The side effects of immune checkpoint inhibitor therapy on the endocrine system.

Immune checkpoint inhibitors (ICIs) are a relatively newer class of drugs approved for the treatment of malignancies such as melanoma, renal, bladder and lung cancer. Immune-related adverse events (IrAEs) involving the endocrine system are a common side effect of these drugs. The spectrum of endocrine adverse events varies by the drug class. Cytotoxic T-lymphocyte-associated antigen-4 inhibitors commonly cause hypophysitis/hypopituitarism, whereas the incidence of thyroid disease is higher with programmed cell death (PD)-1/ ligand (PD-L) protein 1 inhibitors. The focus of this review is to describe the individual endocrinopathies with their possible mechanisms, signs and symptoms, clinical assessment and disease management. Multiple mechanisms of IrAEs have been described in literature including type II/IV hypersensitivity reactions and development of autoantibodies. Patients with pre-existing autoimmune endocrine diseases can have disease exacerbation following ICI therapy rather than de novo IrAEs. Most of the endocrinopathies are relatively mild, and timely hormone replacement therapy allows continuation of ICIs. However, involvement of the pituitary-adrenal axis could be life-threatening if not recognized. Corticosteroids are helpful when the pituitary-adrenal axis is involved. In cases of severe endocrine toxicity (grade 3/4), ICIs should be temporarily discontinued and can be restarted after adequate hormonal therapy. Endocrinologists and general internists need to be vigilant and maintain a high degree of awareness for these adverse events.

HYPOTHYROIDISM AND GOITER IN A YOUNG MALE WITH SUSPECTED DIETARY IODINE DEFICIENCY FOLLOWED BY THYROTOXICOSIS AFTER IODINE SUPPLEMENTATION.

OBJECTIVE: Iodine deficiency disorders (IDDs) remain a major public health concern in most parts of the world but are extremely rare in North America. We describe a case of goiter in a young male with dietary history and findings suggestive of IDD. METHODS: Laboratory and imaging procedures including thyroid function tests, autoantibodies, urine iodine, thyroid ultrasound, and radioactive iodine (RAI) uptake scan were performed. RESULTS: On initial presentation, thyroid-stimulating hormone (TSH) was 24.4 mIU/L (normal range is 0.4 to 5.0 mIU/L), free thyroxine was <0.4 ng/dL (normal range is 0.8 to 1.8 ng/dL), and thyroid peroxidase antibody was positive at 43 IU/mL (normal range is <35 IU/mL). He reported consuming strawberries and peanut butter sandwiches with no intake of dairy or seafood due to gastrointestinal issues (abdominal pain, bloating, and nausea). Physical exam revealed a diffusely enlarged, palpable thyroid gland (grade II goiter). Ultrasound of the neck showed an enlarged thyroid gland with no nodules. RAI uptake scan showed diffuse increased uptake (91%). Given his poor diet, a 24-hour urinary iodine excretion test was ordered which was suggestive of very low iodine intake. He was started on multivitamins with 150 µg of iodine daily. On follow up, clinical exam showed grade I goiter and TSH had normalized to 0.7 mIU/L and free thyroxine was 1.2 ng/dL. He continued on iodine supplementation and tolerated iodine-rich foods. Six months later, thyroid function tests showed hyperthyroidism with TSH of <0.002 ng/dL and free thyroxine was elevated to 2.8 ng/dL. Iodine supplements were stopped. CONCLUSION: Hypothyroidism and goiter due to IDD should be suspected in the setting of poor dietary intake. IDDs can be rapidly diagnosed in a patient on a restricted diet with multiple urinary iodine determinations and RAI study. Regular thyroid labs should be done to monitor for hyperthyroidism that can develop after iodine supplementation.