ODP264 An Unusual Etiology of Hypothyroidism and New-Onset Insulin-Dependent Diabetes: A Rare Side Effect of Opdivo
Authors: Alchalabi Halah , Udongwo Ndausung , Albustani Safa , Amin Tasnuva , Fareen Nusha , Chineyemba Praise , Holland Soemiwati 
Published: November 2022

Introduction

Nivolumab, a monoclonal antibody targeting programmed cell death 1 receptor, is prescribed for many advanced cancers like malignant melanoma, non-small cell lung cancer, renal cell carcinoma (RCC), etc. with increased use of this medication, the incidence of immune-related side effects is also on the rise. A combined medication side effect of new-onset diabetes and hypothyroidism associated with Nivolumab use is rare. We present a case of Nivolumab-induced hypothyroidism with new-onset insulin-dependent diabetes.

Case presentation

A 59-year-male with a past medical history of right RCC status post nephrectomy, non-ischemic cardiomyopathy with an ejection fraction of 25-30% on goal-directed therapy/implantable cardioverter-defibrillator, hypertension, hyperlipidemia, and chronic kidney disease stage 3 who presented to the emergency department with complaints of chest pain at rest. The pain was 5/10 in severity and non-radiating. It was relieved by sublingual nitroglycerine en route to the hospital. It was associated with fatigue, nausea, polyuria, and polyphagia. He denied any history of pre-diabetes/diabetes or thyroid disease. Of note, about six months prior to this admission, he was placed on nivolumab for his RCC. Vitals were BP 121/83, RR 20, HR 85, T 97.8°F, and 97% oxygen saturation on room air. The cardiopulmonary exam was unremarkable. An electrocardiogram showed sinus rhythm with normal rate and no ST/T wave changes. Troponin level was 0. 01 ng/mL (normal:: &lt;0. 04 ng/mL) Chest x-ray revealed no acute pathology. Labs showed glucose of 1090 mg/dL (normal:: 70-100 mg/dL) and thyroid-stimulating hormone (TSH) of &gt;50,000 IU/L (normal:: 0.3-4.2 IU/L). Urinalysis was positive for ketones; 20 mg/dL (normal:: negative). Venous blood revealed a pH level of 7.344. An acute coronary syndrome was ruled out, and he was admitted for management of hyperosmolar hyperglycemic state (HHS) and hypothyroidism. Due to a low level of C-peptide: &lt;0.5 ng/mL (normal:: 1.1-4.4 ng/mL) and high TSH, a new-onset insulin-dependent autoimmune diabetes and hypothyroidism induced as a side effect of nivolumab was suspected. Nivolumab was discontinued from his medication regimen. Endocrinology was consulted for the management of HHS and hypothyroidism. Insulin drip and levothyroxine were started, and he was transferred to the intensive care unit for close monitoring. Thereafter, his metabolic derangements improved with the resolution of hyperglycemia and electrolyte disturbances. On discharge, his symptoms improved and he was advised to stop taking nivolumab.

Discussion

Nivolumab has been reported in the literature to cause worsening of glycemic control and is also rarely reported as a cause of insulin-dependent diabetes due to autoimmune effects. Its effects on the thyroid are usually reported as transient thyrotoxic period which either resolves to euthyroid or rarely hypothyroidism which is what happened with our patient. Recognizing the side effects of Nivolumab and periodic monitoring can help earlier diagnosis and management with better outcomes.

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