title: The impact of transient hypothyroidism on the increasing rate of congenital hypothyroidism in the United States.
abstract: The reported incidence rate of primary congenital hypothyroidism (CH) has been increasing in the United States over the past 2 decades. We have considered the possibility that the inclusion of cases of transient hypothyroidism has inflated the reported incidence rate of CH. Assessing the effects of cases of transient hypothyroidism on the incidence rate is problematic, because the definitions, diagnostic criteria, and differentiation from transient hyperthyrotropinemia vary widely among state newborn screening programs. Among the 4 etiologies for transient hypothyroidism (maternal thyrotropin receptor-blocking antibodies, exposure to maternal antithyroid medications, iodine deficiency, and iodine excess), there is little evidence of increases in the incidence rate from thyrotropin receptor-blocking antibodies. Exposure to antithyroid drugs could contribute significantly to the incidence rate of transient CH, given the high estimated incidence of active maternal hyperthyroidism. Iodine deficiency or excess in the United States seems unlikely to have contributed significantly to the incidence rate of CH, because the secular trend toward lower iodine intake among women of reproductive age in the 1980s and 1990s seems to have plateaued, and perinatal iodine exposure has presumably declined as a result of recommendations to discontinue using iodine-containing disinfectants. Although the female-to-male sex ratio among newborns with thyroid agenesis or dysgenesis (the most common causes of CH) is typically 2:1, analysis of the sex ratio of newborns diagnosed with presumed CH in the United States suggests that a substantial proportion might have transient hypothyroidism or hyperthyrotropinemia, because the sex ratio has been well below the expected 2:1 ratio. Combined ultrasonography and (123)I scintigraphy of the thyroid gland are effective tools for identifying cases of thyroid agenesis and dysgenesis and can help to differentiate cases of transient hypothyroidism from true CH. Imaging is also a vital component in evaluating children who, at 3 years of age, undergo a trial of discontinuation of levothyroxine treatment to test for persistence of hypothyroidism. Ultimately, thyroid gland imaging, in conjunction with long-term follow-up studies that appropriately assess and report whether there was permanence of hypothyroidism, will be necessary to address the true incidence rate of CH and any contribution to the observed rate by transient cases of hypothyroidism or hyperthyrotropinemia.
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA. jparks@emory.edu
authors.forename: John S
authors.initials: JS
authors.lastname: Parks
authors.forename: Michelle
authors.initials: M
authors.lastname: Lin
authors.forename: Scott D
authors.initials: SD
authors.lastname: Grosse
authors.forename: Cynthia F
authors.initials: CF
authors.lastname: Hinton
authors.forename: Margaret
authors.initials: M
authors.lastname: Drummond-Borg
authors.forename: Lynette
authors.initials: L
authors.lastname: Borgfeld
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Sullivan
mesh_terms: D013956:Antithyroid Agents / Q000627:therapeutic use; D003409:Congenital Hypothyroidism / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D015994:Incidence; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D009749:Nutrition Surveys; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000276:immunology; D011877:Radionuclide Imaging; D011989:Receptors, Thyrotropin / Q000276:immunology; D012744:Sex Ratio; D013961:Thyroid Gland / Q000000981:diagnostic imaging; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013997:Time Factors; D014463:Ultrasonography; D014481:United States / Q000453:epidemiology
chemical_list: D013956:Antithyroid Agents; D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones; D013972:Thyrotropin