In vivo dosimetry of thyroid doses from different irradiated sites in children and adolescents: a cross-sectional study.

BACKGROUND: Scattered radiation can be assessed by in vivo dosimetry. Thyroid tissue is sensitive to radiation, even at doses <10 cGy. This study compared the scattered dose to the thyroid measured by thermoluminescent dosimeters (TLDs) and the estimated one by treatment planning system (TPS). METHODS: During radiotherapy to sites other than the thyroid of 16 children and adolescents, seventy-two TLD measurements at the thyroid were compared with TPS estimation. RESULTS: The overall TPS/TLD bias was 1.02 (95% LA 0.05 to 21.09). When bias was stratified by treatment field, the TPS overestimated TLD values at doses <1 cGy and underestimated them at doses >10 cGy. The greatest bias was found in pelvis and abdomen: 15.01 (95% LA 9.16 to 24.61) and 5.12 (95% LA 3.04 to 8.63) respectively. There was good agreement in orbit, head, and spine: bias 1.52 (95% LA 0.48 to 4.79), 0.44 (95% LA 0.11 to 1.82) and 0.83 (0.39 to 1.76) respectively. There was small agreement with broad limits for lung and mediastinum: 1.13 (95% LA 0.03 to 40.90) and 0.39 (95% LA 0.02 to 7.14) respectively. CONCLUSIONS: The scattered dose can be measured with TLDs, and TPS algorithms for outside structures should be improved.

[Thyroid disorders associated with external radiation in children and adolescents]. / Alterações tireoidianas associadas à radiação externa em crianças e adolescentes.

The effects of ionizing radiation on the thyroid have been studied for several decades, and nuclear accidents are the major source of information about the subject. There is an association of hypothyroidism, hyperthyroidism, thyroid nodules and cancer with radiation, but the threshold dose, mechanism of injury, and some risk factors have not been fully established. Children are more susceptible to thyroid injury caused by radiation and require prolonged follow-up after exposure. This issue is especially relevant nowadays, since a large number of people treated with radiation for childhood cancer survive and may have sequelae. Diagnostic radiology tests also represent a source of exposure to radiation in the pediatric population. In this review, we analyze different clinical and pathological changes, and the mechanisms of thyroid lesions caused by radiotherapy and computed tomography in children and adolescents. It is important to understand these data for prevention, early detection, and treatment of thyroid dysfunction.

Alterações tireoidianas associadas à radiação externa em crianças e adolescentes / Thyroid disorders associated with external radiation in children and adolescents

O efeito da radiação ionizante sobre a tireoide vem sendo estudado há várias décadas, e os acidentes nucleares têm sido a maior fonte de informação. Existe associação de hipotireoidismo, hipertireoidismo, nódulos e câncer de tireoide com a radiação, mas os limiares de dose, mecanismos de lesão e alguns fatores de risco ainda não estão bem estabelecidos. Crianças são mais suscetíveis à lesão tireoidiana por radiação e necessitam de seguimento prolongado após a exposição. Esse tema adquire maior relevância atualmente, pois um grande número de pessoas tratadas com radioterapia para câncer na infância sobrevive e poderá apresentar sequelas. Exames radiodiagnósticos também representam fonte de exposição à radiação na população pediátrica. Nesta revisão, analisamos as diferentes alterações clínico-patológicas e os mecanismos de lesões tireoidianas provocadas por tratamento radioterápico e tomografia computadorizada em crianças e adolescentes. É importante conhecer esses dados para prevenção, detecção precoce e tratamento da disfunção tireoidiana.

The effects of ionizing radiation on the thyroid have been studied for several decades, and nuclear accidents are the major source of information about the subject. There is an association of hypothyroidism, hyperthyroidism, thyroid nodules and cancer with radiation, but the threshold dose, mechanism of injury, and some risk factors have not been fully established. Children are more susceptible to thyroid injury caused by radiation and require prolonged follow-up after exposure. This issue is especially relevant nowadays, since a large number of people treated with radiation for childhood cancer survive and may have sequelae. Diagnostic radiology tests also represent a source of exposure to radiation in the pediatric population. In this review, we analyze different clinical and pathological changes, and the mechanisms of thyroid lesions caused by radiotherapy and computed tomography in children and adolescents. It is important to understand these data for prevention, early detection, and treatment of thyroid dysfunction.

Avaliação da tolerência à glicose em crianças e adolescentes com fibrose cística / Glucose tolerance evaluation in children and adolescents with cystic fibrosis

Introdução: Cerca de 20% dos adolescentes com fibrose cística têm diabetes melito (DM) relacionado à fibrose cística (FC). O teste oral de tolerância à glicose (TOTG) tem sido utilizado para identificar alterações no metabolismo da glicose. Objetivo: O objetivo deste estudo foi identificar as alterações no metabolismo da glicose em crianças e adolescentes com FC e descrever as características clínicas e laboratoriais relacionadas à tolerância diminuída à glicose (TDG) e DM nesse grupo de pacientes. Pacientes e métodos: Foi realizado um estudo transversal envolvendo crianças e adolescentes com diagnóstico de FC em atendimento no Hospital de Clínicas de Porto Alegre. TOTG com glicose na dose de 1,75 g/kg de peso com dose máxima de 75 g foi realizado. Resultados: No total foram avaliados 58 pacientes (1,9-16,9 anos). TDG foi encontrada em 6 pacientes e presença de DM em 1, todos acima de dez anos de idade. Estes 7 pacientes foram comparados com os outros 29 pacientes de mesma faixa etária com TOTG normal. Os pacientes com o TOTG alterado eram mais velhos (14±1,2 vs. 10,6±4 anos, P<0,001), apresentaram maior tempo de duração da FC (13±2,6 vs. 9±4 anos, P<0,0006) e apresentaram maior número de internações (6 [5-16] vs. 3 [1,5-8,5], P<0,029). Conclusão: Neste estudo foi observada uma prevalência de alteração da tolerância à glicose de 12% em crianças e adolescentes com FC.

Background: About 20% of adolescents with cystic fibrosis (CF) present diabetes related to this condition. The oral glucose tolerance test (OGTT) has been used to identify alterations in glucose metabolism in these patients. Aim: The aim of this study was to identify changes in glucose metabolism in children and adolescents with CF and to describe the clinical and laboratory characteristics related to impaired glucose tolerance (IGT) and diabetes. Patients and methods: This was a cross-sectional study involving children and adolescents with cystic fibrosis (CF). An OGTT with 1.75 g glucose/kg - max 75 g was performed. Results: Fifty-eight individuals (1.9-16.9 years) were evaluated. IGT was found in six and diabetes in one; all were older than 10 years. These 7 patients were compared to the 29 with normal OGTT with the same age. The patients with altered OGTT were older (14±1.2 vs 10.6±4years, P<0.001), had longer FC duration (13±2.6 vs. 9±4 years, P<0.006), and had a higher number of hospitalizations (6 [5-16] vs 3[1.5- 8.5], P<0.029). Conclusion: In this study the prevalence of impaired glucose tolerance was 12% in children and adolescents with CF.

The actual incidence of congenital adrenal hyperplasia in Brazil may not be as high as inferred--an estimate based on a public neonatal screening program in the state of Goiás.

The incidence of 21-hydroxylase deficiency (CYP21 D) congenital adrenal hyperplasia (CAH) in Brazil is purportedly one of the highest in the world (1:7,533). However, this information is not based on official data. The aim of this study was to determine the incidence of CYP21 D CAH in the state of Goiás, Brazil, based on the 2005 results of government-funded mandatory screening. Of the live births during this period, 92.95% were screened by heel-prick capillary 17alpha-hydroxyprogesterone (17-OHP). Of these, 82,343 were normal, 28 were at high risk for CAH and 232 at low risk for CAH. Eight cases, all from the high risk group, were confirmed. Eight asymptomatic children at 6-18 months of age still have high 17-OHP levels and await diagnostic definition. Based on the number of confirmed CYP21 D CAH cases among the 82,603 screened, the estimated annual incidence of the disease was 1:10,325, lower than the previously reported rate in Brazil.

Reduced thyroid volume and hypothyroidism in survivors of childhood cancer treated with radiotherapy.

AIM: Children treated for cancer may have sequelae due to the treatment. The aim of this study was to assess the frequency of hypothyroidism and the thyroid volume of patients treated with radiotherapy for cancer during childhood. PATIENTS: Fifty-nine patients treated with external beam radiation to different areas of the body during childhood. METHODS: Cross-sectional study of patients assessed for late effects of external beam radiation treatment for childhood cancer. General and anthropometric characteristics, time from radiotherapy, family history of thyroid dysfunction, radiotherapy report, thyroid function tests, antithyroperoxidase antibodies and thyroid ultrasound were analyzed. RESULTS: Hypothyroidism was found in 23 (39%) patients, 3.5 +/- 1.9 years after radiotherapy carried out at the mean age of 7.6 +/- 3.4 years. Site of irradiation had the greatest association with hypothyroidism. Anti-thyroperoxidase antibodies were normal in all patients. Thyroid volume was significantly lower in irradiated patients with hypothyroidism than in those with normal thyroid function (p <0.001). CONCLUSIONS: Hypothyroidism is very common in survivors of childhood cancer treated with external beam radiation. Primary thyroid damage is suggested because of the smaller thyroid volume.

Bone mineral density in girls with classical congenital adrenal hyperplasia due to CYP21 deficiency.

AIM: To verify possible associations among glucocorticoid doses, use of dexamethasone, and bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), in female children with congenital adrenal hyperplasia due to CYP21 deficiency (CAH-CYP21). Classical CAH-CYP21 in females allows the study of the effects of hyperandrogenism and chronic glucocorticoid exposure. DESIGN: Cross-sectional observational study. PATIENTS: Sixteen girls (4-19 years) with CAH-CYP21 and 32 age-matched control girls. MEASUREMENTS: BMD was the main outcome measure assessed by total body and lumbar spine L1-L4 DXA (DXAtot and DXAIs), lumbar spine L1-L4 bone mineral apparent density (BMAD) and spinal L1-L4 QCT of trabecular (QCTtrab) and cortical (QCTcort) bone. The glucocorticoid dose used by patients with CAH-CYP21 was expressed as hydrocortisone equivalents/m2. RESULTS: Mean BMD in both groups was similar by any method. In patients, BMD decreased with the increasing mean dose of glucocorticoid, seen in QCTcort (r = -0.55; p = 0.03) and QCTtrab (r = -0.52; p = 0.04). There was also a negative correlation between cumulative glucocorticoid dose and BMD in QCTcort (beta = -0.0016; p = 0.005) and QCTtrab (beta = -0.0009; p = 0.03). CONCLUSIONS: The dose of glucocorticoid used in the treatment of girls with CAH-CYP21 correlated negatively with BMD, and dexamethasone was not selectively harmful.

Portal vein thrombosis and high factor VIII in Turner syndrome.

BACKGROUNDS/AIMS: Turner syndrome is not usually associated with thrombotic events. The aim of this study is to report 3 Turner syndrome patients with portal vein thrombosis and, in 2 of them, high factor VIII. These findings are compared to values in Turner syndrome patients without thrombosis and controls. METHODS: In different years, 3 patients with Turner syndrome were initially seen at the Gastroenterology Clinic of Hospital de Clínicas de Porto Alegre, Brazil, for portal vein thrombosis. After the most common causes of portal vein thrombosis and thrombophilias had been excluded, the 2 surviving patients were studied for clotting factors VIII, IX and von Willebrand factor. The same factors were also assessed in 25 Turner syndrome patients without thrombosis and 25 normal girls. RESULTS: One of the patients with portal vein thrombosis died before the study. In the 2 surviving patients, factors VIII and von Willebrand levels were >150 IU/dl, which is considered to be high. In Turner syndrome patients without thrombosis, the mean factor VIII level was 127.2 +/- 41.1 IU/dl and for von Willebrand factor 101.2 +/- 26.9 IU/dl, while in control girls these were 116.0 +/- 27.6 and 94.28 +/- 27.5 IU/dl, respectively. Factor VIII and von Willebrand factor were not different between these 2 groups. When non-O blood group Turner syndrome patients and normal girls were compared, the former had significantly higher levels of factor VIII. CONCLUSIONS: This is the first report on the unusual finding of portal thrombosis in patients with Turner syndrome in whom high levels of factor VIII and von Willebrand factor were found. Factor VIII is higher in the non-O blood group Turner syndrome patients without thrombosis when compared to normal girls.

Osteogênese imperfeita / Osteogenesis imperfecta

Osteogênese imperfeita é uma doença genética caracterizada por fragilidade óssea ecausada por alterações no colágeno tipo 1. A incidência em nosso meio ainda é desconhecida.O espectro clínico varia de casos leves a graves. Fraturas de repetição, deformidades ósseas ebaixa estatura são os achados mais comuns. O principal diagnóstico diferencial é com maustratos na infância. Ao tratamento de suporte tem sido acrescido o uso de bisfosfonados – drogas que inibem a reabsorção óssea –, com resposta positiva na diminuição das fraturas e aumento da densidade mineral óssea.

Osteogenesis imperfecta is a genetic disorder characterized by bone fragility and causedby changes in type I collagen. Its incidence in our country remains unknown. Clinical spectrumranges from mild to severe cases, with repeated fractures, bone deformities and poor growthbeing the most common clinical findings. The main differential diagnosis is child abuse.Bisphosphonates, which inhibit bone resorption, are used in addition to supportive measures,with a reduction in the number of fractures and an increase in bone mineral density.

Osteodistrofia de Albright / Albright Osteodystrophy

Paciente feminina de 9 anos de idade, de origem asiática, consulta por parestesias em mãos e pés. Tem história de hipotireoidismo desde o primeiro ano de vida, em tratamento com levotiroxina 50 mg/dia. O exame físico revelou 4º e 5º metacarpianos e metatarsianos curtos, estatura entre o percentil 25-50, calcificações subcutâneas e nódulo localizado em tendão de Aquiles. Os exames laboratoriais demonstraram padrão compatível com pseudohipoparatireoidismo

Usefulness of the free alpha-subunit to diagnose hypogonadotropic hypogonadism.

OBJECTIVE: Differentiating constitutional delay of growth and puberty from hypogonadotropic hypogonadism is still a problem in clinical practice. Our previous study demonstrated that the peak/basal ratio of the free alpha-subunit of the glycoprotein hormones is higher in normal prepubertal boys than in male adults with hypogonadotropic hypogonadism. The objective of this study was to assess the performance of this ratio in normal male patients at different ages and levels of pubertal development, and in patients with hypogonadotropic hypogonadism, both isolated and combined with other pituitary hormone deficiencies. DESIGN: Cohort study. PATIENTS: Twenty-eight normal prepubertal males between 6 and 8 years; 20 normal prepubertal males between 9 and 13 years; 18 males with constitutional delay of growth and puberty; 26 normal pubertal males; 13 adult men with isolated hypogonadotropic hypogonadism; 21 adult men with complete hypogonadotropic hypogonadism combined with other hormone deficiencies; and 11 adult men with partial hypogonadotropic hypogonadism combined with other hormone deficiencies. MEASUREMENTS: Serum levels of free alpha-subunit immediately before (basal), and 30 and 60 min after 100 micro g intravenous GnRH were measured by immunofluorimetry. Median and P25-P75 range of the peak/basal ratio of the free alpha-subunit was determined for each group. A receiver operating characteristics curve was calculated. Results were compared using the Kruskal-Wallis test. RESULTS: The peak/basal ratio of the free alpha-subunit was higher in patients with constitutional delay of growth and puberty (7.46) than in those with isolated hypogonadotropic hypogonadism (2.73), complete combined hypogonadotropic hypogonadism (1.58), and partial combined hypogonadotropic hypogonadism (2.61; P < 0.001). A peak/basal ratio < 3.26 identified hypogonadotropic hypogonadism with 93.2% sensitivity and 94.4% specificity when compared to constitutional delay of growth and puberty. There was no statistical difference between the peak/basal ratio of prepubertal patients between 6 and 8 years (7.20), patients between 8 and 13 years (8.71), normal pubertal males (8.10) and those with constitutional delay of growth and puberty (7.46). In a group of boys with delayed puberty, a cut-off point of 3.69 defined hypogonadotropic hypogonadism with 95.6% sensitivity and 94.4% specificity. A cut-off point of 4.81 gave 100% sensitivity (88.9% specificity), and 3.09 gave 100% specificity (86.7% sensitivity). CONCLUSIONS: The peak/basal ratio of the free alpha-subunit can be used for the differential diagnosis of constitutional delay of growth and puberty and hypogonadotropic hypogonadism, irrespective of age. This distinction allows early investigation and treatment of patients with hypogonadotropic hypogonadism and reassurance for those with constitutional delay of growth and puberty.