Background: Identification of Congenital Hypothyroidism (CH) is an essential part of Newborn Bloodspot Screening (NBS) in the UK. NBS for CH relies on Blood Spot (BS) Thyroid Stimulating Hormone (TSH) measurement in newborns on day 5 of life. Diagnostic confirmation of a screen positive result requires measurement of plasma/serum free thyroxine (fT4) and TSH but technetium thyroid scanning is not mandatory. Technetium-99m scintigraphy can be used to define size and location of the thyroid gland but is not available in all screening centres. We aimed to investigate the utility of scintigraphy to establish the cause of CH and impact on clinical management.
Methods: Scintigraphy outcomes of newborns referred to a regional NBS centre between 2007 and 2017 on the basis of initial screening BS TSH>20 mU/L or >8 mU/L in the second/subsequent sample following a borderline result were retrospectively reviewed in the following categories normal/large gland (dyshormonogenesis), small/absent (dysplasia) and abnormal position (ectopia). Scintigraphy was tested for correlation with BS TSH screening level and venous plasma TSH and free thyroxine (fT4) levels ascertained during diagnostic workup.
Results: 418 newborns were referred for possible CH from 534,783 newborns screened by NBS, of whom 342 were treated with levothyroxine. Based on scintigraphy appearances (n=293) the largest diagnostic CH group was dyshormonogenesis (n=134, 45.7%) followed by ectopia (n=80, 27.3%) and dysplasia (n=79, 27.0%). Median (interquartile range) BS TSH (mU/L) was lower in dyshormonogenesis [23.5(28.0)] than in ectopia [106.0(147.0)] and dysplasia [172.0(183.0)] [P<0.001 for difference between groups] but was non-discriminatory between dysplasia and ectopia [P=0.12]. Plasma TSH showed similar differences. Conversely, fT4 levels (pmol/L) were higher in dyshormonogenesis [12.0(9.5)] than in ectopia [9.6(8.9)] and dysplasia [4.0(11.1)] [P<0.001]. Corresponding initial levothyroxine treatment doses (micrograms/day) were 25.0(12.5), 37.5(12.5) and 37.5(25.0) [P<0.001] respectively, consistent with the severity of thyroid dysfunction in each group. Levothyroxine dose correlated independently with fT4 levels in analysis of covariance for either dyshormonogenesis or ectopia [P=0.009, R2=0.40 for model], but not for dysplasia or ectopia [P=0.22, R2=0.38] suggesting diagnosis-specific influence of scintigraphy on initial treatment dose.
Conclusions: Thyroid scintigraphy demonstrates dyshormonogenesis as the most frequent form of CH. Scintigraphy identifies and locates ectopia which might otherwise be incorrectly classified as dysplasia. Accurate CH classification is crucial for initial levothyroxine dosage. The diagnoses of dyshormonogenesis and ectopia are likely to influence long-term clinical management of CH.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology