McCune-Albright syndrome results from a postzygotic gain-of-function mutation in GNAS1. Constitutive activation of Gsα leads to autonomous hyperfunction of multiple endocrine organs. Which clinical triad is MOST characteristic?

• A Hyperpigmentation, neurofibromas, Lisch nodules
• B Polyostotic fibrous dysplasia, café-au-lait macules with irregular margins, precocious puberty ✓
• C Hypoparathyroidism, mucocutaneous candidiasis, Addison disease
• D Acromegaly, hyperparathyroidism, pancreatic tumour

Explanation

McCune-Albright syndrome presents with polyostotic fibrous dysplasia, coast-of-Maine café-au-lait spots (irregular borders distinguishing them from neurofibromatosis), and GnRH-independent precocious puberty. The activating GNAS1 mutation stimulates cAMP in bone, melanocytes, gonads, thyroid, and adrenal. Options B describes NF-1, C describes APS type 1 (APECED), and D describes MEN-1.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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