A patient with primary adrenal insufficiency (Addison's disease) develops hyperpigmentation of the buccal mucosa and skin creases. Which physiological mechanism explains this finding?

• A Elevated ACTH stimulating melanocortin-1 receptors (MC1R) on melanocytes — ACTH and alpha-MSH share the same N-terminal HFRWG sequence ✓
• B Cortisol deficiency removing negative feedback on melanocytes directly
• C Elevated DHEA-S from adrenal androgen excess stimulating melanin synthesis
• D Hypothalamic CRH directly stimulating pituitary melanocyte-stimulating hormone production

Explanation

In Addison's disease, loss of cortisol feedback leads to massive elevation of ACTH from the anterior pituitary. ACTH is derived from POMC and shares the first 13 amino acids with alpha-MSH (melanocyte-stimulating hormone), including the active core sequence HFRWG. Elevated ACTH binds melanocortin-1 receptors (MC1R) on melanocytes, stimulating melanin production and causing the characteristic hyperpigmentation. Cortisol deficiency itself does not directly affect melanocytes (option B). DHEA (option C) can cause some androgenic effects but not this type of pigmentation. CRH (option D) stimulates ACTH, not MSH directly at the pituitary.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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