颅咽管瘤相关肝脏疾病的致病机制及治疗

程烨; 郑银; 秦洁

doi:10.12449/JCH260834

颅咽管瘤相关肝脏疾病的致病机制及治疗

DOI: 10.12449/JCH260834

山西医科大学附属山西省人民医院内分泌科，太原 030012

基金项目:

山西省卫生健康委员会“四个一批”科技兴医创新计划项目 (2023XM0482023XM048)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：程烨负责设计论文框架，起草论文；郑银负责论文修改；秦洁负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
秦洁， hopejieqin@sohu.com （ORCID： 0000-0002-7249-093X）

计量
- 文章访问数: 13
- HTML全文浏览量: 2
- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2025-11-12
- 录用日期: 2026-03-02
- 出版日期: 2026-08-25

Pathogenesis and treatment of craniopharyngioma-related liver diseases

Department of Endocrinology，Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University，Taiyuan 030012，China

Research funding:

Four “Batches” Innovation Project of Invigorating Medical Through Science and Technology of Shanxi Province (2023XM0482023XM048)

More Information

Corresponding author: Qin Jie， hopejieqin@sohu.com （ORCID： 0000-0002-7249-093X）

摘要

摘要: 颅咽管瘤患者是代谢相关脂肪性肝病及其严重并发症的高危人群，但这一关联在临床上常被忽视，相关系统性总结匮乏。本文系统回顾了颅咽管瘤相关肝脏疾病的临床谱系与流行病学特征，重点分析了其发病的核心机制，并总结了当前以预防下丘脑损伤为导向的肿瘤治疗策略，明确了建立多学科协作诊疗模式并实施早期干预是改善预后的关键。未来研究应致力于深入解析下丘脑损伤导致代谢紊乱的精确通路，并以此为基础开发靶向治疗，为从根本上改变此类患者的临床结局提供新方向。
- 颅咽管瘤 /
- 代谢相关脂肪性肝病 /
- 下丘脑疾病 /
- 生长激素 /
- 治疗学
Abstract: Patients with craniopharyngioma are at a high risk of developing metabolic dysfunction-associated fatty liver disease and its severe complications， yet this association is often neglected in clinical practice， with a lack of systematic reviews. This article systematically reviews the clinical spectrum and epidemiological characteristics of liver diseases associated with craniopharyngioma， with a focus on their core pathogenic mechanisms， and it also summarizes current tumor treatment strategies aimed at preventing hypothalamic injury and highlights that establishing a multidisciplinary collaborative diagnosis and treatment model and implementing early intervention are key to improving prognosis. Future research should focus on elucidating the precise pathways through which hypothalamic injury leads to metabolic disturbances， thereby facilitating the development of targeted therapies， in order to provide new directions for fundamentally improving the clinical outcomes of these patients.
- Craniopharyngioma /
- Metabolic Dysfunction-Associated Fatty Liver Disease /
- Hypothalamic Diseases /
- Growth Hormone /
- Therapeutics

HTML全文

注： GH，生长激素；TSH，促甲状腺激素；ACTH，促肾上腺皮质激素；FSH，卵泡刺激素；LH，黄体生成素；MAFLD，代谢相关脂肪性肝病。

图 1 颅咽管瘤患者发生MAFLD的机制图

Figure 1. Diagram illustrating the mechanism of MAFLD in craniopharyngioma patients

下载: 全尺寸图片幻灯片

参考文献(49)

[1]	Beckhaus J, Friedrich C, Müller H L. Vascular morbidity and mortality in craniopharyngioma patients-a scoping review[J]. Cancers, 2024, 16( 6): 1099. DOI: 10.3390/cancers16061099.
[2]	Wu J, Wu X, Yang Y Q, et al. Association of histological subtype with risk of recurrence in craniopharyngioma patients: A systematic review and meta-analysis[J]. Neurosurg Rev, 2022, 45( 1): 139- 150. DOI: 10.1007/s10143-021-01563-9.
[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.
[4]	Jung S Y, Lee Y J, Lee H J, et al. Nonalcoholic fatty liver disease in long-term survivors of childhood-onset craniopharyngioma[J]. Ann Pediatr Endocrinol Metab, 2017, 22( 3): 189- 196. DOI: 10.6065/apem.2017.22.3.189.
[5]	Jung D, Seo G H, Kim Y M, et al. Hepatopulmonary syndrome caused by hypothalamic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma: A case report[J]. Ann Pediatr Endocrinol Metab, 2018, 23( 1): 51- 55. DOI: 10.6065/apem.2018.23.1.51.
[6]	Mazerkina N A, Savateev A N, Gorelyshev S K, et al. Hepatopulmonary syndrome: A rare manifestation of cirrhosis in patient with diencephalic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma[J]. Probl Endokrinol, 2021, 67( 5): 58- 66. DOI: 10.14341/probl12723.
[7]	Scarano E, Solari D, Riccio E, et al. Craniopharyngioma and metabolic syndrome: A 5-year follow-up single-center experience[J]. Front Neurol, 2022, 13: 783737. DOI: 10.3389/fneur.2022.783737.
[8]	Erfurth E M. Craniopharyngioma-An update on metabolic and cognitive complications and new therapy[J]. J Intern Med, 2023, 294( 3): 269- 280. DOI: 10.1111/joim.13684.
[9]	Ni W M, Shi X E. Interventions for the treatment of craniopharyngioma-related hypothalamic obesity: A systematic review[J]. World Neurosurg, 2018, 118: e59- e71. DOI: 10.1016/j.wneu.2018.06.121.
[10]	Ashhab A A, Albrecht J, Debes J D. The way to the liver is through the pituitary gland[J]. Am J Gastroenterol, 2018, 113( 1): 145- 146. DOI: 10.1038/ajg.2017.434.
[11]	Roth C L, McCormack S E. Acquired hypothalamic obesity: A clinical overview and update[J]. Diabetes Obes Metab, 2024, 26( S2): 34- 45. DOI: 10.1111/dom.15530.
[12]	Romigi A, Feola T, Cappellano S, et al. Sleep disorders in patients with craniopharyngioma: A physiopathological and practical update[J]. Front Neurol, 2021, 12: 817257. DOI: 10.3389/fneur.2021.817257.
[13]	Castro D C, Cole S L, Berridge K C. Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: Interactions between homeostatic and reward circuitry[J]. Front Syst Neurosci, 2015, 9: 90. DOI: 10.3389/fnsys.2015.00090.
[14]	McCormack S E, Blevins J E, Lawson E A. Metabolic effects of oxytocin[J]. Endocr Rev, 2020, 41( 2): 121- 145. DOI: 10.1210/endrev/bnz012.
[15]	Lee M, Park M J, Lee K H, et al. Obesity mechanism after hypothalamic damage: Cohort analysis of neuroimaging, psychological, cognitive, and clinical phenotyping data[J]. Front Endocrinol, 2023, 14: 1114409. DOI: 10.3389/fendo.2023.1114409.
[16]	Wu W, Sun Q Y, Zhu X M, et al. Risk factors for hypothalamic obesity in patients with adult-onset craniopharyngioma: A consecutive series of 120 cases[J]. Front Endocrinol, 2021, 12: 694213. DOI: 10.3389/fendo.2021.694213.
[17]	Mushtaq A, Fayaz M, Bhat A R, et al. Comprehensive analysis of craniopharyngioma: Epidemiology, clinical characteristics, management strategies, and role of radiotherapy[J]. Cancer Diagn Progn, 2024, 4( 4): 521- 528. DOI: 10.21873/cdp.10358.
[18]	Yang Y, Qi Z R, Zhang T T, et al. Rapidly progressive non-alcoholic fatty liver disease due to hypopituitarism. Report of 5 cases[J]. Neuro Endocrinol Lett, 2018, 39( 2): 99- 104.
[19]	Kang S J, Kwon A, Jung M K, 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. DOI: 10.1016/j.eprac.2021.06.003.
[20]	Das L, Sahoo J, Dahiya N, et al. Long-term hepatic and cardiac health in patients diagnosed with Sheehan’s syndrome[J]. Pituitary, 2022, 25( 6): 971- 981. DOI: 10.1007/s11102-022-01282-4.
[21]	Xiao J F, Zhu C G, Zhang X X, et al. Associations among FT₄ level, FT₃/FT₄ ratio, and non-alcoholic fatty liver disease in Chinese patients with hypopituitarism[J]. Endocr J, 2022, 69( 6): 659- 667. DOI: 10.1507/endocrj.EJ21-0536.
[22]	Lonardo A, Mantovani A, Lugari S, et al. NAFLD in some common endocrine diseases: Prevalence, pathophysiology, and principles of diagnosis and management[J]. Int J Mol Sci, 2019, 20( 11): 2841. DOI: 10.3390/ijms20112841.
[23]	Kander M C, Cui Y Q, Liu Z G. Gender difference in oxidative stress: A new look at the mechanisms for cardiovascular diseases[J]. J Cell Mol Med, 2017, 21( 5): 1024- 1032. DOI: 10.1111/jcmm.13038.
[24]	Zhang P Z, Ge Z J, Wang H D, et al. Prolactin improves hepatic steatosis via CD36 pathway[J]. J Hepatol, 2018, 68( 6): 1247- 1255. DOI: 10.1016/j.jhep.2018.01.035.
[25]	Vázquez-Borrego M C, Del Río-Moreno M, Pyatkov M, et al. Direct and systemic actions of growth hormone receptor(GHR)-signaling on hepatic glycolysis, de novo lipogenesis and insulin sensitivity, associated with steatosis[J]. Metabolism, 2023, 144: 155589. DOI: 10.1016/j.metabol.2023.155589.
[26]	Ishikawa M, Brooks A J, Fernández-Rojo M A, et al. Growth hormone stops excessive inflammation after partial hepatectomy, allowing liver regeneration and survival through induction of H2-bl/HLA-G[J]. Hepatology, 2021, 73( 2): 759- 775. DOI: 10.1002/hep.31297.
[27]	Soler Palacios B, Nieto C, Fajardo P, et al. Growth hormone reprograms macrophages toward an anti-inflammatory and reparative profile in an MAFB-dependent manner[J]. J Immunol, 2020, 205( 3): 776- 788. DOI: 10.4049/jimmunol.1901330.
[28]	Kong T T, Gu Y P, Sun L, et al. Association of nonalcoholic fatty liver disease and growth hormone deficiency: A systematic review and meta-analysis[J]. Endocr J, 2023, 70( 10): 959- 967. DOI: 10.1507/endocrj.EJ23-0157.
[29]	Hwang Y A, Lee H W, Ahn S H, et al. Positive association between nonalcoholic fatty liver disease and growth hormone deficiency in patients with nonfunctioning pituitary adenoma[J]. Front Endocrinol, 2022, 13: 1057769. DOI: 10.3389/fendo.2022.1057769.
[30]	Zhang Y W, Chen P Z, Fang X Q. Proteomic and metabolomic analysis of GH deficiency-induced NAFLD in hypopituitarism: Insights into oxidative stress[J]. Front Endocrinol, 2024, 15: 1371444. DOI: 10.3389/fendo.2024.1371444.
[31]	Hassani Zadeh S, Mansoori A, Hosseinzadeh M. Relationship between dietary patterns and non-alcoholic fatty liver disease: A systematic review and meta-analysis[J]. J Gastroenterol Hepatol, 2021, 36( 6): 1470- 1478. DOI: 10.1111/jgh.15363.
[32]	Younossi Z M, Corey K E, Lim J K. AGA clinical practice update on lifestyle modification using diet and exercise to achieve weight loss in the management of nonalcoholic fatty liver disease: Expert review[J]. Gastroenterology, 2021, 160( 3): 912- 918. DOI: 10.1053/j.gastro.2020.11.051.
[33]	Gao Y, Zhang W, Zeng L Q, et al. Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy[J]. Redox Biol, 2020, 36: 101635. DOI: 10.1016/j.redox.2020.101635.
[34]	Babu A F, Csader S, Lok J, et al. Positive effects of exercise intervention without weight loss and dietary changes in NAFLD-related clinical parameters: A systematic review and meta-analysis[J]. Nutrients, 2021, 13( 9): 3135. DOI: 10.3390/nu13093135.
[35]	Oh S, Tsujimoto T, Kim B, et al. Weight-loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD[J]. JHEP Rep, 2021, 3( 3): 100253. DOI: 10.1016/j.jhepr.2021.100253.
[36]	Otte A, Müller H L. Childhood-onset craniopharyngioma[J]. J Clin Endocrinol Metab, 2021, 106( 10): e3820- e3836. DOI: 10.1210/clinem/dgab397.
[37]	Ganau M, Foroni R I, Gerosa M, et al. Radiosurgical options in neuro-oncology: A review on current tenets and future opportunities. Part I: Therapeutic strategies[J]. Tumori, 2014, 100( 4): 459- 465. DOI: 10.1700/1636.17912.
[38]	Horne V E, Bielamowicz K, Nguyen J, et al. Methylphenidate improves weight control in childhood brain tumor survivors with hypothalamic obesity[J]. Pediatr Blood Cancer, 2020, 67( 7): e28379. DOI: 10.1002/pbc.28379.
[39]	Kelly A S, Bensignor M O, Hsia D S, et al. Phentermine/topiramate for the treatment of adolescent obesity[J]. NEJM Evid, 2022, 1( 6): 10.1056/evidoa 2200014. DOI: 10.1056/evidoa2200014.
[40]	Greenway F L, Bray G A. Treatment of hypothalamic obesity with caffeine and ephedrine[J]. Endocr Pract, 2008, 14( 6): 697- 703. DOI: 10.4158/EP.14.6.697.
[41]	Huynh K, Klose M, Krogsgaard K, et al. Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity[J]. Eur J Endocrinol, 2022, 186( 6): 687- 700. DOI: 10.1530/EJE-21-0972.
[42]	van Schaik J, Welling M S, de Groot C J, et al. Dextroamphetamine treatment in children with hypothalamic obesity[J]. Front Endocrinol, 2022, 13: 845937. DOI: 10.3389/fendo.2022.845937.
[43]	van Santen H M, Denzer C, Müller H L. Could setmelanotide be the game-changer for acquired hypothalamic obesity?[J]. Front Endocrinol, 2023, 14: 1307889. DOI: 10.3389/fendo.2023.1307889.
[44]	Shoemaker A H, Silver H J, Buchowski M, et al. Energy balance in hypothalamic obesity in response to treatment with a once-weekly GLP-1 receptor agonist[J]. Int J Obes(Lond), 2022, 46( 3): 623- 629. DOI: 10.1038/s41366-021-01043-6.
[45]	McCormack S E, Wang Z, Wade K L, et al. A pilot randomized clinical trial of intranasal oxytocin to promote weight loss in individuals with hypothalamic obesity[J]. J Endocr Soc, 2023, 7( 5): bvad037. DOI: 10.1210/jendso/bvad037.
[46]	Svendstrup M, Rasmussen A K, Kistorp C, et al. Semaglutide treatment of hypothalamic obesity—a real-life data study[J]. Pituitary, 2024, 27( 5): 685- 692. DOI: 10.1007/s11102-024-01429-5.
[47]	Pan C S, Weiss J J, Fourman L T, et al. Effect of recombinant human growth hormone on liver fat content in young adults with nonalcoholic fatty liver disease[J]. Clin Endocrinol, 2021, 94( 2): 183- 192. DOI: 10.1111/cen.14344.
[48]	Zhang X Y, Yuan K, Fang Y L, et al. Growth hormone ameliorates hepatopulmonary syndrome and nonalcoholic steatohepatitis secondary to hypopituitarism in a child: A case report[J]. World J Clin Cases, 2022, 10( 18): 6211- 6217. DOI: 10.12998/wjcc.v10.i18.6211.
[49]	Nishizawa H, Iguchi G, Murawaki A, et al. Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy[J]. Eur J Endocrinol, 2012, 167( 1): 67- 74. DOI: 10.1530/EJE-12-0252.