Work

SAT-296 Dostarlimab induced Endocrine Dysfunction- A Case of Hypothyroidism, Adrenal Insufficiency, and Autoimmune Diabetes Mellitus

Year: 2025

Type: article

Abstract: Disclosure: A.D. Patel: None. A.D. Andrade: None. C.E. Guillen Lopez: None. S. Abou Khachfe: None. R. Arceo-Mendoza: None. R.M. Patel: None. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enhancing T-cell-mediated antitumor activity, improving outcomes and survival significantly. However, by disrupting immune tolerance, ICIs can trigger immune-related adverse events (irAEs), with endocrine dysfunction being among the most common, affecting approximately 10% of patients. While endocrine irAEs typically involve a single gland, rare cases of multiple concurrent endocrinopathies have been reported. Dostarlimab, a PD-1 inhibitor effective in treating recurrent or advanced mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) endometrial cancer, has been associated with various endocrine complications. A 53-year-old female with a history of type 2 diabetes mellitus (T2DM), rheumatoid arthritis (RA), and recurrent endometrial cancer presented with syncopal episodes, lethargy, and severe depression. Clinical evaluation revealed bradycardia, orthostatic hypotension, and biochemical evidence of severe primary hypothyroidism (TSH > 46, undetectable fT4 and fT3) and primary adrenal insufficiency, confirmed by a failed cosyntropin stimulation test. Thyroid ultrasound showed an atrophic gland, and anti-TPO, TRAB, and TSI antibodies were negative. Prior to this admission, she presented with DKA ( previously well controlled T2DM) and was noted to have positive anti-GAD antibodies, while C-Peptide, insulin autoantibodies, and IA-2 antibodies were all negative.Patient had received one cycle of dostarlimab five months ago for recurrent endometrial carcinoma, which was discontinued due to an RA flare. She was diagnosed with multiple ICI-induced endocrinopathies, including hypothyroidism, adrenal insufficiency, and Autoimmune DM, and was managed with hormone replacement therapy.ICI-induced endocrine dysfunction can target various endocrine glands, with distinct risks associated with CTLA-4, PD-1, and PD-L1 inhibitors. These conditions often present with nonspecific symptoms but may progress to life-threatening complications like DKA or adrenal crisis. Endocrine irAEs can occur at any time during or after ICI therapy, typically within 1.4-4.9 months for PD-1 inhibitors. Patients with pre-existing autoimmune conditions are at higher risk for both exacerbation of their underlying disease and the development of new irAEs.This case underscores the importance of routine endocrine screening and multidisciplinary management for early detection and timely intervention given the rapid apparition of endocrine pathologies. Increased awareness is crucial to optimize cancer treatment while minimizing endocrine complications. Further research is needed to elucidate risk factors, predictive biomarkers, management strategies for ICI-induced endocrinopathies, and their potential classification as autoimmune polyglandular syndrome. Presentation: Saturday, July 12, 2025

Source: Journal of the Endocrine Society