What are the considerations for initiating Synthroid (levothyroxine) at a Thyroid-Stimulating Hormone (TSH) level of mildly elevated?

From the Guidelines

Starting Synthroid at a TSH level of 3.99 mIU/L is not recommended for most adults, as it falls within the normal reference range and may lead to overtreatment and potential harms associated with thyroid hormone therapy. According to the U.S. Preventive Services Task Force recommendation statement 1, treating patients with TSH levels between 4.5 and 10.0 mIU/L is controversial, and a large magnitude of overdiagnosis and overtreatment is likely. The study highlights that it is not possible to differentiate persons who will have advancing thyroid dysfunction of clinical importance from those whose TSH levels will remain biochemically stable or even normalize 1.

Some key points to consider:

• A TSH level of 3.99 mIU/L is within the normal range for most laboratories, and treatment is typically initiated when TSH levels exceed 10 mIU/L or when symptoms of hypothyroidism are present 1.
• Certain populations, such as pregnant women or women trying to conceive, may require treatment at lower TSH levels, but this should be determined on a case-by-case basis.
• Regular monitoring with TSH tests is necessary when initiating thyroid hormone replacement therapy to avoid overtreatment and potential harms.
• The goal of treatment is to normalize TSH levels while alleviating symptoms without causing hyperthyroidism, and this requires careful consideration of the potential benefits and harms of treatment 1.

In general, a more cautious approach is recommended, and treatment with Synthroid should only be considered if symptoms of hypothyroidism are present or if other factors, such as thyroid antibodies or cardiac risk factors, are present. It is essential to discuss individual circumstances with a healthcare provider to determine the best course of action.

From the FDA Drug Label

The recommended starting daily dosage of levothyroxine sodium tablets in adults with primary, secondary, or tertiary hypothyroidism is based on age and comorbid cardiac conditions, as described in Table 1 For adult patients with primary hypothyroidism, titrate until the patient is clinically euthyroid and the serum TSH returns to normal Table 1. Levothyroxine Sodium Tablets Dosing Guidelines for Hypothyroidism in Adults* *Dosages greater than 200 mcg/day are seldom required. An inadequate response to daily dosages greater than 300 mcg/day is rare and may indicate poor compliance, malabsorption, drug interactions, or a combination of these factors

The FDA drug label does not provide a specific starting dose for a patient with a TSH of 3.99. Key points:

• The starting dose is based on age and comorbid cardiac conditions.
• The goal is to titrate the dose until the patient is clinically euthyroid and the serum TSH returns to normal.
• A TSH of 3.99 is slightly elevated, but the label does not provide a specific recommendation for this value. 2

From the Research

Starting Synthroid at TSH 3.99

• The decision to start Synthroid (levothyroxine) at a TSH level of 3.99 should be based on clinical and laboratory findings, not just a simple TSH elevation 3.
• According to the study, a TSH level of less than 4 or 5 mlU/L rules out peripheral hypothyroidism, and between 30% and 60% of high TSH levels are not confirmed on a second blood test 3.
• Subclinical hypothyroidism, characterized by high blood TSH levels and normal free T4 levels, is usually asymptomatic, and the risk of progression to overt hypothyroidism is about 3% to 4% per year overall 3.
• Treatment guidelines recommend levothyroxine therapy, but the adverse effects of levothyroxine, such as signs of thyrotoxicosis, osteoporotic fractures, and atrial fibrillation, should be considered 3, 4.
• The American Family Physician study suggests that treatment is not necessary unless the TSH exceeds 10 mIU/L, and most patients with subclinical hypothyroidism do not benefit from treatment unless the thyroid-stimulating hormone level is greater than 10 mIU per L or the thyroid peroxidase antibody is elevated 4.
• The Journal of Internal Medicine study recommends that treatment is not necessary unless the TSH exceeds 7.0-10 mIU/L, and TSH goals are age-dependent, with a 97.5 percentile (upper limit of normal) of 3.6 mIU/L for patients under age 40, and 7.5 mIU/L for patients over age 80 5.

Considerations for Starting Synthroid

• The dose of levothyroxine should be individualized, and patients older than 60 years or with known or suspected ischemic heart disease should start at a lower dosage of levothyroxine (12.5 to 50 mcg per day) 3, 4.
• The Journal of Clinical & Translational Endocrinology study suggests that lean body mass (LBM) calculation may be a more accurate determination of levothyroxine dose in obese patients, and the recommended daily dose of levothyroxine is 2.3 mcg/kg of LBM 6.
• Treatment monitoring should be based mainly on blood TSH assay, and dose adjustment should only be considered after 6 to 12 weeks, given the long half-life of levothyroxine 3.