ODP319 IGF-1 and BMI are Associated in Obese Patients with Acromegaly
Authors: Khiyami Anamil , Fazeli Pouneh , Mahmud Hussain , Gardner Paul , Zenonos Georgios 
Published: November 2022

Regulation of the growth hormone (GH) axis is complex and influenced by factors including age and nutritional status. Studies of individuals across the weight spectrum demonstrate an inverted U-shaped correlation between BMI and total IGF-1 levels; in both individuals with anorexia nervosa-range BMIs and those who are severely obese, total IGF-1 levels are low. Acromegaly is a disorder of the GH/IGF-1 axis characterized by IGF-1 excess secondary to autonomous GH secretion. The relationship between BMI and IGF-1 levels has not been well studied in acromegaly and whether the association between BMI and IGF-1 observed in non-acromegalic individuals is also present in acromegaly is not known. Patients who underwent endoscopic endonasal resection of pituitary adenomas at our institution between 1/2015-6/1/2021 were studied to investigate the association between BMI and preoperative IGF-1 in acromegaly. Ninety-nine patients were identified who either had evidence of preop biochemical hormone excess [elevated IGF-1 level and/or GH &gt;1ng/ml following 75g oral glucose tolerance test] (n=40) or who had a clinically non-functioning, non-staining (NF) pituitary adenoma, or non-functioning GH-staining adenomas (n=59). We excluded anyone with a prior history of surgery/radiation, those on medical therapy (including somatostatin analogues, cabergoline), and those on oral contraceptives in the 3-months preceding surgery (n=8 in each group). Median age of acromegaly patients (n=32) was 39.5 years [29.3, 51.8], mean BMI was 30.2 +5.3 (SD) kg/m 2 (range: 20.9-40.4 kg/m 2) and 50% were female. Preoperative IGF-1 levels were measured using a clinically available assay. To control for differences in IGF-1 levels based on age/sex, we calculated % upper limit of normal (ULN) for IGF-1 based on age/sex determined normal ranges (mean %ULN IGF-1: 219.7+74.8%). In the acromegalic group, univariate analysis demonstrated a significant positive association between both BMI and IGF-1 (R=0.44, p=0. 01) as well as BMI and IGF-1%ULN (R=0.35, p=0. 047). In contrast, in the NF group (n=51 with 49% female and mean age: 56.4+16.7 years), there was no significant association between BMI (mean: 31.3+6.5 kg/m 2; range: 19.1-47 kg/m 2) and %ULN IGF-1 (median: 38.9% [26.8, 61.4]) (rho=0.15, p=0.30). However, in the subgroup of NF patients with severe obesity (BMI &gt;35 kg/m 2; n=17), a significant inverse association between BMI and %ULN IGF-1 was observed (rho: -0.54; p=0. 03) . These data demonstrate that in contrast to the inverse relationship that is typically observed between total IGF-1 and BMI in obese individuals, which is preserved in a NF adenoma group, there is a significant positive association between %ULN IGF-1 and BMI in patients with acromegaly, including those with severe obesity. Further study is necessary to determine whether obese patients with acromegaly exhibit more severe symptoms related to their disease due to this positive association between BMI and IGF-1 or whether obesity is a secondary effect of their acromegaly.

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