A woman with Addison's disease has elevated plasma ACTH levels despite receiving daily oral hydrocortisone replacement. She also has markedly elevated MSH (melanocyte-stimulating hormone) levels, explaining her skin hyperpigmentation. Both ACTH and MSH originate from the same precursor because:

• A Both are cleavage products of proopiomelanocortin (POMC), a single large precursor protein processed differently in the anterior vs. intermediate pituitary ✓
• B ACTH is enzymatically converted to MSH in peripheral tissues when cortisol is low
• C CRH stimulates separate corticotroph and melanotroph populations that increase both peptides proportionally
• D MSH is released as a byproduct of ACTH receptor activation at the adrenal cortex

Explanation

POMC is a 241-amino-acid precursor whose post-translational processing differs by cell type. In anterior pituitary corticotrophs, prohormone convertase 1 (PC1) cleaves POMC to yield ACTH (1–39) and beta-LPH. In the intermediate pituitary and hypothalamus, PC2 further cleaves ACTH into ACTH(1–13)/alpha-MSH and CLIP, and beta-LPH into beta-endorphin and gamma-MSH. In primary adrenal insufficiency, loss of cortisol negative feedback leads to massively elevated POMC-derived peptides including ACTH(1–39), which itself has weak MSH activity and coexists with alpha-MSH, causing hyperpigmentation.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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