Cushing’s syndrome results from excess cortisol secretion from adrenal adenoma and excessive activation of glucocorticoid receptors.
It can be:
Iatrogenic, due to prolonged administration of synthetic glucocorticoids such as prednisolone.
Endogenous 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.
EPIDEMIOLOGY
Male to female incidence ratio is 5:1 of cushing syndrome due to pituitary or adrenal tumor
Ectopic ACTH production is more common in males than females because of higher incidence of lung tumors in men
Peak incidence of cushing syndrome due to either adrenal or pituitary adenoma is in persons aged 25-40 years
Ectopic ACTH production occurs in later life
AETIOLOGY
ACTH DEPENDENT CUSHING SYNDROME
-primary adrenal lesions
A.Adrenal adenoma
B.Adrenal carcinoma
C.Macronodular or micronodular adrenal hyperplasia
D. McCune-Albright syndrome
-ectopic cortisol secretion from a case of ovarian carcinoma
ACTH INDEPENDENT CUSHING SYNDROME
-ACTH producing pituitary adenoma
Nelson syndrome
-small cell lung carcinoma cause ectopic ACTH secretionAmongst endogenous causes, pituitary-dependent cortisol excess (byconvention, called Cushing’s disease) accounts for approximately 80% of cases.
-Pseudo cushing can be due to hypercortisolism due to the following
-Alcoholism
-Depression
-Obesity
clinical features
-Hair thinning
-Acne plethora
-Moon face
-Hyperglycemia
-Loss of height and back pain
-Menstrual disturbance
-Psychosis
-Cataracts
-Hypertension
-Osteoporosis
-hypokalemia
Hypercalciuria
Bufallo humps and truncal obesity
-Decreased skin tickhness
-Wasting and weakening of proximal thigh and extremities muscles(proteolysis)
-Mild exophthalmos
-Tendency to infections(immune suppression by inhibiting histamine release,intereukins and phospolipase A2)
- poor wound healing
-bruising
-weight increase
-metabolic alkalosis
-hirsutism
-striae(impared collagen synthesis)
Cushing disease is caused by a benign monoclonal pituitary corticotroph adenoma that secretes excess ACTH which in turn causes supraphysiological secretion of glucocorticoids from the adrenal glands. the excess circulating cortisol disrupts normal physiologic dunal variationin the cortisol levels and excerts a negative feedback inhibition on corticotrophin releasing hormone secretion from the hypothalamus.
However the adenoma itself is resistant to inhibition by endogenous circulating cortisol. Consequently cushing disease is associated with suppressed secretion of CRH and elevated levels of ACTH in relation to the degree of cortisol production.
Endogenous excess cortisol overproduction that is independent of ACTH is usually due to an adenoma and rarely a carcinoma. .
Ectopic cortisol secretion from a case of ovarian carcinoma is a cause of ACTH-independent Cushing syndrome. ACTH level in ACTH-independent Cushing syndrome is low due to the negative feedback to pituitary corticotroph cells from a high level of serum cortisol.
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