Hypothyroidism With ACTH Deficiency During Pembrolizumab Therapy for Lung Cancer: Case Report and Literature Review

Immune-checkpoint inhibitors have recently shown great promise in treating various cancers, but often cause immune-related adverse events (irAEs). Simultaneous drug-induced hypothyroidism and isolated adrenocorticotropic hormone (ACTH) deficiency are rare irAEs. This combination of irAEs is associated with paradoxical endocrine dysfunction characterized by large amounts of thyroid-stimulating hormone (TSH) and small amounts of ACTH in the anterior lobe of the pituitary. We herein report a case of hypothyroidism with isolated ACTH deficiency during pembrolizumab therapy for recurrent lung cancer.

Our patient was a 66-year-old man with recurrence of squamous cell lung carcinoma. Four months after chemotherapy that included pembrolizumab, the patient presented with general fatigue and laboratory tests showed high concentrations of TSH with low concentrations of free-T4. He was diagnosed with hypothyroidism and levothyroxine was prescribed. His ACTH concentration was found to be low 1 week later when he developed an acute adrenal crisis with associated hyponatraemia. We then changed his diagnosis to concurrent hypothyroidism with isolated ACTH deficiency. His condition improved after 3 weeks of administration of cortisol.

It is difficult to diagnose a concurrent paradoxical endocrine disorder, such as hypothyroidism with isolated ACTH deficiency, as in the present case. Physicians should pay attention to symptoms and laboratory data to identify various types of endocrine disorders as irAEs.