Normocalcemic Primary Hyperparathyroidism in Adults Without a History of Nephrolithiasis or Fractures: A Prospective Study

Abstract

The prevalence and the diagnostic criterion of “normocalcemic” primary hyperparathyroidism (NPHPT) are still uncertain and there is no consensual definition. This prospective study evaluated the prevalence of NPHPT in 676 adults without a history of fractures or nephrolithiasis and who would be submitted to thyroidectomy, the impact of adopting different cut-off values for 25-hydroxyvitamin D and estimated glomerular filtration rate (eGFR), and the agreement between biochemical diagnosis and the surgical finding of altered parathyroid glands. NPHPT was diagnosed in patients with normal total and ionized calcium and elevated PTH (in 2 measurements) and without a known cause of secondary HPT, including eGFR<40 ml/min/1.73 m2 and 25-hydroxyvitamin D<20 ng/dl. The 4 parathyroid glands were fully explored in these patients. Forty-six patients (6.8%) had a laboratory diagnosis of NPHPT. Altered parathyroid glands were detected in only 4 patients, corresponding to 0.6% of all patients and to 8.7% of those with a biochemical diagnosis of NPHPT. The latter was confirmed in 0/174 men, 1/252 premenopausal women, and 3/250 postmenopausal women. Among the 42 patients with elevated PTH and without altered parathyroid glands, 25 had 25-hydroxyvitamin D between 20 and 30 ng/dl, 7 had eGFR between 40 and 60 ml/min/1.73 m2, and 9 had both. The prevalence of NPHPT was 0.74% in this adult population without a history of nephrolithiasis or fractures. The diagnostic criterion using eGFR>60 ml/min/1.73 m2 and 25-hydroxyvitamin D>30 ng/dl was more appropriate considering the agreement with the surgical finding of altered parathyroid glands.

Normocalcemic Hyperparathyroidism: A Heterogeneous Disorder Often Misdiagnosed?

“…Population-based studies have generally suggested that NHPT is a rare condition. Estimates of prevalence have been variable, presumably because of different selection criteria used to identify NHPT patients (28)(29)(30)(31)(32)(33)(34)(35) (Table 2). The prevalence of the condition in these population-based studies has been estimated to range between 0.1% and 6%.…”

Normocalcaemic primary hyperparathyroidism: An update on diagnostic and management challenges

“…The wide variation in supposed prevalence rates can be attributed to selective cohorts of post‐menopausal women and older patients, absence of ionized calcium measurements, and varied threshold values for estimated glomerular filtration rates (eGFR), vitamin D, calcium, and intact parathyroid hormone (iPTH). Rosario et al accounted for these areas of potential error and found the prevalence of normocalcaemic primary hyperparathyroidism among patients without nephrolithiasis or fractures to be 0.74% in an adult population 5 …”

Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

“…As previously seen, an overestimated upper limit may mask the diagnosis of SHPT and especially of normocalcemic PHPT. In fact, 3/8 cases of normocalcemic PHPT from our series (5,6) would have their diagnosis masked if the values proposed by the kit and not the upper limit obtained in this study were used.…”

“…To analyze the impact of a new reference range of PTH on the diagnosis of asymptomatic PHPT, we reviewed the serum PTH levels of patients diagnosed with this condition among the 676 patients initially evaluated in this study: 6 had hypercalcemic PHPT (3) and 8 had normocalcemic PHPT (5,6). Considering the limit proposed by the manufacturer of the kit, 1/6 hypercalcemic patients and 4/8 normocalcemic patients had normal PTH.…”

“…The four parathyroid glands were fully explored and grossly abnormal parathyroid glands, i.e., enlarged, were removed. Eight patients had parathyroid adenoma detected during surgery (5,6) and were also excluded. Thus, the final sample consisted of 312 subjects (Table 1).…”