Pituitary Enlargement and Hypopituitarism in Patients Treated with Immune Checkpoint Inhibitors: Two Sides of the Same Coin?

Journal of Personalized Medicine · 14 authors, 8 centres

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TL;DR

This retrospective case series of nine cancer patients with immune checkpoint inhibitor hypophysitis found that secondary hypoadrenalism was universal, but pituitary enlargement on MRI was present in only two cases, with MRI abnormalities resolving spontaneously in those two patients.

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The study retrospectively analyzed nine adult cancer patients (six male, mean age 59 years) who developed immune checkpoint inhibitor hypophysitis during treatment with nivolumab or ipilimumab. All patients presented with new-onset asthenia and were diagnosed with secondary hypoadrenalism. Pituitary MRI showed enlargement in two cases and was normal in seven. Anti-pituitary antibodies were positive in 57.1% of cases, and anti-hypothalamus antibodies in 85.7%. All patients received hydrocortisone replacement; ICI therapy was withdrawn in two cases. At three-month follow-up, central hypoadrenalism persisted in all patients, but pituitary MRI normalized in the two patients with initial enlargement. Limitations include the small sample size and lack of pathological examination.

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cohort

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endocrinology

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ORIGINAL PAPER

PMC10056499

Pituitary Enlargement and Hypopituitarism in Patients Treated with Immune Checkpoint Inhibitors: Two Sides of the Same Coin?

Journal of Personalized Medicine

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ABSTRACT

Background: Immune checkpoint inhibitor hypophysitis (IIHs) is an emerging problem in cancer patients treated with immune checkpoint inhibitors (ICIs). We aimed to describe the clinical and molecular features of a multicenter series of IIHs. Methods: Demographic and clinical features were retrospectively collected for all cases. Anti-pituitary and anti-hypothalamus autoantibodies were also measured. Results: Nine patients were included. Six patients were treated with nivolumab and three with ipilimumab. Secondary hypoadrenalism was diagnosed in all patients. Pituitary MRI showed pituitary enlargement in two cases and no abnormalities in the other seven. Anti-pituitary antibodies were positive in 57.1% of cases and anti-hypothalamus antibodies in 85.7% of cases. Multidisciplinary treatments were established by a neuroendocrinologist and oncologists: all patients were treated with hydrocortisone replacement; ICI was withdrawn in two cases. At follow-up, hypoadrenalism persisted in all cases. Pituitary enlargement on MRI spontaneously recovered in the two affected patients. We found that the typical features of hypophysitis involved more frequently females and patients treated with ipilimumab. Conclusions: Although this study did not clarify if autoimmune secondary hypoadrenalism and ICI hypophysitis on brain imaging are two sides of the same disease, our preliminary data underline the need for molecular studies of IIHs and of autoimmune ICIs-related hypopituitarism.

CITATION EXPORT

Sabrina Chiloiro, Antonella Giampietro, Antonio Bianchi et al.. Pituitary Enlargement and Hypopituitarism in Patients Treated with Immune Checkpoint Inhibitors: Two Sides of the Same Coin?. Journal of Personalized Medicine. (2023). https://doi.org/10.3390/jpm13030415

AUTHORS

14 · 8 CENTRES

Sabrina Chiloiro, Antonella Giampietro, Antonio Bianchi, Sara Menotti, Flavia Angelini, Tommaso Tartaglione, Gian Carlo Antonini Cappellini, Federica De Galitiis, Ernesto Rossi, Giovanni Schinzari, Alessandro Scoppola, Alfredo Pontecorvi, Laura De Marinis, Maria Fleseriu

1Pituitary Unit, Department of Endocrinology and Metabolism, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy
2Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00186 Rome, Italy
3Dipartimento di Radiodiagnostica, Istituto Dermopatico dell’Immacolata IDI IRCCS, 00168 Rome, Italy
4UOC Oncologia, Ospedale Sandro Pertini, 00138 Rome, Italy
5UOC Oncologia, Istituto Dermopatico dell’Immacolata IDI IRCCS, 00185 Rome, Italy
6UOC Oncologia, Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy
7UOSD Endocrinologia, Ospedale Santo Spirito, 00193 Rome, Italy
8Departments of Medicine (Division of Endocrinology, Diabetes and Clinical Nutrition) and Neurological Surgery, and Pituitary Center, Oregon Health & Science University, Portland, OR 97232, USA

EDITOR / REVIEWER

Dueng-Yuan Hueng