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French Endocrine Society Guidance on endocrine side effects of immunotherapy

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Castinetti, F, Albarel, F, Archambeaud, F, Bertherat, J, Bouillet, B, Buffier, P, Briet, C, Cariou, B, Caron, Ph, Chabre, O, Chanson, Ph, Cortet, C, Do Cao, C, Drui, D, Haissaguerre, M, Hescot, S, Illouz, F, Kuhn, E, Lahlou, N, Merlen, E, Raverot, V, Smati, S, Verges, B, Borson-Chazot, F·2019·Endocrine Related Cancer
DOI 10.1530/erc-18-0320PMC PMC6347286
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Abstract

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side effects in oncology using 'common terminology criteria for adverse events' (CTCAE) and the difficulties in applying this to endocrine side effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side effects (high-dose corticosteroids, contraindicated in ICPI for example) and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high-dose glucocorticoid intake.

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Figure 1 ICPI mechanisms. (A) The principal pathway of co-stimulation for activation of naïve T lymphocytes is the CD28/B7 pathway, consisting of an activating signal for T lymphocytes following binding of CD28 to B7. CTLA-4 can block this stimulatory pathway. Other inhibitory signals induced by binding of PD-1/PD-L1 occur in the lymph nodes and at the tumor site. (B) The principal treatments currently used are based on inhibition of CTLA-4 and/or of the PD-1/PD-L1 pair. This inhibition which results in prolonged activation of T lymphocytes directed against tumoral neoantigens, aims to neutralize tumor cells.
Figure 1 ICPI mechanisms. (A) The principal pathway of co-stimulation for activation of naïve T lymphocytes is the CD28/B7 pathway, consisting of an activating signal for T lymphocytes following binding of CD28 to B7. CTLA-4 can block this stimulatory pathway. Other inhibitory signals induced by binding of PD-1/PD-L1 occur in the lymph nodes and at the tumor site. (B) The principal treatments currently used are based on inhibition of CTLA-4 and/or of the PD-1/PD-L1 pair. This inhibition which results in prolonged activation of T lymphocytes directed against tumoral neoantigens, aims to neutralize tumor cells.CC BY · PubMed Central
Figure 2 Screening and monitoring of endocrine toxicity in patients treated with ICPI.
Figure 2 Screening and monitoring of endocrine toxicity in patients treated with ICPI.CC BY · PubMed Central
Figure 3 Management and monitoring of ICPI-induced dysthyroidism.
Figure 3 Management and monitoring of ICPI-induced dysthyroidism.CC BY · PubMed Central
Figure 4 Management and monitoring of ICPI-induced hypophysitis.
Figure 4 Management and monitoring of ICPI-induced hypophysitis.CC BY · PubMed Central
Figure 5 Management and monitoring of ICPI-induced primary adrenal insufficiency.
Figure 5 Management and monitoring of ICPI-induced primary adrenal insufficiency.CC BY · PubMed Central
Figure 6 Management and monitoring of ICPI-induced diabetes.
Figure 6 Management and monitoring of ICPI-induced diabetes.CC BY · PubMed Central

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Authors
Castinetti, F., Albarel, F., Archambeaud, F., Bertherat, J., Bouillet, B., Buffier, P., Briet, C., Cariou, B., Caron, P., Chabre, O., Chanson, P., Cortet, C., Do Cao, C., Drui, D., Haissaguerre, M., Hescot, S., Illouz, F., Kuhn, E., Lahlou, N., Merlen, E., Raverot, V, Smati, S., Verges, B., & Borson-Chazot, F.
Affiliations
  • Inserm (FR)
  • 2Service de Médecine Interne B – Endocrinologie, Limoges Cedex, France
  • Hôpital Cochin (FR)
  • CHU Dijon Bourgogne (FR)
  • Centre Hospitalier Universitaire de Nantes (FR)
  • Centre Hospitalier Universitaire de Toulouse (FR)
  • Hôpital Albert Michallon (FR)
  • Université Paris-Saclay (FR)
  • Centre Hospitalier Universitaire de Lille (FR)
  • 11CHRU de Lille – Hopital Huriez, Service d’Endocrinologie, Lille Cedex, France
  • 12CHU de Bordeaux – Hôpital du Haut Lévêque, Service d’Endocrinologie-Diabétologie et Maladies Métaboliques, Pessac Cedex, France
  • Institut Curie (FR)
  • Centre Hospitalier Universitaire d'Angers (FR)
  • 15Département d’Hormonologie Spécialisée, BPR-AS, Pannes, France
  • Hospices Civils de Lyon (FR)
  • 4CHU Dijon, Hôpital François Mitterrand, Service d’Endocrinologie, Diabétologie, Maladies Métaboliques, Dijon Cedex, France
  • 17Hospices Civils de Lyon, Fédération d’Endocrinologie, Université Claude Bernard Lyon 1, Lyon, France
Corresponding author
Castinetti, F
ORCID
Venue
Endocrine Related Cancer
Publisher
Bioscientifica
Published
2019-02
Volume
26
Issue
2
Pages
G1-G18
ISSN
  • 1351-0088 (ISSN-L)
  • 1479-6821
DOI
10.1530/erc-18-0320
PMC
PMC6347286
OpenAlex
W2895782973
Cited by
140
References
91
Citations by year
2026: 4 · 2025: 16 · 2024: 12 · 2023: 22 · 2022: 21 · 2021: 35 · 2020: 20 · 2019: 10
FWCI
6.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrine Related Cancer (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • HAL (submittedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
immune checkpoint inhibitors, endocrine toxicity, immune-related adverse events, hypophysitis, Addison's disease, fulminant diabetes, thyroid dysfunction, CTCAE, glucocorticoid therapy, cancer immunotherapy
MeSH terms
Antineoplastic Agents, Immunological, Endocrine System Diseases, France, Humans, Immunotherapy

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