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儿童鞍区肿瘤术后垂体功能减退合并非酒精性脂肪性肝病的临床特征分析
DOI: 10.3969/j.issn.1001-5256.2023.06.013
伦理学声明：本研究方案于2022年5月10日经由武汉儿童医院伦理委员会审批，批号：2022R039-F01。
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：杜婷婷撰写论文；杜婷婷、姚辉、陈晓红对研究的思路及设计有关键贡献；罗杰、杨禄红、丰利芳、陈晓倩、胡曼、罗娟参与研究数据的获取和解释过程。
Clinical features of hypopituitarism with nonalcoholic fatty liver disease after sellar tumor surgery in children
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摘要:
目的 总结儿童鞍区肿瘤术后垂体功能减退合并非酒精性脂肪性肝病(NAFLD)的临床特征，探索儿童垂体功能减退与NAFLD之间的临床联系。 方法 回顾性分析2017年1月—2021年12月于华中科技大学同济医学院附属武汉儿童医院规律随访的鞍区肿瘤术后垂体功能减退出现NAFLD的患儿临床资料，分析临床特点。 结果 共32例规律随访且临床资料完整的鞍区肿瘤术后患者，其中10例(31.25%)出现NAFLD，其中男5例，女5例，9例为颅咽管瘤，均手术治疗，1例为生殖细胞瘤，局部放射治疗。10例患儿诊断垂体功能减退时的中位年龄为8.4(6.2~9.8)岁；诊断NAFLD的中位年龄为11.9(8.7~12.6)岁。从诊断垂体功能减退至诊断NAFLD的中位年数为2.0(1.4~4.0)年。诊断NAFLD时，10例患者均为肥胖，BMI较诊断垂体功能减退时平均增加(7.26±4.25)kg/m2；10例患者空腹血糖均正常，平均为(4.67±0.55)mmol/L，平均空腹胰岛素水平为(25.40±5.93)μIU/mL；胰岛素抵抗指数(HOMA-IR)平均为(5.26±1.29)；9例患者有高甘油三酯血症，1例患者甘油三酯升高，平均为(3.08±1.09)mmol/L；6例患者有高胆固醇血症，平均为(5.67±1.25)mmol/L；8例患者有高低密度脂蛋白胆固醇血症，平均为(3.97±1.27)mmol/L。2例患者诊断NAFLD予重组人生长激素联合二甲双胍治疗，治疗后患儿BMI、HOMA-IR及甘油三酯均较治疗前下降，总胆固醇、低密度脂蛋白胆固醇均降至正常范围。 结论 鞍区肿瘤术后患儿可出现体质量增加及垂体功能减退，继而出现胰岛素抵抗及血脂异常，从而导致NAFLD的发生。对这类患儿应进行体质量管理和积极的垂体激素替代治疗，并予以常规的脂肪肝相关筛查和管理。 Abstract:Objective To investigate the clinical features of hypopituitarism with nonalcoholic fatty liver disease (NAFLD) in children after sellar tumor surgery and the association between hypopitarism and NAFLD in children. Methods A retrospective analysis was performed for the clinical data of children with hypopituitarism and NAFLD after sellar tumor surgery who were followed up regularly in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2017 to December 2021, and their clinical features were analyzed. Results There were 32 children with regular follow-up and complete clinical data after sellar tumor surgery, and 10 children (31.25%) developed NAFLD, among whom there were 5 boys and 5 girls. Among these 10 children, 9 had craniopharyngioma and underwent surgical treatment, and 1 had germinoma and underwent local radiotherapy. The 10 children had a median age of 8.4(6.29.8) years at the diagnosis of hypopituitarism and a median age of 11.9(8.7-12.6) years at the diagnosis of NAFLD. The median number of years from the diagnosis of hypopituitarism to the diagnosis of NAFLD was 2.0(1.4-4.0) years. At the diagnosis of NAFLD, all 10 children had obesity, and body mass index (BMI) was increased by 7.26±4.25 kg/m2 on average since the diagnosis of hypopituitarism; the 10 children had a mean fasting blood glucose level of 4.67±0.55 mmol/L, a mean fasting insulin level of 25.40±5.93 μIU/ml, and a mean HOMA-IR index of 5.26±1.29. Among these 10 children, 9 had hypertriglyceridemia, and 1 had elevated triglyceride, with a mean level of 3.08±1.09 mmol/L; 6 children had hypercholesterolemia, with a mean level of 5.67±1.25 mmol/L; 8 children had high-density lipoprotein cholesterolemia, with a mean level of 3.97±1.27 mmol/L. After the diagnosis of NAFLD, 2 children were treated with recombinant human growth hormone and metformin and achieved reductions in BMI, HOMA-IR, and triglyceride after treatment, and total cholesterol and low-density lipoprotein cholesterol were reduced to the normal range. Conclusion Children may experience weight gain, hypopituitarism, insulin resistance, and dyslipidemia after sellar tumor surgery, which may lead to the onset of NAFLD. Weight management and active pituitary hormone replacement therapy are recommended for such children, as well as routine screening and management of fatty liver disease. -
Key words:
- Non-alcoholic Fatty Liver Disease /
- Hypopituitarism /
- Signs and Symptoms /
- Child
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表 1 10例患者诊断垂体功能减退时的临床特征
Table 1. Clinical features of the 10 patients when they diagnosed with hypopituitarism
项目 病例1 病例2 病例3 病例4 病例5 病例6 病例7 病例8 病例9 病例10 正常范围 性别 男 男 女 男 女 女 女 男 女 男 年龄(岁) 6 8.1 11 6.3 11.5 9.4 9 8.6 7.8 5.8 鞍区肿瘤 颅咽管瘤 颅咽管瘤 生殖细胞瘤 颅咽管瘤 颅咽管瘤 颅咽管瘤 颅咽管瘤 颅咽管瘤 颅咽管瘤 颅咽管瘤 身高(cm) 108 132 154 114 143 146 112 124 119 112 身高SDS -2.0 0.3 1.0 -1.0 -0.8 1.7 -3.8 -1.5 -1.4 -0.8 体质量(kg) 20.0 43.5 49.0 22.5 41.5 48.5 14.0 29.0 24.0 19.0 BMI(kg/m2) 17.1 (超重) 25 (肥胖) 20.6 (超重) 17.5 (超重) 20.2 (正常) 22.8 (肥胖) 11.2 (消瘦) 18.9 (超重) 16.8 (正常) 15.1 (正常) TSH(μIU/mL) 0.02 0.04 3.61 0.33 1.80 0.71 0.02 0.75 2.80 0.92 0.5~6.2 FT3(pmol/L) 7.36 2.89 3.20 2.66 2.82 1.96 2.74 3.96 2.08 1.98 5.2~8.6 FT4(pmol/L) 3.42 10.96 6.54 7.19 5.65 9.15 9.85 6.47 9.43 9.48 12~22 ACTH(pg/mL) ＜10 ＜10 23.5 14.0 13.2 ＜10 ＜10 ＜10 ＜10 ＜10 0~46 8am皮质醇(nmol/L) ＜13.79 26.50 24.04 ＜13.80 ＜13.80 25.60 16.34 14.56 18.70 32.0 ＞82.8 生长激素峰值(ng/mL) ＜0.05 ＜0.05 ＜0.65 ＜0.05 ＜0.20 ＜0.05 ＜0.46 ＜0.05 ＜0.05 ＜0.05 ＞10 IGF-1(ng/mL) 31.3 59.2 98.3 33.1 75.6 57.4 ＜25 40.0 ＜25 69.5 注：TSH，促甲状腺素；FT3，游离三碘甲状腺原氨酸；FT4，游离甲状腺素；ACTH，促肾上腺皮质素；生长激素峰值为胰岛素和盐酸可乐定片联合激发。 
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表 2 10例患者诊断NAFLD时的临床特征
Table 2. Clinical features of the 10 patients when they diagnosed with NAFLD
项目 病例1 病例2 病例3 病例4 病例5 病例6 病例7 病例8 病例9 病例10 正常范围 性别 男 男 女 男 女 女 女 男 女 男 年龄(岁) 10.0 12.4 12.8 7.8 12.5 11.3 13.8 12.6 9.0 7.9 年龄间隔(年) 4.0 4.3 1.8 1.5 1.0 1.9 4.8 4.0 1.2 2.1 身高(cm) 126.9 149.0 160.0 118.5 147.0 151.6 133.0 140.0 123.0 120.3 身高SDS -2.1 -0.5 0.7 -1.8 -1.1 0.5 -4.3 -2 -1.9 -1.5 体质量(kg) 50.0 60.5 67.0 31.0 52.0 65.5 45.5 54.5 32.5 34.0 BMI(kg/m2) 31.3 (肥胖) 27.3 (肥胖) 26.2 (肥胖) 22 (肥胖) 24 (肥胖) 28.4 (肥胖) 25.7 (肥胖) 27.8 (肥胖) 21.5 (肥胖) 23.5 (肥胖) BMI变化(kg/m2) 14.2 2.3 5.6 4.5 3.8 5.6 14.6 8.9 4.7 8.4 GLU(mmol/L) 4.03 5.20 4.70 5.92 4.84 4.42 4.13 4.56 4.39 4.60 3.9~6.1 INS(μIU/mL) 19.09 23.52 32.52 24.93 17.84 33.41 31.40 23.27 29.38 18.66 3~25 HOMA-IR 3.4 5.4 6.8 6.6 3.8 6.6 5.8 4.7 5.7 3.8 ＜3 ALT(U/L) 42 42 40 22 32 48 10 166 34 18 7~45 AST(U/L) 24 36 32 27 24 44 15 109 45 21 10~50 TC(mmol/L) 6.74 3.74 4.92 6.52 6.19 7.79 5.49 6.16 4.01 5.14 2.8~4.8 TG(mmol/L) 3.46 3.70 1.99 2.14 2.12 5.03 4.04 3.74 3.02 1.62 0.32~1.46 LDL-C(mmol/L) 5.19 2.06 3.69 5.08 4.31 5.65 3.54 4.09 2.74 3.39 1.55~2.86
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表 3 病例3 rhGH治疗前后各项指标的变化
Table 3. Variations of observation indexes before and after rhGH treatment of case 3
项目 治疗前 治疗3个月 治疗6个月 治疗9个月 治疗1年 正常范围 年龄(岁) 13.4 14.4 身高(cm) 161.3 163.5 体质量(kg) 65.0 62.0 BMI(kg/m2) 25.0 23.3 IGF-1(ng/mL) 109 336 336 232 230 537~715 GLU(mmol/L) 4.23 4.40 4.36 4.30 4.59 3.9~6.1 INS(μIU/mL) 37.41 33.56 29.80 28.90 26.96 3~25 HOMA-IR 7.0 6.5 5.7 5.5 5.5 ＜3 TC(mmol/L) 5.57 4.28 4.16 2.8~4.8 TG(mmol/L) 2.60 1.38 1.84 0.32~1.46 LDL-C(mmol/L) 3.53 2.76 2.69 1.55~2.86 ALT(U/L) 17 24 8 7~45 AST(U/L) 19 21 12 10~50 肝脏超声 脂肪肝(中-重度) 轻度脂肪肝
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表 4 病例10 rhGH治疗前后各项指标的变化
Table 4. Variations of observation indexes before and after rhGH treatment of case 10
项目 治疗前 治疗3个月 治疗6个月 治疗9个月 治疗1年 正常范围 年龄(岁) 7.9 8.9 身高(cm) 120.3 127.7 体质量(kg) 34.0 32.0 BMI(kg/m2) 23.5 19.6 IGF-1(ng/mL) 116 268 213 227 201 236~419 GLU(mmol/L) 4.49 4.15 4.61 4.39 3.58 3.9~6.1 INS(μIU/mL) 18.66 2.80 10.40 2.73 1.95 3~25 HOMA-IR 3.7 0.5 2.1 0.6 0.3 ＜3 TC(mmol/L) 5.14 3.50 4.24 4.21 3.92 2.8~4.8 TG(mmol/L) 1.62 1.0 0.80 0.62 0.57 0.32~1.46 LDL-C(mmol/L) 3.39 2.07 2.19 2.19 2.41 1.55~2.86 HDL-C(mmol/L) 1.19 1.13 1.74 1.77 1.34 7~45 ALT(U/L) 18 9 8 10 10~50 AST(U/L) 21 20 14 20 肝脏超声 轻度脂肪肝 正常 注：HDL-C，高密度脂蛋白胆固醇。
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