Investigating the Causes of Congenital Hypothyroidism

  • Research type

    Research Study

  • Full title

    Investigating the Aetiology and Phenotypic Spectrum of Congenital Hypothyroidism

  • IRAS ID

    214073

  • Contact name

    Nadia Schoenmakers

  • Contact email

    naaa2@cam.ac.uk

  • Sponsor organisation

    Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

  • Duration of Study in the UK

    5 years, 0 months, 1 days

  • Research summary

    Congenital hypothyroidism (CH) refers to early-onset thyroid underactivity due to failure of normal development or function of the thyroid gland (primary CH) or more rarely, due to defective stimulation of the thyroid by thyroid stimulating hormone (TSH) produced by the brain (central CH). Untreated CH results in delayed growth and brain development, therefore in the UK we screen newborn babies for primary CH, enabling prompt treatment with levothyroxine.

    In most cases, the cause of CH is unclear, although there are some well-recognized genetic and environmental causes. The whole-body effects of CH have also not been characterized, for example, how CH affects metabolism, and whether gene defects causing CH may also affect other body functions. Additionally, CH is sometimes transient, resolving spontaneously in later childhood, however the risk of transient hypothyroidism recurring (e.g. during pregnancy when thyroid hormone production increases) is not known.

    This study will investigate genetic and environmental factors causing CH, and define the clinical characteristics of affected individuals recruited and studied at Great Ormond Street (GOSH) and Addenbrooke's Hospitals. Individuals with CH and family members will provide DNA for genetic studies and we will compare levels of environmental chemicals and micronutrients which may contribute to CH in samples (e.g. blood, urine) from babies with and without CH, and their mothers. We will characterize specific genetic defects in the laboratory, using additional samples (eg skin biopsy) from some participants and will measure markers of metabolism (eg metabolic rate, body composition, blood and urine markers) in some participants to investigate metabolic effects of CH. We will also investigate whether women with previous transient CH or a genetic predisposition to thyroid dysfunction are at risk of hypothyroidism during pregnancy, and we will assess immune function in individuals with mutations in DUOX genes, since these genes also play a role in immunity.

  • REC name

    East of England - Cambridge South Research Ethics Committee

  • REC reference

    21/EE/0133

  • Date of REC Opinion

    16 Jul 2021

  • REC opinion

    Further Information Favourable Opinion