RESUMO
OBJECTIVE: Increased prevalence of celiac disease (CD) and autoimmune thyroid disorders (ATD) in patients with Type 1 diabetes mellitus (T1D) has been widely reported. Such an association may lead to adverse effects on the growth, bone metabolism and fertility, and response to therapy may become difficult. The aim of this study was to evaluate the clinical findings and HLA typing results in patients with T1D associated with CD or ATD. METHODS: The association of CD and ATD was evaluated in 38 children with T1D aged 1.5-16.8 years who had been followed for 48.3±28 months. Diagnosis of CD was based on positivity for serum endomysial IgA antibody and histopathological findings of intestinal biopsy specimens. Thyroid autoimmunity was assessed by antithyroglobulin and antithyroid peroxidase antibodies and with diagnostic ultrasonographic findings. RESULTS: ATD was detected in 31.5%, and CD-in 7.8% of T1D patients. Subjects with CD showed either no symptoms or suggestive problems such as short stature, hepatosteatosis, pubertal delay and difficulties in the control of diabetes. Patients with ATD had no clinical symptoms. DQ8 was the most prominent finding in CD. CONCLUSIONS: It is essential that patients with T1D, regardless of presence or absence of symptoms, should be investigated for CD and ATD.
Assuntos
Doenças Autoimunes/complicações , Doença Celíaca/complicações , Diabetes Mellitus Tipo 1/complicações , Doenças da Glândula Tireoide/imunologia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/imunologia , Feminino , Antígenos HLA/análise , Humanos , Lactente , Masculino , Prevalência , Doenças da Glândula Tireoide/complicaçõesRESUMO
The management of children with congenital adrenal hyperplasia (CAH) remains a challenge, especially with regard to their growth potential. We aimed to determine the correlation of the final height of Turkish children with classical CAH to their genetic height potential and to determine the effect of hydrocortisone replacement therapy on the final height. A total of 24 CAH (16 simple virilizing and 8 salt-wasting form) were included in this retrospective longitudinal study. The final height (FH), final height standard deviation score (FHSDS), target height (TH), target height standard deviation score (THSDS), corrected height for target height (CHSDS), weight, and body mass index (BMI) were calculated for all patients. We evaluated the adult height taking into consideration the correlation with the genetic height potential and the country standards. The average follow-up time was 14.2 +/- 3.1 years and the average daily hydrocortisone dose was 19.7 +/- 2.9 mg/m2. The mean FH and FHSDS were 152.2 +/- 7.2 cm and -1.0 +/- 1.1 SD, respectively, in females and 163.1 +/- 6.6 cm and -1.2 +/- 1.0 SD, respectively, in males. The CHSDS was found to be -0.73 +/- 0.9 SD. FH was below the TH in 79.1% of our cases. In 20.8% of our patients, FH was less than the third percentile for the standard height for our country. Interestingly, the FH showed no correlation with the dosage of hydrocortisone. Thirteen of our cases (54.2%) reaching FH were obese/overweight. A positive correlation was detected between hydrocortisone treatment and the BMI. The observations that 79.1% of our classical CAH cases receiving an average daily hydrocortisone dose of 19.7 +/- 2.9 mg/m2 ended up with an adult height below the TH and that 54.2% of the cases were overweight/obese lead us to believe that we should be using the lowest possible dose for treatment.
Assuntos
Hiperplasia Suprarrenal Congênita/fisiopatologia , Estatura/fisiologia , Terapia de Reposição Hormonal/métodos , Hidrocortisona/administração & dosagem , Adolescente , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Índice de Massa Corporal , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
Diabetes is an important problem encountered in thalassemic patients. The severity and type of glucose disturbances vary greatly in different studies. Also the pathogenesis seems to be complex; either insulin deficiency or insulin resistance may mediate the glucose disturbances. In a group of thalassemic patients glucose homeostasis was evaluated. Diabetes prevalence was 1.8%. Forty patients were investigated both with an oral glucose tolerance test and first-phase insulin response. Three patients had impaired fasting glucose, 1 patient had impaired glucose tolerance, and 2 patients had hyperinsulinism. Nineteen of 40 patients who were tested had low first-phase insulin response (47.5%) with below 10th centile. Age, BMI, height SDS, age at diagnosis, age at first blood transfusion, number of blood transfusions in a year, percentage of elevated liver enzyme, and hemoglobin and ferritin levels were not different between patients with low first-phase insulin response to patients with normal first-phase insulin response. Four patients are HCV infected, and only 1 of them had low first-phase insulin response. The study group showed a high rate of impairement in insulin secretion by first-phase insulin response to glucose overload, despite the low rate of insulin resistance. Defect of insulin secretion in thalassemic patients may develop earlier than insulin resistance, and then be accompanied by insulin resistance. Increasing insulin resistance with age and the occurrence of additional factors could lead to detoriation of glucose metabolism.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus/etiologia , Resistência à Insulina , Insulina/metabolismo , Talassemia/metabolismo , Adolescente , Adulto , Transfusão de Sangue , Criança , Pré-Escolar , Diabetes Mellitus/epidemiologia , Feminino , Teste de Tolerância a Glucose , Homeostase , Humanos , Insulina/administração & dosagem , Insulina/sangue , Secreção de Insulina , Masculino , Talassemia/complicações , Talassemia/terapia , Adulto JovemRESUMO
AIM: To determine the percentage of patients with inappropriate secretion of TSH (ISTSH) in a large cohort of patients with congenital hypothyroidism (CH), and to examine a probable influence of the pretreatment T4 or TSH levels and the etiology of CH on ISTSH by describing the clinical features of these patients. PATIENTS AND METHODS: We retrospectively examined the records, including anthropometric data, clinical findings, and thyroid function tests (TFT), of 500 children diagnosed with CH. Inclusion criteria of ISTSH were appropriate doses of L-T4, improvement of clinical findings, normalization of serum total T4 levels and persistently high TSH concentrations. A group of patients who demonstrated adequate suppression of TSH (<6 mU/l) with therapy among 500 CH patients were chosen randomly as a control group. Both groups were compared with regard to the etiology of CH, and TFT at baseline and during the treatment period. RESULTS: Overall, 27 (5.4%) out of the 500 patients with CH had ISTSH. Nine patients (1.8%) with ISTHS did not show TSH normalization during the follow-up period. Four out of 27 patients with ISTSH had organic lesions (three empty sella, one corpus callosum agenesis) on cranial imaging. No statistically significant difference was found between the groups for etiological classification. The pretreatment T4 and TSH levels in ISTHS and control groups were not significantly different. CONCLUSIONS: Our results suggest that a minority (5.4%) of adequately treated children with CH have persistently raised TSH levels. The delay in normalization of TSH is not related to pretreatment T4 and TSH values or the etiology of CH.
Assuntos
Hipotireoidismo Congênito/sangue , Hipotireoidismo Congênito/tratamento farmacológico , Triagem Neonatal , Tireotropina/sangue , Tiroxina/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Eletroquímica , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Medições Luminescentes , Masculino , Estudos Retrospectivos , Testes de Função Tireóidea , Tiroxina/sangue , Fatores de TempoRESUMO
BACKGROUND: 45,X Turner syndrome (TS) female subjects have visuospatial skill and social cognition deficits that may arise from X-linked imprinting. The aim of the present study was to compare phenotypic characteristics and neurocognitive pattern of 12 monosomic TS girls, according to X-linked imprinting. METHODS: Microsatellite markers were used to determine the parental origin of the missing chromosome X. Wechsler Intelligence Scale for Children-Revised (WISC-R) was administered as measures of general intellectual functioning. The results were compared in TS patients with maternally derived X chromosome (Xm) and paternally derived X chromosome (Xp). RESULTS: Six out of 12 patients (50%) had Xm, and the other six (50%) had Xp chromosome. There was no difference in the total, verbal and performance IQ score between the TS subgroups with Xm and Xp. When the WISC-R subtest score patterns were compared, the mean arithmetic scores were significantly poorer in the Xm TS than in the Xp TS. CONCLUSION: In monosomic TS cases, paternal imprinting may predict arithmetic ability, on the other hand, reductionist consideration defined by genetic imprinting is not sufficient to confirm this. Further studies should be undertaken to clarify this situation.
Assuntos
Cromossomos Humanos X/genética , Genes Ligados ao Cromossomo X/fisiologia , Síndrome de Turner/genética , Síndrome de Turner/psicologia , Adolescente , Criança , Cognição/fisiologia , Feminino , Humanos , Fenótipo , Síndrome de Turner/patologiaRESUMO
Premature pubarche can be benign, or it can be an early marker of insulin resistance in some girls. The aim of this study was to evaluate insulin resistance in prepubertal girls presenting with premature pubarche (n = 19; mean age = 6.93 +/- 1.78) as compared to age- and Tanner stage-matched controls (n = 10; mean age = 7.55 +/- 1.32) using indirect insulin resistance parameters. Two groups were compared by means of oral glucose tolerance test (OGTT), indirect insulin resistance (IR) parameters [homeostasis assessment (HOMA) models: HOMA-IR, glucose/insulin (G/I)] and serum lipid profiles. In the girls with premature pubarche, mean baseline insulin level and HOMA-IR value were significantly higher and G/I ratio was lower than in the control group. IR was observed in 42.1% and in 31.6% according to HOMA-IR value and G/I ratio, respectively. Even at diagnosis, IR was increased in a significant portion of the girls with premature pubarche.
Assuntos
Homeostase , Resistência à Insulina , Insulina/sangue , Puberdade Precoce/sangue , Estudos de Casos e Controles , Criança , Feminino , Teste de Tolerância a Glucose , Hormônios/sangue , Humanos , Lipídeos/sangue , Estatísticas não Paramétricas , TurquiaRESUMO
OBJECTIVE: The effect of parental rearing on gender identity development in children with ambiguous genitalia remains controversial. The present study aimed to address this issue by investigating the factors that may be associated with sex of rearing in children with male pseudohermaphroditism. METHOD: The study included 56 children with male pseudohermaphroditism that were consecutively referred to a child psychiatry outpatient clinic. At the time of referral the age range of the sample was 6 months-14 years; 28 children had been raised as boys and 28 as girls. Demographic and biological information was obtained from patient charts. An intersex history interview was administered to the children and parents, whereas The Gender Identity Interview and the Draw-A-Person Test were administered only to the children. The children were observed during free play. Comparisons of biological, psychological and social variables were made with respect to gender of rearing. RESULTS: More children reared as boys were younger at time of referral, belonged to extended families, and had higher Prader scores. Although children's gender roles were appropriate for their gender of rearing, findings of the Gender Identity Interview and the Draw-A-Person Test suggested that some of the girls presented with a male or neutral gender self-perception. CONCLUSION: The relationships between age at the time of problem identification, age at the time of diagnosis, and gender of rearing indicate the importance of taking measures to ensure that the intersex condition is identified at birth and children are referred for early diagnosis, gender assignment, and treatment.
Assuntos
Educação Infantil , Transtornos do Desenvolvimento Sexual/psicologia , Identidade de Gênero , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
The most complicated group of sexual differentiation disorders is that of gonadal development. Disorders of gonadal development form a wide clinical, cytogenetic and histopathological spectrum. There are still some unsolved difficulties of diagnosis, development of malignancy and the sex rearing of these patients. We reviewed 23 cases of gonadal developmental disorders among 169 patients with ambiguous genitalia or delayed puberty. Among 169 patients, 87 patients were 46,XY disorders of sex development (DSD), 59 patients were 46,XX DSD without disorders of gonadal development and the remaining 23 patients had disorders of gonadal development. Nine of these 23 patients were diagnosed as 46,XY gonadal dysgenesis, 7 patients had ovotesticular DSD, 5 patients had 45,X/46,XY mixed gonadal dysgenesis. Fourteen patients with disorders of gonadal development had genital ambiguity, 5 patients had a female genital phenotype with a palpable gonad and/or delayed puberty. Four patients had the male genital phenotype. Disorder of gonadal development is a very important clinical problem with different aspects of diagnosis, treatment, rearing sex and prophylaxis. Each patient should be evaluated individually employing a multidiciplinary approach.
Assuntos
Disgenesia Gonadal 46 XX/genética , Disgenesia Gonadal 46 XY/genética , Ovário/patologia , Testículo/patologia , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Disgenesia Gonadal 46 XX/patologia , Disgenesia Gonadal 46 XY/patologia , Humanos , Lactente , Recém-Nascido , Cariotipagem/métodos , Masculino , Prognóstico , Análise para Determinação do Sexo/métodosRESUMO
AIMS: Functional ovarian hyperandrogenism (FOH) is considered to be a form of polycystic ovary syndrome (PCOS) at adolescence. There are almost no data in the prepubertal period, although one of the earliest manifestations of PCOS is premature pubarche. Prepubertal girls with obesity or insulin resistance are also at risk to develop the full PCOS phenotype after puberty. The aim of this study was to evaluate prepubertal girls with premature pubarche and/or obesity for PCOS or FOH. METHODS: Twenty-seven prepubertal girls with premature pubarche and/or obesity aged >6 years were evaluated. FOH was defined as abnormal ovarian 17OHP response to challenge with GnRH analog of >2 ng/ml after exclusion of adrenal dysfunction. All patients underwent a pelvic ultrasound examination. RESULTS: Sixteen patients had premature pubarche, seven were obese, and four had both premature pubarche and obesity. Eleven of 27 patients (40.7%) showed high (>2 ng/ml) 17OHP response to GnRH challenge. Three patients (11%) with FOH also showed PCO morphology on pelvic ultrasound examination. CONCLUSION: In prepubertal girls who carry risk factors, including genetic polymorphisms and/or particular environmental factors, FOH/PCOS could develop at a high rate.
Assuntos
Hiperandrogenismo/epidemiologia , Hiperandrogenismo/etiologia , Obesidade/complicações , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/etiologia , Puberdade Precoce/epidemiologia , Criança , Feminino , Humanos , Resistência à Insulina , Obesidade/epidemiologia , Ovário/patologia , Prevalência , Puberdade , Puberdade Precoce/complicações , Fatores de RiscoRESUMO
AIM: To assess the effect of interferon-alpha (IFN-alpha) therapy on thyroid functions in children with chronic hepatitis B infection (CHB). METHODS: Sixty-eight children (7.8 +/- 3.6 years) were treated with 5 (n = 37, group I) or 10 MU/m2 (n = 31, group II) IFN for 6 months. Thyroid hormones, thyrotropin, thyrotropin-releasing hormone stimulation test, thyroid peroxidase and thyroglobulin autoantibodies were evaluated. RESULTS: Baseline features were not different in the two groups. After therapy, thyroid dysfunction was 27% and 41.9% in groups I and II (n.s.). Subclinical hypothyroidism was 17.9%/ 29%, subclinical hyperthyroidism 5.4%/12.9%, hypothyroidism 2.7%/-, and thyroid antibody positivity 2.7%/- in groups I and II (n.s.). Thyroid dysfunction was 33.8% in the whole group (p = 0.001). Predictors of IFN induced-thyroid dysfunction were female sex and age < 6 years. Thyroid dysfunction resolved within median 6 months in all but three children. CONCLUSION: Although IFN-induced thyroid dysfunction is mostly subclinical and reversible, this side effect should be kept in mind.
Assuntos
Antivirais/efeitos adversos , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/epidemiologia , Glândula Tireoide/fisiopatologia , Adolescente , Antivirais/uso terapêutico , Autoanticorpos/sangue , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Interferon-alfa/uso terapêutico , Iodeto Peroxidase/sangue , Masculino , Fatores de Risco , Tireoglobulina/imunologia , Hormônios Tireóideos/sangue , Tireotropina/sangueRESUMO
Optimal management of differentiated thyroid cancer in childhood is undetermined. During monitoring of thyroid carcinoma, serum thyroglobulin (hTG) levels provide valuable information. hTG levels not only increase in differentiated thyroid cancers but also in iodine deficiency because of compensation by the thyroid gland. A 14.6 year-old girl was diagnosed with nodular goiter, subclinical hypothyroidism and severe iodine deficiency. She had a very high hTG level. Despite benign fine-needle aspiration biopsy (FNAB), because the hTG level was still very high after treatment with LT4, thyroidectomy was undergone. Cytopathological examination showed minimally invasive follicular thyroid carcinoma. During follow-up, to exclude the presence of persistent/recurrent disease, the hTG level rose to an undesirably high level after withdrawal of TSH suppressive therapy, and radioiodine ablation therapy was applied. This report shows that even if there is an explanation for nodular goiter and high hTG levels, such as iodine deficiency, malignancy cannot be ruled out without thyroidectomy. FNAB is not reliable especially in iodine deficient areas. Serum hTG measurement is a valuable tool for both diagnosis and follow-up of differentiated thyroid carcinoma in children.
Assuntos
Carcinoma Papilar, Variante Folicular/diagnóstico , Iodo/deficiência , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Adolescente , Antitireóideos/uso terapêutico , Biópsia , Carcinoma Papilar, Variante Folicular/sangue , Carcinoma Papilar, Variante Folicular/patologia , Feminino , Bócio Nodular/complicações , Bócio Nodular/patologia , Humanos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Tireotropina/antagonistas & inibidores , Tiroxina/uso terapêuticoRESUMO
We present ultrasonographic and magnetic resonance imaging findings of intratesticular adrenal rests in a 16-year-old patient with congenital adrenal hyperplasia. Scrotal ultrasonography showed bilateral well-delineated homogenous hypoechoic lesions located around the mediastinum testis, which were highly vascularized on power Doppler ultrasonography. Relative to normal testicular parenchyma the lesions were iso- or hyperintense on T1-weighted and hypointense on T2-weighted images. T2-weighted images also showed a target-like appearance caused by a more hypointense peripheral halo around the lesions. The lesions enhanced remarkably on post-contrast images. This case suggests that radiological evaluation of testes, even in the presence of normal physical examination findings, should be included in periodical follow-up of patients with congenital adrenal hyperplasia. Magnetic resonance (MR) imaging is useful in demonstrating the lesions, because the contrast resolution better than with ultrasonography.
Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico por imagem , Hiperplasia Suprarrenal Congênita/patologia , Tumor de Resto Suprarrenal/diagnóstico por imagem , Tumor de Resto Suprarrenal/patologia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/patologia , Adolescente , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , UltrassonografiaRESUMO
OBJECTIVE: Long-term replacement treatment with high doses of steroids in congenital adrenal hyperplasia (CAH) is known to have a negative influence on growth. We evaluated the effects of long-term steroid treatment in patients with classical CAH on height development in relation to genetic height potential. PATIENTS AND METHODS: Twenty-three patients with CAH (16 females, 7 males, mean age: 9.8 +/- 3.5 years) were included in this longitudinal study. The effect of steroid treatment on growth was determined by monitoring patients for 8.61 +/- 3.46 years (2-17 years) while they were treated with hydrocortisone at a mean dosage of 17.64 +/- 3.60 mg/m2/day. The height standard deviation scores (Ht-SDS), target Ht-SDS, and corrected Ht-SDS for target height was calculated for all patients. Predicted adult height according to bone age was calculated and it was determined whether height was developing according to the genetic height potential. In addition, patients were grouped as 'tight control' or 'poor control' according to their mean serum 17OH-progesterone or ACTH levels while on treatment. We evaluated whether height development was different for the tight and poor control groups. RESULTS: The mean chronological age of our patients at the time of the study was 9.89 +/- 3.53 years, Ht-SDS -0.77 +/- 1.57, target height (TH) 161.03 +/- 6.54 cm, TH-SDS -0.60 +/- 0.90, predicted height (PH) 157.2 +/- 11.16 cm, PH-SDS -1.1 +/- 1.69, and corrected Ht-SDS -0.75 +/- 1.14. There was no significant difference between the actual Ht-SDS and TH-SDS of our patients (p >0.05) but the corrected Ht-SDS was less than zero. Only 28.5% of our patients had normal height according to their genetic potential while 71.5% were shorter than their genetic height potential. While the Ht-SDS and corrected Ht-SDS were similar in the tight and poor metabolic control groups, the predicted height was significantly greater in the tight control group. CONCLUSION: We demonstrated that a hydrocortisone dose of 17.64 +/- 3.60 mg/m2/day in classical CAH had a negative influence on height development for genetic height potential in 8.5 years of follow-up and that it is necessary to use the lowest possible steroid dosage by individualizing the dose.
Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Estatura/efeitos dos fármacos , Transtornos do Crescimento/induzido quimicamente , Transtornos do Crescimento/fisiopatologia , Hidrocortisona/efeitos adversos , 17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/complicações , Hormônio Adrenocorticotrópico/sangue , Determinação da Idade pelo Esqueleto , Antropometria , Estatura/genética , Criança , Pré-Escolar , Feminino , Seguimentos , Transtornos do Crescimento/sangue , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hidrocortisona/uso terapêutico , Lactente , Estudos Longitudinais , Masculino , Estatísticas não ParamétricasRESUMO
In endemic areas iodine deficiency, and in iodine sufficient regions autoimmune thyroiditis, is the first aetiological factor for goitre. The aims of this study were to determine the incidence of iodine deficiency and autoimmune thyroiditis in patients presenting with goitre, to compare clinical and ultrasonographic assessment of thyroid size and to investigate the relationship between iodine and autoimmune thyroiditis. Patients diagnosed with goitre clinically (n = 204) were evaluated by their anthropometric measurements, ultrasonographic examination of the thyroid gland, thyroid function and TRH stimulation tests, thyroid autoantibodies and morning urinary iodine measurements. Thyroid volumes were evaluated according to three different reference criteria. Incidences of iodine deficiency and autoimmune thyroiditis were 54% and 17%. The incidences of iodine deficiency and excess were not significantly different in the autoimmune group (n = 35) compared to the non-autoimmune group (n = 169). In the autoimmune group, urinary iodine concentration correlated positively with serum thyroid hormones (FT3 r = 0.42, TT3 r = 0.38, TT4 r = 0.34) and negatively with serum TSH levels (r = 0.45). There were discrepancies between clinical and ultrasonographic evaluation of goitre, and between different reference criteria. This study revealed that iodine deficiency is still the first aetiological factor for goitre in our region and failed to show a relationship between iodine intake and autoimmune thyroid disease.
Assuntos
Bócio/epidemiologia , Iodo/deficiência , Glândula Tireoide/metabolismo , Tireoidite Autoimune/epidemiologia , Hormônio Liberador de Tireotropina/sangue , Adolescente , Adulto , Antropometria , Criança , Pré-Escolar , Comorbidade , Feminino , Bócio/diagnóstico por imagem , Bócio/metabolismo , Humanos , Incidência , Iodo/urina , Masculino , Tamanho do Órgão , Fatores Sexuais , Estatísticas não Paramétricas , Estimulação Química , Testes de Função Tireóidea , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Tireoidite Autoimune/diagnóstico por imagem , Tireoidite Autoimune/metabolismo , Turquia/epidemiologia , UltrassonografiaRESUMO
5 alpha steroid reductase 2 (5 alpha SR2) deficiency is an autosomal recessive enzyme defect causing male pseudohermaphroditism (MPH) because of an abnormally low peripheral conversion of testosterone to dihydrotestosterone (DHT), which is required for the normal differentiation of external male genitalia. The present report describes the distribution of 5 alpha steroid reductase gene mutations in the Turkish population in the light of published reports from different centers. Eight Turkish patients from unrelated Turkish families and a large pedigree of one of these patients are also discussed. These patients were followed up at Ankara University Department of Pediatric Endocrinology. The presence of Leu 55 Gln mutation in six patients out of 8 indicates the increased prevalence of this mutation in the Turkish population with different presentations. One patient out of six (patient FG) had a large pedigree of Leu 55 Gln mutation in exon 1. The pedigree of this family with marital consanguinity was very remarkable and extraordinary. A further 85 members of this family were analyzed for exon 1 Leu 55 Gln 5 alpha SR2 gene mutations. Forty two out of the 85 subjects (49.41% ) had this alteration in gene mutation. Thirty-one of them were heterozygous (18 genetic male, 13 genetic female) and 11 of them were homozygous (8 genetic male, 3 asymptomatic female carriers) for this mutation. A trinucleotid deletion at straddling codons 156 and 157 is responsible for a methionize residue at position 157 (delta Met 157) of 5 alpha SR type 2 gene which was first described in our patient NA. Two additional Turkish patients were reported by different investigators with this rare mutation and this also suggests an increased prevalence of this mutation in the Turkish population. In conclusion Leu 55 Gln mutation in exon 1 seems to be a hot spot in Turkish patients. Hence 5 alpha SR2 gene mutation analysis especially Leu 55 Gln mutation in exon 1 and delta Met 157 in exon 3, must be evaluated in Turkish patients with male pseudohermaphroditism according to our results and other Turkish patients reported by different investigators. It is important that homozygous asymptomatic female carriers be taken into consideration in this clinical entity especially in closed populations because of the risk of carrying the disease to their offspring.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/deficiência , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Análise Mutacional de DNA , Transtornos do Desenvolvimento Sexual/genética , Adolescente , Criança , Feminino , Genitália/anormalidades , Humanos , Lactente , Recém-Nascido , Masculino , Linhagem , TurquiaRESUMO
BACKGROUND/AIM: The availability of sensitive thyrotropin (TSH) assays decreased the diagnostic value of thyrotropin-releasing hormone stimulation tests (TRH-ST) in subclinical hypothyroidism. In this study we aimed to evaluate the relation between basal and stimulated serum TSH levels on TRH-ST and to determine the prevalence of patients with normal basal serum TSH and exaggerated TSH responses. METHODS: 179 patients (117 girls, 123 pubertal) with a median age of 12 (2.7-21.4) years who presented with goiter were enrolled and evaluated for their pubertal stage, height, thyroid autoimmunity, ultrasonography, thyroid function, and TRH-ST. Serum TSH concentrations were determined by sensitive assays. At TRH-ST, a peak serum TSH level >25 mIU/l was considered as an exaggerated response. RESULTS: 30 (17%) patients had an exaggerated TSH response. In patients with serum TSH levels between 2 and 4.68 mIU/l (upper half the normal range), an exaggerated TSH response was observed in 19.5%. A positive correlation between basal and TRH-stimulated TSH levels was determined (r = 0.536, p < 0.01). In patients with an exaggerated TSH response, 23 had normal (discordant) and 7 had high basal TSH levels (concordant). The mean basal serum TSH level was lower in the discordant group compared to the concordant group (p < 0.01). CONCLUSION: Basal serum TSH levels might not be sufficient for diagnosing subclinical hypothyroidism. Stimulated TSH levels on TRH-ST are valuable, especially when serum TSH concentrations are in the upper half of the normal range.
Assuntos
Bócio/fisiopatologia , Hormônio Liberador de Tireotropina , Tireotropina/sangue , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Bócio/diagnóstico , Humanos , Hipotireoidismo/diagnósticoRESUMO
CONTEXT: The central clinical feature of GH insensitivity (GHI) is severe growth failure associated with elevated serum concentrations of GH and abnormally low serum levels of IGF-I. GHI can be the result of an abnormality in the GH receptor or aberrancies downstream of the GH receptor. OBJECTIVE: We investigated the GH-IGF-I axis in a young female GHI subject who presented with a height of 114 cm (-7.8 sd score) at age 16.4 yr. PATIENT: The subject, from a consanguineous pedigree, had circulating levels of GH and GH-binding protein that were normal to elevated, whereas IGF-I (7.2 ng/ml; normal, 242-600), IGF-binding protein-3 (543 ng/ml; normal, 2500-4800), and acid-labile subunit (1.22 microg/ml; normal, 5.6-16) levels were abnormally low and failed to increase during an IGF-I generation test. DESIGN: Dermal fibroblast cultures were established with the consent of the patient and family. Immunoblot analysis of cell lysates and DNA sequencing of her signal transducer and activator of transcription 5b (STAT5b), a critical intermediate of the GH-IGF-I axis, were performed. RESULTS: Sequencing of the STAT5b gene revealed a novel homozygous insertion of a single nucleotide in exon 10. The insertion resulted in a frame shift, leading to early protein termination and consequent lack of immunodetectable STAT5b protein. CONCLUSION: The identification of a second case of severe growth failure associated with STAT5b mutation implicates a unique and critical role for STAT5b in GH stimulation of IGF-I gene expression and statural growth.
Assuntos
Proteínas de Ligação a DNA/genética , Mutação da Fase de Leitura , Transtornos do Crescimento/etiologia , Hormônio do Crescimento/farmacologia , Fator de Crescimento Insulin-Like I/genética , Proteínas do Leite/genética , Transativadores/genética , Adolescente , Células Cultivadas , Proteínas de Ligação a DNA/fisiologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Transtornos do Crescimento/genética , Humanos , Fator de Transcrição STAT5 , Transativadores/fisiologiaRESUMO
OBJECTIVES: 1. To evaluate the relationship between plasma leptin and TNFalpha concentrations in obese children and to assess the differences between hyperinsulinemic and normoinsulinemic groups. 2. To evaluate the relationship between plasma leptin and insulin levels in obese children. 3. To investigate the TNFalpha G308A mutation in obese children. METHODS: Body mass index (BMI), fasting plasma glucose and insulin levels, oral glucose tolerance test results, homeostasis model assessment of insulin resistance (HOMA-IR) results, and plasma leptin and TNFalpha concentrations were evaluated in obese children (n = 45) and age- and gender-matched, lean healthy controls (n = 40). RESULTS: In obese children the fasting insulin, HOMA-IR results, plasma leptin and TNFalpha concentrations were significantly higher than in controls (p <0.05). Furthermore, obese females showed higher plasma leptin and insulin resistance compared to obese males. While plasma leptin, TNFalpha levels and HOMA-IR results were similar in the prepubertal and pubertal groups, insulin levels were significantly higher in the pubertal group. Plasma leptin and TNFalpha concentrations were similar in hyperinsulinemic and normoinsulinemic obese children. In control children, plasma leptin concentrations showed a positive correlation with BMI, age, fasting insulin and HOMA-IR results. In obese children, plasma leptin levels did not correlate with BMI, fasting insulin or TNFalpha. CONCLUSION: Plasma leptin concentrations did not show any correlation with TNFalpha levels in obese children. Furthermore, plasma leptin and TNFalpha concentrations were similar in hyperinsulinemic and normoinsulinemic obese children.
Assuntos
Hipoglicemiantes/sangue , Insulina/sangue , Leptina/sangue , Obesidade/imunologia , Obesidade/fisiopatologia , Fator de Necrose Tumoral alfa/análise , Glicemia/análise , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Jejum , Feminino , Homeostase , Humanos , MasculinoRESUMO
Latent autoimmune diabetes mellitus in adults (LADA) is characterized by clinical presentation as type 2 diabetes mellitus after 25 years of age, initial control achieved with oral hypoglycemic agents for at least 6 months, presence of autoantibodies and some immunogenetic features of type 1 diabetes mellitus. An 8.3 year-old girl was referred to our pediatric endocrinology department because of incidental glucosuria. She did not complain of polyuria, polydipsia, or weight loss. Her body mass index (BMI) was at the 80th percentile. Fasting glucose was 126 mg/dl, and OGTT glucose level at 120 min was 307 mg/dl. Although C-peptide levels were normal, her first phase insulin response (FIR) was lower than the 1st percentile. Anti-insulin antibody (AIA), islet cell antibody (ICA), and anti-glutamic acid decarboxylase (antiGAD) were negative. According to the clinical and laboratory findings, she was diagnosed as having type 2 diabetes mellitus. She was started with oral anti-diabetic treatment for a period of 1 year. Insulin had to be initiated for worsening of HbA1c levels. In the fourth year of follow-up, she was admitted to our hospital with diabetic ketoacidosis although she was on an intensive insulin regimen. At this time, C-peptide levels were low, antiGAD and AIA were positive with HLA DR3/DQ2 haplotype. In addition, her thyroid peroxidase antibody and endomysium antibody were found to be high at follow-up. Small intestinal biopsy revealed celiac disease. This patient may represent the first case of latent autoimmune diabetes mellitus in children (LADC) with autoimmune thyroiditis and celiac disease.
Assuntos
Doença Celíaca/complicações , Diabetes Mellitus Tipo 1/etiologia , Tireoidite Autoimune/complicações , Glicemia/metabolismo , Índice de Massa Corporal , Peptídeo C/metabolismo , Criança , Diabetes Mellitus Tipo 1/sangue , Feminino , Glicosúria/etiologia , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
Human chorionic gonadotropin (hCG) stimulation test is a reliable dynamic test for the evaluation of testicular function during childhood. Several protocols have been recommended but their reliability is controversial. In order to decide the best timing to measure stimulated testosterone levels in short- and long-term hCG protocols, we evaluated 83 prepubertal patients in two group. In group A, 34 patients with isolated micropenis and in group B, 49 inguinal cryptorchidic patients were enrolled. In group A short-term hCG protocol (3000 IU/m2/im/3 days) and in group B long-term hCG protocol (1500 IU/m2/im; thrice a week for 3 weeks) was administered. Blood samples were drawn at the initiation of the test and then at the 1st and 4th days after the last hCG injection. Each case's peak stimulated testosterone (Tmax) and the incremenet in plasma testosterone (deltaT) were calculated and compared with the 1st and 4th day responses within the group. In the short-term protocol the 4th day responses were higher than the 1st day responses (p<0.01). Interestingly, while four patients had insufficient responses at the 1st day, three had sufficient Leydig cell response at the 4th day. In the long-term protocol group, in contrast to the short-term group, the 1st day responses were higher than the 4th day (p<0.01). According to our results, while performing hCG test in a patient, if a short-term protocol is planned, it is more convenient to check the 4th day testosterone response. On the other hand, in a long-term protocol it is best to check the 1st day response. We suggest that even if a patient's 1st day response is inadequate, the 4th day response should be checked in order to avoid misdiagnosis.