Primary Hyperparathyroidism Revisited in Menopausal Women with Serum Calcium in the Upper Normal Range at Population‐based Screening 8 Years Ago

Abstract

Population-based screening showed 2.1% prevalence of primary hyperparathyroidism (pHPT) in postmenopausal women. Individuals with total serum (s)-calcium levels of 2.55 mmol/L or more at screening were diagnosed with pHPT when subsequent analysis supported inappropriately elevated intact parathormone (PTH) levels in relation to even normal s-calcium levels. The arbitrary diagnostic criteria were validated by parathyroidectomy. Herein we reinvestigated biochemical signs of pHPT in women not diagnosed with pHPT due to s-calcium 2.50 to 2.54 mmol/L (group A, n = 160) at screening or due to appropriate PTH levels on two occasions after screening (group B, n = 70). Altogether, 99 women in group A and 47 in group B underwent reinvestigation 8.8 years after screening when they were 65 to 84 years old. The s-calcium levels averaged 2.56 mmol/L and had increased in group A (mean 0.04 mmol/L) and decreased in group B (mean 0.05 mmol/L). A total of 48 and 18 females (48%, 38%), respectively, met the previously validated criteria of pHPT. Altogether 21% of them were hypercalcemic (range 2.60-3.12 mmol/L). Subgroup analysis showed that PTH had not increased with time (n = 47) and that atherogenic blood lipids, but not glucose levels, were similar in pHPT patients and matched controls (n = 37). Assuming the existence of pHPT already at screening, the prevalence of pHPT could be adjusted to 3.4%. Even the most liberal diagnostic criteria utilized at pHPT screening seemed to underdiagnose the disease by inefficient cutoff limits for s-calcium and PTH. Because one-fifth of the women with pHPT progressed to hypercalcemia, long-term follow-up is advocated for those with s-calcium in the upper normal range.

Serum calcium and breast cancer risk: results from a prospective cohort study of 7,847 women

“…PHPT is often a mild disease with a protracted course, asymptomatic in its early stages, with gradually rising calcium levels. The prevalence of clinical symptomatic pHPT in postmenopausal women has been estimated to be around 3% [34] and the prevalence of asymptomatic pHPT could be even higher. Whether this prevalence is high enough to affect calcium levels overall in this group might be questioned, but we think it is reasonable to assume a higher percentage of women with undiagnosed, asymptomatic pHPT in the higher serum calcium quartiles.…”

Normocalcemic primary hyperparathyroidism: A newly emerging disease needing therapeutic intervention

“…Moreover, in several studies secondary causes of PTH elevation have not been rigorously excluded. [15][16][17][18][19] Recently, Silverberg and Bilezikian have demonstrated that patients with NCHPT are at risk of disease progression, further developing features of classical hyperparathyroidism in certain cases, such as low bone mass, fragility fracture and kidney stones. Data also suggest that some of these patients will become hypercalcemic over time.…”

“…Lundgren et al 15 studied more than 5,000 postmenopausal women between the ages of 55 and 75 in a Swedish survey. They found that 16% of individuals had normal serum calcium levels (<9.9 mg/dL) and elevated PTH.…”

Mild Primary Hyperparathyroidism: A Literature Review

“…In the U.S., primary hyperparathyroidism (pHPT) has an incidence of approximately 100,000 patients annually with an overall prevalence of 0.2%-1% [1].The prevalence is higher in patients .65 years old (1.5%) [2] and is most common in postmenopausal women (2.1%-3.4%) [3]. pHPT is typically characterized by elevated serum calcium associated with inappropriately elevated parathyroid hormone (PTH) levels.…”