Normocalcaemic primary hyperparathyroidism: is nephrolithiasis more common than osteoporosis?

Abstract

Background Normocalcaemic primary hyperparathyroidism (NPHPT) is often under‐recognised in clinical practice. Aim To determine the prevalence and clinical significance of NPHPT in an unselected sample in an acute hospital setting. Methods Patients aged >18 years who had measurement of an elevated serum parathyroid hormone (PTH ≥ 7 pmol/L) during 12 months from 1 January 2017 to 31 December 2017 were retrospectively studied. NPHPT was defined by the presence of elevated serum PTH with normal albumin‐corrected serum calcium on two or more occasions after excluding secondary causes. Patients were followed up for 2 years. Relevant data were collected by review of electronic medical records. Results Of the 2593 patients who had PTH measured during the study period, 1278 had serum PTH ≥ 7 pmol/L. Hypercalcaemic primary hyperparathyroidism (PHPT) was diagnosed in 174 patients. Secondary causes for elevated serum PTH were identified in 993 patients: 815 (chronic kidney disease – estimated glomerular filtration rate < 60 mL/min/1.73 m2 or renal transplant), 98 (vitamin D deficiency – 25(OH)D < 50 nmol/L), 28 (gastric bypass surgery), 38 (medications), 13 (malabsorption or post‐thyroidectomy) and 1 (hypercalciuria). Data were incomplete for 80 patients. The prevalence of NPHPT with and without the exclusion of hypercalciuria was 0.19% (5) and 0.39% (10) respectively. The prevalence of nephrolithiasis in NPHPT was higher than PHPT (100% vs 15% among five patients (P < 0.001) and 50% vs 15% among 10 patients (P = 0.014)). The prevalence of osteoporosis was not significantly different between NPHPT and PHPT (20% vs 45% among five patients (P = 0.389) and 30% vs 45% among 10 patients (P = 0.518)). Conclusion These findings give further credence to the diagnosis of NPHPT as a clinical entity. Nephrolithiasis may be a greater problem than osteoporosis in NPHPT compared with PHPT. This needs prospective evaluation.

Development and validation of a nomogram for risk prediction of nephrolithiasis recurrence in patients with primary hyperparathyroidism

“…All patients were diagnosed as nephrolithiasis with PHTH. PHTH was defined as PTH level > 69 pg/ml with a normal or elevated albumin-adjusted calcium ( 11 , 12 ). The exclusion criteria were as follows: (1) secondary hyperparathyroidism, such as chronic kidney disease, vitamin D deficiency, and gastrointestinal malabsorption; and (2) intake of medications such as diuretics, hydrochlorothiazide, and lithium.…”

Normocalcemic primary hyperparathyroidism

“…Of note, few studies have monitored biochemical parameters over time, which can overestimate the disease prevalence. The disease appears to be relatively rare, with most studies using established criteria demonstrating a prevalence of 0.1%-0.7% (6,(24)(25)(26)(27)(28)(29)(30)(31)(32)(33).…”

“…In these individuals identified through biochemical testing, there do not appear to be significant differences in clinical indices, bone turnover markers, or bone mass as compared to euparathyroid patients or patients with secondary hyperparathyroidism. The clinical features are summarized in Table 2 ( 6 , 25 , 27 , 30 , 33 – 41 ).…”

Genetic aspects underlying the normocalcemic and hypercalcemic phenotypes of primary hyperparathyroidism

“…NPHPT has been extensively studied to evaluate if complications of the disease were similar to its hypercalcemic counterpart [ 5 – 7 ]. However, a recent consensus statement acknowledges paucity of data concerning some aspects of the disease, such as pathophysiology, natural history, organ damage and management [ 3 ].…”