Effect of Hypothyroidism on Brown Adipose Tissue

Effect of Restoration of Euthyroidism in Patients With Primary Hypothyroidism on Brown Adipose Tissue Thermogenesis - the ThyroBAT Study

The investigators aim to study whether hypothyroidism negatively affects Brown adipose tissue (BAT) function in humans and whether BAT function can be restored to normal by thyroid hormone supplementation.

Study Overview

• Status: Completed
• Conditions: Hypothyroidism

Detailed Description

Hypothyroidism is a frequent endocrine disorder, the prevalence of subclinical disease being 4.3% and of overt disease being 0.3%. Patients suffering from hypothyroidism frequently complain of increased cold sensitivity and involuntary weight gain, indicating changes in energy expenditure and response to cold challenge.

Recently, brown adipose tissue (BAT) has regained attention as an energy expending tissue. While it was previously thought to be of no or negligible relevance in human adults, recent studies clearly demonstrated the presence and metabolic activity of BAT in human adults. Upon activation of BAT by the sympathetic nervous system intracellular lipid stores are rapidly depleted. The generated free fatty acids fuel beta-oxidation and the respiratory chain within the mitochondria and activate at the same time uncoupling protein 1 (UCP1). This protein acts as a protonophore, allowing the flux of protons along the electrochemical gradient into the inner mitochondrial matrix instead of transferring their energy to adenosine triphosphate (ATP)-synthase. The short circuiting of the oxidative phosphorylation within the mitochondria leads to highly active cellular respiration and generation of heat. Basic research highlights the importance of thyroid hormone in the development and function of BAT.

It has recently been shown that hyperthyroidism exerts activating effects on BAT in adult humans.

The investigators aim to study whether hypothyroidism negatively affects BAT function in humans and whether BAT function can be restored to normal by thyroid hormone supplementation.

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• Switzerland
  • BS
    • Basel, BS, Switzerland, 4031
      • University Hospital Basel, Department of Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

currently hypothyroid patients which are started on levothyroxin substitution

Description

Inclusion Criteria:

• informed consent
• Serum thyroid-stimulating hormone (TSH) > 4.5 milli-International unit (mIU)/l
• body mass index (weight/height(m)²) 17.5 to 30 kg/m²

Exclusion Criteria:

• known concomitant disease influencing thyroid hormone metabolism
• chronic heart failure
• liver cirrhosis
• severe kidney failure
• metastasized cancer, except for thyroid cancer
• known hypersensitivity to cold, e.g. primary or secondary Raynaud's syndrome
• abuse of alcohol or illicit drugs
• Women who are pregnant or breast feeding
• Intention to become pregnant during the course of the study
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
• Participation in another study with investigational drug within the 30 days preceding and during the present study
• Previous enrolment into the current study

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
difference in cold induced thermogenesis between baseline and restoration of euthyroidism, assessed as the increase in resting energy expenditure after a mild cold stimulus determined by indirect calorimetry	before and after 3 months after restoration of euthyroidism

Secondary Outcome Measures

Outcome Measure	Time Frame
difference in supraclavicular skin temperature (before and after cold exposure)	before and after 3 months after restoration of euthyroidism
levels of Irisin in serum	before and after 3 months after restoration of euthyroidism
patient's perception of cold	before and after 3 months after restoration of euthyroidism

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Mirjam Christ-Crain, MD, Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: February 13, 2015
• First Posted (Estimate): February 16, 2015

Study Record Updates

• Last Update Posted (Actual): August 28, 2017
• Last Update Submitted That Met QC Criteria: August 25, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hypothyroidism
• Other Study ID Numbers: EKNZ 2015-028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED