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Corticotroph — ACTH cleaved from pro-opiomelanocortin

Pituitary · ACTH POMC MC2R

Corticotrophs cleave POMC to ACTH along with MSH, beta-endorphin and lipotrophin, releasing it in pulses that track CRH. ACTH acts on the melanocortin-2 receptor of the adrenal cortex.

Traced from the start

  1. Corticotrophin-releasing hormone (paraventricular nucleus)
  2. Corticotroph — ACTH cleaved from pro-opiomelanocortin

Detail

Acts on
Zona fasciculata and zona reticularis; the zona glomerulosa answers to angiotensin II and potassium, not ACTH
Half-life
About 10 minutes, so the sample must go to the laboratory on ice
Pigment
ACTH contains the MSH sequence, so only very high levels (Addison disease, ectopic secretion, Nelson syndrome) pigment palmar creases, buccal mucosa and scars

When it goes wrong

Corticotroph microadenoma (Cushing disease, about 70% of endogenous Cushing syndrome)

Raised cortisol with an inappropriately normal or high ACTH; cortisol falls by more than half on 8 mg dexamethasone, ACTH rises with CRH, and petrosal sinus sampling shows a central-to-peripheral gradient

Ectopic ACTH from small cell lung carcinoma or a bronchial carcinoid

Very high ACTH that does not suppress on high-dose dexamethasone; weeks-long onset with weight loss, proximal weakness, pigmentation and hypokalaemic metabolic alkalosis rather than the classic cushingoid habitus

Pituitary ACTH deficiency (secondary adrenal insufficiency)

Low cortisol with a low or normal ACTH: no pigmentation and no hyperkalaemia because aldosterone is intact, though hyponatraemia still occurs through unsuppressed ADH

Practise this structure

2 questions in the bank tagged Pituitary.

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