Objective: Treatment of subclinical hypothyroidism (ScH), especially the mild form of ScH, is controversial because thyroid hormones influence cardiac function. We investigate left ventricular systolic and diastolic function in ScH and evaluate the effect of 5-month levothyroxine treatment. Subjects and methods: Fifty-four patients with newly diagnosed mild ScH (4.2 < TSH < 10.0 mU/L) and 30 euthyroid subjects matched by age were analysed. Laboratory analyses and an echocardiography study were done at the first visit and after 5 months in euthyroid stage in patients with ScH. Results: Compared to healthy controls, patients with ScH had a lower E/A ratio (1.03 ± 0.29 vs. 1.26 ± 0.36, p < 0.01), higher E/e' sep. ratio (7.62 ± 2.29 vs. 6.04 ± 1.64, p < 0.01), higher myocardial performance index (MPI) (0.47 ± 0.08 vs. 0.43 ± 0.07, p < 0.05), lower global longitudinal strain (GLS) (-19.5 ± 2.3 vs.-20.9 ± 1.7%, p < 0.05), and lower S wave derived by tissue Doppler imaging (0.077 ± 0.013 vs. 0.092 ± 0.011 m/s, p < 0.01). Levothyroxine treatment in patients with ScH contributed to higher EF (62.9 ± 3.9 vs. 61.6 ± 4.4%, p < 0.05), lower E/e' sep. ratio (6.60 ± 2.06 vs. 7.62 ± 2.29, p < 0.01), lower MPI (0.43 ± 0.07 vs. 0.47 ± 0.08%, p < 0.01), and improved GLS (-20.07 ± 2.7 vs.-19.55 ± 2.3%, p < 0.05) compared to values in ScH patients at baseline. Furthermore, in all study populations (ScH patients before and after levothyroxine therapy and controls), TSH levels significantly negatively correlated with EF (r =-0.15, p < 0.05), E/A (r =-0.14, p < 0.05), GLS (r =-0.26, p < 0.001), and S/TDI (r =-0.22, p < 0.01) and positively correlated with E/e' sep. (r = 0.14, p < 0.05). Conclusion: Patients with subclinical hypothyroidism versus healthy individuals had subtle changes in certain parameters that indicate involvement of systolic and diastolic function of the left ventricle. Although the values of the parameters were in normal range, they were significantly different compared to ScH and the control group at baseline, as well as to the ScH groups before and after treatment. The results of our study suggest that patients with ScH must be followed up during treatment to assess improvement of the disease. Some of the echocardiography obtained parameters were reversible after levothyroxine therapy.

Aim: During diabetic pregnancy, complex metabolic changes occur in the lipid profile. The aim of the study was to determine the predictive values of maternal serum lipid levels on large-for-gestational age newborns during the third trimester in pregnancies of women with type 2 diabetes mellitus (DM2) and gestational diabetes mellitus (GDM). Material and methods: Data of forty three pregnancies of women with DM2 and two hundred women with GDM were analyzed. The analysis encompassed the following parameters: age, body mass index (BMI), lipid parameters, HbA1c in first, second and third trimester of pregnancy, preeclampsia and baby birth weight. Results: DM2 and GDM groups showed statistically significant differences in the following variables: total lipids, triglycerides, total cholesterol, BMI, age, baby birth weight, incidence of SGA and preterm delivery (9.4 ± 2.3 vs. 11.0 ± 2.3 mmol/L, 2.4 ± 1.4 vs. 3.4 ± 1.6 mmol/L, 5.5 ± 1.2 vs. 6.4 ± 1.4 mmol/L, 30.6 ± 5.4 vs. 26.9 ± 5.2 kg/m 2 , 34 ± 7.8 vs. 31.5 ± 5.6 years, 3183 ± 972 vs. 3533 ± 699 g., 20% vs. 7.5%, 27.9 vs. 14%, respectively, p < 0.05). Linear multiple regression analysis demonstrated that triglycerides, LDL-C and total cholesterol were independent predictors of LGA (p < 0.05). Conclusion: Triglycerides and LDL-C in the third trimester of pregnancy are independent predictors for fetal macrosomia in DM2 and GDM pregnancies. Thus, the maternal serum triglycerides and LDL-C levels determined in the maternal blood taken in the third trimester of pregnancy may indentify women who will give birth to LGA newborns.

Introduction: Gestational Diabetes Mellitus (GDM) is glucose intolerance diagnosed for the first time in pregnancy. It may lead to potentially serious short term and longterm complications for both mother and fetus or newborn. Material and Methods:Prospective study was conducted at the University clinic for gynecology and obstetrics, Skopje for the period of one year. 100 pregnant women in the second trimester which performed oral glucose tolerance test (75g OGTT) were evaluated. The study included 50 women with GDM and control group of 50 women with negative OGTT at the same gestational age, parity and maternal age. Gestational weight gain, blood pressure and urine analysis for proteinuria were recorded monthly. Patients with GDM were more often followed according to the clinical protocol. Maternal and neonatal data was collected after birth from medical records during discharge from the clinic. The perinatal outcome of pregnant women with or without GDM was analysed.Results: There was a significant difference in BMI between the women with GDM and normoglycemic women. Hypertensive disorders of pregnancy, preterm labour and delivery by caesarean section were significantly more often in GDM pregnancies vs control group. Respiratory distress, hypoglycemia, pH <25, lower Apgar score in the first minute and admission in the neonatal intensive care unit was significantly more often in the neonates from mothers with GDM vs controls. Conclusion:Many parameters of the perinatal outcome were significantly associated with GDM in our study. Adequate treatment can achieve better maternal and neonatal outcome.

Aim: To estimate the prevalence of impaired glucose tolerance (IGT) and diabetes mellitus type 2 (DMT2), as well as the predictors for glucose abnormalities in women with polycystic ovary syndrome (PCOS). Material and methods: A cross-sectional study with 80 consecutive patients with newly diagnosed PCOS who underwent the standard 75g oral glucose tolerance test (OGTT) and the measurement of sex steroid hormone and lipid profile. Results: According to the results from the OGTT, 63% had a normal test (NT), 23% had IGT, and 9% had DMT2. The NT group was younger with lower BMI than IGT and DMT2 groups (25.1 ± 7.3, 31.5 ± 6.5, 37.4 ± 4.0 years, and 29.1 ± 8.3 kg/m2, 31.7 ± 4.6 kg/m2, and 34.5 ± 5.6 kg/m2, respectively). The testosterone levels were highest in the group with a normal test (2.7 ± 0.8 nmol/l) and lowest in the DMT2 group (1.9 ± 0.8 nmol/L), with statistical significance. The sex hormone bounding globulin (SHBG) levels were low in all three groups, with statistically significant differences between NG and IGT, and the NT and DMT2 groups. The multivariate linear regression model identified age, BMI, SHBG and testosterone as major independent predictors for abnormal glucose metabolism. Conclusion: It seems that the prevalence of IGT and DMT2 among PCOS women in our country is not as high as in Western countries. Age, BMI, and SHBG increase the risk for the development of IGT and DMT2. Thus, close monitoring of older, obese women with low SHBG is needed because of the higher risk for the development of IGT and DMT2 in such patients.

Objectives: The coronavirus pandemic was associated with a high mortality rate in the Republic of North Macedonia. Finding early markers of the disease’s severity may predict outcomes and guide the treatment of the disease. The aim of our study was to evaluate the role of inflammatory markers in predicting the outcome of COVID-19 in hospitalized patients. Methods: The study included 104 PCR-confirmed COVID-19 patients who underwent hospital treatment at the Institute of Lung Diseases and Tuberculosis in Skopje, North Macedonia, between November 2020 and May 2021. Inflammatory markers were assessed in all patients and correlated with the disease severity and outcome in terms of survival or death. Results: IL-6 and LDH at admission were significantly elevated in patients with a severe or critical form of the disease and among non-survivors. In addition, IL-6 showed 87.9% of sensitivity and 61.8% of specificity for distinguishing non-survivors from survivors with a cut-off value of 21.7 pg/ml in the receiver operator curve (ROC). Procalcitonin was significantly increased in non-survivors. Parallel to the increase of disease severity, the values of CRP and LDH increased significantly during hospitalization. Conclusion: The results of the study indicate that a significant association exists between the highly increased levels of CRP, LDH, IL-6 and procalcitonin and the severity of the disease and mortality in COVID-19 patients. Their measurements and follow-up during the course of the disease could be used as predictors for prognosis and outcome but also as a subject for targeted therapy.