We report the first mutation in DUOXA2, identified in a patient with CH and dyshormonogenic goiter. Results of our studies provide evidence for the critical role of DUOXA2 in thyroid hormonogenesis. Biallelic DUOXA2 mutations are a novel genetic event in permanent CH.

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The marked difference between black and white females in cancellous vertebral bone density occurs during a relatively brief period late in puberty. Metabolic and hormonal events related to the achievement of sexual maturity during adolescence may be important determinants of racial differences in bone mass in women.

This study assesses the value of the Greulich and Pyle method in determining the skeletal ages of healthy American children of European and African descent born after the year 1980. The hand and wrist radiographs of 534 children (265 boys, 269 girls; 260 European-Americans [EA], 274 African-Americans [AA]), ages 0 to 19 y, were analyzed by two experienced pediatric radiologists blinded to the chronological age of the subjects. A difference score was calculated for each subject by subtracting chronological age from the mean bone ages scores provided by the two raters. One group t-tests were performed to verify the hypothesis that the mean difference score was equal to zero. Skeletal age determinations by the two radiologists showed a high degree of agreement by intraclass correlation coefficient (r ϭ 0.994). The range of values for differences in skeletal and chronological ages was very wide, indicating great individual variability. Comparisons between skeletal and chronological age only reached statistical significance in EA prepubertal girls, whose skeletal ages were delayed, on average, by three months (t ϭ Ϫ2.9; p ϭ 0.005). Mean difference between skeletal and chronological age in prepubertal children of African descent was 0.09 Ϯ 0.66 y, while that in children of European descent was Ϫ0.17 Ϯ 0.67 y; (t ϭ 3.13; p ϭ 0.0019). On average, the bone ages of 10% of all prepubertal AA children were 2 SD above the normative data in the Greulich and Pyle atlas, while the bone ages of 8% of all prepubertal EA children were 2 SD below. In contrast to the racial differences observed in prepubertal children, EA postpubertal males had significantly greater values for bone age than AA postpubertal males (t ϭ 2.03; p ϭ 0.05). In conclusion, variations in skeletal maturation in prepubertal children are greater than those reflected in the Greulich and Pyle atlas; prepubertal American children of European descent have significantly delayed skeletal maturation when compared with those of African descent; and, postpubertal EA males have significantly advanced skeletal maturation when compared with postpubertal AA males. New standards are needed to make clinical decisions that require reliable bone ages and to accurately represent a multiethnic pediatric population. Skeletal age is a frequently used diagnostic tool for the evaluation of endocrine, orthopedic, genetic, and renal disorders, to monitor response to medical therapy and to determine the growth potential of children (1). The method most widely used for bone age determination is the reference atlas of Greulich and Pyle, consisting of radiologic examinations of the left hand and wrist from subjects at different stages of skeletal maturation (2). While this method has the advantages of simplicity and availability of multiple ossification centers for the evaluation of maturity, it is, however, qualitative and was compiled solely from Caucasian children who lived in the 1930s. Nevertheless, the Greulich and Pyle standards are, at present, the most commonly used method for ske...

Bone mass and biochemical markers of bone turnover increase significantly during puberty. We studied the possible relationships between markers of bone formation and bone resorption and increases in skeletal size, bone volume, and bone density in healthy children at different stages of sexual development. Serum concentrations of bone specific alkaline phosphatase (BALP) and osteocalcin (bone Gla protein, BGP), urinary levels of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) and computed tomography (CT) measurements of the cross-sectional areas of the vertebrae and the femurs, the apparent density of cancellous bone in the vertebrae, and the volume and the material density of cortical bone in the femurs were determined in 126 boys and 143 girls, ages 7-18 years. Serum levels of BALP and BGP and urinary concentrations of Pyr and Dpyr peaked in early puberty and were lowest in the later stages of puberty. CT measurements for the cross-sectional areas of the vertebrae and the femurs, the femoral cortical bone areas, and the apparent density of cancellous bone increased in all children during puberty, while values for material bone density did not change significantly with the stage of sexual development. BALP and BGP showed significant inverse correlations with the material density of bone (r = -0.23 and -0.24, respectively), but no association with bone volume in the appendicular or axial skeleton. In contrast, Pyr and Dpyr correlated with femoral cross-sectional area (r = -0.24 and -0.33, respectively) and cortical bone area (r = -0.29 and -0.33, respectively), and with the apparent density of vertebral cancellous bone (r = -0.26 and -0.19, respectively), but not with the material density of bone. We conclude that, during puberty, there is a differential association between the two components of bone mass and the markers of bone formation and bone resorption; while markers of bone formation are related to the material density of bone, markers of bone resorption are related to the volume of bone.

Osteoporosis is a common finding in adult celiac disease patients; however, there are still few data regarding children and adolescents. In the present study we measured the bone mineral density (BMD) in children and adolescents at diagnosis of celiac disease and after approximately 1 y of a gluten-free diet. BMD was measured at the lumbar spine and in the whole skeleton by dual-energy X-ray absorptiometry in 44 celiac disease patients aged 2.58-20.42 y at diagnosis. BMD was also measured in a subset of 25 patients after 1.4 +/- 0.04 y of a gluten-free diet. BMD was compared with that of 177 healthy control subjects aged 1.52-20.99 y. Lumbar spine and whole-body BMD values at diagnosis of celiac disease were significantly lower than in control subjects (P = 0.015 and P = 0.0001, respectively) after differences in age and anthropomorphic variables were controlled for. The subjects studied after the gluten-free diet had BMD values not significantly different from those of control subjects. In conclusion, children and adolescents with celiac disease have remarkably reduced lumbar spine and whole-body bone density. A gluten-free diet promotes a rapid increase of BMD that leads to a complete recovery of bone mineralization. These results emphasize the need for an early diagnosis and treatment in patients with celiac disease to obtain an adequate peak bone mass at the end of puberty.

HAART seems a new risk factor for life-long osteoporosis in children. An increased rate of bone turnover causes BMD decrease. Severity of osteopenia seems to be related to lipodystrophy.

Osteoporosis is a complication of celiac disease in adulthood, but little is known about the influence of the disease on bone mineralization in children. In the present study we evaluated radial bone mineral content (BMC) in celiac children and adolescents at diagnosis and after they consumed a gluten-free diet (GFD). The BMC values of 33 celiac patients at diagnosis were significantly lower than those of 255 control subjects (P < 0.001). There was no difference between diabetic and non-diabetic celiac patients. In 14 patients the BMC increased significantly (P < 0.05, ANCOVA) after 1.28 y of GFD. In these patients the mean annual BMC increment was 0.07 g/cm, significantly greater (P < 0.05) than the increment of normal growing children (0.05 g.cm-1.y-1). Our data indicate that although osteoporosis complicates celiac disease during childhood and adolescence, GFD alone is able to remarkably improve bone mineralization.