oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2026-25-2-155-164oncotomsk-4208Research ArticleОБЗОРЫREVIEWSНарушение функции гипоталамо-гипофизарно-надпочечниковой оси на фоне терапии онкологических заболеваний блокаторами контрольных точек иммунного ответаHypothalamic-pituitary-adrenal axis dysfunction induced by cancer therapy with immune checkpoint inhibitorshttps://orcid.org/0000-0002-4802-1340УсынинаА. Ю.UsyninaA. Yu.

Усынина Анна Юрьевна – эндокринолог.

SPIN-код: 3606-5760

ResearcherID (WOS): NFT-7614-2025

634050, Томск, Московский тракт, 2

Anna Yu. Usynina - MD, Endocrinologist.

ResearcherID (WOS): NFT-7614-2025

2, Moskovsky trakt, Tomsk, 634050

annasdvnkv@list.ruhttps://orcid.org/0000-0001-9011-8720СапринаТ. В.SaprinaT. V.

Саприна Татьяна Владимировна - доктор медицинских наук, профессор кафедры факультетской терапии с курсами эндокринологии и клинической фармакологии.

634050, Томск, Московский тракт, 2

Tatyana V. Saprina - MD, DSc, Professor, Department of Faculty Therapy with Courses of Endocrinology and Clinical Pharmacology.

2, Moskovsky trakt, Tomsk, 634050

https://orcid.org/0000-0001-5294-778XПоповаН. О.PopovaN. O.

Попова Наталья Олеговна - кандидат медицинских наук, старший научный сотрудник отделения химиотерапии, Научно-исследовательский институт онкологии.

SPIN-код: 7672-1029

ResearcherID (WOS): I-9417-2017

Author ID (Scopus): 7201879486

634009, Томск, пер. Кооперативный, 5

Natalya O. Popova - MD, PhD, Senior Researcher, Department of Chemotherapy, Cancer Research Institute.

ResearcherID (WOS): I-9417-2017

Author ID (Scopus): 7201879486

5, Kooperativny St., Tomsk, 634009

https://orcid.org/0000-0001-7127-0188УсынинЕ. А.UsyninE. A.

Усынин Евгений Анатольевич - доктор медицинских наук, заведующий отделением общей онкологии, Научно-исследовательский институт онкологии.

SPIN-код: 1804-0292

ResearcherID (WOS): D-1505-2012

Author ID (Scopus): 56204320500

634009, Томск, пер. Кооперативный, 5

Evgeny A. Usynin - MD, DSc, Head of the Department of General Oncology, Cancer Research Institute.

ResearcherID (WOS): D-1505-2012

Author ID (Scopus): 56204320500

5, Kooperativny St., Tomsk, 634009

https://orcid.org/0009-0009-9379-9096ЕреминД. А.EreminD. A.

Еремин Дмитрий Алексеевич – студент.

634050, Томск, Московский тракт, 2

Dmitry A. Eremin – Student.

2, Moskovsky trakt, Tomsk, 634050

ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава РоссииРоссияSiberian State Medical University, Ministry of Health of RussiaRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCancer Research institute, Tomsk National Research Medical Center, Russian Academy of SciencesRussian Federation202617052026252155164Copyright © Усынина А.Ю., Саприна Т.В., Попова Н.О., Усынин Е.А., Еремин Д.А., 20262026Усынина А.Ю., Саприна Т.В., Попова Н.О., Усынин Е.А., Еремин Д.А.Usynina A.Y., Saprina T.V., Popova N.O., Usynin E.A., Eremin D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/4208

Цель исследования – обобщить современные данные о нарушениях функции гипоталамо-гипофизарно-надпочечниковой оси, возникающих на фоне терапии ингибиторами контрольных точек иммунного ответа, с акцентом на гипофизит и первичную надпочечниковую недостаточность.

Материал и методы

Материал и методы. Выполнен обзор публикаций, посвященных эндокринным иммуноопосредованным нежелательным явлениям при применении анти-CTLA-4, анти-PD-1 и анти-PD-L1 препаратов, размещенных в базах Pubmed, Cochrane library, GoogleScholar, Elibrary с января 2015 г. по октябрь 2025 г. Из 876 найденных публикаций 45 были использованы для написания систематического обзора.

Результаты

Результаты. Эндокринные иммуноопосредованные нежелательные явления относятся к наиболее частым осложнениям терапии ингибиторами контрольных точек иммунного ответа. Наиболее значимыми нарушениями со стороны гипоталамо-гипофизарно-надпочечниковой оси являются гипофизит, индуцированный ингибиторами контрольных точек, и первичная надпочечниковая недостаточность. Гипофизит чаще развивается на фоне анти-CTLA-4-терапии и может сопровождаться комбинированным дефицитом гормонов гипофиза либо изолированным дефицитом адренокортикотропного гормона. Первичная надпочечниковая недостаточность встречается существенно реже, однако представляет особую клиническую опасность в связи с риском аддисонического криза. Диагностика затруднена неспецифичностью клинической картины; важную роль играют оценка симптомов, определение уровней адренокортикотропного гормона, кортизола, электролитов, гормонов других осей, а также магнитно-резонансная томография гипофиза и компьютерная томография надпочечников. В большинстве случаев требуется длительная, а нередко пожизненная заместительная гормональная терапия.

Заключение

Заключение. Нарушения функции гипоталамо-гипофизарно-надпочечниковой оси на фоне терапии ингибиторами контрольных точек иммунного ответа остаются недостаточно плохо распознаваемыми осложнениями. Повышение настороженности врачей, разработка алгоритмов скрининга и дальнейшее изучение биомаркеров могут способствовать более ранней диагностике, снижению риска жизнеугрожающих состояний, улучшению качества жизни и сохранению эффективности противоопухолевой терапии. Особое значение имеет мультидисциплинарное взаимодействие онкологов и эндокринологов при ведении таких пациентов на всех этапах лечения и последующего наблюдения.

Objective

Objective: to summarize current data on immune checkpoint inhibitor-induced hypothalamic-pituitary-adrenal axis dysfunction, with an emphasis on hypophysitis and primary adrenal insufficiency.

Material and Methods

Material and Methods. A review of publications on endocrine immune-related adverse events from anti-CTLA-4, anti-PD-1 and antiPD-L1 inhibitors was carried out from January 2015 to October 2025 using Pubmed, Cochrane library, Google Scholar, and Elibrary systems. Of the 876 studies found, 45 were used to write the systematic review.

Results

Results. immune checkpoint inhibitor-induced hypothalamic-pituitary-adrenal axis dysfunction is a serious immune-related adverse event. It commonly presents as hypophysitis (particularly with anti-CTLA-4, causing pituitary deficiency) and primary adrenal insufficiency (risking fatal Addisonian crisis). Diagnosis is complicated by the nonspecific clinical presentation. Essential evaluation includes assessing symptoms, adrenocorticotropic hormone, cortisol, electrolyte levels, and hormones of other axes, as well as magnetic resonance imaging of the pituitary gland and computed tomography of the adrenal glands. in most cases, long-term, and sometimes lifelong, hormone replacement therapy is required.

Conclusion

Conclusion. Hypothalamic-pituitary-adrenal axis dysfunction associated with immune checkpoint inhibitor therapy remains underrecognized immune-related adverse event, requiring early recognition through clinician vigilance and screening algorithms to prevent adrenal crisis, improve quality of life and maintain cancer treatment efficacy. Multidisciplinary collaboration between oncologists and endocrinologists is particularly important in the care of these patients at all stages of treatment and follow-up.

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The authors declare that there are no conflicts of interest present.