Metabolic and Hormonal Profile of Adolescent Girls With Polycystic Ovary Syndrome With Concomitant Autoimmune Thyroiditis.

Introduction: Both polycystic ovary syndrome (PCOS) and autoimmune thyroiditis (AT) are considered to be among the most common endocrinopathies in young women, and they are classified as diseases that affect many processes in the human body. Their role in the development of metabolic disorders and diseases of the cardiovascular system in adult women is also emphasized. However, there are no data available to assess such risk in the teenage girl population. The aim of the study was to assess the hormonal and metabolic profile of adolescent girls with PCOS, additionally diagnosed with AT, as well as to identify possible risk factors for the coexistence of AT and PCOS. Material and
Methods: 80 euthyroidic PCOS patients were qualified for the study (chronological age 16.54 ± 1.00 years, BMI 24.60 ± 4.16 kg/m2). Eighteen girls diagnosed with AT were included in the study group and 62 girls without AT-in the control group. Each patient had biochemical and hormonal tests performed. Additionally, to diagnose AT, the level of antibodies against thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG), as well as the image of the thyroid gland on ultrasound examination, were taken into account.
Results: Estradiol concentration was significantly higher in the study than in the control group (203.00 ± 217.00 vs. 152.00 ± 78.50 pmol/L, p=0.02). Higher DHEAS concentrations were also observed in the AT group compared with the group without AT (391.28 ± 176.40 vs. 317.93 ± 114.27 µg/dl, p=0.04). Moreover, there was a positive correlation between AT and estradiol concentration (ry=0.27; p=0.04). It was also shown that there is a tendency toward statistical significance for the positive correlation between the positive anti-TPO titer and the glucose concentration at 120 min OGTT (rƴ=0.26; p=0.07) and girls with PCOS and AT had higher glucose levels in 120 min OGTT (115.29±41.70 vs. 98.56±28.02 mg/dl, p=0.08).
Conclusion: The study results showed no difference in the metabolic profile between the groups. The high concentration of estradiol found in girls with PCOS and AT may indicate the role of this hormone in the development of the autoimmune process. However, the numbers are small, and more research is needed to confirm our findings.

Introduction

Polycystic ovary syndrome (PCOS) is claimed to be one of the most common endocrine diseases and according to some studies it might affect 6% to 15% of women of reproductive age (1) and 1% to 6% of teenage girls. This disease affects many processes in the human body and often has long-term health consequences, such as an increased risk of metabolic disorders and cardiovascular diseases (2).

Autoimmune thyroid disease is another group of widespread endocrine disorders—dominated by Hashimoto’s disease (HT) (3). As many as 5% to 20% of young women might suffer from this disease (4). Although many genetic and environmental triggers were identified, their connections and interactions are still unclear (5). The adverse influence of hypothyroidism on lipid metabolism disorders is stated (6). It is worth mentioning that the most important independent risk factor for cardiovascular diseases in children is the duration of thyroid dysfunction. The risk of cardiovascular disease seems to be higher if hypothyroidism or subclinical hypothyroidism is associated with autoimmune thyroiditis (AT). Recent studies indicate that the diagnosis of AT itself, without any comorbid disorders of thyroid gland, increases the risk of cardiovascular diseases (7). In adult PCOS women with AT the increase cardiovascular disease risk was identified (8). However, there are no data about such relationship in adolescent girls.

The aim of the study was to assess the hormonal and metabolic profile of adolescent girls with PCOS, additionally diagnosed with AT, as well as to identify possible risk factors for the coexistence of AT and PCOS.

Materials AND METHODS

The study was retrospective and was completed on the basis of the collected hospital medical records of patients aged 12.33 to 18.00 years (median age, 16.54 ± 1.00 years) with newly diagnosed PCOS. The study included data from a total of 80 euthyroidic girls with PCOS. Eighteen girls—additionally diagnosed with AT were enrolled into the study group, while 62 PCOS subjects—without AT coexistence appeared in the control group. Seven patients (8.75%) from study group and 9 (14.06%) from control group had levothyroxine treatment introduced before diagnostic management of PCOS due to hypothyroidism.

The exclusion criteria were as follows: eating disorders (anorexia nervosa, bulimia), hyperprolactinemia (prolactin [PRL] ≥721 mIU/L), adrenal disorders (17hydroxyprogesterone [17OHP] ≥10 ng/ml, in patients with 17OHP between 2.0 and 9.9 ng/ml urine steroid profile results suggestive of congenital adrenal hyperplasia), abnormal thyroid stimulating hormone (TSH) level (TSH <0.4 mIU/L or >10.0 mIU/L), use of medications known to influence sex steroids in last 3 months. In all patients, the following data were analyzed:

anthropometric measurements (body weight [kg], height [cm], BMI [kg/m2], gynecological age [years], age of menarche [years], hirsutism assessed according to the Ferriman-Gallwey scale [points]);

biochemical tests results (total cholesterol — TC [mg/dl], triglycerides — TG [mg/dl], HDL cholesterol — HDL [mg/dl], LDL cholesterol — LDL [mg/dl], fasting glucose, and at 120 min of oral glucose tolerance test (OGTT) after a load of 75 g glucose [mg/dl]);

hormonal tests results (total testosterone — T [ng/dl], estradiol — E2 [pmol/L], luteinizing hormone — LH [mIU/ml], follicle stimulating hormone — FSH [mIU/ml], dehydroepiandrosterone sulfate — DHEAS [µg/dl], 17OHP [ng/ml], androstenedione - A [ng/ml], fasting insulin, and 120 min OGTT [µIU/ml]), parameters of thyroid function (TSH [µIU/ml], free thyroxine — fT4 [ng/dl]),

thyroid antibody (antiperoxydase antibody — anti-TPO [IU/ml], antithyreoglobulin antibody — anti-TG [IU/ml]).

thyroid ultrasound — performed with 12 MHz linear transducer (Siemens Medical Solution USA, Inc). Heterogeneous, hypoechoic echotexture of the thyroid gland was considered to be characteristic for AT.

HOMA IR (assessment of a model of homeostasis), FIGR (fasting insulin to glucose ratio), and LH to FSH ratio (LH/FSH) were calculated.

The diagnosis of PCOS was made according to the recommendations of consensus by Ibanez et al. (9). Menstrual disorders, present more than 2 years after menarche, were defined as oligomenorrhea (periods less frequent than every 45 days), polymenorrhea (cycles shorter than every 21 days), and secondary amenorrhea (no menstrual bleeding in the last 90 days). Clinical hyperandrogenism was considered to be hirsutism rated ≥8 points on the basis of the Ferriman-Gallwey scale. Biochemical hyperandrogenism was defined on the basis of total testosterone concentration >55 ng/dl (9).

The diagnosis of AT was made on the basis of positive anti-TPO (> 35 IU/ml) and/or anti-TG (>40 IU/ml) with the abnormal ultrasound scan of the thyroid gland (10). What is more, thyroid function abnormalities were not required for the diagnosis of AT.

Measurements of the concentrations of the tested hormones were made in the blood serum using the electrochemiluminescence method on the Cobas e411 apparatus (T, E2, TSH, fT4), chemiluminescence on the Immulite 2000XPi apparatus (LH, FSH, DHEAS, anti-TPO, anti-TG) or the ELISA method on the DS2 analyzer (17OHP, A).

Anthropometric data, biochemical, hormonal, and immunological results were compared using the Statistica 12 PL software. All values were expressed as mean ± standard deviation for normal or median (interquartile range) for skewed distribution. Comparison between groups was performed using Student t test for normally distributed data and Mann-Whitney U test for non-normally distributed samples. Correlation analysis was performed using Pearson correlation coefficient for normally distributed, and Spearman correlation coefficient for non-normally distributed data. Gamma correlation was used for non-normal distributions with many tied ranks. To evaluate variables effecting AT occurrence, positive anti-TPO, and anti-TG in PCOS girls, standard multiple regression analysis was performed with β coefficient interpretation with regard to the strength and direction of the relationship between variables. P value <0.05 was considered statistically significant, and 0.05