The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years

Abstract

Context: Primary hyperparathyroidism (PHPT) often presents without classical symptoms such as overt skeletal disease or nephrolithiasis. We previously reported that calciotropic indices and bone mineral density (BMD) are stable in untreated patients for up to a decade, whereas after parathyroidectomy, normalization of biochemistries and increases in BMD ensue.

Objective: The objective of the study was to provide additional insights in patients with and without surgery for up to 15 yr.

Design: The study had an observational design.

Setting: The setting was a referral center.

Patients: Patients included 116 patients (25 men, 91 women); 99 (85%) were asymptomatic.

Intervention: Fifty-nine patients (51%) underwent parathyroidectomy and 57 patients were followed up without surgery.

Main outcome measure: BMD was measured.

Results: Lumbar spine BMD remained stable for 15 yr. However, BMD started to fall at cortical sites even before 10 yr, ultimately decreasing by 10 +/- 3% (mean +/- sem; P < 0.05) at the femoral neck, and 35 +/- 5%; P < 0.05 at the distal radius, in the few patients observed for 15 yr. Thirty-seven percent of asymptomatic patients showed disease progression (one or more new guidelines for surgery) at any time point over the 15 yr. Meeting surgical criteria at baseline did not predict who would have progressive disease. BMD increases in patients who underwent surgery were sustained for the entire 15 yr.

Conclusions: Parathyroidectomy led to normalization of biochemical indices and sustained increases in BMD. Without surgery, PHPT progressed in one third of individuals over 15 yr; meeting surgical criteria at the outset did not predict this progression. Cortical bone density decreased in the majority of subjects with additional observation time points and long-term follow-up. These results raise questions regarding how long patients with PHPT should be followed up without intervention.

Figure 1

Baseline characteristics and outcomes in 116 patients with PHPT. All patients with symptomatic disease had kidney stones. In patients with disease progression, either an indication for surgery, according to National Institutes of Health Consensus Conference guidelines (4,25) developed, or an overt complication of hyperparathyroidism (such as kidney stones or fracture) occurred during follow-up. ^a, Fifteen patients remaining at 15 yr; ^b, three patients remaining at 15 yr; ^c, one patient remaining at 15 yr; ^d, two patients remaining at 15 yr.

Figure 2

A, Mean (± sem) changes in BMD at three sites in patients with PHPT. Data shown are cumulative percent changes from baseline at each site in subjects who did not undergo parathyroidectomy after 1–15 yr of follow-up. *, P < 0.05, compared with baseline. B, Mean (± sem). Changes in BMD at three sites in patients with PHPT are shown only in subjects who completed 10 yr of follow-up. Eleven subjects were followed up for a total of 10 yr. C, Mean (± sem). Changes in BMD at three sites in patients with PHPT are shown only in subjects who completed 15 years of follow-up. Six subjects were followed up for a total of 15 yr.

Figure 2

A, Mean (± sem) changes in BMD at three sites in patients with PHPT. Data shown are cumulative percent changes from baseline at each site in subjects who did not undergo parathyroidectomy after 1–15 yr of follow-up. *, P < 0.05, compared with baseline. B, Mean (± sem). Changes in BMD at three sites in patients with PHPT are shown only in subjects who completed 10 yr of follow-up. Eleven subjects were followed up for a total of 10 yr. C, Mean (± sem). Changes in BMD at three sites in patients with PHPT are shown only in subjects who completed 15 years of follow-up. Six subjects were followed up for a total of 15 yr.

Figure 3

Mean (± sem) changes in BMD at three sites in patients with PHPT after parathyroidectomy. Data shown are cumulative percent changes from surgery at each site after 1–15 yr of follow-up. *, P < 0.05, compared with baseline.