Endocrine Abstracts

Patients affected by adult growth hormone deficiency (aGHD) show worse metabolic profile, with insulin-resistance, increased total cholesterol, LDL, triglycerides, reduced HDL, and higher risk of developing type 2 diabetes mellitus and cardiovascular complications. Adult GHD and metabolic syndrome (MetS) are closely related to each other, since they share the previous depicted clinical features, while obese MetS patients display lower IGF-1 levels due to a functional reduction of GH secretion. Neudesin is a newly discovered peptide mainly secreted in brain and adipose tissue, under evaluation for its possible activity as negative regulator of energy expenditure, as it decreases food intake in mice models. Liver expressed antimicrobial peptide (LEAP)-2 is involved in ghrelin physiological regulation as it acts as a competitive antagonist with slow dissociation from the GSH receptor-1a, blunting the magnitude of ghrelin activities. We have already demonstrated higher LEAP-2 levels and significantly lower ghrelin/lEAP-2 ratio in aGHD. To better characterize the metabolic profile of aGHD patients we performed an observational cross-sectional study testing the hypothesis that neudesin may be affected in this clinical setting. Given the role in energy balance of the two peptides, we also evaluated any eventual relationship between neudesin, LEAP-2 and metabolic and anthropometric parameters. 39 patients were included in the study. Group A: 18 aGHD patients, 7 females and 11 males. Mean±SEM age of the group was 59.7±2.7 years, while BMI was 30.2±2.2 kg/m². Group B: 21 healthy controls (13 females and 8 males). Mean±SEM age of the group was 47.1±2.5 years, while BMI was 24.5±0.9 kg/m². They were evaluated for glucose and insulin, HOMA and QUICKI index, total/lDL/HDL cholesterol, triglycerides, uric acid and IGF-1. Neudesin, LEAP-2 and ghrelin were measured by ELISA, according to manufacturers’ protocols. As expected, aGHD patients showed higher HOMA index, triglycerides and lower HDL than controls. Neudesin is significantly higher in aGHD than controls (2.83±0.37 vs 1.55±0.12 ng/ml). We confirmed significantly lower ghrelin levels and significantly higher LEAP-2 (5.19±0.42 vs 3.69±0.49 nM) in aGHD, leading to lower ghrelin/lEAP-2 ratio. A significant and strong direct correlation between neudesin and LEAP-2 was found both in aGHD (r²=0.76) and in all the analyzed population. While LEAP-2 directly correlated significantly with BMI, neudesin did not. These results, although preliminary, may suggest a possible adaptation to a worse metabolic scenario in aGHD. The presence of two distinct pathways related to food intake and the relative scarce knowledge on neudesin suggest future developments in this field.