[Pseudohypoparathyroidism and the concept of hormonal resistance. Types Ib and II]

TYPE IB PSEUDOHYPOPARATHYROIDISM: Parathormone resistance is the only manifestation of type Ib pseudohyoparathyroidism, the Albright osteodystrophy and multiple hormone resistance described in type Ia are not observed. In type Ib there is a certain preservation of bone sensitivity to parathormone although the main target organ, the kidney, is resistant. Consequently, excessive bone remodeling can be evidenced by X-ray (subperiosteal resorption, fibrocystic osteitis), chemistry (high serum alkaline phosphatase and osteocalcin, and increased urine hydroxyproline), densitometry (lower bone density), and pathology (reduction in trabecular bone volume). The dissociation of the bone and kidney response corresponds to the pseudohypohyperthyroidism described by certain authors. The genetic substratum leading to type Ib pseudohypoparathyroidism remains to be identified. The pathogenic mechanism generally hypothesized concerns a qualitative or quantitative anomaly of the parathormone receptor but seems to be disproved by recent studies. TYPE II PSEUDOHYPOPARATHYROIDISM: Here there is a characteristic lack of a rise in urine phosphorus, signaling parathormone resistance, and stimulated urinary excretion of cyclic AMP, an expression of the integrity of the transmembrane transduction of the parathormone mediated signal and thus protein G and adenylate cyclase. The anomaly could thus involve a transductional effector situated downstream from adenylate cyclase which would explain the symptoms of type II pseudo-hypoparathyroidsm, with both parathormone resistance and Albright osteodystrophy.