Pseudohyperparathyroidism and the concept of hormone resistance - Types Iaand Ic

Type Ia: This familial hereditary condition is characterized by the associa tion of Albright's osteodystrophy, resistance to parathormone (PTH) and a n egative PTH test both for urinary phosphorus and cyclic AMP. The condition is caused by an anomalous or sub-unit of protein G, impairing its function. The result is defective transmembrane transduction of the PTH mediated sig nal. Protein G, coupled with ail heptahelical membrane-spanning receptors, is ubiquitous, explaining the association of multiple hormone and neurosens ory resistances. Resistance of the thyrotrope and gonadotrope axes should b e explored to institute appropriate replacement therapy. Type Ic: This type associates ail the clinical and biological features of t ype Ia pseudohypoparathyroidism but without any protein G defect, suggestin g another effector of signal transduction, perhaps adenylate cyclase, is in volved. Pseudopseudohypoparathyroidism: Often in families with type Ia pseudohypopa rathyroidism, subjects with Albright's osteodystrophy alone, with no featur es of PTH resistance, are said to have pseudopseudohypoparathyroidism. Prot ein G defects are also demonstrated in these subjects, confirming the relat ionship with type ia pseudohypoparathyroidism and explaining the possible m ultiple hormone resistances observed. The phenotypic variability between ty pe ia pseudohypoparathyroidism and pseudopseudohypoparathyroidism would be related to genomic imprinting mechanism.