Pseudohypoparathyroidism

Pseudohypoparathyroidism (PHP) is resistance to parathyroid hormone (PTH), not failure to produce it. Loss-of-function mutations or imprinting defects involving GNAS disrupt signalling in PTH target tissues. The hormone may be present in the circulation, but the target cell cannot transmit its message effectively. Normally, PTH helps the kidney retain calcium, excrete phosphate, and support production of active vitamin D. With PHP, the kidney behaves as though the PTH signal is absent: phosphate accumulates, calcium falls, and active vitamin D production is reduced. Reduced active vitamin D then limits intestinal calcium absorption, adding to the hypocalcemia. This produces the characteristic biochemical combination: - low serum calcium - high serum phosphate - elevated, or inappropriately normal, PTH The PTH result is the decisive clue. True hypoparathyroidism also causes low calcium and high phosphate, but PTH is low or inappropriately normal because the parathyroid glands are not supplying enough hormone. In PHP, the glands are producing PTH; the body is resistant to its action. Some patients have features of Albright hereditary osteodystrophy, including shortened digits, especially brachydactyly, ectopic ossifications, and early-onset obesity. These...