Congenital Hypothyroidism in Children: A Cross-Sectional Study in a Tertiary Centre in Malaysia
Keywords:congenital hypothyroid, thyroid dysgenesis, thyroid dyshormonogenesis, transient hypothyroid, thyroxine, cord blood TSH
Abstract*Visual Abstracts prepared by Dr. Carmen Carina Cabrera
Introduction. The causes of congenital hypothyroidism (CHT) are thyroid dysgenesis (TD), dyshormonogenesis (TDH)or transient (TH).
Methodology. This is a cross-sectional study looking at data over a period of 16 years (2000-2016). Confirmed cases had thyroid scan at the age of 3-years-old and repeated TFT (after 6 weeks off medications). Relevant data was collected retrospectively.
Results. Forty (60% female) children with CHT were included in the study. Thirty (75%) children presented with high cord TSH. Nine (23%) presented after 2 weeks of life. Majority were diagnosed with TDH (42.5%) with TD and TH of 40% and 17.5% respectively. Median cord TSH of children with TD was significantly higher compared to TDH and TH (p=0.028 and p=0.001 respectively). L-thyroxine doses were not significantly different between TD, TDH and TH at diagnosis or at 3 years.
Conclusions. TDH is highly prevalent in our population. TD may present after 2 weeks of life. One in five children treated for CHT had TH. Differentiating TD, TDH and TH before initiating treatment remains a challenge in Malaysia. This study provides clinicians practical information needed to understand the possible aetiologies from a patient’s clinical presentation, biochemical markers and treatment regime. Reassessing TH cases may be warranted to prevent
Henry G, Sobki SH, Othman JM. Screening for congenital hypothyroidism. Saudi Med J. 2002;23(5):529-35. https://www.ncbi.nlm.nih.gov/pubmed/12070574.
Buyukgebiz A. Newborn screening for congenital hypothyroidism. J Clin Res Pediatr Endocrinol. 2013;5(Suppl 1):8-12. https://www.ncbi.nlm.nih.gov/pubmed/23154158. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608007. https://doi.org/10.4274/jcrpe.845.
Rastogi MV, LaFranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis, 2010. 5:17. https://www.ncbi.nlm.nih.gov/pubmed/20537182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903524. https://doi.org/10.1186/1750-1172-5-17.
Joseph R. Mass newborn screening in Singapore. Southeast Asian J Trop Med Public Health. 2003;34(Suppl 3):89-90. https://www.ncbi.nlm.nih.gov/pubmed/15906706.
Zarina AL, Rahman R, Bador KM, Ng SF, Wu LL. Audit of newborn screening programme for congenital hypothyroidism. Med J Malaysia. 2008;63(4):325-8. https://www.ncbi.nlm.nih.gov/pubmed/19385494.
Wong SLW, Jalaludin M, Anuar A, Samingan N, Harun F. Congenital hypothyroidism: An audit and study of different cord blood screening TSH values in a tertiary medical centre in Malaysia. Advances in Endocrinology. 2015;2015. https://doi.org/10.1155/2015/387684.
Kapoor S, Kapoor D, Kapoor VK Congenital hypothyroidism: Its profile in infancy. Thyroid Res Pract. 2013;10(3):47-55. https://doi.org/10.4103/0973-0354.110577.
Euge`ne D, Djemli A, Van Vliet G. Sexual dimorphism of thyroid function in newborns with congenital hypothyroidism. J Clin Endocrinol Metab. 2005;90(5):2696–700. https://www.ncbi.nlm.nih.gov/pubmed/15728201. https://doi.org/10.1210/jc.2004-2320.
Ordooei M, Rabiei A, Soleimanizad R, Fatemeh M. Prevalence of permanent congenital hypothyroidism in children in Yazd, Central Iran. Iran J Public Health, 2013;42(9):1016-20. http://ijph.tums.ac.ir.
Azriyanti AZ, Yazid MJ, Fatimah H, Thyroid gland phenotype in primary congenital hypothyroidism. Hormone Research. 2008;70(Suppl 3):58.
Albert BB, Heather N, Derraik JG, et al., Neurodevelopmental and body composition outcomes in children with congenital hypothyroidism treated with high-dose initial replacement and close monitoring.
Harun F, Ch'ng SL. Congenital hypothyroidism in a developing country. Proceedings of Clinical Thyroidology Meeting. Innsbruck, Austria; 1992.
American Academy of Pediatrics, Rose SR, Section on Endocrinology and Committee on Genertics, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006;117(6):2290-303. https://www.ncbi.nlm.nih.gov/pubmed/16740880. https://doi.org/10.1542/peds.2006-0915.
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(6):1203-9. https://www.ncbi.nlm.nih.gov/pubmed/8502532.
Bernal J. Thyroid hormones in brain development and function.: South Dartmouth (MA): MDText.com, Inc; Updated 2015. https://www.ncbi.nlm.nih.gov/books/NBK285549/.
Eugène D, Djemli A, Van Vliet G. Sexual dimorphism of thyroid function in newborns with congenital hypothyroidism. J Clin Endocrinol Metab, 2005;90(5):2696-700. https://www.ncbi.nlm.nih.gov/pubmed/15728201. https://doi.org/10.1210/jc.2004-2320.
Hofman P. Insights into the diagnosis and management of congenital hypothyroidism. Int J Pediatr Endocrinol. 2015;2015(Suppl 1):O18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428806. https://doi.org/10.1186/1687-9856-2015-S1-O18.
Rosenthal M, Addison GM, Price DA. Congenital hypothyroidism: Increased incidence in Asian families. Arch Dis Child. 1988;63(7):790-3. https://www.ncbi.nlm.nih.gov/pubmed/3415295. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779081. https://doi.org/10.1136/adc.63.7.790.
Grant D, Smith I. Survey of neonatal screening for primary hypothyroidism in England, Wales, and Northern Ireland 1982-4. Br Med J (Clin Res Ed). 1988;296(6633):1355-8. https://www.ncbi.nlm.nih.gov/pubmed/3134984. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2545827. https://doi.org/10.1136/bmj.296.6633.1355.
Albert BB, Cutfield WS, Webster D, et al. Etiology of increasing incidence of congenital hypothyroidism in New Zealand from 1993–2010. J Clin Endocrinol Metab. 2012;97(9):3155-60. https://www.ncbi.nlm.nih.gov/pubmed/22723332. https://doi.org/10.1210/jc.2012-1562.
Current population estimates, Malaysia 2018-2019. Department of Statistics, Official Portal. Available at https://www.dosm.gov.my/v1/index.php?r=column/cthemeByCat&cat=155&bul_id =aWJZRkJ4UEdKcUZpT2tVT090Snpydz09&menu_id=L0pheU43NWJwRWVSZklWdzQ4TlhUUT09.
Lee CC, Harun F, Jalaludin MY, Heh CH, Othman R, Junit SM. Prevalence of c. 2268dup and detection of two novel alterations, c.670_672del and c. 1186C> T, in the TPO gene in a cohort of Malaysian–Chinese with thyroid dyshormonogenesis. BMJ Open. 2015;5(1):p. e006121. https://www.ncbi.nlm.nih.gov/pubmed/25564141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289740. https://doi.org/10.1136/bmjopen-2014-006121.
Lee CC, Harun F, Jalaudin MY, Lin CY, Ng KL, Junit SM. Functional analyses of c.2268dup in thyroid peroxidase gene associated with goitrous congenital hypothyroidism. Biomed Res Int. 2014;2014:Article ID 370538. https://doi.org/10.1155/2014/370538.
Waller DK, Anderson JL, Lorey F, Cunningham GC. Risk factors for congenital hypothyroidism: An investigation of infant's birth weight, ethnicity, and gender in California, 1990–1998. Teratology. 2000;62(1):36-41. https://www.ncbi.nlm.nih.gov/pubmed/10861631. https://doi.org/10.1002/1096-9926(200007)62:1<36::AID-TERA8>3.0.CO;2-W.
Parks JS, Lin M, Grosse SG, et al. The impact of transient hypothyroidism on the increasing rate of congenital hypothyroidism in the United States. Pediatrics. 2010;125(Suppl 2): S54-63. https://www.ncbi.nlm.nih.gov/pubmed/20435718. https://doi.org/10.1542/peds.2009-1975F.
Selamat R, Mohamud WN, Zainuddin AA, Rahim NS, Ghaffar SA, Aris T. Iodine deficiency status and iodised salt consumption in Malaysia: Findings from a national iodine deficiency disorders survey. Asia Pac J Clin Nutrition. 2010;19(4):578-85. PMID: 21147721.
Lim KK, Chan YY, Teh CH, et al. Iodine status among pregnant women in rural Sabah, Malaysia. Asia Pac J Clin Nutr. 2017;26(5):861-6. https://www.ncbi.nlm.nih.gov/pubmed/28802296. https://doi.org/10.6133/apjcn.092016.06.
Report of household income and basic amenities survey 2016. Department of Statistics Malaysia, Official Portal. Available at https://www.dosm.gov.my/v1/index.phpr=column/cthemeByCat&cat=120&bul_id=RUZ5REwveU1ra1hGL21JWVlPRmU2Zz09&menu_id=amVoWU54UTl0a21NWmdhMjFMMWcyZz09
Schoelwer MJ, Tu W, Zhou J, Eugster EA. Targeted levothyroxine therapy for treatment of congenital hypothyroidism. Endocr Pract. 2017;23(9):1067-71. https://www.ncbi.nlm.nih.gov/pubmed/28683242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808429. https://doi.org/10.4158/EP171881.OR.
Mathai S, Cufield WS, Gunn AJ, et al. A novel therapeutic paradigm to treat congenital hypothyroidism. Clin Endocrinol (Oxf). 2008;69(1):142-7. https://www.ncbi.nlm.nih.gov/pubmed/18598275. https://doi.org/10.1111/j.1365-2265.2008.03172.x.
Léger J, Olivieri A, Donaldson M, et al. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab. 2014;99(2):363-84. https://www.ncbi.nlm.nih.gov/pubmed/24446653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207909. https://doi.org/10.1210/jc.2013-1891.
How to Cite
Journal of the ASEAN Federation of Endocrine Societies is licensed under a Creative Commons Attribution-NonCommercial 4.0 International. (full license at this link: http://creativecommons.org/licenses/by-nc/3.0/legalcode).
To obtain permission to translate/reproduce or download articles or use images FOR COMMERCIAL REUSE/BUSINESS PURPOSES from the Journal of the ASEAN Federation of Endocrine Societies, kindly fill in the Permission Request for Use of Copyrighted Material and return as PDF file to firstname.lastname@example.org or email@example.com.
A written agreement shall be emailed to the requester should permission be granted.