Effect of calcium administration on renal responsiveness to parathyroid hormone in pseudohypoparathyroidism type I and II - In comparion with normals, idiopathic and surgical hypoparathyroidism.

Abstract

SynopsisA31-year-old man and a12-year-old girl were diagnosed as pseudohypoparathyroidism (PHP) Type I because of a failure to respond to the administration of parathyroid hormone (PTH) with increased urinary excretion of phosphate and cyclic adenosine-3', 5'-monophosphate (cAMP). A 22-year-old woman was diagnosed as PHP Type II because there was no increase in the urinary excretion of phosphate despite of a marked increase in urinary cAMP excretion.With the combined calcium-PTH infusion or PTH infusion after vitamin D therapy, renal response was improved in these patients.Also dibutyryl adenosine-3'-5'-cyclic monophosphate (dbcAMP) infusion evoked an increased urinary phosphate excretion in all of the patients.The metabolic defect of our patients with PHP Type I may be caused not by a lack or defective form of PTH-sensitive receptor adenylate cyclase complex but rather by an abnormal conformation in the plasma membrane-associated receptor adenylate cyclase enzyme complex in kidney. In the patient with PHP Type II, as cAMP generation is intact, the metabolic defect might be related to a defect of calcium mobilization in renal tubular cells in response to PTH. Pseudohypoparathyroidism(PHP) is a disorder characterized by renal and skeletal refractoriness to the effects of PTH (Albright et al., 1942). The findings that the effects of PTH on kidney and bone are mediated via an activation of adenylate cyclase (Dousa and Rychlik, 1968, Chase et al., 1969a) and that the urinary cAMP excretion can not be stimulated with PTH in this disorder (Chase et al., 1969b) suggest that the metabolic defect may exist in the PTH-sensitive receptor adenylate cyclase complex in kidney. Drezner et al. (1973) first demonstrated that PHP was not a single entity, but rather a heterogenous group of disorders, which could be divided into two types, e. g., PHP Type I and PHP Type II. PHP Type I is a disorder which fails to show an increase in urinary cAMP and phosphate excretion by the administration of PTH, but PHP Type II is that which responds to the administration of PTH with a marked rise in urinary cAMP, but no increase in phosphate excretion. Rodriguez et al. (1974) reported on a patient with PHP Type II who restored renal responsiveness to PTH by calcium administration.In the current study, we compared the. effect of calcium administration on renal response to PTH in these patients with PHP, with that in normal subjects and patients with idiopathic and surgical hypoparathyroidism.

Bartter Syndrome Type 1 Due to Novel SLC12A1 Mutations Associated With Pseudohypoparathyroidism Type II

“…Bando et al furthermore suggested that hypokalemia may have contributed in a BS patient to the development PTH-resistance, as documented by performing an EH test before and after correction of serum potassium levels [ 6 ]. PHP type II has also been reported to be associated with calcium or vitamin D deficiency, but the underlying mechanisms remain unresolved [ 7 , 8 ]. Elevated PGE 2 levels, which are known to cause of hypercalciuria, nephrocalcinosis, and osteopenia in BS type 1, have not yet been implicated in the pathogenesis of PTH resistance.…”