Improvement of Laboratory Diagnostics in Hypothyroid Patients Using Levothyroxine

NCT06083636 | Recruiting

• 1 other identifier: NL81578.018.22
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothyroidism is a thyroid disorder and one of the most common endocrine disorders. Hypothyroidism can have multiple causes; most patients suffer from primary autoimmune hypothyroidism (Hashimoto's disease), but also central hypothyroidism, hypothyroidism after total thyroidectomy due to thyroid carcinoma, or hypothyroidism due to therapy of Graves' disease occur. Most patients with hypothyroidism are treated with levothyroxine (L-T4) to supplement the lack of thyroxine (T4) produced by their own thyroid. Serum thyroid-stimulating hormone (TSH) and/or free T4 (fT4) are currently measured to assess the efficacy of this therapy and to establish euthyroidism. It is known that fT4 concentrations in patients using L-T4 can be above the upper limit of the reference interval, while their TSH is not (completely) suppressed. This raises the question whether fT4 is an accurate reflection of thyroid hormone status in patients using L-T4. TSH is considered a reliable parameter of thyroid hormone status; however, TSH cannot be used to assess thyroid function in specific hypothyroid patient groups (e.g. central hypothyroidism). Free triiodothyronine (fT3), the active thyroid hormone, has been suggested to be an interesting alternative of fT4 to assess thyroid function. Previously, the methods to measure fT3 were not that robust; however, methods to determine fT3 have been improved, are currently reliable and not susceptible to changes due to L-T4 intake. In addition, the fT3/fT4 ratio is thought to be an interesting candidate in assessing thyroid hormone status as well. The aim of this study is to improve laboratory diagnostics of thyroid hormone status in patients with hypothyroidism receiving L-T4 in whom TSH cannot be used as a reflection of thyroid hormone status. We will primarily investigate the additional already available laboratory tests fT3 and fT3/fT4 ratio. We hypothesize that treated hypothyroid participants who are assumed euthyroid based on TSH (e.g. patients with Hashimoto's hypothyroidism) but have fT4 concentrations above the upper reference limit will more often have a fT3 level or a fT3/fT4 ratio within the reference interval. Concentrations of alternative markers in healthy controls and patients with Hashimoto's hypothyroidism with 'normal' TSH concentrations can, thus, be used to predict thyroid hormone status in patients using L-T4 in whom TSH cannot be used to assess thyroid hormone status.

Conditions

Hypothyroidism

Keywords

Hypothyroidism; Levothyroxine; Laboratory diagnostics; Free triiodothyronine; Central hypothyroidism

Outcome Measures

Primary Outcomes (4)

• TSH concentration

  Laboratory measurement

  Single measurement in cross-sectional design during the study period, which is approximately 4 years

• fT4 concentration

  Laboratory measurement

  Single measurement in cross-sectional design during the study period, which is approximately 4 years

• fT3 concentration

  Laboratory measurement

  Single measurement in cross-sectional design during the study period, which is approximately 4 years

• fT3/fT4 ratio

  Ratio derived from abovementioned laboratory measurements

  One-time determination in cross-sectional design during the study period, which is approximately 4 years

Secondary Outcomes (6)

• TT4 concentration

  Single measurement in cross-sectional design during the study period, which is approximately 4 years

• TT3 concentration

  Single measurement in cross-sectional design during the study period, which is approximately 4 years

• rT3 concentration

  Single measurement in cross-sectional design during the study period, which is approximately 4 years

• SHBG

  Single measurement in cross-sectional design during the study period, which is approximately 4 years

• Acylcarnitine(s) (profile)

  Single measurement in cross-sectional design during the study period, which is approximately 4 years

Other Outcomes (9)

• ThyPRO-39

  One-time completion around time of laboratory measurement during the study period, which is approximately 4 years

• DIO polymophisms

  Single measurement in cross-sectional design during the study period, which is approximately 4 years

• Sex

  One-time completion around time of laboratory measurement during the study period, which is approximately 4 years

Study Arms (5)

Hashimoto's hypothyroidism

Group of 100 patients with Hashimoto's hypothyroidism using levothyroxine

Other: Single extra blood draw and completion of single questionnaire

Hypothyroidism after thyroidectomy after thyroid carcinoma

Group of 100 patients with hypothyroidism after thyroidectomy after thyroid carcinoma using levothyroxine

Other: Single extra blood draw and completion of single questionnaire

Central hypothyroidism

Group of 100 patients with central hypothyroidism using levothyroxine

Other: Single extra blood draw and completion of single questionnaire

Hypothyroidism during treatment for Graves' Disease

Group of 100 patients with hypothyroidism during treatment for Graves' Disease using levothyroxine

Other: Single extra blood draw and completion of single questionnaire

Healthy controls

100 healthy euthyroid controls

Other: Single blood draw and completion of single questionnaire

Interventions

Single extra blood draw and completion of single questionnaire OTHER

Single blood draw of 3 tubes (20 mL) additional to regular blood draw will be performed. All participants will complete a single questionnaire that will be 5-10 minutes time-consuming.

Central hypothyroidism; Hashimoto's hypothyroidism; Hypothyroidism after thyroidectomy after thyroid carcinoma; Hypothyroidism during treatment for Graves' Disease

Single blood draw and completion of single questionnaire OTHER

Single blood draw of 3 tubes (20 mL) will be performed. All participants will complete a single questionnaire that will be 5-10 minutes time-consuming.

Healthy controls

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adults with hypothyroidism using levothyroxine (L-T4) attending the outpatient clinic of Amsterdam UMC will be included. Healthy euthyroid controls will be recruited amongst employees of Amsterdam UMC.

You may qualify if:

• In order to be eligible to participate in this study, a hypothyroid subject must meet all of the following criteria:
• Ability to provide informed consent
• Ability to speak and understand Dutch or English
• Intake of a stable dosage of levothyroxine, meaning the dosage of levothyroxine must not be changed during the appointment at the outpatient clinic
• Diagnosis of one these forms of hypothyroidism
• Patients with primary hypothyroidism: euthyroid based on TSH according to physician
• Patients with hypothyroidism after a total thyroidectomy due to thyroid carcinoma (therefore athyroid): on target TSH according to physician (target TSH depending on stage/severity of carcinoma)
• Patients using L-T4 due to therapy of Graves' disease: euthyroid based on TSH according to physician (TSH cannot be suppressed, namely TSH within reference interval of 0,5-5,0 mU/L)
• Patients with central hypothyroidism: euthyroid based on fT4 according to physician (common is fT4 in the upper limit, reference interval is 12-22 pmol/L)
• In order to be eligible to participate in this study, a healthy control subject must meet all of the following criteria:
• Ability to provide informed consent;
• Ability to speak and understand Dutch or English
• Consider themselves healthy

You may not qualify if:

• A potential hypothyroid subject who meets any of the following criteria will be excluded from participation in this study:
• Not euthyroid according to physician
• Pregnancy
• Patients using L-T4 due to therapy of Graves' disease: if TSH is still suppressed
• Any of the following medication
• Liothyronine (Cytomel)
• Iodide
• Oral contraceptives
• Active treatment of malignancy (other than thyroid carcinoma)
• A potential healthy control subject who meets any of the following criteria will be excluded from participation in this study:
• Pregnancy
• Any of the following medication
• Thyroid medication (a.o. levothyroxine, thiamazol, PTU)
• Lithium
• Amiodarone

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC

Amsterdam, North Holland, 1105 AZ, Netherlands

RECRUITING

Related Publications (24)

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Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma and serum samples are retained for 15 years as required for medical research.

MeSH Terms

Conditions

Hypothyroidism

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Annemieke C Heijboer, Prof. dr.

  Amsterdam UMC, VU Amsterdam and UvA, Endocrine Laboratory, Department of Laboratory Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heijboer

CONTACT

+31205665940; a.heijboer@amsterdamumc.nl

Jansen

CONTACT

+31205666434; h.jansen@amsterdamumc.nl

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: October 4, 2023
• First Posted: October 16, 2023
• Study Start: July 26, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 3, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)