Effects of Blue Light on Puberty and Ovary in Female Rats

Objective: This study was designed to examine the effect of blue light exposure and exposure time on puberty in an animal model. Methods: Eighteen 21-day-old female Sprague Dawley rats were divided into three equal groups which were: control group (CG); blue light-6 hours (BL-6); and blue light-12 hours (BL-12). CG rats were maintained with 12/12-hour light-dark cycles. The animals in BL-6 and BL-12 were exposed to blue light of wavelength 450-470 nm and intensity of 0.03 uW/cm2 for 6 and 12 hours, respectively. Exposure to blue light continued until the first signs of puberty. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, dehydroepiandrosterone sulfate (DHEA-S), leptin and melatonin were measured. Subsequently the ovaries and uterus were examined histomorphologically. Results: The median day of puberty start was 38, 32 and 30 for the CG, BL-6, and BL-12 groups, respectively (p=0.001). FSH, testosterone, DHEA-S, and leptin concentrations of all groups were similar. However, LH and estradiol concentrations in BL-6 were higher compared to CG (p=0.02). There was a negative correlation between blue light exposure, exposure time, and melatonin concentrations (r=-0.537, p=0.048). Ovarian tissue was compatible with puberty in all groups. As blue light exposure time increased, capillary dilatation and edema in the ovarian tissue increased. Prolonged exposure was associated with polycystic ovary-like (PCO) morphological changes and apoptosis in granulosa cells. Conclusion: These results suggest that exposure to blue light and the duration of exposure induced earlier puberty in female rats. As the duration of blue light exposure increased, PCO-like inflammation, and apoptosis were detected in the ovaries.

Recommendations for Clinical Decision-making in Children with Type 1 Diabetes and Celiac Disease: Type 1 Diabetes and Celiac Disease Joint Working Group Report

It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients' families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors' own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.

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.

The role of DENND1A and CYP19A1 gene variants in individual susceptibility to obesity in Turkish population-a preliminary study.

Single nucleotide polymorphisms (SNPs), the most common genetic variations in human genome, can manage the predisposition of certain complex diseases or situations such as obesity. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to being overweight or obese and developing related chronic complications such as hypertension, coronary heart disease, diabetes and cancer. The present study comprised of 193 unrelated healthy volunteers (120 females and 73 males) with Turkish origin. Only female adolescents (n = 110) were divided into 2 categories according to their BMI values as overweight (BMI ≥ 25) and normal (18.5 < BMI < 25) according to WHO classification. Genomic DNA was isolated from venous blood samples and genotyping of DENND1A rs10818854 and CYP19A1 rs2414096 variants was performed on Roche Light Cycler 2.0 Real-Time PCR platform. Serum hormone levels were analyzed by Electrochemiluminescent Immunoassay (ECLIA; Roche diagnostics). The genotype distributions were consistent with the Hardy-Weinberg equilibrium for both SNPs in the studied population (p > 0.05). The genotype distribution of DENND1A rs10818854 was determined for the first time in Turkish population and the variant allele frequency was found as 0.095. According to reduced sex hormone-binding globulin levels and increased free androgen index in the present study, obesity was linked with hyperandrogenism in female subjects. Both polymorphisms were investigated as potential genetic susceptibility markers for obesity and neither DENND1A nor CYP19A1 showed any associations.

The relationship between diet quality and insulin resistance in obese children: adaptation of the Healthy Lifestyle-Diet Index in Turkey.

BACKGROUND: Childhood obesity and its complications are serious health problems and diet/lifestyle changes can be beneficial for the prevention of diseases. Adaptation of the Healthy Lifestyle-Diet (HLD) Index in accordance with the dietary guidelines for Turkey (TR) and determination of the relationship between metabolic syndrome risk factors in obese children were the aims of this study. METHODS: This study was conducted on 164 overweight or obese children (87 male, 77 female) aged 9-13 years. For all participants, the HLD-TR Index and a 24-h dietary recall were performed and the mean adequacy ratio (MAR) was calculated. Anthropometric measurements and the body composition of the children were taken. Metabolic syndrome risk factors and insulin resistance were assessed. RESULTS: The mean age of the male and female children was 11.2±1.49 and 11.0±1.40 years, respectively. The majority of the children were obese in both genders. There were no statistically significant differences in the HLD-TR scores between the genders. As the index scores increased, a decrease in the energy intake and an increase in the MAR were observed. Negative correlations between the index scores and body mass, waist circumference and body fat mass were observed. Furthermore, a one-unit increase in the index score decreases the insulin resistance risk by 0.91 times after adjustments for age and gender (odds ratio: 0.91 [0.85-0.97]). CONCLUSIONS: The HLD-TR Index is a valid tool that can give an idea about the quality of the diet in obese children. Furthermore, with the increase in the compliance with recommendations for diet/lifestyle changes, indicators of obesity and metabolic syndrome were decreased.

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.

Age-Specific Frequencies and Characteristics of Ovarian Cysts in Children and Adolescents.

OBJECTIVE: The aim of the present study was to document ovarian cyst frequency and characteristics as well as distribution of these parameters with respect to age in children and adolescents. METHODS: We retrospectively analyzed the medical records of 1009 girls between the ages of 5-18 years who presented to our pediatric emergency department (PED) with pelvic pain and therefore underwent pelvic ultrasound examination between June 2011 and May 2014. RESULTS: In total, 132 of 1009 girls (13.1%) were identified as having ovarian cysts ≥1 cm in diameter. The frequency of ovarian cysts was found to be 1.8% (6/337) in children aged 5-9 years and 18.8% (126/672) in those aged 10-18 years. All the cysts detected in children aged 5-9 years were small (<3 cm) and simple with age-specific frequencies ranging between 1.5-2.7%. With the onset of adolescence, ovarian cyst frequency started to increase with age and ranged between 3.8-31.3% throughout adolescence. Age of peak ovarian cyst frequency was 15 years with a rate of 31.3%. Large ovarian cysts (>5 cm) were identified in 19 adolescents (15.1%) with most occurring during middle adolescence. Of the 19 adolescents, five were found to have cyst-related significant ovarian pathologies including cystadenoma (n=3) and ovarian torsion (n=2). CONCLUSION: In children aged 5-9 years, ovarian cysts were infrequent and small (<3 cm). Peak ovarian cyst frequency was detected at the age of 15 years. All patients diagnosed with cyst-related significant ovarian pathologies were adolescents having a cyst >5 cm in diameter with a complex appearance in most.

The Etiology and Clinical Features of Non-CAH Gonadotropin-Independent Precocious Puberty: A Multicenter Study.

AIM: The causes of gonadotropin-independent precocious puberty are diverse, and often have overlapping clinical and biochemical features. With the exception of congenital adrenal hyperplasia (CAH), disorders that cause gonadotropin-independent precocious puberty (GIPP) are uncommon. The literature is devoid of any large-scale studies on the etiologic distribution of GIPP. The aim of this study was to determine the frequency of each etiology in a cohort of patients with GIPP (excluding those with CAH), and to evaluate the clinical and laboratory features of these patients. MATERIALS AND METHODS: This multicenter, nationwide web-based study collected data on patients who presented with non-CAH GIPP in Turkey. RESULTS: Data were collected for 129 patients (102 girls and 27 boys) from 29 centers. Based on the data collected, the estimated prevalence of non-CAH GIPP in the studied population was 14 in 1 000 000 children. Functional ovarian cyst was the most common etiology, accounting for 37% of all cases, followed by McCune-Albright syndrome (MAS) (26%). Among the patients with MAS, 11.7% had fibrous dysplasia, 32.3% had café-au-lait spots, and 52.9% had both. Human chorionic gonadotrophin-secreting tumors included choriocarcinoma of the liver, hepatoblastoma, and germ cell tumors of the sellar-suprasellar region and mediastinum. Patients with adrenocortical tumors presented at an earlier age than those with other etiologies. Ovarian tumors included mature cystic teratoma, dysgerminoma, juvenile granulosa tumor, and steroid cell tumor. Despite overlapping features, it was possible to identify some unique clinical and laboratory features associated with each etiology. CONCLUSION: This largest cohort of patients with non-CAH GIPP to date yielded an estimation of the frequency of non-CAH GIPP in the general pediatric population and showed that girls were affected at a rate 4-fold greater than that of boys owing to functional ovarian cysts and MAS, which were the two most common etiologies. The data collected also provided some unique characteristics associated with each etiology.

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.

Thyroid abnormalities in survivors of childhood cancer.

OBJECTIVE: To investigate the late side effects of childhood cancer therapy on the thyroid gland and to determine the risk factors for development of thyroid disorder among childhood cancer survivors. METHODS: One hundred and twenty relapse-free survivors of childhood cancer (aged 6-30 years) were included in this study. The diagnoses of patients were lymphoma, leukemia, brain tumor, rhabdomyosarcoma and nasopharyngeal carcinoma (NPC). The patients were divided into two groups depending on the treatment: group 1-chemotherapy (ChT) only (n=52) and group 2-combination therapy of ChT + radiotherapy (RT) (head/neck/thorax) (n=68). Thyroid function tests, urinary iodine levels, and thyroid gland ultrasound examinations were evaluated in both groups. RESULTS: Incidence of thyroid disease was 66% (n=79) in the survivors. The thyroid abnormalities were: hypothyroidism (HT) (n=32, 27%), thyroid nodules (n=27, 22%), thyroid parenchymal heterogeneity (n=40, 33%), autoimmune thyroiditis (n=36, 30%), and thyroid malignancy (n=3, 2%). While the incidence of HT and thyroid nodules in group 2 was significantly higher than in group 1, the incidence of thyroid parenchymal heterogeneity and autoimmune thyroiditis was similar in the two patient groups. HT and thyroid malignancy were seen only in group 2. In multivariate logistic regression analysis, a history of Hodgkin lymphoma (HL), brain tumor and NPC, as well as cervical irradiation and 5000-5999 cGy doses of radiation were found to constitute risk factors for HT. History of HL and 4000-5999 cGy doses of radiation were risk factors for thyroid nodules. Head/neck irradiation and treatment with platinum derivatives were risk factors for autoimmune thyroiditis. In univariate analysis, a history of NPC, cervical + nasopharyngeal irradiation, and treatment with platinum derivatives were risk factors for thyroid parenchymal heterogeneity. CONCLUSION: Our results indicate that there is especially an increased risk of HT and thyroid nodules in patients treated with combination therapy of ChT with head/neck/thorax RT. Although chemotherapeutic agents per se do not seem to cause HT, longer follow-up is needed to assess whether or not there is an increased risk for autoimmune thyroiditis and thyroid parenchymal heterogeneity after antineoplastic therapy.

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.

Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report.

Preterm ovarian hyperstimulation syndrome (POHS) is an uncommon disorder characterized by prematurity, hypogastric and upper leg swelling of various intensities, high serum estradiol and gonadotropin levels, and ovarian follicular cyst/cysts. In this paper, we present the first case of POHS presenting with vaginal bleeding. A female infant was born via spontaneous vaginal delivery at 25 weeks of gestation with a birth weight of 610 g. At 36 weeks of post-conception age, she developed breast enlargement, swelling of the clitoral hood, labia major and minor, hypogastrium and upper legs. Several weeks later, vaginal bleeding started and lasted 3 days. The vaginal bleeding continued to occur at monthly intervals. The elevated levels of gonadotropins and estrogens, vulvar swelling and cysts in both ovaries confirmed the diagnosis of preterm ovarian hyperstimulation syndrome.

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.

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.