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Background. Despite their important clinical benefits, immune checkpoint inhibitors (ICIs) are associated with a spectrum of side effects known as immune‐related adverse events (irAEs). These can be of various organ system backgrounds, including dermatologic, pulmonary, gastrointestinal, and endocrine. Polyglandular endocrinopathies (PLEs) post‐ICIs therapy has been reported in the literature; however, to our knowledge, only a few have been documented with pembrolizumab. Case Report. We present a case of a female patient who developed myxedema coma (MC) and adrenal insufficiency (AI) after 4 months of stopping pembrolizumab, a programed‐cell death‐1 inhibitor. The patient was clinically symptomatic and was subsequently treated with levothyroxine and hydrocortisone. Discussion. It is very important to be vigilant and alert in detecting MC and AI to avoid any mortality. Pembrolizumab's effect on inducing antitumor responses leads to a wide variety of multiorgan alterations. Its role in raising the risk of all‐grade endocrine disorders has been previously highlighted along with thyroidal dysfunctions. Our patient's presentation falls within the literature‐based median time for hypothyroidism and AI with respect to the period from the initiation of pembrolizumab. The patient's predisposition to hypothyroidism and the likelihood of intertwined manifestations of AI and hypothyroidism should always be considered in the setting of critical illness. Conclusion. It is of high significance to explore the mechanism of action of ICIs and their side effects. PLEs can house some endocrinologic emergencies that are life threatening. [ABSTRACT FROM AUTHOR]