Safety and Efficacy of Empiric Levothyroxine (LT4) Dose Increase Versus Individualized LT4 Dose Increase in Hypothyroid Women During Pregnancy

Study Overview
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Brief Summary
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In women who require thyroid hormone replacement medication, the investigators will compare 2 ways to adjust thyroid medication during pregnancy to determine superiority in maintaining optimal blood levels of thyroid hormone. Thyroid hormone requirements increase significantly in pregnancy and it is important that blood levels of thyroid hormone remain normal so the fetus, which cannot make its own thyroid hormone has enough for early prenatal development. This trial compares 2 methods for adjusting thyroid medicine during pregnancy in women with known thyroid disease. Pregnant women (age 18 to 45) who take thyroid medication will be randomized to either 1) a 2-dose per week increase in thyroid medicine once pregnancy is confirmed, followed by dose adjustments every 2-4 weeks, or 2) adjustments in thyroid medication every 2-4 weeks in micrograms per day based on results of blood tests. The investigators will compare thyroid hormone levels throughout pregnancy between the groups of mothers to determine which method is superior in meeting the increased thyroid hormone requirements during pregnancy.

Official Title
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Randomized, Prospective Trial Comparing the Safety and Efficacy of Empiric Levothyroxine (LT4) Dose Increase Versus Individualized LT4 Dose Increase in Hypothyroid Women During Pregnancy

Conditions
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Pregnancy Related, Thyroid

Intervention / Treatment
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* Drug: levothyroxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female between ages of 18-45 who takes thyroid hormone replacement medicine AND pregnant or plan to become pregnant in the near future. Exclusion Criteria: Males Younger than 18 or older than 45 years old More than 10 weeks pregnant at enrollment Iodine deficient Pregnant with more than one baby (i.e., twins, triplets, etc.) NOT taking thyroid hormone medicine before becoming pregnant Levels of thyroid hormone in blood have been too low or too high in the past 6 months Treated with radioactive iodine in the past year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adjustment in number of doses of thyroid hormone per week<br>Patients in this group will increase pre-pregnancy thyroid hormone dose by 2 doses/week (extra dose on Wednesday and Saturday). Further dose adjustment are made every 2-4 weeks based on serum TSH, as shown below: TSH>10mIU/L, increase by 3 doses/week TSH 5.0-9.9mIU/L, increase by 2 doses/week TSH 2.0-4.9mIU/L, increase by 1 dose/week TSH 0.4-1.9mIU/L, no change TSH<0.4mIU/L, decrease by 1 dose/week TSH<0.1mIU/L, decrease by 2 doses/week Thyroid hormone dose will NOT be decreased due to TSH<0.4mIU/L during the 1st trimester unless patient also has elevated circulating T4 and/or T3 levels, indicate of true hyperthyroidism. | Drug: levothyroxine<br>* To compare two different methods of adjusting thyroid hormone replacement during pregnancy to maintain TSH within the normal reference range for pregnancy.<br>* Other names: Levoxyl;|
| Experimental: Adjustment in micrograms per day of thyroid hormone<br>Patients in this group adjust thyroid hormone dose based on Visit 1 TSH and pre-pregnancy thyroid hormone dose. Further dose adjustments are made every 2-4 weeks based on serum TSH, as shown below: TSH>10mIU/L, increase dose by 50mcg/day if dose <125mcg/day or increase by 75mcg/day if dose >125mcg TSH 5.0-9.9mIU/L, increase dose by 25mcg/day if dose <125mcg/day or increase by 50mcg/day if dose >125mcg TSH 2.0-4.9mIU/L, increase dose by 12.5mcg/day if dose <125mcg/day or increase by 25mcg/day if dose >125mcg TSH 0.4-1.9mIU/L, no change TSH<0.4mIU/L, decrease dose by 12.5mcg/day if dose <125mcg/day or decrease by 25mcg/day if dose >125mcg/day TSH<0.1mIU/L, decrease dose by 25mcg/day if dose <125mcg/day or decrease by 50mcg/day if dose >125mcg/day Thyroid hormone dose will NOT be decreased due to TSH<0.4mIU/L during the 1st trimester unless patient also has elevated circulating T4 and/or T3 levels, indicate of true hyperthyroidism. | Drug: levothyroxine<br>* To compare two different methods of adjusting thyroid hormone replacement during pregnancy to maintain TSH within the normal reference range for pregnancy.<br>* Other names: Levoxyl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of TSH values within trimester-specific goal range per patient from study enrollment to delivery | % of TSH values within trimester-specific goal range according to study group | TSH will be assessed every 2 weeks from enrollment to 28 weeks gestation and then every 4 weeks from 29 weeks to delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean number of LT4 dose adjustment | Mean number of LT4 dose adjustments needed per patient in each group | Dose adjustments will be assessed every 2 weeks from enrollment to 28 weeks gestation and then every 4 weeks from 29 weeks to delivery | 
| Mean number of LT4 dose adjustments by hypothyroidism etiology | Mean number of LT4 dose adjustments needed according to etiology of hypothyroidism in each group | Dose adjustments will be assessed every 2 weeks from enrollment to 28 weeks gestation and then every 4 weeks from 29 weeks to delivery | 
| % of TSH values at goal according to anti-thyroid antibody status | TSH values within trimester specific goal range according to anti-thyroid antibody status | TSH will be assessed every 2 weeks from enrollment to 28 weeks gestation and then every 4 weeks from 29 weeks to delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thyroid Stimulating Hormone