Thirty Cases of Concurrent Paget's Disease and Primary Hyperparathyroidism: Sex Distribution, Histomorphometry, and Prediction of the Skeletal Response to Parathyroidectomy

Abstract

Studies of the effect of parathyroidectomy (PTX) on bone turnover in patients with the combination of primary hyperparathyroidism (PHPT) and Paget's disease (PD) are largely limited to case reports. The etiology of the combination is disputed. We report 30 patients and their biochemical (n = 17) and histomorphometric (n = 4) responses to PTX in 18. All 18 patients except one had a post-PTX fall in plasma alkaline phosphatase (pAP). There was a significant positive correlation between the degree of post-PTX fall in pAP and both the preoperative plasma total corrected calcium (CaC) (P < 0.01) and serum ionized calcium (P < 0.05). For the patients with CaC levels >3.0 mmol/liter, the mean % fall in pAP was 68% of pretreatment (to 32%). For those with CaC levels >/=2.68 mmol/liter the fall in pAP was >18%. Of 12 literature cases treated by PTX and followed up, 11 had a postoperative fall in pAP (range 6-83%). Pretreatment bone biopsies (n = 6) could not be distinguished from uncomplicated PD. No significant histomorphometric changes were documented postoperatively in the four patients studied; however, % fibrotic surfaces declined in each of the four. Of the 18 patients, only one had radiologic subperiosteal erosions preoperatively; none had clinical tetany postoperatively-thus distinguishing this combination of diseases from severe PHPT bone disease-a situation easily biochemically confused with this combination. The sex distribution of 2.75:1 F/M in this series resembles reported ratios in pure PHPT of 2.37:1, unlike the ratios found in pure PD (0.49-1.01:1). The prevalence of PHPT in PD is 2.2-6.0% (mean 4.4%) in 1836 patients. In our series, 73% of patients with both diseases were females >60 years of age. In population studies >60 years, PHPT was present in 3% of women and 1% of men. Hypercalcemia in PD is frequently attributed to immobilization. As part of this study, we examined 184 patients referred with PD for the existence of, and cause of hypercalcemia. Of this group, 21 were hypercalcemic, 19 (90%) of whom had PHPT; none had immobilization hypercalcemia. In patients with both disorders, the indications for PTX should include the potential post-PTX improvement in pagetic biochemistry and symptoms. The sex distribution (resembling pure PHPT) and the similar prevalence of PHPT in Paget's, and in the elderly population, support the likelihood, in most cases, that these two common diseases are associated by chance.

Coexistence of Primary Hyperparathyroidism and Paget Disease

“…29 The early findings of normal serum PTH and calcitonin in patients with Paget disease led most investigators to conclude that hormonal factors had no role in the abnormal bone remodeling process. 28 Additionally, patients with primary hyperparathyroidism who exhibit high bone turnover after successful parathyroidectomy should be screened for Paget disease. Both diseases cause bone pain and have high serum bone metabolism markers.…”

Italian Society of Endocrinology Consensus Statement: definition, evaluation and management of patients with mild primary hyperparathyroidism

“…Nonetheless, serum total alkaline phosphatase (ALP), and more specifically bone alkaline phosphatase (BALP), should be obtained at the time of diagnosis to identify significant increases suggestive for Paget's disease, that in 2.2-6.0 % of cases is known to be associated with mild PHPT [44].…”

Pagetʼs disease of bone: thereʼs more than the affected skeletal – a clinical review and suggestions for the clinical practice

“…This probably could reflect, at least in part, a genetic predisposition, but it remains still unknown, as descendants of migrants from this area develop this cancer [103]. GCTs, usually benign, are less common than sarcomas and are often painful [104].…”