Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect

Tillotson, Sarah; Fuggle, Peter; Smith, I.; Ades, A E; Grant, D B

doi:10.1136/bmj.309.6952.440

Cited by 162 publications

(126 citation statements)

References 23 publications

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“…35 When results were compared according to disease and treatment parameters, differences were accounted for mainly by etiology and dosage, whereas there were no effects of age when treatment was started or hormone levels at confirmatory diagnosis, contrary to a British study that showed that hormone levels at time of diagnosis were the strongest predictor of IQ in children with CH. 36 Although the finding of poorer outcome in children with athyreosis than controls is consistent with past research, the present observation that children with ectopic glands were also affected is discrepant with previous research and may reflect this particular sample. Alternatively, it may reflect the increased sensitivity of directly matching the CH child with his or her sibling.…”

Section: Discussioncontrasting

confidence: 57%

Children With Congenital Hypothyroidism and Their Siblings: Do They Really Differ?

Rovet

2005

Pediatrics

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ABSTRACT. Objective. Although favorable outcome is typically described in follow-up studies of children with congenital hypothyroidism (CH) identified by newborn screening, IQ reductions and persistent cognitive deficits are still reported. These findings are accounted for by disease and treatment variables as well as methodologic factors including choice of comparison group. Although siblings are ideal because they control for genetic and environmental influences, by definition they have different ages when tested, which can also introduce bias. Because we followed children with CH and their siblings over an extended period of time, there were a number of occasions when both groups were tested at the same age. The purpose of this study was to compare the results of children with CH and their unaffected siblings at the same age and with the same test. Methods. The sample consisted of 42 children with CH detected between 1975 and 1985 and their 42 siblings, all of whom were tested with the McCarthy or WechslerIntelligence Scale for Children-Revised (WISC-R) intelligence tests. Nineteen pairs of children were evaluated at 6 years with the McCarthy, and 30 pairs of children were evaluated at 7 or 9 years with the WISC-R. Recorded for children with CH were disease etiology, bone age and thyroxine levels at diagnosis, age at onset of treatment, and starting dosage of levothyroxine.Results. Paired t tests revealed that the CH group scored lower than siblings by 8.1 IQ points on the McCarthy and 6.2 points on the WISC-R. Factors contributing to the size of the CH-sibling IQ difference were (1) the etiology of hypothyroidism, reflecting the larger differences by those with athyreosis or an ectopic gland than dyshormonogenesis, and (2) the starting dosage of levothyroxine, with those initially treated with >8.2 g/kg per day having smaller CH-sibling differences than those given lower starting doses. There were no effects of bone age, thyroxine levels at diagnosis, or age at treatment onset. Conclusion It is now Ͼ2 decades since newborn screening programs for congenital hypothyroidism (CH) were first implemented. 1-3 A large number of studies on children so identified 4 have revealed that although screening and early treatment are beneficial in preventing the mental retardation associated previously with cretinism, 5 some children still experience subtle selective cognitive deficits 6-9 that persist into adolescence 10 and adulthood. 11 Their specific deficits depend on disease and treatment-related factors including etiology of hypothyroidism 12 and starting dosage of replacement hormone therapy. [13][14][15][16] Etiology is relevant because it reflects if and when the disease began in utero. 17 Although the fetal thyroid is supplemented by the maternal thyroid, it does not totally compensate all late gestational fetal needs. 18 Treatment factors are relevant because they determine the period of postnatal hypothyroidism. Although prompt treatment with a high initial dose level of levothyroxine (L-T4) is associated with ...

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Section: Discussioncontrasting

confidence: 57%

Children With Congenital Hypothyroidism and Their Siblings: Do They Really Differ?

Rovet

2005

Pediatrics

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“…In previous studies, however, the initial treatment with L-T 4 was not as optimal as in the present investigation and the possibility that other variables related to treatment may have played some role in conditioning the poor psychomotor outcome cannot be excluded.…”

Section: Discussioncontrasting

confidence: 44%

In congenital hypothyroidism bone maturation at birth may be a predictive factor of psychomotor development during the first Year of life irrespective of other variables related to treatment

Waśniewska

Luca

Cassio

et al. 2003

European Journal of Endocrinology

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Objective: To evaluate in a cohort of infants with congenital hypothyroidism (CH): (a) the frequency of bone maturation (BM) retardation at birth and (b) whether BM delay at birth may be considered as a tool to make a prognosis of psychomotor status at the age of 1 year, irrespective of other variables related to treatment. Design: BM at birth, CH severity and developmental quotient (DQ) at the age of 1 year were retrospectively evaluated in 192 CH infants selected by the following inclusion criteria: (a) gestation age ranging between 38 and 42 weeks; (b) onset of therapy within the first month of life; (c) initial thyroxine (L-T 4 ) dosage ranging from 10 to 12 mg/kg/day; (d) normalization of serum thyrotropin (TSH) levels before the age of 3 months; (e) monthly adjustments of L-T 4 dose during the first year of life with serum TSH levels ranging from 0.5 to 4 mIU/l; (f) no major diseases and/or physical handicaps associated with CH; (g) availability of both thyroid scanning and knee X-rays at the time of treatment initiation; (h) availability of DQ assessment at an average age of 12 months. Methods: BM was considered normal if the distal femur bony nucleus diameter exceeded 3 mm (group A) or retarded if either this nucleus was absent (subgroup B1) or its diameter was , 3 mm (subgroup B2). DQ was evaluated with the Brunet -Lézine test. Results: In 44.3% of cases BM was either delayed (23.5%) or severely delayed (20.8%). The risk of BM retardation was higher in the patients with athyreosis than in the remaining patients (41/57 vs 44/135, x 2 ¼ 25.13, P , 0.005). BM-retarded infants showed a more severe biochemical picture of CH at birth and a lower DQ at the age of one year compared with the group A patients. If compared with infants of subgroup B2 those of subgroup B1 exhibited significantly lower T 4 levels at birth and a more frequent association with athyreosis (70.0 vs 30.0%; x 2 ¼ 7.49, P , 0.01), whereas DQ was superimposable in both subgroups. Conclusions: (a) BM at birth is delayed in almost half of CH patients and (b) CH severity per se can affect DQ at the age of 1 year irrespective of other variables related to therapy.

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“…This indicator of prenatal CH severity was preferred to neonatal FT 4 cutoff level according to pre-therapy serum FT 4 concentration (21), because it was considered a more reliable indicator of foetal thyroid hormone supply during the pregnancy (10,11,20). However, Table 1 shows that bone maturation at birth was related to FT 4 serum levels at confirmation; therefore, they were both good parameters for the estimation of prenatal CH severity.…”

Section: Subjectsmentioning

confidence: 99%

“…However, previous studies have indicated that children who receive early treatment for CH have a normal intelligence quotient combined with attention problems (2,3), motor deficits and defects in visuospatial skills, language and memory (4,5). Several studies have correlated these problems with the severity of CH and others with the timing in starting treatment (6)(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Psychological and behavioural aspects in children and adolescents with congenital hypothyroidism diagnosed by neonatal screening: comparison between parents' and children's perceptions

Bisacchi¹,

Bal²,

Nardi³

et al. 2011

European Journal of Endocrinology

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Objective: To compare the psychological adjustment and behaviour of congenital hypothyroidism (CH) children and their parents with a control group. Study design: A cross-sectional study was carried out with 84 CH subjects diagnosed by neonatal screening (range 2.7-18.6 years), subdivided into four age groups: group 1 (2-5 years); group 2 (6-10 years); group 3 (11-13 years); and group 4 (14-18 years) and was compared with an age-matched control group. Patients were assessed using two questionnaires: Child Behaviour Checklist for parents and Youth Self-Report for children over 11 years of age. Results: In groups 1, 3 and 4, total score (TS), internalising score (ISZproblems within the self) and externalising score (ESZconflicts with other people) as reported by parents were not significantly different in CH patients and in controls. In group 2, parents of CH children showed values of TS (P!0.05), IS (P!0.05), ES (P!0.05) and scores on other scales significantly higher than controls. In self-reports of groups 3 and 4, the behavioural scales were not significantly different in CH patients and in controls. Conclusions: Paediatricians should be informed about the increased risk of the development of behavioural problems at primary school age in CH patients. At this age special attention should be paid to parental worries and anxiety. However, it can be reassuring for the patients and parents to know that the problems may be related to CH, and that they may spontaneously disappear.

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Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect

Cited by 162 publications

References 23 publications

Children With Congenital Hypothyroidism and Their Siblings: Do They Really Differ?

Children With Congenital Hypothyroidism and Their Siblings: Do They Really Differ?

In congenital hypothyroidism bone maturation at birth may be a predictive factor of psychomotor development during the first Year of life irrespective of other variables related to treatment

Psychological and behavioural aspects in children and adolescents with congenital hypothyroidism diagnosed by neonatal screening: comparison between parents' and children's perceptions

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