Evaluation of thyroid function in children with undiagnosed short stature in north India

Fifty-five children with short stature were investigated for the aetiology of short stature with special reference to hypothyroidism. Clinical and laboratory parameters including anthropometry were determined to exclude any chronic systemic disorders. Thyroid function tests such as thyroxine (T4) and thyroid stimulating hormone (TSH) estimation by radioimmunoassay, radioactive iodine uptake and thyroid scan, using 131I and perchlorate discharge test, were performed. In addition, growth hormone was estimated under basal conditions and after insulin-induced hypoglycaemia. Thirty-five were boys and 20 were girls. The age at presentation in the boys was 3-12 years whereas in the girls it was 8-13 years. Forty-three of the 55 children had delayed bone age. Abnormal thyroid function was present in 25 children (45.45%). Of these, 11 (20%) had primary hypothyroidism with low or normal uptake, whereas 14 (25.45%) had glands with high uptake of 131I and elevated TSH. Three children with primary hypothyroidism had reduced growth hormone reserve. On follow-up with thyroxine, there was an increase in growth velocity in all. This study indicates that thyroid function tests should be performed routinely in children with undiagnosed short stature.     

The Long-Term Effect of Replacement Therapy in a Short Girl with Autoimmune Atrophic Thyroiditis of Prepubertal Onset

A 9 yr 11 mo old girl was admitted to our hospital because of short stature. Her growth rate gradually decreased and her height was 120 cm (–2.5 SD) on admission. The mother’s and father’s heights were 157 cm (–0.2 SD) and 163 cm (–1.3 SD), respectively. Her bone age was retarded (6 yr 10 mo). An MRI indicated pituitary enlargement, which mimicked adenoma. Evaluation of the pituitary-thyroid axis and thyroid function proved she had primary hypothyroidism (T₃ 0.5 ng/ml, T₄ 1.0 μg/dl, TSH 1,030 μU/ml). These findings, thyroid autoantibody (anti-microsome antibody 400 xs) and histopathology (moderate fibrosis and mild lymphocytic infiltration) suggested acquired hypothyroidism due to autoimmune atrophic thyroiditis of prepubertal onset. Since the evaluation, she has been treated with levothyroxine. The pituitary enlargement disappeared within 3 mo after levothyroxine replacement. The growth rate increased and her height reached 153.2 cm (–1.0 SD) during 10 yr replacement (at 19 yr 11 mo of age). An improvement in her final height was obtained by long-term thyroid hormone replacement therapy. Enough endocrinological study and repeated MRI evaluation are necessary in cases of pituitary enlargement which mimics adenoma before considering surgery.     

Does Congenital Hypothyroidism Have Different Etiologies in Iran?

Objective

To determine the prevalence of congenital hypothyroidism (CH), permanent and transient CH.

Methods

From November 2006 to September 2007, 63031 newborns were screened by measuring serum TSH obtained by heel prick. The neonates who had a TSH≥5mU/L were recalled for measurement of serum T₄, thyroid stimulating hormone (TSH) and TSH receptor blocking antibodies (TRBAb) in venous samples. In 43 primarily diagnosed as cases of CH, treatment was discontinued at age 2–3 years for 4 weeks and T₄ and TSH were measured again. Permanent or transient CH was determined from the results of these tests and radiologic evaluation.

Findings

The incidence of congenital hypothyroidism was found to be 1:1465 with a female to male ratio of 1.19:1. The most common clinical findings were prolonged jaundice (73%), large anterior fontanel (56%) and wide posterior fontanel (55%). In 43 patients with CH, prevalence of permanent and transient form of the disorder was 53.6% and 46.4% respectively. Permanent CH was associated with higher initial TSH level than transient hypothyroidism (P<0.001). The most common etiology of permanent CH was dyshormonogenesis (57%). TRBAb was found in 6.8% of the total 43 cases.

Conclusion

Congenital hypothyroidism in Iran may have different etiologies. Due to higher rate of transient CH than other similar researches, it is reasonable to follow these patients for a longer period to rule out the possibility of permanent hypothyroidism.     

Transient neonatal 'athyreosis' resulting from thyrotropin-binding inhibitory immunoglobulins

Recognition of transient forms of neonatal hypothyroidism is difficult because of the urgency of thyroxine treatment. In the present report the first child born to a mother with Graves' disease developed transient hyperthyroidism during the newborn period. The mother underwent radioactive iodine treatment and was maintained euthyroid on l-thyroxine. Two subsequent children were detected by newborn thyroid screen to have low thyroxine and markedly elevated serum thyrotropin (TSH) levels. Technetium 99 metastable and iodine 123 scans at 22 days of age showed the second child to be athyreotic. The third child was not scanned. All three children were nongoitrous at birth. Patients 2 and 3 had continuous TSH suppression with thyroxine therapy for 3 and 4 years. Thyroid function measurements after discontinuation of therapy for 8 weeks were normal, and both children had normal 123I thyroid scans. The mother was found to have potent TSH-binding inhibitory immunoglobulin (TBII) levels in her serum (85.5%). A fourth child with low thyroxine and elevated TSH was born to a mother on a regimen of l-thyroxine for hypothyroidism. 99mTc scan at 26 days of age showed no thyroid tissue and was normal at 3 months. TBII activity was 35% in the maternal serum and absent in the infant's serum. The above laboratory and clinical data are compatible with the blocking nature of TBII, resulting in transient newborn hypothyroidism and an athyreotic appearance on scan. The TBII measurement can be a useful predictor of neonatal hypothyroidism as well as confirm the transient nature of the disease in newborns.     

甲状腺功能异常患儿血清瘦素水平与甲状腺激素的相关性研究

目的　研究甲状腺功能异常 [原发性甲状腺功能减退 (甲减 )和原发性甲状腺功能亢进 (甲亢 ) ]患儿血清瘦素 (leptin)水平变化 ,探讨血清瘦素与甲状腺功能的关系。方法　采用放射免疫法分别检测 2 0例甲减患儿、17例甲亢患儿和 2 5例健康儿童血清瘦素水平 ,同时采用微粒子化学发光免疫分析法检测血清游离三碘甲状腺原氨酸 (FT3 )、游离甲状腺素 (FT4)、促甲状腺素 (TSH)等指标。结果　甲低组治疗前血清瘦素水平显著低于正常对照组 (P <0 .0 0 1) ,经药物治疗甲状腺功能恢复至正常后 ,其血清瘦素浓度上升至正常水平 ;甲亢组治疗前后血清瘦素水平与正常对照组相比 ,差异无显著性 (P >0 .0 5 )。结论　甲状腺激素对血清瘦素的分泌具有促进作用     

Congenital hypothyroidism with delayed rise in serum TSH missed on newborn screening

We report on a female patient with congenital hypothyroidism (CH) missed on a newborn screening test. She is now 10 years old with retarded development. The patient was born premature at 34 weeks of gestation with birth-weight of 1515 g, and was judged to be normal in the screening programme of Niigata Prefecture. However, she gradually suffered from poor weight gain and retarded development with stridor at breathing. Serum thyroid stimulating hormone (TSH) levels were rechecked and showed high values with normal T3 and T4 levels. She was referred to our hospital at the age of 13 months. She was diagnosed as having CH (ectopic thyroid) with a delayed rise in blood TSH concentration, probably due to the prematurity of the hypothalamic-pituitary-thyroid axis. l -thyroxine therapy brought a decline in TSH levels with partial improvement of her symptoms. Regardless of the result of newborn screening, infants with elevated serum TSH levels should be carefully examined for possible CH, even when T3, T4 and free T4 values are in the normal range.     

Primary hypothyroidism and the low T3 syndrome in thalassaemia major

Basal thyroid function was assessed from the serum thyroxine, triiodothyronine, and thyroid-stimulating hormone concentrations in 114 patients (mean age 13·6 years), designated group 1, with thalassaemia major. Forty of these patients were further evaluated (group 2) for serum-free thyroxine, and free and reverse triiodothyronine concentrations. The response of thyroid-stimulating hormone to thyrotrophin-releasing hormone was measured in 25 patients from this subgroup. Results were compared with those from 53 control subjects. Primary hypothyroidism, defined by a raised thyroid-stimulating hormone level above the upper range limit of 6·5 μIU/ml of the controls, was present in 17·5% of the 114 patients. In group 2 patients, a spectrum of thyroid disease spanning uncompensated and compensated primary hypothyroidism and decreased thyroid reserve was evident. The presence of primary hypothyroidism (uncompensated and compensated) was associated with an age of at least 10 years, an increased incidence of iron toxicity-related systemic complications, and an increased transfusion iron load, but not with an increased serum ferritin level. In the total 114 patients there were 9 who had the low triiodothyronine (sick euthyroid) syndrome. Primary hypothyroidism occurs in a significant proportion of thalassaemia major patients in the absence of obvious clinical signs of hypothyroidism; the low triiodothyronine syndrome associated with non-thyroidal disease is not uncommon.     

Neonatal seizures

AIMS—To define the aetiology of neonatal transient hypothyroidism (NTH) and recommend preventive measures.METHODS—Maternal and perinatal clinical data on the use of antiseptics, drugs, and contrast agents containing iodine were collected from 40 subjects. Thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), thyroglobulin (TG), TSH receptor antibodies, thyroid peroxidase antibodies and urinary iodine were measured in random neonatal samples. In the mothers with known or suspected thyroid disorders, TSH, FT4, TSH receptor antibodies and thyroid peroxidase antibodies were also measured.RESULTS—The NTH aetiology was identified in 85% of cases. More than 50% of the babies with transient hypothyroidism had been exposed to iodine; maternal transfer of antibodies had occurred in a third of them.CONCLUSIONS—It is suggested that the practice of using iodine containing disinfectants should be withdrawn, and chlorhexidine substituted instead; that pregnant women should be advised of the adverse effects of using iodine products; and that thyroid function should be monitored whenever iodine is used.     

Three-year follow-up of borderline congenital hypothyroidism

The purpose of this study was to determine whether children with borderline hypothyroidism in the neonatal period had persistent hypothyroidism after 3 years of levothyroxine replacement therapy. Fourteen term infants with slightly abnormal newborn screening results (thyroxine <10th percentile, thyroid stimulating hormone ?TSH <40 microU/mL) were identified. The subsequent serum confirmatory TSH results of 12 subjects were modestly elevated (5.3 to 18.8 microU/mL, normal 0.6 to 4.6), whereas 2 subjects who had borderline confirmatory TSH (4.6 and 4.7 microU/mL) had abnormal TSH responses to thyrotropin releasing hormone testing. After 3 years of therapy, levothyroxine was discontinued in 13 patients, and repeat thyroid function tests were obtained 1 month later. Levothyroxine was not discontinued in one patient because he had an elevated random TSH (10 microU/mL) while receiving therapy. At 3 years of age, 13 patients had persistently abnormal thyroid function tests (TSH >4.6 microU/mL or a thyroid releasing hormone test result consistent with primary hypothyroidism), and levothyroxine was reinitiated. Only one patient had normal thyroid function studies. Although prospective studies are still lacking, we recommend levothyroxine replacement in newborns with borderline hypothyroidism.     

Congenital hypothyroidism in a child with unsuspected familial dysalbuminemic hyperthyroxinemia caused by a mutation (R218H) in the human albumin gene.

We found familial dysalbuminemic hyperthyroxinemia (FDH) in a 5-month-old boy with congenital hypothyroidism (CH) who had a blood thyrotropin (TSH) level of 479 mU/L but normal total serum thyroxine (T4) and higher than normal total triiodothyronine (T3) levels. Thyroid hormone substitution began at 5 weeks of age when T4 and T3 concentrations were below normal. Until the age of 5 months, treatment with levothyroxine was suboptimal on the basis of high serum TSH levels despite above-normal T4 levels. FDH was confirmed by isoelectric focusing and testing of other family members. DNA analysis of the patient revealed R218H, a mutation in the serum albumin gene associated with FDH, which was also present in the patient's euthyroid father and brother. Thyroid scans, serum thyroglobulin measurements, and free T4 measurements using equilibrium dialysis or 2-step immunoassay methods can identify thyroid hormone-binding protein defects and simplify the diagnosis and treatment of infants with CH.     

Left ventricular systolic and diastolic functions in children living in a moderate-severe iodine deficiency area

Although the effects of impaired thyroid functions on the cardiovascular system is well known, there is no report investigating left ventricular functions in children with iodine deficiency. We evaluated left ventricular functions in children living in a moderate-severe iodine deficient area of northern Turkey. Of 40 children, 13 had stage I, 19 had stage II and eight had stage III goiter. None of the children had clinical signs of hypothyroidism, hyperthyroidism or cardiac dysfunction. Urinary iodine concentration decreased significantly from mild (Group 1) to moderate (Group 2) and severe (Group 3) iodine deficient groups (p <0.05). Mean serum free T3 levels did not differ significantly between the groups. However, a significant difference in mean serum free T4 level was found between Groups 1 and 2 (p <0.05), but remained in the normal range. Although the mean serum TSH level differed significantly between Group 1 and Group 3 and Group 2 and Group 3 (p <0.05), mean values were in the normal range. Mean left ventricular ejection fraction, shortening fraction and diastolic filling parameters did not differ significantly between groups. In conclusion, in case of preserved thyroid hormone levels, a moderate-severe iodine deficiency does not seem to affect left ventricular functions.     

Recovery Period of Hypersecretion of Thyroid-Stimulating Hormone in Patients with Congenital Hypothyroidism Treated with Thyroid Hormone

The recovery periods of serum thyroid stimulating hormone (TSH) were studied in patients with congenital hypothyroidism found on neonatal screening. L-T4 was administered at 37.8 ± 15.1 days of age (M ± SD), and serum T4, T3, and TSH concentrations were measured. After L-T4 therapy with 10 µg/kg, the serum TSH levels decreased to below 10 µU/ml in five patients within a week, and in another two patients, within two weeks, and in the total number of 12 patients out of 15 (80%), by one month. These results suggest that the recovery of serum TSH occurs rapidly in hypothyroid infants. Thus, the serum TSH concentration may be a good measurement for assessing the adequacy of thyroid hormone therapy from early infancy in patients with congenital hypothyroidism.     

Newborn screening for congenital hypothyroidism

Most neonates born with congenital hypothyroidism (CH) have normal appearance and no detectable physical signs. Hypothyroidism in the newborn period is almost always overlooked and delayed diagnosis leads to the most severe outcome of CH, mental retardation, emphasizing the importance of neonatal screening. Blood spot T4 or TSH or both can be used in neonatal screening for CH. The latter, which is more sensitive, is not cost effective, so the first two are used in different programs in the world. TSH screening was shown to be more specific in the diagnosis of CH; T4 screening is more sensitive in detecting newborns especially with rare hypothalamic-pituitary hypothyroidism, but less specific with a high frequency of false positives mainly in low birth weight and premature infants. The time at which the sample is taken may vary between centers, with the majority taking blood from a heel prick after 24 hours of age to minimize the false positive high TSH due to the physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4 and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers postpartum has increased the ratio of false positive TSH elevations. Although transient hypothyroidism may occur frequently, all suspected infants should be treated as having CH for the first 3 years of life, taking into account the risks of mental retardation. A reevaluation after 3 years is needed in such patients. The goal of initial therapy in CH is to minimize neonatal central nervous system exposure to hypothyroidism by normalizing thyroid function, as reflected by T4 and TSH levels, as rapidly as possible. Iodine deficiency is the most important cause of CH worldwide. Iodine is essential for thyroid hormone synthesis and is present in soil, water and air. Prevention of iodine deficiency can be by iodized salt, iodized oil, iodized bread or iodine tablets.     

Familial partial peripheral and pituitary resistance to thyroid hormone: a frequently missed diagnosis?

The diagnosis of partial peripheral and pituitary resistance to thyroid hormone was ultimately made in two boys, 7 and 9 years of age, and a 10-year-old girl who had goiters and hyperthyroxinemia. The boys were treated with propythiouracil and/or thyroidectomy or iodine 131 for suspected thyrotoxicosis but had poorly suppressible serum thyroid-stimulating hormone (TSH) post treatment in spite of the usual L-thyroxine replacement. The girl had increasing goiter size while receiving propylthiouracil, 100 mg every eight hours. These findings led to reevaluation of thyroid hormone dynamics in these children and their families. Twelve additional family members, 3 to 38 years of age, compatible with an autosomal dominant inheritance, were also found to have peripheral and pituitary resistance to thyroid hormone. All affected individuals had elevated serum thyroxine and triiodothyronine levels, normal to slightly elevated triiodothyronine resin uptakes, and a nonsuppressed serum TSH. The five individuals who were given thyrotropin-releasing hormone showed exaggerated TSH responses, which normalized on L-thyroxine therapy. Misdiagnosis in six of 15 family members led to significant morbidity (hypothyroidism, delayed growth, and therapy risk). A nonsuppressed serum TSH in a patient with suspected thyrotoxicosis should lead to suspicion of this disorder. Appropriate management for this condition includes L-thyroxine therapy to decrease goiter size and normalize TSH responses to thyrotropin-releasing hormone.     

Development of contrast sensitivity in infants with prenatal and neonatal thyroid hormone insufficiencies

Thyroid hormone is essential for normal brain development including structures critical for visual processing. While chick and rodent models have demonstrated abnormal visual development following prenatal thyroid hormone loss, comparable data do not exist in the human. To determine whether human infants with intrauterine and early postnatal thyroid hormone insufficiencies have compromised visual abilities, we investigated contrast sensitivity and visual acuity development in 13 infant offspring of women with hypothyroidism during pregnancy (HYPO), 16 preterm infants born between 32 and 35 weeks gestation, 12 infants with congenital hypothyroidism (CH), and 20 typically developing infants. All were assessed with the sweep visual evoked potential technique at 3, 4.5, and 6 months (corrected) age. Results showed significantly reduced contrast sensitivity but normal visual acuity in HYPO and CH groups relative to controls (p < 0.003 and p < 0.05 respectively). Stratification of the HYPO group into subgroups based on maternal TSH levels during the first half of pregnancy revealed lower contrast sensitivities for infants whose mothers' TSH values were above than below the median (p < 0.05). In the CH group, those with an absent thyroid gland and/or a newborn TSH value above 200 mIU/L had lower contrast sensitivities than did those with other etiologies or TSH levels below 100 mIU/L (p < 0.05). There were no significant effects involving the preterm group. These results indicate that thyroid hormone is important for human visual development.     

Assessment of goiter prevalence, iodine status and thyroid functions in school-age children of rural Yusufeli district in eastern Turkey

According to previous studies, Turkey has generally been accepted as a moderate endemic iodine deficient country. However, it has recently been reported that there are regions in Turkey where iodine deficiency is more severe than previously known. The current study was aimed at ascertaining the goiter prevalence by thyroid volumes, iodine status and thyroid functions in school-age children living in an area which is suspected to have moderate or severe iodine deficiency. Overall goiter was found in 47.6% of children, in 22.8% of girls and in 24.8% of boys. Mean thyroid volumes did not differ significantly according to sex. Significant correlation was found between thyroid volume and body surface area and age. There was a negative correlation between the urinary iodine concentration and thyroid volume (r = 0.45, p < 0.01). Median urinary iodine concentrations in subjects with and without goiter were 20 microg/dl and 5.2 microg/dl, respectively. While median urinary iodine levels of the subjects with goiter were consistent with severe-moderate iodine deficiency, levels in subjects without goiter were comparable to moderate-mild iodine deficiency. None of the subjects had the signs or symptoms of hyper-or hypothyroidism. The differences in the mean values of thyroid hormones and TSH levels between subjects with or without goiter were not significant (p > 0.05). No correlation was found between urinary iodine concentrations and thyroid hormone levels. A weak correlation was found between urinary iodine concentration and TSH levels (r = 0.12, p = 0.05). Individuals with goiter were investigated etiologically: biochemical hypothyroidism was detected in 2%, compensated hypothyroidism in 12.6%, autoimmune thyroiditis in 2%, nodular goiter in 3% and isolated high TSH level with autoimmune thyroiditis in 0.08%. In conclusion, although a salt iodization program has been started in Turkey, our study indicates that some regions with severe iodine deficiency are still present. This research suggests that this program should be re-evaluated for remote areas with self-contained economic systems, and should be expanded and more effectively applied nation-wide.     

先天性甲状腺功能减低症患儿治疗前后血清ghrelin的动态变化

目的 观察甲状腺素替代治疗对先天性甲状腺功能减低症(CH)患儿血清ghrelin水平的影响.方法 研究对象为2007年10月-2008年3月在徐州医学院附属医院确诊并行治疗随访的CH患儿40例及健康体检儿童30例.分组:未治疗组包括甲状腺功能减低的CH患儿20例;治疗组包括新诊断或随访中经甲状腺素片治疗后甲状腺功能正常至少1个月的CH患儿20例;健康对照组年龄、性别相当的健康儿童30例.采用夹心法酶联免疫吸附试验测定3组儿童血清ghrelin水平,采用化学发光法测定三碘甲状腺原氨酸(T3)、四碘甲状腺原氨酸(T4)、促甲状腺激素刺激激素(TSH)水平,同时计算每个样本的体质量指数(BMI)用于相关分析.结果 1.未治疗组ghrelin水平[(2.35±0.23) μg·L-1]虽高于治疗组[(2.16±0.25) μg·L-1]和健康对照组[(1.96±0.27) μg·L-1],但差异无统计学意义(P=0.102).2.Ghrelin与年龄呈负相关(r=-0.325,P<0.05),但与性别、BMI、T3、T4、TSH无相关关系(Pa>0.05).结论 甲状腺激素对中枢或外周ghrelin的产生和分泌可能无调控作用.在不同生长发育时期,不同水平的ghrelin可能有不同的生理作用.     

Autoimmunthyreopathien bei Kindern und Jugendlichen mit Typ-1-Diabetes Häufigkeit und sinnvolles Screening

Background. Children and adolescents with type 1 diabetes are at increased risk for the development of autoimmune thyroid disease (Hashimoto thyroiditis and Grave's disease). Recommendations for screening have been very inconsistent. Method. Between 1996 and 1999, yearly determinations of serum TSH, fT4, fT3, thyroid peroxidase (TPO-) and thyroglobulin (Tg-) antibodies were done in 155 children and adolescents with diabetes. In those who were positive for thyroid antibodies and/or had a goiter thyroid sonography was performed. Specific therapy was instituted when overt hypo- or hyperthyroidism or subclinical hypothyroidism with goiter was present. No treatment was given to euthyroid patients who had positive thyroid antibodies but no goiter. Results. Between 1996 and 1999, autoimmune thyroiditis was diagnosed in 7 out of 155 children (all females). Hashimoto thyroiditis was present in 4, Grave's disease in 2 and thyroid antibody negative transient hyperthyroidism in one. Median age at diagnosis was 10.9 years, median duration of diabetes 3.1 years. The long-term course of thyroid autoantibody titers varied widely, there was no correlation with activity of hypo- or hyperthyroidism, predominant were TPO- antibodies. Four euthyroid children had elevated thyroid antibodies only, none developed a goiter or thyroid dysfunction so far. One child had subclinical hypothyroidism without thyroid antibodies and was treated with iodine. Of note were markedly increased HbA1c levels coincident with overt hyperthyroidism which decreased once euthyroidism was achieved. Conclusion. Routine screening for autoimmune thyroid disease in children and adolescents with diabetes is necessary. At onset of diabetes, thyroid function and antibodies should be determined to identify patients at risk. During follow-up, search for symptoms and signs of hypo- or hyperthyroidism or goiter as well as a determination of TSH once yearly is sufficient. If abnormal findings are present an extended work-up is necessary (see Fig. 1). Unexplained high HbA1c levels may be caused by unrecognised hyperthyroidism.     

Familial hypothyroidism with autosomal dominant inheritance.

Three generations of a family with clinical and subclinical hypothyroidism caused by thyroid stimulating hormone (TSH) unresponsiveness are described. Findings were low to normal serum thyroxine, raised serum TSH, and low radioiodine uptake; goitre was notably absent. This family is the first evidence of an autosomal dominant mode of transmission of TSH unresponsiveness and may enable identification of the precise defect by genetic linkage study.     

Longitudinal assessment of L-T4 therapy for congenital hypothyroidism: differences between athyreosis vs ectopia and delayed vs normal bone age

To study the effects of LT4 dose on thyroid hormone serum levels, a prospective, longitudinal and comparative study was designed, including 56 term eutrophic 1-89 day-old infants with congenital hypothyroidism (CH) detected by neonatal screening. Patients were divided into four groups according to delayed or normal bone age at birth, and athyreosis or ectopic thyroid. All received an initial dose of 50 micrograms/day (12.9-13.7 micrograms/kg/day) LT4 and were followed bimonthly (first year) and quarterly (second year) with thyroid profile and bone age determinations at 6, 12 and 24 months. At diagnosis, hormone levels were higher in cases of ectopia than in athyreosis (p < 0.001), and T4 was lower in children with delayed than in normal bone age at birth (p < 0.05). During treatment, all groups were clinically euthyroid despite T4 and FT4 serum levels higher than the upper normal limit (p < 0.0.001), though T3 and FT3 were within the normal limit (p > 0.05). TSH normalized within 8 weeks. Bone age accelerated at 2 years in eight children of the bone age delayed group. No patient had craniosynostosis.