Retrospective, multicentre evaluation of central congenital hypothyroidism in the UK.

OBJECTIVE

Central congenital hypothyroidism (incidence ∼1:13,000) occurs in isolation (40% cases) or with additional pituitary hormone deficiencies. T4 ± TSH-based neonatal screening detects central congenital hypothyroidism within the first two weeks of life, permitting prompt treatment, but the UK TSH-based screening programme will not detect these cases. We delineated clinical characteristics, time-frame and pathway to diagnosis in clinically diagnosed individuals.

METHODS

Records were reviewed for 118 cases diagnosed from 1996 to 2022, in four tertiary centres.

RESULTS

Median age at diagnosis was 68 days (range: 1-5,056). 96% had combined pituitary hormone deficiencies. Non-specific neonatal concerns (hypoglycaemia/jaundice/weight concerns, 83%) and significant neurodevelopmental defects (34%) occurred frequently. Compared with cases diagnosed late ( > 1 year, n = 42), early diagnosis ( ≤ 14 days n = 23) was associated with neonatal intensive care admission (78 vs 29%, P < 0.001) and ACTH deficiency (96 vs 40% P < 0.0001). Mean FT4 was moderately low at diagnosis (-2.7 ± 0.9 SDS), but initial thyroid function was within reported reference ranges in 31 cases. Treatment delays could be substantial, even following detection of subnormal FT4, especially in late-diagnosed cases (mean: 208 ± 486 days).

CONCLUSION

UK central congenital hypothyroidism cases are diagnosed later than screening-detected cases, and isolated TSH deficiency may evade detection entirely. 'Sicker' neonates are diagnosed earlier, but late diagnosis frequently occurs despite neonatal/childhood morbidity attributable to combined pituitary hormone deficiencies. Challenges include non-specific neonatal signs, requirement for bespoke age-specific FT4 reference ranges, lack of biomarkers for alternative diagnoses and masking by concomitant GH deficiency. Our findings mandate further studies to assess practicalities, costs and justification for introducing UK-wide central congenital hypothyroidism screening.