Affected individuals with severe intellectual disability, short stature with incomplete skeletal development, coarse facial features, and a protruding tongue are shown in Fig. 42.12. The most common cause of hypothyroidism in children worldwide is iodide deficiency. Although historically viewed as a major cause of hypothyroidism in certain mountainous regions of South America, Africa, and Asia, recent evidence suggests that the problem is even more widespread. Public health programs that add iodide to table salt or provide yearly injections of a slowly absorbed iodide preparation can prevent this tragic form of endemic hypothyroidism. Congenital defects, specifically thyroid gland dysgenesis, are a less common cause of neonatal/child hypothyroidism. Other less frequent causes of childhood hypothyroidism include mutations in genes involved in thyroid hormone production (e.g. NIS, TPO, thyroglobulin, pendrin) or blocking antibodies to the TSH receptor. The severity of the neurological and skeletal defects is closely linked to the timing of diagnosis and thyroid hormone (T4) replacement, with early treatment resulting in normal cognitive ability and subtle neurological deficits. However, if hypothyroidism at birth remains untreated for only 2 to 4 weeks, the CNS will not mature normally in the first year of life. Developmental milestones such as sitting, standing, and walking will be delayed, and severe irreversible cognitive deficits can result. Hypothyroid babies usually appear normal at birth due to the protection provided by maternal thyroid hormones. Neonatal screening (T4 and TSH levels) has therefore played a critical role in the diagnosis and prevention of congenital hypothyroidism.
Fig.42.12 ]).Affectedindividualshavesevereintellectualdisability,shortstaturewithincompleteskeletaldevelopment,coarsefacialfeatures,andaprotrudingtongue.Themostcommoncauseofhypothyroidisminchildrenworldwideisiodidedeficiency.Historically,iodidedeficiencywasviewedasamajorcauseofhypothyroidismincertainmountainousregionsofSouthAmerica,Africa,andAsia,butrecentevidencesuggeststhattheproblemisevenmorewidespread.Thistragicformofendemic hypothyroidism canbepreventedbypublichealthprogramsthataddiodidetotablesaltorprovideyearlyinjectionsofaslowlyabsorbediodidepreparation.Congenital defects arealesscommoncauseofneonatal/childhypothyroidism.Inmostcasesthethyroidglandsimplydoesnotdevelop(thyroid gland dysgenesis). Lessfrequentcausesofchildhood •Fig. 42.12 A,Normal6-year-oldchild(left) andacongenitallyhypothyroid17-year-old(right) fromthesamevillageinanareaofendemichypothyroidism.Notetheshortstature,obesity,malformedlegs,anddullexpressionoftheintellectuallydisabledhypothyroidchild.Otherfeaturesareaprominentabdomen,aflatbroadnose,ahypoplasticmandible,dryscalyskin,delayedpuberty,andmuscleweakness.Radiographsofthehandcomparinganormal13-year-old(B)tothatofa13-year-oldsufferingfromhypothyroidism(C).Notethatthepatientwithhypothyroidismhasamarkeddelayindevelopmentofthesmallbonesofthehands,ingrowthplatesateitherendofthefingers,andinthegrowthplateofthedistalradius.(A,FromDelangeFM.In:BravermanLE,UtigerRD[eds].Werner and Ingbar’s The Thyroid. 7thed.Philadelphia:Lippincott-Raven;1996.B,FromTannerJMetal.
Assessment of Skeletal Maturity and Prediction of Adult Height (TW2 Method). NewYork:AcademicPress;1975.C,FromAndersenHJ.In:GardnerLI[ed].Endocrine and Genetic Diseases of Childhood and Adolescence. Philadelphia:Saunders;1975.) hypothyroidismaremutationsingenesinvolvedinthyroidhormoneproduction(e.g.NIS,TPO,thyroglobulin,pendrin)orblockingantibodiestotheTSHreceptor.Theseverityoftheneurologicalandskeletaldefectsiscloselylinkedtothetimingofdiagnosisandthyroidhormone(T4)replacement,withearlytreatmentresultinginanormalcognitiveabilityandsubtleneurologicaldeficits.Ontheotherhand,ifhypothyroidismatbirthremainsuntreatedforonly2to4weeks,theCNSwillnotmaturenormallyinthefirstyearoflife.Developmentalmilestonessuchassitting,standing,andwalkingwillbelate,andsevereirreversiblecognitivedeficitscanresult.Hypothyroidbabiesusuallyappearnormalatbirthbecauseofprotectionbymaternalthyroidhormones.Neonatal screening (T4andTSHlevels)hasthereforeplayedacriticalroleindiagnosisandpreventionofcongenitalhypothyroidism.