Analysis of the Wilms' tumor suppressor gene (WT1) in patients 46,XY disorders of sex development.

CONTEXT: The Wilms' tumor suppressor gene (WT1) is one of the major regulators of early gonadal and kidney development. WT1 mutations have been identified in 46,XY disorders of sex development (DSD) with associated kidney disease and in few isolated forms of 46,XY DSD. OBJECTIVE: The objective of the study was the evaluation of WT1 mutations in different phenotypes of isolated 46,XY DSD and clinical consequences. DESIGN: The design of the study was: 1) sequencing of the WT1 gene in 210 patients with 46,XY DSD from the German DSD network, consisting of 150 males with severe hypospadias (70 without cryptorchidism, 80 with at least one cryptorchid testis), 10 males with vanishing testes syndrome, and 50 raised females with partial to complete 46,XY gonadal dysgenesis; and 2) genotype-phenotype correlation of our and all published patients with 46,XY DSD and WT1 mutations. RESULTS: We have detected WT1 mutations in six of 80 patients with severe hypospadias (7.5%) and at least one cryptorchid testis and in one of 10 patients with vanishing testes syndrome (10%). All patients except one developed Wilms' tumor and/or nephropathy in childhood or adolescence. CONCLUSION: WT1 analysis should be performed in newborns with complex hypospadias with at least one cryptorchid testis and in isolated 46,XY partial to complete gonadal dysgenesis. Kidney disease might not develop until later life in these cases. WT1 analysis is mandatory in all 46,XY DSD with associated kidney disease. WT1 analysis is not indicated in newborns with isolated hypospadias without cryptorchidism. Patients with WT1 mutations should be followed up closely because the risk of developing a Wilms' tumor, nephropathy, and/or gonadal tumor is very high.

Is there a further acceleration in the age at onset of menarche? A cross-sectional study in 1840 school children focusing on age and bodyweight at the onset of menarche.

OBJECTIVE: More than 30 years ago Frisch and Revelle proposed a body weight threshold for the onset of menarche. Based on this hypothesis, a further acceleration of age at menarche can be expected in times of childhood obesity. DESIGN: A cross-sectional study of 1840 healthy school girls (Berlin school children's cohort, BSCOC) within the age groups 10-15 years was conducted in 2006-2007. METHODS: Median age of menarche was calculated by Kaplan-Meier survival analysis. Bi- and multivariate analyses were performed to analyze the associations between menarche age and weight status. A locally weighted regression was used to analyze the relationship respectively between height, weight, and body mass index (BMI)-SDS and age stratified by menarche status. RESULTS: Nine hundred and thirty six (50.9%) girls had already experienced menarche at a median age of 12.8 years. Two hundred and thirty six of these girls reached their menarche recently. Obese/overweight girls reached menarche significantly earlier (12.5 years), than normal weight (12.9 years), and underweight girls (13.7 years). The mean total body weight was similar in all girls at menarche irrespective of age (mean 51.1 kg, s.d. 8.1) and height. BMI-SDS remained the only significant factor for onset of menarche within a multiple regression model for early menarche (OR 2.1, 95% confidence interval 1.3-3.3, P=0.002). CONCLUSIONS: Age at onset of menarche did not accelerate even in a childhood population with more than 10% obesity prevalence. Nevertheless, a negative correlation of BMI-SDS with age at onset of menarche exists.

[The pediatric-to-adult transit clinic as a quality-securing measure in endocrinological diseases]. / Complianceprobleme beim Sprung in die Erwachsenenmedizin. Jeder zweite Patient steigt aus.

The establishment of structured transit clinics for pediatric patients with endocrinological diseases entering adulthood is a prerequisite for ensuring the quality of care for patients with chronic endocrine diseases. Since such patients have been receiving constant special pediatric care on a large scale only during the last 20 years, and only now is an improvement in life expectancy and quality of life becoming evident for the individual diseases, a comprehensive store of experience, or even of evaluated data, is lacking. In order to preserve the quality achieved in pediatric care, transitional structures must initially utilize the experience and results achieved in the pediatric setting, and adapt them to the requirements of adult patients. This is an ongoing process, and additional resources are required for the transition, e.g. for joint medical counseling and care, as also for the continuing utilization of non-medical pediatric services. The basis for the implementation of such models is, in principle, provided by the Gesundheitsmodernisierungsgesetz, GMG (health care modernization act), and, for reasons of quality control, the necessary structures should be put in place as quickly as possible.

[Who needs what? New approaches to multidisciplinary diagnostics and therapy for adipose children and youths in a multiethnic city]. / Wer braucht was? Neue Ansätze der multidisziplinären Diagnostik und Therapie adipöser Kinder und Jugendlicher in einer multiethnischen Grossstadt.

Over the past two decades, obesity in children has been increasing worldwide, leading to serious complications. The treatment for childhood obesity remains largely ineffective; therefore preventive measures are crucial. The prevalence of obesity depends on the BMI-percentiles used. Recent BMI-percentiles may underestimate the problem. Currently, the only representative cross-sectional BMI-data are obtained at the school entry examination. These data reveal certain risk groups (migrants, low socioeconomic status). More representative longitudinal data are needed to study the progression of obesity during childhood. Our obesity clinic provides multidisciplinary therapy programs (group or individual) and is also focused on the diagnosis and treatment of comorbidity, especially of the metabolic syndrome. Almost 60% of our severely obese patients are already affected. The molecular diagnosis of rare monogenetic or syndromal forms of obesity may be helpful in providing additional support for these patients. In general, most obesity programs are successful only in families without severe psychosocial problems and with motivation for lifestyle changes. This can be expected in only 3% of our families. Therefore, a substantial societal effort is needed to facilitate prevention for all children, and effective therapies have to be tailored depending on biological and psychosocial risk factors.

The use of L-T4 as liquid solution improves the practicability and individualized dosage in newborns and infants with congenital hypothyroidism.

UNLABELLED: Dosage recommendations for the initial therapy of congenital hypothyroidism (CH) in newborns vary between 8 microg/kg/d and 10-15 microg/kg/d. AIM: To evaluate the practicability of LT4 in liquid form and to define the initial dosage for optimal treatment. METHODS: Liquid LT4 solution was administered to 28 consecutive newborns with primary CH. We measured TSH, T3, T4, free T3 and free T4 before therapy and during follow-up up to 2 years. After 2 years a standardized developmental test (Griffith) was performed. RESULTS: The median dosage at start of therapy was 12.3 microg LT4/kg/d and decreased to about 5 microg LT4/kg/d after 9 months. The median time of normalization of TSH (< or =6 mU/l) was 2 weeks. In 21 patients, who received a median starting dosage of 12.7 microg LT4/kg (range 9.8-17.1 microg/kg), TSH levels normalized within a median of 1 week. Seven patients receiving only 10.1 microg LT4/kg normalized their TSH only after a median of 2 months. CONCLUSIONS: Newborns with CH should normalize their TSH within 1-2 weeks. The initial dose necessary to normalize TSH is not lower when a liquid solution is used. The higher dose used in tablets is not due to inefficient absorption, but rather reflects the increased demand for thyroid hormone in the first weeks of life.

[Hypothyroidism in dizygotic premature twins due to excessive prepartal vaginal iodine application]. / Hypothyreose bei zweieiigen frühgeborenen Zwillingen durch exzessive präpartale vaginale Jodapplikation an die Mutter.

In dizygotic premature twins delivered by Caesarean section after prolonged efforts to effect premature birth we found markedly enhanced thyroid stimulating hormone levels. The mother had been subjected to local polyvidone iodine therapy for seven weeks with PVP suppositories to prevent vaginal infections. Control checks revealed persistently elevated TSH levels, whereas T3/T4 levels were always reduced. Greatly pronounced iodine excretion was seen in the urine of both the babies. This raised the suspicion of iodine-induced hypothyroidism in both children. Substitution with 1-thyroxine was initiated and a withdrawal trial performed after 12 weeks. The patients remained euthyroid after the treatment had been discontinued. Due to possible transfer of iodide to the fetus associated with the risk of iodine-induced hypothyroidism, it is recommended to abstain from vaginal application of iodine during pregnancy.

The prevalence of anti-thyroid peroxidase antibodies and autoimmune thyroiditis in children and adolescents in an iodine replete area.

BACKGROUND: The iodine supply of the population in Berlin has normalized during the last 5 Years. Therefore autoimmune thyroiditis has become the most important differential diagnosis in children and adolescents with goiter. OBJECTIVE: The aim of the present study was to define the prevalence of anti-thyroid peroxidase (TPO) antibodies and autoimmune thyroiditis in children and adolescents with a normalized iodine intake. DESIGN: To enable the measurement of antibodies to thyroid peroxidase (anti-TPO-Ab) in a large cohort, a method to determine anti-TPO-Ab in dried filter paper blood spots was established. In co-operation with pediatricians the antibody prevalence was assessed and data regarding thyroid size, echostructure and the medical history concerning iodine intake and familial thyroid diseases were collected. METHODS: 660 children and adolescents participated in the study; urinary iodine, TSH and TPO-Ab were measured and an ultrasound of the thyroid gland was performed. RESULTS: The sensitivity of the newly established filter paper assay was 91.8% and specificity was 100%. The results confirmed the improved iodine supply, with a median urinary iodine concentration of 139 microg iodine/g creatinine. The prevalence of anti-TPO-Ab was 3.4% with a female to male ratio of 2.7:1. CONCLUSION: The prevalence of anti-TPO-Ab is lower or equal to data reported from other iodine sufficient areas. Data from a moderate iodine deficiency in schoolchildren range from 0.0 to 7.3%. Using the new filter paper method field studies can be implemented to monitor the effect of changes in iodine nutrition on thyroid autoimmunity. Furthermore, this study on the prevalence of anti-TPO-Ab in a cohort of healthy children and adolescents in an iodine replete area can serve as reference data for future investigations and for the comparison with other groups of patients with increased risks for thyroid autoimmunity.

[Gene, fast food and no motion. Causes of childhood obesity]. / Gene, Fast Food und No Motion. Ursachen der kindlichen Adipositas.

Obesity in children and adolescents should be seen as a chronic disorder and not merely as a biological variant. One aspect of the pathological significance of obesity in childhood and adolescence is determined by functional and individual limitation and psychosocial impairment. Another is the fact that these children and adolescents have a higher comorbidity, and appreciably increased morbidity and mortality rates in adulthood. The major causes of the condition are lifestyle related, in particular excessive intake of energy- and fat-rich foods together with increasingly inadequate exercise. In addition, however, there also appears to be a genetic predisposition that manifests as early and massive obesity in young years. Considerable importance attaches to the recording of height and weight development during regular examinations in the doctor's office. In addition, in particular the children of overweight parents, together with their families, should be instructed and advised on the need for a healthy and appropriate diet and regular exercise. In the case of extremely overweight children, a genetic investigation would be worthwhile.

Short stature homeobox-containing gene deletion screening by fluorescence in situ hybridisation in patients with short stature.

UNLABELLED: The short stature homeobox-containing gene (SHOX) on the short arm of the X and Y chromosomes is an important determining factor of stature phenotype. Absence of the SHOX gene is a main cause for short stature in patients with Turner syndrome. Mutations of the SHOX gene can also be responsible for Léri-Weill syndrome (dyschondrosteosis). The aim of this study was to determine the frequency of SHOX deletions in short stature children and to delineate indications for SHOX deletion screening. Out of 50 probands, 35 had idiopathic short stature, 12 cases showed additional anomalies of the forearms (in particular Madelung deformity) and three patients were affected by a congenital heart defect. Chromosomal investigations with fluoresence in situ hybridisation did not reveal a SHOX deletion in any patient with idiopathic short stature. In five of the 12 patients (41.7%) with anomalies of the forearms, a SHOX deletion on one sex chromosome could be detected. No deletion was observed in the three cases with additional heart defects. CONCLUSION: The frequency of short stature homeobox-containing gene deletions in patients with idiopathic short stature appears to be very low and does not require a fluorescence in situ hybridisation analysis. Short stature in association with anomalies of the forearms such as Madelung deformity makes a deletion more probable and therefore screening for such deletions is recommended in these cases.

The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism.

Sporadic and familial nonautoimmune hyperthyroidism are very rarely occurring diseases. Within the last years constitutively activating TSH receptor mutations were identified as one possible pathomechanism. Except for S281N in the extracellular N-terminal domain, all other germline mutations are located in the transmembrane domains 2, 3, 5, 6, and 7 of the TSH receptor, whereas no mutation was reported in transmembrane domains 1 and 4 to date. Here we report the first family with a constitutively active TSHR mutation in transmembrane domain 1 resulting in a substitution of the conserved Gly(431) for Ser. This mutation was found in the investigated patient, his father, and the paternal grandmother. As known from other familial cases of nonautoimmune hyperthyroidism, the age of onset of the disease was variable, ranging from early childhood in the patient and his father to adolescence in the grandmother. Functional characterization of this mutation showed a constitutive activation of the G(s)/adenylyl cyclase system. Moreover, this germline mutation also activates the G(q/11)/phospholipase C pathway. The importance of Gly(431) for receptor quiescence is supported further by introduction of other mutations at this position, all leading to constitutive receptor activity. Our data show now that constitutively activating mutations can be found in the entire transmembrane domain region of the TSH receptor, indicating the important role of all parts of the transmembrane domain region for maintaining the inactive receptor conformation.

Novel mutations of the thyroid peroxidase gene in patients with permanent congenital hypothyroidism.

OBJECTIVE: It is suggested that iodide organification defects account for 10% of all cases with congenital hypothyroidism (CH). One candidate gene for these defects is the thyroid peroxidase (TPO) gene. DESIGN: Exons 2, 8-10 and 14 of the TPO gene were examined in 30 patients with permanent CH without a family history of CH. This group was characterized by the presence of an orthotopic thyroid gland and elevated TSH levels. METHODS: The mutational screening was performed by single-strand conformational polymorphism followed by sequence analysis of fragments with abnormal migration patterns and by restriction enzyme analysis. RESULTS: In four patients we were able to identify mutations on both alleles which have not been described so far. One patient was a carrier of a new homozygous point mutation in exon 9 resulting in an exchange from Leu to Pro at codon 458. Another patient was found to be compound heterozygous for two mutations, a 20 bp duplication in exon 2 and a new mutation in exon 9 (Arg491His). Two brothers of consanguineous parents showed a homozygous T deletion in exon 14 at position 2512. CONCLUSIONS: Our findings confirm the genetic heterogeneity of TPO defects and support the suggested prevalence of organification defects.

Germline Wilms tumor suppressor gene (WT1) mutation leading to isolated genital malformation without Wilms tumor or nephropathy.

Mutations of the Wilms tumor suppressor gene (WT1 ) have been described only in patients with syndromes associated with urogenital malformation and Wilms tumor or nephropathy. We present a male patient with an isolated genital malformation caused by a WT1 mutation.

Constitutively activating TSH-receptor mutations as a molecular cause of non-autoimmune hyperthyroidism in childhood.

BACKGROUND: The glycoprotein hormone TSH (thyroid-stimulating hormone) and its receptor, the TSH-receptor (TSHR), play a crucial role in thyroid growth and function. Constitutively activating germline mutations within the TSHR gene were identified in patients with sporadic or familial non-autoimmune hyperthyroidism. Inheritance of these mutations is autosomal dominant. PATIENTS AND METHODS: We investigated two patients with neonatal onset of non-autoimmune hyperthyroidism and two families in whom the child and one parent are affected. RESULTS: Hyperthyroidism was difficult to treat in all of these patients and was complicated by premature craniosynostosis. Sequencing of all exons of the TSHR gene in one family with hyperthyroidism revealed a mutation in exon 10 (T6321), which was first identified in toxic adenomas and found to constitutively activate the TSHR. In the other family, we identified a new mutation in the first membrane spanning segment (G431S). In both patients with sporadic hyperthyroidism, a heterozygous mutation in exon 9 (S281N) was detected. The functional characterization of S281N and G431S demonstrated that both mutants were constitutively active. Therefore, these mutations are the molecular cause of non-autoimmune hyperthyroidism in the patients. CONCLUSIONS: For patients suffering from non-autoimmune hyperthyroidism, screening for mutations and their functional characterization is recommended. In case of an ineffective hyperthyroidism treatment, thyroidectomy should be performed to prevent lengthy anti-thyroid drug treatment and complications like premature craniosynostosis.

Molecular pathogenesis of neonatal hypothyroidism.

In patients with congenital hypothyroidism (CH), the autosomal recessive inheritance of mutations of thyroid peroxidase, thyroglobulin and the NIS and pendrin genes encoding for sodium iodide transporters has been identified. CH due to thyroid dysgenesis was considered to be a sporadic disease, but recently, inheritable defects of thyroid development have been described. The autosomal recessive inheritance of mutations of the thyroid-stimulating hormone receptor gene was recognized in patients with CH and thyroid hypoplasia, while autosomal dominant mutations of the Pax-8 gene were described in patients with thyroid dysgenesis. In addition, analysis of mutations of the beta-thyrotropin gene has resulted in a new understanding of the pathogenesis of central CH. Molecular genetic studies in patients with CH detected by newborn screening will provide the information necessary for genetic counselling and may help to explain the less favourable outcome present in 5-10% of the patients.

Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency.

Combined pituitary hormone deficiency (CPHD) has been linked with rare abnormalities in genes encoding transcription factors necessary for pituitary development. We have isolated LHX3, a gene involved in a new syndrome, using a candidate-gene approach developed on the basis of documented pituitary abnormalities of a recessive lethal mutation in mice generated by targeted disruption of Lhx3 (ref. 2). LHX3, encoding a member of the LIM class of homeodomain proteins, consists of at least six exons located at 9q34. We identified a homozygous LHX3 defect in patients of two unrelated consanguineous families displaying a complete deficit in all but one (adrenocorticotropin) anterior pituitary hormone and a rigid cervical spine leading to limited head rotation. Two of these patients also displayed a severe pituitary hypoplasia, whereas one patient presented secondarily with an enlarged anterior pituitary. These LHX3 mutations consist of a missense mutation (Y116C) in the LIM2 domain at a phylogenetically conserved residue and an intragenic deletion predicting a severely truncated protein lacking the entire homeodomain. These data are consistent with function of LHX3 in the proper development of all anterior pituitary cell types, except corticotropes, and extrapituitary structures.

Functional characterization of the molecular defects causing nephrogenic diabetes insipidus in eight families.

X-Linked nephrogenic diabetes insipidus (NDI) is a rare inherited disorder characterized by the excretion of abnormal large volumes of diluted urine mainly caused by mutations in the V2 vasopressin receptor (AVPR2) gene. By screening NDI patients for mutations within the AVPR2 gene we have identified three novel (I46K, F105V, I130F) and four recurrent (D85N, R106C, R113W, Q225X) mutations. In addition, a recurrent missense mutation (A147T) within the aquaporin-2 gene was identified in a female patient with autosomal recessive NDI associated with sensorineural deafness. Selected clinical data of the NDI patients were compared with the results from the in vitro studies. Functional analysis of I46K and I130F revealed reduced maximum agonist-induced cAMP responses as a result of an improper cell surface targeting. In contrast, the F105V mutation is delivered to the cell surface and displayed an unchanged maximum cAMP response, but impaired ligand binding abilities of F105V were reflected in a shifted concentration-response curve toward higher vasopressin concentrations. As the extracellularly located F105 is highly conserved among the vasopressin/oxytocin receptor family, functional analysis of this residue implicates an important role in high affinity agonist binding.

Implications of proopiomelanocortin (POMC) mutations in humans: the POMC deficiency syndrome.

The recent discovery of the contribution of proopiomelanocortin (POMC)-derived peptides to the regulation of energy homeostasis and exocrine gland secretion in mice aroused new interest in the complex function of the endocrine POMC network. In addition, the first mutations in the gene encoding POMC have been identified in two patients affected by adrenal insufficiency, early onset severe obesity and red hair pigmentation. Therefore, the focus of this brief review will be the detailed discussion of the implications of these new findings in the physiology of the human POMC ligand-receptor system.

Thyroid function and obesity in children and adolescents.

The aim of this retrospective study was to investigate the frequency of thyroid dysfunction as assessed by TSH, T3 and T4 in a large cohort of 290 obese and 280 healthy children. In addition, thyroid autoantibodies were measured in random subgroups of 123 obese and 80 control children, iodine excretion in 50 and thyroid volume in 23 of the obese children. Elevated TSH levels (>4 U/l) were found in 22 obese children (7.5%), but only in one control (0.3%). The medians of TSH and T3 concentrations were normal, but significantly higher in the obese group than in the controls, while T4 levels did not differ. The prevalence of positive thyroid autoantibodies was increased in the obese children, for the most part in those with elevated TSH. There was no evidence for iodine deficiency as a cause of the average increase of TSH. We conclude that in childhood obesity TSH and T3 levels are significantly increased; in most cases, however, these increases are not accounted for by thyroid autoimmunity or iodine deficiency. As a consequence, TSH elevations with normal thyroid hormone levels in obese children don't need any thyroxine treatment, if thyroid disorders were definitely excluded beforehand.

How a patient homozygous for a 30-kb deletion of the C4-CYP 21 genomic region can have a nonclassic form of 21-hydroxylase deficiency.

A case of nonclassic (NC) 21-hydroxylase deficiency, with a moderately elevated 17-hydroxyprogesterone level (145 nmol/L in filter paper blood spot), was detected in newborn screening. The newborn's phenotype was female, with no sign of virilization. Confirmatory diagnosis revealed elevated serum levels of 17-hydroxyprogesterone and of 21-desoxycortisol, whereas cortisol, PRA, and electrolytes were normal. Hydrocortisone substitution was considered at the age of 6 months, when virilization became obvious. For clinical reasons, this case had to be classified as late-onset congenital adrenal hyperplasia (CAH) with unusually early manifestation. However, the diagnosis of classic 21-hydroxylase deficiency was obtained by Southern blotting studies, showing that she was homozygous for the 30-kb deletion, including the 3' end of CYP21P pseudogene, the C4B gene, and the 5' end of the functional CYP21 gene. Further studies, using PCR and sequencing, were conducted to explain the discrepancy between this genotype, usually associated with a classic salt-wasting form, and the girl's phenotype. Typically, patients homozygous for the 30-kb deletion encoding classic CAH possess a unique CYP21P/21 hybrid gene with the junction site located after the third exon, yielding a nonfunctional pseudogene. The girl in question, however, was heterozygous for the 8-bp deletion, suggesting that the chimeric pseudogene on one allele had a junction site before the third exon. She was compound heterozygous for a 30-kb deletion encoding classic CAH on the paternal allele, and a 30-kb deletion encoding NC CAH on the maternal allele. This novel maternal CYP21P/21 hybrid gene is characterized by a junction site before intron 2 and differs from the normal CYP21 gene only by the P30L mutation in exon 1 and the promoter region of the CYP21P pseudogene. Because the P30L mutation has been described to result in an enzyme with 30-60% activity of the normal P450c21 enzyme, and the CYP21P promoter reduced the transcription to 20% of normal, this puzzling phenotype of a NC CAH with early onset may be fully explained by the genotype of the patient and considered as an intermediate form between the simple virilizing and NC form.

Ocular manifestations in children and adolescents with thyrotoxicosis.

Thyrotoxicosis is a rare disorder in childhood and adolescence. The frequency ranges from 0.1 in 100000 in young children to 3.0 in 100000 in adolescents and the most frequent cause is Graves' disease. Few children and adolescents suffer from thyrotoxicosis during the course of autoimmune thyroiditis and non-autoimmune hyperthyroidism due to constitutively active mutations of the TSH-receptor have been reported in single patients with neonatal hyperthyroidism and rare familial cases. From a survey of the literature it is apparent that infiltrative ophthalmopathy is very rare in children and adolescents. Milder ocular manifestations as retraction of the upper eyelid, upper lid lag and "staring eyes" are reported in varying frequencies ranging from 25 to 60% of all patients. In our own series of 43 children and adolescents (34 females, 9 males) with thyrotoxicosis only 16 (37%) had clear ocular manifestations of upper lid retraction, lid lag and slight protrusio bulbi. However, only three of of them had soft tissue involvement and significant exophtalmus. In none of the patient corneal or optic nerve involvement or paralysis of the extraorbital muscles was observed. Newborns with congenital hyperthyroidism due to maternal Graves' disease seem to present significant transitory ocular manifestations more frequently, but again no infiltrative ophtalmopathy requiring specific therapy is present. Recently at least four different newborns with congenital thyrotoxicosis due to gain-of-function mutations of the TSH-receptor have been reported, who also had significant ocular manifestations. The presence of staring eyes, slight proptosis and lid retraction in these newborns without any autoimmune or inflammatory process supports the hypothesis that these ocular manifestations are caused by the increased thyroid hormone actions. The involvement of the eyes is usually transitory in newborns as well as in children and adolescents and the symptoms usually disappear when euthyroidism is restored. The administration of steroids therefore is restricted to the rare severe cases with eye muscle or soft tissue involvement. There are no reports on surgical decompression or orbital irradiation therapy of ophtalmopathy in children and adolescents, which again indicates that ocular involvement in thyrotoxicosis in children and adolescents is less frequent and much less severe than in adults.