Endocrine Abstracts

Background: Short stature is one of the most common presentations to paediatric endocrinologists. It is estimated that despite all the exams, in 50–90% of cases, children are labelled as having idiopathic short stature. It has been recently reported that genetic ACE2 deficiency is associated with reduced body weight as well as with impaired gestational weight gain and fetal growth restriction in pregnancy. It has been argued that ACE2 deficiency, which is usually associated with an increase of tissue Angiotensin II, could be associated with prenatal as well as postnatal changes leading to reduced growth (such as uterine artery dysfunction and IGF-1 reduction, respectively). Based on these premises, the aim of our study was to evaluate whether there was a difference of ACE2 expression in children with short stature as compared to age-matched controls.

Methods: We designed an exploratory case-control study aiming at recruiting consecutively 40 children with short stature (cases) and 40 controls presenting at the Endocrinology Service, aged 2–13 years, excluding those with acute intercurrent diseases, diabetes, renal insufficiency, syndromes and/or on medications. After signing the informed consent to participating in the study, children underwent a medical visit and a fasting blood sampling. Peripheral blood mononuclear cells (PBMC) were isolated to extract mRNA for gene expression analyses. Sera were collected for protein measurements.

Results: Children with short stature (n = 17) presented with lower height and body weight as compared to controls (n = 18). Our preliminary data show that children with short stature exhibited a significant reduction of ACE2 gene expression, and a significant increase of ACE/ACE2 ratio in PBMC. This was associated with a modest increase of Angiotensin II/Angiotensin 1–7 ratio. Our multivariate analysis showed that across the groups ACE2 was independently associated with height but not with body weight.

Conclusions: To our knowledge, this is the first study investigating ACE2 expression ina paediatric population. Our preliminary results, showing that ACE2 expression is significantly reduced in children with short stature, are in line with the literature. This study could representthe basis for further investigations aiming at establishing the presence of a causal relationship between ACE2 deficiency and growth reduction, with further diagnostic and therapeutic perspectives