Endocrine Abstracts

JOINT872

Introduction: Central congenital hypothyroidism (CeCHT) is a rare disorder occurring due to defective TSH-mediated stimulation of the thyroid, usually as part of multiple pituitary hormone deficiency (MPHD). CeCHT is not targeted by the UK TSH-based neonatal screening programme, in contrast to countries operating primary T4±TSH-based screening methodologies. Arguments in favour of CeCHT screening include the potential to prevent illness and associated neurodevelopmental sequelae through earlier management of otherwise undiagnosed pituitary hormone deficiencies. However, routes to detection and clinical consequences of CeCHT have not been evaluated in the UK, precluding predictions of whether neonatal screening could be beneficial.

Method: We assessed biochemical and clinical characteristics in 118 CeCHT cases diagnosed between 1996 and 2022 at 4 tertiary UK centres and considered diagnostic challenges in the context of the clinical picture, baseline biochemistry and the potential impact of screening. Pseudonymized, electronic case records were reviewed retrospectively, recording markers of neurodevelopmental outcome and comparing percentages or median values in patients with early (‘ED’, <15 days, i.e. within a typical newborn screening window) versus late diagnosis (‘LD’) for whom definitive data was available.

Results: 26% cases were preterm, and 96% exhibited MPHD. Early treatment was commenced in only 19% (‘ED’). Neonatal symptoms included hypoglycaemia, (95% ED, 66% LD) consistent with more frequent ACTH deficiency in ED cases (96% ED, 64% LD) and prolonged neonatal jaundice (61% ED, 62% LD). Hypothyroidism was usually moderate (FT4 SDS -2.4 and -2.6 in ‘ED’ and ‘LD’ groups). FT4 was initially checked at 54 days in LD cases, but fell within the laboratory reference range in 29%, and was first defined as abnormal on testing a median of 474 days later. In 24% cases, levothyroxine commencement was delayed (median 169 days, max. 7 yrs) after the first abnormal biochemistry. Significant neurodevelopmental concerns were noted in 37% patients (36% ED, 38% LD) of whom 75% had concomitant ACTH deficiency and in whom midline defects were common (56% vs 18% cases without significant concerns).

Conclusions: This is the largest evaluation of clinical features and pathways to diagnosis in a UK CeCHT cohort. Our findings demonstrate a vulnerable group of children, in whom frequent, MPHD-associated neurodevelopmental concerns mandate optimal management of thyroid status. However, despite neonatal symptoms, challenges in interpreting thyroid biochemistry and delays in testing frequently impede prompt diagnosis. There is a clear need both for systematic identification of CeCH in early life and for improved biochemical diagnostic tools.