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Article(id=1208144410760561255, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208144409313526368, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2022.03.0251, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1629388800000, receivedDateStr=2021-08-20, revisedDate=null, revisedDateStr=null, acceptedDate=1633708800000, acceptedDateStr=2021-10-09, onlineDate=1765973673757, onlineDateStr=2025-12-17, pubDate=1648396800000, pubDateStr=2022-03-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1765973673757, onlineIssueDateStr=2025-12-17, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1765973673757, creator=13701087609, updateTime=1765973673757, updator=13701087609, issue=Issue{id=1208144409313526368, tenantId=1146029695717560320, journalId=1189873630562394117, year='2022', volume='47', issue='3', pageStart='213', pageEnd='319', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1765973673415, creator=13701087609, updateTime=1765974822867, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1208149230531756320, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208144409313526368, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1208149230531756321, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208144409313526368, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=251, endPage=257, ext={EN=ArticleExt(id=1208144411117077098, articleId=1208144410760561255, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Spectrum and risk factors of growth hormone-secreting pituitary tumor combined with thyroid diseases, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the spectrum and clinical characteristics of growth hormone(GH)-secreting pituitary tumor combined with thyroid diseases and to analyze its risk factors. Methods A retrospective study was used to analyze 133 patients with GH-secreting pituitary tumor who underwent thyroid ultrasound examination in the Second Affiliated Hospital of Army Medical University. The patients with GH-secreting pituitary tumor were divided into thyroid abnormal group and normal thyroid group. The clinical data of the two groups were compared. The correlation between variables was analyzed by multiple linear regression, and the risk of GH-secreting pituitary tumor with thyroid disease was analyzed by binary logistic regression. Results Among the 133 GH-secreting pituitary tumor patients, 108 cases (81.2%) had thyroid diseases. (1) Classified by thyroid ultrasonography, 51 (38.3%) with nodular goiters, 44 cases (33.1%) with simple thyroid nodules, 5 cases (3.8%) with goiters,33 cases (24.8%) without thyroid ultrasound abnormalities. (2) Classified by thyroid function, 34 cases (25.6%) with thyroid dysfunction, 99 cases (74.4%) with normal thyroid function. (3) Classified by pathology of thyroid, 10 cases accomplished thyroid pathological examination, 2 cases (1.5%) with thyroid cancers, 8 cases (6.0%) with benign thyroid nodules, 123 cases (92.5%)without pathological examination. (4) Classified by nosology, 22 cases (16.5%) with thyroiditis, 111 patients (83.5%) with normal thyroid immunological indicators. Univariate analysis showed that the nadir GH levels in patients with GH-secreting pituitary tumor was higher in the thyroid abnormality group than in the normal thyroid group (P<0.05). Multiple linear regression analysis showed that thyroid volume was positively correlated with insulin-like growth fator-1 (IGF-1), age, body mass index (BMI), thyroid stimulating hormone (TSH), thyroxine (T4) and thyroglobulin (Tg), [partial regression coefficient (B)=0.000, 0.006,0.019, 0.001, –0.144, –0.002 respectively, P<0.05]. The diameter of thyroid nodule was only positively correlated with Tg and age(B=0.004 and 0.017, P<0.05). The diameter of thyroid nodule was only positively correlated with Tg and age (P<0.05). The binary logistic regression analysis showed that the patients with the higher of the nadir GH levels, BMI of 24-26 kg/m2 and the sphenoid sinus invasion score >2, the higher the risk of combined thyroid diseases was, the odds ratio (OR) was 11.450, 5.022 and 6.576, respectively. Conclusion The incidence of various thyroid diseases in patients with GH-secreting pituitary tumor was significantly high, particularly nodular goiters and simple thyroid nodules, nadir GH levels of GH-secreting pituitary tumor is an independent risk factor of thyroid diseases, sphenoid sinus invasion score may be a potential predictor.

, correspAuthors=Hong-Ting Zheng, authorNote=null, correspAuthorsNote=
*E-mail:
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目的 探讨垂体生长激素(GH)瘤合并甲状腺异常的疾病谱及其临床特征，并分析相关危险因素。方法 回顾性分析陆军军医大学第二附属医院2015年1月－2021年3月收治的133例行甲状腺超声和功能检查的GH瘤患者的基本临床资料，根据是否合并甲状腺异常，将GH瘤患者分为甲状腺异常组与甲状腺正常组。比较两组患者的临床资料，采用多重线性回归分析变量间的相关性，并采用二元logistic回归分析GH瘤合并甲状腺疾病的危险因素。结果 本组133例GH瘤患者中合并甲状腺疾病者共108例(81.2%)。(1)按影像学分类：结节性甲状腺肿大51例(38.3%)，单纯甲状腺结节44例(33.1%)，单纯甲状腺肿大5例(3.8%)，无甲状腺超声影像学异常者33例(24.8%)；(2)按甲状腺功能分类：甲状腺功能异常者34例(25.6%)，甲状腺功能正常者99例(74.4%)；(3)按甲状腺病理分类：10例患者完善病理检查，其中甲状腺癌2例(1.5%)，良性甲状腺结节8例(6.0%)，其余123例(92.5%)未行病理检查；(4)按疾病种类分类：自身免疫性甲状腺疾病22例(16.5%)，甲状腺免疫学指标正常111例(83.5%)。单因素分析结果显示，GH瘤患者中甲状腺异常组GH谷值明显高于甲状腺正常组(P<0.05)。多元线性回归分析结果显示，GH瘤患者甲状腺体积与胰岛素样生长因子-1(IGF-1)、年龄、体重指数(BMI)及甲状腺球蛋白(Tg)呈正相关，而与促甲状腺激素(TSH)、甲状腺素(T4)呈负相关(偏回归系数分别为0.000、0.006、0.019、0.001、–0.144、–0.002，P<0.05)；而甲状腺结节直径仅与Tg及年龄呈正相关(偏回归系数分别为0.004、0.017，P<0.05)。二元logistic回归分析结果显示，GH瘤患者葡萄糖抑制生长激素试验中GH谷值(简称GH谷值)增高、超重(BMI为24~26 kg/m2)及蝶窦侵犯评分≥2分者，合并甲状腺疾病的风险增高(P<0.05)，比值比(OR)分别为11.450、5.022、6.576。结论 垂体GH瘤患者各种甲状腺疾病发生率高，以结节性甲状腺肿和单纯性甲状腺结节为主。GH谷值是GH瘤合并甲状腺疾病的独立危险因素，且蝶窦侵犯评分可能为其潜在的预测因子。

, correspAuthors=郑宏庭, authorNote=null, correspAuthorsNote=
郑宏庭，E-mail：
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洪翩，住院医师，主要从事垂体瘤方面的研究

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洪翩，住院医师，主要从事垂体瘤方面的研究

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洪翩，住院医师，主要从事垂体瘤方面的研究

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Neuroradiology, 1992, 34(1): 43-51., articleTitle=MRI of pituitary macroadenomas with reference to hormonal activity, refAbstract=null)], funds=[Fund(id=1208144417869906926, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, awardId=2018XLC3049, language=EN, fundingSource=Clinical Research Project of Army Medical University(2018XLC3049), fundOrder=null, country=null), Fund(id=1208144418025096180, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, awardId=2018XLC3049, language=CN, fundingSource=陆军军医大学临床研究项目(2018XLC3049), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1208144411997880958, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, xref=null, ext=[AuthorCompanyExt(id=1208144412023046785, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, companyId=1208144411997880958, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Endocrinology, the Second Affiliated Hospital of Army Medical University, Chongqing 400037, China), AuthorCompanyExt(id=1208144412039824002, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, companyId=1208144411997880958, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=陆军军医大学第二附属医院内分泌科，重庆 400037)])], figs=[ArticleFig(id=1208144417005880243, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, language=EN, label=Tab.1, caption=

Condition of thyroid nodules in 95 patients with GH-secreting pituitary tumor

, figureFileSmall=null, figureFileBig=null, tableContent=
甲状腺结节例(%)甲状腺结节例(%)
数目 结节内钙化 
 单发28(29.5) 有17(17.9)
 多发67(70.5) 无78(82.1)
部位 结节边缘形状 
 左叶17(17.9) 规则84(88.4)
 右叶19(20.0) 不规则2(2.1)
 峡部2(2.1) 混合9(9.5)
 多部位57(60.0)最大边缘直径(cm) 
结节性质  <162(65.3)
 实性26(27.4) ≥133(34.7)
 囊性19(20.0)结节良恶性 
 囊实性13(13.7) 良性85(89.5)
 混合性质37(38.9) 恶性2(2.1)
    可疑恶性8(8.4)
), ArticleFig(id=1208144417098154937, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, language=CN, label=表1, caption=

95例垂体GH瘤合并甲状腺结节患者的结节情况

, figureFileSmall=null, figureFileBig=null, tableContent=
甲状腺结节例(%)甲状腺结节例(%)
数目 结节内钙化 
 单发28(29.5) 有17(17.9)
 多发67(70.5) 无78(82.1)
部位 结节边缘形状 
 左叶17(17.9) 规则84(88.4)
 右叶19(20.0) 不规则2(2.1)
 峡部2(2.1) 混合9(9.5)
 多部位57(60.0)最大边缘直径(cm) 
结节性质  <162(65.3)
 实性26(27.4) ≥133(34.7)
 囊性19(20.0)结节良恶性 
 囊实性13(13.7) 良性85(89.5)
 混合性质37(38.9) 恶性2(2.1)
    可疑恶性8(8.4)
), ArticleFig(id=1208144417169458113, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, language=EN, label=Tab.2, caption=

Effects of GH and IGF-1 levels on thyroid volume and function in patients with GH-secreting pituitary tumora

, figureFileSmall=null, figureFileBig=null, tableContent=
项目GH谷值(μg/L)随机GH值(μg/L)IGF-1指数
≤12.0(n=67)>12.0(n=64)P≤17.4(n=68)>17.4(n=63)P≤2.52(n=66)>2.52(n=65)P
性别[例(%)]  0.240  0.753  0.011
 男33(49.3)25(39.1) 31(45.6)27(42.9) 22(33.3)36(55.4) 
 女34(50.7)39(60.9) 37(54.4)36(57.1) 44(66.7)29(44.6) 
年龄(岁，$\bar{x}±s$)45.3±10.643.7±13.30.40147.0±10.041.8±13.40.01440.7±12.248.6±13.40.000
病程(月，$\bar{x}±s$)65.8±80.174.7±76.10.26969.2±81.071.3±75.30.49068.5±75.872.0±80.90.713
BMI(kg/m2, $\bar{x}±s$)26.26±3.1525.85±3.200.47226.27±3.2525.83±3.090.43125.67±3.4226.48±2.840.147
甲状腺体积(mm3, $\bar{x}±s$)32.30±9.9242.88±14.910.00035.72±12.9239.28±14.210.05835.50±14.4639.66±12.370.004
甲状腺结节数目(个)  0.274  0.373  0.334
 无2314 1918 1720 
 单个1215 1116 1215 
 多个3235 3829 3928 
甲状腺结节最大横截面直径(mm, $\bar{x}±s$)0.80±0.531.18±0.900.0180.94±0.611.07±0.910.8060.89±0.811.13±0.700.014
FT3(pmol/L, $\bar{x}±s$)4.75±0.914.39±1.270.0704.59±0.874.56±1.330.8724.52±1.074.63±1.160.555
FT4(pmol/L, $\bar{x}±s$)14.03±3.0913.55±3.240.38013.52±3.0914.09±3.240.30513.13±3.3614.51±2.790.012
TSH(mU/L, $\bar{x}±s$)1.24±0.831.28±0.910.9741.19±0.821.33±0.910.5001.33±0.931.18±0.100.399
T3(nmol/L, $\bar{x}±s$)1.76±0.481.76±0.590.9651.71±0.511.81±0.560.3211.72±0.561.80±0.530.434
T4(nmol/L, $\bar{x}±s$)99.04±26.5495.98±28.670.52895.08±27.92100.21±27.090.28892.16±27.54103.36±26.540.019
Tg(μg/L, $\bar{x}±s$)19.21±27.2846.11±94.960.18323.46±38.8842.16±92.500.17229.65±68.8635.98±73.490.385
), ArticleFig(id=1208144417270121413, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, language=CN, label=表2, caption=

垂体GH瘤患者GH、IGF-1水平对甲状腺体积及功能的影响a

, figureFileSmall=null, figureFileBig=null, tableContent=
项目GH谷值(μg/L)随机GH值(μg/L)IGF-1指数
≤12.0(n=67)>12.0(n=64)P≤17.4(n=68)>17.4(n=63)P≤2.52(n=66)>2.52(n=65)P
性别[例(%)]  0.240  0.753  0.011
 男33(49.3)25(39.1) 31(45.6)27(42.9) 22(33.3)36(55.4) 
 女34(50.7)39(60.9) 37(54.4)36(57.1) 44(66.7)29(44.6) 
年龄(岁，$\bar{x}±s$)45.3±10.643.7±13.30.40147.0±10.041.8±13.40.01440.7±12.248.6±13.40.000
病程(月，$\bar{x}±s$)65.8±80.174.7±76.10.26969.2±81.071.3±75.30.49068.5±75.872.0±80.90.713
BMI(kg/m2, $\bar{x}±s$)26.26±3.1525.85±3.200.47226.27±3.2525.83±3.090.43125.67±3.4226.48±2.840.147
甲状腺体积(mm3, $\bar{x}±s$)32.30±9.9242.88±14.910.00035.72±12.9239.28±14.210.05835.50±14.4639.66±12.370.004
甲状腺结节数目(个)  0.274  0.373  0.334
 无2314 1918 1720 
 单个1215 1116 1215 
 多个3235 3829 3928 
甲状腺结节最大横截面直径(mm, $\bar{x}±s$)0.80±0.531.18±0.900.0180.94±0.611.07±0.910.8060.89±0.811.13±0.700.014
FT3(pmol/L, $\bar{x}±s$)4.75±0.914.39±1.270.0704.59±0.874.56±1.330.8724.52±1.074.63±1.160.555
FT4(pmol/L, $\bar{x}±s$)14.03±3.0913.55±3.240.38013.52±3.0914.09±3.240.30513.13±3.3614.51±2.790.012
TSH(mU/L, $\bar{x}±s$)1.24±0.831.28±0.910.9741.19±0.821.33±0.910.5001.33±0.931.18±0.100.399
T3(nmol/L, $\bar{x}±s$)1.76±0.481.76±0.590.9651.71±0.511.81±0.560.3211.72±0.561.80±0.530.434
T4(nmol/L, $\bar{x}±s$)99.04±26.5495.98±28.670.52895.08±27.92100.21±27.090.28892.16±27.54103.36±26.540.019
Tg(μg/L, $\bar{x}±s$)19.21±27.2846.11±94.960.18323.46±38.8842.16±92.500.17229.65±68.8635.98±73.490.385
), ArticleFig(id=1208144417387561932, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, language=EN, label=Tab.3, caption=

Comparison of the clinical features and magnetic resonance parameters in GH-secreting pituitary tumor patients between thyroid disorder group and normal thyroid group

, figureFileSmall=null, figureFileBig=null, tableContent=
项目甲状腺异常组(n=108)甲状腺正常组(n=25)P
性别[例(%)]  0.225
  男46(42.6)14(56.0)
  女62(57.4)11(44.0)
年龄(岁，$\bar{x}±s$)45.1±12.242.6±11.20.342
BMI(kg/m2, $\bar{x}±s$)26.26±3.1025.48±3.480.274
甲状腺体积[mm3, M(Q1, Q3)]35.57(29.82, 47.40)27.90(25.11, 32.00)0.000
GH瘤体积[mm3, M(Q1, Q3)]3.87(1.36, 8.05)2.63(1.81, 4.08)0.251
GH谷值[μg/L, M(Q1, Q3)]12.45(5.13, 34.80)6.75(2.66, 12.40)0.018
随机GH值[μg/L, M(Q1, Q3)]17.40(8.31, 37.65)12.10(5.49, 20.30)0.108
GH负荷[月×μg/L, M(Q1, Q3)]806.70(129.12, 2526.60)636.00(215.04, 1699.20)0.364
IGF-1指数($\bar{x}±s$)2.57±0.992.43±0.700.430
病程[月，M(Q1, Q3)]48(12, 102)48(12, 96)0.922
鞍区磁共振检查参数*[例(%)]   
 与正常垂体分界  0.076
  清楚72(75.8)23(92.0) 
  不清楚23(24.2)2(8.0) 
 病变形态  0.453
  规则49(51.6)15(60.0) 
  不规则46(48.4)10(40.0) 
 Hardly分级  0.073
  0~238(40.0)15(60.0) 
  3~457(60.0)10(40.0) 
 Knops分级  0.368
  0~266(69.5)15(60.0) 
  3~429(30.5)10(40.0) 
 海绵窦侵犯评分  0.764
  0~145(47.4)11(44.0) 
  2~350(52.6)14(56.0) 
 蝶窦侵犯评分  0.000
  0~140(42.1)21(84.0) 
  2~355(57.9)4(16.0) 
 鞍上生长评分  0.970
  0~146(48.4)12(48.0) 
  2~349(51.6)13(52.0) 
), ArticleFig(id=1208144417567917015, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, language=CN, label=表3, caption=

垂体GH瘤患者甲状腺异常组与甲状腺正常组临床特征、磁共振参数的比较

, figureFileSmall=null, figureFileBig=null, tableContent=
项目甲状腺异常组(n=108)甲状腺正常组(n=25)P
性别[例(%)]  0.225
  男46(42.6)14(56.0)
  女62(57.4)11(44.0)
年龄(岁，$\bar{x}±s$)45.1±12.242.6±11.20.342
BMI(kg/m2, $\bar{x}±s$)26.26±3.1025.48±3.480.274
甲状腺体积[mm3, M(Q1, Q3)]35.57(29.82, 47.40)27.90(25.11, 32.00)0.000
GH瘤体积[mm3, M(Q1, Q3)]3.87(1.36, 8.05)2.63(1.81, 4.08)0.251
GH谷值[μg/L, M(Q1, Q3)]12.45(5.13, 34.80)6.75(2.66, 12.40)0.018
随机GH值[μg/L, M(Q1, Q3)]17.40(8.31, 37.65)12.10(5.49, 20.30)0.108
GH负荷[月×μg/L, M(Q1, Q3)]806.70(129.12, 2526.60)636.00(215.04, 1699.20)0.364
IGF-1指数($\bar{x}±s$)2.57±0.992.43±0.700.430
病程[月，M(Q1, Q3)]48(12, 102)48(12, 96)0.922
鞍区磁共振检查参数*[例(%)]   
 与正常垂体分界  0.076
  清楚72(75.8)23(92.0) 
  不清楚23(24.2)2(8.0) 
 病变形态  0.453
  规则49(51.6)15(60.0) 
  不规则46(48.4)10(40.0) 
 Hardly分级  0.073
  0~238(40.0)15(60.0) 
  3~457(60.0)10(40.0) 
 Knops分级  0.368
  0~266(69.5)15(60.0) 
  3~429(30.5)10(40.0) 
 海绵窦侵犯评分  0.764
  0~145(47.4)11(44.0) 
  2~350(52.6)14(56.0) 
 蝶窦侵犯评分  0.000
  0~140(42.1)21(84.0) 
  2~355(57.9)4(16.0) 
 鞍上生长评分  0.970
  0~146(48.4)12(48.0) 
  2~349(51.6)13(52.0) 
), ArticleFig(id=1208144417676968926, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, language=EN, label=Tab.4, caption=

Binary logistic regression analysis of the risk factors for thyroid diseases in GH-secreting pituitary tumor patients

, figureFileSmall=null, figureFileBig=null, tableContent=
变量βPOR95%CI
BMI (24~26 kg/m2)2.1040.0168.1961.478~45.438
BMI (≥26 kg/m2)0.3900.4521.4770.535~4.072
高密度脂蛋白胆固醇1.6150.1025.0300.727~34.781
GH谷值2.5040.00412.2352.221~67.394
随机GH值–1.3760.0970.2520.050~1.285
蝶窦侵犯评分(≥2分)1.8830.0036.5761.896~22.806
), ArticleFig(id=1208144417773437926, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144410760561255, language=CN, label=表4, caption=

垂体GH瘤合并甲状腺疾病的二元logistic回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量βPOR95%CI
BMI (24~26 kg/m2)2.1040.0168.1961.478~45.438
BMI (≥26 kg/m2)0.3900.4521.4770.535~4.072
高密度脂蛋白胆固醇1.6150.1025.0300.727~34.781
GH谷值2.5040.00412.2352.221~67.394
随机GH值–1.3760.0970.2520.050~1.285
蝶窦侵犯评分(≥2分)1.8830.0036.5761.896~22.806
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垂体生长激素瘤合并甲状腺异常的疾病谱及相关危险因素分析
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洪翩 , 沈如飞 , 张磊 , 李行 , 彭桂亮 , 周玲 , 张玉玲 , 廖明钰 , 李蔚鑫 , 隆敏 , 郑宏庭 *
解放军医学杂志 | 临床研究 2022,47(3): 251-257
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解放军医学杂志 | 临床研究 2022, 47(3): 251-257
垂体生长激素瘤合并甲状腺异常的疾病谱及相关危险因素分析
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洪翩, 沈如飞, 张磊, 李行, 彭桂亮, 周玲, 张玉玲, 廖明钰, 李蔚鑫, 隆敏, 郑宏庭*
作者信息
  • 陆军军医大学第二附属医院内分泌科，重庆 400037

    • 洪翩，住院医师，主要从事垂体瘤方面的研究

通讯作者:

郑宏庭，E-mail：
Spectrum and risk factors of growth hormone-secreting pituitary tumor combined with thyroid diseases
Pian Hong, Ru-Fei Shen, Lei Zhang, Xing Li, Gui-Liang Peng, Ling Zhou, Yu-Ling Zhang, Ming-Yu Liao, Wei-Xin Li, Min Long, Hong-Ting Zheng*
Affiliations
  • Department of Endocrinology, the Second Affiliated Hospital of Army Medical University, Chongqing 400037, China
出版时间: 2022-03-28 doi: 10.11855/j.issn.0577-7402.2022.03.0251
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摘要
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目的 探讨垂体生长激素(GH)瘤合并甲状腺异常的疾病谱及其临床特征，并分析相关危险因素。方法 回顾性分析陆军军医大学第二附属医院2015年1月－2021年3月收治的133例行甲状腺超声和功能检查的GH瘤患者的基本临床资料，根据是否合并甲状腺异常，将GH瘤患者分为甲状腺异常组与甲状腺正常组。比较两组患者的临床资料，采用多重线性回归分析变量间的相关性，并采用二元logistic回归分析GH瘤合并甲状腺疾病的危险因素。结果 本组133例GH瘤患者中合并甲状腺疾病者共108例(81.2%)。(1)按影像学分类：结节性甲状腺肿大51例(38.3%)，单纯甲状腺结节44例(33.1%)，单纯甲状腺肿大5例(3.8%)，无甲状腺超声影像学异常者33例(24.8%)；(2)按甲状腺功能分类：甲状腺功能异常者34例(25.6%)，甲状腺功能正常者99例(74.4%)；(3)按甲状腺病理分类：10例患者完善病理检查，其中甲状腺癌2例(1.5%)，良性甲状腺结节8例(6.0%)，其余123例(92.5%)未行病理检查；(4)按疾病种类分类：自身免疫性甲状腺疾病22例(16.5%)，甲状腺免疫学指标正常111例(83.5%)。单因素分析结果显示，GH瘤患者中甲状腺异常组GH谷值明显高于甲状腺正常组(P<0.05)。多元线性回归分析结果显示，GH瘤患者甲状腺体积与胰岛素样生长因子-1(IGF-1)、年龄、体重指数(BMI)及甲状腺球蛋白(Tg)呈正相关，而与促甲状腺激素(TSH)、甲状腺素(T4)呈负相关(偏回归系数分别为0.000、0.006、0.019、0.001、–0.144、–0.002，P<0.05)；而甲状腺结节直径仅与Tg及年龄呈正相关(偏回归系数分别为0.004、0.017，P<0.05)。二元logistic回归分析结果显示，GH瘤患者葡萄糖抑制生长激素试验中GH谷值(简称GH谷值)增高、超重(BMI为24~26 kg/m2)及蝶窦侵犯评分≥2分者，合并甲状腺疾病的风险增高(P<0.05)，比值比(OR)分别为11.450、5.022、6.576。结论 垂体GH瘤患者各种甲状腺疾病发生率高，以结节性甲状腺肿和单纯性甲状腺结节为主。GH谷值是GH瘤合并甲状腺疾病的独立危险因素，且蝶窦侵犯评分可能为其潜在的预测因子。

垂体生长激素瘤  /  甲状腺疾病  /  甲状腺结节  /  相关性

Objective To investigate the spectrum and clinical characteristics of growth hormone(GH)-secreting pituitary tumor combined with thyroid diseases and to analyze its risk factors. Methods A retrospective study was used to analyze 133 patients with GH-secreting pituitary tumor who underwent thyroid ultrasound examination in the Second Affiliated Hospital of Army Medical University. The patients with GH-secreting pituitary tumor were divided into thyroid abnormal group and normal thyroid group. The clinical data of the two groups were compared. The correlation between variables was analyzed by multiple linear regression, and the risk of GH-secreting pituitary tumor with thyroid disease was analyzed by binary logistic regression. Results Among the 133 GH-secreting pituitary tumor patients, 108 cases (81.2%) had thyroid diseases. (1) Classified by thyroid ultrasonography, 51 (38.3%) with nodular goiters, 44 cases (33.1%) with simple thyroid nodules, 5 cases (3.8%) with goiters,33 cases (24.8%) without thyroid ultrasound abnormalities. (2) Classified by thyroid function, 34 cases (25.6%) with thyroid dysfunction, 99 cases (74.4%) with normal thyroid function. (3) Classified by pathology of thyroid, 10 cases accomplished thyroid pathological examination, 2 cases (1.5%) with thyroid cancers, 8 cases (6.0%) with benign thyroid nodules, 123 cases (92.5%)without pathological examination. (4) Classified by nosology, 22 cases (16.5%) with thyroiditis, 111 patients (83.5%) with normal thyroid immunological indicators. Univariate analysis showed that the nadir GH levels in patients with GH-secreting pituitary tumor was higher in the thyroid abnormality group than in the normal thyroid group (P<0.05). Multiple linear regression analysis showed that thyroid volume was positively correlated with insulin-like growth fator-1 (IGF-1), age, body mass index (BMI), thyroid stimulating hormone (TSH), thyroxine (T4) and thyroglobulin (Tg), [partial regression coefficient (B)=0.000, 0.006,0.019, 0.001, –0.144, –0.002 respectively, P<0.05]. The diameter of thyroid nodule was only positively correlated with Tg and age(B=0.004 and 0.017, P<0.05). The diameter of thyroid nodule was only positively correlated with Tg and age (P<0.05). The binary logistic regression analysis showed that the patients with the higher of the nadir GH levels, BMI of 24-26 kg/m2 and the sphenoid sinus invasion score >2, the higher the risk of combined thyroid diseases was, the odds ratio (OR) was 11.450, 5.022 and 6.576, respectively. Conclusion The incidence of various thyroid diseases in patients with GH-secreting pituitary tumor was significantly high, particularly nodular goiters and simple thyroid nodules, nadir GH levels of GH-secreting pituitary tumor is an independent risk factor of thyroid diseases, sphenoid sinus invasion score may be a potential predictor.

growth hormone-secreting pituitary tumor  /  thyroid diseases  /  thyroid nodules  /  correlations
洪翩, 沈如飞, 张磊, 李行, 彭桂亮, 周玲, 张玉玲, 廖明钰, 李蔚鑫, 隆敏, 郑宏庭. 垂体生长激素瘤合并甲状腺异常的疾病谱及相关危险因素分析. 解放军医学杂志, 2022 , 47 (3) : 251 -257 . DOI: 10.11855/j.issn.0577-7402.2022.03.0251
Pian Hong, Ru-Fei Shen, Lei Zhang, Xing Li, Gui-Liang Peng, Ling Zhou, Yu-Ling Zhang, Ming-Yu Liao, Wei-Xin Li, Min Long, Hong-Ting Zheng. Spectrum and risk factors of growth hormone-secreting pituitary tumor combined with thyroid diseases[J]. Medical Journal of Chinese People’s Liberation Army, 2022 , 47 (3) : 251 -257 . DOI: 10.11855/j.issn.0577-7402.2022.03.0251
正文
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垂体生长激素(growth hormone，GH)瘤是一种慢性内分泌性疾病，主要特征为GH水平明显增高，进而使血清胰岛素样生长因子-1(insulin like growth facror-1，IGF-1)水平升高[1]。GH和IGF-1水平长期升高可导致进行性躯体畸形及全身多系统并发症[2-4]。随着超声检查及检验技术的发展，作为GH瘤最常见并发症之一的甲状腺疾病检出率明显增高，主要表现为甲状腺肿大、甲状腺结节、甲状腺功能亢进、甲状腺癌、自身免疫性甲状腺疾病等[4-8]。既往研究发现，GH瘤合并结节性甲状腺肿大的超声诊断率高达80%[9]；与未合并GH瘤者相比，GH瘤患者的甲状腺癌患病率明显增高[10-11]。目前国内关于GH瘤合并甲状腺疾病的报道较少，而国际上GH瘤合并甲状腺疾病的发病率及危险因素报道也不一致，少有详细分析各种甲状腺疾病谱临床特征的研究。本研究回顾性分析陆军军医大学第二附属医院近6年收治的垂体GH瘤住院患者的临床资料，了解GH瘤患者合并甲状腺异常的疾病谱，并分析GH瘤合并甲状腺疾病的相关危险因素，以期为临床规范诊治GH瘤提供参考。
1 资料与方法
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1.1 研究对象
收集2015年1月－2021年3月于陆军军医大学第二附属医院就诊且行甲状腺超声和功能检查的垂体GH瘤患者的临床资料进行回顾性分析。纳入标准：(1)典型的垂体GH瘤临床表现：眉弓外凸、下颌前突、鼻大唇厚、手足增大、多汗、关节疼痛等；(2)内分泌诊断标准：随机GH值≥2.5 ng/ml或75 g葡萄糖抑制生长激素试验中GH谷值(以下简称GH谷值)≥1.0 ng/ml或IGF-1水平高于同年龄同性别人群的正常值上限；(3)鞍区增强MRI示垂体瘤；(4)术后病理证实为GH瘤。排除标准：(1)既往于外院接受过治疗且已达到临床缓解标准；(2)就诊期间未接受甲状腺超声检查；(3)诊断GH瘤前已有甲状腺疾病者。共纳入133例患者，年龄44.7(18~70)岁，男60例(45.1%)，女73例(54.9%)，男女比例1:1.2，平均BMI 26.1 kg/m2，中位病程48个月。将133例GH瘤患者分为甲状腺异常组(n=108)与甲状腺正常组(n=25)。133例GH瘤患者中合并甲状腺结节者95例。本研究获陆军军医大学第二附属医院医学伦理委员会审查批准(2021-研第035-01)。
1.2 临床资料收集
通过陆军军医大学第二附属医院临床病例管理系统收集符合纳入标准的133例GH瘤患者的临床资料。(1)患者一般情况：年龄、性别、病程、身高、体重；(2)实验室检查指标：随机GH值、GH谷值、IGF-1、卵泡刺激素(FSH)、黄体生成素(LH)、促甲状腺激素(TSH)、游离甲状腺素(FT4)、游离三碘甲腺原氨酸(FT3)、甲状腺素(T4)、三碘甲腺原氨酸(T3)、甲状腺球蛋白(Tg)、抗甲状腺球蛋白抗体(TgAb)、抗甲状腺过氧化物酶抗体(TPOAb)、空腹血糖(FPG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL)、高密度脂蛋白胆固醇(HDL)、肌酐(Cr)、尿素氮(BUM)、尿酸(UA)、谷丙转氨酶(ALT)；(3)甲状腺彩超检查指标：甲状腺左叶及右叶横径、甲状腺结节个数、最大横截面直径及性质等；(4)鞍区MRI增强检查：除13例于外院行行鞍区MRI检查外，95例甲状腺异常及25例甲状腺正常GH瘤患者均于本院行鞍区MRI检查，检查指标包括垂体腺瘤大小、Knops分级(0~4级)、Hardly分级(0~4级)、蝶窦侵犯评分(0~3分)、海绵窦侵犯评分(0~3分)、鞍上侵犯评分等(0~3分)。计算体重指数(BMI)、甲状腺体积及IGF-1指数[甲状腺体积=13×(左叶横径+右叶横径)－15[12]，IGF-1指数=IGF-1/年龄相匹配的正常值上限[13]]。
1.3 判定标准
(1)甲状腺功能异常：TSH低于正常值下限，但FT4、FT3在正常参考值范围内为亚临床甲状腺功能亢进(甲亢)；TSH低于正常值下限或在正常值范围内，但FT4和(或)FT3减低，且排除因严重疾病等导致的甲状腺病态综合征者为中枢性甲状腺功能减退(简称中枢性甲减)[14]；TSH水平高于正常值上限，但FT4和(或)FT3减低者为原发性甲减。(2)甲状腺肿：本院甲状腺超声检查结果提示甲状腺肿大者，判定为甲状腺肿大(甲状腺超声检查均由经验丰富的超声科医生进行)；含有1个或1个以上甲状腺结节者判定为结节性甲状腺肿，不含结节的甲状腺肿判定为单纯性甲状腺肿。(3)单纯甲状腺结节：甲状腺结节直径>5 mm且甲状腺体积在正常范围内。(4)自身免疫性甲状腺疾病：TPOAb值或TgAb值超出正常值范围。
1.4 垂体GH瘤合并甲状腺疾病的危险因素分析
为分析随机GH值、GH谷值及IGF-1对甲状腺体积及功能的影响，对GH谷值、随机GH值分别采取中位数分组的方法，IGF-1值以IGF-1指数表示，采取平均数分组的方法进行亚组分析。共131例患者同时行3种激素水平检测，GH谷值、随机GH值中位数分别为12.0 ng/ml、17.4 ng/ml，IGF-1指数平均值为2.52。将GH瘤患者的相关临床指标与甲状腺体积及甲状腺结节最大横截面直径进行相关性分析；比较GH瘤合并甲状腺疾病组与未合并甲状腺疾病组患者的临床特征及鞍区MRI参数情况，并筛选出相关的危险因素。
1.5 统计学处理
采用SPSS 23.0软件进行统计分析。符合正态分布的计量资料以$\bar{x}±s$表示，两组间比较采用独立样本t检验，偏态分布的计量资料以M(Q1，Q3)表示，两组间比较采用非参数检验；计数资料以例(%)表示，组间比较采用χ2检验；变量间相关性分析采用多重线性回归分析，危险因素分析采用二元logistic回归分析。P<0.05为差异有统计学意义。
2 结果
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2.1 垂体GH瘤合并甲状腺异常的疾病谱情况
本组133例GH瘤患者中，合并甲状腺疾病者108例(81.2%)，其中男46例、女62例，年龄(45.1±12.2)岁，平均BMI为26.26 kg/m2；甲状腺正常者25例(18.8%)，其中男14例、女11例，年龄(42.6±11.2)岁，平均BMI为25.48 kg/m2。133例患者按不同分类依据划分如下。(1)按影像学分类：甲状腺超声影像学异常者100例(75.2%)，其中结节性甲状腺肿大51例(38.3%)，单纯甲状腺结节44例(33.1%)，单纯甲状腺肿大5例(3.8%)；无甲状腺超声影像学异常者33例(24.8%)。(2)按甲状腺功能分类：甲状腺功能异常者34例(25.6%)，其中甲减21例(15.8%)[包括中枢性甲减20例(15.0%)、原发性甲减1例(0.8%)]，亚临床甲亢11例(8.3%)，仅FT4/FT3异常者2例(1.5%)；甲状腺功能正常者99例(74.4%)。(3)按甲状腺病理分类：10例患者完善病理检查，其中甲状腺癌2例(1.5%)，良性甲状腺结节8例(6.0%)；未行病理检查者123例(92.5%)。(4)按疾病种类分类：自身免疫性甲状腺疾病22例(16.5%)，甲状腺免疫学指标正常者111例(83.5%)。
95例GH瘤合并甲状腺结节的患者中，男36例(37.9%)，女59例(62.1%)；67例为多发性结节，占70.5%；单纯左叶和右叶结节发生率相近，分别为17例(17.9%)和19例(20.0%)，双侧多发性结节57例(60.0%)，峡部结节2例(2.1%)；以结节内无钙化及最大直径<1 cm者为主，分别为78例(82.1%)和62例(65.3%)，结节内有钙化及最大直径>1 cm者分别为17例(17.9%)及33例(34.7%)；结节边缘规则84例(88.4%)，边缘不规则2例(2.1%)，规则及不规则结节均有者9例(9.5%)；良性结节85例(89.5%)，8例(8.4%)超声检查可疑恶性，患者拒绝进一步检查确诊，2例(2.1%)经病理检查确诊为甲状腺乳头状癌(表1)。
2.2 GH及IGF-1水平对甲状腺体积、功能及其他生化指标的影响
GH瘤患者甲状腺体积及甲状腺结节最大横截面直径随GH谷值及IGF-1指数的升高而增大，差异有统计学意义(P<0.05)，而与随机GH值无关；GH瘤患者年龄较大者随机GH值较低，而IGF-1指数较高，差异有统计学意义(P<0.05)；男性患者IGF-1指数较女性高，差异有统计学意义(P=0.011)；IGF-1指数高的GH瘤患者FT4及T4较高，差异均有统计学意义(P<0.05)。GH谷值、随机GH值及IGF-1指数高低组间病程、BMI、甲状腺结节数目、FT3、T3、TSH、Tg值均未见明显差异(表2)。
以性别、年龄、病程、BMI、GH谷值、随机GH值、IGF-1、FT3、FT4、TSH、T3、T4及Tg为自变量，以GH瘤患者甲状腺体积及甲状腺结节最大横截面直径为因变量进行多元线性回归分析，结果显示，甲状腺体积与IGF-1、年龄、BMI、Tg呈正相关，而与TSH、T4值呈负相关(偏回归系数分别为0.000、0.006、0.019、0.001、–0.144、–0.002，P<0.05)；甲状腺结节直径仅与Tg、年龄呈正相关(偏回归系数分别为0.004、0.017，P<0.05)。
2.3 垂体GH瘤合并甲状腺疾病的临床特征及其危险因素分析
2.3.1 临床特征
甲状腺异常组甲状腺体积、GH谷值、鞍区MRI蝶窦侵犯评分高于甲状腺正常组，差异有统计学意义(P<0.05)；而两组性别、年龄、BMI值、病程、随机GH值、GH瘤体积、甲状腺功能、肝肾功能、血脂等生化指标，以及MRI检查中病变形态是否规则、Hardly分级、Knops分级、海绵窦侵犯评分、鞍上生长评分、与正常垂体分界是否清楚等比较差异无统计学意义(P>0.05，表3)。
2.3.2 危险因素分析
将GH瘤患者临床资料及鞍区MRI检查各项参数进行二元logistic回归分析，以α入=0.2分别筛选出自变量：BMI、高密度脂蛋白胆固醇、GH谷值、随机GH值、蝶窦侵犯评分，并设因变量(合并甲状腺疾病=1，不合并=0)，结果提示，GH谷值、蝶窦侵犯评分及超重(BMI为24~26 kg/m2)是GH瘤合并甲状腺疾病的独立危险因素(OR值分别为11.450、5.022、6.576，P<0.05，表4)。
3 讨论
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甲状腺疾病是GH瘤最常见的并发症之一，因其中的甲状腺结节在GH瘤患者中检出率高，且具有潜在恶性可能，故越来越受到临床医师的关注。
既往关于GH瘤合并甲状腺疾病谱的研究报道较少，且多仅关注甲状腺形态异常，缺乏对甲状腺功能异常的分析，不能深入揭示其疾病谱特点及危险因素。为此，本研究从甲状腺形态和功能异常、自身免疫性甲状腺疾病情况、危险因素等方面对GH瘤合并甲状腺疾病进行分析，以期为临床规范诊治GH瘤提供参考。
本组133例GH瘤患者中合并甲状腺疾病者占81.2%(108/133)，远高于一般人群，其发生率与国内外文献报道基本一致[9,15-18]。GH瘤合并的甲状腺疾病以甲状腺结节及甲状腺肿大为主，其中GH瘤患者甲状腺结节的特点与一般人群甲状腺结节的特点一致，均以多发性、无钙化、边缘规则及最大直径<1 cm者为主，不同的是，GH瘤患者多发性结节的比例高于一般人群(70.5% vs. 56.1%)，而无钙化及直径<1 cm者比例略低于一般人群(分别为82.1% vs.90.3%，65.3% vs. 73.0%)[19]。垂体GH瘤合并甲状腺癌的发生率在不同研究中波动较大，国外报道为1.2%~11.0%[11,20-22]，国内杨涵等[9]报道其发生率为8.6%，均明显高于一般人群的甲状腺癌发生率[23]；本研究中其发生率为1.5%(2/133)，相对较低，但由于8例可疑恶性结节患者拒绝进一步检查，故甲状腺癌比例可能高于1.5%。本研究中的甲状腺癌病理类型均为甲状腺乳头状癌，与既往报道GH瘤合并的甲状腺癌以乳头状癌为主一致[20]。对2例甲状腺癌和8例可疑恶性结节患者的各项指标进一步分析发现，与其他GH瘤患者比较，该10例患者性别差异较明显，80%为女性，而GH瘤合并甲状腺良性结节者中，女性仅占60%，因而在临床诊疗过程中，更应重视对女性甲状腺结节患者的进一步检查。
本研究中，GH瘤患者IGF-1指数及GH谷值对甲状腺体积及甲状腺功能有明显影响，尤其是IGF-1指数，而随机GH值对甲状腺形态及功能的影响并不明显，提示IGF-1指数在GH瘤患者甲状腺疾病的发生发展中起重要作用，与既往研究一致[24]。
探讨GH瘤合并甲状腺疾病的危险因素及预测因子有助于指导临床诊疗工作，具有重要意义。与高路等[15]研究不同的是，本研究未证实年龄为其危险因素，提示相较于年龄，临床应更重视GH水平，并尽早通过手术或药物治疗降低GH水平。本研究结果还提示超重为GH瘤合并甲状腺疾病的危险因素，控制超重GH瘤患者的体重可能减少甲状腺疾病的发生，然而肥胖GH瘤患者合并甲状腺疾病的风险却未见明显增高，其具体机制仍需进一步探讨。Lundin等[25]发现，垂体GH瘤更易向下侵犯蝶窦可能与分泌GH的细胞位于垂体的尾部及侧面有关，本研究结果也提示鞍区MRI检查中的蝶窦侵犯评分或许可成为GH瘤合并甲状腺疾病的预测因子。
综上所述，垂体GH瘤患者合并甲状腺疾病的发生率较高，GH谷值是GH瘤合并甲状腺疾病的独立危险因素，蝶窦侵犯评分或可成为其预测因子。GH瘤患者初诊时，临床医师应全面评估患者的甲状腺功能，常规行甲状腺超声检查，尽早降低GH水平，并定期进行随访，尤其是对蝶窦侵犯评分≥2分的患者。本研究尚有一些不足之处：首先，本研究为单中心研究，数据可能存在一定偏倚；其次，未对全部可疑恶性甲状腺结节者进行穿刺活检确定其良恶性；第三，未设置同年龄、性别、地区、碘营养相当的一般人群进行对照。未来应进一步完善研究设计，并组织多中心研究加以证实，以为GH瘤合并甲状腺疾病的早期筛查和预测提供依据。
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2022年第47卷第3期
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doi: 10.11855/j.issn.0577-7402.2022.03.0251
  • 接收时间：2021-08-20
  • 首发时间：2025-12-17
  • 出版时间：2022-03-28
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  • 收稿日期：2021-08-20
  • 录用日期：2021-10-09
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Clinical Research Project of Army Medical University(2018XLC3049)
陆军军医大学临床研究项目(2018XLC3049)
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    陆军军医大学第二附属医院内分泌科，重庆 400037

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郑宏庭，E-mail：
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