Dr. Silverberg and her colleagues found that 53% of 124 U.S. patients with mild pHPT had an insufficient level of vitamin D (less than 20 ng/mL). The researchers also noticed a seasonal variation in the manifestation of pHPT in the summer in which vitamin D levels rose while PTH levels dropped. When the patients were split into tertiles based on vitamin D levels, the investigators found that serum PTH levels and alkaline phosphatase activity were significantly higher among patients in the lowest tertile of vitamin D (less than 16 ng/mL) than in patients in the middle (16–24 ng/mL) and highest tertiles (more than 24 ng/mL). Another analysis of the same data suggested that the relationship was valid throughout the range of levels for vitamin D and serum PTH. Histomorphometric studies of the patients' bones also were consistent with an enhanced effect of PTH in those with a low level of vitamin D (Am. J. Med. 1999;107:561–7). “It is very important, however, to remember that the results we are describing are [cross-sectional] … and that there is absolutely no way, based on anything that we or anybody else knows at this point, to infer a causal association in these data,” she said.
But another study of women with pHPT did not find any association between vitamin D levels and the severity of pHPT. In that study, low vitamin D levels were associated with age and renal function, but there was no association between vitamin D level and bone mineral density after investigators controlled for age, PTH excess, and body mass index (Clin. Endocrinol. [Oxf.] 2004;60:81–6).
The surgical literature shows that after patients with pHPT undergo a parathyroidectomy, a substantial percentage of patients have persistently elevated PTH levels despite others signs of being cured of their hyperparathyroidism. The most consistent finding across these studies is low vitamin D levels either just before or immediately after surgery. In this case, pHPT has become secondary HPT, she noted.
One small study of vitamin D repletion in patients with suspected pHPT did not provide conclusive results. In a study of 229 patients with osteoporosis, 15 had low vitamin D levels and concomitant high PTH levels (J. Clin. Endocrinol. Metab. 2000;85:3541–3). After a single treatment of 500,000 U of vitamin D2, five patients still had elevated PTH levels and were presumed to have pHPT. But two of those five patients had serum calcium levels less than 9 mg/dL, “which certainly raises the question in my mind about the diagnosis,” Dr. Silverberg said.
In those five patients, the bone mineral density after 13 months had increased by 6% in the spine and 8% in the hip. Although the investigators concluded that the increase in BMD resulted from the effect of vitamin D on pHPT, the patients' calcium levels make the diagnosis of pHPT questionable, she said.