Should we treat subclinical hypothyroidism in obese children?
BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i941 (Published 16 March 2016) Cite this as: BMJ 2016;352:i941
Chinese translation
该文章的中文翻译
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
There is a controversy that, although the iodine fortification of salt has decreased goitre due to hypothyroidism, it has paradoxically increased autoimmune thyroiditis (1-6), so it acts as adouble-edged sword. Either lowering or raising the iodine content of the diet will cause iodine deficiency thyroid disorders or autoimmune thyroiditis respectively.
References:
1. Weaver DK, Nishiyama RH, Batsakis JG. Iodine induced thyroid disease. Ann Clin Lab Sci. 1976 Nov-Dec;6(6):545-50.
2. Rink T, Schroth HJ, Holle LH, Garth H. [Effect of iodine and thyroid hormones in the induction and therapy of Hashimoto's thyroiditis]. Nuklearmedizin. 1999;38(5):144-9. .
3. Foley TP Jr. The relationship between autoimmune thyroid disease and iodine intake: a review. Endokrynol Pol. 1992;43 Suppl 1:53-69. Review.
4. Boyages SC, Bloot AM, Maberly GF, Eastman CJ, Li M, Qian QD, Liu DR, van der Gaag RD, Drexhage HA. Thyroid autoimmunity in endemic goitre caused by excessive iodine intake. Clin Endocrinol (Oxf). 1989 Oct;31(4):453-65.
5. Mooij P, de Wit HJ, Drexhage HA. An excess of dietary iodine accelerates the development of a thyroid-associated lymphoid tissue in autoimmune prone BB rats. Clin Immunol Immunopathol. 1993 Nov;69(2):189-98.
6. Markou KB, Georgopoulos NA, Makri M, Vlasopoulou B, Anastasiou E, Vagenakis GA, Kouloubi K, Theodosopoulos N, Lazarou N, Veizis A, Sakellaropoulos G, Vagenakis AG. Improvement of iodine deficiency after iodine supplementation in schoolchildren of Azerbaijan was accompanied by hypo and hyperthyrotropinemia and increased title of thyroid autoantibodies. J Endocrinol Invest. 2003;26(2 Suppl):43-8.
Competing interests: No competing interests
Elevated TSH in children is an indicator of iodine deficiency, which remains a huge problem world-wide, including the industrialised countries such as the UK and Australia. A survey of the UK iodine status in 2009 found that the median urinary iodine (UI) excretion in a sample of 737 schoolgirls was 80 mcg/l, and that more than two-thirds had UI of less than 100 mcg/l (the cut-off point for the diagnosis of iodine deficiency).
Iodine deficiency in children is associated with impaired mental function and retarded physical development, and even mild iodine deficiency is thought to lead to reductions of 10-15 in IQ points.
All children with elevated TSH should be tested for iodine deficiency and receive iodine supplementation if indicated. UI concentration is a good marker of the recent intake of iodine over days, and is the index of choice for evaluating iodine deficiency (spot urine concentrations have been shown to correlate well with 24-hour urine samples for iodine content measurements) .The clear benefits of correcting iodine deficiency in children (and indeed adults) far outweigh any potential risks.
Competing interests: No competing interests
The practice review by Niranjan and Wright [1] highlights the ongoing uncertainty on whether or not subclinical hypothyroidism in obese children should be treated with thyroxine. The authors pointed out that they reviewed the clinicaltrials.gov database and found no current studies that are looking at this specific question. They concluded that subclinical hypothyroidism seems to be a consequence rather than the cause of obesity and thyrotropin levels often normalise after weight loss and therefore thyroxine treatment is not supported by the available evidence.
I just wanted to highlight the fact that in children, a number of studies on subclinical hypothyroidism have been focused on children with Down’s syndrome. [2,3,4] While it seems most of these studies have concluded that subclinical hypothyroidism is often transient in Down’s syndrome and does not require treatment with thyroxine, one area of uncertainty is whether or not a prolonged period with subclinical hypothyroidism has negative consequences on the developing brain and on cardio-metabolic health. The potential cognitive consequences of subclinical hypothyroidism are particularly important for children with Down’s syndrome which is already associated with intellectual impairment.
There is a double blind randomised placebo controlled trial [5] that was registered in 2015 with the clinicaltrials.gov database (ClinicalTrials.gov Identifier: NCT01832753) which will look at the change in non-HDL cholesterol and lipid profiles as the primary outcome in children with Down’s syndrome treated with thyroxine versus placebo. It is expected to conclude sometime in 2017. The investigators are exploring the hypothesis that treatment with thyroxine will improve cardio-metabolic health and quality of life. Results from this trial may be relevant to Niranjan and Wright’s question since a number of children with Down syndrome suffer from obesity. [6] The secondary outcome measures will be measurement of the quality of life and perception of body image. It is worth noting that Down’s syndrome patients may not be necessarily representative of the population of non-syndromic obese children given the complexities of Down’s syndrome but the trial will give more insights into the role if any of thyroxine in subclinical hypothyroidism.
References
[1] Niranjan U, Wright NP. Should we treat subclinical hypothyroidism in obese children? BMJ 2016; 352 :i941
[2] Claret C, Goday A, Benaiges D et al. Subclinical hypothyroidism in the first years of life in patients with Down syndrome. Pediatric Research (2013) 73, 674–678 doi:10.1038/pr.2013.26
[3] Editorial: Subclinical hypothyroidism in children with Down syndrome: To treat or not to treat???. The Egyptian Journal of Medical Human Genetics (2015) 16, 87–88 http://dx.doi.org/10.1016/j.ejmhg.2014.10.005
[4] Toscano E, Pacileo G, Limongelli G, et al. Subclinical hypothyroidism and Down’s syndrome; studies on myocardial structure and function. Archives of Disease in Childhood. 2003;88(11):1005-1008. doi:10.1136/adc.88.11.1005.
[5] Treatment Trial of Subclinical Hypothyroidism in Down Syndrome. ClinicalTrials.gov Identifier: NCT01832753. Link: https://clinicaltrials.gov/ct2/show/NCT01832753
[6] van Gameren-Oosterom HBM, van Dommelen P, Schönbeck Y et al. Prevalence of Overweight in Dutch Children With Down Syndrome. Pediatrics, Nov 2012, doi: 10.1542/peds.2012-0886
Competing interests: No competing interests
Iodine deficiency, not excess, is the cause of autoimmune thyroid disease
The link between iodine intake and thyroid autoimmunity is more complex than Neeru Gupta suggests (Response, 08 April 2016), but increasing evidence implicates iodine deficiency, not excess, as the cause of autoimmune thyroid disease.
‘…several cross-sectional studies have reported that thyroid autoimmunity is increased in populations with deficient iodine intakes…Major benefits of increasing iodine intakes in populations with iodine deficiency…[include] a decrease in the prevalence of…thyrotoxicosis in adults.’(1)
‘Chronic iodine excess does not apparently increase the risk of autoimmune hyperthyroidism, suggesting that excessive iodine intake may not be an environmental factor involved in the occurrence of autoimmune hyperthyroidism.’ (2)
‘Concern has been raised suggesting that iodination of salt led to the emergence or increase in prevalence of autoimmune thyroiditis. In regions where chronic excess consumption of iodine occurs, studies have not found an association between iodine intake and prevalence of this disorder.’ (3)
A study to determine if the introduction of iodized salt induces thyroid autoimmunity in iodine-deficient, goitrous children (baseline median UI was 17 mcg/L), found that none developed clinical or ultrasonographic evidence of thyroid autoimmune disease and/or iodine-induced hypothyroidism or hyperthyroidism. The authors concluded that rapid introduction of iodized salt does not provoke significant thyroid autoimmunity in severely iodine-deficient children followed for 1 year. (4)
In Japan, where dietary iodine intakes are high, it has been shown that ‘The incidence of Graves’ disease and Hashimoto’s disease does not appear to be affected by high intakes of iodine.‘ (5)
Evidence is also accumulating that iodine deficiency is able to precipitate thyroid autoimmune reactivity in humans.’ (6)
‘Iodine deficiency precipitates a mild (physiological) form of thyroid autoimmune reactivity.’ (7)
Whilst it is recognised that iodine supplementation carries a small risk of iodine-induced hyperthyroidism (IIH), this condition usually results from autonomously functioning thyroid nodules (which arise as a result of iodine deficiency and then produce excess thyroid hormones when iodine intake is increased). IIH is thus considered to be one of the iodine deficiency disorders; it is not an autoimmune condition. Ultimately, though, ‘the benefits of correcting iodine deficiency far outweigh its risks.’ (8)
1. Iodine deficiency and thyroid disorders. Michael B Zimmermann, Kristien Boelaert. Lancet Diabetes Endocrinol 2015; 3: 286–95
2. Chronic iodine excess does not increase the incidence of hyperthyroidism: a prospective community-based epidemiological survey in China. Fan Yang et al. European Journal of Endocrinology 2007; 156 403–408
3. Autoimmune Thyroiditis and Iodine Therapy. Flechas, Jorge. Journal of Restorative Medicine, Volume 2, Number 1, October 2013, pp. 54-59
4. Introduction of iodized salt to severely iodine-deficient children does not provoke thyroid autoimmunity: a one-year prospective trial in northern Morocco. Zimmermann MB, Moretti D, Chaouki N, Torresani T. Thyroid. 2003 Feb;13(2):199-203
5. Iodine and Health. WHO, Geneva, 1994: P. 4
6. Iodine deficiency induces thyroid autoimmune reactivity in Wistar rats. MOOIJ, H. J. DE WIT et al. Endocrinology 1993 Sep;133(3):1197-1204
7. Iodine and thyroid autoimmune disease in animal models. Ruwhof C, Drexhage HA. Thyroid. 2001 May;11(5):427-36
8. The Iodine Deficiency Disorders. Creswell J. Eastman, M.D., Michael Zimmermann, M.D. Thyroid Disease Manager (www.thyroidmanager.org); Updated February 12, 2014
Competing interests: No competing interests