Kravchenko Timothy, Finn Caitlin B, Fraker Douglas L, Kelz Rachel R, Cunningham Carrie, Wachtel Heather, Krumeich Lauren N
Department of Surgery, University of Michigan, Ann Arbor, MI; Department of Surgery, Massachusetts General Hospital, Boston, MA.
Department of Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Department of Surgery, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA.
Surgery. 2025 Jan;177:108830. doi: 10.1016/j.surg.2024.04.046. Epub 2024 Oct 4.
Normohormonal primary hyperparathyroidism is characterized by hypercalcemia and inappropriately normal parathyroid hormone levels. We previously reported that intraoperative parathyroid hormone decline of 50-70% for normohormonal and 75-88% for classic primary hyperparathyroidism during parathyroidectomy was predictive of (1) cure and (2) avoidance of hypocalcemia in a single-institution study (derivation cohort). We sought to externally validate these findings.
We performed a multi-institutional retrospective cohort study of patients undergoing parathyroidectomy for primary hyperparathyroidism from 2002 to 2019 (validation cohort). Primary outcomes were biochemical cure (calcium <10.3 mg/dL) and postoperative hypocalcemia (≤8.8 mg/dL) ≥6 months postoperatively. Test characteristics of the previously derived thresholds were evaluated in this cohort.
A total of 163 (16%) of 1,037 patients had normohormonal primary hyperparathyroidism. Cure rates were similar for normohormonal and classic primary hyperparathyroidism (94% vs 92%, P = .41). In patients who were cured, the median intraoperative parathyroid hormone decrease was lower in normohormonal compared with classic primary hyperparathyroidism (56.8 vs 73.3%, P < .0001). Rates of hypocalcemia were similar for normohormonal and classic primary hyperparathyroidism (14.6% vs 11.9%, P = .44), but increasing percent intraoperative parathyroid hormone decrease beyond 65% disproportionately correlated with hypocalcemia in patients with normohormonal primary hyperparathyroidism. When intraoperative parathyroid hormone thresholds from the derivation cohort were applied, positive predictive values for cure were 97% and 94% for normohormonal and classic primary hyperparathyroidism, respectively; negative predictive values for hypocalcemia were 89% for both groups. For both cohorts combined, a minimal intraoperative parathyroid hormone of 50% provided similar cure rates between groups (95.4% vs 93.8%, P = .42), whereas intraoperative parathyroid hormone exceeding 65% correlated with a greater risk of hypocalcemia in normohormonal compared with classic primary hyperparathyroidism (13.4% vs 6.9%, P = .02).
This multi-institutional study externally validated that intraoperative parathyroid hormone decrease of 50-65% predicts cure and hypocalcemia in patients with normohormonal primary hyperparathyroidism.
正常激素水平的原发性甲状旁腺功能亢进症的特征是高钙血症和甲状旁腺激素水平异常正常。我们之前在一项单机构研究（推导队列）中报告，甲状旁腺切除术中正常激素水平的原发性甲状旁腺功能亢进症患者甲状旁腺激素下降50%-70%，经典原发性甲状旁腺功能亢进症患者下降75%-88%，可预测（1）治愈和（2）避免低钙血症。我们试图对这些发现进行外部验证。
我们对2002年至2019年因原发性甲状旁腺功能亢进症接受甲状旁腺切除术的患者进行了一项多机构回顾性队列研究（验证队列）。主要结局是生化治愈（血钙<10.3mg/dL）和术后≥6个月的低钙血症（≤8.8mg/dL）。在该队列中评估先前推导阈值的检验特征。
1037例患者中有163例（16%）患有正常激素水平的原发性甲状旁腺功能亢进症。正常激素水平的原发性甲状旁腺功能亢进症和经典原发性甲状旁腺功能亢进症的治愈率相似（94%对92%，P = 0.41）。在治愈的患者中，正常激素水平的原发性甲状旁腺功能亢进症患者术中甲状旁腺激素下降的中位数低于经典原发性甲状旁腺功能亢进症患者（56.8%对73.3%，P < 0.0001）。正常激素水平的原发性甲状旁腺功能亢进症和经典原发性甲状旁腺功能亢进症的低钙血症发生率相似（14.6%对11.9%，P = 0.44），但在正常激素水平的原发性甲状旁腺功能亢进症患者中，术中甲状旁腺激素下降百分比超过65%与低钙血症的不成比例相关性增加。当应用推导队列中的术中甲状旁腺激素阈值时，正常激素水平的原发性甲状旁腺功能亢进症和经典原发性甲状旁腺功能亢进症治愈的阳性预测值分别为97%和94%；两组低钙血症的阴性预测值均为89%。对于两个队列合并而言，术中甲状旁腺激素最低下降50%时两组的治愈率相似（95.4%对93.8%，P = 0.42），而与经典原发性甲状旁腺功能亢进症相比，正常激素水平的原发性甲状旁腺功能亢进症患者术中甲状旁腺激素超过65%与低钙血症风险增加相关（13.4%对6.9%，P = 0.02）。
这项多机构研究外部验证了术中甲状旁腺激素下降50%-65%可预测正常激素水平的原发性甲状旁腺功能亢进症患者的治愈和低钙血症。
