From the Guidelines
An elevated Thyroid-Stimulating Hormone (TSH) level with normal Free Thyroxine (FT4) indicates subclinical hypothyroidism, a condition where the thyroid gland does not produce enough thyroid hormones to meet the body's needs, but not to the extent of causing overt hypothyroidism.
Key Points
- Subclinical hypothyroidism is defined as an asymptomatic condition with a serum TSH level exceeding the upper threshold of a specified laboratory reference interval (commonly 4.5 mIU/L) but a normal thyroxine (T4) level 1.
- The condition can progress to overt hypothyroidism, with a rate of progression proportional to the baseline serum TSH concentration and higher in individuals with antithyroid antibodies 1.
- Patients with subclinical hypothyroidism are often further classified as having TSH levels between 4.5 and 10.0 mIU/L or greater than 10.0 mIU/L 1.
- The primary screening test for thyroid dysfunction is the serum TSH test, and multiple tests should be done over a 3- to 6-month interval to confirm or rule out abnormal findings 1.
- The principal treatment for hypothyroidism is oral T4 monotherapy (levothyroxine sodium), but treatment is generally recommended for patients with a TSH level that is clearly elevated, typically above 10 mIU/L 1.
From the Research
Elevated Thyroid-Stimulating Hormone (TSH) Level with Normal Free Thyroxine (FT4)
An elevated TSH level with normal FT4 indicates subclinical hypothyroidism, a condition that affects up to 10% of the adult population 2. This condition is characterized by an elevated serum thyrotropin (TSH) level with normal levels of free thyroxine (FT4) 2, 3, 4, 5, 6.
Causes and Associations
Subclinical hypothyroidism is most often caused by autoimmune (Hashimoto) thyroiditis 2. It may also be associated with an increased risk of heart failure, coronary artery disease events, and mortality from coronary heart disease 2. Additionally, middle-aged patients with subclinical hypothyroidism may experience cognitive impairment, nonspecific symptoms such as fatigue, and altered mood 2.
Key Features
Some key features of subclinical hypothyroidism include:
- Elevated TSH levels with normal FT4 levels 2, 3, 4, 5, 6
- Increased risk of adverse cardiovascular outcomes 2, 6
- Possible association with cognitive impairment, fatigue, and altered mood 2
- Higher risk of progression to overt hypothyroidism in patients with circulating thyroid peroxidase antibodies 2
Treatment and Management
Treatment for subclinical hypothyroidism may be indicated for patients with serum TSH levels of 10 mU/L or higher or for young and middle-aged individuals with symptoms consistent with mild hypothyroidism 2. However, levothyroxine therapy may be associated with iatrogenic thyrotoxicosis, especially in elderly patients, and there is no evidence that it is beneficial in persons aged 65 years or older 2.
Diagnostic Strategies
Diagnostic strategies for subclinical hypothyroidism may include the use of thyrotropin-releasing hormone (TRH) stimulation testing to identify an exaggerated TSH response 4. The presence of anti-thyroid peroxidase antibodies (TPOAb) or anti-thyroglobulin antibodies (TgAb) may also be useful in predicting the risk of progression to overt hypothyroidism 2, 4, 5.