Calcium-regulated parathyroid hormone release in patients with mild or advanced secondary hyperparathyroidism

Differences in the regulation of parathyroid hormone (PTH) release by calcium are thought to account for excess PTH secretion in patients with secondary hyperparathyroidism (2 degrees HPTH). To determine whether calcium-regulated PTH release varies with the severity of 2 degrees HPTH in patients with end-stage renal disease, dynamic tests of parathyroid gland function were done using the four-parameter model in 26 patients with 2 degrees HPTH documented by bone biopsy. Estimates of the set point did not differ among patients categorized as mild (basal serum PTH < 400 pg/ml), moderate (basal PTH 400 to 600 pg/ml) or severe (basal PTH > 600 pg/ml) 2 degrees HPTH; values were 1.23 +/- 0.06 mmol/liter, 1.24 +/- 0.06 mmol/liter and 1.23 +/- 0.05 mmol/liter, respectively, and none of these set point estimates differed from results obtained in normal volunteers, 1.21 +/- 0.02 mmol/liter (NS). The slope of the sigmoidal ionized calcium-PTH curve also did not differ among groups. Set point values did not correspond to basal serum PTH levels, to the maximum serum PTH level observed during hypocalcemia or to the minimum serum PTH level seen during hypercalcemia in patients with 2 degrees HPTH. In contrast, basal serum PTH values were positively correlated with both the maximum serum PTH level observed during hypocalcemia (r = 0.76, P < 0.01), and the minimum serum PTH level attained during calcium infusions (r = 0.78, P < 0.01). Calcium-regulated PTH release does not differ with the degree of 2 degrees HPTH, and set point abnormalities do not account for excess PTH secretion in patients with chronic renal failure as judged by in vivo dynamic tests of parathyroid gland function. The results suggest that variations in parathyroid gland size are the major contributor to excessive PTH secretion in patients with chronic renal failure.