Med Endo

Endocrinology Revision 1 17 115
ENDOCRINOLOGY REVISION 1 ----- Active space -----
Classification of hormones 00:05:10
On the basis of structure :

1. Amino acid (AA) derivatives
Tyrosine derivatives Tryptophan derivatives
• T3, T4 . • Serotonin : Produced by
• Catecholamines : Enterochromaffin (EC) cells
Adrenaline (80%), Noradrenaline (Main source) and Raphe nuclei
(20%) and Dopamine. in brainstem.
Produced from adrenal medulla. • Melatonin : From Pineal gland.
2. Peptide hormones
Small peptide Large peptide Glycoproteins
hormones (<50 AA) hormones (>50 AA) (Protein > carbohydrate)
• Posterior pituitary • GH (191 AA) • FSH
hormones • Prolactin (199 AA) • LH
• Hypothalamic • Insulin • TSH
hormones • PTH (Share same α subunit).
• ACTH • Renin
3. Vitamin derivatives
Vitamin A Vitamin D
4. Steroid hormones
Adrenal cortex hormones Sex steroids
• Aldosterone : Zona glomerulosa • Testosterone.
(15% of cortex) • Estrogen.
• Cortisol : Zona fasciculata • Progesterone.
• Adrenal androgens : Zona re-
ticularis
Note : Most abundant androgen is
DHEAS > Androstenedione.
Medicine Revision • v1.0 • Marrow 6.5 • 2023

116 17 Medicine
----- Active space -----

On the basis of mechanism of action :
Group Receptor Property Examples

Intracellular receptor : • Signals mediated Type 1 hormones :
1. Type 1 : Cytoplasmic by : Receptor- • Adrenal cortical
receptor hormone complex. hormones.
(Homodimeric • Effector action : • Sex steroids.
receptor). Gene transcription.
2. Type 2 : Nuclear Type 2 hormones : Vit
receptor A, vit D and thyroid
Group 1
(Heterodimeric hormones.
receptor).
SF 1, DAX 1
Constitutive
(Gonadotroph cells)
Orphan receptors activation without a
and HNF4α (MODY
ligand.
type 1)
Cell membrane • Signal mediated
receptors : by : 2nd messen-
1. G Protein Coupled ger.
Receptor. • Effector
Group 2. Tyrosine Kinase action : Protein
2 Receptor. translocation/
3. Cytokine receptors protein channels.
(Janus kinase).
4. Serine threonine
kinase receptors.
Group 2 hormones receptors :

1. G-protein coupled receptor (GPCR) : 2nd messenger
cGMP (Gt) IP3/DAG (Gq) cAMP (Gs or Gi)
Action Vasodilation Vasoconstriction Vasoconstriction
Activates Ca2+
cAMP PKA pathway
Transducin Calmodulin
Pathway → protein
mediated pathway & Protein
phosphorylation
Kinase C

cGMP IP3/DAG cAMP ----- Active space -----
Hypothalamus
TRH, GnRH CRH
Anterior pituitary
- FSH, LH, ACTH, TSH
Posterior pituitary
V1 & V3 receptor,
V2 receptor
oxytocin
Hormones NO, ANF GIT
Secretin, glucagon
CCK and gastrin and somatostatin,
PTH and calcitonin.
ANS
α1 receptors α2 and β
Ach receptors. (CAMP (Gi) : α2 and
somatostatin.)
2. Tyrosine kinase receptor (Intracellular dimerization) : Insulin, all growth
factors (Except TGF β).
3. Janus kinase receptor : Growth hormone, prolactin and EPO.
4. Serine threonine kinase receptor : Inhibin, activin, BMP 7, TGF β.
Pituitary gland 00:24:32
Development :
Development of anterior and posterior pituitary is independent of each other.
Pituitary dysplasia : M/C cause for congenital hypopituitarism (Only related to
anterior pituitary).
Development
Anterior pituitary Oral ectodermal derivative (Rathke’s pouch).
Posterior pituitary and stalk Neuroectodermal derivative.

118 17 Medicine

Hormones produced by anterior pituitary :
Lateral portion Central portion
Hormone produced GH, PRL ACTH, TSH
Somatotrophs (Most abun- Thyrotrophs (Least abundant
Types of cells
dant cell), Mamotrophs cell), Corticotrophs
Vascular insult (Eg : Growth or mass (lymphocytic
Affected by
Sheehan syndrome) hypophysitis)
Size Major portion Minor portion
Note :
20% of thyroid hormone synthesis is independent of TSH.
Entire gland produces FSH and LH (Gonadotrophs).
Somatotrophs and Mammotrophs are acidophilic cells. Rest are basophilic cells.
Thyro-
Corticotrope Somatotrope Lactotrope Gonadotrope
trope
Tissue
specific Prop-1, Prop-1,
T-pit Prop-1, Pit-1 5F1, DAX-1
transcription Pit-1 Pit-1, TEF
factor
POMC :
• ACTH.
• MSH.
• β Lipotro-
Hormone GH PRL TSH FSH, LH
pins (Most
important
derivative :
Endorphins).
Glyco-
Glycopro-
Polypep- Polypep- protein
Protein Polypeptides tein : α, β
tides tides : α, β
subunits
subunits
POMC : Pro-opiomelanocortin.
Note :
• Prop-1 (M/C cause) > pit-1 : Mutation leads to congenital hypopituitarism..
• GATA-3 : Responsible for transcription of SF-1 and DAX-1.
• First cell to appear : Corticotroph. ----- Active space -----

• Last cell to appear : Lactotroph/Mammotroph.
• 4 hormones of happiness → DOSE :
a. Dopamine : Pleasure hormone.
b. Oxytocin : ↑sed by touch.
c. Serotonin : Regulates the Mood.
d. Endorphins : Pain killer.
Relation of hypothalamus to pituitary gland :

Anterior pituitary Posterior pituitary
Hypothalamo-hypophyseal
Known as Neurohypophyseal system.
portal system.
Type Blood connection Axonal connection
Superior hypophyseal Inferior hypophyseal artery (Mets
Blood supply
artery from breast Ca → Central DI).
Note : Metastasis (M/c Breast Ca) is carried straight to the posterior pituitary
through the Inferior Hypophyseal Artery → Diabetes Insipidus.
Stalk effect :
On T1 weighted sagittal MRI :
• Anterior pituitary : Iso-dense.
• Posterior pituitary : Hyper-dense.
Tumor displacing
stalk
T1 weighted MRI

120 17 Medicine
----- Active space ----- Pituitary Tumor
Hormonal effect Stalk effect Mass effect
Functional tumors : • ↑ ICT symptoms.

• ↑PRL : Prolactinoma (M/c and • Optic chiasma compression
microadenoma). → Heteronymous/
• ↑ GH : GH secreting tumor Bitemporal hemianopia.
(Macroadenoma). • Cavernous sinus thrombosis.
• ↑ACTH : ACTH secreting adenoma • VIth nerve palsy.
(Microadenoma). • Temporal lobe compression.
Disruption of the stalk → loss

of hypothalamic connection →
Leads to :
1. Hypopituitarism.
2. hyperprolactinemia : d/t
loss of inhibition of PRL.
3. Central DI : d/t disruption
of posterior pituitary.
Prolactinoma 00:45:34
Prolactin :
PRL levels
(microg/L or Conditions
ng/mL)
< 25 (At fasting) Normal value
Physiologically seen in REM sleep, stress, pregnancy, chest
25-40
wall stimulation.
• Drugs → Dopamine antagonists :
a. Typical antipsychotics, Risperidone, TCA, SSRI.
40-100 b. Metoclopramide.
• VIP and oxytocin, Estrogen, 1o hyperthyroidism.
• Systemic conditions : CKD, CLD, PCOS.

PRL levels Conditions ----- Active space -----
(microg/L or
ng/mL)
Tumor suspected, size corresponds to PRL level.
Circulating macroprolactin (Inactive form) → No symptoms or
> 100 tumor but ↑ PRL.
Hook effect : Normal PRL levels with symptoms and tumor →
Repeat the test in serial dilution.
> 200 Definite diagnosis of tumor.
Presentation :
M/C age of presentation : >25-30 yrs
If +ve in <20 yrs → Genetic cause :
3. MEN 1 syndrome (10 - 15%).
4. Carney’s complex.
5. McCune Albright syndrome.
Microadenoma Macroadenoma
Size <1 cm >1 cm
Incidence More common Less common
F:M 20 : 1 1:1
Presenta- In females :
tion Galactorrhea-amenorrhea complex (Hormonal effect) :
↑ PRL → ↓Hypothalamopituitarygonadal axis → Hypogonadism :
1. 20 amenorrhea.
2. Infertility.
3. Hot flushes.
Osteoporosis : Spine M/c.
Insulin resistance.
In males :
• Loss of libido
• Erectile dysfunction
• Non specific symptoms.
Present late → Giant adenoma (>4 cm) with stalk and mass
symptoms.

122 17 Medicine

Investigations :
Screening test : Fasting PRL.
IOC : Gadolinium enhanced MRI (Microadenoma does not take up the contrast
→ Hypodense, normal gland surrounding tumor → Hyperdense).
Treatment :
Medical management :
Indications :
1. All macroadenoma.
2. Symptomatic microadenoma.
3. Compression symptoms/enlarging microadenoma.
4. Hypopituitarism.
Asymptomatic accidentally detected microadenoma → Followed up with MRI
after 3-6 months.
Drugs → Dopaminergic agonist :

• Cabergoline (DOC) :
a. Long T1/2 and ↓ side effects.
b. Dose : 0.25 mg, 2/weekly.
• Bromocriptine (Pregnancy).
Medical Rx given irrespective of size of tumor
Follow up after 1 month → PRL levels.
↓↓ PRL ↑↑ PRL ↑↑ PRL with S/E of

↓ ↓ drugs present
Continue Rx for ↑se dose to 2 mg /week. ↓
2 years. (S/E : TR and ILD). Dopamine agonists
resistance (20%)
Surgical management : ----- Active space -----

Transspehnoidal tumor resection/hypophysectomy.
Indications :
1. Dopamine agonist resistance.
2. Pituitary apoplexy.
3. Pregnancy.
4. Persistent compression symptoms.
Growth hormone 01:02:27
T1/2 : 5-20 min, pulsatile → Levels cannot be checked directly.

Mode of action :
• Directly.
• Indirectly : Via Somatomedin-C/IGF-1 (Produced in liver) → Peripheral
actions.
↑ production in stage 2,3 and 4 NREM sleep.
Stimulators : Hypoglycemia (Most important), Ghrelin, GHRH.
Inhibitors : Somatostatin, obesity, hypocaloric state/malnutrition (GH resistance).
Measurement : Measured through IGF + IGFBP-3 (Insulin like growth factor
binding protein-3).
Actions :
GH IGF 1
Bone, epiphyseal growth +++ +++
Anabolic effect on protein +++ +++
Effect on carbohydrates Diabetogenic Anti-diabetogenic
Effect on fats Lipolysis Anti-lipolytic
Salt and water retention + -
Actions of GH independent of IGF 1 :
B : Bone growth.
E : Epiphyseal growth.
A : Adipose tissue : Lipolysis.
M : Muscle protein synthesis.
S : Salt and water retention.
Acromegaly 01:10:13
Causes :
Growth Hormone secreting adenoma (Accounts for 98% of acromegaly cases).
GH secreting ectopic tumor : Pancreatic islet cell tumor.
GHRH secreting hypothalamic tumor : Hypothalamic hamartoma.
GHRH producing ectopic tumor : Bronchial carcinoid.

124 17 Medicine

Salient features :
Generally macroadenomas.
Males > females.
Age > 40 years.
If +ve in < 20 yrs → Genetic cause :
1. MEN 1 syndrome.
2. Carney’s complex Acral enlargement
3. McCune Albright syndrome
20 % tumors associated with → ↑ PRL.
Clinical features :
Acral enlargement : Enlargement of peripheral parts.
All organs enlarge except brain.
Coarse facies :
• ↑ Thickening of lips, tongue, face. Frontal bossing
• Frontal bossing.
• Prominent supraorbital ridges.
Enlarged soft tissue growth.
Features of McCune Albright syndrome :
• Cafe-au lait spots.
• Polyostotic fibrous dysplasia → Asymmetric face.
• Precocious puberty.
• Tumors.
McCune Albright syndrome
Complications :
Structure/system Complication
Nerve Entrapment neuropathy.
Muscle Myopathies
Hypertriglyceridemia
Hypercalcemia (↑ 1α hydroxylase).
Metabolic Hypercalciuria
Hyperphosphatemia.
Diabetes (Uncontrolled, short duration).
Ophthalmic Angle closure glaucoma
Respiratory system OSAS, PAH.
M/C cause of death.
Asymmetrical LVH → HF with prEF.
CVS
↑ incidence of CAD.
HTN
Thyroid Goiter (IGF 1)
GIT Non-malignant colonic polyps
Renal Salt and water retention, renal stones (↑Ca2+)
Menstrual abnormality Oligomenorrhoea

Work-up : ----- Active space -----

Screening test : IGF-1 levels.
Confirmatory test : Glucose induced GH suppression test → 75 g of oral glucose
→ GH levels checked after 1 hr
• <1 ng/mL : Normal.
• >1 ng/mL : Confirmatory.
• >40 ng/mL : Poor prognosis.
IOC : Gadolinium enhanced MRI → Macroadenoma shows heterogenous
enhancement.
Management :
Surgical management :
TOC : Transsphenoidal Surgery
Immediate post-op GH :
• Undetectable : Good prognosis.
• Detectable → ↑ chances of relapse → Medical therapy started and
imaging repeated after 12 weeks.
Medical management (2nd line) :
• Somatostatin Receptor Ligands (SSRL) :
a. Octreotide
b. Lanreotide
c. Pasireotide
• Bromocriptine/Cabergoline.
• Pegvisomant : GH receptor antagonist.
On relapse : 2nd Sx done, curated as much as possible.

If pt unfit for Sx : Gamma knife stereotactic RT.

126 18 Medicine

ENDOCRINOLOGY REVISION 2
Acquired Hypopituitarism 00:00:18
Stalk effect :
Triad : Hypopituitarism + Central diabetes insipidus + Hyperprolactinemia.
Causes : Functional → Macroadenoma (GH secreting)

• Tumors :
Non functional → Rathke cleft cyst, craniopharyngioma.
• Trauma related/Surgery related.
• Infection : HIV, histoplasmosis, toxoplasmosis, tuberculosis.
Langerhans cell histiocytosis
• Infiltration : Sarcoidosis
Hemochormatosis
Pituitary hormones :
Hormone Effects of decreased hormones
• Asthenia, weight loss, fatigue, loss of appetite.
• Repeated episodes of hypoglycaemia/hypotension.
ACTH
• Euvolemic hyponatremia.
Note : Hypovolemic hyponatremia seen in aldosterone insufficiency.
• Cold intolerance, constipation, bradycardia.
TSH Note : 20 % thyroid hormone synthesis independent of TSH. (Frank
hypothyroidism features → Usually not present).
GH Centripetal obesity, hypertriglyceridemia, endothelial dysfunction
PRL Involved only in lactating mothers.
Hypogonadism features : Muscle wasting, dispropotionate
fractures.
FSH, LH
• Male : Loss of libido.
• Female : Irregular cycles, hot flushes, secondary amennorhoea.
Note :
Eosinophils inversely ∝ Cortisol rhythm.
• Cushing syndrome : Eosionopenia.
• ACTH insufficiency : Hypereosinophilia.

Aldosterone insufficiency features not seen with ACTH deficiency. ----- Active space -----
• Aldosterone (Mineralocorticoid) secretion → Controlled by RAAS axis.
• Aldosterone insufficiency features : Salt wasting, postural hypotension,
dehydration and hyperkalemia, hyponatremia (Hypovolemic).
Hormone measurement :
• FSH, LH, TSH, PRL : Direct measurement available.
• GH :
a. IGF -1
b. Growth hormone provoctive test : L-Dopa, glucagon (Preferred),
arginine, clonidine.
Note : Insulin tolerance test (Gold standard) : 0.1 U/kg iv → Induce hypoglycemia
and detect the level of GH, ACTH in response to it.
Pituitary Apoplexy : 00:10:06
Acute intrapituitary hemorrhage.

Etiology :
• Tumor (Adenoma).
• Necrosis (Sheehan syndrome).
• Normal gland (Risk factors : Diabetes mellitus, HTN,
sickle cell anemia).
Presentation :
• Headache ± Meningeal signs ± Ophthalmoplegia.
• Severe hypotension and severe hypoglycaemia.
Management :
Pulsatile methylprednisolone 500 mg, followed by decompression surgery.

128 18 Medicine
----- Active space ----- Sheehan syndrome vs Lymphocytic Hypophysitis : 00:15:15
Sheehan syndrome Lymphocytic hypophisitis

Post partum pituitary
Post partum inflammatory
ischemic necrosis.
Etiology mass : IgG4 containing
Lateral zone affected >
lymphoplasmacytic cells.
Central zone.
• Hypogonadism • Stalk effect
Effects
• ACTH failure. • mass effect.
• ADH (N) • ADH
Hormone • Prolactin, GH • Prolactin
profile • ACTH, TSH
• LH, FSH
• Can present immediately after • Pituitary enlargement.
delivery : Lactational failure. • Headache.
• 3-6 months post delivery : • Visual disturbance.
1. H/o post partum hemorrhage • Hypopituitarism.
with hypotension, shock and DIC → • Hyperprolactinemia.
Needing blood transfusions/fluid • Associated autoimmune
management. disease.
2. Menstrual irregularity, 2o • Diabetes insipidus.
C/F
amenorrhoea, breast atrophy,
decreased libido, genital and
axillary hair loss.
3. Diabetes insipidus.
4. At least 1 anterior pituitary
hormone deficiency.
5. Empty/severely damaged sella
turcica.
Rx Complete hormone replacement. Responds to steroids.
Image
Necrosed gland Inflammatory mass

Empty sella : 00:17:12 ----- Active space -----
Primary Empty sella Secondary empty sella

Tear in the dura : CSF sweeps • Part of necrosis/tumor.
Etiology
across to collect in the sella. • Sella empty.
Benign intracranial HTN
Seen in Sheehan syndrome
(Increased ICT)
Hypopituitarism Absent Present
Anti Diuretic Hormone 00:19:44
Stimuli for ADH release :
Osmotic stimuli (Major) Non osmotic stimuli (Minor)

Osmolality → ADH + Thirst Effective circulating
stimulation volume → ADH.
S. Osmolality = 2 x S. Na+ + (Blood glucose/18) + (BUN/2.8)
Note : ADH doesn’t cause hypernatremia as there is a compensatory in thirst.

Exceptions : Head injury & Intubated patients.
Action of ADH on vasopressin receptors :
Receptors Site & action
• Blood : Vasoconstriction, platelet aggregation.
v 1 receptors :
• Glycogenolysis.
(IP3 DAG pathway).
• Heart : Myocardial thickening.
V2 receptors : • Endothelium : vWF release.
(cAMP protein kinase A pathway). • Cortical collecting duct : Free H2o absorption.
v3 receptors :
• Pituitary : ACTH release.
(IP3 DAG pathway).
ADH binds to basolateral
Note :
membrane
AQP3, AQP4 are expressed on
(V2 receptor)
the basolateral membrane.
Activates cAMP protein kinase A

pathway
Aquaporin (AQP2) expression

on luminal membrane
Free H2O reabsorption

130 18 Medicine
----- Active space ----- Hyponatremia : 00:25:58
Disorder of H2O metabolism.

Psychogenic polydipsia : Intake of >15-20 L H2O/day.
Solute reabsorption at DCT, thick ascending limb
Causes :
(Furosemide < Thiazide diuretics).
Excess ADH release.
Severity of hyponatremia :
• Very severe : S. Na+ → <100 mEq/L → ICT symptoms.
• Severe : S. Na+ → 100-119 mEq/L → CNS symptoms other than
increase in ICT such as ataxia, confusion.
• Moderate : S. Na+ → 120-129 mEq/L → GI symptoms, lethargy.
• Mild : S. Na+ → 130-134 mEq/L → GI symptoms.
Pseudohyponatremia : Normal to osmolality with low Na+.
• Translocational causes : Glucose, mannitol, glycine, maltose (effective
solutes).
• Paraproteinemia.
• Hypertriglyceridemia.
Approach to hyponatremia :
1. Rule out pseudohyponatremia (Normal to osmolality).
2. Evaluate true hyponatremia ( osmolality).
i. Rule out psychogenic polydipsia and diuretic overuse based on clinical history.
ii. Evaluate causes of excess ADH :
Excess ADH (Anti diuretic hormone)
Appropriate Inappropriate
Hypovolemic Hypervolemic Euvolemic
hyponatremia hyponatremia hyponatremia
Low ECF Volume. Low effective SIADH.
Hypovolemic : volume : Note : ADH is usually
(Volume lost via) : • CCF. released when
• GIT. • Cirrhosis. tonicity is and
• Kidney. Excess Volume seen → volume is low.
• 3 space loss. outside the cell.
rd

SIADH (Syndrome of Inappropriate ADH) : ----- Active space -----
Causes :
• Trauma.
• Drugs → Vincristine, NSAIDs, oxytocin, TCA, SSRI, 5 C’s : Chlorpromazine,
Cyclophosphamide, Carbamazepine, Clofibrate, Chlorpropamide.
• Paraneoplastic syndrome (Small cell Lung ca, duodenal tumor, thymus
tumors).
• Acute intermittent porphyria.
• Necrotizing pneumonia.
• Meningoencephalitis.
Clinical criteria for diagnosis :
• Euvolemic.
• Low serum osmolality. Urine
• Urine osmolality.
• Urine Na > 20mEq/L.
Absence of thyroid illness (Hypothyroidism), pituitary problem, adrenal
problem (Hypocortisolism), liver/renal disease.
Cerebral Salt wasting syndrome vs SIADH :

Cerebral salt wasting syndrome SIADH
Hypovolemia Euvolemia
Loss of adrenergic tone →
Mainly d/t trauma, drug induced
Suppressed RAAS
Urine Na
Natriuresis : Present
S. Uric acid : S. Uric acid : (<2 mg/dl)
S. K+ : S. K+ : N or
Diabetes Insipidus : 00:42:23
Name changed to :
• AVP-d : Arginine Vasopressin deficiency (Central DI).
• AVP-r : Arginine Vasopressin resistance (Nephrogenic DI).

132 18 Medicine
----- Active space ----- Polyuria :

> 3L urine/24 hours (Or) >40 ml urine/kg/24 hours.
Water diuresis. Solute diuresis.
Causes :
• Diabetic Patients
Passing > 7 L urine/24 hrs.
• Mannitol therapy.
• Diuretic.
• Post obstruction : Relieve obstruction.
Urine osmolality : Urine osmolality :
<300 mOsmol/kg. > 600 mOsmol/kg.
Note : Urine osmolality → 300-600 mOsmol/kg (Can be both water

diuresis/solute diuresis).
Urine dipstick : Negative. Urine dipstick : Positive.
Nocturnal craving for cold H2o
-
Urine specific gravity : 1.010
Hypotonic polyuria :
Polyuria + Urine osmolality < 600 mOSM/L.
AVP-D : Central DI AVP-r : Nephrogenic DI
Etiology : Deficiency of AVP Etiology : Resistance to action of AVP.
Causes : Causes :
• Vasopressin deficiency. • Fibrosed receptor d/t chronic tubulo
• Genetic causes : AD > AR > XLR. interstitial disease : IgG4, Sjogren’s,
• Pregnancy. sarcoidosis.
• Drugs : Lithium, demeclocycline,
cisplatin, foscarnet.
• Hypercalcemia/hyperuricemia/
hypokalemia.
• Sickle cell anemia (Occlusion of vasa
recta).
• Pregnancy.
Note :
Wolfram syndrome/DiDMOAD syndrome (Autosomal recessive) :
Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness.

Plasma copeptin assay : ----- Active space -----

It has replaced water deprivation test.
Hypotonic polyuria
Unstimulated random plasma copeptin
> 21.4 pmol/L ≤ 21.4 pmol/L

Nephrogenic
diabetes insipidus Arginine stimulation test :
Measure stimulated copeptin levels.
≥ 3.8 pmol/L : < 3.8 pmol/L :

Psychogenic Central diabetes
polydipsia insipidus
Treatment :
Diabetes Insipidus Drug
Desmopression 10-20 mcg intranasally.
Central Diabetes Insipidus
Desmopressin 0.1-0.8 mg daily once.
Peripheral Diabetes Insipidus Thiazides : Best option.
Lithium induced Diabetes Insipidus Amiloride/Triamterene.
SIADH vs Diabetes Insipidus :
SIADH Diabetes Insipidus

Presentation Hyponatremia Polyuria
Plasma volume Euvolemic
Serum Hypotonic Hypertonic
Serum Na
Urine volume Voluminous
Urine osmolarity Relatively high Relatively low
Urine Na >30 mEq/L Normal or variable
Chronic : Fluid restriction +
Treatment Vaptans. Supportive DDAVP
Na < 120 : Hypertonic saline.

134 19 Medicine
----- Active space ----- ENDOCRINOLOGY REVISION 3
Adrenal cortex Hormones produced

Zona glomerulosa Aldosterone.
Zona fasciculata Cortisol.
Zona reticularis Dehydroepiandrosterone (DHEAS), Androstenedione.
Primary Hyperaldosteronism (PHA) 00:01:02
Aldosterone secretion Primary hyperaldosteronism

from adrenal gland Renin (Hyporeninemic hyperaldosteronism).
Renal perfusion pressure/ 2˚ RAS

Aldosterone. 2˚ hyperaldosteronism.
Intra vascular volume activation
Causes of PHA :
Acquired causes Inherited causes
• Micronodular b/l adrenal hyperplasia Familial hyperaldosteronism (Autosomal
(M/C). Dominant) : Type 1 → GRA
• U/L adrenal adenoma (Conn’s syndrome). (Glucocorticoid Remediable Aldosteronism).
Presentation : Basolateral
Lumen
• 20 to 60 years. Principal cell membrane
H2O
• Male = Female. ADH
Aquaporins
• Triad :
1. Hypertension (HTN) with disproportionate K+/H+ 2Na+
target organ damage. ENaC AIP 2K+
Aldosterone
2. Hypokalemia : Weakness. Na +
AIP : Aldosterone
3. Metabolic alkalosis. Induced Protein
PHA (Acquired/GRA).
Note : Hypokalemia + HTN + DDx Cushing syndrome.
Metabolic alkalosis Apparent Mineralocorticoid Excess (AME).
Liddle syndrome.

Management : Screening test ----- Active space -----

Plasma Aldosterone Concentration (PAC) : ≥ 10 ng/dl.
Plasma Renin Activity (PRA) : < 1 ng/ml/hr.
Positive
Confirmatory test
Saline infusion test : 2L of NS over 4hours.
PAC ≥ 10 ng/dl.
Positive
CT adrenal
U/L adenoma B/L hyperplasia
< 35 years > 35 years
U/l adrenalectomy Adrenal Venous Sampling (AVS)

from left & right renal vein
Compare Aldosterone/Cortisol ratio
of both sides
Ratio > 4 : 1 → Lateralization No lateralization
Surgery Medical Mx
(Adrenalectomy) Aldosterone antagonist :
• Eplerenone.
• Finerenone.
• Spironolactone.
Adrenal Cortical Insufficiency/Addison’s Disease 00:11:48
10 Adrenal insufficiency 20 Adrenal insufficiency

Cause Adrenal cortical cause. Pituitary cause/
(Autoimmune > TB) Abrupt steroid withdrawal (M/C).
ACTH (Hyper pigmentation).
Aldosterone Normal
Cortisol, DHEAS, Androstenedione
Salt craving, postural + -

hypotension
Loss of axillary hair + +
Vitiligo + -
S. Potassium High. Normal.
S. Sodium Low.

136 19 Medicine

Primary adrenal insufficiency :
Acquired causes :
• Autoimmune (M/C) : Autoimmune Polyendocrine Syndrome (APS)/
Polyglandular Autoimmune syndrome (PGA) → APS 1/2 :
Produce Anti 21-OH antibody.
• Tuberculosis.
• Waterhouse friderichsen syndrome.
Inherited causes :
• AAA syndrome : Alacrimia, Achalasia cardia, Addison’s disease → Aladin
mutation.
4A syndrome : AAA syndrome + Autonomic nervous system dysfunction.
• X-linked adrenoleukodystrophy → Very long chain fatty acid.
Presentation :
• Cortisol insufficiency Weakness, weight loss, asthenia, fatigue.
Repeated hypoglycemia & hypotension.
Hyponatremia.
Note : Cortisol insufficiency : Euvolemic hyponatremia.
Aldosterone insufficiency : Hypovolemic hyponatremia.
• Aldosterone insufficiency Salt wasting.
Dehydration.
Hyperkalemia.
Postural hypotension.
• Sex steroid insufficiency → Dry skin.
• ACTH → Hyperpigmentation of skin.
• Eosinophilia.
• Normal or small or asymmetrical adrenal gland on CT scan.
• Non-adrenal calcification.
Note : Secondary addison’s : No symptoms of
aldosterone insufficiency & ACTH.
Investigations : Fasting cortisol
< 3 μg/dl 3-20 μg/dl > 20 μg/dl
10 Addison’s disease. Synacthen stimulation test. Addison’s disease

( Synthetic ACTH 250 μg IV/IM). is ruled out.
< 20 μg/dl > 20 μg/dl
10 Addison’s disease. Addison’s disease is ruled out.

Addisonian crisis : ----- Active space -----

Acute abdominal pain + Hypotension + Shock.
Addisonian crisis.
3 to 4L of NS over 8-12 hrs.

100 mg I/V Hydrocortisone Stat.
50 mg I/V Hydrocortisone 6 hrs apart.

Total dose on 1st day : 300 mg.
Gradually taper the dose of I/v hydrocortisone

& Switch to oral hydrocortisone.
Cushing Syndrome 00:23:27
Cortisol (active) : 11 beta hydroxy steroid Cortisone (inactive) :

Has glucocorticoid + dehydrogenase type 2 (11 βHSD-2) Has only
mineralocorticoid activity. glucocorticoid activity.
Deficiency of 11 βHSD-2 Hypercortisolism

Inherited deficiency Apparent Mineralocorticoid Excess.
Acquired deficiency In cushing syndrome.
In excessive licorice consumption.
Causes : Hypercortisolism
Endogenous Exogenous
ACTH dependent : 90% ACTH independent : 10% Steroid intake
ACTH secreting pituitary • Adrenal adenoma : M/C in ACTH

Micro-adenoma : independent.
Cushing disease (M/C overall). • Adrenal carcinoma (Toddlers).
• Mc Cune Albright syndrome (Infants).
Paraneoplastic syndrome (PNS) : • Macronodular adrenal hyperplasia.
• Small cell lung carcinoma. • Micronodular adrenal hyperplasia
• Carcinoid. (Primary Pigmented Nodular Adrenal
• Medullary thyroid carcinoma. Disease : PPNAD).

138 19 Medicine

Presentation of hypercortisolism :
Action Presentation
1 Protein Catabolism : Muscle : Myopathy.
Amino acid uptake in all Bone : Osteoporosis.
tissues except liver. Collagen : Violaceous purplish striae.
Platelet : Bruising.
2 Carbohydrate Alanine in blood : Substrate Gluconeogenesis.
for gluconeogenesis.
3 Fat Redistribution of body fat ± Buffalo hump, moon facies,
minimal lipolysis. centripetal obesity.
4 Mineralocorticoid Increased. Salt & water retention.
Hypokalemia.
Metabolic alkalosis.
5 Sex steroid Increased. Acne, hirsutism.
6 CNS - Steroid psychosis.
Other presentation :
• Eosinopenia. • Deep vein thrombosis.
• Risk of infection. • Menstrual : Amenorrhea or oligomenorrhea.
Presentation with high discriminatory value :

1. Proximal myopathy. 4. Bruising.
2. Facial plethora. 5. Young onset short stature/Osteoporosis.
3. Cutaneous striae. 6. Disproportionate HTN/DM.
Note : Centripetal obesity (M/c symptom) has poor discriminatory value.
Diagnosis & Management :
1. Midnight serum cortisol > 1.8 μg/dl.
To diagnose endogenous hypercortisolism,
2. Midnight salivary cortisol > 5.5 mmol/l
2 out of 3 following criteria should be positive
3. ONDST (OR) LDDST (Specific test) > 1.8 μg/dl.

Midnight serum cortisol ----- Active space -----

Midnight salivary cortisol
positive negative
8 AM plasma cortisol Cushing syndrome

is ruled out
> 1.8 μg/dl. Too low
Exogenous hypercortisolism
Endogenous hypercortisolism is suspected
Suspected cushing syndrome Suspected pseudocushing/Obesity/

Hyperestrogenism/PCOS/on Oral Contaceptive pills
Over Night Dexamethasone Suppression Test (ONDST)
1 mg oral dexamethasone at 11pm Low Dose Dexamethasone Suppression Test
(LDDST) 0.5 mg Q6H for 2 days
Next day 8 AM plasma cortisol
> 1.8 μg/dl.
< 1.8 μg/dl. > 1.8 μg/dl. Endogenous hypercortisolism
Normal Endogenous hypercortisolism
ACTH
< 1o pg/ml > 1o pg/ml
ACTH independent : ACTH dependent

Adrenal cause
1o - 100 pg/ml > 100 pg/ml
CT adrenal
U/L adenoma (M/c) Pituitary cause/PNS Paraneoplastic syndrome (PNS)
U/L adrenelectomy PET scan
MRI brain with gadolinium
≥ 6 mm mass < 6 mm/no mass

Pituitary adenoma Inferior petrosal sinus sampling
Trans-sphenoidal hypophysectomy Petrosal/ peripheral ACTH ratio
>2 : significant Negative
Trans-sphenoidal hypophysectomy PET scan
Drug used in Cushing syndrome : Ketoconazole.

140 19 Medicine

Pheochromocytoma 00:47:54
It is a neural crest cell tumor producing catecholamines or metabolites of

catecholamines.
Hormones produced in adrenal medulla Metabolites
Adrenaline (80%) Metanephrine, Vanillylmandelic acid (VMA).
Noradrenaline (20%) Normetanephrine.
Dopamine Homovanillic acid (HVA).
Phenyl ethanolamine
Nor-Adrenaline Adrenaline
N-methyltransferase (PNMT)
Adrenal pheochromocytoma (M/C) :

Produces adrenaline > Nor adrenaline.
Extra-adrenal pheochromocytoma :
• Also known as paraganglioma (25%).
• Produces only noradrenaline as PNMT is present only in adrenal gland.
• Types :
Sympathetic (Functional) : From organ of Zuckerkandl.
Parasympathetic (Non functional) : From carotid body > jugular bulb.
Association :
• 40 % : Hereditary (MEN-2, Von Hippel Lindau disease, NeuroFibromatosis-1).
• 40 % : Bilateral (MEN-2, Von Hippel Lindau disease).
• 50 % : Malignant → Surest sign of malignancy is metastasis.
Associated mutation : SDH-B mutation (Succinyl Dehydrogenase B).
Note : Pheochromocytoma in NF-1 is unilateral.
Presentation :
• M/c presentation : Panic attack.
• Triad : Severe episodic headache (M/c symptom) + tachycardia + profuse
sweating.
• M/c sign : Episodic hypertension.
Disease of 6 Ps and 1 W :
• Pain (Abdominal pain d/t hypercalcemia). • Perspiration.
• Pallor (Suggestive of malignancy). • Postural hypotension.
• Panic attack. • Weight loss (DM).
• Palpitation.
Investigations : ----- Active space -----

• Screening test:
24-hour urine fractionated metanephrine : 98% sensitivity & specificity ±
Plasma fractionated metanephrine : 100% sensitivity, but low specificity.
• IOC for adrenal pheochromocytoma : MRI abdomen.
IOC for extra-adrenal pheochromocytoma : Gallium DOTATATE PET Scan.
Treatment :
Surgery : Laparoscopic retroperitoneal adrenalectomy.
Days before surgery Drug
10 days Liberal I/V fluids.
7 to 10 days α-Blockers Phenoxybenzamine (m/c used).
(Any one drug given)
Prazosin.
Nicardipine/Metyrosine.
2 to 3 days β-Blockers Atenolol.
HTN crisis during surgery : Sodium nitroprusside/Nicardipine.
Multiple Endocrine Neoplasia (MEN) 00:59:13
• Autosomal dominant.
• Male = Female
MEN 1 :
• Mutation of Menin gene on chr 11q (tumor suppressor gene).
• M/c method of mutation : Intron inversion.
Manifestations of MEN 1 :
3 Major manifestations :
1. Parathyroid manifestation (Primary hyperparathyroidism) : 100%.
Primary hyperparathyroidism in MEN 1 Primary hyperparathyroidism
< 20 years > 50-60 years.
Male = Female. Female >> Male.
Symptomatic : Painful bones, renal stones, abdominal Asymptomatic.
groans, psychotic moans, fatigue overtones.
Asymmetric hyperplasia of all 4 glands. Adenoma (M/C).
2. Entero-pancreatic neuroendocrine tumors : 50-70%.

• M/c cause of death in MEN 1.
• Gastrinoma (M/c).
142 19 Medicine

3. Pituitary manifestation : 30-50%.
Aggressive macro prolactinoma → Presenting feature in 10-15%.
Minor manifestations :
• M/c skin manifestation : Angiofibroma. Others : Collagenoma, lipoma.
• M/c neurological tumor : Meningioma.
• M/c tumor : Adrenocortical tumor (30%).
• Pheochromocytoma in MEN 1 : < 1%.
• PNET(Primitive neuroectodermal tumour) : Thymic & foregut carcinoids.
MEN 2A :
Point mutation of RET proto oncogene mutation on 10q.
Divided into 4 types :
1. Classical MEN 2A.
2. MEN 2A with cutaneous lichen amyloidosis.
3. MEN 2A with Hirschsprung’s disease.
4. Familial Medullary Thyroid Carcinoma (FMTC).
Classical MEN 2A :
3 manifestations :
• Medullary thyroid cancer (100%).
• Pheochromocytoma : Inherited, bilateral (50%).
• Parathyroid hyperplasia (25%).
MEN 2B :
• Medullary thyroid carcinoma.
• Pheochromocytoma.
3/4 M’s :
• Marfanoid habitus.
• Mucosal & intestinal ganglioneuromatosis.
• Myelinated corneal nerve fibres.
• Megacolon (rare).
MEN 4 :
Due to Cyclin Dependent Kinase 1B (CDKN1B) mutation.
• Parathyroid involvement.
• Pituitary involvement.
• Ovarian/testicular tumor.
• Renal/adrenal tumor.

MEON 01:08:43 ----- Active space -----
MEON : Multiple Endocrine and Other Organ Neoplasia syndrome

Syndromes Inheritance/ Genes Endocrine Neoplasia
Mutation manifestation
Hyperparathyroidism Parafibromin Hyperparathyroidism Ossifying fibroma of the jaw.
– Jaw tumor (CDC 73). due to parathyroid
syndrome carcinoma.
Carney’s Complex PRKAR 1A. PPNAD AKA Lean Atrial myxoma.
Cushing.
Acromegaly.
Prolactinomas (rare).
Autosomal
Von Hippel Lindau VHL gene on Pheochromocytoma. • Renal cell cancer.
Dominant
disease (VHL) Chr 3. • Cerebellar
Hemangioblastoma.
NF 1 Neurofibrin Pheochromocytoma. Optic nerve sheath tumors.
on Chr 17.
Cowden syndrome PTEN. Autoimmune • Hamartomatous polyps of GIT.
Hypothyroidism. • CA breast.
Mc Cune Albright Post Zygotic Post Zygotic Adrenal Cushing. Polyostotic fibrous dysplasia.
syndrome Gs α subunit mutation of Acromegaly.
defect GNAS gene. Prolactinoma (rare).
Polyglandular Autoimmune Syndrome (PGA) 01:13:34
Also called �utoimmune Polyendocrine Syndrome (APS).

Features APS-1 APS-II
Age Childhood. Adult.
Skin, nail changes & Candidiasis Present. Absent.
Association APECED gene mutation. HLA-DR3 and DR4 associated.
Inheritance Autosomal recessive. Polygenic.
Gender association Male = Female. Female > Male.
Antibodies Anti 21-OH antibody -
(M/c cause for Addison’s).
Major manifestation Primary Hypoparathyroidism + Addison disease + Hashimoto
Graves > Hashimoto thyroiditis. thyroiditis> Graves.
Minor manifestations Addison disease. Type 1 DM.
Type 1 DM. Hypogonadism.
Hypogonadism.
APECED : Autoimmune Poly Endocrinopathy with Candidiasis & Ectodermal Dystrophy.

144 20 Medicine
----- Active space ----- ENDOCRINOLOGY REVISION 4
Hypercalcemia 00:01:12
Adjusted total Ca2+/Normal S. Ca2+ : 8.6-10.3 mg/dL.

Adjusted total Ca2+ = Measured Ca2+ + 0.8 x (4 - S. Albumin).
Pathophysiology :
↑ S. Ca2+
Inhibition of CaSR (Calcium Sensing Receptor)

(In parathyroid & thick ascending limb of loop of Henle)
↓ Ca2+ reabsorption
↑ Ca2+ excretion
Renal stones formation
Causes :
a. PTH-related : Normal PTH = 50-100 pg/mL.
1. Primary hyperparathyroidism (M/C).
2. Tertiary hyperparathyroidism.
3. Li-induced hyperparathyroidism.
4. Familial hypercalcemia with hypocalciuria (FHH).
5. Paraneoplastic hypercalcemia.
Primary hyperparathyroidism :
Parathyroid adenoma Parathyroid hyperplasia
• 60-80 years • Young
• F>M • F=M
• ↑↑ PTH (500 pg/mL) • Associated with MEN-1, MEN-2A
• ↑ Ca2+
• ↓ PO4

Tertiary hyperparathyroidism : ----- Active space -----

• Consequence of long-standing secondary PTH.
• ↑↑↑ PTH (> 1000 pg/mL). Note : Lithium can also cause
• ↑ S. Ca2+. • Primary hyperparathyroidism.
• ↑ S. PO4. • Nephrogenic DI.
• Seen in advanced CKD. • Chronic tubulointerstitial disease.
• Hypothyroidism
Familial hypercalcemia with hypocalciuria :
Loss of function mutation of CaSR → ↑ Ca2+ reabsorption → Hypercalcemia +
Hypocalciuria.
Paraneoplastic hypercalcemia :
• Aka Humoral Hypercalcemia of Malignancy (HHM).
• Seen in squamous cell carcinoma.
• Pathology : ↑ PTHrp leads to ↓ PTH (<50 pg/mL) and ↑↑ Ca2+.
b. Vitamin D related :
Active form of vitamin D : Calcitriol/1,25-dihydroxy D3.
Functions :
• ↑ Ca2+ absorption (Through calbindin in small intestine).
• Inhibits PTH.
2 forms of vitamin D :
• 1,25-dihydroxy D3 (t1/2 = 6-8 h).
• 25-hydroxy D3 (t1/2 = 2-3 weeks).
Work up :
• Both forms of Vitamin D ↑ : Hypervitaminosis D.
• 1,25-dihydroxy D3 ↑ + 25-hydroxy D3 normal :
a. Sarcoidosis.
b. Acromegaly.
c. Lymphomas.
c. Osteolytic hypercalcemia : d. Endocrine conditions :
• Multiple myeloma. • Pheochromocytoma.
• Ca breast. • Addisonian crisis.
e. Drugs : • Thyrotoxicosis.
• Thiazides. • Acromegaly.
• Lithium.
f. Milk alkali syndrome : Consumption of Ca2+ >4g/day.

146 20 Medicine

Presentation :
Clinical features :
• Painful bones : Seen in osteolytic hypercalcemia.
• Renal stones : Sometimes it is the only presentation.
• Abdominal groans (Pain) : Seen in sarcoidosis, Addisonian crisis.
• Psychotic moans.
• Fatigue overtones : Paraneoplastic hypercalcemia may present with only
fatigue.
O/E : Pseudo clubbing (Normal Lovibond angle).
Investigations :
1. ECG : Short QT interval.
2. X-ray : Shows bone changes.
• Sub-periosteal resorption.
• Rugger jersey sign.
• Diffuse bone resorption.
• Acral osteolysis.
• Osteitis fibrosa cystica.
• Salt & pepper skull. Short QT interval
3. Tc99 Sestamibi scan.
Tc99 Sestamibi scan Subperiosteal resorption

Hyperactive parathyroid glands
Management :
Acute management :
• Hydrate the patient (To prevent nephrogenic diabetes insipidus).
• Bisphosphonates.
• Calcitonin.
Definitive management :
Adenoma : Removal of adenoma.
Hyperplasia : Removal of 3 & 1/2 glands.

Hypocalcemia 00:21:03 ----- Active space -----
Presentations :
1. Arrhythmia : Prolonged QT interval.
2. Pseudotumour cerebri :
• ↑ ICT with seizures, papilledema (or)
• Calcification.
3. Neuromuscular irritation :
• Circumoral tingling.
• Numbness, paresthesia. Prolonged QT interval
• Bronchospasm, laryngospasm (Fatal).
• Latent tetany.
Latent tetany Basal ganglia calcification

Work up :
↓ S. Ca2+
Rule out hypomagnesemia (Gitelman syndrome, PPI use)
↓S. PO4
S. PTH
↑ S. PO4 ↑ S. PO4 ↑ S. PO4

↑ PTH ↓↓↓ PTH Normal PTH
Secondary True hypoparathyroidism Rhabdomyolysis

hyperparathyroidism. Tumour lysis syndrome
E.g : CKD.
Genetic Acquired
Di George syndrome Autoimmune Polyglandular Syndrome-1 (APS-1)

148 20 Medicine

Secondary hyperparathyroidism :
It is a response to hypocalcemia.
Seen in CKD.
Causes for hypocalcemia :
• Inhibition of 1a hydroxylase.
• ↓ Calcitriol.
Biochemistry :
• ↓ S. Ca2+.
• ↑↑ PTH.
• ↑ S. PO4 (↓ Excretion).
Pseudohypoparathyroidism :
↑↑ PTH → Resistance to action → ↓ Ca2+, ↑ PO4.
Types :
1. Type 1 : 1a, 1b.
2. Type 2.
3. Pseudo-pseudo hypoparathyroidism.
GNAS gene mutation :

• Seen in Type 1a & pseudo-pseudo hypoparathyroidism.
• GNAS gene defect → GSa defect → Bone mineral changes.
• Bone mineral changes : Short 4th metacarpal (Albright hereditary
osteodystrophy), short stature.
• Other features : Round facies, mental retardation.
Biochemistry :
1. Type 1 : ↓ S. Ca2+, ↑ PO4, ↑ PTH (Complete resistance).
2. Type 2 :
• Partial resistance.
• ↑ cAMP in urine on administering PTH.
• No bone mineral changes.
3. Pseudo-pseudo hypoparathyroidism : Normal biochemistry.
Treatment :
Acute : 10 mL 10% calcium gluconate over 10 minutes.
Long term : Calcium supplementation.

Thyroid Disorders 00:32:07 ----- Active space -----
Hormone synthesis :
Steps :
1. Sodium-Iodide symport (Basolateral membrane) : Tc99 & I123 use this channel.
2. Iodide-Chloride antiport (Pendrin) : On apical membrane.
3. Organification : I- → I2. Mediated by TPO/DUOX.
4. Iodination : Iodination of Tyrosine residues → MIT, DIT.
5. Coupling (TPO mediated) :
• MIT+ DIT → T3.
• DIT + DIT → T4.
6. Re-uptake into epithelial cells.
7. Proteolysis and release of hormones.
At peripheries : Deiodinase-2 inhibitors :

• Propyl thiouracil.
T4 Deiodinase-2 T3. • Amiodarone.
• Propranolol.
T4 Deiodinase-3 Reverse T3 (rT3). • Steroid.
Properties of thyroid hormone :
• T4 is secreted abundantly but is converted to T3.
• 80% of thyroid hormone in blood is T3.
• Bound to :
a. Thyroid binding globulin (TBG) (60-70%).
b. Albumin (20%).
c. Transthyretin (10%).
Sick euthyroid syndrome :

• Seen in sick patients (Fasting, systemic illness, ICU).
• T4 to T3 conversion is inhibited → T4 is converted into rT3.
• Aka Low T3 syndrome.
• Biochemistry :
a. T4 : Normal to ↑. c. rT3 : ↑↑.
b. T3 : ↓↓. d. TSH : Normal.
• As disease progresses, there is rapid clearance leading to :
a. T4 : ↓. c. rT3 : ↑.
b. T3 : ↓. d. TSH : ↓.

150 20 Medicine

Approach to hyperthyroxinemia :
↑ T3
Hyperthyroxinemia
↑ T4
↑ Free T3 (fT3) RTH Normal fT3, fT4

↑ Free T4 (fT4)
Euthyroid
Thyrotoxicosis hyperthyroxinemia
(Symptomatic) (Asymptomatic)
Overworking gland Stored hormone D/t ↑ TBG :

release • Pregnancy.
Hyperthyroidism • OCPs.
Subacute thyroiditis • Chronic active hepatitis.
• Tamoxifen.
RTH (Resistance to �hyroid Hormone) :

• ↑ fT3 & fT4 but receptors are insensitive → Clinically euthyroid.
• ↑↑ TSH.
↑↑ TSH Normal TSH
↓ TSH
(> 5 mIU/L) (0.5-5 mIU/L)
(<0.5 mIU/L)
1. Symptomatic : Pituitary
Primary hypothyroidism Hypopituitarism
cause.
↓↓ fT3 & fT4 (Autoimmune condition) (Inappropriate
2. Asymptomatic : Last
Hashimoto’s thyroiditis. normal)
stage of sick euthyroid.
Normal fT3 & fT4 Subclinical hypothyroidism. - -
1. Toxic : TSH secreting
↑↑ fT3 & fT4 pituitary adenoma. - Thyrotoxicosis
2. Euthyroid : RTH.
Effects of thyroid hormone :

1. ↑ BMR.
2. ↑ CO, ↑ BP.
3. ↑ Responsiveness to catecholamines.
4. Catabolic action : ↑ Proteolysis seen as muscle wasting, osteopenia/
osteoporosis, hypercalcemia, stones formation.
5. Clearance of cholesterol.

6. ↑ Gluconeogenesis and glucose utilization. ----- Active space -----

7. ↑ O2 consumption except brain and gonads.
8. Thermogenesis : Acts as an uncoupler.
9. Bone growth.
10. Myelination of CNS.
11. Conversion of b carotene to Vitamin A.
12. Stimulation of erythropoiesis.
Hypothyroidism 00:52:31
Types :
1. Primary.
2. Secondary : Acquired hypopituitarism.
3. Congenital : Pediatric population.
4. Consumptive : D/t hemangiomas.
Primary hypothyroidism :
Causes : Features :
• Surgical removal. • Heterogenous, irregular, firm
• Iodine deficiency. enlargement, painless (Nodules
• Li-induced. absent).
• IFN-a. • Incidence : F > M; 45-65 years.
• Amiodarone. • HLA : HLA-DR3/DR4.
• Autoimmune conditions :
a. Hashimoto’s.
b. APS-1 << APS-2.
Thyroid autoantibodies : Evaluation :

• TPO-Ab (90-100%). • ↓/N fT3.
• Thyroglobulin Ab (80-90%). • ↓/N fT4.
• TSH receptor Ab (10-20%). • ↑↑ TSH.
• Antibodies +ve → Hashimoto’s.
Histology :
• Oxyphil metaplasia.
• Follicular atrophy.
• Germinal centre formation.
• Lymphocytic infiltration.
Pre-malignant : MALTOMA (Marginal zone lymphoma) > Papillary thyroid cancer.
152 20 Medicine

Presentation :
1. Slowing of metabolic processes : 2. Accumulation of matrix GAGs :
• Fatigue. • Puffiness.
• Weight gain. • Macroglossia.
• Slowing of speech/hoarse voice. • Non-pitting edema/myxedema.
• Constipation. • Periorbital edema.
• Dryness of skin.
3. Others :
• ↓ HR.
• Poor concentration.
• Cold intolerance.
• Hair loss.
Note : False hypothyroidism seen in
• Menorrhagia/infertility.
Addison’s disease.
• Delayed deep tendon reflexes.
Treatment : Levothyroxine : 1.6-1.8 mg/kg/day.
Myxedema coma :
Presents with ↓ consciousness & seizures.
Findings : Trigger : Infections.
• Profound bradycardia.
• Pericardial effusion. Treatment : IV Levothyroxine + IV steroids.
• Hypothermia.
• Hypoventilation.
• Hypoglycemia.
• Hyponatremia.
Hyperthyroidism 01:02:42
Types :
1. Primary :
a. Diffuse enlargement : Graves disease (Autoimmune).
b. Nodular enlargement : Toxic multinodular goiter.
2. Secondary : TSH secreting pituitary adenoma.
Grave’s disease : Antibodies :

20-40 years. • TSH receptor Ab (80%).
F > M. • TPO Ab (50-80%).
Associated with smoking & HAART. • Thyroglobulin Ab (50-70%).

Presentation : ----- Active space -----

1. ↑ fT3 & fT4 :
• Restlessness, anxiety, tremors. • Proximal myopathy.
• Tachycardia, palpitations. • ↓ Bone mineral density → Fractures.
• Arrhythmia : Atrial fibrillation. • Apathetic thyrotoxicosis.
• Hypokalemic periodic paralysis. • Diarrhoea.
2. TSH receptor Ab → ↑ GAG : Seen only in Grave’s disease.
Ophthalmopathy
Dermopathy : Pretibial myxedema Acropachy
Management :
First line : Carbimazole 5 mg TDS + Propranolol 40 mg QID.
Relapse (50%) → Definitive Rx : Radio-iodine ablation (or) Surgery.
Subacute/De quervain’s thyroiditis :

Aka viral/granulomatous thyroiditis.
Presentation : Fever + Sore throat + Painful thyroid.
Findings :
• ESR ↑↑.
• Low uptake.
Initially presents with toxicosis but it may proceed to hypothyroid state.
Treatment :
• Aspirin (TOC).
• NSAIDS.
• Steroids.
Painless thyroiditis :
Aka Post-partum/silent thyroiditis.
ESR is normal.
Anti-TPO Ab present.
Associated with underlying autoimmune disorder : Type 1 DM (M/C).
No role for steroids.
Propranolol may be used.
Riedel’s thyroiditis :
Chronic thyroiditis.
IgG4 related disease.
Thyroid profile : Normal.
Dense, hard thyroid.

154 20 Medicine

Diabetes Mellitus 01:12:58
Classification :
Type Features
• Autoimmune destruction of pancreas (T & B cell mediated).
1 • ↓↓ Fasting C-peptide.
• Rx : Insulin.
Pathogenesis : Insulin resistance & ↑ lipolysis.
Complications :
• Macrovascular (M/C : Cardiac) : Unrelated to control of diabetes.
2 • Microvascular :
a. Ophthalmopathy.
b. Neuropathy.
c. Nephropathy.
1.5 KPD Type 2 DM behaving like type 1 DM.
• Type 1 DM behaving like type 2 DM.
1.5 LADA
• Antibodies positive.
3 Brain DM/Double DM/Alzheimer’s disease.
Pancreatic DM :
• Tropical chronic calcific pancreatitis.
3c • Hemochromatosis.
• IgG4 related disease.
• Cystic fibrosis.
Drug induced :
• L-asparagine.
3d
• Growth hormone.
• Tacrolimus.
• Elderly patients.
4 • ↑ T regulatory cells.
• Minimal symptoms.
• Seen across generations.
MODY • Good prognosis.
• M/C : MODY 3 (HNF-1a mutation).
KPD : ketosis Prone DM.
LADA : Latent Autoimmune Diabetes in Adults.
MODY : Maturity Onset Diabetes in Young.

Work up : ----- Active space -----

1. Continuous blood glucose monitoring.
2. HbA1c.
3. Ophthalmic evaluation.
4. Nerve conduction studies.
5. Urine routine examination.
6. Treadmill test If +ve Angiography.
Treatment :
Insulin :
Indications : Types of insulin :
• HbA1c ≥ 9.5. 1. Ultra short acting : Lispro.
• Microvascular complications. 2. Short acting : Regular insulin.
• H/o macrovascular events. 3. Intermediate acting : NPH.
• Diabetic ketoacidosis. 4. Long acting : Glargine.
• Type 1 DM/Type 1.5 LADA. 5. Ultra long acting : Degludec.
Target : HbA1c = 7.
Initial regimen :
• Total insulin to be given = 40 U.
• 24U of regular insulin (8 U × 3 times/day) + 16U Glargine (daily)/Degludec
(alternate days).
Oral Hypoglycemic Agents (OHAs) :

1. Metformin :
• MOA : ↑ AMP kinase.
• Dose : 500 mg BD (Upto 1g TDS).
• C/I : GFR <40 mL/minute → ↑ Chances of lactic acidosis
• Advantages :
a. ↓ HbA1c by 1.5%.
b. No hypoglycemia.
c. Promotes weight loss.
d. Helps with insulin resistance.
e. CVS neutral.

156 20 Medicine

Add-on to metformin :
• For comorbidity control.
• Given in :
a. Atherosclerotic vascular disease (ASVD) : GLP-1 analogue/SGLT2
inhibitor.
b. Heart failure with reduced EF : SGLT2 inhibitor.
c. CKD : SGLT2 inhibitor.
2. SGLT2 inhibitor :
• Drugs :
a. Dapagliflozin (10 mg).
b. Empagliflozin (25 mg).
• Advantages :
• ↑ Risk for :
a. Promotes diuresis & natriuresis.
a. Mycotic UTI.
b. No tachycardia.
b. Ketosis.
c. Inhibits RAAS.
d. Prevents proteinuria.
3. GLP-1 analogue & DPP-4 inhibitor :

GLP-1 analogue (Preferred) DPP-4 inhibitor
Liraglutide (S/c)
Drugs Gliptins (Oral)
Semaglutide (Oral)
CVS Benefit Neutral
Weight Weight loss Neutral
4. Sulfonylureas :
• Not used anymore d/t CVS mortality.
• Gliclazide may be tried.
Standard prescription :
• Start with : Metformin 500 mg BD (Can be increased upto 1g TDS).
• Add SGLT2 inhibitor/Liraglutide 0.6-1.8 mg s/c.

Med Endo

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Med Endo

Uploaded by

Copyright:

Available Formats

Endocrinology Revision 1 17 115

ENDOCRINOLOGY REVISION 1 ----- Active space -----

Classification of hormones 00:05:10

On the basis of structure :

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Group Receptor Property Examples

Group 2 hormones receptors :

Medicine Revision • v1.0 • Marrow 6.5 • 2023

cGMP IP3/DAG cAMP ----- Active space -----

Pituitary gland 00:24:32

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

• First cell to appear : Corticotroph. ----- Active space -----

Relation of hypothalamus to pituitary gland :

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space ----- Pituitary Tumor

Hormonal effect Stalk effect Mass effect

Functional tumors : • ↑ ICT symptoms.

Disruption of the stalk → loss

Medicine Revision • v1.0 • Marrow 6.5 • 2023

PRL levels Conditions ----- Active space -----

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Drugs → Dopaminergic agonist :

Follow up after 1 month → PRL levels.

↓↓ PRL ↑↑ PRL ↑↑ PRL with S/E of

Surgical management : ----- Active space -----

Growth hormone 01:02:27

T1/2 : 5-20 min, pulsatile → Levels cannot be checked directly.

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Medicine Revision • v1.0 • Marrow 6.5 • 2023

Work-up : ----- Active space -----

On relapse : 2nd Sx done, curated as much as possible.

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Acquired Hypopituitarism 00:00:18

Causes : Functional → Macroadenoma (GH secreting)

Medicine Revision • v1.0 • Marrow 6.5 • 2023

Pituitary Apoplexy : 00:10:06

Acute intrapituitary hemorrhage.

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space ----- Sheehan syndrome vs Lymphocytic Hypophysitis : 00:15:15

Sheehan syndrome Lymphocytic hypophisitis

Necrosed gland Inflammatory mass

Medicine Revision • v1.0 • Marrow 6.5 • 2023

Empty sella : 00:17:12 ----- Active space -----

Primary Empty sella Secondary empty sella

Stimuli for ADH release :

Osmotic stimuli (Major) Non osmotic stimuli (Minor)

Note : ADH doesn’t cause hypernatremia as there is a compensatory in thirst.

Activates cAMP protein kinase A

Aquaporin (AQP2) expression

Free H2O reabsorption

Medicine Revision • v1.0 • Marrow 6.5 • 2023

----- Active space ----- Hyponatremia : 00:25:58

Disorder of H2O metabolism.

Medicine Revision • v1.0 • Marrow 6.5 • 2023

SIADH (Syndrome of Inappropriate ADH) : ----- Active space -----

Cerebral Salt wasting syndrome vs SIADH :

Diabetes Insipidus : 00:42:23