Vitamin D metabolites and parathyroid hormone in Cushing's syndrome: relationship to calcium and phosphorus homeostasis.

We studied the effects of glucocorticoid excess on calcium and phosphorus homeostasis in relation to vitamin D metabolites and parathyroid hormone (PTH) in seven patients with spontaneous ACTH-dependent Cushing's syndrome. Remission of hypercortisolism resulted in a significant increase in tubular reabsorption of phosphate [from 76 +/- 4% to 89 +/- 2% (mean +/- SEM); P less than 0.01] and serum phosphorus (from 3.1 +/- 0.1 to 4.2 +/- 0.2 mg/dl; P less than 0.005). Serum calcium did not change, although there was a reduction in daily urinary calcium excretion from 0.23 +/- 0.02 to 0.107 +/- 0.02 mg calcium/mg creatinine. Serum immunoreactive PTH (iPTH) levels were normal during Cushing's syndrome (34 +/- 5 microleq/ml), but fell significantly after remission to 22 +/- 2 microleq/ml (P less than 0.05). This small decrease in iPTH did not correlate with the improvement of phosphate homeostasis. Plasma 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH2)D] concentrations in Cushing's syndrome did not differ from measurements in 97 normal subjects. After treatment, 25OHD did not change, but 1,25-(OH)2D fell in each patient from a mean of 44 to 22 pg/ml (P less than 0.02). 1,25-(OH)2D was inversely correlated with serum phosphorus (r = 0.59; P less than 0.01), but did not correlate with iPTH. The known impairment of intestinal calcium absorption in Cushing's syndrome cannot be attributed to a decrease in the circulating levels of 1,25-(OH)2D. Endogenous hypercortisolism decreases tubular phosphate reabsorption and serum phosphorus, increase tubular phosphate reabsorption and serum phosphorus, increases iPTH, and results in an increase in 1,25-(OH)2D. These events may contribute to the severe loss of bone mass in such patients and may account for the calciuria and phosphaturia of Cushing's syndrome.