J. C. Morrison1, H. Wachtel1, S. Zaheer1, L. E. Kuo1, I. Cerullo1, G. C. Karakousis1, R. R. Kelz1, D. L. Fraker1 1University Of Pennsylvania,Endocrine And Oncologic Surgery,Philadelphia, PA, USA
Introduction: Primary hyperparathyroidism (PHP) is a common endocrine diagnosis. While many studies have focused on normocalcemic hyperparathyroidism, less is known about normohormonal primary hyperparathyroidism (NHPHP). NHPHP is characterized by symptomatic hypercalcemia in the presence of normal parathyroid hormone (PTH) levels. We sought to examine the clinical presentation and surgical outcomes of patients with NHPHP in comparison to those of typical patients with PHP (TPHP).
Methods: We identified patients enrolled in our prospective endocrine surgery registry (1997-2013) who underwent a parathyroidectomy for PHP for potential inclusion in the study. Patients were excluded if they had Multiple Endocrine Neoplasia 1 or 2, secondary or tertiary hyperparathyroidism, parathyroid carcinoma, or if they did not have 6 month(6m) follow up data. Patients were classified by pre-operative PTH values as normohormonal (PTH 15-65 pg/mL) or typical (PTH>65 pg/mL). Variables analyzed included age, gender, presence of symptoms (nephrolithiasis, osteopenia, osteoporosis), percent drop in intraoperative PTH (IOPTH), cure by IOPTH (defined as >50% drop in IOPTH and ending within the normal range), and operative findings. The primary outcome of interest was biochemcial cure defined by serum PTH and calcium levels six months post-surgery. Univariate analysis was performed using the Wilcoxon rank sum and the Fisher’s exact test, as appropriate.
Results: We identified 78 NHPHP and 466 TPHP patients for study inclusion. Compared to TPHP patients, NHPHP patients had lower preoperative PTH levels (50.8 vs 136 pg/mL, p<0.01) but equivalent calcium levels (11.1 vs 11.0 mg/dL, p=0.13). There was no significant difference in sex, age, reported symptoms or preoperative localization (via Sestamibi scan) between the two groups. Compared to TPHP patients, NHPHP patients had lower initial IOPTH values (122+/-135 vs 225+/-292 pg/mL, p<0.05). However, NHPHP patients experienced a smaller drop in IOPTH during surgery, and thus had final IOPTH values equivalent to those of TPHP patients (22.9+/-17.8 vs 30.0+/-31.8 pg/mL, p=0.12). Cure by IOPTH standards was lower for NHPHP patients (86% vs 95%, p<0.05). Six months after surgery, there was no difference in PTH levels across the two groups (62.0+/-84.3 vs 58.6+/-63.4 pg/mL, p=0.27), but there was a small clinically insignificant difference in the calcium levels (9.7+/-0.7 vs 9.5+/-0.6 mg/dL, p<0.05). Biochemical cure rates at 6m were statistically equivalent at 92% NHPHP and 97% TPHP(p=0.06).
Conclusion: The cure rate following parathyroidectomy for NHPHP patients is lower using IOPTH criteria than standard criteria at six month follow-up. Moreover, while cure rates (immediate IOPTH cure and biochemical cure at 6m follow up) following parathyroidectomy for NHPHP may be slightly lower than those for TPHP patients, they all exceed 85%. Parathyroidectomy should be strongly considered in patients with NHPHP.