MON-027 Central Adrenal Insufficiency, Central Hypogonadism, and Optic Neuritis Associated with HSV-1 CNS Infection in a Patient Receiving Pembrolizumab Therapy

Abstract Disclosure: M. Shahid: None. A.N. Mukhtar: None. T. Wu: None. Introduction: Immune checkpoint inhibitors (ICIs), such as pembrolizumab, are known to cause endocrinopathies, including thyroiditis, hypophysitis, and adrenalitis, leading to hormonal deficiencies. Additionally, ICIs have been linked to optic neuritis (ON). However, the interplay between ICIs, Herpes Simplex Virus-1 (HSV-1) reactivation, and immune-mediated inflammation remains unclear. In our case, the patient on pembrolizumab therapy developed bilateral ON, central adrenal insufficiency (AI), and central hypogonadism with HSV-1 infection. Clinical Case: A 44-year-old female, former smoker with hypertension and right-sided clear cell renal carcinoma (post-nephrectomy) on pembrolizumab therapy presented with generalized weakness and bilateral vision loss for several days. Previously she had developed ICI-induced thyroiditis, currently on levothyroxine. Laboratory results showed a morning cortisol of 0.2 mcg/dL with low ACTH (2.2 pg/mL, normal 7.2-63.3); DHEAS was low (9.71 ug/dL, normal 60.9-337), estradiol <5 pg/ml with low levels of both LH (<0.1mIU/ml) and FSH (0.4 mIU/mL), consistent with central AI and central hypogonadism. Other pituitary hormones were normal except for mildly elevated prolactin 23.9 ng/mL (normal 4.8-23.3). Cosyntropin stimulation test showed inadequate cortisol response. MRI orbits revealed slight leftward deviation of the pituitary stalk with a 3.5 mm hypoenhancing focus in the left side of the sella, indicating a regional tissue damage. These findings could explain the deficiencies of gonadotropins and corticotropin, as well as slightly elevated prolactin level. Neurology and ophthalmology confirmed bilateral ON, and she was started on pulse-dose steroids. Lumbar puncture detected HSV-1 antibodies, prompting acyclovir initiation. Patient's symptoms improved over the following week. Discussion: While ICI therapy can cause ON, central AI, and central hypogonadism, their simultaneous occurrence with HSV-1 CNS infection suggests an additional factor. HSV-1 is a recognized cause of primary AI, but its role in central AI is unreported. ICIs may contribute to HSV-1 reactivation by disrupting immune evasion mechanisms, triggering immune-mediated inflammation. Latent HSV-1 infection evades immune detection by promoting CD8+ T-cell exhaustion via PD-1, TIM-3, and CTLA-4 pathways. By blocking these pathways, ICIs may enhance T-cell activity against latent HSV-1, leading to inflammation of optic nerve and regional pituitary as seen in our case. Presentation: Monday, July 14, 2025