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Congenital Hypothyroidism - Outcome of Early Treatment« Back to Volume 23, Issue 3, November 2007 - Table of Contents Previous research conducted by Kempers and colleagues, in a cohort born and screened in 1981-1982, demonstrated persistent cognitive and motor deficits associated with congenital hypothyroidism despite initiating T4 replacement at a median age of 28 days after birth. In the present study, the same investigators examined potential benefits of commencing T4 replacement at an earlier age (median = 20 days) for a cohort born in 1992 and 1993. During this time, Dutch pediatricians were advised to start with 6-8μg T4/kg/day with T4 dose adjustments based on thyroid function labs obtained at regular outpatient follow-up visits. Participants included 82 Dutch children (mean age 10.5 years, range 9.6 to 11.4 years) diagnosed with thyroidal congenital hypothyroidism (CH-T). An additional 5 participants were diagnosed with central congenital hypothyroidism (CH-C); results were analyzed separately for these due to differing etiology, treatment regimen, and sequelae. Intelligence was assessed with the Dutch version of the Wechsler Intelligence Scale for Children, third edition (WISC-III), except for the first 10 patients for whom the WISC-R was used (and recalculated into WISC-III scores according to recommended guidelines). Three IQ scores were derived for each participant: full-scale IQ (FSIQ), verbal IQ (VIQ), and performance IQ (PIQ). General population IQ scores for each domain have a mean of 100 (±15). Motor skills were assessed with the Movement Assessment Battery for Children (MABC), designed to identify motor function impairments in children aged 4-12 years, including subscales for manual dexterity, ball skills, and balance; higher scores indicating more motor problems. For the 1981-1982 cohort, motor skills were assessed using a forerunner of the MABC: the Test of Motor Impairment (TOMI). IQ and motor scores were compared among the following subgroups: severe vs. moderate vs. mild CH-T (based on pretreatment free T4 concentration) and early-treated vs. late-treated patients (ie, before or after the mean starting day of treatment) with severe, moderate, or mild CH-T. Although mean FSIQ, VIQ, and PIQ scores for the total 1992-1993 cohort were not significantly different from population norms, those in the severe CH-T subgroup received lower scores in all 3 areas (Table). In contrast, IQ scores were not significantly different from the population means for the moderate or mild CH-T subgroups. With regard to motor development, the mean total MABC was significantly poorer than that of the normative population; and a significantly higher proportion of all CH-T severity subgroups received “subnormal” scores. Patients with severe CH-T had significantly worse total MABC and manual dexterity scores than patients with moderate CH-T. In the severe CH-T group, IQ and motor scores did not differ in patients treated before or later than 19 days after birth. Moreover, IQ and motor scores were not different in the moderate and mild CH-T group when treatment was initiated either before or after 19 and 31 days, respectively. Only the severity of CH-T appeared to be a significant predictor of FSIQ when a multiple regression analysis was conducted using severity of CH-T and starting day of treatment as predictor variables. Compared to patients from the earlier cohort, those from the 1992-1993 cohort with mild or severe CH-T had initiated T4 supplementation at a significantly younger age (days 31 and 19 versus days 68 and 29, respectively). The initial T4 dose and the FSIQ scores of the subgroups were not significantly different between the 2 cohorts. In patients with mild CH-T, the percentage of patients with a subnormal total motor score was significantly higher in the 1992-1993 cohort; differences were not significant for severe and moderate CH-T. The authors speculated the reason for the increased motor problems scores in the latter cohort may be a result of selecting a measurement tool (the MABC vs. TOMI) exhibiting enhanced sensitivity. In summary, patients with severe CH-T, whose treatment with T4 was initiated at a mean age of 19 days after birth, exhibit significant cognitive and motor deficits. Those with mild or moderate CH-T (initiated at a mean age of 31 and 19 days, respectively) had a better prognosis for IQ, but still showed substantial motor deficits. Based on the observed deficits, despite earlier initiation of T4 treatment, the authors speculated that intellectual and motor development deficits may be the consequence of the hypothyroid prenatal state. Kempers MJE, van der Sluijs Veer L, Nijhuis-van der Sanden R, et al. Neonatal screening for congenital hypothyroidism in the Netherlands: cognitive and motor outcome at 10 years of age. J Clin Endocrinol Metab. 2007;92:919-24.
Editor’s CommentIn a review of the earlier paper by Kempers and colleagues in GGH,1 Lanes noted 2 other recent reports of cognitive deficits among those born with severe CH.2,3 In the current report, IQ deficits were evident among those with severe CH and motor deficits were discernable across all 3 severity subgroups. The American Academy of Pediatrics and other professional societies recently published a clinical report “Update of Newborn Screening and Therapy for Congenital Hypothyroidism,”4 in which it was acknowledged that those showing signs of prenatal hypothyroidism may evidence more marked cognitive and other impairments; whether these differences, which were characterized as “minor” are preventable by further optimizing postnatal therapy was considered an open question. David E. Sandberg, PhD References - (linked to
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Volume 25 Number 1
June 2009
www.GGHjournal.com
ISSN 1932-9032
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