• Matthias Kroiß, Bastian Schilling, and Timo Deutschbein.
• Schwerpunkt Endokrinologie/Diabetologie, Medizinische Klinik und Poliklinik I, Universitätsklinikum Würzburg.
• Dtsch. Med. Wochenschr. 2020 Dec 1; 145 (24): 1736-1741.

AbstractImmune checkpoint inhibitors (ICI) have become a cornerstone in the treatment of various human malignancies. Immune-related adverse events (irAE) are common and may affect endocrine organs. Here, we provide a brief introduction to ICI therapy and provide practical guidance for the diagnosis and management of endocrine irAE. The pituitary and the thyroid gland are most frequently affected. The incidence of hypophysitis is up to 10 % in patients treated with combination therapy of programmed death (PD-1) inhibitors with Acytotoxic T lymphocyte 4 (CTLA-4) inhibitor. Clinical manifestations include headache, reduced general condition, and fatigue. Hyponatremia is frequent and elevated markers of inflammation point towards adrenal crisis. Magnetic resonance imaging of the sella is often inconclusive and must not delay treatment. Therapy consists of immediate intravenous glucocorticoid replacement while therapeutic doses of glucocorticoids are rarely necessary. Oral replacement of all affected hormonal axes is the long-term treatment. Thyroiditis is common also in PD-1/PD-L1 monotherapy. An initial phase of hyperthyroidism is usually followed by hypothyroidism. Thyroid ultrasound is the principal tool for the differential diagnosis from other causes of thyroid dysfunction. Treatment of hyperthyroidism may be symptomatic while hypothyroidism requires replacement. Rare but dangerous irAE include primary adrenal insufficiency, diabetes mellitus type I, and hypoparathyroidism. Their immediate treatment is essential. Routine hormonal laboratory testing, a high level of suspicion towards irAE and patient education enable early detection of endocrine irAE.In summary, the increasingly widespread use of ICI causes immune related endocrine disorders that have been hitherto unusual and require the awareness of the practicing physician.Thieme. All rights reserved.

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