BACKGROUND: The immunologically mediated side effects of immune checkpoint inhibitors (CPI) often involve the endocrine system as well, and they can even be fatal, as in the case of unrecognized hypophysitis. Distinguishing such side effects from tumor-related changes is often difficult, because their clinical features can be nonspecific. METHODS: This review is based on publications retrieved by a selective search in PubMed, with special attention to international recommendations. RESULTS: Depending on their target molecules, the CPI now in use differ from one another in the incidence of side effects such as autoimmune thyroid disease (4-16%), hypophysitis (0.1- 18%), adrenalitis (0.7-8%), and autoimmune diabetes mellitus (0.5-2%). The typical clinical warning signs and laboratory constellations of hypophysitis include exhaustion, hyponatremia, and headache. Hypo- and hyperthyroidism and primary adrenocortical insufficiency likewise have nonspecific manifestations. Autoimmune diabetes mellitus often takes a fulminant course. Patients being treated with CPI should be monitored at close intervals, at least as frequently as the administration of the drug, so that endocrine side effects can be recognized in time. In case of doubt, glucocorticoid supplementation should be given whenever hypocortisolism is suspected, even before endocrine evaluation is completed and the results are available. Interrupting or discontinuing CPI treatment is rarely indicated. CONCLUSION: With the increasing number of patients being treated with CPI, more and more physicians from a wide variety of specialties, not necessarily working in specialized centers, now have to consider immunologically mediated endocrine side effects in the differential diagnosis, and treat them properly when they arise. These things should be done in collaboration with endocrinologists. The ongoing study of such side effects of the CPI now in use, and of those that will be introduced in the future, is important and will lead to improved understanding.
BACKGROUND: The immunologically mediated side effects of immune checkpoint inhibitors (CPI) often involve the endocrine system as well, and they can even be fatal, as in the case of unrecognized hypophysitis. Distinguishing such side effects from tumor-related changes is often difficult, because their clinical features can be nonspecific. METHODS: This review is based on publications retrieved by a selective search in PubMed, with special attention to international recommendations. RESULTS: Depending on their target molecules, the CPI now in use differ from one another in the incidence of side effects such as autoimmune thyroid disease (4-16%), hypophysitis (0.1- 18%), adrenalitis (0.7-8%), and autoimmune diabetes mellitus (0.5-2%). The typical clinical warning signs and laboratory constellations of hypophysitis include exhaustion, hyponatremia, and headache. Hypo- and hyperthyroidism and primary adrenocortical insufficiency likewise have nonspecific manifestations. Autoimmune diabetes mellitus often takes a fulminant course. Patients being treated with CPI should be monitored at close intervals, at least as frequently as the administration of the drug, so that endocrine side effects can be recognized in time. In case of doubt, glucocorticoid supplementation should be given whenever hypocortisolism is suspected, even before endocrine evaluation is completed and the results are available. Interrupting or discontinuing CPI treatment is rarely indicated. CONCLUSION: With the increasing number of patients being treated with CPI, more and more physicians from a wide variety of specialties, not necessarily working in specialized centers, now have to consider immunologically mediated endocrine side effects in the differential diagnosis, and treat them properly when they arise. These things should be done in collaboration with endocrinologists. The ongoing study of such side effects of the CPI now in use, and of those that will be introduced in the future, is important and will lead to improved understanding.
Authors: Romualdo Barroso-Sousa; Patrick A Ott; F Stephen Hodi; Ursula B Kaiser; Sara M Tolaney; Le Min Journal: Cancer Date: 2018-01-03 Impact factor: 6.860
Authors: Lars Hofmann; Andrea Forschner; Carmen Loquai; Simone M Goldinger; Lisa Zimmer; Selma Ugurel; Maria I Schmidgen; Ralf Gutzmer; Jochen S Utikal; Daniela Göppner; Jessica C Hassel; Friedegund Meier; Julia K Tietze; Ioannis Thomas; Carsten Weishaupt; Martin Leverkus; Renate Wahl; Ursula Dietrich; Claus Garbe; Michael C Kirchberger; Thomas Eigentler; Carola Berking; Anja Gesierich; Angela M Krackhardt; Dirk Schadendorf; Gerold Schuler; Reinhard Dummer; Lucie M Heinzerling Journal: Eur J Cancer Date: 2016-04-13 Impact factor: 9.162
Authors: Alexander Faje; Kerry Reynolds; Leyre Zubiri; Donald Lawrence; Justine V Cohen; Ryan J Sullivan; Lisa Nachtigall; Nicholas Tritos Journal: Eur J Endocrinol Date: 2019-09 Impact factor: 6.664
Authors: Jürgen Honegger; Sven Schlaffer; Christa Menzel; Michael Droste; Sandy Werner; Ulf Elbelt; Christian Strasburger; Sylvère Störmann; Anna Küppers; Christine Streetz-van der Werf; Timo Deutschbein; Mareike Stieg; Roman Rotermund; Monika Milian; Stephan Petersenn Journal: J Clin Endocrinol Metab Date: 2015-08-11 Impact factor: 5.958