Case Presentation: A 71-year-old man presented with 1 week of progressive fatigue and weakness. Upon arrival, he stated that he could not get out of bed, even to use the bathroom. Notably, he had undergone an infusion of carboplatin, pemetrexed, and pembrolizumab for treatment of lung adenocarcinoma 9 days before presenting. He attributed his symptoms to his most recent infusion. Other significant past medical history included human immunodeficiency virus infection for which he took bictegravir, emtricitabine, tenofovir alafenamide. Vitals were unremarkable. He appeared chronically ill and cachectic with dry mucous membranes. Initial laboratory testing revealed a sodium level of 131 mEq/L, albumin level of 4.1 g/dL, thyroid stimulating hormone (TSH) of 89 mIU/L, free thyroxine of 0.4 ng/dL, thyroglobulin antibody level of 427 IU/mL, random cortisol level of 14 mcg/dL, and white blood cell count of 2.1×103/mm3. Subsequent adrenocorticotropic hormone (ACTH) stimulation testing revealed a baseline cortisol level of 8.8 mcg/dL, with cortisol levels of 9.8 mcg/dL and 9.6 mcg/dL at 30 minutes and 60 minutes post-ACTH administration, respectively, most consistent with primary adrenal insufficiency. Hydrocortisone and fludrocortisone were initiated to treat his primary adrenal insufficiency, and levothyroxine was initiated for his new-onset hypothyroidism. Treatment resulted in significant improvement of his symptoms, and he was able to return home on a stable dose of hydrocortisone, fludrocortisone, and levothyroxine.
Discussion: Fatigue and weakness are problems commonly encountered by practicing hospitalists. This case was found to be primary hypothyroidism and adrenal insufficiency. Common etiologies of these endocrinopathies include autoimmune, infectious, and malignant processes. However, in this case, the patient’s symptoms began shortly after his most recent infusion of carboplatin, pemetrexed, and pembrolizumab, suggesting that one of these medications might be responsible. Pembrolizumab and other immune checkpoint inhibitors (ICIs) have been implicated in a number of endocrinopathies, including hypopituitarism, adrenocortical dysfunction, thyroid dysfunction, and type 1 diabetes mellitus. Adrenal insufficiency caused by ICI treatment is most commonly thought to be due to secondary adrenal insufficiency rather than primary adrenal insufficiency. Hypothyroidism due to ICIs may also be secondary to hypopituitarism. However, the patient’s elevated TSH and poor adrenal response to the ACTH-stimulation test ruled out hypopituitarism as the cause of his symptoms.
Conclusions: The patient’s symptoms and lab results were consistent with a new diagnosis of primary hypothyroidism and adrenal insufficiency, and prompt treatment resulted in a significant improvement in his symptoms and quality of life. While thyroid dysfunction is a relatively common adverse effect of pembrolizumab, primary adrenal insufficiency is rare. This man’s course demonstrated the importance of suspecting a variety of endocrinopathies in patients on ICI treatment for cancer, as the presenting symptoms can be difficult to distinguish from nonspecific symptoms in patients with advanced cancer. Prompt diagnosis and treatment can lead to the avoidance of the more serious consequences of immune-related adverse events, which include significantly reduced organ function and quality of life.