Feminizing Adrenocortical Tumors as a Rare Etiology of Isosexual/Contrasexual Pseudopuberty

Objective: Estrogen-secreting adrenocortical tumors (ACTs) are quite rare with feminizing adrenocortical tumors (FATs) accounting for 0.37-2% of all ACTs. The aim was to evaluate clinical and hormonal characteristics of FATS as well as treatment options and follow-up in the pediatric age group. Methods: Medical records of children with ACTs presenting to a single center in the last two decades were reviewed. Literature review within Pubmed revealed 34 pediatric patients (22 boys) with FAT among 192 articles. Results: Among the 25 children presenting with ACTs in the last two decades, two new pediatric cases of FAT were identified, one benign and the other malignant, in two genders with different clinical presentations. Literature review showed that FATs are extremely rare tumors that are most commonly seen in men and boys presenting with gynecomastia. FATs are more common in children ≤8 years of age, with a median age at diagnosis of six years. While boys present with contrasexual pseudopuberty signs, girls present with isosexual pseudopuberty. A high estrogen level strongly supports diagnosis, while elevations in other adrenal hormones may be seen. FATs are usually malignant in adults and prognosis is generally very poor. However, in children approximately half are benign although assessment of malignant potential depends on clinical behavior of the tumor. FATs are very unpredictable so even after surgery long-term follow-up is required. FATs presenting in childhood may have a better prognosis than adult presentation tumors as most FATs in children are followed without recurrence of tumor. Conclusion: FATs are more common in children ≤8 years of age, with a median age at diagnosis of six years. FATs in childhood may have a better prognosis than in adult males.

Approach to pheochromocytoma and paraganglioma in children and adolescents: A retrospective clinical study from a tertiary care center.

AIM: Pheochromocytoma (PCC) and paraganglioma (PGL) are rare tumors in childhood. They are catecholamine secreting tumors and present with signs or symptoms related to their excess. Most common signs and symptoms are hypertension, headache and diaphoresis. The management of children usually depend on experience of adulthood. This study is conducted to present the clinical characteristics, surgical management and outcome of childhood PCC and PGL in a tertiary care center. MATERIAL AND METHODS: We reviewed clinical records of all patients operated for PCC and PGL between 2000 and 2020 retrospectively. RESULTS: There were 18 children operated for PCC and PGL in the study period. The female to male ratio was 1:1. The median age at diagnosis was 13 (IQR, 9-15) years. The most common presenting symptoms were headache and diaphoresis. Hypertension was the most common sign. Three patients had von Hippel-Lindau (VHL). Tumors of two patients with VHL were detected during routine follow-up. Three patients had multifocal disease. Medical preparation for surgery was carried out in all patients. Antihypertensive treatments were administered preoperatively. Since the patients are at risk for postoperative hypotension due to chronic vasoconstriction and blood volume contraction, high salt diet was recommended. Intravenous normal saline at a rate of 3000 ml/m2 body surface area per day was started for intravascular volume expansion preoperatively. The mean duration for preoperative medication to achieve normal blood pressure was 22 days (range, 16-30). Twenty-five tumors were excised in eighteen patients. One patient who had bone metastases on diagnosis and is on I131MIBG therapy. The median follow-up time was 5.6 years (range, 1 months - 21 years). Five patients reached adulthood during the study period. Four of these had recurrent metastases (n = 2) and new tumors (pancreatic neuroendocrine tumor, n = 1 and pancreatic neuroendocrine tumor and renal cell carcinoma, n = 1) after the age of 18. CONCLUSION: Multidisciplinary approach is necessary to achieve safe surgical treatment and surveillance of PCC and PGL. Detection of associated familial cancer susceptibility syndromes and long-term follow-up is essential to detect late recurrences and new tumors.

Which parameters predict the beneficial effect of GnRHa treatment on height in girls with central precocious puberty?

OBJECTIVE: Data about GnRHa on adult height in girls with central precocious puberty (CPP) have shown variable results, ranging from improvement of growth prognosis to lack of any benefit. This study was designed to delineate the criteria to decide which girls with idiopathic CPP (iCPP) will have a height benefit from GnRHa treatment. DESIGN: Retrospective PATIENTS: 102 girls with iCPP who had reached final height (FH) were included. MEASUREMENTS: Auxological, hormonal and radiological findings at treatment onset, and FHs were extracted from records. RESULTS: Most important factor affecting height gain was chronological age (CA) at treatment onset. All the girls treated ≤6.4 years of age achieved a height gain of ≥1SDS, while none of the girls treated ≥8.3 years of age made the target. 75.6% of patients who started GnRHa between the ages of 6.4 and 8.3 years had a height gain of ≥1SDS. Most important factors affecting height gain in those treated 6.4-8.3 years were advanced bone age (BA), basal estradiol (E2 ) and pubertal stage (r2 : 0.906; P < .001). All individuals with BA advancement of ≥2.6 years or E2 of ≥32.6 pg/ml or pubertal stage of ≥3 had significant height gain, and none of the cases with BA advancement of <2 years or E2 of <21.5 pg/ml or pubertal stage of <2 had a height gain of ≥1SDS. CONCLUSIONS: Treatment with GnRHa is unquestionably beneficial to improve FH in girls with iCPP when initiated ≤6.4 years of age. GnRHa treatment after 8.3 years of age may not improve FH. Girls between the ages of 6.4 and 8.3 years at presentation can have a better height gain if BA (≥2.6 years over CA) and pubertal findings (pubertal stage ≥3 or E2 ≥32.6 pg/ml) are well-advanced.

Adrenocortical tumours in children: a review of surgical management at a tertiary care centre.

BACKGROUND: Adrenocortical tumours (ACT) are rare tumours of childhood usually presenting with endocrine dysfunction. This retrospective study is designed to review our institutional experience in surgical management. METHODS: Records of children treated for ACT between 1999 and 2019 were reviewed retrospectively. RESULTS: The median age of 24 children was 78 months. Fourteen patients had adrenocortical carcinoma, nine had adrenocortical adenoma and one had neuroendocrine differentiation of ACT. Endocrine dysfunction was noted in 79% of the patients. Five patients had preoperative chemotherapy but none had a decrease in tumour size. Transabdominal approach was used in all but two patients who had thoracoabdominal incision for excision of giant tumours and ipsilateral lung metastases. Two patients had visceral excision to achieve R0 resection. Five patients, four of whom had spillage and one with partial resection died of widespread disease. Two patients with stage 4 adrenocortical carcinoma are still on chemotherapy. All patients with stage I-III disease who had total excision without spillage (n = 17) are disease-free for 2-170 months. CONCLUSIONS: Our results show the importance of excision in ACT without spillage for survival. However, multicentre prospective studies should enhance the knowledge of children about ACT and develop alternative therapies for stage III and IV cases.

Alpha-Melanocyte-Stimulating Hormone is Elevated in Hypothalamic Obesity Associated with Childhood Craniopharyngioma.

OBJECTIVE: The purpose of this study was to investigate the peripheral concentrations of leptin and neuropeptides taking part in the melanocortin pathway in hypothalamic obesity (HO) associated with craniopharyngioma (CP) and to find a peripheral marker for diagnosis. METHODS: Thirty-one patients (52% girls; median age 16 years) with CP were enrolled in the study group. They were grouped as CP with obesity (CPobesity , n = 17) and CP without obesity (CPnonobesity , n = 14). Two control groups without CP consisted of 27 children with obesity (OC) (55% girls; median age 13.8 years) and 25 children without obesity (normal control [NC]) (72% girls; median age 14.5 years). Obesity was defined as BMI percentile ≥ 95%. Fasting serum concentrations of leptin, brain-derived neurotrophic factor (BDNF), and alpha-melanocyte-stimulating hormone (α-MSH) were measured in the groups. RESULTS: Leptin and BDNF concentrations were correlated with BMI SD score (SDS) in controls (OC + NC) and CP. However, there was no correlation between α-MSH and BMI-SDS in CP or control groups. After adjusting for age, sex, and BMI-SDS, α-MSH was found to be significantly higher in CPobesity than in other groups, whereas leptin and BDNF were comparable among the four groups. CONCLUSIONS: Serum BDNF, just like leptin, increased with BMI, regardless of hypothalamic damage. On the contrary, α-MSH concentration was significantly high in HO, designating a potential biomarker for HO in CP.

Obstructive sleep apnea in children with hypothalamic obesity: Evaluation of possible related factors.

INTRODUCTION: Hypothalamic obesity (HO) is a type of obesity that is caused by hypothalamic damage. HO can be complicated by obstructive sleep apnea syndrome (OSAS) due to anatomical narrowing of the upper airway and hypothalamic damage-induced dysfunction of the sleep control mechanisms. We aimed to explore the presence and severity of OSAS in children with HO and hypothesized that OSAS is more severe and frequent in HO than exogenous obesity (EO). METHODS: This cross-sectional study was conducted among children aged 6.6-17.9 years. Subjects with HO (n = 14) and controls with EO (n = 19) were consecutively recruited through an endocrinology clinic. All patients underwent full-night polysomnography. The primary outcomes were obstructive apnea-hypopnea index (OAHI) and the severity of OSAS. We analyzed the polysomnography findings, biochemical parameters, Brodsky and modified Mallampati scores, and blood pressure compared with the controls. We explored the different obesity types and these variables in association with OAHI using multiple linear regression (MLR). RESULTS: Age and body mass index z scores (BMI-z) were similar between the EO and HO groups. The OAHI of HO (5.8) was higher than that of EO (2.2). In MLR, the predicted OAHI was formulated as an equation using regression coefficients of obesity type (HO), age, and BMI-z (R2 = .41). In the logistic regression analysis, the odds ratio of moderate/severe OSA was 5.6 for HO. CONCLUSIONS: Children with HO have a higher risk of moderate/severe OSAS than children with EO. Polysomnography should be considered in all patients with HO.

Treatment with Depot Leuprolide Acetate in Girls with Idiopathic Precocious Puberty: What Parameter should be Used in Deciding on the Initial Dose?

Objective: Doses of gonadotropin releasing hormone (GnRH) analogues used to treat idiopathic central precocious puberty (iCPP) vary among clinicians. Study aims were to evaluate the efficacy of a monthly 3.75 mg dose of leuprolide acetate (LA) to suppress the hypothalamo-pituitary-gonadal (HPG) axis in girls with iCPP and to determine factors that may have an impact on the supressing dose. Methods: Study subjects were 220 girls receiving LA for iCPP. LA was started at a dose of 3.75 mg/28 days. Suppression was assessed using the GnRH test at the third month. To assess clinical suppression signs and symptoms of puberty were also evaluated. The dose of LA was increased to 7.5 mg/28 days in those who had a peak luteinising hormone (LH) ≥2 IU/L and in whom adequate clinical suppression of puberty was absent. Receiver operating characteristic curves were used to determine thresholds for clinical and hormonal factors affecting the suppressing dose of LA. Logistic regression analyses were used to investigate thresholds which might differentiate between those requiring high dose for suppression and those in whom lower dose LA was adequate. Results: Peak stimulated LH <2 IU/L was achieved in 88.6% with a dose of LA of 3.75 mg (0.11±0.03 mg/kg). Significant variables for differentiating the two doses were body weight (Wt) of 36.2 kg and/or body mass index (BMI)-standard deviation scores (SDS) of 1.64 (p<0.001). Multiple logistic regressions showed that Wt and BMI-SDS values above thresholds indicated requirement of LA at a dose of 7.5 mg/28 days (p<0.001). Conclusion: Monthly injections of 3.75 mg LA is an effective treatment in the majority of girls with iCPP. However, a higher initial dose may be preferred in patients with a Wt ≥36 kg or BMI-SDS ≥1.6 for effective suppression of the HPG axis.

A pheochromocytoma case diagnosed as adrenal incidentaloma.

Vuralli D, Kandemir N, Clark G, Orhan D, Alikasifoglu A, Gönç N, Ekinci S, Özön A. A pheochromocytoma case diagnosed as adrenal incidentaloma. Turk J Pediatr 2017; 59: 200-206. There are two problems that needs to be addressed in cases of an adrenal incidentaloma. The first is to decide whether the adrenal mass is benign or malignant, and the second is to determine whether the mass is hormonally active or not. A 17-year-old male was admitted with the complaint of progressive weight gain. Abdominal ultrasonography was performed for elevation in transaminases which revealed a hypoechoic mass located in the left adrenal gland. Hormonal investigations revealed an increase in fractionated catecholamine and metanephrine levels in 24-hour urine. Surgery was performed and pathological examination was in accordance with pheochromocytoma. Mutation analysis was carried out. This is a rare case of pheochromocytoma presenting as adrenal incidentaloma during adolescence. In view of this case, we review the approach to incidentally discovered adrenal masses and the approach to pheochromocytoma. A mutation analysis should be performed on all cases with pheochromocytoma that are diagnosed below age 20.

Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes.

Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of pituitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients.

Growth Hormone Deficiency in a Child with Neurofibromatosis-Noonan Syndrome.

Neurofibromatosis-Noonan syndrome (NFNS) is a distinct entity which shows the features of both NF1 (neurofibromatosis 1) and Noonan syndrome (NS). While growth hormone deficiency (GHD) has been relatively frequently identified in NF1 and NS patients, there is limited experience in NFNS cases. The literature includes only one case report of a NFNS patient having GHD and that report primarily focuses on the dermatological lesions that accompany the syndrome and not on growth hormone (GH) treatment. Here, we present a 13-year-old girl who had clinical features of NFNS with a mutation in the NF1 gene. The case is the first NFNS patient reported in the literature who was diagnosed to have GHD and who received GH treatment until reaching final height. The findings in this patient show that short stature is a feature of NFNS and can be caused by GHD. Patients with NFNS who show poor growth should be evaluated for GHD.

Surgical and clinical strategies in the management of thyroid medullary carcinoma in children with and without ret proto-oncogene mutations.

Medullary thyroid carcinoma (MTC) may arise sporadically or in familial manner. We presented sporadic and familial cases with MTC in order to raise awareness on management of such patients. Three medullary thyroid carcinoma (MTC) cases were presented. Case 1 had RET634 mutation; managed with total thyroidectomy (TT) and cervical lymph node dissection (CLND). Case 2 had RET804 mutation; managed with prophylactic TT. Case 3 had thyroid nodule; managed with TT and CLND. Case 1 had micro-carcinomatosis foci, Case 2 had normal thyroid tissue in histopathological examination and Case 3 had medullary thyroid carcinoma with tumor negative surgical borders. Case 1 was re-operated for persisting focus of disease. Follow-up of cases were uneventful. Clinicians and surgeons should be aware of critical timing for surgery and various surgical and clinical strategies in the management of MTC in children.

Biochemical markers of glucose metabolism may be used to estimate the degree and progression of iron overload in the liver and pancreas of patients with ß-thalassemia major.

The use of cardiac and hepatic T2* MRI measurements to predict the amount of iron accumulation in these organs has been studied extensively and was suggested to be used reliably. However, it may not be practical to screen other organs with MRI related to economical issues and also the prolonged imaging durations. Herein, we aimed to test the use of fasting glucose, fasting, and postprandial insulin, homeostasis model assessment-insulin resistance (HOMA-IR) (calculated as insulin (µIU/ml) × glucose (mg/dl)/22.5), and homeostasis model assessment B score (HOMA-B) (calculated as insulin (µIU/ml) × 20/glucose (mg/dl) - 3.5) to estimate the tissue iron measured with MRI. A total of 37 patients with ß-thalassemia major (BTM), age 20.8 ± 6.3 years (7.1-36.8), were enrolled. MRI measurements were done concomitantly to the biochemical tests for glucose metabolism. A positive correlation between HOMA-IR and hepatic iron loading and a negative correlation between pancreatic T2* and fasting blood glucose were found. A positive correlation was found between fasting insulin levels and pancreatic R2* measures. Additionally, a correlation was detected between cardiac and pancreatic iron accumulations. In centers where T2*/R2* MRI facilities are unavailable, fasting insulin, fasting glucose, and HOMA-IR measurements may be used to predict iron overload and may urge the physician for MRI assessment in case of a deterioration in these biochemical tests. Since hepatic iron loading correlated with insulin resistance development, the insulin resistance among patients with BTM may partially be explained with decreased hepatic insulin clearance from heavily iron-loaded liver.

Hyperthyroidism After Allogeneic Hematopoietic Stem Cell Transplantation: A Report of Four Cases.

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many hematological disorders, primary immunodeficiencies, and metabolic disorders. Thyroid dysfunction is one of the frequently seen complications of HSCT. However, hyperthyroidism due to Graves' disease, autoimmune thyroiditis, and thyrotoxicosis are rare. Herein, we report a series of 4 patients who were euthyroid before HSCT but developed hyperthyroidism (3 of them developed autoimmune thyroid disease) after transplantation.

Severe Undervirilisation in a 46,XY Case Due to a Novel Mutation in HSD17B3 Gene.

17-ß-hydroxysteroid dehydrogenase type 3 (17ß-HSD3) is an important enzyme involved in the final steps of androgen synthesis and is required for the development of normal male external genitalia. 46,XY individuals with deficiency of this enzyme present a wide clinical spectrum from a female appearance of the external genitalia through ambiguous genitalia to a predominantly male genitalia with micropenis or hypospadias. This paper reports a one-year-old 46,XY patient with 17ß-HSD3 deficiency who presented with female external genitalia and bilaterally palpable gonads in the inguinal region. The low T/Δ4 ratio after human chorionic gonadotropin (hCG) stimulation suggested 17ß-HSD3 deficiency. A homozygous mutation, c.761_762delAG, was determined at the intron 9/exon 10 splice site of the HSD17B3 gene. To the best of our knowledge, this mutation has not been reported thus far, but its localization and type would imply a complete disruption of the 17ß-HSD3 which may explain the phenotype of our patient.

Evaluation of hypothalamic-pituitary function in children following acute bacterial meningitis.

BACKGROUND: Previous studies in adults and case reports in children have shown increased frequency of hypothalamo-pituitary dysfunction after infectious diseases of the central nervous system. The aim of this study was to evaluate the function of hypothalamo-pituitary axis in children with a history of bacterial meningitis. METHODS: Patients diagnosed with bacterial meningitis between April 2000 and June 2011 was included. Baseline and stimulated hormonal tests were performed as required for hormonal evaluations following a diagnosis of meningitis. RESULTS: Pituitary function was assessed following a period of 8-135 months (mean 53 months) after bacterial meningitis. Thirty-seven cases (27 male, 15 pubertal) with mean age of 11.1 ± 4.4 years were included. Mean height SDS was 0.01 ± 1.07 and mean BMI SDS was 0.54 ± 1.15 all patients had a SDS above -2 SD. Baseline cortisol and low dose ACTH stimulation revealed normal adrenal functions in all patients. Gonadotropin deficiency was not detected in any of the pubertal cases. Four cases (10.8%) had low IGF1 and IGFBP3 z-scores (<-2 SD) according to age, sex and Tanner stage, but peak GH response in clonidin test was >10 ng/ml in three of them suggesting neurosecretary dysfunction of GH in these cases. The fourth case has died before the test. No one had TSH deficiency and diabetes insipidus, only one case had mild hyperprolactinemia. CONCLUSIONS: Our findings suggest that hypothalamo-pituitary dysfunction is not as common in childhood as in adulthood. The most remarkable finding was neurosecretary dysfunction of GH in some cases.

Hypophosphatasia presenting with pyridoxine-responsive seizures, hypercalcemia, and pseudotumor cerebri: case report.

Hypophosphatasia (HPP) is an inborn error of metabolism characterized by defective bone mineralization caused by a deficiency in alkaline phosphatase (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The clinical expression of the disease is variable. Six forms of HPP are identified according to age at presentation and clinical features. Patients with the infantile form are normal at birth. First symptoms appear within the first 6 months of life. Along with skeletal findings, HPP patients may present with hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency. Seizures in HPP are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine. Herein, we report a case of HPP who presented with pyridoxine-responsive seizures in the early neonatal period and was found to have hypercalcemia, skeletal demineralization and increased intracranial pressure.

Frequency of mutations in PROP-1 gene in Turkish children with combined pituitary hormone deficiency.

Mutations in the prophet of Pit-1 (PROP-1) gene are responsible for most of the cases of combined pituitary hormone deficiencies (CPHD). We performed this study to determine the prevalence of PROP-1 mutations in a group of Turkish children with CPHD. Fifty-three children with the diagnosis of CPHD were included in this study. Clinical data were obtained from medical files, and hormonal evaluation and genetic screening for PROP-1 mutations were performed. A homozygous S109X mutation was found in the second exon in two brothers, and they had growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies and normal prolactin levels. In the third exon of the PROP-1 gene, a heterozygous A142T polymorphism was found in 14 patients and a homozygous A142T polymorphism was found in 3 patients. In the first exon, a homozygous A9A polymorphism was found in 7 patients and a heterozygous A9A polymorphism was found in 31 patients. We assumed that mutations in the PROP-1 gene in cases with CPHD were expected to be more prevalent in our population due to consanguinity, but it was found that these mutations were far less than expected and that it was rare in non-familial cases.

Two pediatric patients with Von Hippel-Lindau disease type 2b: from patient to screening, from screening to patient.

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor susceptibility disease characterized by the development of hemangioblastomas of the brain, spinal cord and retina; pheochromocytomas and renal cell carcinoma. The disease is caused by mutations in the VHL tumor suppressor gene located on chromosome 3p26-p25. In this paper, we present two patients with VHL disease type 2B confirmed by genetic analysis. Diagnosis in the first patient was based on demonstration of retinal hemangioblastoma in association with bilateral pheochromocytoma. Family screening revealed renal cell carcinoma in her father and uncle. The second patient was discovered during family screening of another index case in adult age. VHL disease should be clinically suspected in any individual with a pheochromocytoma especially when there is bilateral and/or multifocal disease or family history. Screening of patients and at-risk family members for VHL-associated tumors should be essential in management of VHL.

GnRH stimulation test in precocious puberty: single sample is adequate for diagnosis and dose adjustment.

OBJECTIVE: Gonadotropin stimulation test is the gold standard to document precocious puberty. However, the test is costly, time-consuming and uncomfortable. The aim of this study was to simplify the intravenous gonadotropin-releasing hormone (GnRH) stimulation test in the diagnosis of precocious puberty and in the assessment of pubertal suppression. METHODS: Data pertaining to 584 GnRH stimulation tests (314 tests for diagnosis and 270 for assessment of pubertal suppression) were analyzed. RESULTS: Forty-minute post-injection samples had the greatest frequency of "peaking luteinizing hormone (LH)" (p<0.001) in the diagnostic tests when the cut-off value was taken as 5 IU/L for LH, 40th minute sample was found to have 98% sensitivity and 100% specificity in the diagnosis of precocious puberty, while the sensitivity and specificity of the 20th minute sample was 100% in the assessment of pubertal suppression. CONCLUSION: LH level at the 40th minute post-injection in the diagnosis of central precocious puberty and at the 20th minute post-injection in the assessment of pubertal suppression is highly sensitive and specific. A single sample at these time points can be used in the diagnosis of early puberty and in the assessment of pubertal suppression.

The relationship between serum adiponectin, tumor necrosis factor-alpha, leptin levels and insulin sensitivity in childhood and adolescent obesity: adiponectin is a marker of metabolic syndrome.

OBJECTIVE: This study aimed (a) to investigate the relationship between the degree of obesity and serum adiponectin, tumor necrosis factor (TNF)-α, leptin, insulin levels and the lipid profile; (b) to clarify the relationship between insulin resistance/glucose tolerance and adipocytokine levels; and (c) to investigate the value of adipocytokine levels as a marker of metabolic syndrome (MS). METHODS: We studied 151 obese children and adolescents (86 boys and 65 girls; mean age was 12.3±2.4 years). We defined obesity as a body-mass index (BMI) z-score more than 2 SD above the mean for age and sex. The control group consisted of 100 children (48 boys, 52 girls, mean age 12.4±2.5 years). Fasting glucose, insulin levels and lipid profiles were measured in all cases and controls after a 12-hour fast. Adiponectin, TNF-α, and leptin levels were measured in the subjects who participated in the adipocytokine branch of the study. An oral glucose tolerance test (OGTT) was also performed in all obese patients. Obese patients were grouped into three subgroups according to their glucose tolerance and insulin sensitivity assessment, and also according to whether they were grouped as MS or not. RESULTS: Serum levels of total cholesterol, LDL and VLDL cholesterol, log triglyceride, insulin, leptin and TNF-α were higher, whereas HDL and square root adiponectin levels were lower in the obese group when compared with controls. Multiple regression analysis among BMI-z score, LDL, triglyceride, HOMA-IR, leptin and TNF-α as determinants of adiponectin revealed that BMI-z score was the only determinant for adiponectin (r:-0.45, p<0.0001). Adiponectin levels in hyperinsulinemic and impaired glucose tolerance groups (IGT) tended to be lower than in normoinsulinemic obese children, however, the difference was not significant. There was a weak negative correlation between adiponectin levels and increasing severity of insulin resistance (r=-0.23, p=0.005) in the groups of obese subjects. Mean serum adiponectin level in subjects with MS was lower than in subjects without MS (p=0.008). CONCLUSIONS: Evaluation of serum adiponectin levels might contribute to an early intervention in obese children with MS.