Endocrine Abstracts

Immune-checkpoint inhibitors have been increasing used in the field of medical oncology for treatment of various early to late-stage malignancies, however, rare occurrences of adrenal insufficiency and thyroid dysfunction may occur. Pembrolizumab, a PD-1 inhibitor, has been associated with adrenal insufficiency in 1-2% of patients, while thyroid related adverse events occurred in 3.2-10.1%. This is a case report of an 81 year-old male, known to have a cutaneous melanoma stage IV (CTxN0M1A of the muscle), with a prolonged use of Pembrolizumab eventually developing both Pembrolizumab-induced hypothyroidism and adrenal insufficiency. This patient had a wide excision with split-thickness skin graft of the right lower extremity back in June 2022 showing a histopathology of melanoma. He was then started on Pembrolizumab therapy on July 2022. Routine laboratories done showed normal TSH. On the 15th cycle (February 2023), there was an incidental finding of an elevated TSH of 17.632, with normal FT4 (1.11 ng/dl) and FT3 (2.56 pg/ml). the patient was then started on Levothyroxine 25 mg once daily. On the 16th cycle of Pembrolizumab showed persistence of an elevated TSH 8.355 uIU/ml, with normal FT4 (1.24 ng/dl) and FT3 (2.47 pg/ml). Levothyroxine supplementation was continued with TSH serially monitored prior to immunotherapy. On his scheduled 24th cycle of Pembrolizumab (Dec 7, 2023), he developed a 1-week history of productive cough, generalized weakness, and exertional dyspnea, managed as pneumonia and was given Azithromycin 500 mg but due to persistence, prompted further evaluation. Vital signs were normal, thyroid function test showed nonthyroidal illness syndrome (TSH 3.383 uIU/ml, FT4 1.16 ng/dl, FT3 1.97 pg/ml), sodium and potassium were normal (142 mEg/l, 4.1 mEq/l respectively), Creatinine was slightly elevated (1.29 mg/dl), Cortisol level was low at 1.82 (mg/dl). Due to low cortisol levels, referral to endocrinology service was done where an ACTH stimulation test was subsequently done. Baseline cortisol was at 1.68 mg/dl, cortisol 30 minutes and 60 minutes post cosyntropin were 7.79 mg/dl and 11.19 mg/dl respectively. Baseline ACTH was low prior to ACTH stimulation test at 3.51 pg/ml. He was diagnosed to have secondary adrenal insufficiency and was initially started on Hydrocortisone 50 mg q6 and was sent home with tapering doses of Prednisone. Both thyroid dysfunction and adrenal insufficiency can occur in patients treated with Pembrolizumab. Thyroid related dysfunction may occur earlier compared to adrenal insuffiency and must be monitored in patients being treated with Pembrolizumab. Levothyroxine and Steroid supplementation still remain to be the treatment of choice.