Polikistik Over Sendromlu Adolesanlarda Anti Müllerien Hormon (Amh) ve İnsülin Like Peptit 3 (Insl3) Düzeylerinin Belirlenmesi ve Tanı Belirteci Olarak Kullanımının Değerlendirilmesi

Abstract

ABSTRACT Kömürlüoğlu A. Level determination of Anti Mullerien hormone (AMH) and Insulin Like Peptid-3(INSL3) and evaluation of diagnostic use as a marker in adolescent with polycyctıc ovary syndrome, Hacettepe University, Faculty of Medicine, Department of Pediatrics, Ankara, 2015. Polycystic Ovary Syndrome (PCOS) is a disorder characterized by chronic anovulation and hyperandrogenism, due to a combination of genetic and environmental factors. The onset is peripubertal. Usually, there is oligomenorrhea or amenorrhea characterized by chronic anovulation. Moreover, clinical signs of hyperandrogenism as hirsutism, acne, and alopecia may occur. Insulin resistance, hyperandrogenism, elevated luteinizing hormone (LH), and polycystic ovaries in ultrasound imaging are laboratory findings. Insulin-Like Peptide-3 (INSL3) and Anti-Mullerian hormone (AMH) are peptides produced by mammalian gonads. AMH, is a member of the transforming growth factor-β (TGF-β) family and AMH expression occurs in ovarian granulosa cells. INSL3 is a member of the insulin relaxin family, synthesized in the ovary, particularly by the theca interna cells of antral follicles as well as by the corpora luteum and ovarian stroma. In previous studies, it is shown that AMH levels of adult patients with PCOS were 2-3 fold or even more elevated. This is due to the preantral and small antral follicles proliferation resulting overcrowding in folliculogenesis and excessive AMH production from granulosa cells of PCOS patients compared to healthy women. Women with polycystic ovarian syndrome are found to have almost double the normal circulating levels of INSL3 and this is associated with increased number of the cystic follicles. The increase in AMH and INSL3 levels in PCOS patients is considered to reflect a dysfunction in the theca and granulosa cells. There are studies showing that monitoring AMH and INSL3 levels can be valuable in PCOS diagnosis and follow-up. However, there is no similar study in adolescence PCOS population. The aim of this study is to determine the serum AMH and INSL3 levels in adolescents with polycystic ovary syndrome and compare this levels respect to healthy control group to evaluate AMH and INSL3 as diagnostic markers for PCOS. In addition, the vii correlation between androgen and gonadotropin levels, ultrasound findings and INSL3 and AMH levels are also investigated. This study was conducted in Hacettepe University Ihsan Dogramaci Children's Hospital Pediatric Endocrinology Department between 01/07/2014 and 01/03/2015. 50 adolescents aged between 12-18 years, diagnosed as PCOS based on 2003 Rotterdam criteria participated in the study as case group. 25 healthy age matched adolescent girls comprised the control group. Adolescents treated for PCOS were excluded from the study. All participants had menstruation cycles for at least 2 years or more. AMH levels was statistically significantly higher in PCOS adolescents compared to the control group. There was no significant difference in INSL3 level between PCOS group and control group. AMH levels was found strongly correlated with averaged over volume and average antral follicle count. AMH levels were also correlated with androgen levels and this results shows that AMH can be used as a marker for hyperandrogenism. AMH levels were higher in amenorrheic and oligomenoreik adolescents. This finding suggests that AMH may play a role in the pathogenesis of anovulation. AMH cut-off value for PCOS diagnosis in adolescents was found as 5.05 ng/ml (94% sensitivity, 80% specificity, 90.4% positive predictive value, 87% negative predictive value) Positive correlation between the levels of AMH and INSL3 in PCOS group was present. This correlation was more evident in overweight and obese adolescents. This may also be considered as an evidence of interrelation between AMH levels and the severity of symptoms in PCOS. In conclusion, correlation of androgen levels and the number of folliculles with AMH levels shows that AMH may be a diagnostic criteria for PCOS. AMH level over the value of 5.05 ng/ml supports the diagnosis of PCOS with high sensitivity and specificity. Unlike adult PCOS cases, INSL3 is not a diagnostic marker in the adolescent age group. Keywords: Polycystic ovary syndrome, anti-Müllerian hormone, insulin like peptide-3