目的: 对经外科治疗后出现甲状旁腺激素(parathyroid hormone, PTH)升高伴正常血钙(normocalcemic parathormone elevation,NPE) 的原发性甲状旁腺功能亢进症(primary hyperparathyroidism,PHPT)患者的临床特征进行分析,提高该病的诊治能力,完善PHPT患者的术后管理。方法: 选取2017年8月至2019年11月中日友好医院内分泌科诊断为PHPT且术后6个月内出现NPE的9例患者作为研究对象,回顾性分析其临床资料和转归,并进行相关文献总结。结果: 临床特点:9例患者中6例为中老年女性,3例为男性。除1例为无症状性PHPT,其余8例主要临床表现为骨痛、肾结石及恶心、乏力。实验室检查:就诊时均血钙升高[(3.33±0.48) mmol/L],血磷降低[0.76 (0.74,0.78) mmol/L],24 h尿钙升高[8.1 (7.8,12.0) mmol/24 h],全片段甲状旁腺激素(intact parathyroid hormone, iPTH)明显升高[(546.1±257.7) ng/L],维生素D缺乏[25羟维生素D₃水平(21.0±5.7) nmol/L],骨源性碱性磷酸酶[7例41.3 (38.6,68.4) μg/L,2例>90 μg/L]及N端中段骨钙素(>71.4 μg/L)明显升高,2例患者存在肾功能异常。影像学检查:7例骨质疏松,3例患者肾脏超声见肾结石。所有患者甲状旁腺影像学检查均发现明确病灶, 其中2例为多发病灶,7例为单发病灶。治疗及转归:2例患者行甲状旁腺切除术治疗,其余患者予甲状旁腺微波热消融治疗;术后1个月患者均出现PTH升高[(255.0±101.4) ng/L],血钙正常,甲状旁腺超声未发现复发病灶。给予钙剂及维生素D联合治疗至术后6个月,PTH均显著下降,术后血钙水平始终正常。结论: PHPT术后发生NPE与术前PTH高水平、维生素D缺乏及肾功能受损可能相关,但并不意味着PHPT的复发或者存在残余病灶;术后充足的钙剂及维生素D的补充可能使患者获益;应规范对PHPT患者的术后随访,以预防和治疗术后NPE。

Objective: To summarize and analyze the clinical characteristics of primary hyperpara-thyroidism (PHPT) with normocalcemic parathormone elevation (NPE) after surgical treatment, so as to improve the therapeutic ability and standardized post-operative follow-up of PHPT patients. Methods: Nine patients who were diagnosed with PHPT in the Department of Endocrinology of China-Japan Friendship Hospital from August 2017 to November 2019 were selected as the subjects. They all developed NPE within 6 months after surgical treatment. The clinical features and outcomes were collected and analyzed retrospectively, in addition, the related literature was reviewed. Results: Clinical features: among the 9 patients, 6 were middle-aged and elderly females and 3 were male. The main clinical manifestations were bone pain, kidney stones, nausea and fatigue except for one case of asymptomatic PHPT. Pre-operative examination showed high serum calcium [(3.33±0.48) mmol/L], low serum phosphorus [0.76 (0.74,0.78) mmol/L], high 24-hour urinary calcium [8.1(7.8,12.0) mmol/24 h], obviously elevated intact PTH [(546.1±257.7) ng/L], vitamin D deficiency [25-hydroxyvitamin D₃ (21.0±5.7) nmol/L]. Serum levels of bone alkaline phosphatase [7 patients 41.3(38.6,68.4) μg/L,2 patients >90 μg/L] and N-terminal midcourse osteocalcin (>71.4 μg/L) were significantly elevated. The estimated glomerular filtration rate decreased in 2 patients. Imaging examination: 7 patients had osteoporosis. Renal calculi were found in 3 patients by renal ultrasound. Imaging examination of parathyroid glands found definite lesions in all the patients, including 2 cases of multiple lesions and 7 cases of single lesions. Treatment and outcome: two patients underwent parathyroidectomy, while other patients were treated with microwave thermal ablation. PTH increased 1 month after therapy [(255.0±101.4) ng/L], and no recurrent lesions were found by parathyroid ultrasound. After combined treatment with cal-cium and vitamin D for six months, PTH decreased significantly and the level of serum calcium remained normal at anytime during the follow-up period. Conclusion: The occurrence of postoperative NPE may be related to the higher pre-operative PTH, vitamin D deficiency and lower creatinine clearance. However, NPE may not predict recurrent hyperthyroidism or incomplete parathyroidectomy. Adequate calcium and vitamin D supplementation after surgery seems to be beneficial for patients with NPE. Post-operative follow-up of PHPT patients should be standardized to prevent and treat post-operative NPE.