Improving White Matter Integrity With Thyroid Hormone
Condition: Hypothyroidism
MeSH terms: Hypothyroidism
Study type: Observational

Summary: 
      Animal studies have shown that thyroid hormone can improve white matter integrity after
      damage to myelin, which insulates and protects nerves. It is currently unknown whether this
      type of repair can occur in humans. The purpose of the proposed study is to examine the
      impact of thyroid hormone on white matter integrity in humans using two complementary,
      state-of-the-art neuroimaging techniques: high angular diffusion imaging and multicomponent
      relaxometry.
    

Detailed description: 
      The ability to promote and support remyelination has wide-ranging implications for a number
      of neuropsychiatric conditions from multiple sclerosis to major depression. Pre-clinical
      evidence has demonstrated that thyroid hormone treatment, in the form of triiodothyronine
      (T3) or tetraiodothyronine (T4), can promote and support remyelination by increasing myelin
      basic protein mRNA and protein, oligodendrocyte proliferation and maturation, and fractional
      anisotropy (a diffusion imaging measure of white matter integrity). Pilot data from the
      investigator's studies suggest that baseline thyroid status is correlated with the integrity
      of white matter tracts associated with major depression. To date, the impact of thyroid
      hormone administration on white matter tracts has not been studied in vivo in adult humans.
      The purpose of the proposed pilot study is to examine changes in white matter tract integrity
      using high angular diffusion imaging and multi-component relaxometry in a population of
      subjects clinically indicated to receive thyroid hormone for hypothyroidism. The
      investigators will scan patients with hypothyroidism at the initiation of treatment and at
      three and six months after starting thyroid hormone treatment. The investigators will also
      administer scales assessing mood and cognition which have been shown to correlate with white
      matter integrity. The investigators hypothesize that thyroid hormone treatment will be
      associated with an increase in fractional anisotropy, a decrease in radial diffusivity, and
      an increase in the myelin water fraction (markers of improved myelination) that will
      correlate with improvements in cognition and mood ratings. If successful, this will be the
      first demonstration of improved white matter integrity with thyroid hormone replacement and
      pave the way for therapies designed to restore structural brain connectivity.
    

Intervention name(s): Levothyroxine
Intervention type(s): Drug
Intervention description(s): All participants will be treated for their hypothyroidism according to the standard of care as reflected in recent guidelines from the American Thyroid Association.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        We are seeking a population of subjects clinically indicated to receive thyroid hormone for
        hypothyroidism.
      
Keywords: neuroimaging; thyroid; white matter