One of a series of leaflets available from the Down's Syndrome Association Down's Syndrome Association Medical Series 2. THYROID DISORDER AMONG PEOPLE WITH DOWN'S SYNDROME Notes for doctors THYROID DISORDER AMONG PEOPLE WITH DOWN'S SYNDROME Thyroid disorder is more frequent at all ages among people with Down's syndrome than among the non-Down's syndrome population. Around 15% of adolescents with Down's syndrome are hypothyroid, and there is evidence for a steady decline in thyroid function as age increases (Pueschel et al. 1991). Congenital hypothyroidism is also over-represented (Cutler et al. 1986). The aetiology is heterogeneous but an auto-immune type thyroiditis is often causitive. Thyroid microsomal antibodies are found in around 30% of people with Down's syndrome and have been detected in children with the syndrome as early as age 2 years. The presence of microsomal antibodies does not necessarily imply thyroid disfunction but should be taken as an indication to check thyroxine levels frequently. The absence of antibodies does not preclude hydrothyroidism from other causes. Some young children with Down's syndrome run abnormally high TSH levels which subsequently normalise (Cutler et al. 1986; Selikowitz 1993). High TSH alone does not therefore necessarily predict incipient hypothyroidism. However, those with high TSH levels should be kept under close surveillance. Sharav et al. (1988) found evidence of additional growth retardation among under 4s with high TSH levels but this was not confirmed by Selikowitz (1993). Hypothyroidism can be difficult or even impossible to diagnose on clinical grounds in a person with Down's syndrome because of major overlap of symptoms with normal features of the syndrome (Prasher 1995). One USA study showed 20% of community based patients had previously undetected hypothyroidism (Friedman et al. 1989). As in the general population, 1 Down's Syndrome Association. www.downs-syndrome.org.uk Down's Syndrome Association Medical Series 2. THYROID DISORDER AMONG PEOPLE WITH DOWN'S SYNDROME. Notes for doctors Revised June 2000 onset of thyroid deficiency is usually insidious. Unexpected physical or affective change or functional deterioration at any age is an indication for thyroid function tests. It is particularly important to differentiate hypothyroidism from depression and/or dementia (Prasher and Krishnan 1993). Hyperthyroidism, though much less frequent, is also over-represented among the population with Down's syndrome (Takahasi et al. 1979). There is thus a need for a high index of clinical suspicion for thyroid dysfunction among those with Down's syndrome and for biochemical screening protocols to be followed. There is insufficient information about the natural history of the development of the disorder and the effectiveness of different screening protocols to make firm recommendations. Some doctors check T4 and TSH every year. Some check less frequently and take a high TSH as an indicator for more frequent checks (but see above). Some check less frequently but test for thyroid microsomal antibodies and use the presence of these, if found, as an indication for more frequent monitoring of T4. Our current recommendation is that at a minimum every child should have T4, TSH, and thyroid antibodies checked at age 1 and thereafter 2 yearly for life. Currently the effectiveness of annual Guthrie testing using fingerprick blood to check TSH levels is being evaluated (Noble et al. 2000). If successful this will reduce the need for venous sampling, will increase the screening frequency, and will be more acceptable to parents and health care professionals. Thyroxine replacement therapy, when indicated, should be instituted and monitored as in the general population. There are occasional reports of adverse behavioural sequalae at the onset of treatment. If this occurs, the dose should be increased in smaller increments and, if necessary, over a longer time scale. There is no evidence of any advantage conferred by thyroxine replacement therapy for those with low-borderline thyroid function (Tirosh et al. 1989), but treatment can have a dramatic effect on quality of life when frank hypothyroidism is present. Further information is available in: `Basic Medical Surveillance Essential for People with Down's Syndrome' produced by the Down's Syndrome Medical Interest Group. Available from: DSMIS, Childrens Centre, Nottingham NG5 1PB. 2 Down's Syndrome Association. www.downs-syndrome.org.uk Down's Syndrome Association Medical Series 2. THYROID DISORDER AMONG PEOPLE WITH DOWN'S SYNDROME. Notes for doctors Revised June 2000 CLINICAL POINTERS Increased prevalence of hypothyroidism at all ages, rising with age · Small increase in hyperthyroidism · Clinical diagnosis unreliable · Biochemical screening protocols essential ­ venous protocol at age 1 and 2 yearly for life or ­ annual fingerprick screen if available · Young children may have transitory high TSH without hypothyroidism · Thyroxine treatment only indicated if hypothyroidism is biochemically confirmed · Treatment as for general population REFERENCES Cutler A T, Benezra-Obeiter R, Brink S J, (1986). Thyroid function in young children with Down's Syndrome. Am J Dis Child. 140. 479-483 Friedman D L, Kastner T, Pond W S, et al. (1989). Thyroid dysfunction in individuals with Down's Syndrome. Arch Intern Med. 149. 1990-93 Noble S E , Leyland K, Findlay C A, Clark C E, et al. (2000). School based screening for hypothyroidism in Down's syndrome by dried blood spot TSH measurement. Arch. Dis. Child. 82. 27-31 Prasher V, (1995). Reliability of Diagnosing Hypothyroidism in Adults with Down's Syndrome. Aus. and NZ J. or Developmental Disabilities. 20. 223-233 Prasher V, Krishnan VHR, (1993). Hypothyroidism presenting as dementia in a person with Down's Syndrome. Mental Handicap. 21. 147-149 Pueschel S M, Jackson I M D, Giesswein P, et al. (1991). Thyroid function in Down's Syndrome. Res Dev Disabil Res. 12. 287-296 Selikowitz M, (1993). A five year longitudinal study of thyroid function in children with Down's Syndrome. Dev Med Child Neurol. 35. 396-401 3 Down's Syndrome Association. www.downs-syndrome.org.uk Down's Syndrome Association Medical Series 2. THYROID DISORDER AMONG PEOPLE WITH DOWN'S SYNDROME. Notes for doctors Revised June 2000 Sharav T, Collins R M, Baab P J, (1988). Growth studies in infants and children with Down's Syndrome and elevated levels of thyrotropin. Am J Dis Child. 142. 1302-1306 Takahashi H, Bordy M D, Sharma V, Grunt J A, (1979). Hyperthyroidism in patients with Down's syndrome. Clinical paediatrics; 18. 273-275. Tirosh E, Taub Y, Scher A et al. (1989). Short term efficacy of thyroid hormone replacement for patients with Down's Syndrome and borderline thyroid function. Am J Mental Retardation. 93. 654-656 Dr Jennifer Dennis Medical Advisor to the Down's Syndrome Association January 1995 (revised June 2000) 4 Down's Syndrome Association. www.downs-syndrome.org.uk