From the Guidelines
High TSH with low T3 typically indicates hypothyroidism, and treatment usually involves thyroid hormone replacement therapy with levothyroxine (T4). The principal treatment for hypothyroidism is oral T4 monotherapy (levothyroxine sodium) 1. The dose is adjusted every 6-8 weeks based on TSH levels until they normalize, with a target TSH of 0.5-2.5 mIU/L for most adults.
Key Considerations
- Morning administration on an empty stomach, at least 30-60 minutes before food or other medications, ensures optimal absorption.
- Common brand names include Synthroid, Levoxyl, and Tirosint.
- Full therapeutic effects may take 4-6 weeks to develop.
- Regular monitoring of thyroid function is essential, typically every 6-12 months once stable, to ensure proper dosing.
Causes and Risk Factors
- The most common cause of hypothyroidism in the United States is chronic autoimmune (Hashimoto) thyroiditis.
- Risk factors for an elevated TSH level include female sex, advancing age, white race, type 1 diabetes, Down syndrome, family history of thyroid disease, goiter, previous hyperthyroidism, and external-beam radiation in the head and neck area 1.
Screening and Diagnosis
- The serum TSH test is the primary screening test for thyroid dysfunction.
- Multiple tests should be done over a 3- to 6-month interval to confirm or rule out abnormal findings.
- Follow-up testing of serum T4 levels in persons with persistently abnormal TSH levels can differentiate between subclinical (normal T4 levels) and “overt” (abnormal T4 levels) thyroid dysfunction 1.
From the FDA Drug Label
Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine (T3) and L-thyroxine (T4) diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA. The physiological actions of thyroid hormones are produced predominantly by T3, the majority of which (approximately 80%) is derived from T4 by deiodination in peripheral tissues.
The patient has high TSH and low T3 levels.
- TSH is high, indicating that the pituitary gland is trying to stimulate the thyroid gland to produce more thyroid hormones.
- T3 is low, which could be due to a problem with the conversion of T4 to T3 in peripheral tissues. The use of levothyroxine (T4) may help to increase T4 levels, which can then be converted to T3 in peripheral tissues, potentially improving T3 levels 2.
From the Research
High TSH and Low T3 Levels
- High TSH (thyroid-stimulating hormone) and low T3 (triiodothyronine) levels can be an indication of hypothyroidism, a condition where the thyroid gland does not produce enough thyroid hormones 3, 4, 5.
- Levothyroxine (LT4) monotherapy is the standard treatment for hypothyroidism, but some patients may not respond well to this treatment and may have persistent symptoms despite normal TSH levels 6, 7.
- Combination therapy with LT4 and liothyronine (LT3) may be considered for patients who have not responded to LT4 monotherapy, as it can help restore normal T3 levels and alleviate symptoms 3, 4, 5.
Treatment Options
- Reducing the LT4 dose by 25 mcg/day and adding 2.5-7.5 mcg LT3 once or twice a day can be an appropriate starting point for combination therapy 3.
- Desiccated thyroid extract (DTE) is another form of combination therapy, but its use is not formally regulated by the FDA and its consistency can vary 3.
- Slow-release LT3 preparations are being developed and may be used in future clinical trials to study the effectiveness of combination therapy 5, 6, 7.
Clinical Guidelines
- Clinical guidelines recommend optimizing LT4 doses to achieve a TSH level between 0.3-2.0 mU/L before considering combination therapy 4.
- Patients with persistent symptoms despite optimal LT4 treatment may be considered for a trial of combination therapy with LT4 and LT3 4, 6, 7.
- The decision to start combination therapy should be made on a case-by-case basis, taking into account the patient's individual needs and preferences 4, 6, 7.