SUN-583 - Dual Immune-Mediated Endocrinopathies Following Checkpoint Blockade: A Case Report

Introduction:
Immunotherapy has become a revolutionary approach in modern medicine, particularly in oncology, significantly improving survival and response rates. However, immune activation can lead to immune-related adverse effects, many involving the endocrine system, most commonly the thyroid, pituitary, adrenal glands, and pancreas. We report a case of a 74-year-old man who developed type 1 diabetes mellitus and thyroiditis five weeks after starting Tremelimumab and Durvalumab.

Case Presentation:
The patient is a 74-year-old male with hypertension and clear cell hepatocellular carcinoma status post resection with local recurrence and lung metastases who presented with a 2-week history of weight loss and polyuria. He was found to have diabetic ketoacidosis with serum glucose 609 mg/dL, beta-hydroxybutyrate 6.7 mmol/L, anion gap 23, bicarbonate 16 mmol/L. He was started on insulin drip and IV fluids, with resolution of DKA and transition to subcutaneous insulin. He had no prior personal or family history of diabetes or prediabetes. Five weeks earlier, he started Tremelimumab and Durvalumab, receiving two doses; the last dose was two weeks ago. Labs showed low C-peptide 0.30 ng/mL (0.9–4.3), HbA1c 7.7%, and negative glutamic acid decarboxylase antibodies, consistent with immunotherapy-induced type 1 diabetes.

He was also found to have hyperthyroidism. He had a history of thyroid nodules not meeting biopsy criteria under endocrinology follow-up, with no prior hyperthyroidism. Labs revealed TSH < 0.02 uIU/mL (0.24–5.6), free T4 2.57 ng/dL (0.58–1.64), and total T3 87 ng/dL (70–200). Previous TSH was 0.37 one day before his last treatment. Thyroid stimulating and TSH receptor antibodies were negative. He was diagnosed with thyroiditis. Ultrasound showed stable nodules with no increased blood flow. ACTH and 8AM cortisol were normal.

At one-month outpatient follow-up, repeat C-peptide was undetectable, confirming type 1 diabetes. Insulin therapy improved glycemia, HbA1c 7.1%. Free T4 normalized while TSH remained suppressed, with TSH normalizing at four months, consistent with thyroiditis resolution.

Conclusion:
Tremelimumab (anti-CTLA-4) and durvalumab (anti-PD-L1) combination therapy can rarely induce both thyroiditis and type 1 diabetes mellitus as immune-related adverse events. Thyroiditis occurs in ~1.5% of patients receiving this therapy. The overall incidence of type 1 diabetes is ~0.2–1.9%, with combination therapy conferring higher risk than monotherapy. This case adds to the limited literature on dual endocrine immune-related adverse events following combination therapy. Early recognition and close monitoring of glucose and thyroid function are critical to minimize morbidity in patients receiving combination checkpoint inhibition.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*