Congenital Hypothyroidism—Monitoring Thyroid Function in Infants
AbstractGuidelines for monitoring thyroid function in congenital hypothyroidism (CH) are published by the American Academy of Pediatrics, the European Society for Paediatric Endocrinology, and the UK Newborn Screening Programme Centre. The fact that the recommendations are not uniform reflects management uncertainty. In addition, clinical care may not always be informed by these guidelines. Recent studies suggest that more frequent monitoring is indicated in some infants. Monitoring to identify delayed thyroid stimulating hormone (TSH) rise is indicated in pre-term, low birth weight, and sick full-term newborns. Monitoring thyroid function in infants with CH monthly after normalization of TSH until six months of age, and every one to two months between six and 12 months of age, will decrease exposure to suboptimal thyroid hormone levels. Assessment for permanency of hypothyroidism should be done only in children in which there is likelihood of resolution and not earlier than three years of age. In some instances when TSH elevations persist after normalization of the free thyroxine, it may be reasonable to try combined therapy with triiodothyronine.
Congenital hypothyroidism (CH) screening was introduced in 1974 and has become common practice, preventing the devastating neurological and developmental outcomes of untreated CH. Thyroid hormones are essential for normal brain development during early years. It is uniformly agreed that screening programs are essential for early identification and treatment, and that adequate thyroxine (T4) dosing both initially and during the first three years of life correlates with good outcomes.1–3 There is, however, controversy regarding the timing of repeat thyroid function tests (TFTs) after the initial screen, as well as the frequency of monitoring required to optimize the outcomes of children diagnosed with CH who are being treated. This paper discusses current monitoring guidelines and reviews recent studies suggesting the need for changing these guidelines.
Incidence of Congenital Hypothyroidism
Before the use of newborn screening programs was widespread, the reported incidence of CH was 1:7,000–1:10,000. As expected, the CH incidence rate increased significantly—to approximately 1:4000—after the introduction of screening programs.4 Another significant increase in reported incidence has occurred during the last two decades. It is unclear whether this increase is the result of increased detection or a true increase in incidence due to a change in unidentified risk factors.
One possible reason for the higher reported incidence of CH is the change in screening methods and cut-offs used for its diagnosis. The use of a thyroid stimulating hormone (TSH) assay for initial screening is associated with a reported CH incidence higher by 24 % than that reported by laboratories using a T4 assay.5 During the 1990s, many laboratories switched to an initial TSH testing method, possibly contributing to the higher current measured incidence of CH. A recent paper by Hertzberg and colleagues, however, concluded that there was indeed an increased incidence rate, even after adjusting for the screening methodologies and parameters.5
- Fisher DA, Foley BL, Early treatment of congenital hypothyroidism, Pediatrics, 1989; 83:785–9.
- American Academy of Pediatrics, Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS; Public Health Committee, Lawson Wilkins Pediatric Endocrine Society, Foley T, et al., Update of newborn screening and therapy for congenital hypothyroidism, Pediatrics, 2006;117:2290–303.
- Heyerdahl S, Oerbeck B, Congenital hypothyroidism: developmental outcome in relation to levothyroxine treatment variables, Thyroid, 2003;13:1029–38.
- Rastogi MV, LaFranchi SH, Congenital hypothyroidism, Orphanet J Rare Dis, 2010;5:17.
- Hertzberg V, Mei J, Therrell BL, Effect of laboratory practices on the incidence rate of congenital hypothyroidism, Pediatrics, 2010;125(Suppl 2):S48–53.
- Mitchell ML, Hsu HW, Sahai I, Massachusetts Pediatric Endocrine Work Group, The increased incidence of congenital hypothyroidism: fact or fancy? Clin Endocrinol (Oxf), 2011;75:806–10.
- Mandel SJ, Hermos RJ, Larson CA, et al. Atypical hypothyroidism and the very low birthweight infant, Thyroid, 2000;10:693–5.
- Bijarnia S, Wilcken B, Wiley VC, Newborn screening for congenital hypothyroidism in very-low-birth-weight babies: the need for a second test, J Inherit Metab Dis, 2011;34:827–33.
- Woo HC, Lizarda A, Tucker R, et al., Congenital hypothyroidism with a delayed thyroid-stimulating hormone elevation in very premature infants: incidence and growth and developmental outcomes, J Pediatr, 2011;158:538–42.
- Working Group on Neonatal Screening of the European Society for Paediatric Endocrinology, Revised guidelines for neonatal screening programmes for primary congenital hypothyroidism, Horm Res, 1999;52:49–52.
- Jones JH, Gellén B, Paterson WF, et al., Effect of high versus low initial doses of L-thyroxine for congenital hypothyroidism on thyroid function and somatic growth, Arch Dis Child, 2008;93:940–4.
- Balhara B, Misra M, Levitsky LL, Clinical monitoring guidelines for congenital hypothyroidism: laboratory outcome data in the first year of life, J Paediatrics, 2011;58:532–7.
- Baloch Z, Carayon P, Conte-Devolx B, et al., Guidelines Committee, National Academy of Clinical Biochemistry, Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease, Thyroid, 2003;13:3–126.
- American Academy of Pediatrics (AAP) Section on Endocrinology and Committee on Genetics, and American Thyroid Association Committee on Public Health, Newborn screening for congenital hypothyroidism: recommended guidelines, Pediatrics, 1993;91:1203–9.
- Escobar-Morreale HF, Botella-Carretero JI, Escobar del Rey F, et al., REVIEW: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine, J Clin Endocrinol Metab, 2005;90:4946–54.
- Akcay T, Turan S, Guran T, et al., T4 plus T3 treatment in children with hypothyroidism and inappropriately elevated thyroid-stimulating hormone despite euthyroidism on T4 treatment, Horm Res Paediatr, 2010;73:108–14.
- Jones JH, Donaldson MD, Audit of initial management of congenital hypothyroidism in the United Kingdom–comparison of UK practice with European and UK guidelines, J Pediatr Endocrinol Metab, 2009;22:1017–25.