The Role of Thyroid Status in Regulating Brown Adipose Tissue Activity, White Adipose Tissue Partitioning and Resting Energy Expenditure
Condition: Hyperthyroidism
MeSH terms: Hyperthyroidism
Study type: Observational [Patient Registry]

Summary: 
      To determine how thyroid status regulates the relationship between brown adipose tissue (BAT)
      volume/activity, white adipose tissue (WAT) partitioning and basal metabolic rate (BMR) in
      hyperthyroid patients transitioning to euthyroidism via antithyroid drugs.

      To compare euthyroid outcomes (BAT, WAT, BMR, body composition, body weight and insulin
      resistance) achieved by hypothalamus-pituitary-thyroid (HPT) set point vs. normal ranges of
      plasma free thyroxine 4 (FT4) and throxine stimulating hormone (TSH).
    

Detailed description: 
      Study Visit 1 is meant to confirm if subject's hyperthyroidism is due to Graves' disease via
      a blood test called TSH receptor autoantibody (TRAb). This is a standard test that the doctor
      will routinely order as part of clinical practice to diagnose the cause of the subject's
      hyperthyroidism and is not part of the research procedure. If this TRAb blood test has been
      done before the subjects have been referred to the endocrinology clinic at TTSH, the doctors
      will review that result and decide if a repeat test is needed. If subjects are confirmed by
      blood tests to have Graves' disease type of hyperthyroidism, they are eligible to take part
      in this study. However, approximately 2 teaspoons (~ 10 mL) of blood will be taken for
      baseline thyroid function test just prior to the initiation of anti-thyroid drugs.
      Pre-menopausal women will also undergo a urine pregnancy test to exclude pregnancy prior to
      participation at study entry. Once subjects have consented to participate in this study, they
      will receive standard antithyroid drug (ATD) therapy as indicated clinically which in current
      practice will either be carbimazole (CMZ) or thiamazole (TMZ).The clinic endocrinologists at
      TTSH will be in charge of deciding on the ATD dose required based on the latest FT4, FT3 and
      TSH blood test results as per standard medical practice. . Subjects will then be scheduled
      for Visit 2 for baseline research measurements while you are still hyperthyroid.

      On Study Visit 2, subjects will be asked to come to the Clinical Nutrition Research Centre
      (CNRC) at the Centre for Translational Medicine at the National University of Singapore in
      the morning at 0830 h after an overnight fast of 8-10 hours. Subjects will undergo
      anthropometry (ie. measures of body weight, height, waist and hip circumference),
      non-invasive percentage fat estimation using bioelectrical impedence analysis (BIA) and body
      composition evaluation using dual energy X-ray absorptiometry (DXA) which allows
      quantification of fat, lean and bone mass. Subjects will then undergo metabolic rate
      measurement in a whole body calorimeter coupled with infrared thermography using a thermal
      camera mounted on a tripod stand (IRT) focusing on the neck and area above the collar bone in
      a whole body room calorimeter for the next 45 minutes.

      Subjects will then proceed to the Clinical Imaging Research Centre (CIRC) also located in the
      same building at the basement where an intravenous indwelling cannula will be inserted into
      an arm vein from which a fasting blood sample will be taken. At first, 30 mL of blood will be
      taken (about 6 teaspoons) in which 10 mL will be tested for thyroid function while the other
      10 mL will be tested for liver and kidney function and the remaining 10mL for fasting
      glucose, insulin and lipids. An additional 20 mL blood (about 4 teaspoons) will be taken for
      analysis of markers of fat metabolism and protein profiles reflective of brown fat activity.
      A urine sample will also be collected. Subsequently, subjects will be given an intravenous
      injection of a radioactive labeled glucose called 18-FDG through the intravenous cannula and
      followed by PET and fat fraction MRI scanning for BAT and MRI-MRS of abdominal white fat for
      the next 1 hour.

      After that, subjects will then be required to go to the endocrinology clinic at TTSH for
      control of their hyperthyroidism via ATD. This may take about 6 months to attain stable
      thyroid hormones levels (FT4, FT3, TSH). Subjects will be followed up every 6-8 weeks as per
      standard medical practice by theTTSH endocrinologist and have their ATD doses adjusted till
      their thyroid function tests are stable'. When this happens, subjects will continue with the
      remaining part of the research, which is Study Visit 3. With the exception an additional
      urine pregnancy test, Study Visit 3 is exactly the same as Study Visit 2.
    

Intervention name(s): carbimazole (CMZ) or thiamazole (TMZ)
Intervention type(s): Drug
Intervention description(s): CMZ or TMZ will be used to treat the hyperthyroidism till the FT4/TSH is in normal range.
Intervention MeSH terms: Carbimazole
Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        Hyperthyroid patients diagnosed with Graves' disease
      
Biospecimen description: 
      Blood samples for thyroid function, liver and kidney function, fasting glucose, insulin and
      lipids, analysis of fat metabolism and protein profiles.

      Urine samples for fat metabolism and protein profiles.