ARLINGTON, VA. — A level of vitamin D that is low but near or within the normal range may mask the presentation of patients with primary hyperparathyroidism, Dr. Shonni J. Silverberg reported at a conference sponsored by the American Society for Bone and Mineral Research.
In the United States, the presentation and epidemiology of primary hyperparathyroidism (pHPT) and vitamin D deficiency have developed concomitantly since food began to be fortified with vitamin D about 75 years ago. During this period, the prevalence of vitamin D deficiency has declined dramatically while the clinical manifestations of pHPT have become less severe. Symptomatic pHPT, or osteitis fibrosa cystica, has decreased because of lower levels of parathyroid hormone (PTH) in the disease. The weight and size of parathyroid adenomas also has declined substantially during this period, said Dr. Silverberg, professor of clinical medicine at Columbia University in New York.
“The question [was] whether or not calcium and vitamin D nutrition affects clinical expression of tumor growth in primary hyperparathyroidism. There has long been a hypothesis of 'double trouble,' which states that the clinical manifestations of primary hyperparathyroidism may be more severe in the presence of vitamin D deficiency,” she said.
Epidemiologic data show that classical pHPT still exists in areas of the world where vitamin D deficiency is endemic. When one analyzes the relationship between the two conditions in the United States and in developing countries where vitamin D deficiency is endemic, vitamin D (25-hydroxyvitamin D) levels are “somewhat inversely proportional” to the degree of PTH elevation, according to Dr. Silverberg. In this situation, people with very low vitamin D levels and pHPT may have PTH levels 15–20 times the upper limit of normal, but those with higher vitamin D levels—while still being in the lower range of normal—and pHPT may have PTH levels 1.5–2 times the upper limit of normal.
In patients with mild pHPT, sufficient—but still low-normal—levels of vitamin D oppose the hypercalcemic effect of excess PTH and thereby lower serum calcium levels and urinary calcium excretion back to their normal ranges.
Many of these people may be referred from doctors in the community who are reluctant to make a diagnosis of pHPT in patients with an elevated PTH level, normal serum calcium level, and a sufficient level of vitamin D, Dr. Silverberg said.
A study of women in New York and Beijing found that nearly all New Yorkers with pHPT were asymptomatic, whereas 94% of women with pHPT in Beijing were symptomatic and often had fractures and severe bone disease. There were very marked differences in serum levels of calcium, PTH, and vitamin D levels between women in the two cities (Int. J. Fertil. Womens Med. 2000;45:158–65).
In a study of 49 patients in Saudi Arabia (where vitamin D deficiency is endemic) who underwent a parathyroidectomy for pHPT, 19 patients had severe bone disease. These 19 patients had high levels of PTH and alkaline phosphatase, and increased thyroid gland size and weight, but their vitamin D levels were not significantly different from those without severe bone disease. The study investigators concluded that marked vitamin D deficiency may play a part in osteitis fibrosa cystica, but manifestation of bone disease with pHPT is multifactorial (J. Endocrinol. Invest. 2004;27:807–12).
A study in France showed that 38% of normal individuals were vitamin D insufficient (using a 20-ng/mL cutoff), compared with 91% of those with pHPT, regardless of its severity. The proportion of patients with pHPT who had vitamin D insufficiency also was similar regardless of whether their serum calcium level was lower or greater than 12 mg/dL (J. Endocrinol. Invest. 2006;29:511–5).
These results raise the question of whether there is a cutoff level of vitamin D at which pHPT becomes symptomatic, Dr. Silverberg said.
A study of patients with pHPT in Turkey found that individuals with vitamin D levels less than 15 ng/mL had significantly higher serum PTH, alkaline phosphatase, and parathyroid adenoma weight than did those with vitamin D levels of 15–25 ng/mL or more than 25 ng/mL (World J. Surg. 2006;30:321–6). Similar results were found in a study of U.S. patients.
The investigators of a separate case-control study that controlled for the effects of age, sex, body mass index, and season corroborated the finding that low vitamin D levels could worsen the clinical presentation of pHPT, but they did not find any association between low vitamin D levels and thyroid adenoma size. The percentage of patients with a vitamin D level less than 20 ng/mL varied significantly between the summer and winter months in the study's two control groups, but not among patients with pHPT (Clin. Endocrinol. [Oxf.] 2005;63:506–13).