ESPE Abstracts (2018) 89 P-P2-355

ESPE2018 Poster Presentations Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology P2 (38 abstracts)

Adiponectin as a Marker of Peripheral Insulin Resistance in Adolescents with Polycystic Ovarian Syndrome (PCOS) and as a Tool to Suspect Insulin Receptor Defects

Analía Freire a , Mirta Gryngarten a , María Gabriela Ballerini a , Andrea Arcari a , Sonia Viviana Bengolea b , Paula Scaglia a , Ignacio Bergadá a & María Gabriela Ropelato a

aCentro de Investigaciones Endocrinológicas ‘Dr César Bergadá’ (CEDIE) CONICET – FEI – División de Endocrinología, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina; bEndocrinología Pediátrica, Hospital ‘Dr Juan A Fernández’, Buenos Aires, Argentina

Background: Decreased serum adiponectin levels are associated with obesity and peripheral insulin resistance (IR). PCOS is characterized by hyperandrogenism and chronic anovulation and frequently is associated to IR. Some defects of Insulin Receptor have been proposed as mechanisms to explain ovarian hyperandrogenism in PCOS.

Objectives: To explore adiponectin levels in adolescents with PCOS and to evaluate if adiponectin would identify potential patients with hyperandrogenism associated to defects in the insulin receptor or its intracellular signal pathway.

Patients and methods: Prospective cross-sectional study. Twenty PCOS adolescents (16.4±2 years) diagnosed according to AES criteria and 10 healthy normal cycling adolescents (16.0±1.5 years) were studied. Fasting glucose, insulin, adiponectin, androgens (total and free testosterone, androstenedione), were measured. HOMA-IR > 2.5 was used a surrogate of IR.

Results: 11/20 (55%) PCOS patients showed IR (4 with normal BMI and 7 with high BMI). There were no differences between patients with or without IR in hirsutism score, menstrual cycle abnormalities or in the grade of hyperandrogenemia. Adiponectin levels in PCOS patients with increased BMI and insulin resistance were lower than in both PCOS and controls with normal BMI (ANOVA on way P<0.05). Significant inverse correlations between adiponectin, BMI (r=−0.79, P<0.001) and HOMA-IR (r=−0.53, P=0.02) were observed in patients with PCOS. Two patients with high adiponectin levels were excluded from the regression model as bivariant outliers. Both had unexpectedly high levels of adiponectin in spite of having the highest values of HOMA-IR. In one of them, a novel heterozygous missense variant in the tyrosine kinase domain of INSR was identified (NM_000208.3 (INSR): c.3449T>C (p.Leu1150Pro)). This variant is classified as likely pathogenic applying ACMG guidelines. Molecular study of insulin receptor gene from the other patient is currently under process.

Conclusions: Adiponectin levels are negatively associated with BMI and the severity of peripheral insulin resistance, while serum androgens do not seem to be related to them. Unexpectedly high levels of Adiponectin in patients with PCOS who exhibit insulin resistance should lead towards molecular studies to rule out insulin receptor defects.

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