Clinical meaning
Pseudohypoparathyroidism (PHP) is a group of disorders characterized by end-organ resistance to parathyroid hormone (PTH) despite elevated or normal PTH levels. In Type 1a (Albright hereditary osteodystrophy), there is a loss-of-function mutation in the GNAS gene encoding the Gs-alpha stimulatory protein, which is required for PTH to activate adenylyl cyclase and produce cAMP in renal tubular cells. Without this signaling, the kidneys cannot respond to PTH: phosphate reabsorption continues unchecked (hyperphosphatemia), calcium reabsorption fails (hypocalcemia), and 1,25-dihydroxyvitamin D synthesis is reduced. The result is biochemically identical to hypoparathyroidism (low calcium, high phosphate) but with ELEVATED PTH levels, distinguishing it from true hypoparathyroidism. Type 1a patients also display characteristic physical features called Albright hereditary osteodystrophy: short stature, round facies, obesity, brachydactyly (shortened 4th and 5th metacarpals), and subcutaneous calcifications. Hypocalcemia symptoms include neuromuscular irritability (tetany, Chvostek sign, Trousseau sign), paresthesias, and seizures.