Thursday, June 17, 2004

THE ADRENAL CORTEX

Embryology: Unlike the medulla, which is of ectodermal origin, the cortex of the adrenal is mesodermal in origin. It arises in a ridge, which appears just by the side of the mesonephros (Wolffian body).

Structure: The adrenal cortex is composed of large polyhedral cells, rich in lipoids, and the cells are arranged in three different layers, which, from outside inwards are named:-
1.Zona glomerulosa which produces Aldosterone
2.Zona fasciculate which is store house of Steroids
3.Zona reticularis.which manufactures rest of coricoid hormones

Adrenal Cortical Hormones: The hormones of the adrenal cortex are all esters of cholesterol; the polycylic nucleus of cholesterol is modified by the addition of O2, OH2, or other complex groups, by the action of different enzymes. More than fifty such compounds have been isolated. The more important of these are divided into three groups:
1.Glucocorticoids.
(2)Mineralocorticoids or salt-regulating hormones.
3.Sex hormones.’

Glucocorticoids: These hormones are so named because they favor neoglucogenesis. The are concerned in the metabolism of protein and carbohydrate., favoring formation of glucose from non-carbohydrate sources. Hydrocortisone (cortisol) is the chief of these hormones. It is so called because it possesses a hydroxyl (OH) group at the 11-position- it thus belongs to the class of 11-oxysteroids. It is essential for life because it has an overall effect on general metabolism and also some effect on water and electrolyte balance. Cortisone is a synthetic preparation and converted into hydrocortisone in the body, exerting same effects.
Hydrocortisone, after metabolism is excreted in the urine chiefly as 17-hydroxycorticoids.
Hyperplasia or tumours of those cells which produce Glucocorticoids, results in what is known as Cushing’s syndrome. The Glucocorticoids are chiefly produced in zona fasciculate and zona reticularis.

Mineralocorticoids: These are concerned in the maintenance of water and electrolyte balance. Aldosterone is the most important of these hormones. It is also known as 11-desoxycorticoid because it possesses neither an oxygen atom nor a hydroxyl group at the 11 position (e.f. hydrocortisone). The control on water and electrolyte balance is effected mainly by the agency of the cells in the renal tubules. Excess of the hormones causes increased tubular Reabsorption of sodium and chloride, which are retained along with water in the blood (oedema, hypertension); there is loss of potassium in the urine resulting in hypopotassaemia. Conversely, a deficiency of the hormones results in loss of sodium in the urine and retention of potassium. The excess loss of sodium causes a fall in the osmotic tension of plasma and extracellular fluid; water now leaks into the cells and a dehydration (extra-cellular) results.
The synthetic mineralocorticoid is desoxycorticosterone (D.O.C.A.) and it has the same effects as Aldosterone.
Hyperpl;asia r neoplasm of those cells, which produce Aldosterone, results in what is known as Conn’s syndrome ( primary aldosteronism). Aldosterone is produced in the zona glomerulosa.

Sex Hormones: Both androgenic and oestrogenic hormones are produced in the adrenal cortex. The sex hormones are known as 17-ketosteroids or 17 oxosteroids because they possess an oxygen atom at the 17 position.
The male (androgenic) hormone is androsterone.
The female (oestrogenic) hormones are oestrone, oestriol and oestradiol-17B.
Excess of the Oestrogens may (very rarely) cause effeminancy in the males.

Control of Cortical Function: The adrenal cortex is under control of anterior pituitary through agency of A.C.T.H. i.e. adrenocorticotrophic hormone (corticotrophin) which stimulates the adrenal cortex. Conversely hydrocortisone of the adrenal cortex inhibits the secretion of ACTH (feed back mechanism).

Role of Adrenal Cortex in ‘Stress’: The adrenal cortex quickly responds to all types of stress (trauma, haemorrhage, burn, acute infection, acute perforations etc) and this is well demonstrated by the microscopical appearance of the gland. The cells of the adrenal cortex are normally laden with lipid materials, which represent the storehouse of the hormones of the gland. Under conditions of stress, there is a depletion of this lipid storage (as the hormones are discharged into circulation). Thereafter, there is a phase of cellular overgrowth, associated with re-accumulation of the lipid materials (suggesting return of normalcy).

Tests for Adrenal Cortical Function:
A. By measuring the blood level of the hormone directly:-
1.Plasma cortisol (hydrocortisone) level.- Normally 8 to 28 micrograms per 100 ml.
2.Other cortical hormones- Using radio-activation techniques, it is now possible to estimate the levels of the other cortical hormones individually.
B.By measuring the urinary output (24 hours) of the metabolites of individual cortical hormones or of the hormones themselves:
1.17- Hydroxycorticoid ( for hydrocortisone)
(2) 17=oxosteroid i.e. 17=ketosteroid (for androgens and Oestrogens)
3.Aldosterole itself
4. The three Oestrogens themselves.(1 & 2 are usually measured for testing cortical function)
C.Similar estimations made after stimulating the adrenal cortex by administering A.C.T.H. (A.C.T.H. stimulation tests):-
-- These are done with the idea that patients with adrenal hyperplasia respond much more than persons with normal cortical function.
--The urinary output of the 17-hydroxycorticoid and 17-ketosteroid in 24 hours are measured first. Thereafter, the cortex is stimulated by ACTH gel ( 40 units given intramuscularly, twice, in a span of 24 hours). The urinary output of the two metabolites are measured in the urine of the next 24 hours.
D.Similar estimation made after suppressing the adrenals by inhibiting A.C.T.H.
A.C.T.H. suppression is usually done by injecting hydrocortisone, or more commonly, dexamethasone (which suppresses the pituitary by the same feedback mechanism as hydrocortisone). The urinary excretion of 17-hydroxycorticoid and 17 ketasteroid in 24 hours prior and after the injection is measured. It is found that there is a far more severe depression in the excretion of the metabolites in patients with adrenal hyperplasia than in normal subjects. Curiously, however, in patients of adrenal tumours with over activity, this depression is not noticed. This is explained by the fact that the secretion of the cortical hormones from adrenal tumours is autonomous, i.e. not under control of ACTH. Thus the ACTH suppression test is valuable not only in diagnosing cortical over-activity but also making a differential diagnosis between adrenal hyperplasia and neoplasm.
Therapeutic Uses of Hydrocortisone (and Cortisone):
1. In Endocrine (adrenocortical) Deficiency:
a. After bilateral adrenalectomy.
b.Adrenocortical insufficiency i.e. hypocorticism- acute or chronic (Addison’s disease)
2.In Non-endocrine Conditions:
a. Allergic conditions.
b.Blood dyscrasias
c. Collagenoses
d. Granulomatous disorders
e.Rheumatoid arthritis
f.Different skin and eye conditions, acting as an anti-allergic agent (applied locally).


CUSHING’s SYNDROME
This is the commonest form of hypercorticism and is due to an excessive production of the Glucocorticoids, chiefly hydrocortisone. It occurs in the adults and is, therefore, also known as post-pubertal or adult hypercorticism.
The other types of hypercorticism are:-
1.Infantile
2.Pre-pubertal
3.Post-menopausal.

Pathology:
The excessive production of the hydrocortisone (cortisol) may be brought about by one of the following conditions:
 Primary:
 Cushing disease: Pituitary Tumors : 30% (Basophil adenoma or invasive carcinoma of the anterior pituitary )
 Hyperplasia of adrenal gland: 60%
 Ectopic ACTH producing Tumour
 (Ulcerogenic islet-cell tumour of the pancreas, . Bronchial carcinoma ,Small cell carcinoma of lung and thymic carcinoma
 Tumor of adrenal cortex(35%)
 Adenoma
 Carcinoma
 In some of these cases there may be a tumour of the thymus or of the pineal glands (located between the posterior parts of the thalamus of the two sides).

 Secondary:
Excessive steroid Therapy for long time can induce clinical picture of Cushing Syndrome. Thae therapy may be for
 Rheumatoid arthritis
 Transplants Patients receiving Steroid therapy
 Auto immune disorders

Clinical Features: Females suffer more commonly than males (3:1). A typical patient is a female between 15 and 30 years of age (excepting the cases where the condition is drug-induced).
The clinical features may be divided into 5 broad groups:-
1.Those due to metabolic disorders.
2.Those due to fluid and electrolyte disturbances.
3.Sexual disorders.
4. Mental changes
5. Other features.




A.Those due to Metabolic Disturbances:
Disturbances releted to fat, protein, sugar and calcium metabolism: -
1.Obesity: Although overall weight is not increased
Deposition of fat in certain areas There is an excessive deposit of fat over
 Protuberant abdomen
 Buffalo lump (fatty pads over the scapulae)
 Moon face with pursed lips
 Obliteration of supraclavicular fossae.

2.Protein breakdown::
 Thinning of arms and legs due to muscle breakdown
 (the swollen abdomen with the thinned-out legs may be compared to
‘a lemon on the match-sticks’).
 Increasing muscular weakness.

3.Atrophy of the dermis and inhibitory effect on fibrous tissue:
 Skin gets inelastic and assumes a tissue-paper consistency; on the abdomen :
striae gravidarum.
 Purpura and bruising to minimal trauma

4. Diabetes, due to increased neoglucogenesis.

5. Negative calcium balance causing gross osteoporosis and, sometimes, pathological fractures (particularly of the vertebrae)
These disturbances are releted to fat, protein, sugar and calcium metabolism: -
1.Obesity: There is an excessive deposit of fat over some particular parts, resulting in:
a. Protuberant abdomen
b.Buffalo lump (fatty pads over the scapulae)
c. Moon face with pursed lips
d. Obliteration of supraclavicular fossae.
e.Increased body weight.

2.Protein breakdown::
a.Thinning of arms and legs due to muscle breakdown (the swollen abdomen with the thinned-out legs may be compared to ‘a ,lemon on the match-sticks’).
b.Increasing muscular weakness.
3.Atrophy of the dermis and inhibitory effect on fibrous tissue:
a.Skin gets inelastic and assumes a tissue-paper consistency; on the abdomen this gives the same pattern as striae gravidarum.
b.There is a high-colored complexion due to transparency of the skin.
c. Purpura and bruising to minimal trauma (due to atrophy of capillary walls).
4. Diabetes, due to increased neoglucogenesis.
5. negative calcium balance causing gross osteoporosis and, sometimes, pathological fractures (particularly of the vertebrae)

B Those due to Fluid and Electrolyte Imbalance: These occur because hydrocortisone has a weak Aldosterone effect. There is retention of sodium and water with excessive loss of potassium. This results in:
1)Hypertension, may lead to cardiac hypertrophy, myocardial ischaemia, cerebro-vascular accidents, and congestive heart failure.
2.)Hypokalaemic alkalosis.

C)Sexual Disorders:
1)Common types:
(a)Sterility and impotency in the males.
(b) Sterility and menstrual disorders in the females (oligomenorrhoea, amenorrhoea or menorrhagia).
(2)Uncommon type i.e. Adreno-genital Syndrome: These are the cases where sexual disorders are more predominant than the metabolic disorders:
a) Most commonly it occurs in females due to excessive secretion of androsterone. The condition usually starts at about the age of 20. There is oligomenorrhoea, atrophy of the breasts, enlargement of the clitoris, deepening of the voice, and a change of body structure to a manly build.
b) Very rarely it may occur in young males due to excessive seceretion of Oestrogens. There is gynaecomastia, atrophy of the testes, change in voice etc.

A. Mental Changes: Various types of psychosis may set in ( more than half of the cases).
B. Other Features:
(1)Increased growth of lanugo hairs, sometimes frank hirsutims.
(2) Acne and skin infections (due to suppressed inflammatory reaction).
(3) Recurrent itntercurrent infections (due to same reason)
(4) Excessive pigmentation of the skin (this is not due to excess of hydrocortisone but because of increased A,.C.T.H.)

Special Investigations:
(1)Blood Count – Polycythemia and leucocytosis (with lymphopaenia and cosinopaenia).
(2) Urine Examination
(a)Glycosuria
(b) Hypercalciuria
(3) Blood Biochemistry:
(a)Hyperglycaemia
(b) Hypercholesterolaemia.
4. B.M.R. – Low.
5. X-Ray:
(a)Skeleton- There may be gross osteoporosis, particularly in the vertebrae and pelvis.
(b) Pituitary fossa (sella turcica)- An enlargement may sometimes be seen if the condition is due to a pituitary tumour.
(c) Lungs- Rarely presence of stones and nephrocalcinosis.
(d) Kidneys- Rarely presence of stones or nephrocalcinosis.
(e) X-rays to demonstrate adrenal tumours ( see under phaeochromocytoma)
6. Hormone Assays:
(a)Estimation of Plasma cortisol level.
(b) Estimation of urinary 17-hydroxycorticoid and 17-ketosteroid.
© A.C.T.H. stimulation test.
(d) A.C.T.H. suppression test. (see tests for adrenal cortical function)

Treatment:
(1)When the pathology is primarily in the adrenal:
(a)In cases of adrenal hyperplasia ( which is bilateral)- Total adrenalectomy on one side and resection of seven-eighth of the adrenal gland on the other side.
(b) In cases of adrenal neoplasm) adenoma or carcinoma)- Excision of the adrenal gland that contains the tumour.
If the diagnosis is a tumour and the side is ascertained, an extraperitoneal approach by the lumbar route (as for the kidney) is done; the twelfth rib (sometimes also the eleventh) is excised to expose the adrenal. In other cases, a Tran peritoneal approach has to be made, so that both the adrenals can be examined.

(2)When the adrenal condition is secondary to a pituitary tumour: Two forms of treatment are available:
(a)Surgical removal of the pituitary (hypophysectomy)
(b) Radiation=ablation of the pituitary by implanting Ytrrium –90 pellets into the gland.

Cortisone Replacement in Adrenalectomy: The daily output of hydrocortisone from the adrenals, in a normal subject, is about 25 mg. After bilateral adrenalectomy, this amount has tobe supplied from outside throughout the life time of the patient. Following subtotal adrenalectomy, however, the remnant of the adrenal tissue gradually picks up function and the external supply may be withdrawn after sometime. Similarly, even after bilateral adrenalectomy, the adrenal cortical rests in the body may be geared into action in some cases and the external supply may be discontinued.

Again the stress of the operation and anaesthesia, for adrenalectomy, requires a high supplement during and after the operation. It is desirable that the higher supplement is instituted from one or two days prior to the date of operation.

The following is a tentative routine of cortisone replacement in cases of adrenalectomy- A)Before Operation : For 1 or 2 days- Cortisone acetate, intramuscularly, 100 mg daily
(B)On the day of Operation:
(1)1 to 2 hours before operation- Cortisone acetate, intramuscularly,100mg
(2) During Operation – Hydrocortisone hemisuccinate, 100 mg in the intravenous drip. Alternatively, the hydrocortisone is pushed directly intravenous just after extirpation of the adrenals.
(3) After Operation: Cortisone acetate, intramuscularly, every 6 hours.

C. Until 5th Post-Operative Day: Cortisone Acetate, 100 mg, intramuscularly or orally, according to the patient’s condition.
(D)After 5th Day : Cortisone acetate is given, but the dose is gradually reduced to 25 to 50 mg in cases of total adrenalectomy and to nil in subtotal adrenalectomy (the remaining adrenal tissue picks up function).

2 Comments:

Blogger Dr Arun said...

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June 22, 2004 at 8:17 PM  
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May 11, 2010 at 10:47 AM  

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