Should a patient taking lithium (lithium) with elevated Thyroid-Stimulating Hormone (TSH) levels, indicating subclinical hypothyroidism, and normal free Thyroxine (T4) and anti-Thyroid Peroxidase (anti-TPO) antibodies be treated for subclinical hypothyroidism?

From the Guidelines

A patient taking lithium with elevated Thyroid-Stimulating Hormone (TSH) levels, indicating subclinical hypothyroidism, and normal free Thyroxine (T4) and anti-Thyroid Peroxidase (anti-TPO) antibodies should be treated for subclinical hypothyroidism if the TSH level is greater than 10.0 mIU/L. The decision to treat subclinical hypothyroidism is based on the potential benefits of preventing progression to overt hypothyroidism and improving clinical outcomes, as well as the potential harms of treatment, including false-positive results, labeling, and overdiagnosis and overtreatment 1. According to the US Preventive Services Task Force, a TSH level greater than 10.0 mIU/L is generally considered the threshold for initiation of treatment, as it is associated with a higher likelihood of progression to overt thyroid dysfunction 1. In patients with subclinical hypothyroidism, treatment with levothyroxine may be considered, especially if symptoms are present or if the TSH level is elevated, as it may improve clinical outcomes and prevent progression to overt hypothyroidism 1. Key considerations in the treatment of subclinical hypothyroidism include:

• Starting with a low dose of levothyroxine (25-50 mcg daily) and adjusting the dose every 6-8 weeks based on TSH levels until reaching the target TSH of 0.5-2.5 mIU/L
• Regular monitoring of thyroid function (every 3-6 months) throughout lithium therapy
• Informing the patient about hypothyroid symptoms to report
• Balancing the potential benefits of treatment against the potential harms, including the inconvenience, expense, and potential risks of therapy. It is essential to weigh the potential benefits and harms of treatment and to consider the individual patient's circumstances, including the presence of symptoms and the likelihood of progression to overt hypothyroidism.

From the FDA Drug Label

Where hypothyroidism exists, careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters, if any Where hypothyroidism occurs during lithium stabilization and maintenance, supplemental thyroid treatment may be used.

The patient with subclinical hypothyroidism, as indicated by elevated TSH levels and normal free T4 and anti-TPO antibodies, may require careful monitoring of thyroid function while taking lithium.

• Supplemental thyroid treatment can be considered if hypothyroidism occurs or worsens during lithium treatment. 2

From the Research

Treatment of Subclinical Hypothyroidism

The decision to treat subclinical hypothyroidism in a patient taking lithium with elevated Thyroid-Stimulating Hormone (TSH) levels, normal free Thyroxine (T4), and normal anti-Thyroid Peroxidase (anti-TPO) antibodies depends on several factors.

• The patient's age, symptoms, and presence of other risk factors such as cardiovascular disease should be considered 3, 4, 5.
• According to some studies, treatment with levothyroxine should be considered in patients with TSH levels >10 mIU/L, especially in younger patients and those with cardiovascular risk factors 6, 3, 4, 5.
• However, for patients with TSH levels ≤10 mIU/L, treatment should be considered in symptomatic patients, patients with infertility, and patients with goitre or positive anti-thyroid peroxidase (TPO) antibodies 6.
• It is also important to note that levothyroxine treatment may not improve symptoms such as weight, quality of life, vitality, and cognition in subclinical hypothyroidism, and other causes should be explored 4.
• Additionally, caution is necessary when treating elderly subjects with levothyroxine, and lifelong treatment with levothyroxine should normally only be considered in manifest hypothyroidism 4, 5.

Considerations for Treatment

• The European Thyroid Association suggests a TSH level of 0.1 mU/l for patients with subclinical hyperthyroidism older than 65 years as threshold, and a TSH level < 0.1 mU/l is a clear indication for treatment while concentrations > 0.1 mU/l are relative treatment indications 5.
• Patients older than 65 years with subclinical hypothyroidism and a TSH level > 10 mU/l should also be treated, in particular when cardiovascular comorbidities are present 5.
• For patients with TSH concentrations between 7 and 10 mU/l there is no clear indication to initiate a levothyroxine treatment, as they do not have a clearly elevated mortality and morbidity, also quality of life does not improve 5.
• Levothyroxine treatment has to be monitored on a regular basis, as overdosing is also harmful 5.

Monitoring and Treatment

• Levothyroxine monotherapy remains the current standard for management of primary, as well as central, hypothyroidism 6.
• Treatment can be started with the full calculated dose for most young patients, but treatment should be initiated at a low dose in elderly patients, patients with coronary artery disease, and patients with long-standing severe hypothyroidism 6.
• In primary hypothyroidism, treatment is monitored with serum TSH, with a target of 0.5-2.0 mIU/L 6.
• In patients with persistently elevated TSH despite an apparently adequate replacement dose of LT4, poor compliance, malabsorption, and the presence of drug interactions should be checked 6.