儿童鞍区肿瘤术后垂体功能减退与代谢相关脂肪性肝病关系的研究

doi:10.12372/jcp.2025.24e0929

Abstract

Abstract:

Objective To investigate the clinical relationship between hypopituitarism and metabolic-associated fatty liver disease (MAFLD) in children with sellar region tumor after surgery. Methods From January 2017 to December 2023, patients with hypopituitarism resulting from sellar tumors were consistently monitored for over a year. All patients were categorized into either the MAFLD (+) group or the MAFLD (-) group based on liver ultrasonography. A comparison was then made between the clinical and biochemical parameters of the two groups. Results A total of 33 patients were included, with 16 patients (48.5%) in the MAFLD (+) group and 17 patients (51.5%) in the MAFLD (-) group. There were no significant differences in age or gender between the two groups. All patients had GHD (100%) and CH (100%). AI was present in 30 patients (91%), with equal distribution between the MAFLD (+) and (-) groups (50% each). CDI was diagnosed in 22 patients (66.7%), with more patients in the MAFLD (-) group (63.6%) compared to the MAFLD (+) group (36.4%). Hypernatremia hypodipsia occurred in 7 patients (21.2%), all belonging to the MAFLD (+) group. All CH patients were treated with oral levothyroxine sodium tablets, while 30 AI patients received oral hydrocortisone tablets. The height SDS and BMI were significantly higher in the MAFLD (+) group compared to the MAFLD (-) group (P<0.001). Fasting blood glucose, insulin, HOMA-IR, ALT, γ-GT, UA, PRL, and TG levels were significantly elevated in the MAFLD (+) group compared to the MAFLD (-) group, while HDL-C levels were significantly lower (P<0.05). No significant differences were observed in IGF-1 SDS, FT₃, FT₄, T₃, T₄, TSH, TBil, AST, Alb, TC, and LDL-C between the two groups. After treatment with recombinant human growth hormone (rhGH), there was a statistically significant decrease in TG and LDL-C levels among the patients. Conclusion After surgery for sellar region tumors, patients with hypopituitarism often experience a high incidence of MAFLD and hypothalamic dysfunction. This dysfunction can manifest as hypothalamic obesity, hypernatremia, and elevated prolactin levels, all of which increase the risk of developing MAFLD. Furthermore, treatment with rhGH may help improve metabolic markers among these patients.

Key words: hypopituitarism, metabolic-associated fatty liver disease, recombinant human growth hormone, child

CLC Number:

DU Tingting, YAO Hui, CHEN Xiaohong, YANG Luhong, FENG Lifang, CHEN Xiaoqian, HU Man, LI Yakun. A study examining the association between hypopituitarism and metabolic-associated fatty liver disease following surgery for tumors in the sellar region among children[J].Journal of Clinical Pediatrics, 2025, 43(6): 438-444.

Figures/Tables 3

Table 1

Table 2

Table 3

References 32

[1]	Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement[J]. J Hepatol, 2020, 73(1): 202-209. doi: S0168-8278(20)30201-4 pmid: 32278004
[2]	Li J, Ha A, Rui F, et al. Meta-analysis: global prevalence, trend and forecasting of non-alcoholic fatty liver disease in children and adolescents, 2000-2021[J]. Aliment Pharmacol Ther, 2022, 56(3): 396-406.
[3]	Hoffmann A, Bootsveld K, Gebhardt U, et al. Nonalcoholic fatty liver disease and fatigue in long-term survivors of childhood-onset craniopharyngioma[J]. Eur J Endocrinol, 2015, 173(3): 389-397. doi: 10.1530/EJE-15-0422 pmid: 26088821
[4]	Kang SJ, Kwon A, Jung MK, et al. High prevalence of nonalcoholic fatty liver disease among adolescents and young adults with hypopituitarism due to growth hormone deficiency[J]. Endocr Pract, 2021, 27(11): 1149-1155.
[5]	杜婷婷, 姚辉, 李亚坤, 等. 儿童颅咽管瘤术后出现肝肺综合征1例报告[J]. 临床肝胆病杂志, 2022, 38(7): 1620-1625.
	Du TT, Yao H, Li YK, et al. Hepatopulmonary syndrome after craniopharyngioma operation in children: a case report[J]. Linchuang Gandanbing Zazhi, 2022, 38(7): 1620-1625.
[6]	Yoshikawa S, Takatani T, Takatani R, et al. Case report: pediatric hepatopulmonary syndrome despite strict weight control after craniopharyngioma surgery[J]. Front Endocrinol (Lausanne), 2024, 15: 1459451.
[7]	Farrell GC, Chitturi S, Lau GK, et al. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary[J]. J Gastroenterol Hepatol, 2007, 22(6): 775-777.
[8]	Hwang YA, Lee HW, Ahn SH, et al. Positive association between nonalcoholic fatty liver disease and growth hormone deficiency in patients with nonfunctioning pituitary adenoma[J]. Front Endocrinol (Lausanne), 2023, 13: 1057769.
[9]	颅咽管瘤治疗专家共识编写委员会, 中华医学会神经外科学分会小儿神经外科学组. 颅咽管瘤患者长期内分泌治疗专家共识(2017)[J]. 中华医学杂志, 2018, 98(1): 11-18.
	Consensus Expert Committee on the Treatment of Craniopharyngioma, Pediatric Neurosurgery Group of the Chinese Neurosurgical Society. Expert consensus on long-term endocrine treatment for craniopharyngioma patients (2017)[J]. Zhonghua Yixue Zazhi, 2018, 98(1): 11-18.
[10]	Vokes TJ, Robertson CI. Disorders of antidiuretic hormone[J]. Endocrinol Metab Clin North Am, 1988, 17(1): 281-299.
[11]	Xu S, Gu X, Pan H, et al. Reference ranges for serum IGF-1 and IGFBP-3 levels in Chinese children during childhood and adolescence[J]. Endocr J, 2010, 57(3): 221-228. pmid: 20051649
[12]	Elmlinger MW, Kühnel W, Weber MM, et al. Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3)[J]. Clin Chem Lab Med, 2004, 42(6): 654-664. pmid: 15259383
[13]	中华医学会糖尿病学分会胰岛素抵抗学组(筹). 胰岛素抵抗评估方法和应用的专家指导意见[J]. 中华糖尿病杂志, 2018, 10(6): 377-385.
	Subspecialty Group of insulin Resistance, Chinese Diabetes Soociety, Chinese Medical Association (in preparation). Expert guidance on methods and application of insulin resistance assessment[J]. Zhonghua Tangniaobing Zazhi, 2018, 10(6): 377-385.
[14]	Hoffmann A, Bootsveld K, Gebhardt U, et al. Nonalcoholic fatty liver disease and fatigue in long-term survivors of childhood-onset craniopharyngioma[J]. Eur J Endocrinol, 2015, 173(3): 389-397. doi: 10.1530/EJE-15-0422 pmid: 26088821
[15]	Kang SJ, Kwon A, Jung MK, et al. High prevalence of nonalcoholic fatty liver disease among adolescents and young adults with hypopituitarism due to growth hormone deficiency[J]. Endocr Pract, 2021, 27(11): 1149-1155.
[16]	Choe Y, Lee YJ, Lee YA, et al. Hepatopulmonary syndrome secondary to metabolic associated fatty liver disease in childhood - novel treatment with growth hormone replacement therapy: a case report and systematic review of literature[J]. Front Endocrinol (Lausanne), 2024, 15: 1407686.
[17]	Marchisello S, Di Pino A, Scicali R, et al. Patho-physiological, molecular and therapeutic issues of nonalcoholic fatty liver disease: an overview[J]. Int J Mol Sci, 2019, 20(8): 1948.
[18]	Eslam M, Sanyal AJ, George J, et al. MAFLD: A Consensus-driven proposed nomenclature for metabolic associated fatty liver disease[J]. Gastroenterology, 2020, 158(7): 1999-2014. doi: S0016-5085(20)30171-2 pmid: 32044314
[19]	Lustig RH. Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment[J]. Front Endocrinol (Lausanne), 2011, 2: 60.
[20]	Müller HL, Tauber M, Lawson EA, et al. Hypothalamic syndrome[J]. Nat Rev Dis Primers, 2022, 8(1): 24. doi: 10.1038/s41572-022-00351-z pmid: 35449162
[21]	Ch'ng SS, Lawrence AJ. The subfornical organ in sodium appetite: recent insights[J]. Neuropharmacology, 2019, 154: 107-113. doi: S0028-3908(18)30506-9 pmid: 30118727
[22]	Phillip M, Moran O, Lazar L. Growth without growth hormone[J]. J Pediatr Endocrinol Metab, 2002, 15 (Suppl 5):1267-1272.
[23]	Maor G, Rochwerger M, Segev Y, et al. Leptin acts as a growth factor on the chondrocytes of skeletal growth centers[J]. J Bone Miner Res, 2002, 17(6):1034-1043. pmid: 12054158
[24]	Attia N, Tamborlane WV, Heptulla R, et al. The metabolic syndrome and insulin-like growth factor I regulation in adolescent obesity[J]. J Clin Endocrinol Metab, 1998, 83(5): 1467-1471.
[25]	Jonas MM, Krawczuk LE, Kim HB, et al. Rapid recurrence of nonalcoholic fatty liver disease after transplantation in a child with hypopituitarism and hepatopulmonary syndrome[J]. Liver Transpl, 2005, 11(1): 108-110.
[26]	Zhang Y, Chen P, Fang X. Proteomic and metabolomic analysis of GH deficiency-induced NAFLD in hypo-pituitarism: insights into oxidative stress[J]. Front Endocrinol (Lausanne), 2024, 15: 1371444.
[27]	Hwa V. Human growth disorders associated with impaired GH action: defects in STAT5B and JAK2[J]. Mol Cell Endocrinol, 2021, 519: 111063.
[28]	Sos BC, Harris C, Nordstrom SM, et al. Abrogation of growth hormone secretion rescues fatty liver in mice with hepatocyte-specific deletion of JAK2[J]. J Clin Invest, 2011, 121(4): 1412-1423.
[29]	Kaltenecker D, Themanns M, Mueller KM, et al. Hepatic growth hormone - JAK2 - STAT5 signalling: Metabolic function, non-alcoholic fatty liver disease and hepatocellular carcinoma progression[J]. Cytokine, 2019, 124: 154569.
[30]	茅江峰, 王曦, 熊舒煜, 等. 重组人生长激素替代治疗对颅咽管瘤术后成人患者代谢指标的影响[J]. 中华医学杂志, 2017, 97(42): 3286-3290.
	Mao JF, Wang X, Xiong SY, et al. Effect of recombinant human growth hormone therapy on metabolic parameters in patients with craniopharyngioma[J]. Zhonghua Yixue Zazhi, 2017, 97(42): 3286-3290.
[31]	Appelman-Dijkstra NM, Claessen KM, Roelfsema F, et al. Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review[J]. Eur J Endocrinol, 2013, 169(1): R1-R14.
[32]	赵方圆, 陈永花, 王卡娜, 等. 特纳综合征染色体核型与自身免疫性甲状腺疾病的相关性分析[J]. 临床儿科杂志, 2024, 42(1): 70-74.
	Zhao Fangyuan, Chen Yonghua, Wang Kana, et al. Analysis of correlation between Turner syndrome karyotype and autoimmune thyroid disease[J]. Linchuang Erke Zazhi, 2024, 42(1): 70-74.

项目	MAFLD(+)组（n=16）	MAFLD(-)组（n=17）	统计量	P
年龄($\bar{x}±s$)/岁	10.1±2.4	9.0±4.3	t=0.94	0.361
性别（男）[n(%)]	10(62.5)	7(41.2)	χ²=1.50	0.303
随访时间[M(P₂₅~P₇₅)]/a	2.4（1~4.9）	2.8（1~11）	Z=1.91	0.085
手术时BMI($\bar{x}±s$)/kg·m^-2	17.9±4.4	16.3±2.0	t=1.17	0.254
身高SDS($\bar{x}±s$)	-1.3±1	-3±1.1	t=4.61	<0.001
BMI($\bar{x}±s$)/kg·m^-2	24.3±3.2	17.6±2	t=7.16	<0.001
GHD[n(%)]	16(100)	17(100)	-	-
甲状腺功能减退[n(%)]	16(100)	17(100)	-	-
优甲乐剂量($\bar{x}±s$)/μg	50.8±9.6	37±12.6	t=3.49	0.002
肾上腺皮质功能减退[n(%)]	15(93.8)	16(94.1)	χ²=0.00	1.000
氢化可的松剂量($\bar{x}±s$)/mg	8.1±3.8	8.2±3.9	t=1.98	0.845
中枢性尿崩症[n(%)]	8(50.0)	14(82.4)	χ²=3.88	0.071
渴感减退性高钠血症[n(%)]	7(43.8)	0(0)	χ²=9.44	0.003

项目	MAFLD(+)组（n=16）	MAFLD(-)组（n=17）	统计量	P
IGF-1 SDS($\bar{x}±s$)	-2.7±0.6	-2.8±0.6	t=0.06	0.58
GLU($\bar{x}±s$)/mmol·L^-1	4.74±0.4	4.24±0.4	t=3.40	0.002
INS[M(P₂₅~P₇₅)]/μIU·mL^-1	20.1（16.7~26.4）	4.7（2.92~7.92）	Z=4.86	<0.001
HOMA-IR[M(P₂₅~P₇₅)]	4.0（3.6~5.4）	0.9（0.5~1.5）	Z=4.79	<0.001
UA($\bar{x}±s$)/μmol·L^-1	469±120	299±92	t=4.56	<0.001
FT₃($\bar{x}±s$)/pmol·L^-1	5.0±0.9	4.9±1.1	t=0.32	0.753
FT₄($\bar{x}±s$)/pmol·L^-1	13.6±3.7	15.3±3.3	t=1.40	0.173
TSH[M(P₂₅~P₇₅)]/μIU·mL^-1	0.07（0.2~1.4）	0.02（0.01~0.4）	Z=0.33	0.326
TBil[M(P₂₅~P₇₅)]/μmol·L^-1	7.4（3.8~10.6）	6.6（5.8~10.4）	Z=0.07	0.958
Alb[M(P₂₅~P₇₅)]/g·L^-1	45.5（42.6~47.2）	45.1（43.9~49.2）	Z=0.54	0.102
ALT[M(P₂₅~P₇₅)]/IU·L^-1	22.0（14~53）	13．0（9~15）	Z=3.45	<0.001
AST[M(P₂₅~P₇₅)]/IU·L^-1	34.0（21~41）	26.0（22~33）	Z=1.43	0.157
γ-GT[M(P₂₅~P₇₅)]/IU·L^-1	27.0（16~41）	11.0（9~13）	Z=3.34	<0.001
TC($\bar{x}±s$)/mmol·L^-1	5.6±1.7	4.8±1.1	t=1.55	0.126
TG[M(P₂₅~P₇₅)]/mmol·L^-1	2.7（1.6~4.4）	0.9（0.7~1.6）	Z=3.82	<0.001
LDL-C($\bar{x}±s$)/mmol·L^-1	3.7±1.5	3.2±1.8	t=1.08	0.287
HDL-C($\bar{x}±s$)/mmol·L^-1	0.86±0.2	1.33±0.3	t=5.67	<0.001
PRL[M(P₂₅~P₇₅)]/μIU·mL^-1	360.8（209.5~502.0）	89.6（15.1~187.2）	Z=3.67	<0.001

项目	rhGH治疗组				未予rhGH治疗组
项目	基线	治疗后	统计量	P	基线	随访后	统计量	P
身高SDS($\bar{x}±s$)	-2.4±1.4	-1.1±1.0	t=2.75	0.011	-1.8±1.8	-2.2±1.4	t=0.74	0.465
BMI($\bar{x}±s$)/kg·m^-2	20.8±4.2	19.1±3.7	t=1.03	0.312	20.9±4.5	22.2±3.9	t=0.97	0.338
GLU($\bar{x}±s$)/mmol·L^-1	4.4±0.4	4.2±0.5	t=1.48	0.153	4.5±0.5	4.3±0.4	t=1.55	0.130
INS[M(P₂₅~P₇₅)]/μIU·mL^-1	10.5（3.7~20.3）	6.2（3.8~14.9）	Z=0.69	0.511	14.5（9.7~21.2)	16.6（4.8~22.3）	Z=0.41	0.698
HOMA-IR[M(P₂₅~P₇₅)]	2.0（0.7~4.2）	1.3（0.7~2.7）	Z=0.95	0.362	3.5（0.9~4.4）	2.7（1.6~4.1）	Z=0.16	0.883
TC($\bar{x}±s$)/mmol·L^-1	5.3±0.9	4.4±0.7	t=2.64	0.014	5.0±1.7	5.0±1.3	t=0.0	0.998
TG($\bar{x}±s$)/mmol·L^-1	1.8±0.8	1.3±0.5	t=1.96	0.062	2.4±1.7	2.2±1.4	t=0.32	0.751
LDL-C($\bar{x}±s$)/mmol·L^-1	3.8±0.9	2.8±0.6	t=3.49	0.002	3.3±1.6	3.4±1.3	t=0.35	0.725
HDL-C($\bar{x}±s$)/mmol·L^-1	1.2±0.4	1.2±0.2	t=0.52	0.607	1.1±0.3	1.2±0.8	t=0.66	0.511
ALT[M(P₂₅~P₇₅)]/IU·L^-1	14（12~34.5）	11（8.5~18）	Z=1.52	0.139	16（11.3~27.3）	14（11~27.8）	Z=0.30	0.779
AST[M(P₂₅~P₇₅)]/IU·L^-1	30（22~34.5）	25（18.5~27）	Z=1.75	0.081	26.5（21.2~34）	23.5（19.3~41.5）	Z=0.61	0.547

A study examining the association between hypopituitarism and metabolic-associated fatty liver disease following surgery for tumors in the sellar region among children

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 3

References 32

Related Articles 15

Metrics

Comments

Recommended 0

[1]	ZHANG Hongwen. Application and consideration of eculizumab in the treatment of childhood systemic lupus erythematosus [J]. Journal of Clinical Pediatrics, 2025, 43(6): 403-407.
[2]	LI Qiuyu, LIU Fei, ZHAO Manli, GU Weizhong, FENG Chunyue, FU Haidong. Clinicopathological analysis of 3496 pediatric patients with renal disease: a single-center retrospective study [J]. Journal of Clinical Pediatrics, 2025, 43(6): 411-417.
[3]	WANG Ruixue, WANG Runjie, LI Xiaolu, ZHANG Ting, XIAO Yongmei. Analysis of clinical characteristics, endoscopic and pathological manifestations of children with positive lactulose hydrogen-methane breath test [J]. Journal of Clinical Pediatrics, 2025, 43(6): 418-425.
[4]	YUE Yang, ZHANG Zhihua, LI Mei, LIU Zhifeng, GUO Hongmei. Predictors of efficacy of infliximab induction therapy in children with Crohn's disease [J]. Journal of Clinical Pediatrics, 2025, 43(6): 426-431.
[5]	XIE Lilin, XU Jinping, YAO Yonghua. Pediatric arterial ischemic stroke: a single-center retrospective study [J]. Journal of Clinical Pediatrics, 2025, 43(6): 432-437.
[6]	XU Shiyi, LIU Yi, YU Yongguo, GAN Jing, XIAO Bing, SUN Yu. Optimized high-throughput sequencing for diagnosing childhood-onset Huntington's disease and analysis of clinical features [J]. Journal of Clinical Pediatrics, 2025, 43(6): 445-451.
[7]	WANG Xiao, LI Quanheng, ZHAO Zhai, ZHAO Pei, HAO Pengli, LIANG Xingsi, GENG Wenjin. Clinical analysis of eight cases with diquat poisoning in children and literature review [J]. Journal of Clinical Pediatrics, 2025, 43(6): 452-457.
[8]	ZHANG Liming, LIU Lei, YANG Jianwei, SUN Hongqi, YANG Junmei, CHEN Yongxing. Clinical feature and genetic analysis of two children with isolation glycerol kinase deficiency [J]. Journal of Clinical Pediatrics, 2025, 43(6): 458-463.
[9]	FU Mengzhen, SHI Kaili, GAO Chunlin, SHI Zhuo, ZHANG Pei, JIA Lili, MA Chenxi, LIU Jiuyu, XIA Zhengkun. Eculizumab treatment for thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus in children: a case report [J]. Journal of Clinical Pediatrics, 2025, 43(6): 464-469.
[10]	MA Yuzhi, YAO Zhirong, ZHANG Jia. Clinical and genetic analysis of atypical erythrokeratodermia variabilis: a case report [J]. Journal of Clinical Pediatrics, 2025, 43(6): 470-474.
[11]	ZHANG Yixin, HONG Siqi. Pharmacologic and upcoming treatment of pediatric narcolepsy [J]. Journal of Clinical Pediatrics, 2025, 43(6): 475-482.
[12]	ZHOU Fan, WANG Jiandong, SU Yu, WEI Yongwei, WANG Huaili. Clinical features comparison of hypertensive encephalopathy in children with different etiologies: a single-center 12-year retrospective analysis [J]. Journal of Clinical Pediatrics, 2025, 43(5): 323-328.
[13]	ZHOU Zibei, ZHOU Wei, ZHANG Juan, LI Zailing. Clinical analysis of eight cases of food-dependent exercise-induced anaphylaxis in children [J]. Journal of Clinical Pediatrics, 2025, 43(5): 334-339.
[14]	CAI Meihong, XU Leiming, QU Chunying, LI Zhenghong, SHEN Feng, LI Mingming, ZHANG Yi. Application and effect evaluation of single balloon enteroscopy in long-term follow-up of patients with Peutz-Jeghers syndrome [J]. Journal of Clinical Pediatrics, 2025, 43(5): 340-344.
[15]	SUN Yunteng, WU Wenyong, CHEN Hong, CAI Binbin, SU Yiqun, CHEN Ruimin. A case of retinitis pigmentosa with or without skeletal abnormality syndrome caused by CWC27 gene variation and literature review [J]. Journal of Clinical Pediatrics, 2025, 43(5): 350-355.