What are the next steps for a patient with hypothyroidism and elevated Thyroid-Stimulating Hormone (TSH) levels who is already on levothyroxine (thyroxine) therapy?

From the Guidelines

For a patient with hypothyroidism who is already on levothyroxine but has a high TSH level, the next step is to increase the levothyroxine dose. This is because a high TSH level in a patient with hypothyroidism on levothyroxine indicates that the current dose is not sufficient to achieve euthyroidism. The study by 1 provides guidelines for the management of subclinical thyroid disease, but it primarily focuses on subclinical hyperthyroidism and does not directly address the management of high TSH levels in patients with hypothyroidism on levothyroxine. However, in clinical practice, the goal is to achieve a TSH level within the reference range (typically 0.4-4.0 mIU/L) to alleviate symptoms and prevent long-term complications. Some key considerations when adjusting the levothyroxine dose include:

• Increasing the dose by 12.5-25 mcg daily
• Repeating the TSH test in 6-8 weeks to assess response
• Ensuring the patient takes levothyroxine on an empty stomach, at least 30-60 minutes before breakfast or 3-4 hours after the last meal of the day, with a full glass of water
• Separating levothyroxine from certain medications and supplements (such as calcium, iron, antacids, and proton pump inhibitors) by at least 4 hours to minimize interference with absorption. It is also essential to assess for poor adherence, as this is a common cause of persistently elevated TSH levels. By adjusting the levothyroxine dose and addressing potential factors contributing to the high TSH level, the goal is to achieve a TSH level within the reference range and improve the patient's quality of life.

From the FDA Drug Label

Instruct patients to notify their healthcare provider if they are taking any other medications, including prescription and over-the-counter preparations Instruct patients to notify their physician of any other medical conditions they may have, particularly heart disease, diabetes, clotting disorders, and adrenal or pituitary gland problems, as the dose of medications used to control these other conditions may need to be adjusted while they are taking levothyroxine sodium tablets The next steps for a patient with high TSH and hypothyroidism already on levothyroxine are to:

• Notify their healthcare provider about their current medications and medical conditions
• Adjust their levothyroxine dose as needed, under the guidance of their healthcare provider, to achieve normal TSH levels
• Monitor their blood and/or urinary glucose levels if they have diabetes, and report any changes to their physician
• Check their clotting status frequently if they are taking anticoagulants 2

From the Research

Next Steps for High TSH and Hypothyroidism on Levothyroxine

• Review medications and medical history to identify potential factors affecting levothyroxine absorption, such as gastrointestinal disorders or drug interactions 3
• Check serum free T4 level to assess levothyroxine efficacy and consider an LT4 pharmacodynamic absorption test to evaluate absorption issues 3
• Consider a trial of combination therapy with levothyroxine and liothyronine (LT4+LT3) for patients who remain symptomatic on levothyroxine monotherapy, starting with a reduced LT4 dose and adding 2.5-7.5 mcg LT3 once or twice a day 4, 5
• Assess for other comorbidities that may be contributing to persistent symptoms and optimize levothyroxine doses to achieve a TSH level within the target range (0.3-2.0 mU/L) before considering combination therapy 5, 6
• Discuss the potential benefits and limitations of combination therapy with the patient and make a shared decision about proceeding with LT4+LT3 treatment 5

Considerations for Combination Therapy

• Desiccated thyroid extract (DTE) is another form of combination therapy, but its use is not formally regulated and may have inconsistent T4 and T3 content 4
• Genetic polymorphisms, such as those affecting deiodinase genes, may influence the response to levothyroxine and combination therapy, but widespread genotyping is not currently recommended 3, 6
• Patient preference and quality of life should be considered when evaluating the effectiveness of combination therapy, as some patients may experience improved symptoms and satisfaction despite limited improvements in quality of life 7