北京大学学报(医学版) ›› 2021, Vol. 53 ›› Issue (3): 573-579. doi: 10.19723/j.issn.1671-167X.2021.03.022

• 论著 • 上一篇    下一篇

原发性甲状旁腺功能亢进症术后甲状旁腺激素升高9例并文献复习

谢玲玎,王娜,张金苹,王昕,陈晓平,张波,卜石Δ()   

  1. 中日友好医院内分泌科,北京 100029
  • 收稿日期:2020-07-20 出版日期:2021-06-18 发布日期:2021-06-16
  • 通讯作者: 卜石 E-mail:13366901921@163.com

Normocalcemic with elevated post-operative parathormone in primary hyperpara-thyroidism: 9 case reports and literature review

XIE Ling-ding,WANG Na,ZHANG Jin-ping,WANG Xin,CHEN Xiao-ping,ZHANG Bo,BU ShiΔ()   

  1. Department of Endocrinology, China-Japanese Friendship Hospital, Beijing 100029, China
  • Received:2020-07-20 Online:2021-06-18 Published:2021-06-16
  • Contact: Shi BU E-mail:13366901921@163.com

摘要:

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。

关键词: 原发性甲状旁腺功能亢进症, 甲状旁腺激素, 维生素D

Abstract:

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.

Key words: Primary hyperparathyroidism, Parathyroid hormone, Vitamin D

中图分类号: 

  • R582.1

表1

9例PHPT患者术前临床特点及实验室检查"

Item Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9 Reference (range)
Gender Female Female Female Female Male Female Male Female Male
Age/years 54 55 76 56 55 54 59 58 31
Body mass index/(kg/m2) 18.8 37.1 28.5 22.3 24.5 26.4 25.4 23.8 21.3
Ostealgia Yes No No Yes Yes Yes Yes No Yes
Fatigue Yes No Yes Yes Yes Yes Yes No Yes
Nausea Yes No Yes Yes Yes Yes Yes No Yes
Fracture No No No No No No No No No
Kidney stone Yes No No Yes Yes No No Yes Yes
25OHD3/(nmol/L) 27.4 17.8 19.5 31.3 11.5 20.3 22.4 19.8 19.0 Lack<25,
insufficient
25-74,
enough 75-250
Ca/(mmol/L) 3.51 2.96 2.80 3.06 3.43 3.32 3.41 3.09 4.46 2.00-2.75
P/(mmol/L) 0.75 0.74 0.54 0.93 0.76 0.74 0.78 0.78 0.76 0.81-1.78
ALP/(U/L) 295 109 176 112 207 189 207 168 721 40-150
iPTH/(ng/L) 589.4 255.5 571.8 358.6 669.2 522.5 485.6 330.4 1 131.8 12-88
24 h UCa/(mmol/24 h) 14.9 8.1 7.8 7.6 8.0 8.6 9.1 7.7 31 2.7-7.5
Bone-derived alkaline phosphatase/(μg/L) >90 41.3 40.5 38.6 79.4 60.5 68.4 38.2 >90 8.5-17.9
N-MID OC/(μg/L) >71.4 >71.4 >71.4 >71.4 >71.4 >71.4 >71.4 >71.4 >71.4 11.7-55.2
TRACP/(U/L) 6.56 3.01 3.97 4.10 2.56 4.23 4.35 3.42 6.42 2.05-4.53
β-CTX/(μg/L) 1.25 1.07 0.80 0.90 0.28 0.82 0.94 0.56 8.56 0.128-1.292
eGFR [mL/(min·1.73m2)] 81.6 111.3 44.4 100.4 111.4 90.3 92.4 88.6 56.4 80-120
Albumin/(g/L) 40.0 41.2 39.6 47.6 42.7 41.5 40.6 40.8 38.5 35.0-55.0
Bone mineral density
TL2-4 -3.9 -2.7 -2.6 -2.9 -0.8 -2.7 -2.9 -2.1 -0.1(Z)
Tfemoral neck -3.7 -2.6 -1.7 -2.6 -1.8 -2.8 -2.4 -2.0 -3.4(Z)
Ttotal hip -3.5 -2.4 -1.5 -2.7 -1.8 -2.6 -2.5 -2.1 -3.0(Z)
Parathyroid ultrasonography Single
lesion:
2.8 cm×
2.7 cm
Lesion 1:
1.1 cm×
0.6 cm;
Lesion 2:
1.1 cm×
0.8 cm
Single
lesion:
2.1 cm×
1.2 cm
Single
lesion:
2.0 cm×
0.5 cm
Lesion 1:
1.3 cm×
0.8 cm;
Lesion 2:
1.5 cm×
0.8 cm;
Lesion 3:
1.8 cm×
1.2 cm
Single
Lesion:
2.4 cm×
2.5 cm
Single
lesion:
2.8 cm×
1.5 cm
Single
lesion:
2.1 cm×
0.9 cm
Single
lesion:
2.6 cm×
2.1 cm
Technetium-99m sestamibi and
computed tomography
Single
lesion
Two
lesions
Single
lesion
Single
lesion
Three
lesions
Single
lesion
Single
lesion
Single
lesion
Single
lesion

图1

治疗前后iPTH、血钙及25OHD3变化"

表2

9例患者术后治疗方案"

Items Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9
Post-operative 1-month therapy Rocaltrol
0.25 μg, 2/d; Calcium
carbonate
1.5 g, 2/d
Rocaltrol
0.25 μg, 2/d; Calcium
carbonate
1.5 g, 2/d; VitD3 800
IU, 1/d
Rocaltrol
0.25 μg,
2/d
Rocaltrol
0.25 μg, 2/d; Calcium
carbonate
0.75 g, 2/d
Rocaltrol
0.25 μg, 2/d; Calcium
carbonate
0.75 g, 2/d
Rocaltrol
0.25 μg, 2/d; Calcium
carbonate
0.75 g, 1/d
Rocaltrol
0.25 μg, 2/d; Calcium
carbonate
0.75 g, 1/d
Rocaltrol
0.25 μg, 1/d; Calcium
carbonate
0.75 g, 2/d
Rocaltrol
0.25 μg, 3/d; Calcium
carbonate
0.75 g, 3/d; VitD3 2 000
IU, 1/d
Post-operative 3-month therapy Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg,2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 1.5 g,
2/d;
Rocaltrol
0.25 μg,3/d;VitD3
2 000 IU,1/d
Post-operative 6-month therapy Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg,2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate 750
mg, 2/d;
Rocaltrol
0.25 μg, 2/d; VitD3
2 000 IU,1/d
Calcium carbonate
1.5 g, 2/d;
Rocaltrol
0.25 μg, 3/d; VitD3
2 000 IU,1/d
[1] Silverberg SJ, Clarke BL, Peacock M, et al. Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop[J]. J Clin Endocrinol Metab, 2014,99(10):3580-3594.
doi: 10.1210/jc.2014-1415
[2] Sun B, Guo B, Wu B, et al. Characteristics, management, and outcome of primary hyperparathyroidism at a single clinical center from 2005 to 2016[J]. Osteoporos Int, 2018,29(3):635-642.
doi: 10.1007/s00198-017-4322-7 pmid: 29198075
[3] Yao XA, Wei BJ, Jiang T, et al. The characteristics of clinical changes in primary hyperparathyroidism in Chinese patients[J]. J Bone Miner Metab, 2019,37(2):336-341.
doi: 10.1007/s00774-018-0922-3
[4] 中华医学会骨质疏松和骨矿盐疾病分会, 中华医学会内分泌分会代谢性骨病学组. 原发性甲状旁腺功能亢进症诊疗指南[J]. 中华骨质疏松和骨矿盐疾病杂志, 2014,7(3):187-198.
[5] Wei Y, Peng L, Li Y, et al. Clinical study on safety and efficacy of microwave ablation for primary hyperparathyroidism[J]. Korean J Radiol, 2020,21(5):572-581.
doi: 10.3348/kjr.2019.0593
[6] Fan BQ, He XW, Chen HH, et al. US-guided microwave ablation for primary hyperparathyroidism: a safety and efficacy study[J]. Eur Radiol, 2019,29(10):5607-5616.
doi: 10.1007/s00330-019-06078-y
[7] Biskobing DM. Significance of elevated parathyroid hormone after parathyroidectomy[J]. Endocr Pract, 2010,16(1):112-117.
doi: 10.4158/EP09122.RA pmid: 19789155
[8] Goldfarb M, Gondek S, Irvin GL, 3rd, et al. Normocalcemic parathormone elevation after successful parathyroidectomy: long-term analysis of parathormone variations over 10 years[J]. Surgery, 2011,150(6):1076-1084.
doi: 10.1016/j.surg.2011.09.017 pmid: 22136824
[9] Carsello CB, Yen TW, Wang TS. Persistent elevation in serum parathyroid hormone levels in normocalcemic patients after parathyroidectomy: does it matter?[J]. Surgery, 2012,152(4):575-581.
doi: 10.1016/j.surg.2012.07.005 pmid: 23021134
[10] Beyer TD, Solorzano CC, Prinz RA, et al. Oral vitamin D supplementation reduces the incidence of eucalcemic PTH elevation after surgery for primary hyperparathyroidism[J]. Surgery, 2007,141(6):777-783.
pmid: 17560254
[11] Lang BH, Wong IY, Wong KP, et al. Eucalcemic parathyroid hormone elevation after parathyroidectomy for primary sporadic hyperparathyroidism: risk factors, trend, and outcome[J]. Ann Surg Oncol, 2012,19(2):584-590.
doi: 10.1245/s10434-011-1846-5
[12] Duke WS, Kim AS, Waller JL, et al. Persistently elevated parathyroid hormone after successful parathyroid surgery[J]. Laryngoscope, 2017,127(7):1720-1723.
doi: 10.1002/lary.v127.7
[13] Caldwell M, Laux J, Clark M, et al. Persistently elevated PTH after parathyroidectomy at one year: experience in a tertiary referral center[J]. J Clin Endocrinol Metab, 2019,104(10):4473-4480.
doi: 10.1210/jc.2019-00705
[14] Westerdahl J, Valdemarsson S, Lindblom P, et al. Postoperative elevated serum levels of intact parathyroid hormone after surgery for parathyroid adenoma: sign of bone remineralization and decreased calcium absorption[J]. World J Surg, 2000,24(11):1323-1329.
pmid: 11038201
[15] Cao S, Hu Y, Zhao Y, et al. A retrospective study of elevated post-operative parathormone in primary hyperparathyroid patients[J]. Oncotarget, 2017,8(60):101158-101164.
doi: 10.18632/oncotarget.v8i60
[16] Nordenstrom E, Westerdahl J, Isaksson A, et al. Patients with elevated serum parathyroid hormone levels after parathyroidectomy: showing signs of decreased peripheral parathyroid hormone sensiti-vity[J]. World J Surg, 2003,27(2):212-215.
doi: 10.1007/s00268-002-6600-5
[17] Mittendorf EA, McHenry CR. Persistent parathyroid hormone elevation following curative parathyroidectomy for primary hyperparathyroidism[J]. Arch Otolaryngol Head Neck Surg, 2002,128(3):275-279.
doi: 10.1001/archotol.128.3.275
[18] Rianon N, Alex G, Callender G, et al. Preoperative serum osteocalcin may predict postoperative elevated parathyroid hormone in patients with primary hyperparathyroidism[J]. World J Surg, 2012,36(6):1320-1326.
doi: 10.1007/s00268-012-1432-4 pmid: 22278606
[19] Silverberg SJ, Gartenberg F, Jacobs TP, et al. Increased bone mineral density after parathyroidectomy in primary hyperparathyroidism[J]. J Clin Endocrinol Metab, 1995,80(3):729-734.
[20] Ning L, Sippel R, Schaefer S, et al. What is the clinical significance of an elevated parathyroid hormone level after curative surgery for primary hyperparathyroidism?[J]. Ann Surg, 2009,249(3):469-472.
doi: 10.1097/SLA.0b013e31819a6ded
[21] Wang TS, Ostrower ST, Heller KS. Persistently elevated parathyroid hormone levels after parathyroid surgery[J]. Surgery, 2005,138(6):1130-1135.
doi: 10.1016/j.surg.2005.08.026
[22] Carty SE, Roberts MM, Virji MA, et al. Elevated serum parathormone level after “concise parathyroidectomy” for primary sporadic hyperparathyroidism[J]. Surgery, 2002,132(6):1086-1092.
doi: 10.1067/msy.2002.128479
[23] Press D, Politz D, Lopez J, et al. The effect of vitamin D levels on postoperative calcium requirements, symptomatic hypocalcemia, and parathormone levels following parathyroidectomy for primary hyperparathyroidism[J]. Surgery, 2011,150(6):1061-1068.
doi: 10.1016/j.surg.2011.09.018
[24] Aberg V, Norenstedt S, Zedenius J, et al. Health-related quality of life after successful surgery for primary hyperparathyroidism: no additive effect from vitamin D supplementation: results of a double-blind randomized study[J]. Eur J Endocrinol, 2015,172(2):181-187.
doi: 10.1530/EJE-14-0757
[25] Norenstedt S, Pernow Y, Zedenius J, et al. Vitamin D supplementation after parathyroidectomy: effect on bone mineral density: a randomized double-blind study[J]. J Bone Miner Res, 2014,29(4):960-967.
doi: 10.1002/jbmr.v29.4
[26] Rolighed L, Rejnmark L, Sikjaer T, et al. Vitamin D treatment in primary hyperparathyroidism: a randomized placebo controlled trial[J]. J Clin Endocrinol Metab, 2014,99(3):1072-1080.
doi: 10.1210/jc.2013-3978
[27] Grubbs EG, Rafeeq S, Jimenez C, et al. Preoperative vitamin D replacement therapy in primary hyperparathyroidism: safe and beneficial?[J]. Surgery, 2008,144(6):852-858.
doi: 10.1016/j.surg.2008.06.032
[28] de la Plaza Llamas R, Ramia Angel JM, Arteaga Peralta V, et al. Elevated parathyroid hormone levels after successful parathyroidectomy for primary hyperparathyroidism: a clinical review[J]. Eur Arch Otorhinolaryngol, 2018,275(3):659-669.
doi: 10.1007/s00405-017-4836-9
[1] 邹健梅,武丽君,罗采南,石亚妹,吴雪. 血清25-羟维生素D与系统性红斑狼疮活动的关系[J]. 北京大学学报(医学版), 2021, 53(5): 938-941.
[2] 刘凯宁,孟焕新,侯建霞. 维生素D受体FokⅠ多态性对牙周组织细胞CYP24A1表达的影响[J]. 北京大学学报(医学版), 2018, 50(1): 13-19.
[3] 曹晓静, 和璐, 孟焕新, 李蓬, 陈智滨. 维生素D受体基因多态性与慢性牙周炎的相关性[J]. 北京大学学报(医学版), 2015, 47(4): 697-702.
[4] 卓滋泽, 刘玲, 马文军, 赵茜, 赵欣, 王永志, 张国义. 长波紫外线和中波紫外线对去卵巢骨质疏松大鼠1,25-二羟基维生素D3和骨代谢影响的比较[J]. 北京大学学报(医学版), 2013, 45(03): 392-397.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 田增民, 陈涛, Nanbert ZHONG, 李志超, 尹丰, 刘爽. 神经干细胞移植治疗遗传性小脑萎缩的临床研究(英文稿)[J]. 北京大学学报(医学版), 2009, 41(4): 456 -458 .
[2] 郭岩, 谢铮. 用一代人时间弥合差距——健康社会决定因素理论及其国际经验[J]. 北京大学学报(医学版), 2009, 41(2): 125 -128 .
[3] 成刚, 钱振华, 胡军. 艾滋病项目自愿咨询检测的技术效率分析[J]. 北京大学学报(医学版), 2009, 41(2): 135 -140 .
[4] 卢恬, 朱晓辉, 柳世庆, 郑杰, 邱晓彦. 白细胞介素2促进宫颈癌细胞系HeLaS3免疫球蛋白G的表达[J]. 北京大学学报(医学版), 2009, 41(2): 158 -161 .
[5] 袁惠燕, 张苑, 范田园. 离子交换型栓塞微球及其载平阳霉素的制备与性质研究[J]. 北京大学学报(医学版), 2009, 41(2): 217 -220 .
[6] 徐莉, 孟焕新, 张立, 陈智滨, 冯向辉, 释栋. 侵袭性牙周炎患者血清中抗牙龈卟啉单胞菌的IgG抗体水平的研究[J]. 北京大学学报(医学版), 2009, 41(1): 52 -55 .
[7] 董稳, 刘瑞昌, 刘克英, 关明, 杨旭东. 氯诺昔康和舒芬太尼用于颌面外科术后自控静脉镇痛的比较[J]. 北京大学学报(医学版), 2009, 41(1): 109 -111 .
[8] 祁琨, 邓芙蓉, 郭新彪. 纳米二氧化钛颗粒对人肺成纤维细胞缝隙连接通讯的影响[J]. 北京大学学报(医学版), 2009, 41(3): 297 -301 .
[9] 李宏亮*, 安卫红*, 赵扬玉, 朱曦. 妊娠合并高脂血症性胰腺炎行血液净化治疗1例[J]. 北京大学学报(医学版), 2009, 41(5): 599 -601 .
[10] 李伟军, 邢晓芳, 曲立科, 孟麟, 寿成超. PRL-3基因C104S位点突变体和CAAX缺失体的构建及表达[J]. 北京大学学报(医学版), 2009, 41(5): 516 -520 .