7815 Pembrolizumab-Induced Autoimmune Hypophysitis with “Isolated” ACTH Deficiency: Need for Heightened Awareness and Action Among Medical Fraternity
Authors: Shankar Srushti , Sundar Sumal Sri , Vaishnav Madhumati Shrikrushna , Lekkala Leena , Thummala Kamala , Srikanta Sathyanarayana , Deepak Tejeswini , Vijay Reshma B , Muniraj Kavitha , Nath Vasanthi , Siddlingappa Chandraprabha , Ravikumar Pushpa , Chitra Mandyam D 
Published: October 2024

Abstract
Disclosure: S. Shankar: None. S.S. Sundar: None. M.S. Vaishnav: None. L. Lekkala: None. K. Thummala: None. S. Srikanta: None. T. Deepak: None. R.B. Vijay: None. K. Muniraj: None. V. Nath: None. C. Siddlingappa: None. P. Ravikumar: None. M.D. Chitra: None.
Introduction: Autoimmune hypophysitis caused by immune checkpoint inhibitors [ICIs; anti-CTLA-4 (Ipilimumab alone 7.9%), anti-PD-1 (Pembrolizumab alone 1.7%; nivolumab alone 0%)] are being increasingly documented, with anterior hypopituitarism affecting corticotrophs more commonly than thyrotrophs and gonadotrophs (large time span of onset; different recovery patterns). Clinical Case 2021 Sep Age 65 years (type 2 diabetes, hypertension). Renal Cell Carcinoma S/P radical nephrectomy. 2023 Jul PET-CT= Metastatic pleuropulmonary nodules. Four admissions to Specialist Oncology Hospital [Four 2 weekly cycles of Inj Pembrolizumab 200 mg (with Tab Axitinib 10 mg/day)]. After first cycle: progressive fatigue, body aches, drowsiness. S Sodium= Pre-pembrolizumab= 137 mEq/L (135-145); Post-pembrolizumab= 124, 134, 132, 124; T3= 1.63 to 0.60 to 1.24 to 1.35 ng/mL (0.97-1.69); T4= 6.83 to 4.93 to 10.44 to 11.44 mcg/dL (5.53-11); TSH= 10.46 to 6.28 to 5.39 to 9.48 mIU/mL (0.46-4.68); S Cortisol 8 am= 1.54 mcg/dL (5-25); S Potassium= 4.59 mEq/dL (3.5-5.1)]. One episode of loss of consciousness; EEG= abnormal; MRI Brain= normal. During every hospital admission, oncology, medical, endocrinology and nephrology teams attributed the same to “illness” (no specific diagnosis) and provided symptomatic treatment (IV 3% saline, tolvaptan and sodium bicarbonate tablets).2023 Nov Medicine: Very severe nausea, anorexia, generalised weakness, myalgia, hiccoughs, and inability to walk. Frustrated family members sought admission in “new” General Hospital. S Sodium= 119, 120; S Potassium= 4.8; S Creatinine= 1.67 mg/dL (0.7-1.3); S Uric acid= 4.5 mg/dL (4.40-7.60); Urine spot Sodium= 84 mmol/L; ESR= 144 mm. Endocrinology: S Cortisol 8 am= 0.09 mcg/dL;S Cortisol post 250 mcg Inj Synacthen= 3.76 (&gt;20);Plasma ACTH= 5.4 pg/ml (9-52). S T3= 1.35; S T4= 11.44; S TSH= 9.48; LH= 3.61mIU/mL (1.5-9.3); FSH= 1.4mIU/mL (1.4-18.1); PRL= 30.1 (2.6-13.3); Testosterone total= 314 ng/dL (241-827); TPO antibodies negative. MRI-Pituitary: Partial empty sella; infundibulum neurohypophysis normal; mild asymmetric enhancement (5.5 mm) left cavernous sinus. Treatment: Tab Hydrocortisone 25 mg/day, with complete clinical and biochemical response [Suggestion of gonadotroph dysfunction and partial recovery of thyrotrope dysfunction/ injury. Hence, not on thyroxine replacement]. Clinical Lessons: Mechanisms for differential cellular vulnerability for ICI induced autoimmune pathologies [thyroid (destructive versus stimulatory), islet beta cells, adrenal cortical cells, various anterior pituitary cells (corticotrophs vs thyrotrophs and gonadotrophs] need elucidation. Specific molecular and cellular immunopathogenic pathways in different autoimmune endocrinopathies appear distinct and disparate.
Presentation: 6/2/2024