Pseudoidiopathic hypoparathyroidism: Hypoparathyroidism with ineffective parathyroid hormone

Abstract

A patient with hypoparathyroid manifestations—hypocalcemia, hyperphosphatemia, chronic tetany and cataracts—was found to have normal to high levels of serum immunoreactive parathyroid hormone (i-PTH) in a number of assay systems; clinical features of pseudohypoparathyroidism were lacking. Although the bones appeared undermineralized roentgenographically, evidence of rickets and osteomalacia was absent; other causes of hypocalcemia were eliminated by appropriate determinations. Cortical bone dynamics indicated a low bone formation rate and undermineralization, whereas intravenously administered calcium was avidly retained. Calcium balance was negative despite hypocalcemia, primarily because of fecal losses. Gastrointestinal radiocalcium absorption was diminished but correctable by administration of large amounts of vitamin D 2 or magnesium. Magnesium deficiency and gastrointestinal malabsorption as a cause of the findings were excluded (normal fat, xylose and lactose absorption). Renal responsiveness to exogenous PTH was demonstrated by increased cyclic adenosine 3′5′monophosphate (AMP) excretion, decreased mean maximal tubular reabsorption rate for phosphate, and phosphaturia. High levels of i-PTH, which rose markedly in response to phosphate infusion, were found in one radioimmunoassay system; in another system, these same serum specimens showed normal concentrations of i-PTH and no response to phosphate infusion. These data indicate that the patient has ineffective endogenous parathyroid hormone, presumably because of a defect in conversion of secreted proparathyroid hormone into an active form. The varying concentrations in different radioimmunoassay systems support this thesis. The syndrome resembles idiopathic hypoparathyroidism clinically and pseudohypoparathyroidism in that i-PTH is measurable; hence it is suggested it be called pseudoidiopathic hypoparathyroidism.