Cushing’s Syndrome

Normal plasma cortisol level is 5-20 mcg/dl in early morning which is reduced to less than half by 11pm. Loss of this diurnal variation is the first characteristic change in cushings syndrome and is usually observed in children above 3years.

Ref: Harrison’s Internal Medicine, 18th Edition, Pages 2897, 2945 ; Pathophysiology of Disease: An Introduction to Clinical Medicine, 6th Education, Stephen J. McPhee, Chapter 21 ; Pediatric Endocrine Disorders By Desai, Meena P, Page 232 ; Diagnosis and Management of Pituitary Disorders By Brooke Swearinge, Pages 164, 192

Tumors responsible for ectopic secretion of ACTH are small cell carcinoma, bronchial carcinoid, medullary thyroid carcinoma, pancreatic carcinoma and pheochromocytoma. It can lead to Cushing’s syndrome.

Common clinical features of Cushing’s syndrome are central obesity with moon face, buffalo hump, thin extremities, muscle weakness, diabetes, hypertension, amenorrhea, osteoporosis, poor wound healing and psychosis.

Hypokalemia and metabolic alkalosis is seen particularly in patients with ectopic ACTH secretion. Earliest screening test for diagnosing Cushing’s syndrome is dexamethasone supression test. If its abnormal a high 24 hour urine free cortisol helps in confirming diagnosis. Late night salivary cortisol test have high sensitivity and specificity for Cushing’s syndrome.

Answer is D (Distal Duodenum)

Distal duodenum has not been mentioned on a site for cushing ulcers

Cushings ulcers:

Are acute ulcers of the upper GI tract associated with intracranial injury or an increase in intracranial pressure.

These ulcers my involve the

Stomach^Q

Proximal duodenum e Esophagus ^Q

Complication : Haemorrhage and perforation^Q

Treatment:  Correction of increased intracranial pressure + usual treatment of acute erosions and ulceration.

Memo: Curling’s ulcers : Stress ulcerations after severe burns –

Answer is B (Pituitary adenoma):

Cushing’s Syndrome

Endogenous Cushing’s Syndrome

Most common cause of endogenous Cushing’s syndrome is an ACTH secreting pituitary adenoma (Cushing’s disease)

Exogenous Cushing’s Syndrome

The most common cause of exogenous Cushing’s syndrome is iatrogenic administration of steroids.

ACTH producing pituitary adenoma are the most common cause of endogenous Cushing syndrome.

Answer is C (Medulloblastoma) :

Medulohlastoma is not associated with Cushing’s syndrome

Answer is D (None — All are seen):

Cushing’s syndrome may be associated with all features mentioned in the question.

Answer is D (Increased ACTH secretion is the commonest endogenous cause):

The most common endogenous cause of Cushing’s syndrome is increased ACTH secretion by a pituitary adenoma.

In Cushing syndrome low dose dexamethasone fails to suppress cortisol secretion

‘In normal subjects administration of supraphpiological doses of glucocorticoid results in suppression of ACTH and hence of cortisol secretion. In Cushing’s syndrome of whatever cause there is failure of this suppression when low doses of synthetic glucocorticoid dexamethasone are given’. – Oxford Textbook of Medicine 4th/246

Carcinoma of Adrenal is not more common than Adrenal Adenoma as a cause for Cushing’s syndrome 

‘Adrenal Adenoma are responsible for about the same number of cases as Adrenal Carcinomas’. – Oxford Textbook ‘Adrenal Neoplasms are usually unilateral and about half are malignant’ – Harrison

The size of pituitary Adenoma is usually < 1 cm and not > 2 cm

Most common cause of Cushing’s syndrome (endogenous) is a Pituitary microadenoma which is less than 10 mm in diameter – Harrison

Answer is A (Loss of Diurnal variation) :;

“Owing to circadian variability plasma cortisol and to a certain extent ACTH determinations are not meaningful when determined in isolation, but the absence of normal fall of plasma cortisol at midnight (Loss of diurnal variation) is consistent with Cushing’s syndrome” — Harrison 15^‘h / 2092

From the statement above, options of increased ACTH and increased plasma cortisol are ruled out as desirable early manifestation of Cushing’s syndrome.

We are then left with the options of loss of diurnal variation and increased urinary metabolites of cortisol.

Although free cortisol’ in urine is used as a screening test for Cushing’s syndrome, no mention has been made about use of ‘increased metabolites of cortisol in urine’ for the same purpose. Secondly, manifestation in serum level of cortisol are certain to precede changes in urine and hence loss of diurnal variation in serum cortisol is certain to be the earliest manifestation of Cushing’s syndrome amongst the options provided.

Ans. is ‘a’ i.e., Hypotension

A rise in intracranial pressure causes impaired blood supply to VMC (RVLM) neurons and the local hypoxia and hypercapnia increase their discharge to the systemic resistance vessels, i.e., cushing reflex. The resultant rise in BP tends to restore cerebral blood flow and over a considerable range, the BP rise is proportional to the increase in intracranial pressure. The increase in BP causes reflex bradycardia through arterial baroreceptors. That is why bradycardia rather than tachycardia is characteristically seen in patients with increase (ICP).

Cushing reflex consists of hypertension (increased BP), bradycardia and tachyponea.