Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism warranted?

Abstract

When newborn screening (NBS) for congenital hypothyroidism (CH) using thyroid-stimulating hormone (TSH) as a primary screening test was introduced, typical TSH screening cutoffs were 20–50 U/L of whole blood. Over the years, lowering of TSH cutoffs has contributed to an increased prevalence of detected CH. However, a consensus on the benefit deriving from lowering TSH cutoffs at screening is lacking. The present paper outlines arguments both for and against the lowering of TSH cutoffs at NBS. It includes a review of recently published evidence from Australia, Belgium and Italy. A section focused on economic implications of lowering TSH cutoffs is also provided. One issue that bears further examination is the extent to which mild iodine deficiency at the population level might affect the association of neonatal TSH values with cognitive and developmental outcomes. A debate on TSH cutoffs provides the opportunity to reflect on how to make NBS for CH more effective and to guarantee optimum neurocognitive development and a good quality of life to babies with mild as well as with severe CH. All authors of this debate article agree on the need to establish optimal TSH cutoffs for screening programs in various settings and to ensure the benefits of screening and access to care for newborns worldwide.

The impact of demographic factors on newborn TSH levels and congenital hypothyroidism screening

“…Optimal newborn screening TSH cut‐offs are contentious, and selected thresholds vary greatly between programmes . Analysis of the demographic factors that impact screen TSH levels may help explain this variance and provide guidance to screening programmes.…”

“…Furthermore, the use of group‐specific rather than whole‐population TSH reference thresholds can reduce misclassification of subclinical hypothyroidism and limit unnecessary treatment . Recognition of demographic determinants of TSH levels adds further complexity to the diagnostic dilemma of subclinical hypothyroidism in the newborn period . Conversely, both the sensitivity of screening and PPV were higher amongst baby girls, reflecting the increased prevalence of thyroid dysgenesis amongst females (83% of cases within the New Zealand population) …”

“…Primary TSH measurement is the most common screening model used to detect CH worldwide. However, despite decades of experience, optimal TSH cut‐offs remain controversial and the value of detecting increasingly mild or subclinical CH is subject to much debate . International variation in cut‐offs reflects both screening goals and programme factors, including the age at sample collection (and duration from the TSH surge at birth) and assay used.…”

“…However, despite decades of experience, optimal TSH cut-offs remain controversial and the value of detecting increasingly mild or subclinical CH is subject to much debate. [1][2][3] International variation in cut-offs reflects both screening goals and programme factors, including the age at sample collection (and duration from the TSH surge at birth) and assay used. Most recently, a British group reported ethnic differences in blood spot TSH levels and proposed that ethnicity should also be considered when setting and interpreting screening TSH cut-offs.…”

Permanent Decompensated Congenital Hypothyroidism in Newborns with Whole-Blood Thyroid-Stimulating Hormone Concentrations between 8 and 10 mU/L: The Case for Lowering the Threshold

“…International consensus recommends screening with thyroid-stimulating hormone (TSH) measurement as this is the most sensitive for detecting primary CHT [2, 3], but the optimal cut-off for whole-blood TSH concentrations used to identify infants requiring further investigation is controversial [4]. While the majority of international screening programmes historically used a whole-blood TSH cut-off of 20 mU/L, many have lowered this cut-off over time [2].…”