Surgical treatment of PHPT is a viable option for patients with laboratory diagnosed, "nonclassic" PHPT. Formal NP testing and evaluation of HRQL are useful tools that may assist physicians in choosing whom to refer for parathyroidectomy. Further longitudinal study of NP functioning and HRQL in patients with laboratory diagnosed PHPT is warranted.

To determine whether 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] regulates PTH secretion, we have tested its effects in both short term incubations (30-120 min) and long term primary cell cultures (24-96 h) of bovine parathyroid cells. In short term incubations, 10(-11)-10(-7) M 1,25-(OH)2D3 had no consistent effect on PTH secretion. In primary cultures of bovine parathyroid cells, significant suppression of PTH secretion occurred, as measured by both N-terminal and C-terminal PTH assays. Suppression of PTH secretion was dose dependent when 10(-11), 10(-9), and 10(-7) M 1,25-(OH)2D3 were tested for 48 h in culture, and the effects of 10(-7) M, 1,25-(OH)2D3 were noted as early as 24 h. Reversal of suppression of PTH secretion was observed after an additional 48 h in the absence of 1,25-(OH)2D3. Other studies from our laboratory have demonstrated that 1,25-(OH)2D3 suppresses levels of pre-pro-PTH mRNA in cultured bovine parathyroid cells, and we found a strong correlation at 48 h between the decrease in PTH release and that in mRNA. We conclude that 1) 1,25-(OH)2D3 suppresses PTH secretion rates in a dose-dependent manner in cells grown for 24-48 h in culture, but does not have a significant effect on short term PTH release (30-120 min); 2) cultured cells exhibiting suppression by 1,25-(OH)2D3 demonstrate nearly full recovery of PTH secretion after an additional 48 h in the absence of added 1,25-(OH)2D3; and 3) PTH secretion closely parallels levels of pre-pro-PTH mRNA in cultured cells, suggesting that the observed effects of PTH secretion reflect, at least in part, suppression of synthesis of PTH by 1,25-(OH)2D3.

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The in vitro secretion of PTH by dispersed human parathyroid cells was examined under conditions of low and high extracellular Ca+2 using tissue from patients with primary hyperparathyroidism and hyperparathyroidism resulting from chronic renal failure (CRF). The PTH secretion rate (nanograms of PTH per 10(5) cells/h) was lower in adenomatous tissues than in either primary hyperplastic cells or CRF cells under conditions of low (0.5 mM) or high (2.0-3.0 mM) extracellular Ca+2. Among the adenomas, a wide spectrum of degree of suppressibility of PTH secretion by high Ca+2 was found, ranging from 0% (completely nonsuppressible) to 98%. Suppression of the hyperplastic tissues in general was similar. The most suppressible adenomas demonstrated 2-fold greater PTH secretion rates in low Ca+2 conditions than the least suppressible adenomas, but in high Ca+2 conditions, the two groups had similar secretory rates. We conclude that the rate of PTH secretion by cells from adenomas was substantially lower than that of cells from tissues exhibiting either primary hyperplasia or hyperplasia resulting from CRF under these in vitro conditions. Thus, in adenomas, an increase in absolute cell number as well as alterations in the degree of calcium responsiveness may prove to be important etiological factors in the expression of hyperparathyroidism.