Lec 5 endocrine cushing syndrome

THE ADRENAL GLANDS
The adrenals comprise several separate endocrine glands within a single anatomical structure. The adrenal medulla is an extension of the sympathetic nervous system which secretes catecholamines into capillaries. Most of the adrenal cortex is made up of cells which secrete cortisol and adrenal androgens, and form part of the hypothalamic–pituitary–adrenal (HPA) axis. The small outer glomerulosa of the cortex secretes aldosterone under the control of the renin– angiotensin system. These functions are important in the integrated control of cardiovascular, metabolic and immune responses to stress.
Cushing’s syndrome
Cushing’s syndrome is caused by excessive activation of glucocorticoid receptors. It is most commonly iatrogenic, due to prolonged administration of synthetic glucocorticoids such as prednisolone. Endogenous Cushing’s syndrome is uncommon but is due to chronic over-production of cortisol by the adrenal glands, either as the result of an adrenal tumour or because of excessive production of ACTH by a pituitary tumour or ectopic ACTH production by other tumours.
Causes:
1- ACTH-dependent – 80%
• Pituitary adenoma secreting ACTH (Cushing’s disease) – 70%
• Ectopic ACTH syndrome (bronchial carcinoid, small-cell lung carcinoma, other neuro-endocrine tumour) – 10%
2- Non-ACTH-dependent – 20%
• Adrenal adenoma – 15%
• Adrenal carcinoma – 5%

Hypercortisolism due to other causes (also referred to as pseudo-Cushing’s syndrome)
a- Alcohol excess (biochemical and clinical features)
b- Major depressive illness (biochemical features only, some clinical overlap)
c- Primary obesity (mild biochemical features, some clinical overlap)

Both Cushing’s disease and cortisol-secreting adrenal tumours are four times more common in women than men.

Clinical feature: as shown in figure below
Note 1: There are many diseases causes same clinical feature of Cushing syndrome such as obesity, alcoholism and depression so the features which favour Cushing’s syndrome in an obese patient are:
1- Bruising
2- Myopathy
3- Thin skin.
Note 2: Any clinical suspicion of cortisol excess is best resolved by further investigation.
Note 3: The high ACTH levels are associated with marked pigmentation because of binding to melanocortin 1 receptors on melanocytes in the skin.
Note 4: When the tumour that is secreting ACTH is malignant, then the onset is usually rapid and may be associated with cachexia.