Abstract

Abstract Introduction Craniopharyngioma (CP) is a rare, parasellar tumor associated with metabolic dysfunction and panhypopituitarism. We investigated the impact of growth hormone (GH) replacement on metabolic complications in patients with adult-onset CP or pituitary adenoma (PA) using data collected between 1996 and 2012 in HypoCCS, an open-label, global prospective surveillance study of GH replacement in GH deficiency. Methods GH-treated (≥6 months) vs untreated groups in CP and PA patients were compared using ANOVA or Wilcoxon rank-sum test for continuous variables and chi-square test or Fisher's exact test for categorical variables. Multivariable analysis adjusted for GH use prior to enrollment, IGF-1 level, adrenal insufficiency, androgen replacement, and BMI. Results Of 8418 GH-treated and 1268 untreated patients in HypoCCS, 592 had CP, with 544 on GH and 48 untreated. Mean (±SD) follow-up was 5.39 (±4. 07) and 3.91 (±3. 07) years, respectively. Adverse hepatic outcomes (primary endpoint) were slightly improved with GH (19% vs 27%; p=NS). Mean lean BMI increased 0.93 (±1.56) kg/m2 with GH vs decreased 1.57 (±1.4) without GH (p=0. 022). Median (IQR) waist-hip ratio decreased -0. 01 (-0. 03-0. 03) with GH and increased 0. 03 (0-0. 06) without GH, significant on univariable (p=0. 01) and multivariable analysis (parameter estimate -0. 03 [-0. 05, -0. 004]; p=0. 02). Median blood pressure (BP) was unchanged with GH (-10-10) but increased 5.5 (0-17) mmHg without GH, significant on univariable (-5.99 [-11.44, -0.54], p=0. 032). Mortality was slightly lower with GH (3.5% vs 5.9%; p=NS). Of 3972 PA patients, there were 3346 on GH and 626 untreated; mean (±SD) follow-up was 5.38 (±3.97) and 3.93 (±3.22) years, respectively. GH did not impact hepatic outcomes (17%). Median (IQR) fasting glucose increased 6 (0-13) mg/dL with GH vs 1 (-10-7) without (p=0. 04), mean HbA1C decreased -0.12% (±1.94) with GH vs -1.95% (±1.84) without (p=0. 037), and rate of lipid medication use was in 46% on GH vs 56% without (p<0. 001). BMI increased 0.23 (-0.99-1.56) kg/m2 with GH vs 0 (-1.4-1.12) without (p=0. 002), and GH was associated with increased BMI (0.32 [0. 04-0.59]; p=0. 024). Median mean arterial pressure was 94.67 (87.33-101.67) mmHg with GH vs 93.33 (86.67-100) without (p=0. 007) and median diastolic BP was 80 (70-84) mmHg with GH vs 76 (70-82) without (p<0. 001); GH was associated with higher diastolic BP (1.43 [0.43, 2.44]; p=0. 005). Mortality was lower with GH than without (2.9% vs 5.1%), significant on univariable (p=0. 017) and multivariable analysis (0.60 [0.35-1. 03]; p=0. 066). Conclusion HypoCCS data show GH replacement in adult-onset CP lowers waist-hip ratio and slightly improves hepatic outcomes and mortality while untreated patients had increased BP. In PA patients, BMI and hypertension worsened with GH and mortality decreased, while hepatic outcomes were unchanged. The results suggest a favorable impact for GH on metabolic complications and a potential benefit for GH replacement in adult-onset CP. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

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