Thyroid Functions

Thyroid Hormones1
 T4 (Thyroxin): secreted from thyroid gland only.
 T3 (Tri-iodothyronine): secreted from liver, kidney, muscles.
 rT3 (reversed T3): inactive part of the hormone ( ‫)مبتشتغلش هورمون‬.

Synthesis of the thyroid hormones:

a. Trapping of serum iodide by the thyroid gland is the first step in synthesis.
b. Iodide oxidation: Inside the thyroid gland the iodide is oxidized by peroxidase to iodine which
is combined with tyrosyl to form mono- & di- iodotyrosins. By coupling they form T3 & T4.
c. Released in the circulation as T3, T4 & rT3 all bound to plasma proteins:
i. Thyroid binding globulin (TBG): binds to 70% of T4 & 80% of T3.
ii. Thyroxin binding pre-albumin (TBPAL).
iii. Thyroxin binding albumin (TBAL).
N.B:
 99% of total T3 & T4 are bound (bound thyroxine cannot get into cell & cannot work)
cannot produce function.
 Circulating T3 & rT3 are formed by T4 de-iodinization rather than direct secretion from the
thyroid gland. This occurs in different body tissues. If this de-iodinization occurs in the outer
ring the results will be T3, & if this occurs in the inner ring the results will be rT3.
 Free T4 = 0.05% of total T4. Free T3 = 0.2% of total T3.
 Free thyroid hormones can cross all membranes & affect intracellular metabolism.
 Free thyroid hormones correlates better with thyroid status than total plasma thyroid
hormones.

Fate of thyroid hormones:

1. Inactivation by deamination.
2. 10% of T3 & T4 produced each day is excreted in bile then re-enter the pool of thyroid
hormones.
3. Small amount is excreted in urine.

Regulation of thyroid hormones:

- Hypothalamus releases the hypothalamic thyrotrophin releasing hormone (TRH) that
stimulates the anterior pituitary to release TSH that stimulates the thyroid to release T3 & T4.
- if T3 & T4 increase, negative feedback occurs.
Thyroid investigations2:
 TSH: 0.4 - 4.2 mIU/L
 tT3: 1.08 – 3.14 nmol/L & fT3: 3.2 – 6.8 pmol/L
 tT4: 59 – 135 nmol/L & fT4: 10.3 – 34.7 pmol/L
 Thyroid antibodies (antithyroglobiluin & antimicrosomal), serum thyroglobulins, gland
biopsy, in vivo radio-active iodine test

‫ سوسن سعٌد‬.‫د‬.‫ محاضرة أ‬1

‫ سؤال تحرٌري االرقام لٌست للحفظ‬2

1
 Thyroid Functions

Investigations of thyroid disorders:

I. Primary hypothyroidism diagnosis:
1. Very high TSH (> 20 mIU/L): TSH elevation may precede the decrease of T4 & T3
2. Low free & total T4 May be just low normal
3. Low free & total T3 (?? Why? Normal concentrations ‫ال ٌتوقف تشخٌص النقص على انخفاض‬
are often observed) )‫ له مصادر أخرى‬T3( ‫شدٌد فٌهم‬
4. Low T3 uptake & FTI (Free Thyroid Index)
5. Positive antimicrosomal or antithyroglobulin antibodies in Hashimoto's thyroiditis.
Follow up of tretment: The return of hormones to normal levels is as follows:
- T4: in few days.
- T3: in 2 - 4 wks.
- TSH: 6 - 8 wks.
T4 T3 TSH
First few days 1wk 2wk 3wk 4wk 5wk 6wk 7wk 8wk
Thus, early follow up is according to period of treatment
Long term follow up TSH is enough.

II. Secondary hypothyroidism diagnosis:

1. Low TSH.
2. Low total & free T4.
3. Low total & free T3.
4. TRH (thyrotrophin) stimulation test: (give external TRH)
- Delayed normal response: hypothalamic lesion.
- Blunt response: pituitary lesion.

III. Primary hyperthyroidism diagnosis:

1. Low TSH
2. High total & free T4.
3. High total & free T3: alone can cause T3 thyrotoxicosis.
4. High T3 uptake & FTI.
5. TRH stimulation test: -
- Blunted response to TRH stimulation.
- Positive thyroid stimulation Igs in Grave's disease (TSH receptor antibodies).
Follow up of treatment:
- Follow up is done every two months and thereafter every year.
- In the first 6 months depends on T4 (or T3 in T3 thyrotoxicosis) since TSH is still
suppressed and is not reliable.
- Patients treated with thiouracil should also be followed up by CBC (to detect
agranulocytosis) and LFTs.
N.B:
 90% of 1ry hypothyroidism patients have both high T4 & T3.
 T3 thyrotoxicosis: High T3, normal T4 & low TSH.
IV. Secondary hyperthyroidism diagnosis:
1. High TSH.
2. High total & free T4
3. High total & free T3
4. High T3 uptake & FTI (free thyroxin index).
5. TRH stimulation test: blunt response.

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 Thyroid Functions

Thyroid function tests in pregnancy

Pregnancy is accompanied by the following changes in TFTs:
1. Elevated TBG leading to elevated total T3 & T4, so measurement of free T3 & T4 is a more
accurate index of thyroid status.
2. In the 1st & 2nd trimester there is a low or undetectable TSH due to the thyrotrophic effect of
β-HCG that causes elevation in T3 & T4 leading to decreased TSH, but after 20 wks TSH
becomes a reliable index of thyroid status.

Non thyroidal illness (NTI) & the sick euthyroid syndrome:

Definition: Disturbances in TFTs (T3, T4, TSH), however, the patient is euthyroid requiring no
treatment for thyroid status.
Causes: Various illnesses affecting extrathyroid tissues e.g.
1. Chronic Heart Failure,
2. DM,
3. Febrile illness,
4. Renal failure,
5. Acute and chronic liver diseases,
6. Major surgery
7. Other diseases.
Causes of elevated TBG Causes of decreased TBG
= Causes of false high tT4 & tT3 = Causes of false low tT4 & tT3
1. Pregnancy.
2. Estrogen therapy 1. Androgen therapy
3. Estrogen producing tumors 2. Testosterone producing tumors.
4. Viral hepatitis 3. Liver cirrhosis.
5. Heroin addiction. 4. Nephrotic syndrome.
6. Hereditary elevation of TBG or 5. Malnutrition.
variants of albumin & pre-albumin
Significance: Diagnosis of thyroid diseases in such cases must depend on the presence of
clinical features & biochemical abnormalities.
Reversed T3: it differentiates between non thyroidal illness (elevated rT3 & decreased T3) &
hyperthyroidism (both are elevated).
Free T3 & T4: It can better discriminate between hypo-, hyper- & eu- thyroid state and is not
affected by TBG changes.
S TSH: Only sensitive TSH (sTSH) can distinguish between normal individuals with TSH level in
range of 0.34 – 1.0 IU/ml, and those with 1ry hyperthyroidism showing levels below 0.3 IU/ml
down to 0.03 IU/ml.

T3 Resin uptake & free thyroxin index: ‫غير مهم‬

 Free thyroxin index is used to correlate the effect of changes in TBB.
 Free thyroxin index (FTI) = T4 x T3 resin uptake.
 Now, FTI is replaced by measurement fT4 & fT3

3
 Adrenal Gland

Adrenal Gland3
Adrenal Anatomy and Physiology
A. Adrenal Cortex
Three zones are responsible for corticosteroid synthesis:
a. Outermost layer, the zona glomerulosa, synthesizes aldosterone, which is the
predominant mineralocorticoid responsible for Na retention and K excretion.
b. The middle and inner layers, the zona fasciculata and the zona reticularis, produce:
- Glucocorticoids (principally cortisol which functions to promote protein and lipid
catabolism and gluconeogenesis).
- Sex steroids and their precursor, dehydroepiandrosterone (DHEA).

B. Adrenal Medulla:
Catecholamines are synthesized in the adrenal medulla and they are regulated via the
autonomic nervous system.
Regulatory Systems for Cortisol and Aldosterone.

3
‫ منال عبدالعزٌز‬.‫د‬.‫أ‬

4
 Adrenal Gland

Glucocorticoids
Adrenocortical Hyperfunction
(Cushing's Syndrome)
Definition: A group of symptoms, signs, and biochemical abnormalities that result from
prolonged exposure to excess levels of glucocorticoids.
NB Cushing disease is the term used with the gland dysfunction (not including iatrogenic causes)
Pathogenesis: The principal glucocorticoid, cortisol, results in:
1. Catabolic effects in most tissues (Primarily)  muscle wasting and weakness due to
generalized protein catabolism.
2. Impaired collagen production tensile strength of dermal structures, including blood
vessels  spontaneous ecchymosis, purple striae, and poor wound healing.
3. Diffuse fine body hair growth.
4.  intestinal calcium absorption bone reabsorption and hypercalciuria, progressing to
osteoporosis.
5. Hyperglycemia: results from the direct anti-insulin effect of cortisol and a cortisol-mediated
increase in hepatic gluconeogenesis and glycogenolysis.
6. Impaired immune and inflammatory response is seen due to a variety of immunologic
effects, including:
- Impairment of PMN phagocytosis; susceptibility to
- Depletion of T lymphocytes, monocytes, and eosinophils;  bacterial and fungal
-  antibody formation. infections
7. The permissive effect of cortisol on catecholamine activity results in:
Hypertension.
Positive inotropic effects on the heart.
8. Lipolytic effects by  mineralocorticoids and cortisol  affect adipocytes differentially 
fat wasting in the extremities and fat deposition centrally in the face, neck, and trunk 
typical Cushing's features of centripetal obesity, moon facies, and buffalo hump.

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 Adrenal Gland

Clinical Features of Cushing's Syndrome

Features Unique to Iatrogenic
Nonspecific Features Specific Features
Cushing's Syndrome
- Generalized obesity - Central obesity - Aseptic necrosis of femoral
- Hypertension - Ecchymoses and humeral heads
- Abnormal glucose tolerance - Pigmented striae (> 1 cm) - Glaucoma
- Amenorrhea or impotence - Osteopenia - Cataracts
- Hirsutism - Muscle weakness - Benign intracranial
- Spontaneous hypokalemia hypertension
- Erythrocytosis - Pancreatitis
Cushing's syndrome: Etiology and differential diagnosis:
Type Frequency Unique features
Iatrogenic Common Absence of signs of androgen excess due to suppression of
adrenal androgen production
Pituitary (Cushing's 60 % Signs of androgen excess present; pituitary tumor; suppresses
disease) with high-dose dexamethasone testing
Adenoma 30% Absence of signs of androgen excess; no suppression with
high-dose dexamethasone testing
Carcinoma Rare Mayor may not have features of androgen excess; 50%
metastatic at diagnosis; no suppression on testing
Bilateral nodular Uncommon Features of androgen excess present; suppression with high-
hyperplasia dose dexamethasone testing; may be Cushing's disease
without visible pituitary lesion
Ectopic ACTH 10% Tumors associated with this are small cell carcinoma of lung,
syndrome pancreatic carcinoma, bronchial adenoma, thymoma;
features of androgen excess may be present; lack of
suppression to high-dose dexamethasone .

Laboratory Diagnosis of Cushing's Syndrome: ‫هام‬

Cushing's
Normal Adrenal tumour Ectopic ACTH
Syndrome
Screening Tests
U. Free Cortisol <100 μg/d >120 μg/d >120 μg/d >120 μg/d
Overniqht
dexamethasone test 4
s. Cortisol (8 am) <3 μg/dL >10 μg/dL >10 μg/dL >10 μg/dL
Differential Diagnostic Tests
PI. ACTH (8 am) 10-85 pg/mL 40-260 <10 N or 
s. Cortisol (8 am) 5-23 μg/dL N N or  N or 
High-dose Overnight
dexamethasone test 5
s. Cortisol (8 am) 50% supp. Most supp No supp No supp
CRH stimulation test
PI. ACTH Not indicated  response  response  response
CT or MRI - Pituitary Adrenal Other locations

4
1mg dexamethazone given.
5
8mg dexamethazone given

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 Adrenal Gland

Workup for Cushing's syndrome 6

Dexamethasone Suppression Test

a. Overnight dexamethasone suppression test:
1 mg of dexamethasone (cortisol analougue) at 12 pm then determine s. cortisol at 8 am
b. High dose dexamethasone suppression test:
4 mg of dexamethasone at 12 pm then determine s. cortisol at 8 am
NB Kits in the market measures external cortisone along with internal cortisol.

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‫الجدول أهم للكلٌنٌكال باثولوجً والفلوشارت أهم للباطنة‬

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 Adrenal Gland

Adrenocortical Hypofunction
Primary is the main cause of Addison's disease and is mainly due to TB
Hypofunction is more difficult to diagnose than hyperfunction.
Primary Secondary
Aetiology:
Destruction of adrenal cortex, with consequent diminished ACTH production by the
loss of all corticosteroid hormone production pituitary
In this type,
- Glucocorticoid and androgen production
are affected.
- Mineralocorticoid production remains
largely intact because ACTH plays only a
small role in aldosterone regulation.
Causes
- Autoimmune/idiopathic (70%) - Iatrogenic (following exogenous
- Tuberculosis (20%) glucocorticoids) (common)
- Other (10%) - Isolated ACTH deficiency (uncommon)
Fungal infections - Hypothalamic/pituitary lesions
Adrenal hemorrhage (uncommon)
Congenital adrenal 'hyperplasia
Sarcoidosis
Amyloidosis
HIV/AIDS
Adrenoleukodystrophy
Metastatic disease
Clinical Features of Primary Adrenal Insufficiency:
Symptoms:
- Weakness and fatigue (100 %)
- Anorexia (100%)
- Nausea and diarrhea (56%)
Signs:
- Weight loss (100%)
- Hyperpigmentation (97%)
- Hypotension (91%)
- Vitiligo (rare)
Laboratory Findings:
- Hyponatremia (90%)
- Hyperkalemia (66%)
- Hypoglycemia (40%)
- Hypercalcemia (6%)
Diagnostic Procedures:
A. Plasma ACTH Level: differentiates between primary and secondary adrenal insufficiency.
Patients have elevated ACTH levels, Patients have normal or low levels
B. Rapid ACTH stimulation Test (Cosyntropin test):
Procedure: Baseline s. cortisol is determined followed by injection of 250 μg cosyntropin (1-
24 ACTH), then measurement of s.cortisol at 30 and 60 min after injection.
Interpretation:
- Highly accurate in establishing or excluding adrenal insufficiency.
- Measures only adrenal response to injected synthetic ACTH and does not test for
endogenous ACTH or corticotropin-releasing hormone (CRH) deficiency.

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 Adrenal Gland

Primary Secondary
C. The metyrapone test:
Metyrapone block final step in cortisol synthesis  stimulating an ACTH response to a
temporary decrease in cortisol production.
Procedure: Metyrapone is given at 12 pm orally with milk or snack to delay absorption, then
at 8 am measure 11-deoxycortisol, cortisol and ACTH.
Interpretation: Those who are confirmed to have secondary adrenal insufficiency may
require additional testing to rule out secondary thyroid or gonadal failure.
Laboratory Studies and Diagnostic Procedures

PPD = tuberculin test

NB Tertiary hypoadrenalism: due to hypothalamic lesion
Normal Adrenal insufficiency
1ry 2ry 3ry
Screening tests
Pl ACTH (8 am) 10-85 pg/mL  N or  N or 
s.Cortisol (8am) 5-23 μg/dL  N or  N or 
Challenge tests
Rapid ACTH stimulation
Peak cortisol >20 μg/dL <20 μg/dL Any Any
Overnight metyrapone test
Pl.11deoxycortisol >7 μg/dL Not indicated <7 μg/dL <7 μg/dL
Pl. ACTH >150 pg/mL Not indicated <150 pg/mL <150 pg/mL
CRH stimulation test
Pl. ACTH Not indicated Not indicated  response  response

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 Adrenal Gland

Mineralocorticoids
Aldosterone:
- The major mineralocorticoid produced by the adrenal gland.
- Its Production is affected by:
Angiotensin II and extracellular K (Primarily)
ACTH plays a small role.
Angiotensin II:
- Responsive to renin secreted by the renal JGA in response to low renal perfusion pressure
and low extracellular sodium concentration.
- Renin stimulates hepatic conversion of angiotensinogen  angiotensin I, which is in turn
converted in the lungs to angiotensin II.
Stimulation of this axis results in increased aldosterone production, resulting in distal tubular Na
retention and in renal K excretion.

Hyperaldosteronism
Pathogenesis:
Excess mineralocorticoid results in
1. Hypokalemia: Hypokalemia and sodium retention occur because aldosterone acts on the
cortical collecting tubules via sodiumpotassium-ATPase, which in turn activity of the
Na-K pump that draws Na into the tubular cells and secretes K into the lumen.
2. Metabolic alkalosis: results from excess secretion of hydrogen ion into the tubular
lumen, occurring in the renal medullary collecting tubules under aldosterone's influence
as well.
3. Na retention: leads to volume expansion and hypertension.
4. Renin and angiotensin II levels: due to primary overproduction of aldosterone.
Causes of Hyperaldosteronism:
A. Primary Hyperaldosteronism
 Aldosterone-producing adenoma (APA) (65%)
 Idiopathic hyperaldoesteronism (IHA) (34 %)
 Aldosterone-producing carcinoma (APC) (1%)
 Glucocorticoid-suppressible hyperaldosteronism (GSH) (1%)

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 Adrenal Gland

B. Secondary Hyperaldosteronism
Renin-mediated aldosterone excess (high renin and aldosterone levels)
(1) Secondary Hyperaldosteronism with Edema
Nephrotic syndrome
Hepatic cirrhosis
Congestive heart failure
Severe malabsorption
(2) Secondary Hyperaldosteronism with Hypertension Renovascular hypertension
Malignant hypertension
Primary hyperreninism Juxtaglomerular cell tumor)
(3) Secondary Hyperaldosteronism (Miscellaneous)
Diuretics
Vasodilators (except prazosin)
Chronic self-induced vomiting
Excess licorice ingestion

Diagnosis of hyperaldosteronism
A. Saline suppression test: (saline Na aldosterone)
Procedure:
- The subject awaked at 6 am,
- be sure that he is not hypokalemic,
- kept in upright posture for 2 hours.
- PI. Aldosterone is measured at 8 am,
- Give 2 L saline infusion over 4 hs
- Measure pI. Aldosterone again.
Interpretation:  aldosterone = normal, no  in aldosterone = tumor
B. Furosemide Stimulation Test:
Procedure:
- Patient is kept in upright posture during the test
- Measure Renin/aldosterone,
- Give 40-80 mg of Furosemide (Lasix)
- Measure renin/aldosterone after 4 hs .
Interpretation: Normal: aldosterone and renin 

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 Adrenal Gland

Aldosterone renin ratio


Saline infusion test

Aldosterone

 
No 1ry hyperaldosteronism 1ry hyperaldosteronism

Adrenal CT

Negative Positive

0. Renin aldosterone
stimulation test

 No 

Normal

Scheme for the laboratory work-up of suspected aldosteronism causing hypertension

PRA, plasma renin activity; 18P-OH, 18P-hydroxycorticosterone.

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 Adrenal Gland

Hypoaldostero nism
Pathogenesis:
 aldosteronemediated synthesis of Na-K ATPase in renal tubular cells resulting in:
- Hyperkalemia: can be severe  arrhythmias and even sudden death.
- and sodium wasting: The sodium wasting is more modest:
- Decreased effective blood volume,
with no clinical evidence of
- Mild hyponatremia,
volume depletion.
- Postural hypotension
- Metabolic acidosis may also be present due to decreased aldosterone-mediated renal
tubular secretion of hydrogen ion.

Causes:
A. Hyporeninemic Hypoaldosteronism:
- Diabetes mellitus
- Hypertensive nephrosclerosis
- Adrenergic blocking agents
- Chronic volume expansion
B. Hyperreninemic Hypoaldosteronism
- Aldosterone enzyme defect
- Heparin
- Lead poisoning
- ACE inhibitor .
- Severe illness
C. Pseudohypoaldosteronlsm
- Chronic interstitial nephritis
- SLE
- Amyloidosis
- Spironolactone

Diagnosis of Hypoaldosteronism
Renin-aldosterone stimulation test:
 Low stimulated renin and aldosterone levels point to a diagnosis of hyporeninemic
hypoaldosteronism
 High stimulated renin and low aldosterone levels point to a defect at the level of the adrenal
 High stimulated renin and aldosterone levels point to end-orqan resistance to aldosterone's
effects.

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 Adrenal Gland

Adrenal Medulla
- Composed of chromaffin tissue derived from neural crest ectoderm.
- The source of all epinephrine (norepinephrine is produced by extra-adrenal chromaffin cells).
- The enzyme critical to epinephrine formation is inducible by high levels of glucocorticoids,
delivered from the cortex to the medulla by a rich blood supply.

Pheochromocytoma
Definition: A tumor of the chromaffin cells that is serious cause of hypertension
Pathogenesis:
 Renal effect: Excess production of catecholamines  stimulate renal Na retention via a direct
tubular effect, increased renin secretion, and reduced intrarenal hydrostatic pressure.
 Metabolic effects:
- Hyperglycemia: due to catecholamlne-medlated increases in glycogenolysis and
gluconeogenesis.
- hyperlipidemia, Most of these effects occur due to increased β-receptor-
- hypokalemia, mediated stimulation of adenyl cyclase which results in
- tissue oxygen consumption. increased conversion of ATP to c.AMP.
Diagnosis of Pheochromocytoma
1) Measurement of 24hour urine excreted metabolites (metanephrines, VMA, and
catecholamines):
Best determinant of production of epinephrine and/or norepinephrine: most sensitive and
specific urinary test.
Preanalytical precautions:
a) 24 hr Collection must be performed carefully.
b) Drugs should be eliminated 2 weeks before testing can interfere with the test results.
- α-methyldopa,
- Amphetamines,
- β-blockers.
- Benzodiazepines,
- Chlorpromazine,
If antihypertensive agents must be continued,
- Clofibrate,
diuretics or vasodilators e.g. hydralazine and
- Disulfiram.
minoxidil cause minimal interference.
- Ethanol,
- Quinidine,
- Reserpine,
- Tetracycline,
- Theophylline,
c) Foods that cause analytical interference (co-eluted with VMA) must be stopped 72
hours before test: chocolate, vanilla, banana
Analysis: HPLC
Interpretation:
-Twofold elevations in over95% of patients with pheochromocytoma.
-Mildly elevated values of all the catecholamine metabolites are common among
hypertensives; only very high values are consistent with a diagnosis of pheochromocytoma.
2) Plasma catecholamine measurements:
As reliable as urinary measurements,
Can be artificially elevated by stress, volume depletion, activity, anoxia, smoking, and
medications; thus they must be performed under idealized conditions at complete
bed rest.

14
 Adrenal Gland

3) Clonidine7 suppression test:

Indication: Used when the diagnosis is uncertain and plasma norepinephrine levels are
only modestly elevated (500 to 1000 pg/ml).
Procedure:
- Clonidine, 0.3 mg, is given
- Plasma norepinephrine levels are measured 3 hours later.
Interpretation:
Essential hypertension suppress norepinephrine levels <500 pg( ml,
Pheochromocytoma do not.
Normal Catecholamine Values
Urine Plasma
Metanephrine <1.3 mg/24 hr
VMA 2-7 mg/24 hr
Norepinephrine 0-34 μg/24 hr 60-400 pg/ ml
Epinephrine 550 μg/24 hr 10-55 pg/ ml
Dopamine <l00 pg/ml

Incidental Adrenal Masses

 The ability of abdominal CT scan or MRI performed for unrelated reasons to detect adrenal
masses of 0.5 cm or smaller has resulted in a diagnostic dilemma.
 Incidental masses: The prevalence of such incidentally discovered masses is 1% to 4%
 Hormonal evaluation: should be performed for all patients. Identification of hormonal
activity indicates the need for surgical removal.
 Nonhypersecretory masses: Adrenal masses found to be nonhypersecretory require an
investigation to rule out malignancy via CT, MRI or biopsy.
 Screening tests for Incidental Adrenal Masses:
Hypersecretory State Frequency Screening test
Pheochromocytoma 0-11% 24-hr urine catecholamines
Cushing's syndrome 0-12% Overnight dexamethasone suppression
test
Aldosterone-producing adenoma 0-7% Blood pressure and serum K+; if HTN, do
renin/aldosterone ratio
Masculinizing tumor 0-11% Serum dehydroepiandrosterone sulfate
Feminizing tumor Rare Serum estradiol in Feminized men

7
Antihypertensive, also used in GH (stimulation test)

15
 Adrenal Gland

Congenital Adrenal Hyperplasia

Definition: A family of genetic conditions affecting adrenal glands that can interfere with normal
growth and development in children including normal development of the genitals.
Incidence: It affects both males and females
Pathogenesis: This inherited
genetic defect (autosomal
recessive) formation of either:
a) 21-hydroxylase (commonest)
b) 11β-hydroxylase
c) 3β hydrxysteroid
dehydrogenase isomerase
(worst).

Formation of Steroids:
Types
A. Classic congenital adrenal hyperplasia, the more severe form of the disease affecting very
young children
B. Nonclassic congenital adrenal hyperplasia, a milder form that usually develops in late
childhood or early adulthood
Symptoms
1. Shorter height (compared with either parent).
2. Severe acne
3. Fatigue.
4. Low blood pressure
5. Low bone density
6. High blood cholesterol.
7. Obesity
8. Slow recovery from infections, such as colds
9. Girls may have:
- Abnormal-appearing genitals (ambiguous external genitalia),
- Masculine characteristics, such as facial hair, excessive body hair, a deepening voice,
- Absence or irregularities of menstruation at the time of puberty.
- Later in life, they may have difficulty becoming pregnant.
10. Boys may have:
- signs of puberty as early as 2 to 3 years of age.
- As infants, boys may have an enlarqed penis. Their testes, however, will remain smaller
than normal throughout childhood and adulthood.
Complications:
Babies with congenital adrenal hyperplasia could experience a life-threatening adrenal crisis:
- serious Na deficiency in the blood, related to the malfunctioning of the adrenal glands.
- diarrhea,
- vomiting,
- dehydration,
- low blood sugar levels
- shock.

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 Adrenal Gland

Diagnosis
A. Prenatal screening:
Indications: Fetuses whose family members are known to carry the gene defect
Sample: Amniocentesis or chorionic villous sampling.
B. After birth:
Indications: child with ambiguous external genitalia
Technique:
- karyotyping to definitively determine the sex of the child.
- Pelvic ultrasound can provide images of female reproductive structures (cervix, uterus
and fallopian tubes) to help in the process of determining child's sex.
C. DHEA
D. 21 hydroxylase (21 OHase) deficiency:
Blood tests include:
- 17 α-hydroxyprogesterone,
- progesterone,
- 17 α-hydroxypregnenolone
- pregnenolone. Also DHEA-s, androstenedione, testesterone are elevated
E. 11β hydroxylase (11 OH ase) defficiency,
- 11 deoxycortisol,
- androstenedione
- DEHA-s are elevated
F. In 3 β hydrxysteroid dehydrogenase isomerase (3 β SDH Iso) defficiency
-  ratio of 17 α hydroxypregnenolone to 17 α hydroxy progesterone
-  ratio of DHEA to androstenedione.

mohammad_emam@hotmail.com

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