High frequency of transient congenital hypothyroidism among infants referred for suspected congenital hypothyroidism from the Turkish National screening program: thyroxine dose may guide the prediction of transients.

PURPOSE: We aimed to determine the frequency of transient congenital hypothyroidism (TCH) in 17 participating centers in Türkiye, evaluate the etiological distribution in permanent congenital hypothyroidism (PCH) cases, and investigate the role of laboratory and clinical findings in predicting TCH. METHODS: This retrospective observational multicenter study included patients from 17 pediatric endocrinology centers identified by "National Newborn Screening Program" (NNSP) who were born in 2015 and followed for 6 years. Demographic, clinical, and laboratory information of the cases were compiled through the database http://cedd.saglik-network.org (CEDD-NET). RESULTS: Of the 239 cases initially treated for CH, 128 (53.6%) were determined as transient in whom a trial of levothyroxine (LT4) withdrawal was performed at a median age of 36 (34-38) months. Among the patients with PCH (n = 111), thyroid dysgenesis was diagnosed in 39.6% (n = 44). The predictive factors for TCH were: LT4 dose at the withdrawal of treatment, and initial newborn blood screening (NBS)-TSH level. Based on the receiver operating characteristic (ROC) curve analysis to predict optimal cut-offs for TCH predictors, LT4 dose < 2.0 µg/kg/day at treatment discontinuation was predictive for TCH and was associated with 94.5% specificity and 55.7% sensitivity, with an area under the curve (AUC) of 0.802. The initial NBS-TSH level value < 45 µIU/mL was predictive for TCH with 93.1% specificity and 45.5% sensitivity, with an AUC of 0.641. In patients with eutopic thyroid gland only LT4 dose < 1.1 µg/kg/day at withdrawal time was predictive for TCH with 84.7% sensitivity and 40.4% specificity, with an AUC of 0.750. CONCLUSION: According to our national follow-up data, the frequency of TCH was 53.6%. We determined the LT4 dose < 2.0 µg/kg/day at discontinuation of treatment and the initial NBS-TSH level < 45 µIU/mL as the best cut-off limits to predict TCH.

Nutritional status and body composition in children with inflammatory bowel disease: a prospective, controlled, and longitudinal study.

BACKGROUND: Malnutrition and growth retardation (GR) are major extraintestinal presentations of inflammatory bowel disease (IBD) in childhood and are especially prevalent among those with Crohn's disease (CD). We aimed to evaluate nutritional and growth status and body composition (BC) of children with IBD during a 1-year follow-up. METHODS: Thirty-eight children with IBD and 57 age- and sex-matched controls were recruited prospectively. Anthropometry (weight, height, body mass index (BMI), and triceps skinfold thickness (TSFT) indicated as z scores for age and sex and mid-arm circumference) and bioelectrical impedance analysis were performed at baseline (T0) and after 1 year (T1). Disease activity was evaluated by clinical scoring systems. GR was defined as HAZ < -2, undernutrition as WAZ < -2, severe malnutrition (SM) as BMIZ < -2, and obesity was defined as BMIZ > +2. A p value of <0.05 was considered statistically significant. RESULTS: Thirty-six children with IBD (22 ulcerative colitis, 12 CD, and 2 indeterminate colitis) and 43 controls completed the study. Most patients were in remission during the study period (T0:71.4%; T1:72.2%). No significant differences were found regarding the frequency of GR (5.6%/8.3%), undernutrition (11.1%/2.8%), and SM (11.1%/5.6%) between T0 and T1 in the IBD group. The changes in anthropometrics and BC measurements during the study period did not differ between the groups except for the TSFT z score. CONCLUSION: Most patients with IBD were well nourished and grown, although some children were underweight and had GR. Our results suggest that, in IBD patients, the fat mass (FM) showed a gradual increase over time compared with controls.

Genotype-phenotype correlation, gonadal malignancy risk, gender preference, and testosterone/dihydrotestosterone ratio in steroid 5-alpha-reductase type 2 deficiency: a multicenter study from Turkey.

BACKGROUND: Studies regarding genetic and clinical characteristics, gender preference, and gonadal malignancy rates for steroid 5-alpha-reductase type 2 deficiency (5α-RD2) are limited and they were conducted on small number of patients. OBJECTIVE: To present genotype-phenotype correlation, gonadal malignancy risk, gender preference, and diagnostic sensitivity of serum testosterone/dihydrotestosterone (T/DHT) ratio in patients with 5α-RD2. MATERIALS AND METHODS: Patients with variations in the SRD5A2 gene were included in the study. Demographic characteristics, phenotype, gender assignment, hormonal tests, molecular genetic data, and presence of gonadal malignancy were evaluated. RESULTS: A total of 85 patients were included in the study. Abnormality of the external genitalia was the most dominant phenotype (92.9%). Gender assignment was male in 58.8% and female in 29.4% of the patients, while it was uncertain for 11.8%. Fourteen patients underwent bilateral gonadectomy, and no gonadal malignancy was detected. The most frequent pathogenic variants were p.Ala65Pro (30.6%), p.Leu55Gln (16.5%), and p.Gly196Ser (15.3%). The p.Ala65Pro and p.Leu55Gln showed more undervirilization than the p.Gly196Ser. The diagnostic sensitivity of stimulated T/DHT ratio was higher than baseline serum T/DHT ratio, even in pubertal patients. The cut-off values yielding the best sensitivity for stimulated T/DHT ratio were ≥ 8.5 for minipuberty, ≥ 10 for prepuberty, and ≥ 17 for puberty. CONCLUSION: There is no significant genotype-phenotype correlation in 5α-RD2. Gonadal malignancy risk seems to be low. If genetic analysis is not available at the time of diagnosis, stimulated T/DHT ratio can be useful, especially if different cut-off values are utilized in accordance with the pubertal status.

Disorders of sexual development: an overview of 18 years experience in the pediatric Endocrinology Department of Ankara University.

INTRODUCTION: Disorders of sexual development (DSD) occur when the appearance of the internal and/or external genitalia is at variance with normal development for either sex. We reviewed the characteristics of patients with DSD. PATIENTS: Two hundred and eight children aged from newborn to 19 years with DSD from 1990 to 2008. RESULTS: 46,XY DSD (52.4%) was more common than 46,XX DSD (34.6%) and gonadal differentiation disorders (12.99%). Thirty-six (33.02%) patients were diagnosed with androgen resistance syndrome, 41 (37.61%) had 5alpha-reductase deficiency, 23 (21.10%) had testosterone synthesis disorders. Congenital adrenal hyperplasia was the most frequent underlying cause of 46,XX DSD. CONCLUSION: There are many difficult aspects in the diagnosis and management of DSD. Gender assessment teams of endocrine centers need a multidisciplinary approach for the diagnosis, medical and surgical treatment, genetic counseling, and psychosocial support of these patients.

Cytokines as a common components of two different disorders: metabolic syndrome and hemophagocytic lymphohystiositosis.

Increased cytokines secretion occurs in several different disorders. Hemophagocytic lymphohystiositosis (HLH) and metabolic syndrome (MS) are consist two of them. Hemophagocytic lymphohystiositosis results from uncontrolled macrophage activation and huge amounts of cytokine secretion. The metabolic syndrome is a multicomponent condition characterized by insulin resistance, dyslipidemia, abdominal obesity, hypertension, and increased level of proinflammatory cytokines. It was presented a 6.8 years old girl, diagnosed as HLH. Because she was morbid obese, endocrinological investigation had been done and metabolic syndrome, thyroid hormone dysfunction, and hypercortisolemia with disturbances of diurnal rhythm were detected. During follow-up of patient, metabolic syndrome components disappear gradually while haemophagocytosis was recovered. Endocrine system can be affect during HLH attack, and MS can be developed. Cytokines seems to act central role of pathological changes for both diseases.

Gender dysphoria and gender change in an adolescent with 45,X/46,XY mixed gonadal dysgenesis.

This is a report of a 13-year-old 45,X/46,XY patient who was assigned as female gender and had feminizing surgery during infancy. Psychological problems became progressively more severe from childhood to incapitation by age 13 years. Gender identity reversal was performed after extensive physiological testing. Because he wanted to have corrective surgery, his external genitalia sex reassignment was made male from female. There were surgical problems with his phalloplasty; after surgery at infancy there was reduction of the phallus with recession of the glans to the typical clitoral location. Genital response during sexual activity and satisfaction after reconstructive surgery for male genitalia are as yet unknown. This patient is a typical example for medical, psychological and surgical dilemmas of sex reassignment and the problems of early corrective surgery. Sufficient brain virilisation associated with undervirilised external genitalia is an important problem for assignment of gender identity.

"Maternal/Neonatal" iodine status in patients with prolonged physiological jaundice.

BACKGROUND: The increasing knowledge indicated that borderline hypothyroidism may cause neurodevelopmental disorders. Borderline compensated congenital hypothyroidism could caused by iodine deficiency or iodine overload. One of the most important etiological factors causing prolonged jaundice in the neonatal period is congenital hypothyroidism. Aimed of this study is to investigate the frequency of borderline or overt hypothyroidism in a group of newborn with prolonged physiological jaundice, and to evaluate iodine status of these babies and their mothers. METHODS: Fifty-five apparently healthy newborn were evaluated. Twenty-five of them showed borderline thyroid dysfunctions. Remained 30 babies had normal thyroid function, considered as euthyroid group. Iodine status was evaluated by measuring urinary iodine excretion. RESULTS: According to UIE, maternal iodine deficiency (55%) associated with neonatal iodine overload (65%) had came to attention. Although mean urinary iodine levels in both mother groups were similar, the mean urinary levels of borderline hypothyroidic and euthyroid groups were 432+/-129 microg/l and 271.5+/-137 microg/l, respectively. Iodine overload was also presence in newborn with normal thyroid function tests. CONCLUSION: We considered that individual sensitivity to iodine overload could make the differentiation on thyroid function. Iodine overload in important degree seen in borderline hypothyroidic babies emphasize the harmful effect of topical antiseptic iodine application that given to mothers during labor. This application could also mask possible prenatal iodine deficiency.

Identification of frequency and distribution of the nine most frequent mutations among patients with 21-hydroxylase deficiency in Turkey.

UNLABELLED: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders mainly due to defects in the steroid 21-hydroxylase (CYP21A2) gene. METHODS: To determine the mutational spectrum in the Turkish population, the CYP21A2 active gene was analyzed in 100 unrelated patients with the classical form of 21-hydroxylase deficiency using PCR and RFLP. RESULTS: Mutations were detected in 78 patients: 64 patients were homozygous for one mutation, seven patients were compound heterozygous with different mutations on each chromosome, two patients were homozygous for two different mutations, five patients were heterozygous, and 22 patients harbored none of the tested mutations. The most frequent mutation was IVS2-13A/C (28.5%), followed by large gene deletion (17%), Q318X (11.5%), I172N (4%), V281L (3.5%), R356W (3.5%), 8-bp (3%), complex alleles (2%), P30L (1%) and E6 cluster (1%). CONCLUSION: The distribution of mutation frequencies in our study was slightly different from those previously reported in Turkey and in other parts of the world.

Plasminogen activator inhibitor-1 (PAI-1) gene polymorphism (-675 4G/5G) associated with obesity and vascular risk in children.

UNLABELLED: Atherothrombotic complications in insulin resistance are partly attributed to impaired fibrinolysis caused by increased PAI-1 plasma levels, and 4G/5G promotor polymorphism of the PAI-1 gene may modulate PAI-1 transcription. OBJECTIVE: To investigate PAI-1-675 4G/5G allele gene polymorphism and its relationship with obesity in children. CHILDREN AND METHOD: The study participants were 133 apparently healthy non-obese children, 24 probable exogenously obese without family history (Group I), 66 probable familial obese (Group II), and 44 obese children who were referred to the pediatric endocrinology department with any complication of obesity (Group III). Group I and Group II obese children were gathered from a school-based epidemiological study. RESULTS: Incidence of obesity was 19% in a school with high socio-economic status, whereas it was 4% in a school with low socio-economic status. Frequencies of 4G/4G gene polymorphisms were 24.81%, 37.50%, 64.80% and 61.11% in the control group, and groups I, II, and III, respectively. In groups II and III, 4G/4G gene polymorphism, and in non-obese control children 5G/5G gene polymorphism, was common. In obese children in the presence of family history for obesity and metabolic syndrome (odds ratio [OR]: 4.48, 95% confidence interval [CI]: 1.26-15.82), carriage of the 4G allele either in heterozygous or homozygous state increased the risk of vascular disease (OR: 6.10, 95% CI 1.64-22.90). In patients with acanthosis nigricans, high HOMA-IR values, hypertriglyceridemia and elevated atherogenic index, 4G/4G genotype frequency was remarkably higher compared to patients with other features of metabolic syndrome. CONCLUSION: The increasing prevalence of childhood obesity in high socio-economic status is associated with health risks. In obese children with family history of obesity and cardiovascular disease or type 2 diabetes mellitus and in obese children who had any feature of metabolic syndrome, frequency of 4G/4G genotype was more than the 4G/5G and 5G/5G genotypes in the PAI-1 gene. These patients can be at increased risk for developing vascular disease. Acanthosis nigricans, high HOMA-IR value, hypertriglyceridemia and high atherogenic index can also reflect the high risk of vascular disease in metabolic syndrome.

Response to growth hormone with respect to pubertal status on increased dose in idiopathic growth hormone deficiency: an analysis of Turkish children in the KIGS database (Pfizer International Growth Study).

AIM: To compare the growth response to growth hormone (GH) treatment in patients with idiopathic GH deficiency (IGHD) who were prepubertal with the response of those who were pubertal at the onset of GH therapy on an increased GH dose. PATIENTS AND METHODS: Among the Turkish patients enrolled in the Pfizer International Growth Study (KIGS) database with the diagnosis of IGHD, the growth data over 2 years of GH therapy were analyzed longitudinally of 113 (79 M) prepubertal (Group 1) and 44 (33 M) pubertal (Group 2) patients. Pubertal signs were reported to be present initially or to have appeared within 6 months of GH therapy in Group 2. Mean +/- SD age at onset of therapy was 8.7 +/- 3.5 and 13.5 +/- 1.8 years; height SDS -4.2 +/- 1.4 and -3.2 +/- 1.1 (p < 0.05) in Groups 1 and 2, respectively. Mid-parental height (MPH) SDS did not show a significant difference between the two groups (-1.5 +/- 1.1 vs -1.7 +/- 1.1). RESULTS: Delta height SDS over 2 years of therapy was significantly higher in Group 1 (1.1 +/- 1.0) than in Group 2 (0.7 +/- 0.6) (p <0.05) in spite of a significantly lower dose of GH (14.6 +/- 3.3 in Group 1 vs 17.0 +/- 3.1 IU/m2/week in Group 2, p < 0.05). Ht--MPH SDS showed an increase from -2.4 +/- 1.7 to -1.4 +/- 1.5 in Group 1 and from -1.5 +/- 1.5 to -0.8 +/- 1.3 in Group 2. Overall delta height SDS showed negative correlations with age (r = -0.32), height SDS (r = -0.41) and height--MPH SDS (r = -0.40) at onset of therapy (p < 0.001). CONCLUSIONS: These data show that in IGHD the slight increase (15-20%) in the dose of GH during puberty was not adequate to maintain height velocity at the same magnitude as in prepuberty, and thus was not cost effective.

Multiple dose IVIG treatment in neonatal immune hemolytic jaundice.

Isoimmune hemolytic jaundice due to ABO and Rh blood group incompatibility is an important problem in the neonatal period. Intravenous immune globulin (IVIG) treatment in isoimmune jaundice has been shown to be effective, but the response to treatment is variable. In this study, the effect of multiple doses IVIG therapy versus single dose MG therapy was investigated in 61 babies who had ABO and Rh hemolytic disease. Patients were divided into three groups. Group I received multiple dose IVIG treatment, group II received single dose MG treatment, and group III was not given any IVIG. All three groups received phototherapy. No exchange transfusion was needed in group I. The rate of exchange transfusion was 12 per cent in group II and 33 per cent in group III. Duration of phototherapy was shorter in group I than in groups II and III. It was concluded that IVIG treatment reduces the need of exchange transfusion in neonatal isoimmune hemolytic jaundice by lowering hemolysis. Multiple doses IVIG treatment appears to be better at blocking ongoing hemolysis.

Hajdu-Cheney syndrome with growth hormone deficiency and neuropathy.

A Hajdu-Cheney syndrome is a very rare congenital dysplastic bone disease including acro-osteolysis, short stature, characteristic facies, osteopenia, abnormalities of spine, skull and long bones. A 9 year-old boy presented at our clinic with a chief complaint of short stature and frequent lower respiratory tract infections. He had typical physical and radiographic features of Hajdu-Cheney syndrome associated with growth hormone (GH) deficiency and peripheral motor neuropathy. To our knowledge, this is the first report describing GH deficiency and neuropathy in Hajdu-Cheney syndrome.