Question

Which hormone is elevated in Addison's disease, leading to hyperpigmentation?

• A. Cortisol
• B. ACTH
• C. Aldosterone
• D. Renin

Hint:

Primary adrenal insufficiency causes high ACTH and hyperpigmentation.

Answer 1

The Correct Option is B

Step 1: Understanding the Question:
Addison's disease is primary adrenal insufficiency where the adrenal cortex is damaged. We need to identify the hormone responsible for the characteristic skin and mucosal hyperpigmentation seen in these patients.
Step 2: Detailed Explanation:

The Feedback Loop: In primary adrenal insufficiency, the loss of negative feedback from low cortisol levels causes the pituitary gland to significantly overproduce Adrenocorticotropic Hormone (ACTH).

The Precursor Molecule: ACTH is derived from a large precursor protein called Pro-opiomelanocortin (POMC). POMC is cleaved to form ACTH, as well as Melanocyte-Stimulating Hormone (MSH).

Hyperpigmentation Mechanism: ACTH itself shares structural homology with alpha-MSH. When ACTH levels are very high, it binds to and stimulates the Melanocortin-1 receptors (MC1R) on melanocytes in the skin. This leads to increased melanin production.

Clinical Distribution: Hyperpigmentation is typically most prominent in areas exposed to sun, pressure points (elbows, knees), palmar creases, and mucous membranes (buccal mucosa).

Differentiation: In secondary adrenal insufficiency (pituitary failure), ACTH is low, so hyperpigmentation does not occur. Aldosterone and Renin (Options C and D) do not affect skin pigmentation.

Step 3: Final Answer:
Excessive production of ACTH (which has MSH-like activity) is the direct cause of hyperpigmentation in Addison's disease.