Improvement of Laboratory Diagnostics in Hypothyroid Patients Using Levothyroxine

Trial details

Who runs it

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Trial code

NCT06083636

Record updated

3 October 2025

Original description

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.Read full original descriptionShow less

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.

Inclusion: 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.

Exclusion: 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:; Any of the following medication; Thyroid medication (a.o. levothyroxine, thiamazol, PTU); Lithium; Amiodarone; Propranolol; Iodide; Glucocorticoids; Oral contraceptives; Heparin; Growth hormone; Active treatment of malignancy; 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; Pregnancy.

ClinicalTrials.gov NCT06083636