Page 813 - Textbook of Pathology, 6th Edition

ADRENAL MEDULLA. The adrenal medulla is a component doses of dexamethasone which suppresses ACTH secretion 797
of the dispersed neuroendocrine system derived from and causes fall in plasma cortisol level.
primitive neuroectoderm; the other components of this 2. Adrenal Cushing’s syndrome. Approximately 20-25%
system being paraganglia distributed in the vagi, cases of Cushing’s syndrome are caused by disease in one or
paravertebral and visceral autonomic ganglia. The cells both the adrenal glands. These include adrenal cortical
comprising this system are neuroendocrine cells, the major adenoma, carcinoma, and less often, cortical hyperplasia.
function of which is synthesis and secretion of catecholamines This group of cases is characterised by low serum ACTH
(epinephrine and norepinephrine). Various other peptides levels and absence of therapeutic response to administration
such as calcitonin, somatostatin and vasoactive intestinal of high doses of glucocorticoid.
polypeptide (VIP) are also secreted by these cells. The major 3. Ectopic Cushing’s syndrome. About 10-15% cases of
metabolites of catecholamines are metanephrine, nor-me- Cushing’s syndrome have an origin in ectopic ACTH elabo-
tanephrine, vanillyl mandelic acid (VMA) and homovanillic ration by non-endocrine tumours. Most often, the tumour is
acid (HVA). In case of damage to the adrenal medulla, its an oat cell carcinoma of the lung but other lung cancers,
function is taken over by other paraganglia. malignant thymoma and pancreatic tumours have also been
Diseases affecting the two parts of adrenal glands are
quite distinctive in view of distinct morphology, and function implicated. The plasma ACTH level is high in these cases
and cortisol secretion is not suppressed by dexamethasone
of the adrenal cortex and medulla. While the disorders of administration.
the adrenal cortex include adrenocortical hyperfunction
(hyperadrenalism), adrenocortical insufficiency (hypo- 4. Iatrogenic Cushing’s syndrome. Prolonged therapeutic
adrenalism) and adrenocortical tumours, the main lesions administration of high doses of glucocorticoids or ACTH may
affecting the adrenal medulla are the medullary tumours. result in Cushing’s syndrome e.g. in organ transplant
recipients and in autoimmune diseases. These cases are
ADRENOCORTICAL HYPERFUNCTION generally associated with bilateral adrenocortical
(HYPERADRENALISM) insufficiency.
Hypersecretion of each of the three types of corticosteroids CLINICAL FEATURES. Cushing’s syndrome occurs more
elaborated by the adrenal cortex causes distinct often in patients between the age of 20-40 years with three CHAPTER 27
corresponding hyperadrenal clinical syndromes: times higher frequency in women than in men. The severity
1. Cushing’s syndrome caused by excess of glucocorticoids of the syndrome varies considerably, but in general the
(i.e. cortisol); also called chronic hypercortisolism. following features characterise a case of Cushing’s syndrome:
2. Conn’s syndrome caused by oversecretion of mineralo- 1. Central or truncal obesity contrasted with relatively thin
corticoids (i.e. aldosterone); also called primary hyper- arms and legs, buffalo hump due to prominence of fat over
the shoulders, and rounded oedematous moon-face.
aldosteronism.
3. Adrenogenital syndrome characterised by excessive produc- 2. Increased protein breakdown resulting in wasting and
tion of adrenal sex steroids (i.e. androgens); also called adrenal thinning of the skeletal muscles, atrophy of the skin and
subcutaneous tissue with formation of purple striae on the
virilism.
Mixed forms of these clinical syndromes may also occur. abdominal wall, osteoporosis and easy bruisability of the thin The Endocrine System
skin to minor trauma.
Cushing’s Syndrome (Chronic Hypercortisolism) 3. Systemic hypertension is present in 80% of cases because
of associated retention of sodium and water.
Cushing’s syndrome is caused by excessive production of 4. Impaired glucose tolerance and diabetes mellitus are found
cortisol of whatever cause. The full clinical expression of the in about 20% cases.
syndrome, however, includes contribution of the secondary 5. Amenorrhoea, hirsutism and infertility in many women.
derangements. 6. Insomnia, depression, confusion and psychosis.

ETIOPATHOGENESIS. There are 4 major etiologic types Conn’s Syndrome (Primary Hyperaldosteronism)
of Cushing’s syndrome which should be distinguished for
effective treatment. This is an uncommon syndrome occurring due to overpro-
duction of aldosterone, the potent salt-retaining hormone.
1. Pituitary Cushing’s syndrome. About 60-70% cases of
Cushing’s syndrome are caused by excessive secretion of ETIOPATHOGENESIS. The condition results primarily due
ACTH due to a lesion in the pituitary gland, most commonly to adrenocortical diseases as follows:
a corticotroph adenoma or multiple corticotroph 1. Adrenocortical adenoma, producing aldosterone.
microadenomas. This group of cases was first described by 2. Bilateral adrenal hyperplasia, especially in children
Harvey Cushing, an American neurosurgeon, who termed (congenital hyperaldosteronism).
the condition as Cushing’s disease. Also included in this 3. Rarely, adrenal carcinoma.
group are cases with hypothalamic origin of excessive ACTH Primary hyperaldosteronism from any of the above causes
levels without apparent pituitary lesion. All cases with is associated with low plasma renin levels. Secondary
pituitary Cushing’s syndrome are characterised by bilateral hyperaldosteronism, on the contrary, occurs in response to high
adrenal cortical hyperplasia and elevated ACTH levels. These plasma renin level due to overproduction of renin by the
cases show therapeutic response on administration of high kidneys such as in renal ischaemia, reninoma or oedema.