Background: Thyroglobulin (Tg) is exclusively synthesised by thyroid tissue and a potentially useful aid to diagnosis in congenital hypothyroidism (CH). However, its role has yet to be fully evaluated.
Objective: To examine the sensitivity and specificity of Tg in helping define the etiology of CH.
Patients and methods: Tg was measured in a single laboratory by Immulite 2000 chemiluminescent immunometric assay (CVs 9.8, 5.7 and 5.7% at 1.6, 8.5 and 55 μg/l) in 29 healthy iodine-sufficient babies from Czech Republic (20082012), and 80 infants (51 female) referred with TSH elevation on the Scottish screening program (20042013). Tg was measured on day 3 for controls, usually days 1020 for patients.
Results: Median (interquartile range) Tg in normal infants was 123(91148) μg/L. Equivalent values were 168(23977) μg/L for thyroid ectopia [n=31] (<90 μg/L in 8 and >150 μg/L in 17); 34(3173) μg/L for apparent athyreosis [n=13] (<90 μg/L in 11), undetectable (<2 μg/L) in true athyreosis [n=2]; and 63(32219) μg/L in thyroid hypoplasia [n=5] (<90 μg/L in 2). Tg was < 20 μg/L in 4 patients with dyshormonogenesis due to Tg mutation; and mean/median (range) 1198/1141 (3002301) μg/L in 8 patients (3 transient) with other dyshormonogenesis (300359 μg/L [n=3], 705 μg/L [n=1] and >1000 μg/L [n=4]). Tg varied widely (84995 μg/L) in 18 patients with transient hypothyroidism related to dyshormonogenesis (n=3), TSH receptor mutation (n=3), maternal blocking antibodies (n=1) and other causes (n=11). High levels (>1000 μg/L) of Tg were seen in 2 patients with transient hypothyroidism (cause unknown), one with thyroid ectopia, and one with permanent CH of unknown etiology as well as the 4 with dyshormonogenesis. Tg was significantly lower in patients with athyreosis (P<0.001). Analysis failed to show an overall correlation between serum Tg and TSH levels for the patient group.
Conclusion: Serum Tg shows low specificity for different forms of CH, with considerable overlap. However, levels are unrecordable in true athyreosis, very low in dyshormonogenesis due to Tg mutation; low in apparent athyreosis and thyroid hypoplasia; variable but usually elevated in thyroid ectopia and often high in other forms of dyshormonogenesis. Tg is a useful adjunct to diagnosis in CH but should be interpreted together with thyroid function and imaging. Further work is required to determine whether Tg, in combination with fT4, is useful in predicting thyroxine dose requirement for CH.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology