The Continuing Health Burden of Congenital Hypothyroidism in the Era of Neonatal Screening

Abstract

Biochemical screening of neonates for congenital hypothyroidism (CH), followed by appropriate treatment, results in the disappearance of overt intellectual disability among those affected by this condition (1). However, this does not mean that neonatal screening necessarily results in the same health outcomes as among unaffected individuals. Indeed, numerous studies have reported subtle neurological and cognitive differences in cohorts of children with CH detected by screening (2). Few studies, however, have assessed health status, educational attainment, and labor market outcomes among adults with CH in populations that have benefited from screening for the disorder. Such studies necessarily reflect the screening, diagnostic, and initial treatment practices of more than two decades ago, practices that are continually evolving. Nevertheless, findings from such studies are important to guide how practices can be “fine tuned” to optimize outcome even in severely affected subjects. In the present issue of JCEM, Leger et al. (3) report the result of a large postal questionnaire survey of 1202 French patients with CH at an average age of 23.4 yr. This survey was carried out in 2007–2008, and its results are compared with those of face-to-face interviews for a national sample of 5718 control subjects aged 18–30 yr. Patients with CH significantly more often reported having another chronic disease or hearing impairment, or being overweight; they were less likely to have attained the highest socioeconomic category, to be in full-time employment, and to be living independently; lastly, their mental health score calculated from the Short-Form Health Survey-36 was 0.35 SD below that of the comparison sample. All of the differences were modest in magnitude, mostly less than 5 percentage points, between cases and controls. The authors speculate that the nonresponders (31% of sample) may have been too handicapped to participate, although the opposite hypothesis, i.e. that they felt so healthy that they did not bother responding, seems equally plausible. In addition, questionnaire studies can be influenced by the way in which they are constructed, a phenomenon that has been called a “focusing illusion” (4). What should we make of the differences found by Leger et al. (3)? Although most young adults with CH treated with levothyroxine soon after birth appear clinically indistinguishable from their peers, a minority reports modestly poorer health, educational, economic, and social outcomes. For example, 49.6% of adults with CH had higher secondary or tertiary education, compared with 51.5% of controls. These differences are not random but are concentrated among CH patients with greater severity of CH, worse treatment adequacy, and the presence of associated chronic conditions. For example, among those with CH, the percentage with higher secondary/tertiary education was 53% of those who had no other chronic disease, no hearing impairment, and were not obese, compared with 33% of those who had one or more of these associated conditions. Similarly, 54% of those with adequate treatment during early adulthood had higher educational attainment, compared with 42% of those with TSH greater than 5 mU/liter (range, 7.6–27.6 mU/liter) at the most recent assessment of thyroid function, which was within 2 yr of the questionnaire study. Not all adult patients with