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 < 0.01] and serum phosphorus (from 3.1 ± 0.1 to 4.2 ± 0.2 mg/dl; P < 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 µleq/ml), but fell significantly after remission to 22 ± 2 µleq/ml (P < 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 sub- jects. 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 < 0.02). (1,25-(OH)2D was inversely correlated with serum phosphorus (r = 0.59; P < 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, 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 phospha-turia of Cushing's syndrome. (J Clin Endocrinol Metab54: 1039,1982)