The natural history of euthyroid Hashimoto's thyroiditis in children

OBJECTIVE: To study the natural history of Hashimoto's thyroiditis (HT) in children and identify factors predictive of thyroid dysfunction. STUDY DESIGN: We evaluated 160 children (43 males and 117 females, mean age 9.10 +/- 3.6 years, with HT and normal (group 0; 105 patients) or slightly elevated (group 1; 55 patients) serum thyroid-stimulating hormone (TSH) concentrations. The patients were assessed at presentation and then followed for at least 5 years if they remained euthyroid or if their TSH did not rise twofold over the upper normal limit. RESULTS: At baseline, age, sex, thyroid volume, free thyroxine, free triiodothyronine, thyroid peroxidase antibody (TPOab), and thyroglobulin antibody (TGab) serum concentrations were similar in the 2 groups. During follow-up, 68 patients of group 0 remained euthyroid, and 10 patients moved from group 0 to group 1. In 27 patients, TSH rose twofold above the upper normal limit (group 2), and 9 of these patients developed overt hypothyroidism. Sixteen patients of group 1 ended up in group 0, 16 remained in group 1, and 23 moved to group 2. A comparison of the data of the patients who maintained or improved their thyroid status with those of the patients whose thyroid function deteriorated revealed significantly increased TGab levels and thyroid volume at presentation in the latter group. However, none of these parameters alone or in combination were of any help in predicting the course of the disease in a single patient. CONCLUSIONS: The presence of goiter and elevated TGab at presentation, together with progressive increase in both TPOab and TSH, may be predictive factors for the future development of hypothyroidism. At 5 years of follow-up, more than 50% of the patients remained or became euthyroid.     

Thyroid function in young children with Down syndrome

A retrospective review of thyroid function tests (TFTs) was performed on 49 young children (aged 4 months to 3 years) with Down syndrome compared with age-matched controls screened for hypothyroidism because of developmental delay or failure to thrive. Three of the 49 children with Down syndrome had congenital hypothyroidism; of the three, one had Hirschsprung's disease and two had duodenal atresia. Thyroiditis was uncommon, with only two children having thyroid antibodies present: one had acquired hypothyroidism and the other acquired hyperthyroidism. Twenty-seven percent of the Down syndrome cohort had mildly increased thyrotropin (TSH) and normal thyroxine levels. When compared with children with Down syndrome who had normal TFTs, no significant differences in sex, growth rate, maternal age, associated anomalies, developmental or specific thyroid symptoms were present. Transient elevations of TSH level were common in children with Down syndrome whether or not TSH values were initially normal or elevated. Routine neonatal and sequential thyroid screening in young children with Down syndrome is warranted.     

Maternal TSH-Receptor Antibodies and TSH Antibodies in Screening for Congenital Hypothyroidism

ABSTRACT. Serum samples from 30 mothers who had given birth to at least one child with a positive neonatal thyrotropin (TSH) screening test were analysed for TSH-receptor antibodies. One mother with hypothyroidism after thyroiditis who had two sons who had had transient congenital hypothyroidism, showed significantly elevated concentrations of TSH receptor blocking IgG antibodies in her serum. The three daughters of another mother had neonatal hyper-thyrotropinaemia but normal thyroid hormone levels. This woman had elevated serum levels of TSH but was clinically and biochemically euthyroid. The apparent hyperthyrotropinaemia in this family was due to an artifact in the TSH radioimmunoassay caused by maternal anti-TSH IgG antibodies. It is obvious that placental transfer of maternal IgG antibodies to the thyroid TSH receptor is one cause of transient congenital hypothyroidism. Likewise, maternal IgG directed against TSH interferes with radioimmunoassays of TSH and the results may be falsely interpreted as hyperthyrotropinaemia. It is concluded that in neonatal hyperthyrotropinaemia analysis of the mother's serum is indicated, and that maternal TSH receptor blocking antibodies must be considered as a cause of congenital hypothyroidism, especially if the mother has a history of thyroid dysfunction.     

Effect of phototherapy on thyroid stimulatory hormone and free thyroxine levels

Objective : To study the effect of phototherapy for neonatal hyperbilirubinaemia on thyroid function as neonatal thyroid screening is sometimes performed during exposure to phototherapy. Methodology : Infants with non-haemolytic hyperbilirubinaemia were sequentially allocated to fibre-optic phototherapy, conventional daylight phototherapy, or a combination of both. Bilirubin concentration was monitored 12 hourly by capillary blood sampling; venous blood was sampled for thyroid stimulating hormone (TSH) and free thyroxine (fT₄) determinations, at start of exposure, at 24 h, end of exposure and 1 day later. Comparable unexposed infants served as controls. Results : All 123 study infants and 25 controls remained well during the study. Bilirubin levels declined during phototherapy, being most rapid in the combination group. The TSH and fT₄ values at start of exposure were 3.86 ± 0.41 mU/L (mean ± SEM) and 33.20 ± 1.16 pmol/L, respectively, in the fibre-optic group, 3.62 ± 0.38 mU/L and 37.22 ± 1.76 pmol/L in the daylight group, and 4.40 ± 0.48 mU/L and 29.91 ± 1.13 pmol/L in the combined group, compared with 5.77 ± 0.40 mU/L and 34.46 ± 1.68 pmol/L in the control group. The TSH and fT₄ values declined with increasing age in the phototherapy and control groups with end of exposure values of 2.90 ± 0.28mU/L and 27.71 ± 0.71 pmol/L, 2.77 ± 0.31 mU/L and 33.52 ± 1.22pmol/L, and 3.44 ± 0.30 mU/L and 27.54 ± 0.88 pmol/L, respectively, compared with 4.21 ± 0.61 mU/L and 27.19 ± 2.33 pmol/L (at 72 h) in the control group. The pattern of TSH and fT₄ decline in the exposed and control groups was similar, being related to increasing age. Conclusions : The validity of neonatal thyroid screening is not affected by fibre-optic or conventional phototherapy or by both combined.     

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.     

Maternal TSH-receptor antibodies and TSH antibodies in screening for congenital hypothyroidism

Serum samples from 30 mothers who had given birth to at least one child with a positive neonatal thyrotropin (TSH) screening test were analysed for TSH-receptor antibodies. One mother with hypothyroidism after thyroiditis who had two sons who had had transient congenital hypothyroidism, showed significantly elevated concentrations of TSH receptor blocking IgG antibodies in her serum. The three daughters of another mother had neonatal hyperthyrotropinaemia but normal thyroid hormone levels. This woman had elevated serum levels of TSH but was clinically and biochemically euthyroid. The apparent hyperthyrotropinaemia in this family was due to an artifact in the TSH radioimmunoassay caused by maternal anti-TSH IgG antibodies. It is obvious that placental transfer of maternal IgG antibodies to the thyroid TSH receptor is one cause of transient congenital hypothyroidism. Likewise, maternal IgG directed against TSH interferes with radioimmunoassays of TSH and the results may be falsely interpreted as hyperthyrotropinaemia. It is concluded that in neonatal hyperthyrotropinaemia analysis of the mother's serum is indicated, and that maternal TSH receptor blocking antibodies must be considered as a cause of congenital hypothyroidism, especially if the mother has a history of thyroid dysfunction.     

SERUM LEVELS OF THYROTROPIN, THYROXINE AND TRIIODOTHYRONINE IN FULLTERM, SMALL-FOR-GESTATIONAL AGE AND PRETERM NEWBORN BABIES

Abstract. Simultaneous serum concentrations of TSH, total thyroxine (T₄) and triiodothyronine (T₃) were determined in 93 fullterm (FT), 37 small-for-gestational age (SGA) and 38 preterm (PT) babies with a postnatal age from 2 to 144 hours. In addition, TSH, T₄ and T₃ concentrations were measured in cord sera from 27 FT, 4 SGA and 5 PT babies and in venous blood from 20 mothers at delivery. Cord blood concentrations of TSH were higher and T₄ and T₃ concentrations were lower than seen in the mothers. Serum concentrations of TSH were high during the first day of life followed by a decline. There was no statistically significant difference between serum TSH concentrations of the three groups of newborns. On the 5th day of life no elevated serum TSH values were found in any of the groups (TSH<5mU/l). Serum concentrations of thyroid hormones increased after birth and reached maximum levels within 24 hours in all groups. The relative increases above cord level were of the same magnitude in the newborns: Two times for serum T₄ and six times for serum T₃. The thyroid hormone concentrations in blood samples from FT babies decreased from the second day of life, whereas in low birth weight newborns the decreases were more variable. The serum levels of T₄ and T₃ were significantly different in the three groups of newborns, the highest values were seen in FT and the lowest values in PT babies. In contrast, the ratios between molar serum concentrations of T₄ and T₃ were found to be highest in PT, lower in SGA and lowest in FT babies, approaching maternal values during the first week of life. The data are discussed with regard to hormone secretion, thyroxine-binding capacity and peripheral T₄ to T₃ conversion in the three groups of newborns. It is concluded that from day 5 after birth serum TSH determinations, alone or in combination with serum T₄, seem to be the method of choice in screening for congenital hypothyroidism.     

Thyroid diseases in a school population with thyromegaly.

A survey of 5462 schoolchildren was conducted for signs of thyroid disease in the seaside region of Sibenik, Croatia. In this region, salt is regularly iodised with 0.01% potassium iodide. Thyromegaly was found in 152 children (2.8%). The most common disorder was simple goitre, which was established in 126 of these, 12 boys and 114 girls (combined prevalence of 2.3%, and of 0.45% in boys and 4.07% in girls). Juvenile autoimmune thyroiditis was found in 19 of the children (prevalence 0.35%), with a female:male sex ratio of 8:1. Diagnosis was confirmed in all cases by fine needle biopsy. Thyroglobulin antibodies were detected in all 19 of the patients with juvenile autoimmune thyroiditis, but microsomal antibodies in only eight. Three patients had decreased concentrations of thyroxine and raised concentrations of thyroid stimulating hormone (TSH), one of these also with clinical hypothyroidism. Raised concentrations of TSH but with normal triiodothyronine and thyroxine were seen in two patients. Graves' disease was diagnosed in four children, three girls and one boy (combined 0.07%). Thyroid nodules were identified in three children (0.055%; two benign adenomas and one cyst). Only seven of the 152 patients with thyromegaly (three with hyperthyroidism and four with simple goitre) had previously sought medical advice, which points to the need for careful thyroid examination of apparently healthy children even in regions where the regular iodide intake is assumed to be sufficient.     

Influence of long-term carbamazepine treatment on thyroid function

We have studied the effects of carbamazepine on thyroid function in sixteen recently diagnosed epileptic children and thirteen epileptic children receiving long-term carbamazepine therapy and compared these findings with the thyroid function of thirteen healthy control subjects. Thyrotropin (TSH), tri-iodothyronine (T₃), thyroxine (T₄), free tri-iodothyorinine (FT₃) and free thyroxine (FT₄) serum levels were determined in both recently diagnosed but as yet untreated epileptic children and normal controls. These hormone levels were determined again after 2 months of treatment and 12 months of treatment in epileptic children. No statistically significant difference was found in the endocrine parameters of untreated epileptic children and the normal control group. After both 2 months and 12 months of carbamazepine therapy, serum levels of T₄, FT₄ and FT₃ were found to be low, but the serum T₃ concentration was unaffected. Baseline TSH levels were not changed during carbamazepine therapy either. Serum TSH levels increased rapidly after thyrotropin-releasing hormone stimulation in both the before and 12 months after carbamazepine treatment groups, but the response was higher in the 12 months treatment group. The findings of the present study suggest that accelerated hormone metabolism is responsible for hormonal changes found in patients treated with carbamazepine. Carbamazepine also had effects on the function of the hypothalamo-pituitary axis.     

School based screening for hypothyroidism in Down's syndrome by dried blood spot TSH measurement

OBJECTIVE—To determine the feasibility of annual hypothyroid screening of children with Down''s syndrome by measuring thyroid stimulating hormone (TSH) on dried blood spots at school, and to describe the outcome in positive children.DESIGN—Establishment of a register of school children with Down''s syndrome, and procedures for obtaining permission from parents, annual capillary blood samples, TSH measurement, and clinical assessment of children with TSH values > 10 mU/litre.SUBJECTS—All school age children with Down''s syndrome within Lanarkshire and Glasgow Health Boards during 1996-7 and 1997-8.RESULTS—200 of 214 school children with Down''s syndrome were screened. Four of the unscreened children were receiving thyroxine treatment, and only 5 remained unscreened by default. 15 of the 200 children had capillary TSH > 10 mU/litre, and all but 1 had evidence of Hashimoto''s thyroiditis. Seven of the 15 children started thyroxine treatment immediately, 6 with a pronounced rise in venous TSH and subnormal free thyroxine (fT4), and one with mildly raised TSH and normal fT4 but symptoms suggesting hypothyroidism. Eight children with mildly raised venous TSH and normal fT4 were left untreated; 1 year after testing positive, fT4 remained > 9 pmol/litre in all cases, but 4 children were started on thyroxine because of a rise in TSH. TSH fell in 3 of the 4 remaining children and there was a marginal rise in 1; all remain untreated. The prevalence of thyroid disease in this population is ? 8.9%.CONCLUSION—Dried blood spot TSH measurement is effective for detecting hypothyroidism in Down''s syndrome and capillary sampling is easily performed at school. The existing programme could be extended to the whole of Scotland within a few years.     

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.     

Chronic urticaria: association with thyroid autoimmunity.

BACKGROUND: Though autoimmune phenomena have been regularly associated with chronic urticaria in adults, data in children are sparse. AIM: To describe our experience with children and adolescents with chronic urticaria and autoimmunity. METHODS AND RESULTS: Of 187 patients referred for evaluation of chronic urticaria during a 7.5 year period, eight (4.3%), all females aged 7-17 years, had increased levels of antithyroid antibody, either antithyroid peroxidase antibody (n = 4, >75 IU/ml), antithyroglobulin antibody (n = 2, >150 IU/ml), or both (n = 2). The duration of urticaria was four months to seven years. Five patients were euthyroid, one of whom was found to have increased antithyroid antibody levels five years after onset of the urticaria. One patient was diagnosed with Hashimoto thyroiditis three years before the urticaria, and was receiving treatment with thyroxine. Two other hypothyroid patients were diagnosed during the initial work up for urticaria (thyroxine 9.2 pmol/l, thyroid stimulating hormone (TSH) 40.2 mIU/l) and five years after onset of the urticaria (thyroxine 14 pmol/l, TSH 10.3 mIU/l). Both were treated with thyroxine but neither had remission of the urticaria. Five patients had a low positive titre of antinuclear antibodies. CONCLUSION: Children with chronic urticaria should be screened periodically for thyroxine, TSH, and antithyroid antibodies, as thyroid autoimmunity and hypothyroidism may appear several years after onset of the urticaria.     

Intellectual development and thyroid function in children who were breast-fed by thyrotoxic mothers taking methimazole

OBJECTIVE: Recent studies have shown normal thyroid function in infants whose mothers receive methimazole (MMI) during breast-feeding. This study evaluates the long-term effect of MMI on thyroid function and intellectual development of such children. DESIGN AND METHODS: Eighty-two children aged between 48 and 86 months were studied. Forty-two children had been breast-fed while their thyrotoxic lactating mothers received daily doses of MMI 20-30 mg in the first, 10 mg in the second and 5-10 mg for additional 10 months of therapy. Thyroid function of infants remained normal during the one year of MMI therapy of their mothers. Forty other infants served as controls. Serum T4, T3, and TSH concentrations, urinary iodine, thyroid antibodies, intelligence quotient (IQ), verbal and functional (performance) components (Wechsler and Goodenough tests) were measured in all children of the two groups. RESULTS: Height, weight, serum T4, T3, TSH and antithyroid antibody titers were not different between children in the two groups. The mean IQ was 107 +/- 17 vs 106 +/- 16 (Goodenough test) and 103 +/- 10 vs 103 +/- 16 (Wechsler test) for children of thyrotoxic mothers and control children, respectively. There was no difference in verbal and functional IQ and their components between children of thyrotoxic MMI treated mothers and control children. CONCLUSION: Thyroid function and physical and intellectual development of breast-fed infants whose thyrotoxic lactating mothers were treated with 20-30 mg doses of MMI daily are normal at age 48 to 86 months.     

Frequency of genetic diseases and health coverage of children requiring admission in a general pediatric clinic of northern Greece

Background

evaluation of thyroid function in neonates born from mothers affected by autoimmune thyroiditis in order to define if a precise follow-up is necessary for these children. The influence of maternal thyroid peroxidase antibody (TPOAb) and L-thyroxine therapy during pregnancy on neonatal thyroid function was also investigated.

Methods

129 neonates were tested for thyroid function by measurement of free thyroxine (FT4) and thyroid stimulating hormone (TSH) in 3^th day, 15^th day and at one month of life. TPOAb were measured in all patients; periodical control of thyroid function were performed until 6 months of life if Ab were positive. Data concerning etiology of maternal hypothyroidism and maternal replacement therapy with L-thyroxine during pregnancy were retrospectively collected.

Results

28% neonates showed at least a mild increase of TSH value at the different determinations. In the majority of them, a spontaneous completely normalisation of TSH value was observed within the first month life. L-thyroxine replacement therapy was started in 3 neonates. TPOAb titer and maternal L-thyroxine replacement therapy were not related to alteration of thyroid hormone function in our study population.

Conclusions

transient mild elevation of serum TSH above the normal reference value for age is frequently observed in the first month of life in infants born from mothers affected by autoimmune thyroiditis. Persistent hyperthyrotropinemia requiring replacement therapy is observed in 2.2% of these neonates. According to our experience, follow-up is recommended in these newborns; the most accurate and not invasive way to carefully monitor these infants after neonatal screening for CH seems to be serum-testing TSH between 2^ndand 4^th week of life.     

Chlorinated contaminants, growth and thyroid function in schoolchildren from the Aral Sea region in Kazakhstan

It has been shown by others that offspring of mothers who had been exposed to dioxins and polychlorinated biphenyls (PCBs) during pregnancy have elevated plasma levels of thyroid-stimulating hormone (TSH) for at least 3 months after birth and reduced plasma levels of free and total thyroxine during the second week after birth. As elevated levels of dioxins and PCBs can thus alter thyroid hormone status, the relation between the levels of some polychlorinated organic compounds in the blood lipids and growth and thyroid hormone status was studied in 12 hospitalized schoolchildren from the Aral Sea region known to have high exposure to such compounds. Their level of PCBs was two to four times higher than in healthy Stockholm children. Their height was found to be lower than in healthy Swedish children of the same age mean (SDS -0.52) and the body mass index (BMI) was inversely correlated to the total concentrations of PCBs and dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorophenyldichloroethylene (DDE) in the blood lipids. As the levels of insulin-like growth factor-1 were reduced to the same extent as the BMI it seems likely that PCBs and DDT cause malnutrition as a result of malabsorption. None of the children had any impairment of thyroid function, as revealed by the plasma levels of TSH and thyroxine. Although the concentrations of β-hexachlorocyclohexane (β-HCH) and DDE were extremely high in some of the children there was no relation between thyroid hormone status and the blood lipid levels of PCBs, hexachlorocyclohexane and DDT. However, the concentration of dioxins was not analysed.     

Chronic urticaria: association with thyroid autoimmunity

Background: Though autoimmune phenomena have been regularly associated with chronic urticaria in adults, data in children are sparse. Aim: To describe our experience with children and adolescents with chronic urticaria and autoimmunity. Methods and Results: Of 187 patients referred for evaluation of chronic urticaria during a 7.5 year period, eight (4.3%), all females aged 7–17 years, had increased levels of antithyroid antibody, either antithyroid peroxidase antibody (n = 4, >75 IU/ml), antithyroglobulin antibody (n = 2, >150 IU/ml), or both (n = 2). The duration of urticaria was four months to seven years. Five patients were euthyroid, one of whom was found to have increased antithyroid antibody levels five years after onset of the urticaria. One patient was diagnosed with Hashimoto thyroiditis three years before the urticaria, and was receiving treatment with thyroxine. Two other hypothyroid patients were diagnosed during the initial work up for urticaria (thyroxine 9.2 pmol/l, thyroid stimulating hormone (TSH) 40.2 mIU/l) and five years after onset of the urticaria (thyroxine 14 pmol/l, TSH 10.3 mIU/l). Both were treated with thyroxine but neither had remission of the urticaria. Five patients had a low positive titre of antinuclear antibodies. Conclusion: Children with chronic urticaria should be screened periodically for thyroxine, TSH, and antithyroid antibodies, as thyroid autoimmunity and hypothyroidism may appear several years after onset of the urticaria.     

The clinical course of Hashimoto's thryoiditis in children and adolescents: 6 years longitudinal follow-up

Forty-six children and adolescents with Hashimoto's thyroiditis were followed up for 5.9 +/- 0.3 years. The mean age at diagnosis was 12.4 +/- 1.7 years (range 9-15.4 yr). The patients were divided into three groups according to thyroid function: group 1 (n = 28) included patients who had normal concentrations of free thyroxine (FT4) and thyrotropin (TSH); group 2 (n = 8) included patients who had normal FT4 and elevated TSH, consistent with compensated hypothyroidism; group 3 (n = 10) included patients who had low FT4 and elevated TSH consistent with overt hypothyroidism. After 5.9 years of follow-up, four out of eight patients with compensated hypothyroidism had normal thyroid function and the other four patients developed overt hypothyroidism. Thyroxine therapy was administered in patients with overt hypothyroidism including the four patients with compensated hypothyroidism who later presented with overt hypothyroidism. All patients in both euthyroid and hypothyroid groups had normal growth and puberty. Final adult height was 0.43 +/- 0.80 SDS which was 1.58 +/- 3.03 cm above mid-parental height. The mean age at menarche (n = 43) was 12.4 +/- 1.1 years, which was not different from normal children. The goiter remained the same size in most of the patients with euthyroidism without thyroxine therapy, but decreased in patients with overt hypothyroidism after thyroxine therapy.     

Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone status, and daily dose of thyroxine

Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first four years of treatment in 418 children with congenital hypothyroidism, identified by neonatal screening, were examined in relation to paired measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836), triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to severity of hypothyroidism at diagnosis. Mean values for thyroxine and free thyroxine, and to a lesser extent free triiodothyronine, were consistently lower in samples with TSH concentrations over 7 mU/l and this was the case in patients with either severe or less severe hypothyroidism. Raised TSH concentrations were also associated with lower mean doses of thyroxine (micrograms/kg/day) but here the mean doses of thyroxine in children with severe hypothyroidism were higher than in the children with less severe hypothyroidism. The mean dose of thyroxine associated with low/normal TSH values was highest in the first 6 months and fell progressively. Thyroxine dose was significantly related to thyroxine and free thyroxine concentrations but not to triiodothyronine and free triiodothyronine and the latter appeared to be of limited value as measures of plasma thyroid hormone status during treatment.     

Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone status, and daily dose of thyroxine.

Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first four years of treatment in 418 children with congenital hypothyroidism, identified by neonatal screening, were examined in relation to paired measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836), triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to severity of hypothyroidism at diagnosis. Mean values for thyroxine and free thyroxine, and to a lesser extent free triiodothyronine, were consistently lower in samples with TSH concentrations over 7 mU/l and this was the case in patients with either severe or less severe hypothyroidism. Raised TSH concentrations were also associated with lower mean doses of thyroxine (micrograms/kg/day) but here the mean doses of thyroxine in children with severe hypothyroidism were higher than in the children with less severe hypothyroidism. The mean dose of thyroxine associated with low/normal TSH values was highest in the first 6 months and fell progressively. Thyroxine dose was significantly related to thyroxine and free thyroxine concentrations but not to triiodothyronine and free triiodothyronine and the latter appeared to be of limited value as measures of plasma thyroid hormone status during treatment.     

The natural clinical course of children with an initial diagnosis of simple goiter: a 5-year longitudinal follow-up

A total of 154 children initially diagnosed as simple goiter were evaluated annually for 5 years. The mean age at diagnosis was 12.8 +/- 1.8 years. The annual evaluation consisted of clinical assessment for height, weight, pubertal status, goiter size, and laboratory measurements for free thyroxine (FT4), thyrotropin (TSH), anti-thyroglobulin and anti-microsomal antibodies. At initial diagnosis, goiter was grade I in 117 children (76%) and grade II in 37 children (24%). All children had normal FT4, TSH and negative thyroid antibodies. After 5 years of follow-up, there were 6 children who later had positive thyroid antibodies in the 3rd and 4th year and the diagnosis was changed to chronic lymphocytic thyroiditis. In one patient TSH level was elevated in the third year and later increased which is strongly suggestive of compensated hypothyroidism. All children had normal growth as shown by the average final adult height of 2.67 +/- 1.25 cm above the midparental height. In girls the average age at menarche was 12.5 +/- 1.4 years which was not different from normal children. The goiter decreased in size in 36 children (23.4%) and remained the same size in 113 children (73.4%) without any medication. We concluded that 1) children who were initially diagnosed as simple goiter need to be followed annually for at least 5 years, and 2) the minimal annual laboratory evaluation should be TSH and thyroid antibodies to detect the early stage of chronic lymphocytic thyroiditis and compensated hypothyroidism.