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

Abstract

Background: Congenital hypothyroidism (CHT) has a reported incidence of approximately 1 in 2,000–4,000 births. There is no consensus on the optimal cut-off whole-blood thyroid-stimulating hormone (TSH) concentration that should be used for newborn screening (NBS). The NBS programme in the Republic of Ireland has used a cut-off of 8 mU/L since 1979. The aim of this study was to determine if raising the cut-off to 10 mU/L would have resulted in undetected cases of permanent or decompensated CHT. Methods: All cases of CHT with a screening whole-blood TSH concentration between 8.0 and 9.9 mU/L were identified from the Republic of Ireland’s NBS programme. Baseline demographics and imaging results were recorded. All cases over 3 years of age were evaluated to determine if CHT was permanent or transient. Results: Of 2,361,174 infants screened in the Republic of Ireland between July 1979 and December 2016, a total of 1,063 babies were diagnosed with CHT and treated with levothyroxine. This included 33 (3.5%) infants with a whole-blood TSH concentration between 8 and 9.9 mU/L. Thirteen of these 33 infants had decompensated hypothyroidism with low plasma free thyroxine level at diagnosis and 9 (41%) of the 21 evaluable cases have confirmed permanent CHT. Conclusion: Although lowering screening TSH cut-offs can increase the cost of NBS, as well as anxiety for families, many infants with borderline increases in whole-blood TSH concentrations on NBS have persistent CHT and low thyroxine concentrations in infancy. We recommend that this is considered when developing and reviewing NBS protocols for identifying infants with CHT.

Incidence of Congenital Hypothyroidism Over 37 Years in Ireland

“…Many screening programs' cutoff levels have changed over time, which may partially explain the increased case ascertainment rate. 10, [14][15][16] Newborn screening for CHT in the Republic of Ireland began in July 1979 with a centralized newborn screening program for the entire country. Unlike other screening programs, the same assay and a consistent screening whole-blood thyroid-stimulating hormone (TSH) cutoff level of 8 mU/L has been used in the newborn screening program since the program's inception in 1979.…”

Evolution of congenital hypothyroidism in a cohort of preterm born children

“…17e20 Suggested factors contributing to this phenomenon are the lowering in TSH screening cut-off levels over time and the increasing survival of preterm infants. 19,21 It is estimated that approximately one in nine babies born in the Table 1 Characteristics of all patients (n Z 28). Quantitative data are expressed as the median (IQR) or mean AE SD, and qualitative data are expressed as frequency (%).…”

Infants Diagnosed with Athyreosis on Scintigraphy May Have a Gland Present on Ultrasound and Have Transient Congenital Hypothyroidism

“…Congenital hypothyroidism (CHT) affects approximately 1 in 2,000-4,000 births and is a cause of preventable neurodevelopmental disability [1][2][3][4][5][6]. Newborn screening programs have increased the rate of early detection of this condition and almost eradicated this complication of disease [7]. Knowing the underlying aetiology of CHT can help predict if treatment is likely to be lifelong and can inform discussions with parents at diagnosis.…”

“…Hypothyroidism is transient in up to 40% of children diagnosed with CHT who have a eutopic thyroid gland in situ [5][6][7]. Thyroid-stimulating hormone (TSH) concentrations are elevated at birth, regardless of whether the diseases will be permanent or transient.…”