*Aleksandra Kruszyńska1, Jadwiga Słowińska-Srzednicka1, Aleksandra Wycisk2, Piotr Glinicki1, Katarzyna Podkowska2, Renata Kapuścińska1
High prevalence of autoimmune thyroiditis in Polish PCOS women and its association with insulin resistance
Zwiększona częstość autoimmunizacyjnego zapalenia tarczycy u polskich kobiet z zespołem PCO i jej związek z insulinoopornością
1Department of Endocrinology, Centre of Postgraduate Medical Education, Bielański Hospital, Warsaw
Head of Department: Professor Wojciech Zgliczyński, MD, PhD
2Students Endocrinology Club, Centre of Postgraduate Medical Education, Bielański Hospital, Warsaw
Head of Club: Aleksandra Kruszyńska
Streszczenie
Wstęp. Zarówno zespół policystycznych jajników (PCOS), jak i przewlekłe autoimmunizacyjne zapalenie tarczycy (AZT) są częstymi endokrynopatiami, wiążą się z niepłodnością i zwiększają ryzyko poronień. Insulinooporność odgrywa istotną rolę w patogenezie PCOS. Dane dotyczące częstości AZT i powiązań z insulinoopornością w PCOS są ograniczone.
Cel pracy. Ocena częstości AZT i niedoczynności tarczycy u pacjentek z PCOS oraz zbadanie, czy nasilenie insulinooporności, objawów klinicznych i hiperandrogenizmu wiąże się z obecnością AZT.
Materiał i metody. Przeanalizowano dane 195 kobiet z PCOS rozpoznanym zgodnie z kryteriami rotterdamskimi. Oznaczono TSH, przeciwciała przeciwtarczycowe, wykonano test OGTT i USG tarczycy.
Wyniki. AZT rozpoznano u 68 (34,9%) kobiet z PCOS, jawna bądź podkliniczna niedoczynność tarczycy występowała u 45 (23%) chorych. Kobiety z PCOS i AZT w porównaniu do kobiet bez AZT cechowały wyższe wartości wskaźnika HOMA (1,52 vs. 1,18, p = 0,01) i stężeń insuliny na czczo. Poziom androgenów w obu grupach nie różnił się istotnie.
Wnioski. AZT i niedoczynność tarczycy występują bardzo często u kobiet z PCOS. Pacjentki z PCOS i AZT nie mają istotnie innych poziomów androgenów niż pacjentki z PCOS bez AZT, ale mają bardziej nasiloną insulinooporność. Wszystkie pacjentki z PCOS powinny być badane w kierunku wykrycia AZT (choroby Hashimoto) i niedoczynności tarczycy.
Summary
Introduction. Both polycystic ovary syndrome (PCOS) and chronic autoimmune thyroiditis (AIT) are common endocrinopathies, are connected to infertility and cause the increase in miscarriage rate. In PCOS patients insulin resistance plays a significant role in pathogenesis. There is only limited data concerning prevalence of AIT in PCOS and its association with insulin resistance in PCOS.
Aim. To assess the prevalence of AIT and hypothyroidism in PCOS patients and to determine if the degree of insulin resistance, clinical symptoms and hyperandrogenism are connected with AIT presence.
Material and methods. We analyzed data of 195 PCOS women diagnosed based on Rotterdam criteria. TSH, thyroid antibodies, thyroid USG and OGTT were performed.
Results. AIT was present in 68 (34.9%) PCOS women while evident or subclinical hypothyroidism was present in 45 (23%) patients. PCOS women with AIT had higher HOMA (1.52 vs 1.18, p = 0.01) and fasting insulin than women without AIT. The androgen levels did not differ between both groups.
Conclusions. AIT and hypothyroidism are very common in patients with PCOS. PCOS patients with AIT do not differ in androgens level, but are more insulin resistant than the patients without AIT. All PCOS patients should be screened for AIT (Hashimoto disease) and hypothyroidism.
Abbreviations:
AIT – autoimmune thyroiditis
AUC ins – insulin area under the curve
DHEA-S – dehydroepiandrosterone sulphate
HOMA – homeostasis model assessment
OGTT – oral glucose tolerance test
PCOS – polycystic ovary syndrome
TSH – thyroid stimulating hormone
USG – ultrasonography
INTRODUCTION
Chronic autoimmune thyroiditis (AIT, Hashimoto’s disease) is a common endocrinopathy. In areas with sufficient iodine intake it is the most prevalent cause of hypothyroidism. Women are five to ten-fold more susceptible to develop AIT in comparison with men (1). Both hypothyroidism and autoimmune process could cause infertility (ovulatory and menstrual disturbances and pregnancy complications including miscarriages).
Polycystic ovary syndrome (PCOS) is a heterogeneous condition, affecting 5-19% of women of reproductive age (2, 3), making it the most prevalent endocrine disorder among premenopausal women and the main cause of infertility. There is a strong relationship of PCOS to obesity, insulin resistance, diabetes, chronic inflammation and other metabolic disturbances. Oligo- or anovulation in PCOS women causes low progesterone secretion and thus, high estrogen-to-progesterone ratio, resulting in increased likelihood of developing autoimmune diseases (4, 5), including AIT.
Pathogenesis of both AIT and PCOS is thought to be a combination of genetic susceptibility and environmental factors. Sex steroid hormones and another factors such as stress and viral infections, contribute to the development of AIT and the hormones play probably the most important role (6).
There are some studies in which coexistence of PCOS and autoimmune diseases, like AIT (1, 7), rheumatoid diseases (8), APS2, and other, are described (9-13). In some studies (14, 15) the higher than in general population prevalence of AIT in PCOS women was not confirmed. However, there is no population data and no recommendations are available for diagnosis of Hashimoto’s disease in all PCOS patients.
AIM
In our study we assessed the prevalence of AIT and subclinical or evident hypothyroidism in our PCOS population and the correlations of the AIT with insulin resistance and clinical manifestations and different phenotypes of PCOS (16).
MATERIAL AND METHODS
Subjects
We analyzed data of 195 young (aged 18-40) PCOS women, admitted to our Endocrinology Department, and diagnosed based on Rotterdam criteria.
The institutional ethics committee gave the opinion that, because of retrospective character of the study, their consent is not necessary.
Protocol
All subjects underwent a physical examination and detailed past and present medical history including menstrual history, fertility, thyroid dysfunction in the past, taken drugs esp. thyroxin.
All hormonal and biochemical measurements were performed in the early follicular phase of spontaneous or progestin-induced menstrual cycle.
Hashimoto disease was recognized if thyroid antibodies were present and there were changes in ultrasonography typical for AIT, or if thyroid antibodies were present with concurrent hypothyroidism.
Hormonal measurements
Venous blood samples were collected in the morning (between 7-9 a.m.) following an overnight fast.
Blood samples were collected into plane tube with clot activator and centrifuged (3500 rpm, 10 minutes).
Routine determinations included: TSH, thyroid antibodies (anti-TPO and anti-TG), testosterone, androstenedione and DHEA-S.
Oral glucose tolerance test
After an overnight fast, all subjects underwent OGTT with a load of 75 g glucose; glucose and insulin at 0, 30, 60 and 120 min were determined, insulin resistance indexes: HOMA and AUC for insulin were calculated as previously described.
Assays
Insulin levels were determined by immunoradiometric (IRMA) assay (BI-INSULIN IRMA, CIS bio International, France).
Levels of thyroid stimulating hormone (TSH-3rd generation), thyroid autoantibodies (anti-TPO and anti-TG), androstenedione, DHEA-S and total testosterone were measured by chemiluminescent immunometric assay on Immulite 2000 (Siemens Healthcare Diagnostics, USA).
Plasma glucose concentrations were determined by an oxydase method (Cobas Integra 400, Roche, Switzerland).
Thyroid ultrasound
Ultrasound of the thyroid was performed using a 7.5 MHz transducer with Duplex sonography. The thyroid was considered hypoechogenic when its signal was equal or below the echogenicity of the surrounding neck muscles.
Statistical analysis
The calculations were done using the statistica analysis package.
Normality of distribution was assessed by Shapiro-Wilk test.
In the case of variables deviating from the normal distribution, the median values with interquartile ranges were calculated.
Because of the absence of normality, nonparametric testing U-Mann Whitney was used.
For further analysis Fisher’s exact test and logistic regression were used.
The limit of statistical significance was set at P < 0.05.
RESULTS
In the group of 195 PCOS women, AIT was recognized in 68 women (the prevalence of 34.9%). Markedly increased thyroid antibodies (anti-TPO or anti-TG or both) were present in 62 patients (31.8%) and the ultrasound changes typical for AIT were found in 86 women (44.1%).
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