Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment.

Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment

ABSTRACT Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Relationship between obesity and iron deficiency anemia: is there a role of hepcidin?

OBJECTIVES: Iron deficiency is common in obese children although the underlying mechanism is unclear. The aim of this study was to investigate the associations between iron parameters, leptin, hepcidin and adiponectin levels in obese children. METHODS: A total of 237 children, ranging in age from 5 to 18 years, 180 with primary obesity and 57 healthy children and adolescents, were enrolled. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, leptin, hepcidin and adiponectin levels were studied. RESULTS: White blood cell and platelet count, iron-binding capacity, high-sensitive C-reactive protein, leptin and hepcidin values in the obese group were higher than those of the control group (p < 0.001, p = 0.002, p < 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively). However, mean corpuscular volume, adiponectin and transferrin saturation values in the obese group were lower than in the control group (p = 0.026, p = 0.003, and p < 0.001, respectively). No significant differences were found in terms of hemoglobin, serum ferritin, iron and IL-6 levels. CONCLUSIONS: Our study suggests that hepcidin levels do not contribute to the development of iron deficiency anemia in pediatric obese individuals.

Assessment of bone turnover markers and bone mineral density in normal short boys.

AIM: To investigate whether there is a change in bone turnover-related biochemical markers and bone mineral density of children with constitutional delay of growth and puberty (CDGP) in the prepubertal period. METHODS: We measured serum calcium, phosphorus, alkaline phosphatase, parathormone, 25-OH vitamin D, osteocalcin, osteoprotogerin and urinary deoxypyridinoline levels (D-pyd), and bone mineral density (BMD) in 31 prepubertal boys with CDGP. These children were compared with 22 prepubertal boys with familial short stature (FSS) and 27 normal prepubertal boys. RESULTS: Urinary D-pyd was significantly high in CDGP group as compared to control group (p=0.010). Volumetric BMD did not significantly differ between CDGP, FSS, and control groups (p=0.450). Volumetric BMD and urinary D-pyd levels of FSS and control groups were similar. Mean or median levels of calcium, phosphorus, alkaline phosphatase, parathormone, and osteoprotegerin did not significantly differ between CDGP, FSS, and control groups. CONCLUSIONS: Our data suggest that prepubertal boys with CDPG have normal bone turnover. However, their significantly higher urinary D-pyd levels relative to those of FSS and control groups might be an indicator of later development of osteoporosis. Therefore, long-term follow-up studies monitoring bone mineral status of prepubertal boys with CDPG from prepuberty to adulthood are needed to better understand bone metabolism of these patients.

Gonadoblastoma with Dysgerminoma in a Phenotypically Turner-Like Girl with 45,X/46,XY Karyotype.

Individuals with 45,X/46,XY karyotype are at increased risk for germ cell tumor development. We report a case with a diagnosis of 45,X/46,XY gonadal dysgenesis who presented with short stature, physical stigmata of Turner syndrome. Her pubertal development was at Tanner stage 3. At follow-up, bilateral prophylactic gonadectomy was performed when considering the risk factors. Pathological assessment was consistent with gonadoblastoma in the left gonad, and dysgerminoma and gonadoblastoma in neighboring areas in the right gonad. The karyotype analysis of the right and left gonadal tissues reveled 45,X[97,3]/46,XY[2,7] and 45,X[92,7]/46,XY[4,5]/47,XYY [2,8] mosaic, respectively. The clinical management of such patient should be individualized according to the present risk factors. Additionally, signs of estrogenization like advanced breast development always suggest the possible presence of germ cell tumor.

Extensive middle cranial fossa arachnoid cysts and different clinical presentation in two patients.

Arachnoid cysts (ACs), particularly suprasellar cysts, cause a wide spectrum of endocrine disorders. Herein, we report two patients diagnosed with an extensive AC in the middle cranial fossa while being investigated for etiologies of precocious puberty and short stature. One of them required surgery due to his pubertal disorders associated with compression effects of cyst. After surgery, his puberty progression was regressed within one year. On the other hand, surgery was not planned for the second patient considering of his cranial imaging findings and the extremely low incidence of growth hormone (GH) deficiency caused by middle fossa AC (MFAC). We started treatment with recombinant human GH and no complication was found during treatment follow-up. Endocrine disorders associated with MFACs are extremely rare. By presenting with these two cases, we aimed to remain our fellow physcians that ACs can be possibly cause of endocrine disorders. Clinicians should be careful evaluating endocrine disorders because real cause may not be cyst itself but masked by it.

Cardio-facio-cutaneous syndrome with precocious puberty, growth hormone deficiency and hyperprolactinemia.

Cardio-facio-cutaneous (CFC) syndrome is a rare disorder characterized by craniofacial dysmorphia, ectodermal abnormalities, cardiac malformations, as well as growth and developmental delay. Although some endocrine abnormalities have been reported in this syndrome, very little is known about CFC syndrome-related endocrine disorders. A 7.5-year-old boy was admitted to our endocrinology clinic with the complaint of short stature. He had a height of 103 cm [-4 standard deviation (SD)], a weight of 16 kg (<3(th) percentile, -1.7 SD), a facial appearance typical for the CFC syndrome, optic nerve hypoplasia and pulmonary stenosis. Genetic investigation revealed a heterozygous mutation in exon 3 of the MEK1 gene, c.389A>G (p. Y130C). During his long-term follow-up, the patient developed a variety of endocrine disorders including precocious puberty, growth hormone deficiency and hyperprolactinemia.

Octreotide-induced long QT syndrome in a child with congenital hyperinsulinemia and a novel missense mutation (p.Met115Val) in the ABCC8 gene.

BACKGROUND/AIMS: Congenital hyperinsulinism (CHI) denotes an inappropriate secretion of insulin from pancreatic ß-cells in the presence of a low blood glucose level due to various genetic causes. Diazoxide is the first-line medical treatment for CHI. In case of failure, a somatostatin analogue called octreotide is used. A prolonged QT interval is an unusual side effect of octreotide which can be lethal if unrecognized. CASE PRESENTATION: We report on a 35-day-old infant who was diagnosed with CHI on the 3rd day of his life and underwent pancreatectomy due to failure of medical treatment at 8 months. His genetic analysis revealed a compound heterozygosity for a novel missense mutation (p.Met115Val) and a nonsense mutation (p.Trp1339X) in the ABCC8 gene. Furthermore, at the 6th month of follow-up, a long QT (0.49 s) was determined by ECG examination, which was normalized following discontinuation of octreotide treatment after pancreatectomy. Thus, the long QT was considered to be secondary to octreotide medication. CONCLUSION: We recommend ECG monitoring before and during octreotide treatment in order to recognize a prolonged QT interval and to prevent related complications in cases with congenital hyperinsulinemia.

Serum adiponectin, leptin, resistin and RBP4 levels in obese and metabolic syndrome children with nonalcoholic fatty liver disease.

AIM: To investigate the relationship of adiponectin, leptin, resistin and RBP4 levels in obese and metabolic syndrome children with nonalcoholic fatty liver disease (NAFLD). PATIENTS & METHODS: Group I consisted of 63 obese children with liver steatosis, group II consisted of 12 obese children with elevated serum ALT activity from group I, and group III included 85 obese children without liver steatosis. RESULTS: Leptin levels were higher in the NAFLD children than in the control group. Serum RBP4 levels in obese children with NAFLD were higher than those in obese children without NAFLD and controls. Adiponectin and resistin levels were negatively correlated and RBP4 levels positively correlated with ALT activity and ultrasonographic grading. CONCLUSION: These data suggest that adiponectin, resistin and RBP4 may have a role in the pathogenesis of NAFLD in obese children. Adiponectin, leptin, resistin and RBP4 may be suitable markers for predicting metabolic syndrome and NAFLD.

Relationship of adipokines (adiponectin, resistin and RBP4) with metabolic syndrome components in pubertal obese children.

AIM: To investigate the relationship between serum adiponectin, resistin and RBP4 levels and the components of metabolic syndrome. PATIENTS & METHODS: Serum adiponectin, resistin and RBP4 levels were detected and analyzed in 148 8-18-year-old Turkish obese pubertal children with/without metabolic syndrome. RESULTS: Adiponectin and resistin concentrations were significantly inversely correlated with BMI standard deviation score, homeostatic model assessment insulin resistance, waist circumference, triglyceride levels and diastolic and systolic blood pressure, and were directly correlated with high-density lipoprotein cholesterol. RBP4 concentrations were directly correlated with homeostatic model assessment insulin resistance, waist circumference, triglyceride levels and diastolic and systolic blood pressure, and inversely correlated with high-density lipoprotein cholesterol. CONCLUSION: Adiponectin, RBP4 and, in particular, resistin levels may be used as suitable predictive biomarkers of metabolic syndrome.

Clinical significance of serum vascular endothelial growth factor, endostatin, and leptin levels in children with lymphoma.

BACKGROUND: A number of clinical studies conducted in adults have demonstrated the prognostic significance of angiogenic factors in malignancies, however, only a limited number of studies have been conducted in children. The aim of this study was to determine serum vascular endothelial growth factor (VEGF), endostatin, and leptin levels in children with lymphoma and to investigate whether these factors provide prognostic information. PROCEDURE: Serum samples from 36 children with lymphoma (non-Hodgkin lymphoma (NHL) N = 21, Hodgkin lymphoma (HL) N = 15) were collected at diagnosis and during remission. Serum samples were also collected from 18 healthy children as the control group. Serum VEGF and endostatin levels were quantified by using enzyme-linked immunosorbent assay (ELISA) and serum leptin by immunoradiometric assay. RESULTS: The serum VEGF levels were found elevated in patients compared to controls (P = 0.033), while endostatin and leptin levels were lower in patients than in controls (endostatin, 43.9 ± 5.8 ng/ml vs. 123.6 ± 13.5 ng/ml, P < 0.001; leptin, 5 ± 1.5 ng/ml vs. 6.7 ± 1.2 ng/ml, P = 0.013). VEGF levels declined (pre, 151.6 ± 55.9 pg/ml vs. post, 16.2 ± 7.9 pg/ml, P = 0.041), while endostatin and leptin levels increased in patients who achieved remission (33 of 36 patients) when compared to pre-treatment levels (endostatin pre, 43.1 ± 5.9 ng/ml vs. post, 65.9 ± 6.8 ng/ml, P = 0.047; leptin, pre, 5.3 ± 1.6 ng/ml vs. post, 9.8 ± 2.7 ng/ml, P = 0.012). Serum VEGF, endostatin, and leptin levels were not predictive of survival. CONCLUSION: Serial measurement of serum VEGF, endostatin, and leptin levels could potentially be used to predict response to treatment or progressive disease in children with lymphoma.

Prevalence of Celiac disease in Turkish children with type 1 diabetes mellitus and their non-diabetic first-degree relatives.

BACKGROUND/AIMS: The objective of this study was to determine the prevalence of Celiac disease in Turkish children with type 1 Diabetes Mellitus and their non-diabetic first-degree relatives. METHODS: Forty-eight children with type 1 Diabetes Mellitus (18 males, 30 females; age range: 3.5 to 23 years; mean age: 12.09 +/- 4.78 years), 29 non-diabetic siblings, 40 non-diabetic parents, and 103 healthy children were screened for celiac disease using the IgA and IgG anti-tissue transglutaminase antibody and total serum IgA. Small intestinal biopsy was offered to all antibody-positive patients. RESULTS: Eight of 48 diabetic patients had positive anti-tissue transglutaminase IgA. Selective IgA deficiency was detected in 2 diabetic children and both were positive to anti-tissue transglutaminase IgG. Intestinal biopsy was accepted by 8 of 10 (80%) diabetic children with positive celiac serology. Pathologic examination showed total villous atrophy in 3 (6.3%) diabetic children. Positive anti-tissue transglutaminase IgA was found in 1/29 siblings and 2/40 parents. Celiac disease was confirmed by biopsy in the sibling. Two parents refused the biopsy. The frequency of biopsy-proven celiac disease was found as 1.4 in relatives of diabetic children. None of the serum samples of healthy children comprising the control group showed selective IgA deficiency or positivity for anti-tissue transglutaminase IgA antibody. CONCLUSIONS: These findings indicate that the prevalence of celiac disease in Turkish children with type 1 diabetes mellitus is higher than in healthy controls. The 1.4% frequency of Celiac disease in relatives of diabetic children is close to that of controls.

Prevalence of anticardiolipin antibodies in type 1 diabetes and autoimmune thyroiditis.

INTRODUCTION: High levels of anticardiolipin (aCL) antibodies may predict vascular complications that could develop in type 1 diabetes and autoimmune thyroiditis (AIT). However, the clinical relevance of these antibodies in subjects with type 1 diabetes and AIT is unclear. OBJECTIVES: The aim of the study was to determine the prevalence and significance of aCL antibodies in patients with type 1 diabetes and AIT. PATIENTS AND METHODS: The study involved 74 patients with type 1 diabetes (mean age 12.9 +/-4.2 years), 64 patients with AIT (mean age 14.1 +/-3.7 years), and 35 healthy control subjects (mean age 12.8 +/-3.3 years). The levels of aCL immunoglobulin (Ig) G and aCL IgM antibodies were measured by enzyme-linked immunosorbent assays. Low-positive and medium/high-positive cut-off values were selected for aCL antibody positivity. RESULTS: The prevalence of aCL antibodies was higher in AIT patients compared with diabetic and healthy subjects with low positive levels (P <0.05), while the frequency of medium/high aCL positive levels in AIT and diabetic subjects was not statistically different from that observed in healthy subjects. CONCLUSIONS: Our study showed an increased prevalence of aCL antibody positivity in patients with AIT at a low-positive aCL cut-off level, while the frequency of aCL antibody positivity at a moderate/high aCL cut-off level was not significantly different between the groups. We believe that routine investigation of aCL levels may not have clinical relevance in children with type 1 diabetes or AIT.

Genetic polymorphisms of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes in adolescent girls with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS), whose genetic basis is not completely well understood, is the most common endocrine disorder in women and it typically develops during adolescence. The aim of this study is to investigate the possible association between single nucleotide polymorphisms (SNPs) of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes and PCOS in adolescent girls. METHODS: DNA samples from forty-four adolescent girls with PCOS and 50 healthy controls were analyzed by PCR-RFLP and direct DNA sequencing to determine the genotypic frequency of 17 different polymorphic loci on the FSHR (A307T, N680S), CYP17 (-34 T/C), CYP1A1 (T6235C), CAPN10 (44, 43, 19, 63), INSR (exon 17 C/T), SERPINE1 (4G/5G) genes. Genotyping of exon 12 (six polymorphisms) and intron 12 (one polymorphism) of INSR gene by direct DNA sequencing was performed for the first time in this study. RESULTS: No significant differences were observed in the genotype and allele distributions of above mentioned polymorphisms between cases and control groups. CONCLUSION: Our data does not support an association between SNPs of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes and susceptibility to PCOS or related traits in Turkish adolescent girls.

Dyskeratosis congenita with corneal limbal insufficiency.

We describe a newly diagnosed Turkish adolescent female with Dyskeratosis congenita along with the novel ocular finding of corneal limbal insufficiency. Corneal limbal insufficiency was suggested to be a premature aging sign resulting from a deficiency in corneal stem cell activity, a biological process caused by underlying telomeric defect in this disease.

Hungry bone syndrome after parathyroidectomy caused by an ectopic parathyroid adenoma.

Hungry bone syndrome (HBS), i.e., persistent hypocalcemia and hypophosphatemia as a result of extensive remineralization, is rarely encountered in children after parathyroid surgery. Herein, we report a 12-year-old girl who was diagnosed to have an ectopic parathyroid adenoma, and HBS was observed in the postsurgical follow-up. The diagnosis and the risk factors are discussed in the light of the literature.

Serum ghrelin, leptin and resistin levels in adolescent girls with polycystic ovary syndrome.

AIM: The aim of the present study was to investigate the levels of leptin, resistin and ghrelin in polycystic ovary syndrome (PCOS), and to assess their possible correlations with the hormonal and metabolic features of PCOS. METHODS: Sixteen obese (ObPCOS) and 12 lean (LeanPCOS) subjects with PCOS and 19 obese control subjects were enrolled in the study. RESULTS: Ghrelin, leptin and resistin concentrations were similar between groups when body mass index (BMI) was used as a covariate (P > 0.05). Mean androgen, SHBG, luteinizing hormone (LH) levels and luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio tended to be similar between polycystic ovary syndrome (PCOS) groups. However, when compared with the control group, SHBG was lower and androgen, LH levels and LH/FSH ratio were higher in the PCOS groups. Free testosterone levels significantly correlated with resistin (r = -0.38), SHBG correlated significantly with body mass index (BMI) (r = -0.45) and resistin (r = -0.67), LH/FSH ratio was significantly correlated with ghrelin (r = -0.52) and estradiol (E2) levels (r = 0.51). CONCLUSION: ObPCOS and LeanPCOS groups having higher LH/FSH ratios and lower SHBG levels suggest that there could be factors other than adiposity responsible for the clinical features of PCOS patients. In the light of our results, those factors can be suggested as ghrelin and E2 for the elevated LH/FSH ratio and resistin for the lowered SHBG.

CTLA4 gene polymorphisms in children and adolescents with autoimmune thyroid diseases.

Two common forms of autoimmune thyroid diseases are Graves' disease and Hashimoto's thyroiditis. Cytotoxic T lymphocyte antigen 4 (CTLA4) encoded by the CTLA4 gene on chromosome 2q33 plays a role in susceptibility to Graves' disease and is probably important also for Hashimoto's thyroiditis as well as for the other endocrine autoimmune disorders. The CTLA4 locus is the only nonhuman leukocyte antigen locus that has been found in association with Graves' disease repeatedly. Particularly, association of three polymorphic markers of CTLA4 gene, namely, C(-318)T, A49G, and (AT)n dinucleotide repeat, with Graves' disease was demonstrated in most of the population-based investigations. On the other hand, there are few studies to reveal the association of these markers with Hashimoto's thyroiditis. A49G polymorphism was proposed to be associated with Hashimoto's thyroiditis, and C(-318)T was suggested to be not associated. The patient groups consisted of 88 patients (10 males and 78 females; mean age: 14.5 +/- 3.2 years [4.6-21.0 years]) with a previous diagnosis of Hashimoto's thyroiditis and 112 euthyroid volunteers (51 males and 61 females; mean age: 14.1 +/- 2.9 years [5.2-18 years]). The frequency of A/G (A49G) genotype was high and statistically significant in patients with Hashimoto's thyroiditis in comparison with the control group. Although the frequency of C/T [C(-318)T] genotype is not significantly high in children with Hashimoto's thyroiditis according to the control group, the risk of Hashimoto's thyroiditis in A/G genotype group was 4.66 times greater than the group with A/A genotype. In this study, we documented that the A49G polymorphism might increase the susceptibility for Hashimoto's thyroiditis.

A 46XX disorder of sex development with a prostate gland and increased level of prostate-specific antigen.

A 5-year-old child with precocious puberty and complete masculinization of the genitalia was diagnosed to have 21-hydroxylase deficiency. The patient was also found to have a prostate gland and increased prostate-specific antigen. The presence of a prostate and its relation to prostate-specific antigen and prostate adenocarcinoma are discussed in the light of the relevant literature.