Thyroid Hormone Replacement After Radio Iodine: Value and Efficacy (THRIVE)

This study will be a multicentre prospective cohort study on TH-substitution after thyroid hormone withdrawal preceding radioiodine treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Thyroid Cancer; Differentiated Thyroid Cancer; Thyroid Hormones; Levothyroxine; Liothyronine
• Intervention / Treatment: Drug: Euthyrox (levothyroxine); Drug: Cytomel (liothyronine)

Detailed Description

While treatment with L-T4 after TH-withdrawal is widely used in DTC patients to suppress TSH and improve hypothyroid symptoms, the value of L-T3 addition in initiation of TH treatment has not been evaluated in this context. Lifelong monotherapy with L-T3 should not be preferred over L-T4 yet, short-term use of L-T3 to initiate TH-supplementation can be safely implemented. We hypothesize that initial treatment with L-T4+L-T3 combination treatment can have a more direct effect on TSH-levels and earlier relieve of hypothyroid symptoms resulting in a better QoL. We will conduct a prospective cohort study comparing the initiation of TH-supplementation after TH-withdrawal in two cohorts of DTC patients: patients receiving L-T4+LT3 with a gradually decrease of L-T3 dose in time, and patients receiving L-T4 only. We will compare potency to suppress TSH, effect on QoL and effects on thyroid- and cardiovascular parameters. Patients (18-75 years) diagnosed with high-risk DTC after TH-withdrawal will be eligible for inclusion. The primary objective is to compare the proportion of patients reaching target TSH-levels after two weeks of substitution with L-T3 or L-T4.

Secondary objectives are to compare the effects of L-T4+L-T3 or L-T4 in the first 3 months of treatment on serum thyroid parameters TSH and Tg, quality of life, and cardiovascular parameters

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Mirthe Links, Bsc; Phone Number: +31 50 3610973; Email: m.h.links@umcg.nl
• Study Contact Backup: Name: Wouter Zandee, MD/PhD; Phone Number: +31 50 3613731; Email: w.t.zandee@umcg.nl

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboud University Nijmegen
    • Contact: Mirthe Links, Bsc; Phone Number: +31 50 3610973; Email: m.h.links@umcg.nl
  • Provincie Groningen
    • Groningen, Provincie Groningen, Netherlands, 9700RB
      • University Medical Center Groningen (UMCG)
      • Contact: Mirthe Links, Bsc; Phone Number: +31 50 3610973; Email: m.h.links@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This study will include patients with a histologically confirmed high-risk DTC, men and women aged 18-75 years. Patients have to be prepared to RAI with TH-withdrawal and treated according to the ATA guidelines.

Description

Inclusion Criteria:

• Histologically confirmed DTC (papillary thyroid carcinoma, follicular thyroid carcinoma, oncocytic thyroid carcinoma)
• Classified as high-risk DTC according to the ATA guidelines or, patients for whom the risk of a recurrence is estimated to be higher based on clinical features (assessed by their treating physician).
• Prepared for RAI-therapy with TH-withdrawal
• Patients must be fit to adhere to the study protocol
• Patients must be able to read and understand the Dutch language

Exclusion Criteria:

• Pregnancy
• Patients with comorbidities, such as severe heart failure, (poorly controlled) atrial fibrillation, of which the treating physician decides that L-T3 is unsuitable.
• Conditions or drugs interfering with thyroid hormone uptake:
• Patients with a history of atrophic gastritis
• Patients using proton-pomp inhibitors

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TH-combination cohort; L-T4+L-T3 combination according to local protocol.	Drug: Cytomel (liothyronine); Cytomel (liothyronine sodium tablets; L-T3) is a thyromimetic synthetic drug identical to T3. The patients in this cohort recieve L-T4+L-T3 combination therapy. The L-T4 dose will be 2 μg × kg body weight / day, equal to the dose in the other interventional arm. L-T3 will be added twice daily from the first day of combination treatment, in dosages gradually decreasing from 25 ug 2/day to 5 ug 2/day over a time span of 3 weeks after which L-T3 is stopped.
Levothyroxine cohort; L-T4 monotherapy according to local protocol.	Drug: Euthyrox (levothyroxine); Euthyrox (levothyroxine sodium tablets; L-T4) is a thyromimetic synthetic drug identical to T4. Patients will recieve levothyroxine (euthyrox) in a dose of 2 μg × kg body weight / day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TSH after two weeks of TH substitution	The percentage of patients reaching target TSH (<0.5 mU/L) after two weeks of L-T3+L-T4 substitution compared to patients with L-T4-substitution.	Before and after 2 weeks of TH-substitution

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TSH (mU/L)	The % of decrease of serum thyroid parameters TSH after 1, 2, 4, 6, and 12 weeks of TH-substitution.	Before and after 1, 2, 4, 6, and 12 weeks of TH-substitution.
Thyroglobulin (Tg; ng/mL)	The % of decrease of serum thyroid parameters Tg after 1, 2, 4, 6, and 12 weeks of TH-substitution. Tg is a precursor of T3 and T4 and is a measurement for remaining thyroid (cancer) cells. Tg-levels are affected by TSH and therefore, we expect by reducing TSH-levels to also reduce Tg levels. Consecutive Tg-measurements in this study act as a secondary measure for TH substitution. Since Tg-values between patients variable, we will use the % decrease instead of absolute values.	Before and after 1, 2, 4, 6, and 12 weeks of TH-substitution
QoL in patients treated with L-T3 or L-T4	Quality of life will be assessed using standardized QoL questionnaires for thyroid- and thyroid cancer patient reported outcome. Our aim is to compare improvement of hypothyroid symptoms after initiation of therapy, and evaluate whether sings of hyperthyroidism and possible overtreatment are present. We will use the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (core measure QoL questionnaire) in combination with the THYCA-QoL (additional thyroid cancer-specific part).	Before and after 2, 6, and 12 weeks of TH-substitution
Heart rate (HR; bpm)	Cardiovascular parameters will be assessed during visits to the outpatient clinic before initiation of TH-substitution (during hypothyroidism) and after 6 weeks of TH-treatment. Patients will be compared intra- and interindividually.	Before and after 6 and 12 weeks of TH-substitution
Blood pressure (BP; mmHg)	Cardiovascular parameters will be assessed during visits to the outpatient clinic before initiation of TH-substitution (during hypothyroidism) and after 6 and 12 weeks of TH-treatment. Patients will be compared intra- and interindividually.	Before and after 6 and 12 weeks of TH-substitution

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Radboud University Medical Center
• Investigators: Principal Investigator: Wouter Zandee, MD/PhD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 11, 2024
• First Submitted That Met QC Criteria: October 16, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Peptides, and Proteins; Amino Acids; Amino Acids, Aromatic; Amino Acids, Cyclic; Thyroid Hormones; Thyronines; Thyroxine; Triiodothyronine
• Other Study ID Numbers: 11432; 2024-511668-10-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Handling of personal data complies with the General Data Protection Regulation (GDPR; in Dutch: De uitvoeringswet algemene verorderning gegevensbescherming [UAVG]). Encoded data will be kept for 15 years after closure of the study and can only be used for ancillary studies after strict approval of the study protocol by the project leader (dr. W. Zandee).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No