Metabolomics of Thyroid Hormones

Completed

• Conditions: Hypothyroidism; Central Hypothyroidism; Hyperthyroidism
• Interventions: Diagnostic Test: Indirect calorimetry; Diagnostic Test: Dual energy X-ray Absorptiometry (DXA); Diagnostic Test: Blood sampling

• Registration Number: NCT03823859
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

The aim of this study is to develop a metabolome signature of thyroid hormone status. The metabolome signature could be useful in diagnosis and treatment of thyroid dysfunction diseases, especially in cases where TSH cannot be reliably used.

Detailed Description

Primary Hypothyroidism is a frequent endocrine disorder, where the thyroid gland does not produce sufficient amounts of thyroid hormones. The substitution therapy is guided by measurement of the pituitary gland hormone thyrotropin (TSH). Patients with central hypothyroidism in whom pituitary insufficiency leads to hypothyroidism, TSH cannot be used to guide therapy. So far there are no reliable methods for therapy control in patients with central hypothyroidism.

The measurement of small endogenous metabolites might give investigators a metabolomics profile. This could help to discriminate between euthyroid, hypothyroid and hyperthyroid state and therefore could be used for diagnosis and therapy control of thyroid dysfunction diseases.

Study Timeline

• Study Start: 2018-12-12
• Study First Submitted: 2019-01-28
• Study First Submitted QC: 2019-01-28
• Study First Posted: 2019-01-31
• Primary Completion: 2021-07-28
• Study Completion: 2021-12-31
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-16
• Last Update Posted: 2022-05-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 332

Inclusion Criteria

All participants:

• Age 18 to 80 years
• BMI 19 to 35 kg/m2
• Informed consent as documented by signature

A) Patients with primary hyperthyroidism TSH < 0.2 mIU/l and free thyroxine (fT4) > 25 pM or fT3 > 8 pM

B) Patients with primary hypothyroidism, currently not sufficiently substituted TSH > 8 milli-International unit (mIU)/l or fT4 < 10 pM

C) Patients with diagnosis of primary hypothyroidism, sufficiently substituted Documented diagnosis of primary hypothyroidism Substitution with L-Thyroxin TSH in target range between 0.5 and 2.5 mIU/l

D) Patients with secondary hypothyroidism Pituitary disease with documented secondary hypothyroidism

Exclusion Criteria

• Diabetes mellitus (HbA1c >6.5%)
• Severe concomitant diseases: chronic heart failure, liver cirrhosis, kidney failure, active cancer
• Abuse of alcohol or illicit drugs
• Women who are pregnant or breast feeding
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
• Previous enrolment into the current study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with thyroid dysfunction	Indirect calorimetry	Patients with Primary hypothyroidism newly diagnosed, Primary hypothyroidism substituted, hyperthyroidism, secondary hypothyroidism * Blood sampling (fT3, fT4, TSH, Lipids, Glucose, HbA1c) * Indirect calorimetry * Dual energy X-ray Absorptiometry (DXA)
Healthy volunteers	Dual energy X-ray Absorptiometry (DXA)	* Blood sampling (fT3, fT4, TSH, Lipids, Glucose, HbA1c) * Indirect calorimetry * Dual energy X-ray Absorptiometry (DXA)
Healthy volunteers	Blood sampling	* Blood sampling (fT3, fT4, TSH, Lipids, Glucose, HbA1c) * Indirect calorimetry * Dual energy X-ray Absorptiometry (DXA)
Patients with thyroid dysfunction	Dual energy X-ray Absorptiometry (DXA)	Patients with Primary hypothyroidism newly diagnosed, Primary hypothyroidism substituted, hyperthyroidism, secondary hypothyroidism * Blood sampling (fT3, fT4, TSH, Lipids, Glucose, HbA1c) * Indirect calorimetry * Dual energy X-ray Absorptiometry (DXA)
Healthy volunteers	Indirect calorimetry	* Blood sampling (fT3, fT4, TSH, Lipids, Glucose, HbA1c) * Indirect calorimetry * Dual energy X-ray Absorptiometry (DXA)
Patients with thyroid dysfunction	Blood sampling	Patients with Primary hypothyroidism newly diagnosed, Primary hypothyroidism substituted, hyperthyroidism, secondary hypothyroidism * Blood sampling (fT3, fT4, TSH, Lipids, Glucose, HbA1c) * Indirect calorimetry * Dual energy X-ray Absorptiometry (DXA)

Primary Outcome Measures

Name	Time	Method
Metabolome signature of thyroid Hormone Status (MSTH)	baseline/single visit	The MSTH will be tested against the current standard of diagnosis which is serum TSH level by multiple linear regression.

Secondary Outcome Measures

Name	Time	Method
Resting energy expenditure (REE)	baseline/single visit	Comparison of REE of healthy volunteers and Patients with thyroid dysfunction, measured by indirect calorimetry.
Body composition concerning fat mass	baseline/single visit	Comparison of fat mass of healthy volunteers and patients with thyroid dysfunction, measured by DXA
Body composition concerning muscle mass	baseline/single visit	Comparison of muscle mass of healthy volunteers and patients with thyroid dysfunction, measured by DXA

Trial Locations

Locations (1)

University Hospital Basel, Department of Endocrinology; 🇨🇭 Basel, BS, Switzerland