Effect of Acetazolamide on Calcium and Phosphate Metabolism in Type I Pseudohypoparathyroidism: Interaction with Parathyroid Hormone*

Abstract

The effect of acetazolamide (4 mg/kg-day) on calcium and phosphate metabolism in four patients with type I pseudohypoparathyroidism was contrasted with the effects produced by a 36-h calcium infusion. Whereas both acetazolamide and calcium infusion resulted in comparable increases in serum ionized calcium levels, acetazolamide treatment was associated with a 100% increase in the fractional excretion of phosphate, whereas calcium infusion was associated with a 70% decrease in this parameter. The increment in the fractional excretion of phosphate observed during acetazolamide occurred independent of changes in urinary cAMP excretion, while calcium infusion was attended by a significant decrease in urinary cAMP. Despite the fact that both acetazolamide treatment and calcium infusion resulted in similar decrements in circulating immunoreactive parathyroid hormone levels and similar filtered loads of calcium, calcium clearance was increased during calcium infusion whereas it was not altered by acetazolamide, suggesting that acetazolamide actually enhanced the renal tubular reabsorption of calcium in this disorder. Although acetazolamide therapy was attended by a 35% increase in the phosphaturic response to exogenous parathyroid hormone, this effect was not statistically significant. Thus, the accumulated data suggest that small doses of acetazolamide, by increasing serum ionized calcium, could help to normalize renal responsivity to parathyroid hormone with resultant increases in the fractional excretion of phosphate and in the renal tubular reabsorption of calcium. This in turn could lessen requirements for pharmacological doses of vitamin D in pseudohypoparathyroidism thereby decreasing the ever present risk of hypercalcemia consequent to such treatment.