What is the treatment for severely elevated Thyroid-Stimulating Hormone (TSH) levels, specifically hyperthyrotropinemia?

From the Guidelines

For a patient with a TSH level of 120 mIU/L, immediate treatment with levothyroxine (T4) is strongly recommended as this indicates severe hypothyroidism. The typical starting dose for adults is 1.6 mcg/kg/day, which is approximately 100-125 mcg daily for most adults 1. Elderly patients or those with cardiac disease should start at a lower dose, typically 25-50 mcg daily, with gradual increases every 4-6 weeks to avoid cardiac complications. The medication should be taken on an empty stomach, 30-60 minutes before breakfast, and separated from other medications that may interfere with absorption such as calcium, iron supplements, or antacids by at least 4 hours. TSH levels should be rechecked after 6-8 weeks of therapy to adjust the dose as needed, with a target TSH within the normal range (typically 0.4-4.0 mIU/L) 1. This extremely elevated TSH indicates profound thyroid hormone deficiency, which can lead to serious complications including myxedema coma if left untreated. Levothyroxine works by replacing the thyroid hormone that the body is unable to produce in sufficient quantities, thereby normalizing metabolism and reversing the symptoms of hypothyroidism.

Some key points to consider in the treatment of hypothyroidism include:

• The principal treatment for hypothyroidism is oral T4 monotherapy (levothyroxine sodium) 1.
• Hyperthyroidism is treated with antithyroid medications (such as methimazole) or nonreversible thyroid ablation therapy (for example, radioactive iodine or surgery) 1.
• Although definitive data are lacking, treatment is generally recommended for patients with a TSH level that is undetectable or less than 0.1 mIU/L, particularly those with overt Graves disease or nodular thyroid disease 1.
• Treatment is typically not recommended for patients with TSH levels between 0.1 and 0.45 mIU/L or when thyroiditis is the cause 1.
• The USPSTF found no direct evidence that treatment of thyroid dysfunction based on risk level alters final health outcomes 1.

It is essential to note that the evidence for the treatment of thyroid dysfunction is largely based on expert opinion and observational studies, and more research is needed to determine the optimal treatment strategies for different patient populations 1.

From the FDA Drug Label

The general aim of therapy is to normalize the serum TSH level TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback. Failure of the serum T4 to increase into the upper half of the normal range within 2 weeks of initiation of levothyroxine sodium therapy and/or of the serum TSH to decrease below 20 IU per litre within 4 weeks may indicate the patient is not receiving adequate therapy New onset hypothyroidism (TSH ≥10 IU per liter) 1. 6 mcg/kg/day New onset hypothyroidism (TSH < 10 IU per liter) 1. 0 mcg/kg/day

The treatment for a TSH of 120 is not directly addressed in the label. However, levothyroxine sodium dosage for new onset hypothyroidism is provided. For a TSH of 120, which is significantly higher than 10, a dosage of 1.6 mcg/kg/day may be considered, but this is an extrapolation and not a direct answer from the label. The goal of therapy is to normalize the serum TSH level. Monitoring of TSH and free-T4 levels is necessary to assess the adequacy of therapy 2.

From the Research

Treatment of TSH 120

• The treatment of TSH 120, which is considered elevated, depends on various factors such as age, symptoms, and cardiovascular disease risk 3, 4.
• According to the study published in the Journal of Internal Medicine, treatment is not necessary unless the TSH exceeds 7.0-10 mIU/L 4.
• For patients with subclinical hypothyroidism, levothyroxine treatment may only provide benefit in certain subgroups, such as patients who are younger or at higher risk of cardiovascular disease 3.
• The study published in the Journal of Clinical Endocrinology and Metabolism found that levothyroxine treatment in patients with subclinical hypothyroidism and heart disease was not associated with a significant benefit nor risk of all-cause mortality, major adverse cardiac events, or hospital admission 5.
• However, another study published in Thyroid found that the use of liothyronine, which may be used in combination with levothyroxine, was associated with increased incidence of heart failure and stroke in patients with a longer duration of use and history of thyroid cancer 6.

Considerations for Treatment

• Treatment decisions should be individualized based on patient age, degree of serum TSH elevation, symptoms, cardiovascular disease risk, and other co-morbidities 3, 4.
• 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 4.
• The diagnosis of subclinical hypothyroidism should be confirmed by repeat thyroid function tests ideally obtained at least 2 months later, as 62% of elevated TSH levels may revert to normal spontaneously 4.

Cardiovascular Disease Risk

• Subclinical hypothyroidism has been associated with risk factors for cardiovascular disease, such as hypertension and dyslipidemia 3.
• The use of levothyroxine in subclinical hypothyroidism to reduce cardiovascular disease risk is not clearly beneficial, but may be beneficial in certain subgroups 3, 5.
• The study published in Heart Failure Clinics found that patients with overt or subclinical hypothyroidism should be treated with levothyroxine to improve their cardiovascular function and potential risk of heart failure 7.