PREMATÜR ADRENARŞLI OLGULARDA İNFLAMATUAR BELİRTEÇLERİN DEĞERLENDİRİLMESİ

GÖZDE KÖYLÜ

PREMATÜR ADRENARŞLI OLGULARDA İNFLAMATUAR BELİRTEÇLERİN DEĞERLENDİRİLMESİ

Thesis Type: Expertise In Medicine

Institution Of The Thesis: Sivas Cumhuriyet University, Tıp Fakültesi, ÇOCUK SAĞLIĞI VE HASTALIKLARI ANABİLİM DALI, Turkey

Approval Date: 2021

Thesis Language: Turkish

Student: GÖZDE KÖYLÜ

Supervisor: Nurullah Çelik

Open Archive Collection: AVESIS Open Access Collection

Abstract:

Premature adrenarche (PA); is defined as the onset of hair growth in the armpit and/or genital area before the age of eight in girls and before the age of nine in boys. It is diagnosed by excluding androgen-secreting tumors and late-onset congenital adrenal hyperplasia (CAH). The most typical laboratory finding of adrenarche is that the serum Dehydroepiandrosterone-Sulphate (DHEAS) level exceeds 40 µg/dl. The mechanisms that cause the onset of adrenarche and ensure its control have not been fully clarified. In a study carried out in our country, the frequency of premature adrenarche in girls aged 4-8 was found to be 4.3%. Premature adrenarche is a benign condition that does not require treatment, but studies have reported that diseases such as hyperinsulinism, ovarian hyperandrogenism and abnormal lipid profile are observed more frequently in the follow-up of patients with PA. Some studies about obese adolescents with PA have examined the role of lipid accumulation in the abdominal cisterna and insulin-sensitive tissues, in relation to the presence of insulin resistance. It is accepted that coagulation factors, blood flow and lipid infiltration are important in atherosclerosis development and its clinical sequelae. This indicates that in cases with PA, metabolic syndrome (MeS) risk factors may be seen with more than one component. A chronic subclinical inflammation may play a role in the etiopathogenesis of these complications, which are also observed in premature adrenaritis. Our aim in this study is to compare the serum inflammatory markers interleukin-6 (IL-6), highly sensitive C-reactive protein (hsCRP) and Fetuin-A levels of patients with PA with the control group. The secondary aim of our study is to compare metabolic syndrome risk factors (insulin resistance, dyslipidemia, hypertension, obesity) in patients with PA with the control group and to investigate their correlations with inflammatory markers. Patients who applied to Sivas Cumhuriyet University Medical Faculty Hospital Pediatric Department, Pediatric Endocrinology outpatient clinic between October 1, 2020 and January 31, 2021 were included in the study. After 8-12 hours of fasting, blood was taken from all cases and IL-6, hsCRP and Fetuin-A levels were studied. In addition, by scanning the patients' files, the levels of the following values that were routinely taken for diagnosis and differential diagnosis in all patients diagnosed with PA were evaluated; hemogram (hemoglobin (Hgb), white blood cell (WBC), red blood cell (RBC), platelet (PLT), mean cell volume (MCV), mean platelet volume (MPV)), blood sugar, urea, creatinine, aspart aminotransferase (AST), alanine aminotransferase (ALT), high density lipoprotein (HDL), low density lipoprotein (LDL), triglyceride cholesterol, sodium, potassium, chlorine, calcium, magnesium, phosphorus, alkaline phosphatase (ALP), free T4, thyroid stimulating hormone (TSH), insulin, DHEAS, total testosterone, 17-hydroxyprogesterone (17-OH PG). Besides, the tests performed on the control group were used if they had been present in the file, otherwise only special parameters (IL-6, hsCRP and Fetuin-A) were evaluated. The mean age at admission to our study was 7.19 ± 0.71 years. The mean age in the case group was 7,34±0,62 years, while the mean age in the control group was 7,09±0,77 years. There was no statistically significant difference in age between the case group and the control group (p>0,05) 82% (n=70) of the children participated in the study were girls. 85,7% (n=30) of the cases with PA were girls. At cases with premature adrenarche, the mean bone age was 8,07 ± 0,88 years. Bone age measurements of the cases included in the control group were not routinely performed, they were included in the study if they were available in the system scan. The mean bone age of the control group was 6,7 ± 1,6 years, while the lowest measurement was 4,5 years and the highest measurement was 10 years. In the children with PA participating in the study, the mean body weight (BW) was 27,6±4,7 kg, while it was 23,4±5,03 kg in the control group (p 0.05). When the hematological parameters of the study participants were examined, the mean Hgb value was 13,8±0,90 g/dL in the case group and 13,3±0,7 g/dL in the control group. The difference between the Hgb values of these two independent groups was statistically significant (p=0.015). There was no significant difference between the case and control groups in terms of WBC, PLT, mean cell volume (MCV), mean platelet volume (MPV) values (p>0.05). When lipid parameters (HDL, LDL, triglyceride, cholesterol) were evaluated, no significant difference was found between the case and control groups. No significant difference was found between the case and control groups in the plasma atherogenic index (PAI) calculated from lipid parameters. When the case and control groups were compared in terms of biochemical parameters (fasting blood glucose, urea, creatinine, AST, ALT, sodium, potassium, chlorine, magnesium, phosphorus, ALP), no difference was found (p>0.05). However, there was a significant difference in calcium levels between the PA and control groups (p<0.05). Mean insulin levels were 10,9±6,21 Uu/mL in premature adrenarche patients, while it was 7,4±5,9 Uu/mL in the control group. When these two independent groups were compared statistically, fasting insulin value was found to be significantly higher in patients with PA (p<0.05). When androgen levels were examined in the participants, the mean testosterone level was 0,62±2,2 ng/dL in all cases participating in the study. A significant difference was obtained since the testosterone level was 1,25±3 ng/dL in PA patients, while it was 0,18±1,2 ng/dL in the control group (p<0.05). DHEAS levels were resulted as 52,4±47,02 µg/dL in all cases, 76,3±45,2 µg/dL in PA patients and 31,5±38.1 µg/dL in the control group. This situation was found to be significant as expected (p<0.05). Inflammatory markers evaluated in our study were IL-6, Fetuin-A and hsCRP. When the PA and control groups were compared, Fetuin-A and hsCRP levels were similar. However, the mean value of IL-6 levels was 5,41±10,98 among all cases, while it was 8,5±16,01 in the patients with PA and 3,02±2,62 in the control group. This difference was statistically significant (p<0.05) In conclusion, the high levels of IL-6 we show in patients with PA are an indicator of a chronic subclinical inflammation in these children. These children have an increased risk of MeS risk factors and polycystic ovary syndrome (PCOS) later in life. Therefore, these children should be followed closely in terms of metabolic parameters. Prospective studies with higher case numbers are needed on this subject. Keywords: Adrenarche, DHEAS, IL-6, hsCRP, Fetuin-A