Clinical Study of Pseudohypoparathyroidism Type I & Type II

Abstract

Pseudohypoparathyroidism (PHP) is a disorder characterized by renal and/or skeletal refractoriness to the effect of parathyroid hormone (PTH). In 1973, it was first proposed by Drezner et al that PHP 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 the increase of urinary c-AMP and phosphaturia by the administration of PTH, but PHP Type II is that which responds to the administration of PTH with a marked rise of urinary c-AMP, but no increase of phosphate excretion, In 1974 Rodriguez et al demonstrated a patient with PHP Type II who restored normal renal responsiveness to PTH by calcium administration. Here we present two patients who fitted in the categories of PHP Type I & II, respectively, and restored normal renal responsiveness by the combined Ca-PTH administration or dibutyryl-cAMP infusion. Case I (PHP Type I) was a 31 yr old male with marked hypocalcemia and hyperphosphatemia, who showed neither increase of urinary c-AMP nor phosphate excretion in response to PTH infusion. Case II (PHP Type II), also diagnosed as Sjögren syndrome was a 22 yr old female with relatively mild hypocalcemia and hyperphosphatemia, who showed a marked rise of ordinary c-AMP, but no increase of phosphate excretion by PTH administration. Acute infusion of calcium, followed by PTH administration restored renal responsiveness to PTH in both types, though calcium infusion showed only little effects. The patient of PHP Type I received calcium gluconate and Vitamin D therapy and serum Ca improved, when PTH or DBc-AMP was given with the reappearance of PTH-like action. Thus in PHP Type I, the lack of c-AMP response to PTH, coupled with the ability of infused DBc-AMP to evoke a normal renal response suggests that the metabolic defect in this disorder may exist in hormone receptor-adenyl cyclase complex. Calcium infusion followed by PTH administration probably might evoke calcium influx and c-AMP production, resulting in the reappearance of hormone action. In PHP Type II, as c-AMP generation system is intact, the metabolic defect can be thought to exist in the rather poorly defined process beyond c-AMP generation. The combined Ca-PTH administration also restored normal renal response, probably partly due to the improved calcium environment of renal tubular cells. Though it is difficult to explain why endogenously generated c-AMP had no effect, but DBc-AMP had on reappearance of PTH-like action, it is speculated that DBc-AMP may have much more stronger effects for intracellular receptor site of c-AMP in PHP Type II. Conclusively these results clearly suggest that the nature of the metabolic defects in PHP is not a genetically determined inrreversible disorder, but rather a functional one which can be reversibly restored by special conditioning.