6819 Adult-Onset Craniopharyngioma Patients Are at High Risk for Hepatic and Metabolic Dysfunction in the First Year After Surgery
Authors: Cooper O , Bonert V S , Noureddin M , Ader M , Goodarzi M O , Mamelak A N 
Published: October 2024

Disclosure: O. Cooper: None. V.S. Bonert: None. M. Noureddin: Advisory Board Member; Self; GlaxoSmithKline, Novo Nordisk, Merck, Takeda, Altimmune, BI, Northsea Therapeutics, Terns, 89BIO, Madrigal, Cytodyn, Corcept. Research Investigator; Self; Bristol-Myers Squibb, Akero, BI, GlaxoSmithKline, Allergan, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis Pharmaceuticals, Novo Nordisk, Shire, Takeda, Terns, Viking, Zudus, Gilead, Corcept. Stock Owner; Self; Rivus Pharma, CIMA, Cytodyn, ChronWell. M. Ader: None. M.O. Goodarzi: Advisory Board Member; Self; Nestle Health Science, Organon Laboratories. A.N. Mamelak: None.

Background: Observational studies of adult-onset craniopharyngioma (AoCP) suggest that hepatic and metabolic dysfunction begin perioperatively, but rigorous evidence is lacking. We assessed prevalence of these sequelae in AoCP to better understand their long-term impact. Methods: The retrospective study included all patients with AoCP who underwent surgery at our center from 1993 to 2017. In the prospective study, newly diagnosed patients were assessed preoperatively and at 3 and 12 months postoperatively with MRI-PDFF/elastography, frequently sampled intravenous glucose tolerance test (FSIGT), and cardiometabolic biomarkers. The primary endpoint was hepatic fat fraction change from baseline. Secondary endpoints were changes in fibrosis, glucose/insulin metabolism, hypertension (HTN), and lipids. Data are summarized as median (IQR) or mean ± SD. Results: 35 patients were followed retrospectively for a mean of 116 months. After surgery, 73% had new-onset obesity. Mean BMI increased by 5.0 ± 5.8 kg/m2 and 40% progressed from overweight to obese. 43% had new-onset type 2 diabetes mellitus (T2DM) and 39% hyperlipidemia. In 16 patients with liver imaging, 11 had metabolic dysfunction-associated steatotic liver disease (MASLD), 5 metabolic dysfunction-associated steatohepatitis (MASH), and 4 cirrhosis. In the prospective study, data from 6 patients were analyzed, 4 for ≥12 months. Median age was 48.5 (40.5, 59); 50% were female. At baseline, 17% had HTN, 50% hyperlipidemia, 67% prediabetes, 50% obesity class 1, and 17% class 2. 40% had mild steatosis and none had fibrosis. Median A1C was 5.9% (5.3, 6.1). By 3 months postop, 83% had elevated liver enzymes and median hepatic fat fraction increased 213%, with steatosis in 67%. BMI increased by 4% (-1.8, 12.5); 1 patient remained normal weight, 1 progressed to overweight, 3 remained class 1 obesity and 1 class 2. By 12 months, 50% had elevated liver enzymes and all had steatosis, with fibrosis grade 3 in 1 patient. Median hepatic fat fraction increased 670% from baseline and 62% from month 3. 50% had T2DM and 50% prediabetes. Median A1C was 6.4% (5.9, 7.3). On FSIGT, disposition index decreased by 69% (-91, 50) and insulin sensitivity decreased by 51% (-70, 46). Median BMI was 30.8 kg/m2 (25.3, 37.1); 1 patient remained normal weight, 1 was overweight, 1 class 1 obesity, and 1 class 2. 50% had HTN and 50% had hyperlipidemia. Conclusion: By 10 years after surgery, most patients with AoCP have MASLD, with some progressing to MASH, fibrosis, and cirrhosis. T2DM, hyperlipidemia, and obesity are prevalent. In our small prospective cohort, by 1 year after surgery, all patients had developed MASLD, and BMI, blood pressure, and insulin and lipid profiles worsened. These results underscore the need for early interventions to halt progression of metabolic sequelae in patients with AoCP undergoing surgical resection and impede long-term comorbidity development.

Presentation: 6/3/2024