SAT-294 Immune Checkpoint Inhibitor Therapy Induced Hypophysitis; A Single Tertiary Care Centre Experience; Highlighting Importance of Awareness of Peak time of Onset, Potential Markers, Treatment Outcomes and Long term Endocrinopathies/Recovery

Abstract Disclosure: S.A. Mathara Diddhenipothage: None. J. Warden: None. K. Herbert: None. R. Pofi: None. N. Coupe: None. M. Payne: None. J.W. Tomlinson: None. H.E. Turner: None. Introduction: Acute Hypophysitis (Hp) is a serious adverse effect of Immune checkpoint inhibitor (ICI) therapy. Methods: Retrospective audit of all patients with ICI-Hp (n=22) referred to a dedicated Endocrine-ICI clinic (January 2017- Oct 2024), to determine clinico-radiological characteristics, features to flag for early diagnosis, treatment outcomes and recovery of hormonal axes. Results: Onset 13 w (IQR 9,17), after a median of 3rd (IQR 3,4) cycle, 55% females, age 67 y (IQR 53,74). Metastatic melanoma 77%. 68% received Ipilimumab (Ipi) with Nivolumab, 5% Ipi alone, and 27% anti PD-1 monotherapy. Majority (91%) were symptomatic; headache (64%), fatigue (77%), nausea (64%), vomiting (23%), anorexia (23%); hyponatremia 41%: mild (Na+ 130-135 mmol/L) 35%, severe (<125 mmol/L) 12%. All had acute secondary hypocortisolism (SHC); morning cortisol <100 nmol/L (82%) and <50 nmol/L (59%). Secondary hypothyroidism (SH) in 41%. Low prolactin (PRL) (<110 mIU/L) 32%: undetectable (<13 mIU/L) n=3: onset preceded SHC by 2 w (n=1). High PRL (446-1119) n=23%. Secondary hypogonadism (SHG) in 27%; onset preceded SHC by 11 w (n=1). Pituitary imaging ≤13 w (n=20); enlarged gland 64%, thickened stalk 50% [thickness 2.8 mm (IQR 2,3.4)], supra-sellar extension 46%, mild optic chiasm compression n=3 (pituitary biopsy n=1: lymphocytic Hp). Asymptomatic pituitary enlargement (n=1) preceded SHC onset by 4 w. Non-pituitary metastases 18%. Treatment used different glucocorticoid (GCs) regimens; IV methylprednisolone (MPP)(n=4), prednisolone (n=8), dexamethasone (n=1), and hydrocortisone (HC) oral stress dose for 48 h (n=6). All symptoms recovered fully: 33% within 48h (No data n=4). Acute psychosis with IV MPP (n=1). Significant resolution of scan findings in all (n=14) at 15 w (IQR 13, 21). No recovery of SHC in those evaluated (n=13), at 3 m (n=3), 2 y (n=3), 3 y (n=4), 4 y (n=2), and 8 y (n=1). In those with SH, 33% recovered at 5 w (IQR 4,16) and no recovery in 44% on reassessment at 3 y (IQR 1,6). Recovery of SHG was seen in 67% at 10 w (IQR 7,16), whilst no recovery n=2 (3 y) Acute onset ICI-related type 1 diabetes (T1D) was common 18% (overall prevalence of ICI-T1D 0.6-1.4%), median onset 20 w (IQR 10, 54) of ICI, 3/4 presented with DKA. Cancer progression free survival 59% [3 y (IQR 1, 6)]. Mortality 14% [3 y (2,6)]. Treatment with high dose GCs not associated with cancer progression (p=0.674), or mortality (p=0.544). Conclusions: Acute ICI-Hp is a heterogenous clinical entity. However, important practice points highlighted to improve care; 1. Raised awareness for symptom safety netting recommended for Ipi based therapy particularly after 3rd cycle; 2. SH, SHG and low PRL may precede SHC; 3. GCs useful for symptom control but higher dose had no effect on disease course and may increase adverse effects; 4. Recovery of SH and SHG should be actively sought during follow up; 5. ICI related T1D may be more commonly associated with ICI-Hp. Presentation: Saturday, July 12, 2025