Prematür Adrenarşlı Hastalarda Parmak Oranları İle Hormon Düzeyleri Ve Metabolik Sendrom Komponentlerinin Karşılaştırılması

PINAR KOÇ

Prematür Adrenarşlı Hastalarda Parmak Oranları İle Hormon Düzeyleri Ve Metabolik Sendrom Komponentlerinin Karşılaştırılması

Thesis Type: Expertise In Medicine

Institution Of The Thesis: Sivas Cumhuriyet University, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Turkey

Approval Date: 2021

Thesis Language: Turkish

Student: PINAR KOÇ

Principal Supervisor (For Co-Supervisor Theses): Ayça Kömürlüoğlu Tan

Co-Supervisor: Nurullah Çelik

Open Archive Collection: AVESIS Open Access Collection

Abstract:

Introduction: Premature adrenarche (PA) is a clinical term used for the presence of pubic and / or axillary hair growth before the age of 9 in boys and 8 years in girls, without other clinical signs of puberty. PA is a common variation of normal; in which adrenal androgen production, particularly dehydroepiandrosteronsulfate (DHEAS) production begins at an unusually early age. PA, which is an early increase in adrenal androgen production, is a benign condition and does not require treatment, but the association of hyperinsulinism, ovarian hyperandrogenism, polycystic ovarian syndrome (PCOS), abnormal lipid profile has been reported in the long-term follow-up of cases with PA. Metabolic syndrome (MetS); is a condition with obesity, insulin resistance, high blood pressure, high fasting blood sugar, low high density lipoprotein (HDL) and high triglycerides. The diagnosis of MetS in adults has been linked to an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). PA is thought to be the precursor of MetS and PA may be associated with one or more components of MetS. Digit ratio (2P: 4P) is a biomarker of exposure levels to intrauterine sex hormones; There is strong evidence that this biomarker is negatively associated with prenatal androgen exposure; and positively associated with prenatal estrogen exposure. The fourth finger length is accepted as an indicator of the amount of testosterone and the second finger length as an indicator of the amount of estrogen. In this context, the low 2P: 4P value detected in men is associated with the high testosterone and low estrogen concentration exposed during the prenatal period. The number of interdisciplinary studies are increasing day by day on 2P: 4P, which has been a subject of interest recently in terms of reflecting the conditions that the individual is exposed to during prenatal process. In this study, anthromopetric measurements, sociodemographic characteristics, hormonal and other biochemical parameters, digit ratios of PA cases will be determined, compared with individuals in the control group, and the relationship between metabolic syndrome components and digit ratios will be examined. Materials and Methods: Patients who were admitted to Sivas Cumhuriyet University Medical Faculty Hospital Pediatric Endocrinology and General Pediatrics outpatient clinics between 15.03.2020-15.10.2020, diagnosed with PA and prebupertal healthy control group children without pubic hair growth at the time of admission; and who met the inclusion criteria and whose parents agreed to participate in the study were included in the study. Participants' age of onset, body weight (BW), BW SDS, height, height SDS, BMI, BMI SDS, calendar age, bone age, pubic hair growth, axillary hair growth, systolic and diastolic blood pressure, waist circumference, hip circumference, length of the 2nd and 4th fingers of both hands and the ratio of 2P: 4P were recorded on the follow-up form. 2P: 4P was calculated as the length of the 2nd finger divided by the length of the 4th finger. AIR (Average of index and ring finger) was calculated with the formula 2P + 4P / 2, MIDRL (Multiplying index of digit ratio and length) ((2P + 4P) / 2) X (2P / 4P) formula. Fasting blood glucose, insulin, insulin resistance parameters (HOMA-IR, FIGR, OUICKI), androgen levels (DHEAS, testosterone), lipid profile (total cholesterol, LDL, HDL, TG, VLDL) and other biochemical parameters were recorded. The data were evaluated with the SPSS 22. package program. The study was approved by Sivas Cumhuriyet University Non-Interventional Clinical Research Ethics Committee. Results: 49 patients diagnosed with premature adrenarche and 41 control group individuals were included in the study. 88.9% of the cases were female. The mean age of the case group was 7.078 ±, 74 years, and the mean age of the control group was 7.38 ± 0.78 years. The average bone age of patients with PA is 8.1 ± 1.15 years (minimum 5.8 years – maksimum 10.8 years). The mean age of onset of the complaints was 6.63 ± 1.07 years. The mean birth weight of the patients with PA was statistically significantly lower than the control group (p 0.05). Fasting blood glucose, fasting insulin, HOMA-IR values were statistically significantly higher in patients with premature adrenarche compared to the control group (p 0.05). The mean DHEA-S level was 85.92 ± 53.61 μg / dl in the case group and 27.33 ± 26.9 μg/dl in the control group, and it was statistically significantly higher in PA patients compared to the control group (p = 0.001) . There was no significant difference between the case and control groups in terms of total testosterone level (p = 0.096). When digit ratios were examined, the mean right 2P: 4P value was 0.958 ± 0.033 in the case group and 0.95 ± 0.032 in the control group. The mean left 2P: 4P value was 0.972 ± 0.037 in the case group and 0.96 ± 0.039 in the control group. There was no statistically significant difference in digit ratios between the case and control groups (p> 0.05). Right hand and left hand AIR and MIDR averages were statistically significantly higher in the premature adrenarche group compared to the control group (p <0.05). When digit ratios were evaluated by gender, the mean right 2P: 4P value was 0.958 ± 0.031 in girls and 0.929 ± 0.036 in boys. Right 2P: 4P ratio was higher in girls than boys and the difference was statistically significant (p = 0.009). There was no statistically significant correlation between right 2P: 4P ratio and fasting blood glucose, fasting insulin, HOMA-IR, FIGR, and QUICK1.Birth weight, week of gestation, onset age of complaints, bone age, waist circumference / hip circumference ratio, body weight, height, mean BMI and SDS, DHEA-S, total testosterone, 17-OH PG in patients with premature adrenarche. When the correlation between left hand 2P:4P and the same parameters was examined, there was a negative, moderate, statistically significant correlation between left 2P:4P and the DHEAS level (r = -0.341 p = 0.017). There was a negative, weak and statistically significant correlation between the left hand 2P:4P ratio and SBP SDS (r = -0.294 p = 0.04). There was a positive, weak, statistically significant correlation between the left hand 2P:4P ratio and the waist circumference / hip circumference ratio (r = 0.299, p = 0.037). There was a positive, high and statistically significant correlation between the right MIDRL ratio and height SDS (r = 0.648 p <0.001). There was a positive, moderate and statistically significant correlation between left MIDRL ratio and bone age, BW SDS (r = 0.505 p <0.001) (r = 0.430 p = 0.002). There was a positive, high and statistically significant correlation between left MIDRL ratio and height SDS (r = 0.612 p <0.001). There was a weak and positive correlation between BMI SDS and right and left MIDRL ratios, and it was statistically significant (r = 0.250 R = 0.295 p <0.05). When the right and left-hand MIDRL ratios of individuals in the case group were compared with metabolic syndrome parameters and androgen levels, there was a moderate and statistically significant positive correlation between left MIDRL ratio and fasting blood glucose, HOMA- IR and DHEAS levels (r = 0.389, p = 0.006), (r = 0.357, p = 0.0012), (r = 0.253, p = 0.016). There was a moderate and statistically significant negative correlation between left MIDRL ratio and insulin resistance parameters FIGR and QUICKI (r = -0.324 p = 0.023) (r = -0.420 p = 0.003). There was a moderate and statistically significant negative correlation between the right MIDRL ratio and QUICKI (r = -0.340 p = 0.017). Discussion: In our study, in accordance with the literature, individuals with PA had higher BW, height, BMI averages and SDS compared to the control group, and bone age was moderately advanced. Our SGA rate was considered to be lower than the literature. Fasting blood glucose, insulin and insulin resistance parameters were found to be significantly higher in PA patients compared to the control group. There was a high rate of type 2 DM, CVD and PCOS in the families of our PA cases. In line with the findings, PA should not be seen as just a normal puberty variant, it should never be forgotten that it is a prenatal-onset polyendocrine metabolic disorder, and all patients should be closely followed in terms of risk factors (insulin resistance, PCOS, etc.). In our study, no difference was found between the digit ratios of patients with PA and control group. This result; did not support the hypothesis that PA developed with intrauterine androgen exposure. However, it was thought that the insufficient number of cases and gender imbalance may also cause this situation. The main reason for the relationship between MIDRL ratio and height SDS was considered to be the parallelism between finger lengths and growth of individuals. In line with our findings showing the relationship between metabolic syndrome components and digit ratio parameters (DHEA-S level, systolic blood pressure SDS, correlation between waist / hip circumference ratio and left hand 2P: 4P ratio, correlation between HOMA-IR, FIGR and QUICKI and left MIDRL ); We think that in premature adrenarche cases, digit ratio 2P:4P can be used to give an idea about metabolic syndrome components. More comprehensive studies with a higher number of cases to be conducted will provide more informative data on this subject.