What is the significance of elevated Thyroid-Stimulating Hormone (TSH) levels, specifically hyperthyrotropinemia, in a patient taking Synthroid (levothyroxine) 112mg twice daily (BID)?

From the Guidelines

I strongly recommend immediately reducing the Synthroid (levothyroxine) dose and obtaining urgent endocrinology consultation. A TSH of 89 indicates severe hypothyroidism despite the patient taking a very high dose of Synthroid (112mg twice daily, which is much higher than typical dosing) 1. This suggests either poor medication absorption, non-adherence to therapy, drug interactions reducing effectiveness, or possibly laboratory error. The patient should temporarily decrease their Synthroid dose to a standard range (typically 100-150mcg once daily, not twice daily) and have free T4 levels checked along with a repeat TSH.

Common causes of poor levothyroxine absorption include taking it with food, calcium supplements, iron supplements, or certain antacids. Levothyroxine should be taken on an empty stomach, 30-60 minutes before breakfast or 3-4 hours after the last meal of the day. Certain medications like proton pump inhibitors, cholestyramine, and some seizure medications can also interfere with absorption. Some studies suggest that a TSH level greater than 10.0 mIU/L is generally considered the threshold for initiation of treatment 1. However, the decision of whether and when to begin therapy in patients with TSH levels between 4.5 and 10.0 mIU/L is more controversial 1.

Key considerations for management include:

• Monitoring for improvement in hypothyroid-type symptoms
• Understanding the natural history of subclinical hypothyroidism and the small but definite risk of progression to overt hypothyroidism
• Recognizing the potential risks of therapy, including overdiagnosis and overtreatment 1. Untreated severe hypothyroidism can lead to myxedema coma, a life-threatening condition, so prompt medical attention is essential.

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

The patient's TSH level is 89, which is above the normal range, and the patient is currently taking 112mg of Synthroid BID.

• The patient is likely not receiving adequate therapy, as the TSH level is not decreasing below 20 IU per liter.
• The dosage of levothyroxine sodium may need to be adjusted to achieve a normal TSH level.
• It is recommended to assess compliance, dose of medication administered, and method of administration prior to increasing the dose of levothyroxine sodium 2.

From the Research

TSH Levels and Levothyroxine Treatment

• A TSH level of 89 is significantly elevated, indicating that the current levothyroxine dose of 112mg BID may not be sufficient to achieve a normal serum TSH level 3.
• The goal of levothyroxine treatment is to normalize serum TSH levels, as elevated TSH levels have been associated with increased mortality in hypothyroid patients 3.
• However, the optimal TSH goal may vary depending on age, with higher TSH levels considered normal in older adults 4.

Levothyroxine Dosing and TSH Targets

• The current dose of 112mg BID may need to be adjusted to achieve a normal TSH level, but the optimal dose and TSH target should be individualized based on patient factors such as age and symptoms 4, 5.
• Some studies suggest that 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 use of combination therapy with levothyroxine and liothyronine may be considered in some patients who are dissatisfied with levothyroxine monotherapy, especially those with a polymorphism in type 2 deiodinase 4, 5.

Monitoring and Adjusting Treatment

• Regular monitoring of TSH levels is necessary to adjust the levothyroxine dose and achieve a normal TSH level 3, 6.
• 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.
• Treatment is not necessary unless the TSH exceeds 7.0-10 mIU/L, and cardiovascular events may be reduced in patients under age 65 with subclinical hypothyroidism who are treated with levothyroxine, but treatment may be harmful in elderly patients with subclinical hypothyroidism 4.