From the Guidelines
When a patient has high thyroid stimulating hormone (TSH), the most important add-on test to confirm hypothyroidism is free thyroxine (free T4). This test directly measures the level of unbound thyroid hormone in the bloodstream, which is the active form available to tissues. A combination of elevated TSH with low free T4 definitively establishes the diagnosis of primary hypothyroidism, as indicated by the US Preventive Services Task Force recommendation statement 1. This pattern indicates that the thyroid gland is not producing enough thyroid hormone despite stimulation from the pituitary gland. In some cases, measuring free triiodothyronine (free T3) may provide additional information, but it's less reliable for diagnosing hypothyroidism since T3 levels may remain normal in early hypothyroidism. Thyroid antibody tests, particularly thyroid peroxidase antibodies (TPOAb), can also be useful to determine if the hypothyroidism has an autoimmune etiology (Hashimoto's thyroiditis), which is the most common cause of primary hypothyroidism in iodine-sufficient regions, as noted in the guidelines for diagnosis and management of subclinical thyroid disease 1. However, free T4 remains the essential add-on test for confirming the diagnosis when TSH is elevated.
Some key points to consider in the diagnosis and management of hypothyroidism include:
- The serum TSH test is the primary screening test for thyroid dysfunction, and multiple tests should be done over a 3- to 6-month interval to confirm or rule out abnormal findings 1.
- 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.
- The principal treatment for hypothyroidism is oral T4 monotherapy (levothyroxine sodium) 1.
It's also important to evaluate patients for signs and symptoms of hypothyroidism, previous treatment for hyperthyroidism, thyroid gland enlargement, or family history of thyroid disease, and to review lipid profiles, as suggested in the guidelines for diagnosis and management of subclinical thyroid disease 1. Women who are pregnant or hope to become pregnant in the near future deserve special consideration.
Overall, the diagnosis and management of hypothyroidism require a comprehensive approach that takes into account the patient's clinical presentation, laboratory results, and medical history.
From the FDA Drug Label
In patients with hypothyroidism, assess the adequacy of replacement therapy by measuring both serum TSH and total or free-T4. Monitor TSH and total or free-T4 in pediatric patients as follows: 2 and 4 weeks after the initiation of treatment, 2 weeks after any change in dosage, and then every 3 to 12 months thereafter following dosage stabilization until growth is completed The general aim of therapy is to normalize the serum TSH level 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 add-on test that is diagnostic of hypothyroidism in a patient with high thyroid stimulating hormone (TSH) is free-T4.
- Key points:
- Measure both serum TSH and total or free-T4 to assess the adequacy of replacement therapy.
- Free-T4 levels should be in the upper half of the normal range in patients with secondary and tertiary hypothyroidism.
- TSH levels should be normalized as the general aim of therapy.
- Monitoring of TSH and free-T4 levels is necessary to adjust the dosage of levothyroxine sodium and to assess the adequacy of therapy 2
From the Research
Diagnostic Tests for Hypothyroidism
If a patient has high thyroid stimulating hormone (TSH), the add-on test that is diagnostic of hypothyroidism is:
- Free Thyroxine (FT4) and Free Triiodothyronine (FT3) levels, as they are essential for confirming the diagnosis of hypothyroidism 3, 4, 5
- Thyroid hormone replacement with levothyroxine (LT4) alone does not restore physiological tissue levels of thyroid hormones, particularly T3, and combination therapy with LT4 and T3 may be considered in some cases 3, 4, 5
Importance of Thyroid Function Tests
- Thyroid function tests, including TSH, FT4, and FT3, are crucial for diagnosing and managing hypothyroidism 3, 4, 5
- Elevated TSH levels are associated with an increased risk of type 2 diabetes, highlighting the need for regular thyroid screening and integrated clinical management 6
Clinical Considerations
- The management of hypothyroidism with combination thyroxine (T4) and triiodothyronine (T3) hormone replacement in clinical practice requires careful consideration of individual patient needs and monitoring of thyroid function, benefits, and adverse effects 5
- Patients with hypothyroidism are highly heterogeneous, and personalized medicine approaches may be necessary to optimize treatment outcomes 3, 4, 5