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 iodinecontaining 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 123I 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 longterm 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. Pediatrics 2010;125:S54–S63 AUTHORS: John S. Parks, MD, PhD,a Michelle Lin, MD,a Scott D. Grosse, PhD,b Cynthia F. Hinton, PhD, MS, MPH,b Margaret Drummond-Borg, MD,c,d Lynette Borgfeld, MT,c and Kevin M. Sullivan, PhD, MPH, MHAe aDivision of Pediatric Endocrinology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; bNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia; cDepartment of State Health Services, Austin, Texas; dCook Children’s Physician Network, Fort Worth, Texas; and eDepartment of Epidemiology, Rollins School of Pubic Health, Emory University, Atlanta, Georgia