A 24-year-old woman of short stature has a round face, obesity, subcutaneous ossifications, and shortening of the fourth metacarpal. Serum calcium is 7.6 mg/dL, phosphate 5.8 mg/dL, and PTH markedly elevated at 320 pg/mL. What is the underlying defect?

• A Destruction of parathyroid glands
• B End-organ resistance to PTH due to GNAS mutation ✓
• C Renal failure with phosphate retention
• D Defective 25-hydroxylation of vitamin D in the liver

Explanation

This is Albright hereditary osteodystrophy of pseudohypoparathyroidism type 1A: loss-of-function mutation of the maternal GNAS gene impairs the Gs alpha subunit, so target tissues cannot respond to PTH despite very high hormone levels, giving low calcium, high phosphate, and the characteristic skeletal phenotype. Primary gland destruction would give low PTH, ruling out option A, and renal failure would raise creatinine.

Reference: Williams Textbook of Endocrinology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.