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2.
J Dev Behav Pediatr ; 33(8): 633-40, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23027136

ABSTRACT

OBJECTIVE: The Dutch neonatal congenital hypothyroidism (CH) screening procedure and treatment modality has been adapted several times since its national institution in 1981. These changes enabled us to investigate whether earlier treatment has resulted in improved cognitive and motor outcomes. The present study examined whether the advancement of treatment modality has resulted in improved cognitive and motor outcomes. METHODS: In 95 toddlers with thyroidal CH (CH-T), born in 2002 through 2004 and treated at a median age of 9 days, cognitive and motor outcomes were assessed with the Bayley Scales of Infant Development-II-NL at 1 and 2 years of age. This outcome was also analyzed in relation to treatment variables. RESULTS: The mean mental developmental index (MDI) scores of the severe (initial free thyroxine [FT4] ≤0.4 ng/dL (≤5 pmol/L), moderate (0.4 < initial FT4 ≤ 0.8 ng/dL (5.0 < initial FT4 ≤ 10.0 pmol/L), and mild (initial FT4 > 0.8 ng/dL (>10.0 pmol/l) CH-T groups at 1 year and the moderate and mild CH-T groups at 2 years were similar to the population mean. The mean MDI scores of the total CH-T group and severe CH-T group at 2 years were significantly lower than the population mean (p < .0001). In all 3 severity subgroups, significant lower psychomotor developmental index scores (p < .0001) were observed. No correlations were found between starting day of treatment and developmental outcome. Initial T4 concentration and initial T4 dose were weak predictors for developmental outcome. CONCLUSION: Essentially, comparable with our earlier findings, children with CH, especially those with severe CH, are still at risk for motor and cognitive problems, which are probably due to the consequence of the prenatal hypothyroid state or the thyroid hormone deficiency in early life.


Subject(s)
Child Development/physiology , Congenital Hypothyroidism/physiopathology , Child Development/drug effects , Child, Preschool , Congenital Hypothyroidism/diagnosis , Congenital Hypothyroidism/drug therapy , Congenital Hypothyroidism/psychology , Female , Humans , Infant , Infant, Newborn , Intelligence , Male , Neonatal Screening , Netherlands , Neuropsychological Tests , Psychomotor Performance/physiology , Thyroxine/therapeutic use , Treatment Outcome
3.
J Clin Endocrinol Metab ; 92(3): 919-24, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17164300

ABSTRACT

CONTEXT: Patients with thyroidal congenital hypothyroidism (CH-T) born in The Netherlands in 1981-1982 showed persistent intellectual and motor deficits during childhood and adulthood, despite initiation of T(4) supplementation at a median age of 28 d after birth. OBJECTIVE: The present study examined whether advancement of treatment initiation to 20 d had resulted in improved cognitive and motor outcome. DESIGN/SETTING/PATIENTS: In 82 Dutch CH-T patients, born in 1992 to 1993 and treated at a median age of 20 d (mean, 22 d; range, 2-73 d), cognitive and motor outcome was assessed (mean age, 10.5 yr; range, 9.6-11.4 yr). Severity of CH-T was classified according to pretreatment free T(4) concentration. MAIN OUTCOME MEASURE: Cognitive and motor outcome of the 1992-1993 cohort in comparison to the 1981 to 1982 cohort was the main outcome measure. RESULTS: Patients with severe CH-T had lower full-scale (93.7), verbal (94.9), and performance (93.9) IQ scores than the normative population (P < 0.05), whereas IQ scores of patients with moderate and mild CH-T were comparable to those of the normative population. In all three severity subgroups, significant motor problems were observed, most pronounced in the severe CH-T group. No correlations were found between starting day of treatment and IQ or motor outcome. CONCLUSIONS: Essentially, findings from the 1992-1993 cohort were similar to those of the 1981-1982 cohort. Apparently, advancing initiation of T(4) supplementation from 28 to 20 d after birth did not result in improved cognitive or motor outcome in CH-T patients.


Subject(s)
Congenital Hypothyroidism/complications , Congenital Hypothyroidism/diagnosis , Intelligence , Motor Skills , Neonatal Screening , Child , Cohort Studies , Congenital Hypothyroidism/drug therapy , Female , Follow-Up Studies , Humans , Infant, Newborn , Male , Netherlands , Thyroxine/therapeutic use , Time Factors
4.
J Clin Endocrinol Metab ; 88(12): 5851-7, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14671180

ABSTRACT

Much worldwide attention is given to the adverse effects of maternal Graves' disease on the fetal and neonatal thyroid and its function. However, reports concerning the adverse effects of maternal Graves' disease on the pituitary function, illustrated by the development of central congenital hypothyroidism (CCH) in the offspring of these mothers, are scarce. We studied thyroid hormone determinants of 18 children with CCH born to mothers with Graves' disease. Nine mothers were diagnosed after pregnancy, the majority after their children were detected with CCH by neonatal screening. Four mothers were diagnosed during pregnancy and treated with antithyroid drugs since diagnosis. Another four mothers were diagnosed before pregnancy, but they used antithyroid drugs irregularly; free T(4) concentrations less than 1.7 ng/dl (<22 pmol/liter) were not encountered during pregnancy. All neonates had decreased plasma free T(4) concentrations (range 0.3-0.9 ng/dl, 3.9-11.5 pmol/liter); plasma TSH ranged between 0.1 and 6.6 mU/liter. TRH tests showed pituitary dysfunction. Seventeen children needed T(4) supplementation. Because all mothers were insufficiently treated during pregnancy, it is hypothesized that a hyperthyroid fetal environment impaired maturation of the fetal hypothalamic-pituitary-thyroid system. The frequent occurrence of this type of CCH (estimated incidence 1:35000) warrants early detection and treatment to minimize the risk of cerebral damage. A T(4)-based screening program appears useful in detecting this type of CCH. However, the preferential and presumably best strategy to prevent CCH caused by maternal Graves' disease is preserving euthyroidism throughout pregnancy.


Subject(s)
Graves Disease/complications , Hyperthyroidism/congenital , Hyperthyroidism/etiology , Pregnancy Complications , Antithyroid Agents/therapeutic use , Female , Fetal Blood , Graves Disease/drug therapy , Humans , Hyperthyroidism/diagnosis , Hyperthyroidism/drug therapy , Infant , Infant, Newborn , Male , Neonatal Screening , Pregnancy , Pregnancy Complications/drug therapy , Thyrotropin/blood , Thyrotropin-Releasing Hormone , Thyroxine/blood , Thyroxine/therapeutic use
5.
Clin Endocrinol (Oxf) ; 57(4): 529-37, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12354136

ABSTRACT

OBJECTIVE: The dynamics of the plasma concentrations of various diagnostic determinants of thyroid function were analysed in children with congenital hypothyroidism (CH) after the start of T4 supplementation. The description of the biochemical dynamics of TSH and free T4 (FT4) during the first period of thyroxine treatment is important to depict the practical outlines of the initial dosage of T4 and dosage adjustments for newborns with variable forms of CH. DESIGN: A retrospective analysis was performed of frequent plasma TSH, total T4 (T4), FT4 and total T3 (T3) measurements in 30 CH neonates during the first weeks of treatment, treated with initial daily T4 dosages ranging from 4.8 to 11.1 microg/kg. RESULTS: A 50% reduction in the initial plasma TSH concentration was achieved after 3-4 days of treatment, independent of CH severity. At a median of 32 days after the start of T4 supplementation, plasma TSH ranged between 0.4 and 4.0 mU/l. The mean interval needed for FT4 to reach the age-related normal values (12-29 pmol/l) was 3 days. The increase in plasma T3 concentrations levelled off within a few days, when T4 reached concentrations of around 100 nmol/l. CONCLUSIONS: Plasma T3 and FT4 concentrations reach the normal range a few days after thyroxine treatment is started. By contrast, normalization of plasma TSH concentration takes several weeks. At the time that plasma TSH is normalized, CH neonates show a higher range of plasma FT4 concentrations than the normal range. When TSH normalization is the goal of treatment in CH, the target range for plasma FT4 during treatment in the first months needs to be adapted. During the first month of treatment the plasma TSH concentration is not helpful in assessing the proper T4 supplementation dosage. Once plasma TSH has reached normal values, it becomes a reliable determinant in addition to plasma FT4.


Subject(s)
Congenital Hypothyroidism , Thyrotropin/blood , Thyroxine/therapeutic use , Biomarkers/blood , Drug Administration Schedule , Female , Humans , Hypothyroidism/blood , Hypothyroidism/drug therapy , Infant, Newborn , Male , Retrospective Studies , Severity of Illness Index , Thyroxine/blood , Time Factors , Triiodothyronine/blood
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