To evaluate the effects of primary hyperparathyroidism (PHPT) on bone mass and structure, we have studied the iliac crest biopsies of 27 patients, 10 males (28-68 yr old) and 17 females (26-72 yr old) with mild PHPT after in vivo tetracycline labeling. All patients had mild hypercalcemia in the absence of any other cause and elevated levels of PTH without radiological evidence of bone disease. Static parameters of bone turnover (osteoid surface, osteoid volume, and eroded surface) were elevated in both men and women compared to normal values; the midmolecule RIA for PTH (PTHMM) was positively correlated with osteoid surface (r = 0.44; P less than 0.025) and eroded surface (r = 0.58; P less than 0.005). Dynamic parameters of bone turnover (mineralizing surface, expressed as double plus half single labeled surface, and bone formation rate at tissue level) were elevated compared to normal values; PTHMM was positively correlated with double plus half single labeled surfaces (r = 0.33; P less than 0.05) and with bone formation rate at the tissue level (r = 0.37; P less than 0.05). The mineral apposition rate was within the limits of normal values and positively correlated with PTHMM (r = 0.34; P less than 0.05). Histomorphometric parameters of bone structure [cancellous bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), cortical thickness (Ct.Th), and total bone density (TBD)] were compared to those in 20 autopsy control subjects, 12 men (33-60 yr old) and 8 women (27-75 yr old). BV/TV and Tb.N were significantly higher in PHPT patients than controls (P less than 0.02 and P less than 0.001, respectively). Tb.Sp was significantly lower in PHPT patients than controls (P less than 0.001), whereas Tb.Th was not significantly different between PHPT patients and controls. Ct.Th was significantly lower in PHPT patients than in controls (P less than 0.001), whereas TBD was not significantly different between the two groups. BV/TV was negatively correlated with age in both controls and PHPT patients. Tb.N showed a negative correlation and Tb.Sp a positive correlation with age in controls (r = -0.47; P less than 0.05 and r = 0.52; P less than 0.02, respectively), but they were not significantly dependent on age in PHPT patients. Tb.Th, while showing no significant age-related change in controls, was negatively correlated with age in PHPT patients (r = -0.42; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
HRPT2 and parafibromin studies improved the diagnostic accuracy in two patients with primary hyperparathyroidism (PHPT) referred to us after surgery, in whom the clinical data were at variance with the pathological diagnosis of adenoma and carcinoma, respectively. Patients were referred to us after parathyroidectomy. Patient #1 had had a 1.5-cm tumor easily removed with a histological diagnosis of parathyroid carcinoma and normocalcemia for 2 years. Re-examination of the histology showed no cardinal signs of parathyroid cancer. Patient #2, with severe PHPT, had had the removal of a 3.5-cm tumor described histologically as adenoma. Ten years later PHPT recurred and persisted despite removal of two mildly enlarged parathyroid glands that were histologically normal. Re-review of the initial histology showed a trabecular pattern, fibrous bands, and atypical mitoses, suggesting an atypical adenoma. Because of the suspicion that case #1 could be an atypical adenoma and case #2 a carcinoma further molecular studies were performed. No HRPT2 and parafibromin abnormalities were identified in patient #1, strongly indicating a benign lesion. In patient #2, an HRPT2 germline mutation was found (E115X in exon 4) and associated with no parafibromin staining. These data, together with the clinical features, supported the suspicion of a parathyroid carcinoma that was confirmed by histological examination of further slides of the tumor, showing capsular and vascular invasion. A lung 1.5-cm nodule detected by computed tomography was excised. Histology showed a metastasis of parathyroid carcinoma. HRPT2 gene studies improved the diagnostic accuracy in 2 parathyroid tumors that are of uncertain type.
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