reduced after 4-6 weeks to 10 mg tds.
- Duration of TTT : 12 - 24 months .
- Follow up: CBC ( to exclude aplastic anemia) & TSH (doses adjusting).

53
S. Side effects :
- Allergy : fever, rash, generalized lymphadenopathy, arthritis.
- Granulocytopenia: sore throat, fever.
- GIT : N & V, cholestatic jaundice.
- SLE (drug induced).
- Goiter due to tTSH.
- Hypothyroidism especially in newborn with thyrotoxic mother.
- Relapse : on sudden stoppage.
NB: Block & Replacement therapy May be used

!Radio iodine treatment :I

• Iodine is uptaken only by thyroid gland So its effect on body is minimal But destroys
thyroid cells
• Indications :

1. Failure of medical ttt .

2. Patient unfit for surgery.
3. Patient age > 40 y .
4. Recurrence after thyroidectomy.
5. Toxic adenoma.
• Contraindications :
1. During pregnancy, lactation, childhood.
2. better not in child bearing period).
3. Huge goiter & retrosternal goiter.

• Side effects :

1. Hypothyroidism.

2. BM inhibition .

3. Fetal anomalies if taken in pregnant females.

4. t Incidence of thyroid or other malignancy ( not proved).

54
ISurgical treatment ~
• Indications :
1. Secondary Thyrotoxicosis.
2. Failure of medical ttt in primary cases.
3. Huge goiter - retrosternal.
4. Suspicion of malignancy.
• Contra Indications : - malignant exophthalmos.
• Pre operative preparation :
Lugol's iodine (5% 12 in 10% Kcl 15 drops TDS for 10 days. It reduces size &
vascularity of gland.
• Complications of surgery
8 Recurrence after surgery in 2 : 9 % of patients
8 Hypothyroidism directly related to extent of surgery
8 Hypocalcemia deu to removal of parathyroid glands
8 Recurrentlaryngealnerveinjury

[reatment of compllcatlons ~
❖ Ocular Complications: In addition to usual treatment add:

1. Protect eye by ointment, and sun glasses.

2. Guanethedine 5% eye drops or B-blocker to lid retraction, & conjunctiva)
injection.
3. Lateral tarsorrhaphy.
4. Severe cases: prednisone 120 mg /day, or decompression operation
(supraorbital deroofing called Nafziger's operation).
❖ Pretibial myxedema: Local betamethazone cream.
❖ Heart Failure;
1. Bed rest, salt restriction, diuretics.
2. Carbimazol till the patient becomes euthyroid, then stop for 4-7 days & give
radio-iodine, then restart Carbimazol for 3-4 months.
3. Persistence of AF after control of thyrotoxic state need B, blockers or DC shock.

55
 Life-threatening complication of sever thyroid activity with about 10% mortality.

lff\1hi
a) Lack of preoperative preparation.
b) 1-131 in thyrotoxic patient.
c) Stress, infections in untreated patients.

Clinical picture:
may be masked by B-blocker ;
1. Feyer : hyperpyexia -Temperature may reach > 41 Co
2. tNS: marked irritability. In old age there is apathy, bulbar palsy from myopathy.
3. ~ : tachycardia, acute HF, arrhythmia.
4. !ii.I: nausea, vomiting diarrhea. Later collapse, shock, delirium up to coma.

reatment: emergency
al Anti-thyroid:
1. Carbimazol or better propyl-thiouracil : 40 mg at the start, then 10 mg/6 h.
2. Nal or KI : 500 mg/8 h infusion to decrease the release of thyroid hormones.
3. Propranolol : 0.5 mg lV then 0.5 mg/min till a max. of 5 mg for tachyarrhythmia.
4. Dexamethazone or hydrocortisone: J.release ofT4 - !conversion ofT4 to T3.

bl Symptomatic:

1. Chlorpromazine: as sedative & hypothermic .

2. Antipyretics (acetaminophen not aspirin) & foments: for fever.
3. Digoxin & diuretics for AF & HF.
4. Nasogastric tube for bulbar palsy, nausea, vomiting.

cl Treatment of cause & precipitating factor: e.g. antibiotics for infection

56
 MYXEDEMA

IA.Primary:!

1. Endemic myxoedema: prolonged 12 deficiency.

2. Goitrogenous substance: cabbage, 12 containing cough mixture, PAS, Amiodarone.

3. Destruction of thyroid gland:

a) Primary idiopathic atrophy: auto-immune (circulating abs).

b) Hashimoto's disease "Lymphadenoid goiter":

• Autoimmune disease.
• Gland structure is replaced by dense lymphocytic infiltration.
• A short period of Thyrotoxicosis followed by hypothyroidism.
• Other autoimmune disease:- as Addison's, Rh arthritis, pernicious anemia.
c) de Quervein disease: "Sub acute viral thyroiditis ".
d) Riedel's thyroiditis: Fibrous tissue infiltration of thyroid "woody thyroid" .
e) Iatrogenic: thyroidectomy, radio-iodine, antithyroid drugs.
1B. Secondary:!
Simmond's disease (Pituitary myoxedema).
! t~ir dry. c:oarsA,

Clinical picture :
lalera
t!yebmws
11- General :I 1h1n
·, Per;orbi'.a
edema
1. Intolerance to cold.
2. Tiredness, weakness & weight gain.
3. Face : - Expressionless, bloated.
- Puffy eye lids & loss of outer 1/3 of eye brows.
- Malar flush and thick skin.
- Red glazed tongue.
- May be cataract.

57
~- Thyroid gland :I according to cause :

1. Enlarged: in Hashimoto's disease, endemic goiter & goitrogenous substance.

2. Atrophic: in primary idiopathic forms.
Symptoms of
3. Scars of previous operation. HYPOTHYROIDISM

los,; of eyebrow hair

4. Hard & fibrotic in Riedel's thyroiditis.
Enlarged Ihyrold

~-Genital~
Dry and - • ' Slow heartbeat

I':.~
coarse <kin
1. In Males: Menorrhagia, Galactorrhea,
Poor appetite
Constipation - '
sterility (hyperprolactinerma due to feed ~ Infertility
Heavy
menstruatio"
back tTRH). eoo1-
e~1rem1t1es and - Carpal tunnel
swelling of the limbs syndrome
2. In females: impotence, gynecomastia.

~- GIT :I The thyroid gland

does not produc"
Weight gain
Poor memory
-ugh thyroid Intolerance to cold
hormone Feeling of tiredness
1. Tongue : red glazed.

2. Stomach: dyspepsia, hypochlorhydria (leading to Fe deficiency anemia).

3. Intestine : low motility -+ constipation & slow absorption -+ steatorrhea.

1- Dry, cold, non sweaty, pale (anaemia - oedema) may be scaly and rough.
2- Non pitting edema : due to SC mucinous .
3- Nails : thick - body hair is sparse & brittle.
4- Yellowish : due to carotinemia (lack of conversion of carotene to Vit A).

16- CNS~
1. Slow celebration, apathy, poor memory and Rarely myxoedema madness.
2. Speech: slurred speech (mucinous material in tongue) with hoarseness of voice.
3. Nerve deafness.
4. Peripheral neuritis, carpal tunnel syndrome.

58
 5. Suspended jerks: delayed relaxation of tendon jerks.
6. Others: ataxia, vertigo, convulsions.
7. Myxoedema coma :

Rare life threatening emergency occure in long standing untreated

hypothyroidism , usually in elderly
Precipitating facors :
Exposure to cold
Illness & infections
Trauma
Drugs : anesthesia and narcotics
Clinical picture
• Hypothermia leads to muscle rigidity with both metabolic & resp.
acidosis and resp. depression
• Co2 retention & multi-organ dysfunction
• bradycardia, hypotension.
• Areflexia , seizures , altered mental status
• Hypoglycemia + High mortality is at least 50%.

1. Hypertension : due to tt peripheral resistance & atherosclerosis

(hypercholesterolemia).
2. Angina & intermittent daudication especially on start of treatment.
3. Cardiomyopathy.
4. Pericardia] effusion (cholesterol pericarditis).
5. ECG : low voltage, sinus bradycardia, flat or inverted T (reversible).

I
~- Blood: (all forms of anemia):

1- Normocytic normochromic (BM inhibition).

2- Microcytic (Fe deficiency): !absorption + l loss due to menorrhagia.
3- Macrocytic anemia: due to associated pernicious anemia.

59
Jn.docdna'D911-

Investigations :
a) TSH level : high in thyroid failure & low in pituitary failure (test of choice).

b) T4 & T3, PBI, FTI, radio iodine uptake are low.

c) T3 resin uptake is low •

d) Prolactin, cholesterol, CPK, GOT & GPT levels are high.

e) Glucose tolerance: flat curve.

f) Thyroid antibodies.

g) Blood: 3 forms of anemia- see before.

h) ECG: see before.

Differential Diagnosis :
• Thyroid from pituitary myxedema
• Nephrotic syndrome. • CRF / nephrotic syndrome
• Pernicious anemia. • Myotonic syndrome.
reatment:
A- Cretinism:
- Treatment should start before first 6 months to prevent mental retardation.
- L-Thyroxin 0.025 mg/ day to be increased up to 0.2 mg/ day.
B- Adult hypothyroidism:

- L-Thyroxin for life: start by 50 ug/day & ++ gradually up to 100 - 200 ug/day.
- Old people & those with IHDs need lower dose (to avoid HF & angina).
- Follow up: ECG: cholesterol level, TSH level (most important).

C- Myxoedema coma :
- Gradual warming.
- 02, ventilation & CVS support.
- Glucose IV for hypoglycemia.
-Drugs:
- T3 -2.5-5-Lgm/Bh. or by nasogastric tube.
- Hydrocortisone.
- Antibiotics for infection.

60
 Cretinism
Deficiency of thyroid hormones during infancy (infantile hypothyroidism)

etiology:

1) Congenital absence of thyroid gland.

2) Congenital enzymatic defect in synthesis ofT4 "cretinoid goiter".
3) Pendred's syndrome: cretinism+ congenital deafness.
4) Iodine deficiency (endemic cretinism).
Juvenile Myxedema
5) Excess antithyroid drugs during pregnancy.
1. Age of onset: 4-12 years.
Clinical picture : 2. Mentality : normal.
3. Main presentation : dwarfism.
1, CNS : mental retardation, slow speaking.
4. x-ray : epiphyseal dysgenesis
2. General features ; (multiple stippled foci instead
of a single focus of ossification
Face : puffy eye lids, depressed nose, big lips,
in epiphysis).
protruded tongue, delayed dentition.
Hands: square-shaped, with short fingers.
Stature : Disproportionate dwarfism: height> span.
walking is delayed with waddling gait.
Hypothermia.

3, CVS : bradycardia, low voltage ECG with flat T-wave.

4. Skin : dry, cold, scaly, with SC myxoedematous tissue deposition in hands, face &
supraclavicular region.
5, Muscle ; weakness, constipation, pot-belly abdomen.

Investigations :
- Low T3 T4, FT3, FT4 levels.
- TSH level : high "characteristic".
- Serum cholesterol : high.
- X-ray carpal bones : delayed appearance of ossification centers.

61
 GOITER (THYROID ENLARGEMENT)
Causes and tvpes of goiter
• Diffuse goiter
1. Simple: Physiological (puberty, pregnancy)
- 1' iodine requirements, so the gland is usually smooth and soft.
- It may be associated with thyroid growth-stimulating antibodies.
2. Autoimmune : Graves' disease / Hashimoto's disease
- both associated with firm diffuse goitre of variable size.
- A bruit is often present in thyrotoxicosis.
3. Thyroiditis : Acute (de Quervain's thyroiditis)
Acute pain, tenderness & diffuse swelling is suggestive of an acute viral thyroiditis (de
Quervain's). & may show transient clinical hyperthyroidism with an increase in T4.
4. Iodine deficiency (endemic goitre)
5. Dyshormonogenesis
6. Goitrogens (e.g. sulfonylureas)
• Nodular goiter
1. Multinodular goiter
✓ The Most common especially in older patients
+
✓ Usually euthyroid but may be hyperthyroid or borderline ( TSH & normal T4 T3)
✓ Commonly associated with tracheal and/or oesophageal compression and can cause
laryngeal nerve palsy.
✓ It may also extend retrosternally.
2. Solitary nodular
• Such a goitre presents a difficult problem of diagnosis.
• Malignancy should be considered in any solitary nodule however, the majority is cystic
or benign
3. Fibrotic (Reidel's thyroiditis)
4. Cysts
• Tumours
1. Adenomas 2. Carcinoma 3. Lymphomas
• Miscellaneous
1. Sarcoidosis 2. Tuberculosis.

62
 EUTHYROID_ _ GOITER
Thyroid enlagement without clinical or laboratory evidence of thyroid dysfunction

• Physiological : puberty, pregnancy, menupause and

• drugs : lithium or aminosalicylic acid
• May occure in iodine deficiency or large dose of iodine
resented as =
Asymptomatic soft symmetrical swelling or less commonly huge goiter
lnvestig_ations
• Thyroid scan is normal
• Thyroid ultrasound •
• TSH : may be slightly elevated
• Thyroid antibodies are normal .

✓ Iz supply in salt, water and crops

✓ Levothyroxine : may decrease size of goiter but contraindicated in elderly.
✓ Large goiter : may need surgery for cosmotic reasons or deu to compression
symptoms or malignancy.

63
 THYROID NEOPLASM
CLA&&IFICAflf>N
Thyroid gland contains follicular and para follicular (C) cells so thyroid tumors are
classified ino :
Benign : follicular adenoma
Malignant:
• Differentiated
papillary carcinoma , follicular carcinoma or mixed carcinoma
• Un differentiated carcinoma: Anaplastic carcinoma
medullary carcinoma

malignant lymphoma (tumors from lymphoid elements)

by metastatic deposits or by local infiltration from a nearby lesions

Follicular adenoma: present as solitary nodule

Nb : follicular adenoma is differentiated from f carcinoma only by histological examination to detect
evidence of capsular or vascular invasion by carcinoma, so it is not reliable and adenoma is treated as
carcinoma by lobectomy of the side of the adenoma plus isthmusectomy

1- Irradiation : head and neck external irradiation

2- Follicular carcinoma: is the commonest type in endemic goitrous areas
3- Genetic element may be present
4- On top of hashimoto's thyroiditis

lf!PE& l>f lHf!Rl>IP CANCER

Papillary 70% Occurs in young people local, sometimes lung/bone secondaries Good, especially in young
Follicular 20% More common in females Metastases to lung/bone Good if resectable
Ana plastic <5% Aggressive locally invasive Very poor
lymphoma 2% Variable Sometimes responsive to
radiotherapy
Medullary cell 5% Often familial Local and metastases Poor, but indolent course

64
 THYROIDITIS

Oiagnosis r>uration &

tljf)GS Cause Cinical features (not all tests needed) resolution
Anti-thyroid Hypothyroidism, -Thyroid function -Hypothyroidism
Hashimoto's antibodies, rare cases of - thyroid antibody usually
thyroid its autoimmune transient permanent
disease thyrotoxicosis
Possible viral Painful thyroid, Thyroid function + - Resolves within
Subacute
cause thyrotoxicosis ESR 12-18 months,
thyroiditis ( de
followed by + Radioactive - 5% possibility of
Quervain's
hypothyroidism iodine uptake permanent
thyroldltis
hypothyroidism.
Anti-thyroid Thyrotoxicosis Thyroid function Resolves within
Silent
antibodies, followed by thyroid antibody 12-18 months,
thyroiditis,
autoimmune hypothyroidism radioactive 20% possibility of
Painless
disease iodine uptake permanent
thyroiditis
hypothyroidism.
Anti-thyroid Thyrotoxicosis - Thyroid function - Resolves within
antibodies, followed by - thyroid antibody 12-18 months,
Postpartum autoimmune hypothyroidism. - radioactive -20%
thyroiditis disease iodine uptake possibility of
(Cl if the women permanent
is breast-feeding) hypothyroidism
Drugs as: Either Thyroid function continues as long
amiodarone, thyrotoxicosis or thyroid antibody as the drug is
Drug induced lithium, hypothyroidism. taken
interferons,
cytokines
Follows TTT with: Occasionally Thyroid function Thyrotoxicosis is
radioactive iodine thyrotoxicosis, tests transient,
for thyrotoxicosis more frequently hypothyroidism is
Radiation
or external beam hypothyroidism.
induced usually
radiation therapy
permanent
for certain
cancers.
Bacteria mainly, Occasionally Thyroid function Resolves after
Acute but any infectious painful thyroid, radioactive iodine treatment of
thyroiditis, organism generalized uptake, fine infectious cause,
Suppurative illness, needle aspiration may cause severe
thyroiditis occasional mild biopsy illness
hypothyroidism
Source: American thyroid association .

65
 Ql:segsesQf Parathyroid glands
• Calcium metabolism :
• Total body content of Ca is 1100 gm, mainly concentrated in bone and teeth
• Serum calcium is 9-11 mg%, it's present in 2 forms:
1- Non diffusible portion :
Thyroid
45% Protein bounded portion and acts as reservoir gland

2- Diffusible portion 55%

ParMhymid
glands
- Ionized : 50%, Active form .
- Non ionized : 5%, non active form.

• Function of Calcium :
1. Blood clotting. (Factor iv)
2. Excitability of nervous and muscular tissues.
3. Muscle contraction. (ca blocks Na channels)
4. Cardiac function: rhythmicity and contraction.
5. Formation of intercellular cement substance.
6. Secondary intracellular messenger.

• Regulation of Calcium absorption :

❖ ca is absorbed under the control of;

• Ionized Ca and protein-bound Ca can be affected by acid-base balance:

- Acidosis • i ionized Ca . - Alkalosis • J. ionized Ca.
• Serum Ca-P solubility product kept constant around 40.

66
• Parathormone Hormone : tCalcium

❖ ttt serum Ca level by :

1- i Ca reabsorption from kidney .
2- i Ca absorption from intestine through Vitamin D.
3- i the activity of osteoclasts -+ i Ca mobilization
from bone.

It stimulated with Hypocalcaemia but needs Vit D and Mg .

• Calcitonin :
tCalclum

- Secreted by parafollicular C cells of thyroid glands.

- Increase Ca & P uptake by the bone. (4- Serum Ca)

• Vitamin D:
- Produced in SC tissue by UV light on cholesterol or absorbed as Vit D from diet.
a) intestine
- Increase Ca absorption from the intestine.
b) At Bones;
• if Rickets it increases Ca deposition in bone while in normal cases it causes Ca
resorption.
c) At Kidney;
✓ if small doses • P. retention - iflarge doses • P excretion .
✓ Stimulates differentiation and inhibits proliferation of keratinocytes.
✓ Inhibits the production of gamma interferon and iL-2 by monocytes.

67
 Hyper paraThyroidism
Aetiology:
• Primary: (80-85%)
- Adenoma of parathyroid gland (may be a part of MEN I)
- Parathyroid carcinoma is rare.
• Secondary :
• Chronic hypocalcaemia (e.g. malabsorption syndrome or CRF) with secondary
hyperplasia of parathyroid gland.
• Tertiary:
• Prolonged secondary hyperparathyroidism will lead to adenomatous
transformation (hyperplastic changes).
• Paramalignant :
• as oat cell carcinoma of the lung.

Clinical Picture : Disease of Bone/ Renal stone/ Growns / Thrown / Psychic over tone

It- on Bone:I
- Cause Ca mobilization from the bone which lead to :

• Osteoporosis: bone aches, pathological fractures

(heal rapidly secondary to hypercalcemia).
• Bone cysts: (Osteitis fibrosa cystica).
• Premature loosening of the teeth : due to
resorption of lamina.
12- On kidney~
• Polyurea (Ca diuresis) with Polydepsia and thirst.
• Stones:
- Bilateral , Multiple & recurrent
- presents by colic, haematuria, recurrent urinary tract infection and CRF
• Nephrocalcinosis: due to metastatic calcification ends with CRF.

68
13· Hypercalcemia: IResults in
1) CNS : apathy, drowsiness, malaise and personality changes.

2) CVS: bradycardia ( Calcification of AV node) and short Q-T interval+ HTN.

3) Eye: band keratopathy (calcification of cornea), conjunctival injection.

4) GIT: a. Constipation with hard stools.
b. Acute pancreatitis.
c. Peptic ulcer, nausea and vomiting.
5) Renal: Polyurea and polydepsia (Nephrogenic diabetes insipidus) & Nephrocalcinosis.
6) Muscles: Hypotonia and waddling gait.
Acute Hypercalcemia
7) Joint: Chondrocalcinosis (pseudo gout). Emergency condition characterized
by elevatedMnlln Qllil-12·13 mg%.
8) Skin : Dry and puriritis.

12- C/P Of cause:I e.g. Chronic Renal Failure

Investigations:
HORMONAL ASSESSMENT:
- Elevated Parathyroid hormone
- Urinary C-AMP increase: Characteristic ofhyperparathyroidism.
HORMONAL EFFECT:
t) Kidney:
1. l Urinary 24 h. Ca.
2. l Urinary 24 h. P.
3. Renal X-ray : Stones and Nephrocalcinosis.
2) Serum ca -P -alkaline phosphatase.
Cause Ca p Alkaline Ph.
Primary
econdary

ertiary

69
13- Images~
1. Subperiosteal erosion of phalanges (especially middle phalanges)
2. Resorption of lamina Dura of teeth.
3. Osteoporosis of bones manifested by:
1- Cod fish spine : soft spine & indentation of
the vertebral bodies by discs.
2- Ground glass bones : due to poor
calcification.
3- Mottling of skull (pepper - pot skull).
4- Milkman pseudo fracture or looser zone:
a zone of radiolucency extending 1cm into
bone from surface due to decalcification
around nutrient artery.
1. Bone cysts :
Osteitis fibrosa cystic generalisata.

~- Detection of the cause:!

1) Renal function tests,
2) investigation for Malabsorption syndrome.
3) Radio isotopic scanning: for parathyroid using thallium
& technetium.
4) Steroid suppression test: "Dent test"
.:. Hydrocortisone 40 mg orally 8 hourly for 10 days.
- lowers serum Ca in hypercalcemic states other than hyperparathyroidism
(cortisone-! action ofVit D).

70
 DIFFERENTIAL DIA8NOSIS OF HYPERCALCEMIA
1) t Ca Intake:
• Milk alkali syndrome: "excess alkali or ingestion antacid for ttt of peptic ulcer".
• Over treatment of hypocalcaemia.

2) t Ca absorption:

a)Endocrinal
1. Hyperparathyroidism (lry, 3ry, ectopic - not 2ry).
2. Acromegaly.
3. Thyrotoxicosis.
4. Addison's disease.
5. Vit-D intoxication, chronic granulomas (T.B., sarcoidosis)
due to secretion of a-1 hydroxylase enzyme.
b) Idiopathic: idiopathic hypercalcemia with Nephrocalcinosis.

3) t moblllzatlon from bone:

1. Hypercalcemia of malignancy: e.g. multiple myeloma & lymphoma 2ry to
a) Bone metastases.
b) Secretion of hypercalcemic substances as:
- PTH like - 1,25 DHCC like
- Interleukin 1 (ILi) - Tumor necrosis factor (TNF)
- Osteoclasts activating factor "OAF" especially in multiple myeloma

2. Prolonged immobilization: Heart Failure , fractures & post operative

4) ! calclum excretion by kidney:

1. Thiazides, lithium.
2. Familial hypocalciuric hypercalcemia:
- benign AD symptomless disease. - PTH level is normal.

71
 Treatment of hyperparathyroidism & hypercalcemia
I- Symptomatic treatment:
1. Decrease intake: avoid Ca in drugs or food (e.g. milk)
2. Decrease absorption: phosphate, Phytate.
3. Increase loss :
a) Fluids in excess to correct dehydration & wash out Ca in urine.
b) Frusemide diuretic (not Thiazides) - dialysis in severe cases.
c) Chelating agent:-
• EDTA - Oral cellulose PO4 15mg/day.
• IV PO4 infusion lower Ca rapidly by causing microscopic
precipitation of Ca phosphate in soft tissue (dangerous).

II- Hormone antagonism:

1- Precipitate in bone: Calcitonin IV amp. 10-25 ug/kg.
2- Hydrocortisone: (--Vit D action).
3- indomethacin : especially in malignancy (prevent PG. mediated Ca release from
bone).
4- Drugs inhibiting osteoclasts activity: of choice in hypercalcemia of malignancy.
- Bisphosphanate Pamidronate IV infusion (in hypercalcemic crisis).
- Mithramycin: cytotoxic drug-25 Ug/kg IV infusion.

III- Surgical:
surgical removal of parathyroid followed by Ca & Vit-D to prevent
tetany (Hungary bone syndrome).

Indications of sur,:ea
❖ Serum Ca more than 1 mg above the upper limit of normal
❖ 24 hour urine calcium: some still regard 24H Ca > 400 is indication for surgery
❖ Creatinine clearance less than 60 mg /min
❖ Age less than 50 years

72
 '

Hypocalcemia (Tetany)
Increased neuromuscular irritability due to decreased ionized Ca or Mg.

1-HYPOCALCAEM IA: (Quantitative defect)

A- Diminished Ca intake : starvation, dysphagia.

8- Diminished Ca absorption:
1. Hypoparathyrodism:

• Surgical removal.
• Autoimmune destruction.
• Goiter: diversion of blood supply to the enlarged thyroid gland.
• Di-George syndrome: congenital absence of thymus and parathyroid.
• Tetania neonatorum (intraglandular hemorrhage).
2. Deficiency of Vit D: rickets or osteomalacia.
3. Myx:edema, Panhypopituitirism ,Cushing.
4. Gastrectomy, atrophic gastritis, and gastric carcinoma.
5. Malabsorption syndrome.
C- Increased Ca loss in urine:
- Loop diuretics.
- Renal rickets.
- CRF (associated acidosis usually increases ionized Ca).
D- Increased Ca precipitation in tissues:
- In acute pancreatitis.
- Hungry bone syndrome following parathyroidectomy.
- Over treatment by Calcitonin, phosphate or Biphosphanate.
11-ALICALOSIS : J. ionized calcium "Qualitative defect"
- Respiratory: encephalitis lethregica, high altitudes, hysterical.
- Metabolic: vomiting, Conn's syndrome, diuretics.
- Citrated blood : in massive blood transfusion

73
111-M.4 DEFICIENCY:
• Excessive diuretics
• Malabsorption syndrome

a) Latent Tetany: {serum Ca 7-9 mg%)

- There are no spontaneous manifestations but it can be induced by provocative tests:
1- Chovestek's:
- Tapping of facial n. in front of the ear causes facial muscle
contraction.
- Tapping the peroneal nerve over the of fibula causes peroneal muscle '
contraction.
2- Trousseau's :
- Sphygmomanometer inflation above systolic pressure for 5 minutes • Carpal
spasm.
3- Erb's: - Current< 4mA causes muscle contraction (normally at least 8 mA).

b} Manifest Tetany (Ca <7 mg%)

1- Muscle spasm in the form of:

- Spasm of the facial muscle (risus sardonicus).
- Spasm of jaw (trismus).
- Spasm of larynx (Laryngismus stridulous).
- Spasm of the diaphragm (hiccough).
- Spasm of Wall of the urinary bladder (enuresis) or the sphincter (retention).
- Spasm of the back muscles (opithotonus).
- Carpopedal spasm, muscle twitches & conwlsions

74
 2- Effect on ectodermal structures:

- Nails: Loss of luster & brittle.

- Skin: desquamation, atrophy, roughness, alopecia, and monilial infection.
- Hair: Premature loss of hair.
- Lens: cataract.
- Teeth: Hypoplastic,transverse furrows and punctuate holes if the condition
develops before formation of permanent teeth.
- GIT: Malabsorption due to desquamation of GIT mucosa.
c) C/P of the cause: e.g. primary Hypoparathyrodism:
A. Calcification of basal ganglia • Parkinsonism.
B. Pseudotumor cerebri.

A) For Hypocalcemia:
• !Serum Ca: (N=9-1 mg%).
• tSerum P: (N=3-4.5 mg%) in Hypoparathyrodism.
• Urine: l Ca, lP+.
• Prolonged Q-T interval in ECG.
• of cause : high Parathormone level in all cases " due to feedback "other than
Hypoparathyrodism.

8) For alkalosis: -
- High blood pH.
- Normal total Ca & P, but low ionized Ca level.
C) For hypomagnesenemia:
- l serum Mg (N=l.7-2.4 mg%)+ Resistant Hypokalemia.

75
1. In acute attacks: Ca gluconate 10 ml (10 mg%) SLOWLY over 10 minutes.

2. Treatment of the cause

1) In hypocalcaemia:

- Oral Ca lactate 2 gm TDS.

- Active Vit D (1-25 DHCC, or 1-alpha HCC) 1 ug daily.
- Thiazides diuretics to decrease Ca excretion in urine.
2) In Alkalosis: treatment of the cause.
3) in hypomagnesaemia: oral Mg

76
 Introduction to diabetes mellitus
✓ What is insulin ?
• peptide hormone secreted from the B-cells of pancreas formed of 2 peptide chains
bound together with disulphide bound
• secreted as pro-insulin(Insulin+ C-peptide) the C-peptide split out to let the active
form.

✓ Action of Insulin : Mainly Metabolic action.

20
I. Carbohydrate: Glucose lowering effect through

- Increase glucose uptake :

- in skeletal muscles and adipose tissue (glucose transporter (GLUT 4).
- In liver (by increasing the activity of glucokinase enzyme).
No role on brain, lens, intestinal mucosa, RBCs, and kidney.
- Increase glycogenesis and inhibits glycogenolysis .
- Inhibits gluconeogenesis.

II. Fat: Anabolic Action through :

- Increase lipogenesis (excess glucose in converted into FFA).

- Inhibits lipolysis: inhibits hormone sensitive lipase enzyme in adipose tissue.
III. Protein:

❖ anabolic • Inhibits proteolysis and gluconeogenesis.

IV. Electrolytes: intracellular shift of K • ! K .

✓ Factors regulating it :

Stimulatory factors Inhibitory factors

- Glucose - CCk - Cortisol - GH
-AAS (Arginine, glycine} - Catecholamines
- Glucagon like peptide • Thyroxine
(From intestine) - Estrogen-progesterone
- Gastrin & Secretin

77
 Diabetes Mellitus
Definition :
It is a metabolic disorder of carbohydrate metabolism due to relative or absolute
insulin deficiency • hyperglycemia, glucosuria.

With secondary disturbance oflipid (lipolysis and ketosis) and protein metabolism
( catabolic = negative N2 balance).
Usually complicated with micro and macro•angiopathy.

~etiology : (lry, 2ry & Gestational )

1• Prl•• [Y DM : include 4 types.

• Type 1 DM (of old age)

• Type 2 DM (of young age)

• MODY (See below)
• LADA (see below)

❖ Mature onset diabetes In the young (MODY):

- Intermediate between type I & type II.

- Autosomal dominant. Almost occure around 50 Vs old

- Occurs in young obese patients.

- Treated by oral antidiabetic drugs.

- Associated by Chlorpropamide alcohol flush phenomenon due to release of VD

material as Pgs or encephallns.

❖ LADA : Latent Autoimmune Diabetes in Adults

2· Secondary DM:
❖ Pancreatic causes:
Chronic pancreatitis Cystic fibrosis
Pancreatectomy Heamochromatosis
Cancer body
• Fibrocalculus pancreatopathy (Chronic malnutrition)

78
 ❖ Endocrinal causes:
• Pheochromocytoma • Acromegaly
• Cushing • Gulcagonoma
• Thyrotoxicosis • Somatostatinoma
• Conn's syndrome Diazoxide causes Damage
❖
of pancreartic cells
Others:
- Drugs : Thiazides, Cortisol , diazoxide , COC Pills.
- Receptor defect :
• Down's, Klienfilter and Turner's syndromes.
• Fredreich's ataxia, myotonia congenital, Huntington's chorea.
• DID MOAD (DI, OM, Optic Atrophy & Deafness) syndrome.
- Liver cirrhosis. (.(l. insulin Resistance c> .(l. glycogenesis )

I• a..tatlonal DM;•
- It develops in 3% of pregnancies especially in 3 rd trimester.
- The insulin reserve is not sufficient in pregnancy.
- Glucose level return to normal few weeks after labor.
- 30-50% develop OM after 10-15 years.

- Placenta release substances that .JJ. insulin resistance.

Diagnosis of Gestational diabetes By one of the following :

1. Fasting blood sugar > 126 mg% .
2. Oral glucose tolerance test :
• Patient is screened at 25th week of pregnancy with 50 gm oral glucose.
• Suggested by blood glucose~ 140-150 mg% one hour after glucose ingestion.
• Oral glucose tolerance test: after 100 gm oral glucose:
• Fasting ~ 105 mg%
• 1st hour~ 190 mg%
• 2nd hour~ 165 mg%
• 3rd hour~ 145 mg%

79
 Type I DM
Juvenlle-lnsulln dependent
DM
5-15%
0.3%
<40 years
Chromosome 6-recessive
Thin
Insulinopenia
Ketolabile
Insulin
Type IA: Transient antibodies
(80%)
Type IB: Persistent antibodies
(20%)
In genetically predisposed patients
- (DLA- DR3 & DR4),
- infection by certain viruses
(Coxackie B4, mumps or
retroviruses)
- antibody against island cells.
Evidences of genetic predisposition
• 30% in identical twins
• Negative family history:-
2.5-5% in Child of diabetic father
1.25-5% in Child of diabetic
mother
• The islet cells are infiltrated by
lymphocytes with destruction of
islet cells
80
Type II DM
Maturity onset-Non Insulin
dependent DM
85%
3-5%
>40 years
Chromosome-11 multlfactorlal
Obese 80%-non obese 20%
Early increase-Late decrease
Diet - Oral drugs - Insulin
• Obese (mainly central) 80%:
may lead to insulin resistance by
adipocyte secretion of leptln,
resistin.
• Non-Obese 20%
Po sibilities:
• Insulin exhaustion
• Decreased insulin receptors
number or responsiveness.
• Dyshormonogenesls
• Incl'eased glucagon Evidences
of genetic predis :
• 100% in identical twins.
• highly positive family history:-
25% of patients have 1st degree
relative with type-II DM.
✓ The islet cells show deposition of
amyloid material (amylin) which
is co-secreted with insulin.
Clinical picture of DM : 6P + 2 sym

• Aum,ptomatic: in 1/3 of cases and accidentally diagnosed by blood sugar test.

• f olyurea: osmotic dieresis due to hyperglycemia (nocturnal enuresis in children)
• f olyphagia : with loss of body weight: defect in the satiety center or in Leptin.
• f olydepsia
• f ain and parasthesia secondary to peripheral neuritis.
• f remature loosening of teeth.
• .Blurred vision: due to osmotic swelling of lens.
• ,Sxmptoms of complication.

Stages of DM :

1) Pre diabetes : impaired glucose tolerance "IGT"

• between the normal and diagnostic values of OM (FBS:- 110-126 mg%)
• Potential DM : normal GTT with increased risk of DM as :
- Positive family history.
-Obesity.
- Renal glucosuria.
- Female with history of overweight baby.

2) Latent diabetes: Diabetes appears only on exposure to stress (e.g pregnancy).

3) Chemical diabetes ; Raised blood glucose with no symptoms.

4) Clinical diabetes (Overt): Symptoms of DM + hyperglycemia which may be

complicated or non-complicated.

.............................................................................
CRll'cRIA OF i>IAGNO&I& OF om @
1. Classical Symptoms of DM
2. Random Plasma Sugar~ 200 mg/di
3. Fasting Plasma Sugar~ 126
4. Postprandial glucose~ 200
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••

81
Investigations For a Case of DM :

!Hormonal level~
Plasma insulin level (N=20 McU/ml):
• if Type I DM -+! insulin level
• if type II DM -+ r insulin level early then ! later on

!Hormonal effect:!
a) Blood sugar test:
• fasting : >126 mg% ( N = 80-120 mg%).
• 2 Hours PP: >200 mg% ( N = <140 mg%).
NB: Plasma glucose level is higher than blood glucose level by 20% as plasma represents
60% of the whole blood.
b) Glucose tolerance test:
• Patient should be fasting (overnight).
• Fasting blood sugar is done (FBS).
• Bladder is emptied.
• The patient is fed 75 gm glucose orally, and blood sugar level and urine testing
for glucose is performed every 1/2 hr for 2 hrs.
• Diagnosis of diabetes is done according to the above mentioned criteria.
C) Corticosteroid-glucose tolerance test:
• Dexamethzone 3 mg is given before GIT,
• Patients with latent DM give a diabetic curve.
d) Urine analysis:
• Glucosuria: occurs when glucose serum level exceeds 160 mg %,
but it is not a good indicator for DM diagnosis or assessment of treatment. why?!
• Ketonuria: for diagnosis of diabetic Ketoacidosis.

P------------------------------
NB. Causes of Glucosuria
I ✓ Renal glucosuria : hereditary low renal threshold
I
I
1
I ✓
✓ Low storage curve (Alimentary glucosuria): late dumping$ & thyrotoxicosis I
1
I Stress hyperglycemia I
1 ✓ Reducing substances in urine e.g. vit C & salicylates I
------------------------------~ 82
!Other~
• C- peptide: reflecting endogenous level (islet cells activity).

• Investigations for secondary DM: e.g. Hormones level, LFTs.

• Investigations for complications: e.g. blood ketone level, KFTs, ECG.

I
~~----------------------------,
m
Glycosalated hemoglobin (Hb A 1c) for assessment of efficacy
\
I I
• Non enzymatic glycosalation of hemoglobin. I
I
I • Hb A 1 c is synthesized over the life of RB Cs in proportion to the degree of I
I I
glycemia.
r I
I • Gives an index of the blood glucose over the life of Hb molecule (2-3 months). I
I I
- Normally: it is less than 6%
I I
\ - if> 12% : Poor glycemic control in the past 3 months. J
' ~----------------------------~ ~

• Glycosated Albumin : but has more rapid turnover than Hb.

83
 Management of Diabetes mellitus
It. Diet control & Exersice :I
a- Indication;
1. Mild cases of type II DM.
2. Adjuvant treatment in other cases.

b- Method of Diet re~ulation:

i. Caloric requirements = ideal weight x activity :
Mild activity: 25-30 Cal/Kg/ d (about 1600-1800 cal/d).
Moderate activity : 30-35 Cal/kg/d (about 2400 calf d).
Over activity & pregnancy: 60 Cal/kg/d (about 3000 calfd).
ii. Food components:-
· CHO: 50%
• Avoid simple sugars (mono saccharides)
• Polysaccharides are absorbed slower with lower blood glucose peak.
• Avoid alcohol : high calories+ potentiates hypoglycemia of insulin & sulphonyl urea
+ potentiates lactoacidosis of biguanides
• Artificial Sweeteners could be used: aspartame (carcinogenic ?)
- Fats: 30%: Avoid saturated fats. Olive oil contain Omega 3 fatty acides
- Proteins: 20%. that protect from Atherosclerosis.

- Vitamins: Supply Vitamins: B complex & Vit A

- Fibers (non-absorbable polysaccharides e.g. bran) to delay glucose absorption and
form bulk to decrease appetite.
iii. Number of meals:
3 main meals + 2 snacks in between
c- Reduction of body weight by diet & Regular exercise

12. Drugs :I
Oral Anti-diabetic Drugs :
1. Sulfonyl Urea 2. Biguanides 3.Newdrugs

84
 pancrease. 2- Sensitize insulin receptors
2- Sensitize insulin receptors 3- Decrease glucose absorption from

3- Reduce glucose release by liver the gut

• Used alone in obese type II OM after

C:
0 • Type II OM not controlled by diet alone diet failure
~
n,
CJ
'0
• Combined with sulfonyl urea or
C: • MODYtype
insulin (obese)

1- Type I OM & history of OKA.

• Any acldotlc condition:
C:
C:
2- During pregnancy.
1· Renal impairment
-
...
(1l

C:
0
u
0
·.;:;
(1l
u
"O
3- Type II OM during stress: e.g. trauma,
operations, severe infection. 2- Lung impairment

1-Allergy (skin rash).

-
~
(/)

u
Cl)

Cl)
2- Hypoglycemia.
3- Cholestatic jaundice.
2- Metallic taste of mouth.
3- Anti vitamin 812 absorption.
4- Weight gain. (Due to polyphagia)
Cl)
:E 5- Chlorpropamlde: alcohol Intolerance. 4• Lactacidosis.
en
6- Aplastlc anemia.
7- Cardlomyopathy.

Sulfonyl Urea drues;

First generation
Pharmacological name

• Tolbutamide
• Acetohexamide
• Chlorporpamide
-----
Rastinon
Dimelor
Pamidine
6-12
8-24
24-72
0.5-2gm
0.25-1.5gm
0.1-0.5gm
(renal)
Second generation
• Glipizide Minidiab 6-12 2.5-30 mg
• Glicazide (liver) Diamicron 10-12 40-320mg
• Glibenclamide (renal) Daonil 10-20 2.5-15 mg
• Glimepride Amaryl 7-12 1-Smg

85
 ~ - New Drur:s:
1) Alpha Glucosidase inhibitors: Acarbose & glucobay .
Action ~Inhibits glucosidase enzyme on the brush border of intestine, thus
inhibiting carbohydrate absorption.
Side effects .;, flatulence & diarrhea - rarely liver dysfunction .
Dose ~50 mg TDS.
2) Glitazones: as Pioglitazone
insulin sensitizer, inhibits gluconeaogenesis and improve dyslipidemia.
S/E : liver impairment, fluid retention & mild edema and weight gain
CI : Hepatic, renal < heart filure
3) Glinides (non sulfonylurea secretagogues)
As Repaglinide (Novonorm) or Neteglinide :
Action : stimulate insulin production at meal time.
Dose: 0.50-1 mg before meals.
4) Dipeptidyl Peptidase-4 Inhibitors (DPP4) : Galvus - Januvia - Onglyza
Mechanism : inhibit DPP-4 Activity, increasing post-prandial active incretins and
glucose dependant active insulinotropic peptides
Advantages : well tolerated ,effective , no hypoglycemia
S/E: Urticaria, Angioedema & pancreatitis.
5) Na glucose transporter 2 inhibitors (ganagliflozin , dapagliflozin)
Mechanism: inhibit SGLT-2 in the proximal nephrons thus blocking glucose
reabsorption by kidney increasing glucosuria.
Advantage: No hypoglycemia, decrease weight ,Decrease BP, Lower CVD events
S/E: UTI, polyuria (hypotension) Increased LDL & decreased creatinine
6) Incretins mimetics (Exenatide)
• Used as adjunctive therapy with metformin or sulfonylurea
• Mechanism : Amplify glucose stimulated insulin secretion (GLP-1 agonist or
inhancing its activity)
• It also suppresses glucagon and slows gastric emptying
• Not used with insulin

86
 • S/E : nausea, vomiting and diarrhea
7) Amylino-mimetics : pramlintide
• Synthetic amylin analogue used in type 1 DM or type 2 requiring insulin
• It is injected with prandial insulin subcutaneously ( in conjunction with insulin)
• Mechanism : it decreases glucagon but doesn't alter insulin level.
• slows gastric emptying
• S/E: nausea, vomiting and frequent injection (3 times daily)

13· Insulin Treatment :I

✓ Indications;
1. TypeIDM.
2. Type II DM in special circumstances :
• Uncontrolled by diet or oral drugs.
• Pregnancy.
• Stress: infections, trauma, operations.
3. other indications :
• Treatment of Hyperkalemia.
• Test of growth hormone level.
• Insulin tolerance test in Panhypopituitirism.

✓ Types of insulin :
Regular insulin = uli.=.11 / ~ I / ~1_)1
1. Bovine insulin: obsolete (not used now). Intermediate Acting= _fo....11

2. Human insulin : by genetic engineering:

- Regular Insulin - Intermediate acting insulin .

Onset : begins within 30 minutes, Onset : begins within 2-4 hrs.
peaks : from 2-3 hrs Peaks : in 4 -12 hrs
Duration : last for 3-6 hrs. Duration : effective for 12-18 hours.
Types: Humulin R, Novolin R Types: NPH (Humulin N, Novolin N).

87
3. Insulin analogue : Synthetic-made insulin like :

- Rapid-acting - Long-acting
Onset : begins after 15 minutes, Onset :
peaks : in 1 hr and last for 2-4 hrs. Duration : lasts for 24-hour period.
Types:
Types :
• Insulin detemir (Levemir)
• Insulin glulisine (Apidra) • insulin glargine (Lantus) .
• insulin lispro (Humalog)
• insulin aspart (NovoLog)
N.Bl'. : Biphasic (mixture) formed of Short + long Types :- Rapitard, Mixtard, initard
N.82 : Oral insulin and Intra nasal insulin are now Used.

o Dose of Insulin :
A. Conventional method:
1. Start with 10 units regular insulin before every meal and monitor blood sugar
before and after meals to adjust insulin dose accordingly.
• Calculate the total daily dose. Alternatively start by 10-20 U/day in normal weight
individuals, and 25-30 U/day in obese ones.
2. Give mixed insulin (Mixtard) once in the morning.
3. Poorly controlled patients should be placed on twice daily insulin injections with
2/3 of the total dose before breakfast and 1/3 before supper.
4. Modify the dose as follows:
o Day time hyperglycemia is an indication to increase morning dose.
o Bed time & breakfast hyperglycemia is an indication to increase evening dose.
B. Multiple subcutaneous insulin injection:
1. Administration of 25% of the daily dose as intermediate insulin before sleeping.
2. 75% of the dose is given as regular insulin 30 min before meals (3 doses).
C. Infusion devices (pumps): continuous subcutaneous insulin infusion (CSU):
• Small pump is strapped around the waist.

88
 • Insulin is delivered at a basal rate continuously throughout the day via a needle in
the subcutaneous tissue of the abdominal wall.
• The patient can deliver meal time doses by touching a button on the machine.

✓ Compllcatlons of Insulin :
1. Hypoglycemia & hypoglycemic coma.
2. Smoggy effect :
• nocturnal hypoglycemia (resulting in night sweats, night mares, lassitude and
morning headache) which causes rebound morning hyperglycemia
• treatment is by reducing night doses.
3. Eleven O'clock hyperglycemia: due to high level of cortisol.
treatment by : increasing dose of neutral insulin before breakfast + mid day light snack.

4. Blurring of vision: osmotic changes of lens.

5. Acute neuropathy: may occur paradoxically with controlling hyperglycemia by
insulin.
6. Insulin oedema: mild LL edema (salt & water retention)

7. Weight gain : insulin is anabolic hormone

8. Insulin lipodystrophy:
• Insulin lipoatrophy: Autoimmune reaction to non- human insulin
• Insulin lipohypertrophy: lipogenic effect of insulin
9. Allergy: use human insulin
10. Insulin resistance: defined as daily requirements > 200 lU due to:
• Obesity: commonest cause for mild resistance.
• Antibodies against insulin receptors: as in acanthosis Nigricans.

89
 Conclusion of treatment of diabetes

A. Treatment of type 1 QM ;
1. Diet
2. Oral Hypoglycemic
3. Insulin therapy (if the initial Oral hypoglycemic drugs are not effective)
4. Interventions in prediabetic stage : ( +ve antibodies)
• Neonatal and early infancy deprivation of cow milk.
• Immunosuppression by cyclosporine or azathioprin ??
• Antioxidants.
B. Treatment of type 2 PM ;
1. Diet: as mentioned but with targeting weight reduction in obese patients.
2. Oral hypoglycemic: in patients not controlled by diet alone.
3. Insulin: Used in lry failure (no control by oral drugs) or 2ry failure (initial response to
oral therapy followed by failure).
• Because of insulin resistance, higher doses than type I may be required.
4. Prevention of type II:

• Indicated in patients with strong family history of DM or those with impaired

glucose tolerance.
• Metformin, ramipril and parvastatin may be helpful in delaying DM.
• Diet control and exercise.
,, ,----------------------------------------------------------------, ...
I
I ' '\
I I
I I

I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
\ I

'' ,, ________________________________________________________________ , , , I

90
 Complications of Diabetes MelHtus
1. Acute diabetic complications : hypoglycemia, DKA, hyperosmolar hyperglycemic
nonketotic state and lactic acidosis ............. etc.
2. Chronic diabetic complications : it is mostly due to vasculopathy
• Microangiopathy : retinopathy, nephropathy, neuropathy .......... etc.
• Macroangiopathy : cardiovascular, cerebrovascular , peripheral vascular ds ..... etc.

PATHOGENESIS OF CHRONIC DIABETIC COMPLICATIONS :

Top Ten
I· Neurolog1Cal
A) CARBOHYDRATES ti- Ocular
1. Glucosuria: if it exceeds renal threshold " polyurea with washing of H20 Ill - CVS
IV - Respiratory
soluble materials e.g. vitamins. V- GIT
VI- Urinary
2. Glucose toxicity: VII - Gen ital
VIII Cutan eo us
i. Hyperglycemia : impaires the function of P-cells and the action of IX - Foot
X· BrittlP OM
insulin on the peripheral tissue "further rise in glucose level.
ii. Polyol pathway "Sorbitol theory" :
Activation of polyol pathway: glucose reduction to sorbitol by aldose reductase
"sorbitol exerts osmotic effect " cell injury in nerves, lens, kidneys, & BVs.
iii. Glycosylation of:-
• Proteins and collagen : this will affect Hb, plasma proteins, BVs wall, lipids
(become more atherogenic).
• Collagen of capillaries --+ narrowing of their lumens with increased vascular
stiffness and permeability.
8 ) LIPID :
• Release of fatty acids from adipose tissue " deposition in the liver "fatty liver.
• Formation of ketone bodies (as a source of energy) which is toxic

C) PROTEIN!

• as amino acids converted to glucose (-ve nitrogen balance) & muscle wasting.
D) OTHER MECHANISMS :
.0,, RBCs deformability, platelets aggregation, .(). fibrinolysis and hyperlipedmia.

91
 1- Neurological complications:
1) Cerebral Complications :

I. Hypoglycemia
II. Diabetic Ketoacidosis "OKA"

Ill. Hyperglycemic Hyperosmolar Non Ketotic

IV. Diabetic Lactacidosis

v. Diabetic Nephropathy (CRF & coma)

VI. Cerebral Atherosclerosis : Long term complication Common in diabetics & may
end in coma
2) Spinal Cord Complications.

• Amyotrophic lateral sclerosis.

• Anterior spinal artery occlusion.
3) Diabetic Neuropathy.

I-Hypoglycemia & Hypoglycemic Coma

jc auses :I
• Commonest: missed meal after insulin or oral anti-diabetics.
• Others: brittle "early" DM.
• Severe exercise
• poor drug elimination

• renal or liver failure.

• Factitious.
• Unrecognized other endocrine disorders e.g. Addison disease.

• Gastroparesis.

~linical picture :I
t} Neuraglycapenic symptmns;
1. Rapid fall of glucose lead to convulsions then coma
2. Gradual fall of glucose will lead to headache, confusion and end in coma

92
 2) Premonitory (adrenerwc t warnin&) symptoms i
• tachycardia, palpitation, tremors, anxiety, sweating, pallor and fatigue.
3} Nocturnal hypo.:Iycemia:
• night mares, morning lack of concentration, hallucination, parasthesia.
4) Hypoglycemia may be asymptomatic.

~reatment :I
- Concentrated glucose 50% - 50 cc IV - followed by 10% infusion.
- IV or IM glucagon 1 mg.
- Oral glucose in early cases.
- Treatment of cause (close observation is needed in patients with long acting
insulin or oral hypoglycemic drugs and need close observation.

W Differential Diagnosis of hypoglycemia :

Glucose thresholds for hypoglycemia induced symptoms vary widely. accordingly the
diagnosis depends on presence of Whipple triad:

• Symptoms of hypoglycemia.
• Low blood glucose level.
• Improvement of symptoms by glucose.

1) Enclocrlnal causes:

A) Hyperinsulinism due to :

1- Reactive hypoglycemia (Alimentary hypoglycemia):

following gastrectomy (dumping syndrome) rapid glucose absorption leads to
excessive insulin release.
2- Therapeutic: over treated DM either by insulin or sulphonylurea.

93
J.ndoc"Cino.

3- Early diabetics: Excessive release of insulin after a carbohydrate diet.

4- Insulinoma.
5- Paramalignant:- produce Insulin like growth factor-I (IGF-1).
B) Decreased Anti-insulins:
Addison's disease, Simmond's disease, myxedema.

Z) Non•endocrlnal causes:
1- Deficient CHO intake: starvation & malnutrition, ethanol, anorexia nervosa,
obstructive gut lesions.
2- Defect in absorption:
• After Gastrectomy, gastrojujenostomy (late dumping syndrome).
• Malabsorption syndrome.
3- Defective storage: liver cirrhosis, glycogen storage diseases.

4- Increased glucose breakdown: exercise, pregnancy, malignancy.

5- Increase renal glucose loss: renal glucosuria, de Toni-Fancom syndrome.

6- Idiopathic post prandial hypoglycemia.

N.B. Post prandial hypoglycemia:

Reactive hypoglycemia - Early diabetes - ethanol induced ... While other causes are fasting
hypoglycemia.

94
 2-Diabetic Ketoacidosis OKA

I
jD efinition Potentially life-threatening complication of DM characterized by triad of
(Hyperglycemia - Acidosis - Ketosis.)
/c auses :I
• Neglected treatment.
• Severe exertion or stress
• steroid therapy or infection.
• Tissue damage:
✓ trauma, operation, burns,
✓ shock, stroke, myocardial infarction.
✓ Pregnancy, labor & lactation.

jP athogenesis :I
Diabetic Ketoacidosis
1- Glucose can't inter muscles & fat cells in absence of

'
insulin • hyperglycemia & glucosuria .
Muscle cell

2- Glucosuria leads to :
severe polyuria & polydepsia Resulting in :
'\Fatty
• dehydration with dry inelastic skin. acid
......,._,...,
• sunken eyes, thirst. &..

• low BP & low temperature.

3- Fat is mobilized for energy production leading to

excess production of ketone bodies
(acetoacetic & B - hydroxybuteric acids) with
ketosis, ketonemia & Ketonuria.

4- Shift of K+ outside cells (in absence of insulin)

which is then lost in urine.
NB: KetONE bodies Are seen in type ONE diabetes.
Increased ketone and
glucose In bloodstream

95
~ finical pictur~ • Effects of ketosis:

a. Muscles: generalized weakness & muscle pain due to absence of energy.

b. Kidney: Ketonuria, together with glucosuria

c. GIT: -.. "'""''•• ·u~

\ ,....
✓ acute abdomen "epigastric pain, 1...
.. I
✓ nausea, vomiting , constipation,
✓ hematemesis " this is due to ketone
bodies in stomach mucosa.
'- \ i...-..
ti~1-~,;,;::-1
At,d,,,n

d. Respiration: I HHS

deep rapid Kussmaul breathing " air hunger" with acetone breath .
e. CVS: depressed contractility, with peripheral VD.
f. End stage: collapse & coma due to acidosis, ketosis, dehydration & electrolyte
imbalance.

!Investigations ~

• Hyperglycemia & ketonemia. • glucosuria (4 +) .

• Acidosis (-- plasma HC03). • Ketonuria.
• dehydration (++PCV) . • polyurea
• ++ FFA&TG.
• ++ K (extracellular shift).
• ++ Na (Dehydration).

~ omplications :I

a) Cerebral oedema: due to rapid reduction of blood glucose.

b) Acute Respiratory Distress Syndrome.
c) DIC & Thrombo-embolism.
d) Serious infections e.g. mucormycosis.
e) Acute circulatory failure.

96
~ reatment :I
1. Hospitalization and ordinary care of comatosed
2. Estimation of :
- Blood glucose - urine glucose - Urine Acetone
- blood urea nitrogen - Serum creatinine - serum electrolytes (Na & K) -
- ABG - ECG

3. Fluid replacement;
• Saline (0.9%) .5 Lover 15 min repeated 2 times • 0.5 L/30 min • 0.5 L/1 hr
• 0.5 L/2 hrs till HR & BP return normal.
• Once blood sugar drops below 200 mg%: Replace by 5% glucose (lL /4-6 h)
to avoid hypoglycemia.
N.B: Average fluid deficit 6 L (3L extracellular+ 3L intracellular).
N.B : If plasma Na> 155 mg%, give saline 0.45% till Na falls to 140 mg%.
NB : Correction of dehydration and shock allows maintainance of renal blood flow to preserve kidney
functions , decrease associated acidosis and decrease blood glucose

4. Regular insulin_"low dose regimen" :

0.1 U/kg/hr continuous infusion (6 units/hr) m: deep IM.

Follow up by blood sugar every hour & give further insulin according to it.
5. Treatment of acidosis:
main points of DkA m
in severe case (PH< 7.1, HCO3 < 12 mEq)
1- Fluids (Crystalloids)
we give 1/2 -1 L of 1/6 molar NaHCO3 IV.
2- Urea (check it)
6. Correct plasma K level. 3- Creatinine (check it) &
Catheterization
- Hyperkalemia is present at first due to extracellular shift.
4- B + (Potassium)
- Hypokalemia occurs with insulin ttt due to intracellular shift: 5- Insulin (Su /Hour)
• lfK < 3.5 mg% : add 20 ml KCI (40 mEq) to 6- Nasogastric tube
7- Glucose (If Sr.level drops)
each 1L of fluid given.
• If K 3.5-5. Mg%: add 10ml KCI (20 mEq) to each 1 L of fluid given.
• lfK > 5.5 mg% : add no KCI.
7. Others:

• Correct cause & precipitating factors.

97
 • Prophylactic antibiotics.
Nasogastric tube : to aspirate gastric content in cases with severe vomiting.
Heparin IV: in old & dehydrated patients to guard against DIC.
• 02 : if p02 < 80 mmHg.
8. Every hour do assessment & clinically re-estimate the condition and repeat laboratory

tests to direct therapy accordingly

lcomplications during treatment of DKAj

1- Hypoglycemia : prevented by monitoring Blood gluose during therapy and a
replacing salin by glucose 5% once glucose level drops to 250 mg/di
2- Hypervolemia : prevent by monitoring CVP
3- Hypokalemia : Add kcl with insulin
4- Rebound cerebral edema : due to rapid drop of glucose level with consequent
reduction of plasma osmolarity resulting in fluid shift intra cellularly so decrease
glucose gradually.
5- CNS acidosis : add NaHCO3 in severe acidosis

98
 3-Hyperglycemic Hyperosmolar Non Ketotic Coma

Acute life threatening complication of OM in old neglected patients especially those who are
consuming excessive glucose containing diet , steroids or thiazides and usually predisposed
by intercurrent illness

\causes :I
it occurs in old type II DM due to :
• Absence of fat reserve or fat mobilization ( relative lack of GH or Cortisol).
• Insensitive thirsty center lead to dehydration aggravated by use of diuretics.
• Precipitating factors : infection, infarction.

\clinical picture :I
- Severe hyperglycemia :
• often > 900 mg%.
• severe dehydration (with marked++ PCV, ++Na).
- No ketosis.
- Pre-renal uremia may occur due to dehydration.
- Neurologic symptoms : convulsions, hemiparesis.
Stupor & coma occur when serum osmolarity is > 340 mosm/L (normal 290 mosm/L).

/Treatment :I as OKA
1. Fluids: 1/2 normal saline lL/hour not faster to avoid cerebral edema.

2. Insulin: smaller amount than Ketoacidosis.

3. Heparin : since there is ++ incidence of DIC.

,,

99
 Diabetic Neuropathy

!Pathogenesis :I
- Microangiopathy: due to ischemia of vasa nervosa.
- Macroangiopathy: 2ry to atherosclerosis.
- Hypovitaminosis: Polyurea wash water soluble Vit B complex
- Metabolic ketosis: toxic effect of ketones bodies.
- Transformation of glucose to sorbitol : by aldose reductase
enzyme (polyol pathway).

!Clinical picture :I
1. Features of PN : may precede the discovery of DM.
2. Starts as Mononeuropathy or mononeuritis multiplex :
a. Peripheral.N : sciatic, femoral, ulnar, median
b. Cranial N.: optic neuritis, 3,4,6 palsy, facial palsy, Argyl-Robertson pupil

3. Polyneuropathy:
a. Mainly sensory: early tender calf, paresthesia, later on stock & glove hyposthesia
occur.
b. Early loss of deep sensations: vibration sense, lost muscle sense "pseudotabes"
c. Motor weakness is late and rare.
4. Autonomic neuropathy:
a) CVS: - Postural hypotension (orthostatic syncope).
- Tachycardia & fixed H.R.
- Silent myocardial infarction.
b) Chest: respiratory arrest (unknown cause).
c) Genito-urinary: - Impotence (Neuorogenic -vasogenic - psychogenic).

- Bladder (sensory, motor, autonomic bladder).

d) GIT: - Delayed gastric emptying, with indigestion (gastroparesis diabeticorum).

100
 - Early nocturnal diarrhea, stagnant. Loop syndrome, late constipation.

e) Skin: - hyper-hydrosis or anhydrosis

- VD (with edema) or VC.

f) Trophic changes: ulcers, rough Nail, loss of hair, tapering of finger, Charcot's
neuropathic joint.

~reatment :I
1. Strict control of DM : diet, oral hypoglycemic, better insulin.
2. Physiotherapy : for muscle weakness.
3. Drugs:
a) Vasodilators: nicotinic acid, nifedipine.
b) Anti-platelets: aspirin, diopyridamol.
c) Capillary modulators: Ca dobesilate (Doxium).
d) Vitamins: BI, B6, B12-ATP (adenoplex).
e) Analgesics: aspirin, Carbamazepin (Tegretol).
f) Aldose reductase inhibitor: Sorbinil

4- Diabetic Lactoacidosis

✓ Patient is usually Diabetic patients taking biguanides.

✓ Precipitating factors : pneumonia, myocardial infarction (ischaemia).
✓ Clinical Picture : as of acidosis i.e. Kussmaul respiration - late CNS, CVS inhibition.
✓ Treatment: as acidosis • NaHC03 + insulin - glucose combination.

HHNK Lactic acidosis

- Hyperglycemia . Hyperglycemia(>600mg/dl). high Severe acidosis pH < 7 .3 H2CO3 < 15

- Acidosis (pH< 7.3). serum osmolarity. meq/l.

- H2CO3 < 15 meq/L. No acidosis (pH> 7.3). No ketones.

- Positive ketones. No ketones. Serum lactate > 5 mmol/L.

101
 2- Occular Complications
jclinical picture :I
1) Lid: blepharitis, stye, xanthelasma (from hypercholesterolemia)
2) Conjunctiva: conjunctivitis.
3) Pupil : Argyll Robertson pupil - Horner's syndrome.
4) Ocular muscles: external ophthalmoplegia (3,4,6 palsy).
5) Iris: Rubeosis iridis (vascularization ending in glaucoma).
6) Lens : errors of refraction - diabetic cataract.
7) Macola: macuelopathy, macular edema which may end in loss of vision.
8) Optic nerve: retro bulbar neuritis ending in optic atrophy.
9) Retina : "diabetic retinopathy"
❖ Pathogenesis of Retinal Diseases :
• DM causes increased thickness of capillary basement membrane with increased
permeability.
• Aneurismal dilatation may occur in some vessels while others become occluded
• Chronic retinal hypoxia may lead to neovascularisation and increased vascular
permeability. (Especially in type I DM of long duration). diai~~!i~~~~:;athy
❖ Types
• Proliferative: neo-vasculatures: this will lead to
hemorrhage and retinal detachment.
• Non-proliferative: micro aneurysms, hemorrhages,
Growth of abnormal
exudates (benign form) blood vessels

Non•proliferative
❖ Treatment: diabetic retinopathy

• Strict diabetic control with insulin .

• Photocoagulation by laser to destroy new vessels.
• Viteroretinal surgery:
- Remove vitreous hemorrhage
- repair detached retina.
• Calcium dobesilate "doxium" regulates capillary Hard
exudate
permeability & neovascularistion.

102
 3- CVS Manifestations
)Pathological changes & clinical Picture : I See sorbitol theory for pathogenesis

1. Microangiopathy: retinal, renal, vasa nervosa.

2. Macroangiopathy: due to atherosclerosis •
a. Cerebral: thrombosis, ischemia.
b. Coronary: angina, Ml, arrhythmia. Recently coronary microangiopathy is
described.
c. Peripheral: intermittent claudication, gangrene.
d. Renal: renovasular hypertension, due to renal artery atherosclerosis.
3. Cardiac: cardiomyopathy, probably due microangiopathy.
4. Blood pressure:
a. Hypertension.
b. Hypotension: postural (autonomic neuropathy).

~ reatment :I
1. Treatment of hypertension:
• Avoid thiazides: they are hyperglycemic.
• Avoid non selective B-Blocker: mask warning symptoms of hyperglycemia.
• Best drugs : ACEI , Angiotensin II blockers , Ca channel blockers.
2. Treatment of hyperlipidemia:
• low fat in diet, polyunsatutated oils , hypocholestrolemic drugs.
3. Stop cigarettes: risk of microangiopathy & coronary heart disease.

4- Respiratory Complications
• Pulmonary infection especially TB (TB follows OM as its shadow).

• Dyspnea, air hunger (Kussmaul respiration), acetone odor during ketosis.

103
 5- Urinary Complications
1. Infections : cystitis, pyelonephritis esp necrotizing paoillitis.

2. Neurogenic bladder: sensory atonic bladder.

3. Stones : from stasis & recurrent infection.

4. Diabetic nephropathy : see below .

Diabetic Nephropathy
• Can be differentiated into : glomerular injury and interstitial injury

1- GLOMERULAR INJURY: DIABETIC GLOMERULOSCLEROSIS

Aetlology:
- Long standing DM (type I, type II) especially poor controlled.
- Onset within 10-20 years.
- High correlation occur with diabetic retinopathy & diabetic neuropathy.

Pathol9,JIY_J 2 types

1) Nodular glomerulosclerosis: ("Kimmelesteil-Wilsons" syndrome)

• 25% of cases.
• Thickening of BM due to muco-polysaccharide nodules deposition in between &
inside glomeruli.
• Microaneurysms of small blood vessels, hyalinization of afferent arterioles.
2) Diffuse glomerulosclerosis:
• 75% of cases.
• Diffuse thickening of BM (in absence of nodules)+ interstitial atrophy.
• Hyalinization of afferent & efferent arterioles with atherosclerotic changes.

104
 jclinical Picture :J
- Onset: asymptomatic proteinuria " micro albuminuria" .
- Later on: frankproteinuria occur, which may extend to the classic nephrotic syndrome.
- Renovascular hypertension.
- Years later: the picture of CRF supervenes.

NB: Deterioration of renal functions and acute renal failure can develop in patients having diabetic
nephropathy with :
- Some drugs as: NAS/Ds And Aminoglycosided
- After injection of radiocontrast dye for diagnostic study so adequate hydration before and after the
procedure is very necessary

jclinical Stages :I
Urinary albumin
Stages Clinical terms Histological features GFR& BP
excretion
Glomerular hypertrophy May be increased
Stage 1
Normal BP
Thickening of glomerular Normal or less Normal or 1' GFR
Stage 2 basement membrane and than 30-300 Normal BP
mesangial expansion mg/d
Further Thickening of 30-300 mg/d GFR begins to fall
glomerular basement Normal or 1' BP
Stage 3
membrane and mesangial
expansion
Diffuse or nodular More than 300 Gradual .J., of GFR
Stage 4
glomerulosclerosis mg/d 1' BP
End stage renal Glomerular closure and Decreasing GFR less than 15
Stage 5
absolescence ml/min - 1' BP

!Investigations :I
- Of DM : see above .

- Urine Analysis :
• Earliest: there is microalbuminuria by radio-immunoassay of urine (dipstick is
less accurate).
• Late: frank proteinuria with hyaline & granular casts.
- Renal function test: late rise in urea, creatinine.

105
!Treatment :I
a) Strict control of OM:
• we may use multiple SC insulin injection, but with l in insulin dose (insulin
being metabolized in kidney).
b) Strict control of hypertension:
• Best is ACE inhibitors as "captopril" or ARB II as Losartan.
c) Control ofnephropathy
1. In early stages ( no micro -albuminuria)
Routine screening for asymptomatic UTI and bladder dysfunction
2. In micro-albuminuria
Only control af DM an HTN are sufficient especially with ACEis or ARBs
3. In overt nephropathy (Macro-albuminuria)
• Aggressive control of DM & HTN delays and slows the progression
• Deitary protein restriction .8 gm/kg
• Symptomatic control
4. End stage renal disease
• The decision between dialysis & renal transplantation should be indivisualised :
✓ Renal transplantation represents the treatment of choice for most young
patients (pancreatic transplantation is also done in association of renal
transplantation.)
✓ Most older type 2 patients are offered dialysis.

2- INTERSTITIAL INJURY "INTERSTITIAL NEPHROPATHY"

A. Ischemic injury; interstitial injury leads to :
Diminished GRF.
✓ Renovascular hypertension.
✓ RTA (hyporeninemic hypoladosteronism) with hyperkalemia,
hyperchloremic acidosis & hypertension.
B. Acute pyelonephritis.
C. Acute necrotizing papillitis. (Seenephrologybook)

106
 6- Genital complications:
1- M, .. :
- Impotence together with lost deep testicular pain, due to autonomic neuropathy.
- Intact testicular sensation indicates psychogenic impotence.
z. ...... :
-Menorrhagia - Pruritus vulvae - Sterility
J. Pl•bett• with 1mnancy;
✓ Effects of pregnancy on DM:
1. 'fr Needs for insulin due to anti-insulin (estrogen, progesterone, lactogenic H.)

2. .JJ. Renal threshold for glucose (lost in urine).

3. 'fr Incidence of complications e.g. nephropathy.
✓ Effects of DM on pregnancy:
A Maternal:
• Abortion • Puerperal sepsis • Pre-eclampsia
• Premature labor • Post partum hemorrhage
6 Baby:
• High birth weight "macrosomia"
• .JJ. Incidence of neonatal death
• Hypoglycemic baby ( overactive pancreas)
• Congenital anomalies esp. anencephaly.
• Hyaline membrane disease ( .JJ.surfactant) RDS

a- MANAGEMENT OF nm t)lfll PREGNANCf ;

1- Monitor DM frequently : by blood glucose monitoring
2- Both types are treated with insulin and avoid oral hypoglycemic
they are teratogenic and cause fetal B cell hypertrophy, hence tendency of macrosomia.
3- Keep fasting blood glucose at: 110 mg% & 2h PP below 150mg.
4- Avoid weight gain .
5- Hospitalization at 36-38 weeks.
6- Discontinue insulin after labor & shift to oral drugs. -

107
 7- Skin complications :
1) Recurrent Infections:
• carbuncle, furuncle , abscesses, cellutitis,
• fungal infections.

2) Delayed healing of wound

3) Pruritus: Pruritus vulvae

4) Necrobiosis lipoidica diabeHcorum:

• Painful violaceous plaque with central yellowish area surrounded by brownish
border, usually on shin ofleg (cutaneous B1,vessels occlusion) Central ulcaeration,
healing by scar.

5) Diabetic dermopathy "spotted leg syndrome" :

• Painless reddish pa pules usually over shins of tibia, may heal leaving scar &
pigmentation.

6) Bullosis diabeticorum: superficial bullae, with clear serum which may be hemorrhagic.

7) Granuloma annulare: pa pules arranged in ring, with depressed center, over extensor
surface of fingers.

8) Xanthomata & xanthelasma: due to hyperlipidemia.

9) Caroteinemla:

• defect conversion of carotene to vitamin A in liver+ excess vegetable intake.

10) Complications of insulin Ht: lipoatrophy & lipohypertrophy

Try to identify each of these lesions from the description Above©

108
 8- foot complications :
1- lschemla:
• Acute: pain, pallor and cyanosis ending in gangrene.
• Chronic: -0- skin temp, loss of hair, Trophic ulcers, loss of distal pulse.

2- Neuropathy:
• Trophic ulcers: over pressure points.
• Neuropathic joint: Charcot's joint(painless, deformed & hyper mobile).

3- lnftc;llons: fungal & bacterial infections are due to:

• Suppressed immunity.
• Microangiopathy with ischemia.
• Hyperglycemia in tissue.

iTreatment :
a) Control of diabetes.

b) Foot care & hygiene: Repeated wash, drying, powdering, cutting toenail straight to
avoid in growing toenails.
c) For infection: antibiotics, drainage of pus, excision of infected tissue & bone.

d) For ischemia: revascularization or amputation in gangrene.

DIABETI C FooT Sore ankles

Ulcer

109
 9- GIT Complications
1. Mouth : inflamed gums, dental caries, loose teeth, red glazed tongue.
2. Stomach:
- Dyspepsia : due to hypochlorhydria, and autonomic neuropathy.
- In ketosis : pain, nausea, vomiting, hematemesis.
3. Intestine : autonomic neuropathy leads to nocturnal diarrhea & stagnant loop syndrome.
4. Liver :
- Fatty infiltration.
- Tender during ketosis due to glycogen depletion.
5. Gall bladder : chronic non-calcular cholecystitis due to hyperlipedmia and hypomotility

10- Brlttle DM
• Unpredictable fluctuations of blood glucose with recurrent attack of
hyperglycemia and/ or hypoglycemia.

1) Causes of recurrent hypoglycemia:

1. Over treatment by insulin. 2. Renal failure.
3. Uncooperative patient. 4. Low renal threshold.
5. Other hidden endocrinal problems e.g. pituitary or adrenal insufficiency.
6. Gastroparesis: may lead to difficulty in matching the time of food absorption to that of
insulin peak.
2) Causes of recurrent hyperglycemia:
• Inappropriate insulin dose
• Inter-current illness e.g. infection.

Treatment :
1. Revision of treatment schedule 2. Insulin pump
3. Patient education.

110
 PANCREAllC ENl>l>CRINAL l<AMC>R&
Endocrine tumours of the pancreas arise from the APUD (Amine precursor uptake and

decarboxylation) cells. They may occur with other endocrine tumors as a part of MEN.

GLUCAGONOMAS
8 Arise from P-cells and secrete glucagon.

A C/P: OM and abdominal rash

GA&lRINfJMA (ZfJLLINGER-ELLl&IJN &f}Nl>RtJME)

Definition :
• Tumor arise within the" gastrinoma triangle" formed by porta hepatis, neck of
the pancreas and the third portion of the duodenum.
• The tumor secretes large amount of gastrin that stimulates acid secretion.

Clinical Picture :

- Peptic ulcer: tend to be large, difficult to treat and recur rapidly.

- Malabsorbtion and diarrhea
- high HCL : inactivates pancreatic juice.

Investigations :

• Endoscopy: huge or multiple peptic ulcers± watermelon stomach

• High HCL.
• Secretin test: IV secretin (2u/Kg) produces rise in serum gastrin > 200 pg/ml
• High fasting serum gastrin level(> 150 pg/ml)
• CT, MRI, in Indium-labeled octreotide scintigraphy, angiography and portal venous

sampling of gastrin to l*ocalize the tumor.

Treatment:
- Surgical removal of the tumor.

- Metastatic tumors are treated by Omeprazole or chemotherapy.

111
 lnsullnoma
Clinical Picture ;
• 95% benign.
• The main presentation is fasting hypoglycemia.
• May be psychiatric manifestation (bizarre behavior, amnesia & automatism).
• Focal neurological manifestations may occur.

Diaa::uosis;
• is based on fulfilling the whipple triad:
Symptoms of hypoglycemia with fasting or exercise.
Low blood glucose level when symptoms are present.
Symptoms are relieved by glucose administration.
InvestiKations :
- FBS and insulin: (3 occasions) hypoglycemia with high insulin level(> 5
mU/L).

- High proinsulin serum level .

- High level of c-peptide .

- CT, MRI, Indium-labeled Octreotide scintigraphy, angiography and portal

venous sampling to localize the tumor site.
Treatment;
• Surgical removal of the tumor
• For inoperable tumors : diazoxide or octeotride may suppress insulin secretion.

- Arise from D-cells.

- C/P:- OM, steatorrhoea, and weight loss.

112
 • symptoms do not appear by age 13 for girls and age 14 for boys.
• Typically girls present at age 16 years or later because of primary amenorrhea.
• but young boys present because of failure to initiate pubertal development.
IN GIRLS
• Absence of any secondary sex characteristics byage of 13
• Failure to menstruate by age of 15
• More than five years to complete geneital enlargement
IN BOYS
• Lack of testicular enlargement by age of 15
• Lack of pubic hair by Age of 15
• More than 5 years to complete the genital enlargement.

Causes of delayed pube

1. Constitutional and idiopathic (Commonest)

• Development is slower than expected but complete development eventually occure.

• It runs in families and diagnosed by exclusion of other causes of delayed puberty.
• Short child but normal adult
2. Abnormal anatomy of the genital tract
3. Hyergonadotropic hypogonadism:
- Gonadal dysgenesis (turner or down $) , Ovarian or testicular failure.
4. Hypogonadotropic hypogonadism :
- Isolated gonadotropin deficiency
- idiopathic hypopituitarism
- neoplasm of hypothalamic pituitary axis (craniopharyngioma )
5. Chromosomal abnormality : turner or down syndromes
6. Chronic diseases :
thalassemia major, chronic renal failure , malabsorption $ ,.,,,,,
7. Endocrinal disorders : hypothyroidism & cushing ......

113
• Early and progressive sexual development with advancement of skeletal maturation as
measured by bone age.
• It is defined as appearance of any signs of 2ry sexual maturation in boys younger than 9
years and in girls younger than 8 years.

MANIFESTATIONS
o Early increase in growth velocity resulting on tall stature but rapid bone maturation
causes cessation of linear growth • short adult.
o Emotional distress • early appearance of breasts & menses in girls and increases
lipido in boys
o Contrasexual physical development : Girls with congenital adrenal hyperplasia or
with androgen secreting ovarian tumor.
1- lsosexual precocity

- signs of premature sexual development consistent with phenotypic sex.

Central precocious puberty CPP Peripheral p. puberty PPP

Gonadotropin dependant Gonadotropin independent
,. premature activation of • Increased production of sex steroids &

Mech.
I hypothalamic pituitary gonadal axis androgens from adrenal gland or testis
I. so 1- GnRH activation • but with low Gonadotropin level.
1. idiopathic {Constitutional) • Endogenous as:
2. Damage to the inhibitory system of - Gonadal tumor
the brain (due to infection,trauma - Adrenal tumor
and irritation). - Germ cell tumor

Causes
3. Hypophthalmic hamartoma :
produces pulsatile (GnRH).
4. Langerhans cell histiocytosis ..
5. Mccune-albright syndrome.
- Tumors secreting HCG
- Congenital adrenal hyperplasia
• Aromatase excess syndrome
• Exposure to exogenous sex steroids
• Mccune-albright syndrome.

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2- Hetero-sexual precocity
Premature development of stigmata of puberty of the opposite sex e.g. estrogenic
features in male as breast development

DIAGNOSIS
o Growth charts, x-ray of left wrist for bone age
o Hormonal Assessment: LH , FSH , estradiol, testosterone, estradiol, HCG, TSH , T4
o MRI brain and pituitary
o Criteria:
1- Feamles : - Menstruation before 10 years in females.
- breast dev. Before 7 years. or pubic hair before 8 years.
2- ~ : - breast dev. Before pubic hair or testicular enlargement.
- pubic hair or genital enlargement before 9 years.

TREATMENT
1- Surgical treatment :
o removal of any tumor (testicular, ovarian, adrenal, brain) plus radiation
therapy if surgical resection is incomplete
o removal of the tumor rarely cause regression of precocious puberty
2- Long acting synthetic gonadotropin Analogues
o Used in CCP suppress pituitary production of gonadotropin as they provide
constant stimulus where as the pituitary respond only to pulsatile Gnrh
stimulation.
o ~ LH & FSH lead to suppression of ovarian & testicular steroidogenesis
✓ Leuprolide acetate im monthly
✓ Nafareline acetate: nasal spray
✓ Histreline : SC implant
3- Drugs inhibit synthesis or action of sex hormones
o Steroid synthesis inhibitors : ketoconazole
o Anti-androgens : spironolactone
o Anti-estrogen : tamoxifen
o Aromatase inhibitors : testolactone

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 Hairsuitism
Definition 1
- unusual hair growth in abnormal places(Androgen dependant areas) of female
body (beard, mustache, chest, axilla, abdominal midline, pubic area and thigh).
- Represents a state of hyperandrogenism from the ovary or the adrenals.
Aetiology I (excess androgens)
- Familial - Racial - Idiopathic
- Polycystic ovarian syndrome - Ovarian androgenic tumors
- Congenital adrenal hyperplasia - Cushing
- Adrenal tumors - Obesity
- Drugs : androgen, diazoxide and cyclosporine.

NB.It is always associated with other syptoms and signs according to the cause
Investigations
• Serum free testosterone, DHEAS, 17 hydroxy progesterone, LH & FSH
• Serum TSH , prolactin , 24 hour urine cortisol

Treatment :

3- Weight reduction is recommended in overweight.

4- Weight loss efficiently decrease Androgens in obese and increase SHBG.
5- Pharmacological therapy :
• Estrogens : oral contraceptive pills
• Anti-androgens : spironolactone
• GnRH agonists : leuprolide
• Progestational agents : cryoteron Acetate
• Topical agents : Eflornithine , inhibit hair follicle cell division
• Cosmotic means (bleaching, shaving, waxing ) and laser

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 Gynecomastia
Definition : Hyperplasia of glandular tissue of the male breast .
N.B: (increase fatty tissue of the breast is called lipomastia).
Aetiology:
❖ Physiological:
1. Neonatal 2. Puberty 3. Old age
❖ Pathological:
1. Liver disease

2. Estrogen producing tumors (testis & adrenals)

3. Acromegaly

4. Carcinoma of the breast

5. Hyperthyroidism

6. Drugs:

✓ Non-hormonal: Spironolacton - Digitalis - cannabis - Cimitidine -cytotoxic.

✓ Hormonal: Anti-androgen - Estrogen (in cancer prostate) - Gonadotrophins.

Obesity
Definition :
Increase in body fat content with increased BMl > 30 in males and > 28 in females.
Aetiology:

1- Simple obesity :

It have been linked to several•factors :

a. Genetic factor: A new gene (ob gene) in chromosome 7 has been

found to be responsible for the production of new protein (Leptin)
that causes suppression of feeding center in the hypothalamus.
b. Decreased energy expenditure: if associated with over feeding.
c. Excessive energy intake: high caloric diet (high fat and carbohydrate).

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 d. Familial or racial: sharing the same pattern of life or genetically. (as catecholamines
induce lipolysis)
2- Endocrinal causes:
a. Frolich's and Laurance Moon Bielde syndromes
b. Hypothyroidism
c. Cushing syndrome
d. Pregnancy
e. Hypogonadism.
3- Hypothalamic disturbances:
- as tumors or inflammation.
- It presents by polyphagia, polydipsia, polyurea and hypersomnia.
- Drugs: corticosteroids, contraceptive pills, phenothiazines and antiepileptics.

Diagnosis:
1. Comparison of individual weight with charts for ideal body weight to height.
__ Body weight (kg)
2. Calculation of body mass index (BMl) BM/
Height (M2)

• 20-25 Kg/m (Acceptable)

2 "Apple"~. "Pear"

• 25-30 Kg/m (Over weight)

2

• > 30 Kg/m (Obese)

2

• 40 Kg/m (Morbidly obese)

> 2

3. Measurement of skin fold thickness over the

middle of the triceps muscle
(Normally in Male< 20 mm and in females < 30 mm) .
4. Regional fat distribution can assessed: (type of obesity)

trunkal " visceral " or "apple Gluteo-femoral "pear

shaped obesity" shaped obesity "

w;G ratio < 0.85 In males

<0.75 In females

Incidence of CVS diseases

5. CT or MRI of the abdomen to provide accurate estimation of the visceral fat.

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jc omplications :I
1. Cardiovascular:

• Hypertension is partly related to insulin resistance and hyperinsulinemia.

• Atherosclerosis due to increased levels of LDL and decreased level of HDL.
• Ischemic heart disease.
• Arrhythmia and sudden death.
• Varicose veins.
2. Neurological:

• Pseudotumor cerebri - Stroke. - Depression

3. Pulmonary:

• Obstructive sleep apnea.

• Obesity hypoventilation syndrome.
4. Gastro-intestinal:

- Fatty liver. - Hiatus hernia.

- Gall bladder stones and cholecystitis.
5. Endocrinal:

- Non-insulin dependent diabetes mellitus.

- Earlier menarche and menopause and irregular cycles.
- Growth hormone is reduced.
6. Musclo-skeletal:

- Osteoarthritis.
- Gout due to impaired urate clearance.
7. Cutanouse:

- Increased skin friability with increased risk of fungal and yeast infection.
- Acanthosis nigricans.
- Delayed healing of wounds.
8.Cancer:

increased incidence of:

- Endometrial and postmenopausal cancer breast.
- Cancer prostate in men.

119
 1) value of reducing 10 Kg in a patient with 100 weight:
* Reduction in mortality: 25%. * Reduction in risk of DM: 50%.

*Fallin BP: 10 mmHg.

* Fall 10% in cholesterol, 15% LDL, 30% in TGs, and 1l' HDL 8%

IT reatment:I

the aim is to reduce 1 Kg I week

1. Diet:
- Reduction of caloric intake to 1000 Kcal/day.

- Diet should be made of 100 gm complex carbohydrates, 50 gm of proteins, and 40 gm of

fat.

2. Exercise: this not enough to lose body weight without dietary restriction.
a. Appetite Suppressing drugs:
should be used as an adjuvant to diet control Only in patients with BM/> 30 Kg/m 2•
1. Drugs enhance release of epineohrine:
Mazindol 1-2 mg POf
Diethyl propion : 25 mg TDS
2. Drugs block reuptake of epinephrine: phenylpropanolamine 25 mg TDS.
3. Drugs block the release and reuptake of serotonin :
• Fenfluramine : 25 mg TDS.
4 . Silbutramine (Meridia 10-15 mg/day):
• It reduces food intake (through Pl activation) & increases metabolic rate (through
P3 activation).
5. Orlistat (Xenical): 120 mg/8 hrs, it inhibits intestinal lipase.
4. Surgical:
✓ Indication:
• BMl> 40
• BMl > 35 with family history of heart attack or diabetes.

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 ✓ Methods: • Jejuno-ileal bypass: causes malabsorption Syndrome
• Gastric placation: Creating a small gastric pouch.
• Gastric balloon: By endoscopy.
• Liposuction for regional obesity.

Multipe Endocrine Neoplasia

it's also named Poly-endocrine Adenomatosis "PEA"
I- Hvper-fundlon :
1. MEN I : Wermer syndrome (3Ps)
- Hyperparathyroidism : ++Ca.
- Pancreatic islet cell tumor : gastrinoma (Zollinger Ellison) or insulinoma.
- Pituitary adenoma : ++GH, prolactin.
- Less common: adrenal & thyroid tumors ± multiple cutaneous lipomatas.
2. MEN II A : (Sipple's disease)
- pheochromocytoma.
- Cushing.
- Thyroid tumors: medullary thyroid carcinoma (++ calcitonin).
- Hyperparathyroidism.
3. MEN II 8 : As Sipple+ mucosal neuromas + skeletal abnormality.
II- Hvpo-functlon:
1. SHMIDT DISEASE
- Hypoadrenalism : Addison's. - Hypothyroidism: Myxoedema.
2. MULTIPLE ENDOCRINE AUTOIMMUNE CANDI DIASI S :
• Hypoadrenalism.
• Hypoparathyroidism.
• Candidiasis of skin & mucous membranes.

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 Osteoprosis
jDeflnltlon:I

Decrease in the absolute amount of bone mass leading to enhanced bone fragility with
increased risk of pathological fractures.
The bone is normally mineralized but is deficient in Quantity. quality and structural integrity.

!Risk factors 3
Female Family history Menopause Low Ca intake Corticosteroids
Excessive Smoking Alcohol Antacid (Al type) Immobilization
caffeine

~ypes :I
a) 1ry Osteoporosis:

• Type I : Post menopausal osteoporosis.

• Type II : Senile osteoporosis.
b) 2ry osteoporosis:

• Cushing's syndrome.
• Hyperthyroidism.
• Acromegally, D.M.
• Rheumotoid disease.
• Chronic renal failure
• Chronic liver disease. - Rheumatoid arthritis.
• Immobilization.
• Drugs e.g corticosteroids.

IClinlcal Picture :I
- Boney aches & Back pain.
- Loss of Height: due to deformities (thoracic kyphosis -collapsed vertebrae).
- Pathological fractures (commonly at the forearm (colles fracture), spine
(vertebral fracture) and femur (hip fracture).

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jlnvestigatlons 3
1- Plasma chemistry: is normal (normal serum ca, P and alkaline P).
2- Alkaline phosphatase: may bet following a recent fracture.
3- X ray: low bone density (rarefaction or osteopenia).
4- DEXA scan:
II 11
• to measure bone density by dual-energy x ray absorption most diagnostic
• it may show osteopenia (low bone mass), osteoporosis or severe osteoporosis.
5- Investigations of the cause:
e.g serum creatinine, blood urea, thyroid function tests, Cortisol level.

~reatment ~
❖ Prevention: (avoid risk factors)
• Exercise.
• Calcium supplements: 1000-1500 mg/day, also diary products are
recommendede.g Milk, cheese and Yogurt.
• Restriction of caffeine intake .
• Stop smoking and alcohol intake .
• Estrogen replacement therapy in early menopause.

❖ Drug therapy:

• Bisphosphonates:
they are osteoclast antagonist e.gAlendronate 10 mg/day (osteomax or
fosamax) orally at morning, it can be given 70 mg one dose/week.
Bisphosphonates should be used with caution in patient with renal impairment
• Calcitonin: 100 LU every' other day by S.C or IM injection. It can be given by
nasal spray 200u/day.
• Calcium: 1000- 1500 mg/d orally.
• Vitamin D: 400-800 IU/d orally, alfacalcidol (vit D analogue) can be used.
• Estrogen therapy.

123
 '

Osteomalacia
!Definition ~
Defective bone mineralization (Osteomalacia is the adult counterpart of rickets).
leading to Bone pain, muscle weakness and pathological fractures.

!Pathogenesis :I
• There is failure to replace the turn over of Ca and P in bone matrix.
• bone become demineralised and the bony substance becomes replaced by soft osteoid
tissue so it is mainly a qualitative bone defect.
• The most common cause is vitamin D deficiency. the low levels of vit D. causes a
reduction of calcium absorption from the intestine.
• The low calcium absorption stimulates parathyroid hormone secretion which restores
serum calcium levels towards normal by increasing bone resorption and renal tubular
calcium reabsorption.
• The level of parathyroid hormone also promotes phosphaturia and causes phosphate
depletion.
• It is the combination of calcium loss from bone and phosphate depletion that leads to
impaired bone mineralization.

jEtlology :I
❖ Vit D deficiency
- Dietary Lack of synthesis in skin.
- absorption.
- Defective metabolism
- Anticonvulsants
- CRF

❖ Low P with normal vitD

- Familial hypophosphatemic rickets.
- Renal tubular disease.

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 ❖ Osteomalacia with normal Ca, P and vit.D
- Hypophosphatasia.
- Fibrogenesis imperfecta.
- Aluminium bone disease.

lcnnical picture ~

- Skeletal discomfort (from bone and muscle pain).

- Bone tenderness.
- Tetany may be manifested.
- Muscular weakness with marked proximal myopathy with
waddling gait.
\Investigations :I
- J.Serum Ca.
- J.Serum P.
- 'tAlkaline phosphatase.
- 'tparathyroid hormone.
- J.vit D level.
- X ray : bone rarefaction with translucent band (pseudofraction or
looser's zones) i.e linear areas of low density surrounded by sclerotic
borders.

~reatment ~
- Treatment of the cause.
- Vit. D, Ca supplements.
- Diet : e.g milk, cheese or yoghurt.
- Alfacalcidol : especially in cases of renal failure.

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 DYSLIPIDEMIA
Definition :
disorder oflipoprotein metabolism, including lipoprotein overproduction or deficiency.
Which may be manifested by elevation of the total cholesterol, LDL and triglyceride
concentrations, and a decrease in HDL concentration in the blood

(ii!tii
PRIMARY DYSLIPIDEMIA : familial or polygenic
• Hyperlipoproteinemia resulting in hypercholesterolemia
- Elevated LDL with characteristic xanthomas in tendon and xanthelasmas
- Associated with early coronary heart disease , PVD & Cerebrovascular disease
• Hyperlipoproteinemia resulting in hyper-triglyceridemia
- Pateints may suffer from recurrent episodes of pancreatitis and eruptive
xanthomas
• Hyperlipoproteinemia resulting in mixed hyperlipidemia.

SECONDARY DYSLIPIDEMIA
• OM.
• Hypothyroidism.
• Nephrotic syndrome
Eruptive xanthoma
• CRF and dialysis
• obstructive liver disease.
• Alcohols and drugs as : beta-blockers , estrogens, corticosteroids

Management

❖ General management
• Treatment of secondary causes if available
• Weight reduction if obese & regular exercise
• Cessation of smoking
• Lipid lowering deit : for at least 3 months with more fibers

126
 ❖ Drug treatment (choice of drugs)

A) If predominant disturbance is in choleseterol level

6- HMG CoA reductase inhibitors (Statins) : Simvastatin & pravastatin

• S/E : myositis , liver impairment and teratogenicity
7- Cholesterol Absorption inhibitors: Ezetimibe
• Used as monotherapy or in addition to HMGCoA reductase inhibitors
• S/E : diarrhea, abdominal pain, joint pain, sinusitis
8- Bile Acid binding resin (cholestyramine)
• Bind to bile acids in gut and promote liver to convert cholesterol into bile acids
• Safe in pregnancy
• S/E : Nausea, abdominal bloating & bind to other drugs
9- Nicotinic acid
• Inhibit lipid synthesis in liver but contraindicated in pregnancy and lactation.
• S/E : Glucose intolerance , flushing, nausea , vomiting, hyperuricemia,
hyperpigmentation and activation of peptic ulcer

B) If the predominant disturbance is in triglyceride level

1- Fibrates : gemfibrozil (the drugs of choice)

• Promote lipoprotein lipase action

• S/E : myositis , predisposing for gall stones and liver impairment
• Cl : pregnancy , gall bladder diseases , advanced liver and renal diseases
2- Omega 3 marine triglyceride

• Reduce hepatic VLDL secretion

• S/E : it may aggravate hypercholesterolemia in few pateints

127
 POL YCYSTIC OVARY SYNDRQME"reedonly"

is a condition in which a female's levels of the sex hormones estrogen and progesterone are
out of balance. This leads to the growth of ovarian cysts (benign masses on the ovaries).
Which cause problems with menstrual cycle, fertility, cardiac function, and appearance.

Pathophysiology

o 1' rate of pulsatile GnRH secretion from hypothalamus • 1' secretion of LH from
pituitary gland ( not FSH) • stimulate ovarian sica cells to increase • increase
production of androgens (testosterone & androstenedione)
o As FSH level is low in relation to LH • ovarian granulosa cells can't convert the excess
androgens into estrogens • estrogen level is decreased with subsequent anovulation.
o It is associated also with peripheral insulin resistance , hyper-insulinemia & obesity

Clinical picture
• It is varying : some patients may have minimal findings
• Menstrual abnormality , amenorrhea, oligomenorrhea,
• Hyperandrogenism , hirsutism , Acne , baldness
• Infertility temporary due to anovulatory cycle
• Obesity in 50% & impaired glucose tolerance in 35%
• Acanthosis nigricans

Investigations
✓ Sex hormone levels: 1' free testosterone+ increased LH relative to FSH (LH/FSH >2).
✓ Blood glucose : impaired glucose tolerance
✓ Ovarian US: PCOS is defined as 12 or more follicles in one overy measuring 2-9 mm
diameter

01¥\h,M,U
1- Metabolic control: Diet and exercise improves the condition and ease ovulation
2- Menstrual abnormalities : Amenorrhea is treated by oral contraceptive pills
3- Anovulation: metformin combined with clomiphene cause ovulation in 75% of
patients

128
 4- Hirsuitism :
✓ Hair removal , exercise & weight reduction decreases androgens in obese women
✓ Oral contraceptives essential in hirsutism
✓ Spironolactone is effective in hirsutism
✓ Elfornithine : topical cream to slow hair growth
5- Metformine: to improve insulin resistance and decrease hyperinsulinemia
6- Surgical : ovarian wedge resection to restore ovulation.

My Best Wishes for All Medical Students

'E/tl.. M«Mafkm ~DJ:

;(/,,,,J;Mt,
«02.'JO'Tl,86

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