Endocrine Abstracts

Introduction: Hypophysitis (Hp) is a serious adverse effect (AE) of Immune check-point inhibitor (ICI) therapy in malignancy. We evaluated 6 yeas of clinical expereince with ICI against the recent ESE CPG 2023 which provides practical guidance on the management of this condition based on up-to-date evidence.

Methods: A quality improvement project (QIP) included all patients with ICI-Hp (n=17) referred to a dedicated Endocrine-ICI clinic (January 2017-November 2023), to determine presentation, management, and outcomes.

Results: There were 50% males, median age 63 y (IQR 51,73)] and symptom onset occurred 12 w (IQR 9,15) of ICI therapy, after the 3^rd (IQR 3,4) cycle; underlying malignancy: metastatic melanoma (76%), renal cell carcinoma (12%) and mesothelioma (12%). All received Ipilimumab (Ipi), alone (5.8%) or in combination with Nivolumab (82%). Fatigue (76%), headache (71%) and nausea (65%) were common symptoms; 12% were asymptomatic. Hyponatremia 41%. All had acute secondary hypocortisolism (SHC) (random morning cortisol <100 nmol/l in 82%, <50 nmol/l in 53%). Acute secondary hypothyroidism (SHT) and hypogonadism (SHG) were reported in 35%. Low prolactin (PRL) (<110 mIU/l) 30%; elevated PRL (446-1119) 18%. Enlarged pituitary was the commonest (75%) pituitary imaging abnormality (n=16, performed ≤12 w), followed by thickened stalk (31%), supra-sellar extension (12%), mild optic-chiasm compression (n=1, biopsy: lymphocytic Hp). Specific management of Hp varied; IV methylprednisolone (MPP) 1 mg/kg per day (n=4) (indication severe headache), oral prednisolone 30–40 mg/d (n=6), oral dexamethasone 10 mg/d (n=1), and hydrocortisone (HC) 40 mg/d for 48 h (n=4). Symptomatic Hp recovery occurred in all; (33% within 48 h) and scan abnormalities [at 15 w (IQR 13, 22), n=14). One patient developed acute psychosis with high-dose MPP. Long term, all received standard HC (20 mg/d) replacement and age/weight-based levothyroxine in persistent SHT. None required sex hormone replacement. In those evaluated for pituitary recovery; There was no recovery in SHC (n=10), whilst recovery of SHT and SHG was reported in 43% [at 5 w (IQR 4,10)] and 67% [at 10 w (IQR 8,13)] respectively. Lack of cancer progression was noted in 65% [2.5 y (IQR 2, 6)]. Treatment with high dose GCs was not associated with cancer progression (P=1.00), or all-cause mortality (P=0.515).

Conclusions: Despite antedating ESE CPG, our practice is aligned with current guidance. GC dose (not strictly aligned with CPG) chosen for symptom severity had no effect on disease course. SHC following ICI-HP was irreversible, however recovery of SHT and SHG should be actively sought on long term follow up.