Differentiated Thyroid Cancer, Levothyroxine, Liothyronine, Thyroid Cancer, Thyroid Hormones
Conditions
Brief summary
This study will be a multicentre prospective cohort study on TH-substitution after thyroid hormone withdrawal preceding radioiodine treatment.
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
Interventions
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.
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.
Sponsors
University Medical Center Groningen
Radboud University Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TSH after two weeks of TH substitution | Before and after 2 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TSH (mU/L) | Before and after 1, 2, 4, 6, and 12 weeks of TH-substitution. | The % of decrease of serum thyroid parameters TSH after 1, 2, 4, 6, and 12 weeks of TH-substitution. |
| Thyroglobulin (Tg; ng/mL) | Before and after 1, 2, 4, 6, and 12 weeks of TH-substitution | 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. |
| QoL in patients treated with L-T3 or L-T4 | Before and after 2, 6, and 12 weeks of TH-substitution | 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). |
| Heart rate (HR; bpm) | Before and after 6 and 12 weeks of TH-substitution | 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. |
| Blood pressure (BP; mmHg) | Before and after 6 and 12 weeks of TH-substitution | 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. |
Countries
Netherlands
Contacts
CONTACTMirthe Links, BSc
CONTACTWouter Zandee, MD/PhD
PRINCIPAL_INVESTIGATORWouter Zandee, MD/PhD
University Medical Center Groningen
Outcome results
None listed