FRI253 Concurrent Adrenal Insufficiency And Hyperthyroidism In A Breast Cancer Patient Treated With Pembrolizumab Therapy
Authors: Kulkarni Abhigna U , Patel Disha T , Ruby Edward B 
Published: October 2023

Disclosure: A.U. Kulkarni: None. D.T. Patel: None. E.B. Ruby: None.

Anti-programmed cell death-1 (Anti-PD1) antibodies (e.g., Pembrolizumab) are immune checkpoint inhibitors that are widely in use for the treatment of many advanced malignancies. This has resulted in various side effects known as irAEs (immune-related adverse events). Endocrine irAEs include hypophysitis, adrenal insufficiency (AI), hypothyroidism, and hyperthyroidism. A 40-yo female with a history of recently diagnosed triple-negative breast cancer, status post chemotherapy, and immunotherapy with Pembrolizumab (last treatment a month prior to presentation) came in with fatigue, weight loss, and persistent vomiting for two weeks. Her initial BP was noted to be 80/50 mmHg, with HR 108bpm. She appeared weak and tired with no other abnormalities on physical exam. The thyroid was normal with no enlargement. Significant labs were creatinine 1.4mg/dL (0.4-1.3mg/dL), corrected calcium 12.8mg/dL, TSH of &lt;0.01mUI/L and fT4 of 4.47ng/dL (0.61-1.12ng/dL) (thyroid tests were previously normal). The patient was admitted to the ICU for hypovolemic shock refractory to IV fluids and endocrinology was consulted for multiple hormonal abnormalities. AKI and hypercalcemia were likely from dehydration as they subsequently resolved with IV fluids. AM cortisol level was low at 0.7ug/dL(3-16ug/dL). The cosyntropin test was positive, confirming AI. ACTH level was &lt;5pg/mL (normal&lt;46pg/mL) indicating a diagnosis of secondary AI, likely from immunotherapy. She was initiated on IV hydrocortisone. MRI brain was obtained to evaluate for hypophysitis which was unremarkable. Further thyroid testing was pursued which showed negative Thyroid peroxidase and anti-thyroglobulin antibodies. Thyroid scan showed a focal hot nodule in the left lobe suspicious for an autonomous nodule. She was started on beta blockers and methimazole with the goal of optimizing her thyroid function prior to her elective mastectomy. Pembrolizumab was discontinued with the plan to re-challenge after surgery. BP stabilized and she was discharged home on hydrocortisone with close outpatient follow-up with Endocrinology and Oncology. The clinical manifestations of Anti-PD1-associated AI are very non-specific and difficult to diagnose as they can be confused with the cancer-related illness itself or chemotherapy. Multiple endocrine abnormalities on initial labs with recent Pembrolizumab therapy in our patient raised suspicion for irAEs. Even though the occurrence of AI from anti-PD1 drugs is extremely rare, being &lt;1%, it can be life-threatening. Very few cases of Anti-PD1-induced thyroid dysfunction have been reported, however further testing in our patient confirmed hyperthyroidism from a toxic thyroid nodule. With the increasing popularity of these drugs, endocrinological complications are on the rise, and we as clinicians need to be vigilant and intervene at an early stage to prevent irreversible and fatal outcomes.

Presentation: Friday, June 16, 2023