Increased Severity of Presentation Signs in Children with Newly Diagnosed Type 1 Diabetes during the COVID-19 Pandemic: A Tertiary Center Experience.

INTRODUCTION: Diabetic ketoacidosis (DKA) is an important complication of type 1 diabetes mellitus (T1DM) which is worsened when the diagnosis of T1DM is delayed. The aim of this study was to evaluate the presentation patterns, severity, autoantibody status, and seasonal variability of newly diagnosed T1DM patients during the pandemic period of 2 years compared to those in the pre-pandemic period. METHODS: In this single tertiary center retrospective cohort study, newly diagnosed T1DM patients were grouped as pre-pandemic and pandemic period. Age, gender, the month of diagnosis, hemoglobin A1c, venous blood gas parameters, duration of symptoms, glutamic-acid-decarboxylase-antibody (anti-GAD), islet-cell antibody (ICA), and insulin autoantibody levels were recorded. The data obtained were compared between the groups. RESULTS: Number of patients presenting with DKA was significantly higher during the pandemic period (92 [65.7%] vs. 62 [40.8%] patients, p < 0.001). In terms of clinical severity of DKA, pH, and HCO3 levels were lower during the pandemic period (p < 0.001), while the number of patients presenting with severe DKA was significantly higher during the pandemic period (41 [44.6%] vs. 17 [27.4%] patients, p = 0.031). ICA positivity was significantly higher in patients admitted during the pandemic period (47 [36.4%] vs. 21 patients [16.9%], p < 0.001), especially in the second year of the pandemic (p < 0.001). Anti-GAD-ICA co-positivity was significantly higher in patients admitted during the pandemic period and also in second year of the pandemic (p < 0.001). CONCLUSION: DKA rates increased in newly diagnosed T1DM cases during the pandemic. Despite the relaxation of bans, the second year of the pandemic also saw increased rates of DKA and severe DKA compared to the pre-pandemic period. The significantly increased ICA positivity in the pandemic may support the effects of COVID-19 on autoimmune T1DM.

Pathogenic variants in RNPC3 are associated with hypopituitarism and primary ovarian insufficiency.

PURPOSE: We aimed to investigate the molecular basis underlying a novel phenotype including hypopituitarism associated with primary ovarian insufficiency. METHODS: We used next-generation sequencing to identify variants in all pedigrees. Expression of Rnpc3/RNPC3 was analyzed by in situ hybridization on murine/human embryonic sections. CRISPR/Cas9 was used to generate mice carrying the p.Leu483Phe pathogenic variant in the conserved murine Rnpc3 RRM2 domain. RESULTS: We described 15 patients from 9 pedigrees with biallelic pathogenic variants in RNPC3, encoding a specific protein component of the minor spliceosome, which is associated with a hypopituitary phenotype, including severe growth hormone (GH) deficiency, hypoprolactinemia, variable thyrotropin (also known as thyroid-stimulating hormone) deficiency, and anterior pituitary hypoplasia. Primary ovarian insufficiency was diagnosed in 8 of 9 affected females, whereas males had normal gonadal function. In addition, 2 affected males displayed normal growth when off GH treatment despite severe biochemical GH deficiency. In both mouse and human embryos, Rnpc3/RNPC3 was expressed in the developing forebrain, including the hypothalamus and Rathke's pouch. Female Rnpc3 mutant mice displayed a reduction in pituitary GH content but with no reproductive impairment in young mice. Male mice exhibited no obvious phenotype. CONCLUSION: Our findings suggest novel insights into the role of RNPC3 in female-specific gonadal function and emphasize a critical role for the minor spliceosome in pituitary and ovarian development and function.

Breakfast and dinner insulin index and insulin load in relation to overweight in children and adolescents.

PURPOSE: Hyperinsulinemia is related to the development of several chronic diseases, particularly obesity. Therefore, this study aimed to examine the association between the insulinemic potential of both total diet and meals, measured by the glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL), and overweight risk among children and adolescents. METHODS: This cross-sectional study was conducted on 205 overweight and 146 normal-weight participants aged 6-18 years. Overweight was defined as body mass index ≥ 85th percentile of Turkish growth-reference data. Through the use of standard methodology, dietary and meal GI, GL, II, and IL were derived from dietary data collected via a 3-day dietary record. Associations were investigated using multivariable-adjusted regression analysis. RESULTS: When controlling for potential covariates, a greater dietary II (OR 2.69, 95% CI 1.28, 5.68) and IL (OR 5.22, 95% CI 2.39, 11.38), as well as GL (OR 3.89, 95% CI 1.77, 8.56), was strongly associated with higher odds of overweight (both Pfor trend < 0.001). Furthermore, breakfast GL (OR 4.87, 95% CI 2.15, 11.01), II (OR 3.88, 95% CI 1.79, 8.39), IL (OR 4.93, 95% CI 2.20, 11.05) and dinner GL (OR 2.39, 95% CI 1.10, 5.20), II (OR 3.81, 95% CI 1.73, 8.41), IL (OR 3.63, 95% CI 1.67, 7.91) were found to be a significant independent predictor of overweight (all Pfor trend < 0.001) in pediatric population. CONCLUSION: Our results suggest that dietary insulin demand, particularly for breakfast and dinner, was independently associated with overweight in children and adolescents. These findings may shed light on the relevance of considering meal insulin demand while developing dietary strategies in this population.

A potential serious complication in infants with congenital obstructive uropathy: Secondary pseudohypoaldosteronism.

Patients who have secondary pseudohypoaldosteronism (PHA) in addition to hyponatraemia, hyperpotassaemia and high serum aldosterone levels for the age were included in this retrospective study.Among eight patients, seven patients were diagnosed with PHA secondary to obstructive uropathy (OUP), whereas one patient had PHA secondary to ileostomy. Six patients with OUP had simultaneous urinary tract infection (UTI) and in all except one patient, secondary PHA recovered with only UTI treatment before applying surgical correction. All the patients were younger than 3 months age. In three patients with PUV diagnosis, salt wasting recurred in an UTI episode under 3 months of age.

Urinary levels of pyridinoline and deoxypyridinoline and bone mineral density in children with type 1 diabetes mellitus.

OBJECTIVE: There is still controversy over the impact of diabetes mellitus (DM) on bone mass in children. Pyridinoline (Pyr) and deoxypyridinoline (DPyr), which stabilize the collagen chains within the extracellular matrix, are known as specific bone turnover markers. The aim of this study was to investigate the relationship between urinary Pyr and DPyr excretions and bone mineral density (BMD) in children with type 1 DM. METHODS: Serum levels of Ca, phosphorus (P), magnesium (Mg), and parathormone (PTH), alkaline phosphatase (ALP) activity, and urinary excretions of Pyr and DPyr were evaluated in 50 diabetic and 130 healthy control subjects aged between 7 and 15 years. The BMD was measured using DEXA at the lumbar vertebrae 2-4. RESULTS: Serum levels of Ca, P and PTH, and BMD were similar between the two groups (p > 0.05). The serum ALP activity was significantly higher in diabetics than in healthy subjects (257.7 ± 86.5 vs. 188.2 ± 61.8, p < 0.05, respectively). Both urinary Pyr and DPyr excretions were significantly higher in diabetic subjects compared to control subjects (127.4 ± 95.5 vs. 88.7 ± 63.7, p < 0.05, respectively, and 23.6 ± 12.7 vs. 17.2 ± 9.6, p < 0.05, respectively). The urinary excretions of Pyr and DPyr were similar in male and female subjects within both groups. CONCLUSION: The urinary excretions of Pyr and DPyr are higher in diabetic subjects than in healthy controls, suggesting the presence of increased bone turnover in diabetic patients, but we could not observe any negative effect of childhood diabetes on BMD. These results may suggest that diabetic patients are at risk for a decreased peak bone mass.

Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome.

To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups.

The endocrine disruptor bisphenol A may play a role in the aetiopathogenesis of polycystic ovary syndrome in adolescent girls.

AIM: Experimental in vitro studies have shown that bisphenol A affects steroidogenesis, folliculogenesis and ovarian morphology. The aim of this study was to investigate the role of the endocrine disruptor bisphenol A in the aetiopathogenesis of polycystic ovary syndrome (PCOS) in adolescents and its relationship with metabolic parameters, insulin resistance and obesity in this population. METHODS: A total of 112 girls with PCOS and 61 controls between 13 and 19 years of age were enrolled in the study. Serum bisphenol A levels were measured by high-pressure liquid chromatography. An oral glucose tolerance test was also performed. RESULTS: Adolescents with PCOS had markedly increased serum bisphenol A levels (mean: 1.1 ng/mL 95% CI: 1.0-1.2) than controls (mean: 0.8 ng/mL 95% CI: 0.6-0.9, p = 0.001). When we compared the subgroups according to obesity, the main factor determining the significant increase in bisphenol A was the presence of PCOS, but not obesity (p = 0.029). Bisphenol A was significantly correlated with total testosterone (r = 0.52), free testosterone (r = 0.44), dehydroepiandrosterone sulphate (r = 0.37) and Ferriman-Gallwey score (r = 0.43) (p < 0.05). CONCLUSION: Adolescents with PCOS had higher serum bisphenol A levels than controls, independent of obesity. Bisphenol A concentrations were significantly correlated with androgen levels, leading us to consider that bisphenol A might play a role in the aetiopathogenesis of PCOS in adolescents.

Fatty liver is a good indicator of subclinical atherosclerosis risk in obese children and adolescents regardless of liver enzyme elevation.

AIM: To investigate the presence of association between nonalcoholic fatty liver disease (NAFLD) and subclinical atherosclerosis using carotid intima media thickness (c-IMT) in obese children and adolescents. Additionally, we wished to investigate the relationship between fatty liver and elevated liver enzymes. METHODS: A total of 157 obese patients (78 boys and 79 girls, mean age: 11.3 ± 2.6 years, age range: 6-16 years) were enrolled in the study. Aminotransferase, fasting glucose and lipid levels were determined. An oral glucose tolerance test was performed. The c-IMT was measured. Infectious and metabolic causes of elevated liver enzymes were excluded. The diagnosis of NAFLD was based on ultrasound scan. RESULTS: Obese patients with NAFLD had markedly increased carotid IMT (mean: 0.48 mm, 95% CI: 0.47-0.49) than those without NAFLD (mean: 0.45 mm 95% CI: 0.44-0.45, p < 0.001). The presence of NAFLD significantly increased c-IMT whether the patient had elevated liver enzyme or not (ANOVA, p < 0.001). In a multiple-regression model, only the presence of NAFLD was associated with increased c-IMT (ß = 0.031, SE (ß) = 0.008, p < 0.001). CONCLUSION: Obese children and adolescents with NAFLD are at risk of early atherosclerotic changes. As liver function tests are not sufficient to identify patients with fatty liver, ultrasonographic evaluation of NAFLD might be considered in all obese children and adolescents.

Iodine deficiency: a probable cause of neural tube defect.

INTRODUCTION: Iodine deficiency is the most devastating event in developing brain in the fetus and neonate. Iodine is absolutely necessary on the myelination, neuronal differentiation, and formation of neural processes, synaptogenesis, and neuronal migration by thyroidal hormones throughout pregnancy and shortly after birth. Neural tube defects (NTD) form after third and fourth gestational weeks and their etiologies are multifactorial. CASE REPORT: We herein present a male newborn with iodine deficiency and thoracic neuroenteric cyst bound to a myelomeningocele via a pedinculi. We hypothesize that iodine deficiency may be a cause of NTD, and iodine supplementation in preconception and pregnancy may prevent NTD.

A National Multicenter Study of Leptin and Leptin Receptor Deficiency and Systematic Review.

CONTEXT: Homozygous leptin (LEP) and leptin receptor (LEPR) variants lead to childhood-onset obesity. OBJECTIVE: To present new cases with LEP and LEPR deficiency, report the long-term follow-up of previously described patients, and to define, based on all reported cases in literature, genotype-phenotype relationships. METHODS: Our cohort included 18 patients (LEP = 11, LEPR = 7), 8 of whom had been previously reported. A systematic literature review was conducted in July 2022. Forty-two of 47 studies on LEP/LEPR were selected. RESULTS: Of 10 new cases, 2 novel pathogenic variants were identified in LEP (c.16delC) and LEPR (c.40 + 5G > C). Eleven patients with LEP deficiency received metreleptin, 4 of whom had been treated for over 20 years. One patient developed loss of efficacy associated with neutralizing antibody development. Of 152 patients, including 134 cases from the literature review in addition to our cases, frameshift variants were the most common (48%) in LEP and missense variants (35%) in LEPR. Patients with LEP deficiency were diagnosed at a younger age [3 (9) vs 7 (13) years, P = .02] and had a higher median body mass index (BMI) SD score [3.1 (2) vs 2.8 (1) kg/m2, P = 0.02], which was more closely associated with frameshift variants (P = .02). Patients with LEP deficiency were more likely to have hyperinsulinemia (P = .02). CONCLUSION: Frameshift variants were more common in patients with LEP deficiency whereas missense variants were more common in LEPR deficiency. Patients with LEP deficiency were identified at younger ages, had higher BMI SD scores, and had higher rates of hyperinsulinemia than patients with LEPR deficiency. Eleven patients benefitted from long-term metreleptin, with 1 losing efficacy due to neutralizing antibodies.

The absence of insulin resistance in metabolic syndrome definition leads to underdiagnosing of metabolic risk in obese patients.

This study explores in a group of obese children and adolescents aged 10 to 16 years, the prevalence of metabolic syndrome (MS) according to the criteria of International Diabetes Federation (IDF). In addition, the prevalence of insulin resistance (IR) was investigated to find correlations between MS and IR. IDF definition was compared to a modified WHO definition. A total of 159 obese patients (74 male and 85 female; median age 12.7 years) were included in the study. Anthropometric measurements, blood pressure, and serum fasting lipids were evaluated. An oral glucose tolerance test (OGTT) was performed, and serum glucose and insulin levels were measured at 0, 30, 60, 90, and 120 min. Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), fasting glucose/insulin ratio (FGIR), Matsuda index, and total insulin levels during OGTT were calculated. For the IR diagnosis, we used cutoff values described in previous publications (HOMA-IR of >3.16, QUICKI of <0.357, FGIR of <7, and/or the sum of insulin levels during OGTT of >300 mIU/mL). MS prevalence, defined according to IDF criteria, was 34.6 %. Using the IDF definition, there was no statistically significant difference for the surrogate IR indices between patients with or without MS (QUICKI, 94.5 vs. 83.7 %), FGIR (81.1 vs. 78.8 %), HOMA-IR (70.9 vs. 63.5 %), and total insulin levels during OGTT (61.8 vs. 51.9 %). The Matsuda index values, the prevalence of fasting hyperinsulinemia, and impaired glucose tolerance were also similar in these two groups. In conclusion, IR was prominent in obese patients with and without MS. IDF definition of MS fails to discover individuals with IR, unless it is specifically investigated.

A case of diabetes mellitus associated with Rett syndrome.

Rett syndrome (RS) is a neurodevelopmental disorder mainly affecting girls. It is characterized by a normal prenatal and perinatal period, apparently normal development for the first 6 months of life, and then a decelaration in head growth, loss of hand and communication skills, psychomotor retardation, as well as the development of sterotyped hand movement and truncal or gait apraxia. It has been shown to be related to mutations in the MECP2 gene located on Xq28. Diabetes mellitus (DM) type 1 may be associated with certain genetic disorders such as Down syndrome, Turner syndrome, and Klinefelter syndrome. In this work, we report the case of a 9-year-old girl with RS who developed DM at the age of 6. To our knowledge, our patient is the third case reported to date of DM associated with Rett syndrome.

Increased endothelial microparticles in obese and overweight children.

BACKGROUND: Obesity in children increases the risk of atherosclerosis. Endothelial dysfunction is an important factor in the pathogenesis of atherosclerosis, and endothelial microparticles (EMPs) are considered as markers of endothelial dysfunction. In this study, we aimed to evaluate circulating EMPs in obese and overweight children and to disclose the measure of obesity with the strongest relation with circulating microparticles and carotid atherosclerosis. METHODS: This prospective study included 55 obese and overweight children and 23 healthy controls. Insulin resistance was studied. Both in vivo and in vitro human umbilical vein endothelial cell evaluations were used for the study. Circulating EMPs (CD144 and CD146) were measured by flow cytometry. The carotid artery intima-media thickness (cIMT) and left ventricular mass index (LVMI) were measured using ultrasound and echocardiography, respectively. Study groups were compared for anthropometric measurement, insulin resistance, circulating EMP, cIMT, and LVMI. The relationship among overweight, obesity, and circulating EMPs were investigated. RESULTS: Blood pressure, CD144+EMP levels, and LVMI were statistically higher in the patients group than in the control group. The multiple logistic regression analysis and the backward elimination method showed that CD144+EMP and systolic blood pressure had a linear relationship with overweight and obesity. CONCLUSION: Our results suggest that endothelial damage starts in the early stage of childhood obesity and that obese and overweight children have increased circulating CD144+EMPs, showing that endothelial dysfunction and increased CD144+EMPs may be related to obesity.

Health Effects Associated With Kratom (Mitragyna speciosa) and Polysubstance Use: A Narrative Review.

Background: Kratom (Mitragyna speciosa) consumption and associated health effects have raised debates in the United States. Although most people using this herb do not experience adverse health effects associated with kratom use, medical providers should be knowledgeable of emerging substances and concurrent, sequential, or simultaneous use of other drugs which may impact healthcare recommendations and prescribing practices. Methods: The objective of this narrative review was to elucidate selected health effects associated with using kratom-either alone or with other substances. Since scientifically controlled human subjects research on kratom use is still limited, relevant case reports were also described. Results: Cardiovascular, gastrointestinal, neurological, and psychiatric effects associated with kratom use were especially notable, and in-utero exposure accompanied concern regarding a neonate's risk for developing neonatal abstinence syndrome. Our ability to identify and understand the role of this herb in kratom-associated fatalities is complicated since kratom is not routinely screened for in standard forensic toxicology. If a screening is performed, it is usually for the major alkaloid, mitragynine, as a surrogate for kratom use. In addition to lacking a standard practice of screening decedents for kratom alkaloids, the association between mortality and kratom use may be confounded by polysubstance use, adulteration of kratom products, and drug-herb interactions. Conclusions: Increasing medical awareness of this herb is vital to ensuring prompt administration of best-practice medical advice or treatment for people seeking information related to kratom use or for patients experiencing an adverse health effect that may be associated with using or withdrawing from kratom. Knowledge gained from continued surveillance and study of kratom and its associated health effects may assist in guiding clinical decision-making and preventing development of adverse health effects among people using kratom.

The association of serum sialic acid with carotid intima-media thickness and anthropometric and metabolic parameters in obese children and adolescents.

BACKGROUND: Sialic acid (SA) has been shown to be a strong predictor of cardiovascular mortality in adults. No study in children regarding the association of SA with cardiovascular risks exists in the literature. AIM: We aimed to investigate the association of SA with anthropometric and metabolic parameters and its correlation with metabolic syndrome (MS) and carotid intima-media thickness (IMT) in obese children. METHODS: A total of 154 obese children were included in the study (74 females, 80 males; mean age 11.3 ± 2.6 years). Anthropometric measurements including body fat percentage (BFP) were recorded. Fasting lipids and SA levels were measured. The carotid IMT was evaluated with ultrasonography. RESULTS: We found a significant correlation between serum total SA (TSA) levels and BFP (r = 0.25, p = 0.01 in the whole group; r = 0.43, p = 0.00 in girls). The group with BFP ≥95th percentile had higher TSA levels than the group with BFP <95th percentile (p = 0.04). TSA and carotid IMT were weakly correlated (r = 0.20, p = 0.01), but the significance was lost after correcting for BFP. No correlations were found between TSA and other anthropometric measurements. TSA did not correlate with serum fasting glucose, lipids, insulin or homeostasis model assessment-insulin resistance. TSA levels were not different between children with or without MS. CONCLUSION: Serum TSA levels are significantly correlated with BFP in obese children.

Post-operative subcutaneous fat necrosis in a newborn: a case report.

Subcutaneous fat necrosis of the newborn (ScFN) is an uncommon condition of neonates and infants. The disorder is caused by generalized and local tissue hypoperfusion. The ScFN tends to improve spontaneously with or without some severe complications such as hypercalcemia. The ScFN may occur as iatrogenic after hypothermic surgical interventions. We present iatrogenic ScFN in a newborn with uncomplicated hypercalcemia due to cold exposure on operating table during at an umbilical cord hernia operation. To our knowledge, this is the first report of a patient in whom ScFN occurred during a commonly performed and relatively short-term "nonhypothermic" operation.

Evaluation of micronutrient levels in children and adolescents with obesity and their correlation with the components of metabolic syndrome.

BACKGROUND: Obesity is a significant public health problem worldwide. Vitamin deficiencies, developing due to monotype nutrition, are more likely to be observed in patients than healthy children. The present study evaluates vitamin and micronutrient levels in children and adolescents with obesity and metabolic syndrome compared to healthy controls. METHODS: The study included 73 patients with obesity, 64 patients with metabolic syndrome and 71 healthy children (control group) aged 10 to 16 years. Physical examinations were performed, and waist circumference and systolic blood pressure measurements were recorded. Fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, insulin, vitamin A, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, folic acid and free carnitine levels were analyzed. The homeostatic model of assessment-insulin resistance (HOMA-IR) index was calculated and recorded. RESULTS: The mean age of all patients was 11.9±2.6 years. The serum insulin level and HOMA-IR index were found to be significantly higher in the obesity and metabolic syndrome groups. No significant difference was found between the groups in terms of vitamin A, vitamin B6 and free carnitine levels. Significantly decreased vitamin E, vitamin B2, vitamin B12 and folic acid and increased vitamin B1 levels were observed in the obesity and metabolic syndrome groups. CONCLUSIONS: Compared to healthy children, children with obesity and metabolic syndrome may have varying degrees of micronutrient and vitamin deficiency due to poor and unbalanced eating habits. These deficiencies should also be considered in the treatment and follow-up of obesity and metabolic syndrome.

Primary adrenal failure due to viral infection in an infant.

Acquired primary adrenal insufficiency is a rare disorder in childhood. The most common cause is autoimmune adrenalitis, especially as a part of polyendocrinopathy syndromes. Impaired adrenal function is seen in patients infected with HIV. In adult patients with AIDS, cytomegalovirus (CMV)-associated adrenal insufficiency is a well-known condition, whereas CMV infection as a causing adrenal insufficiency in children is very rare. Here, we report an infant with transient adrenal insufficiency associated with CMV infection but without HIV. She was treated successfully with steroid replacement and ganciclovir. Early diagnosis and treatment is lifesaving in these patients.

Endocrine Disruptors and Polycystic Ovary Syndrome: Phthalates

Objective: We aimed to investigate a possible role of the endocrine disruptors phthalates, di-2-ethylhexyl phthalate (DEHP) and mono (2-ethylhexyl) phthalate (MEHP), in polycystic ovary syndrome (PCOS) aetiopathogenesis. We also wished to evaluate the relationship between phthalates and metabolic disturbances in adolescents with PCOS. Methods: A total of 124 adolescents were included. Serum MEHP and DEHP levels were determined by high-performance liquid chromatography. Insulin resistance was evaluated using homeostasis model assessment-insulin resistance, quantitative Insulin Sensitivity Check Index, fasting glucose/insulin ratio, Matsuda index, and total insulin levels during oral glucose tolerance test. Participants were further subdivided into lean and obese subgroups according to body mass index (BMI). Results: Sixty-three PCOS and 61 controls, (mean age 15.2±1.5; range: 13-19 years) were enrolled. Serum DEHP and MEHP concentrations were not significantly different between PCOS and control groups. The mean (95% confidence interval) values of DEHP and MEHP were 2.62 (2.50-2.75) µg/mL vs 2.71 (2.52-2.90) µg/mL and 0.23 (0.19-0.29) µg/mL vs 0.36 (0.18-0.54) µg/mL in PCOS and the control groups respectively, p>0.05. Correlation analysis, adjusted for BMI, showed that both phthalates significantly correlated with insulin resistance indices and serum triglycerides in adolescents with PCOS. Conclusion: Serum DEHP and MEHP concentrations were not different between adolescents with or without PCOS. However, these phthalates are associated with metabolic disturbances such as dyslipidemia and insulin resistance, independently of obesity, in girls with PCOS.