Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation

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 mUll 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 ofthyroxine (,ug/Ikgday) 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. (Arch Dis Child 1993; 69: 555-558) MRC Register of Children with Congenital Hypothyroidism, Institute of Child Health, London D B Grant PW Fuggle I Smith Correspondence to: Dr D B Grant, Hospital for Sick Children, Great Ormond Street, London WC1N 3JH. Accepted 11 June 1993 Over the past decade several publications have reported that a raised plasma thyroid stimulating hormone (TSH) is relatively common in children receiving treatment with thyroxine for congenital hypothyroidism, particularly in early infancy. For example, 34% of the children with congenital hypothyroidism reported by Hulse et al had raised TSH concentrations at the age of 1 year. Abrusewil et al found TSH values above 10 mU/l in 38% of cases tested between 5 and 11 months,2 and Chiovato et al found high TSH values in 42% of their patients with congenital hypothyroidism between the ages of 1 and 2 years.3 The MRC register of children with congenital hypothyroidism has recorded the results of serial thyroid function tests over the first five years of life in children with congenital hypothyroidism detected on routine neonatal screening and born in the UK between 1982 and 1984. The present study examines the frequency of raised plasma TSH and relates the findings to the severity of the underlying disorder at diagnosis, plasma thyroid hormone status, and dose of thyroxine. Subjects and methods DATA COLLECTION Details of the subjects with congenital hypothyroidism and documentation of the initial diagnosis and treatment have been published previously.4 5 Subjects were then followed up annually to the age of 5 years. Paediatricians were sent a questionnaire asking for dated measurements of height, weight, and head circumference closest to each birthday, details of changes in the dose of thyroxine during the previous year, and the results of all thyroid function tests. SUBJECTS Altogether 472 children with congenital hypothyroidism were born between 1982 and 1984. Of these, 418 (132 males, 286 females) who had a measurement of plasma thyroxine concentration before treatment and also had complete follow up data to the age of 4 years are the subjects of this study. These children were split into two approximately equal sized groups according to the pretreatment plasma thyroxine concentration as described previously5; 195 had pretreatment thyroxine concentrations of 30 nmolIl or less, and 223 had concentrations over 30 nmol/l. In the first group, treatment was started at a median age of 18 days (5th-95th centiles 10-38 days) and in the second at 20 days (5th-95th centiles 12-173 days); three of the latter cases did not start treatment until after the age of 1 year. TSH AND THYROID HORMONE RESULTS Altogether 3752 measurements of plasma TSH obtained after starting treatment and up to the age of 4 years were recorded by the register. Six hundred and forty three of these values were obtained within 28 days after a change in thyroxine dose (including temporary withdrawal of treatment) and were excluded to avoid difficulties of interpretation due to recent 555 group.bmj.com on June 23, 2017 Published by http://adc.bmj.com/ Downloaded from