Anorexia nervosa as a cause of endocrine disorders

Obviously, obesity is currently a global health problem. Eating disorders, including anorexia nervosa, a neuropsychiatric disorder characterized by a conscious refusal to eat and a significant decrease in body weight, are discussed much less frequently. The high probability of a fatal outcome in anorexia nervosa is due to a wide range of its complications, primarily in the reproductive and endocrine systems. The most common adverse effects of anorexia nervosa are hypogonadotropic hypogonadism and amenorrhea, impaired growth hormone action, hypercorticism, decreased bone mineral density, and the risk of fractures. These complications do not always resolve on their own even after the resumption of rational nutrition and normalization of body weight. Moreover, anorexia nervosa is most common among females in adolescence, that is, during the period of active linear growth, reaching peak bone mass, and puberty. Awareness of the pathophysiology and clinical manifestations of endocrine disorders associated with anorexia nervosa can help in examining patients and choosing a further therapeutic strategy, especially since a unified protocol for the treatment of anorexia nervosa has not yet been developed.

anorexia nervosa, body weight deficit, leptin, ghrelin, functional hypothalamic amenorrhea, hypogonadotropic hypogonadism, bone metabolism

1. Zakharova L.I. Anorexia nervosa: prevalence, diagnostic criteria and psychosomatic relations (review). Research Results in Biomedicine. 2019;5(1):108-121 (In Russ.) doi: 10.18413/2313-8955-2019-5-1-0-8.@@ Захарова Л.И. Нервная анорексия: распространенность, критерии диагностики и психосоматические соотношения (обзор). Научные результаты биомедицинских исследований. 2019;5(1):108-121. doi: 10.18413/2313-8955-2019-5-1-0-8.

2. Støving R.K. MECHANISMS IN ENDOCRINOLOGY: Anorexia nervosa and endocrinology: a clinical update. Eur J Endocrinol. 2019;180(1): R9-R27. doi: 10.1530/EJE-18-0596.

3. Peterson K., Fuller R. Anorexia nervosa in adolescents: An overview. Nursing. 2019;49(10):24-30. doi: 10.1097/01.NURSE.0000580640.43071.15.

4. Himmerich H., Treasure J. Anorexia nervosa: diagnostic, therapeutic, and risk biomarkers in clinical practice. Trends Mol Med. 2024;30(4):350-360. doi: 10.1016/j.molmed.2024.01.002.

5. Lackner S., Mörkl S., Müller W. et al. Novel approaches for the assessment of relative body weight and body fat in diagnosis and treatment of anorexia nervosa: A cross-sectional study. Clin Nutr. 2019;38(6):2913-2921. doi: 10.1016/j.clnu.2018.12.031.

6. Misra M., Klibanski A. Endocrine consequences of anorexia nervosa. Lancet Diabetes Endocrinol. 2014;2(7):581-592. doi: 10.1016/S2213-8587(13)70180-3.

7. Galmiche M., Déchelotte P., Lambert G., Tavolacci M.P. Prevalence of eating disorders over the 2000-2018 period: a systematic literature review. Am J Clin Nutr. 2019;109(5):1402-1413. doi: 10.1093/ajcn/nqy342.

8. Hebebrand J., Gradl-Dietsch G., Peters T., Correll C.U., Haas V. The Diagnosis and Treatment of Anorexia Nervosa in Childhood and Adolescence. Dtsch Arztebl Int. 2024;121(5):164-174. doi: 10.3238/arztebl.m2023.0248.

9. Sosnova E.A., Sarkisyan R.A., Akhmetgaryaev. et al. Anorexia nervosa: a new look at an old problem. V.F. Snegirev Archives Of Obstetrics And Gynecology. 2024;11(2):105-113 (In Russ.) doi: 10.17816/aog623869.@@ Соснова Е.А., Саркисян Р.А., Ахметгаряев и др. Нервная анорексия: новый взгляд на старую проблему. Архив акушерства и гинекологии им. В.Ф. Снегирева. 2024;11(2):105-113. doi: 10.17816/aog623869.

10. Cost J., Krantz M.J., Mehler P.S. Medical complications of anorexia nervosa. Cleve Clin J Med. 2020;87(6):361-366. doi: 10.3949/ccjm.87a.19084.

11. Fichter M.M., Quadflieg N. Mortality in eating disorders - results of a large prospective clinical longitudinal study.Int J Eat Disord. 2016;49(4):391-401. doi: 10.1002/eat.22501.

12. van Eeden A.E., van Hoeken D., Hoek H.W. Incidence, prevalence and mortality of anorexia nervosa and bulimia nervosa. Curr Opin Psychiatry. 2021;34(6):515-524. doi: 10.1097/YCO.0000000000000739.

13. Neale J., Hudson L.D. Anorexia nervosa in adolescents. Br J Hosp Med (Lond). 2020;81(6):1-8. doi: 10.12968/hmed.2020.0099.

14. Dobranowska K., Plińska S., Dobosz A. Dietary and Lifestyle Management of Functional Hypothalamic Amenorrhea: A Comprehensive Review. Nutrients. 2024;16(17):2967. Published 2024 Sep 3. doi: 10.3390/nu16172967.

15. Merzlova P. Ya., Bulgakova S.V., Kurmaev D.P., Sharonova L.A., Dolgikh Yu. A., Treneva E.V., Kosareva O.V. Male hypogonadism is associated with obesity. Experimental and Clinical Gastroenterology. 2024;(8): 65-75. (In Russ.) doi: 10.31146/1682-8658-ecg-228-8-65-75.@@ Мерзлова П.Я., Булгакова С.В., Курмаев Д.П., Шаронова Л.А., Долгих Ю.А, Тренева Е.В., Косарева О.В. Мужской гипогонадизм, ассоциированный с ожирением. Экспериментальная и клиническая гастроэнтерология. 2024;(8): 65-75. doi: 10.31146/1682-8658-ecg-228-8-65-75.

16. Chou S.H., Mantzoros C. 20 years of leptin: role of leptin in human reproductive disorders. J Endocrinol. 2014;223(1): T49-T62. doi: 10.1530/JOE-14-0245.

17. Cui H., López M., Rahmouni K. The cellular and molecular bases of leptin and ghrelin resistance in obesity. Nat Rev Endocrinol. 2017;13(6):338-351. doi: 10.1038/nrendo.2016.222.

18. Andreeva V.O. Amenorrhea in patients with nervous anorexia - to expect or to treat? Effective pharmacotherapy. Obstetrics and gynecology. 2015;25(3): 32-36. (in Russ.)@@ Андреева В.О. Аменорея у пациенток с нервной анорексией - ожидать или лечить? Эффективная фармакотерапия. Акушерство и гинекология. 2015;25(3): 32-36.

19. Odle A.K., Akhter N., Syed M.M. et al. Leptin Regulation of Gonadotrope Gonadotropin-Releasing Hormone Receptors As a Metabolic Checkpoint and Gateway to Reproductive Competence. Front Endocrinol (Lausanne). 2018;8:367. Published 2018 Jan 5. doi: 10.3389/fendo.2017.00367.

20. Tanaka M., Naruo T., Yasuhara D. et al. Fasting plasma ghrelin levels in subtypes of anorexia nervosa. Psychoneuroendocrinology. 2003;28(7):829-835. doi: 10.1016/s0306-4530(02)00066-5.

21. Misra M., Klibanski A. Anorexia Nervosa and Its Associated Endocrinopathy in Young People. Horm Res Paediatr. 2016;85(3):147-157. doi: 10.1159/000443735.

22. Haines M.S. Endocrine complications of anorexia nervosa. J Eat Disord. 2023;11(1):24. Published 2023 Feb 15. doi: 10.1186/s40337-023-00744-9.

23. Jacoangeli F., Masala S., Staar Mezzasalma F. et al. Amenorrhea after weight recover in anorexia nervosa: role of body composition and endocrine abnormalities. Eat Weight Disord. 2006;11(1): e20-e26. doi: 10.1007/BF03327748.

24. Herpertz-Dahlmann B., Dahmen B. Children in Need-Diagnostics, Epidemiology, Treatment and Outcome of Early Onset Anorexia Nervosa. Nutrients. 2019;11(8):1932. Published 2019 Aug 16. doi: 10.3390/nu11081932.

25. Herpertz-Dahlmann B., Dempfle A., Egberts K.M. et al. Outcome of childhood anorexia nervosa-The results of a five- to ten-year follow-up study.Int J Eat Disord. 2018;51(4):295-304. doi: 10.1002/eat.22840.

26. Bulik C.M., Hoffman E.R., Von Holle A. et al. Unplanned pregnancy in women with anorexia nervosa. Obstet Gynecol. 2010;116(5):1136-1140. doi: 10.1097/AOG.0b013e3181f7efdc.

27. Westmoreland P., Krantz M.J., Mehler P.S. Medical Complications of Anorexia Nervosa and Bulimia. Am J Med. 2016;129(1):30-37. doi: 10.1016/j.amjmed.2015.06.031.

28. Wabitsch M., Ballauff A., Holl R. et al. Serum leptin, gonadotropin, and testosterone concentrations in male patients with anorexia nervosa during weight gain. J Clin Endocrinol Metab. 2001;86(7):2982-2988. doi: 10.1210/jcem.86.7.7685.

29. Grinspoon S, Thomas E, Pitts S. et al. Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann Intern Med. 2000;133(10):790-794. doi: 10.7326/0003-4819-133-10-200011210-00011

30. Jada K., Djossi S.K., Khedr A., Neupane B., Proskuriakova E., Mostafa J.A. The Pathophysiology of Anorexia Nervosa in Hypothalamic Endocrine Function and Bone Metabolism. Cureus. 2021;13(12): e20548. Published 2021 Dec 20. doi: 10.7759/cureus.20548.

31. Miller K.K., Lee E.E., Lawson E.A. et al. Determinants of skeletal loss and recovery in anorexia nervosa. J Clin Endocrinol Metab. 2006;91(8):2931-2937. doi: 10.1210/jc.2005-2818,

32. Villa P., Cipolla C., Amar I. et al. Bone mineral density and body mass composition measurements in premenopausal anorexic patients: the impact of lean body mass. J Bone Miner Metab. 2024;42(1):134-141. doi: 10.1007/s00774-023-01487-y.

33. Fazeli P.K., Klibanski A. Bone metabolism in anorexia nervosa. Curr Osteoporos Rep. 2014;12(1):82-89. doi: 10.1007/s11914-013-0186-8.

34. Lucas A.R., Melton L.J. 3rd, Crowson C.S., O’Fallon W.M. Long-term fracture risk among women with anorexia nervosa: a population-based cohort study. Mayo Clin Proc. 1999;74(10):972-977. doi: 10.4065/74.10.972.

35. Belaya Zh.E., Belova K. Yu., Biryukova E.V. et al. Osteoporosis and Bone Diseases. 2021;24(2):4-47. (In Russ.) doi: 10.14341/osteo12930.@@ Белая Ж.Е., Белова К.Ю., Бирюкова Е.В. и др. Федеральные клинические рекомендации по диагностике, лечению и профилактике остеопороза. Остеопороз и остеопатии. 2021;24(2):4-47. doi: 10.14341/osteo12930.

36. Gibson D., Filan Z., Westmoreland P., Mehler P.S. Loss of Bone Density in Patients with Anorexia Nervosa Food That Alone Will Not Cure. Nutrients. 2024;16(21):3593. Published 2024 Oct 23. doi: 10.3390/nu16213593.

37. Schorr M., Drabkin A., Rothman M.S. et al. Bone mineral density and estimated hip strength in men with anorexia nervosa, atypical anorexia nervosa and avoidant/restrictive food intake disorder. Clin Endocrinol (Oxf). 2019;90(6):789-797. doi: 10.1111/cen.13960.

38. Clemente-Suárez V.J., Ramírez-Goerke M.I., Redondo-Flórez L. et al. The Impact of Anorexia Nervosa and the Basis for Non-Pharmacological Interventions. Nutrients. 2023;15(11):2594. Published 2023 Jun 1. doi: 10.3390/nu15112594.

39. Misra M., Soyka L.A., Miller K.K. et al. Serum osteoprotegerin in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab. 2003;88(8):3816-3822. doi: 10.1210/jc.2003-030088.

40. Misra M., Klibanski A. Anorexia nervosa and bone. J Endocrinol. 2014;221(3): R163-R176. doi: 10.1530/JOE-14-0039.

41. Smetnik V.P. Estrogens and bone tissue. Pharmateka. 2013;256(12):17-21. (in Russ.)@@ Сметник В.П. Эстрогены и костная ткань. Фарматека. 2013;256(12):17-21.

42. Fazeli P.K., Klibanski A. Effects of Anorexia Nervosa on Bone Metabolism. Endocr Rev. 2018;39(6):895-910. doi: 10.1210/er.2018-00063.

43. Robinson L., Micali N., Misra M. Eating disorders and bone metabolism in women. Curr Opin Pediatr. 2017;29(4):488-496. doi: 10.1097/MOP.0000000000000508.

44. Misra M., Klibanski A. Bone health in anorexia nervosa. Curr Opin Endocrinol Diabetes Obes. 2011;18(6):376-382. doi: 10.1097/MED.0b013e32834b4bdc.

45. Indirli R., Lanzi V., Mantovani G., Arosio M., Ferrante E. Bone health in functional hypothalamic amenorrhea: What the endocrinologist needs to know. Front Endocrinol (Lausanne). 2022;13:946695. Published 2022 Oct 11. doi: 10.3389/fendo.2022.946695.

46. Schorr M., Miller K.K. The endocrine manifestations of anorexia nervosa: mechanisms and management. Nat Rev Endocrinol. 2017;13(3):174-186. doi: 10.1038/nrendo.2016.175.

47. Thavaraputta S., Ungprasert P., Witchel S.F., Fazeli P.K. Anorexia nervosa and adrenal hormones: a systematic review and meta-analysis. Eur J Endocrinol. 2023;189(3): S64-S73. doi: 10.1093/ejendo/lvad123.

48. Fricke C., Voderholzer U. Endocrinology of Underweight and Anorexia Nervosa. Nutrients. 2023;15(16):3509. Published 2023 Aug 9. doi: 10.3390/nu15163509.

49. Calcaterra V., Magenes V.C., Siccardo F. et al. Thyroid dysfunction in children and adolescents affected by undernourished and overnourished eating disorders. Front Nutr. 2023;10:1205331. Published 2023 Sep 29. doi: 10.3389/fnut.2023.1205331.

50. Wronski M.L., Tam F.I., Seidel M. et al. Associations between pituitary-thyroid hormones and depressive symptoms in individuals with anorexia nervosa before and after weight-recovery. Psychoneuroendocrinology. 2022;137:105630. doi: 10.1016/j.psyneuen.2021.105630.

51. Yaroshetskiy A.I., Konanykhin V.D., Stepanova S.O., Rezepov N.A. Hypophosphatemia and refeeding syndrome in the resumption of nutrition in critical care patients (review). Alexander Saltanov Intensive Care Herald. 2019;2:82-91. (In Russ.) doi: 10.21320/1818-474X-2019-2-82-91.@@ Ярошецкий А.И., Конаныхин В.Д., Степанова С.О., Резепов Н.А. Гипофосфатемия и рефи-динг-синдром при возобновлении питания у пациентов в критических состояниях (обзор литературы). Вестник интенсивной терапии имени А.И. Салтанова. 2019;2:82-91. doi: 10.21320/1818-474X-2019-2-82-91.

52. Luft V.M., Tyavokina E. Iu., Sergeeva A.M., Lapitsky A.V. Refeeding syndrome and its prevention in patients with anorexia nervosa. Consilium Medicum. 2021; 23 (2): 144-147. (In Russ.) doi: 10.26442/20751753.2021.2.200696.@@ Луфт В.М., Тявокина Е.Ю., Сергеева А.М., Лапицкий А.В. Рефидинг-синдром и его профилактика у больных нервной анорексией. Consilium Medicum. 2021; 23 (2): 144-147. doi: 10.26442/20751753.2021.2.200696.

53. Mosuka E.M., Murugan A., Thakral A. et al. Clinical Outcomes of Refeeding Syndrome: A Systematic Review of High vs. Low-Calorie Diets for the Treatment of Anorexia Nervosa and Related Eating Disorders in Children and Adolescents. Cureus. 2023;15(5): e39313. Published 2023 May 21. doi: 10.7759/cureus.39313.