Addison Disease MCQ — NEET PG Practice Question | NEETPGAI
Addison Disease
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stethoscope Medicine
A 45-year-old woman presents with a 6-month history of progressive fatigue, weight loss, and salt craving. On examination, you note the finding marked **A** in the diagram — a striking hyperpigmentation of the buccal mucosa and gingival margins. Her serum sodium is 128 mEq/L (normal 135–145), potassium is 5.8 mEq/L (normal 3.5–5.0), and morning cortisol is 2.1 μg/dL. Which of the following best explains the pathophysiology of the hyperpigmentation marked **A**?
A. Autoimmune destruction of melanocyte-inhibiting factors in the basal epidermis
B. Elevated ACTH stimulating melanocytes via melanocortin-1 receptor (MC1R) signaling due to loss of cortisol negative feedback
C. Increased melanin synthesis secondary to chronic hypoglycemia and sympathetic activation
D. Deposition of lipofuscin and hemosiderin in the dermis from chronic hemolysis
Explanation
Why "Elevated ACTH stimulating melanocytes via melanocortin-1 receptor (MC1R) signaling due to loss of cortisol negative feedback" is right
The hyperpigmentation marked A (buccal/gingival mucosa) is a hallmark of primary adrenal insufficiency (Addison disease) and is caused by elevated ACTH and POMC-derived melanocyte-stimulating hormone (MSH) stimulating melanocytes through the MC1R receptor. In primary adrenal insufficiency, destruction of the adrenal cortex causes severe glucocorticoid deficiency, which removes the normal negative feedback inhibition of ACTH secretion by the anterior pituitary. The resulting ACTH excess directly stimulates melanin production, particularly in sun-exposed areas and mucous membranes (buccal, gingival, palmar creases, knuckles, areolae). This distinguishes primary from secondary adrenal insufficiency, where ACTH remains low and hyperpigmentation is absent. The patient's clinical triad of hyponatremia (128), hyperkalemia (5.8), and low morning cortisol (2.1 μg/dL) confirms primary adrenal insufficiency, and the buccal hyperpigmentation is pathognomonic. [Endocrine Society Primary Adrenal Insufficiency Guidelines 2024]
Why each distractor is wrong
Increased melanin synthesis secondary to chronic hypoglycemia and sympathetic activation: While hypoglycemia does occur in Addison disease, it does not directly stimulate melanin synthesis. Hyperpigmentation in Addison disease is ACTH-driven, not metabolic stress-driven. Secondary adrenal insufficiency (with hypoglycemia and no ACTH elevation) does not produce hyperpigmentation.
Deposition of lipofuscin and hemosiderin in the dermis from chronic hemolysis: Addison disease does not cause hemolysis or lipofuscin/hemosiderin deposition. The patient has normocytic anemia (not hemolytic), and the hyperpigmentation is active melanin synthesis, not pigment deposition from tissue breakdown.
Autoimmune destruction of melanocyte-inhibiting factors in the basal epidermis: While autoimmune adrenalitis is the mechanism of Addison disease (antibodies against 21-hydroxylase), the hyperpigmentation is not due to loss of inhibitory factors but rather to positive ACTH-driven stimulation of melanocytes. Vitiligo (loss of melanocytes) may coexist in autoimmune polyglandular syndromes, but it causes depigmentation, not hyperpigmentation.
High-YieldNEET PG
Hyperpigmentation in primary adrenal insufficiency = elevated ACTH + intact MC1R signaling; its absence in secondary AI (low ACTH) is a key diagnostic clue.
[Endocrine Society Primary Adrenal Insufficiency Guidelines 2024]
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