Free Thyroxine (FT4) in Patients with Low TSH

In patients with a low Thyroid Stimulating Hormone (TSH) level, free thyroxine (FT4) is typically normal or elevated, but not low. 1

Relationship Between TSH and FT4

When TSH is low, this typically indicates one of two main conditions:
- Hyperthyroidism (primary thyroid overactivity) - characterized by low TSH with normal to high FT4 1
- Central hypothyroidism (pituitary or hypothalamic dysfunction) - characterized by low TSH with low FT4 1
In subclinical hyperthyroidism, TSH is suppressed while FT4 remains within the normal reference range 1
When evaluating thyroid function, both TSH and FT4 should be measured together, especially when patients are symptomatic, as this helps distinguish between different thyroid disorders 1

Endogenous overproduction of thyroid hormone (Graves' disease, toxic nodular goiter) 1
Exogenous thyroid hormone administration (intentional or inadvertent) 1
Recovery phase after treatment for hyperthyroidism 1
Normal pregnancy 1
Various non-thyroidal illnesses (euthyroid sick syndrome) 1
Medications such as dopamine, glucocorticoids, and possibly dobutamine 1

Central hypothyroidism due to pituitary or hypothalamic failure 1
This is less common than primary thyroid disorders 1
In patients with non-thyroidal illness who have low TSH, the FT4 is typically in the lower part of the normal range, in contrast to subclinical hyperthyroidism where FT4 is usually in the high-normal range 1

When TSH is found to be low (below 0.45 mIU/L), FT4 and either total T3 or free T3 should be measured to determine the cause 1
If TSH is between 0.1 and 0.45 mIU/L, repeat testing is recommended for confirmation, along with FT4 and T3 measurements 1
If TSH is below 0.1 mIU/L, repeat measurement along with FT4 and T3 is recommended within 4 weeks 1
In patients with suspected central hypothyroidism, additional pituitary hormone testing may be needed 1

Subclinical hyperthyroidism (low TSH with normal FT4) affects approximately 2% of the population when excluding those with known thyroid disease 1
The prevalence increases to 3.2% when including all patients 1
Subclinical hyperthyroidism is more common in women, blacks, the elderly, and in areas with low iodine intake 1
Approximately 1-2% of patients with TSH below 0.1 mIU/L will progress to overt hyperthyroidism per year 1

For patients with low TSH and normal FT4 (subclinical hyperthyroidism), monitoring depends on the degree of TSH suppression 1
For TSH between 0.1-0.45 mIU/L, retesting at 3-12 month intervals is recommended 1
For TSH below 0.1 mIU/L, closer monitoring is advised, especially in patients with cardiac disease or atrial fibrillation 1
In patients receiving levothyroxine treatment, a low TSH may indicate overtreatment, and dose adjustment should be considered 1

Failing to measure both TSH and FT4 together can lead to misdiagnosis, especially in central hypothyroidism 1
Non-thyroidal illness can cause low TSH without hyperthyroidism 1
Undetectable TSH (<0.01 mIU/L) in non-thyroidal illness is rare unless patients are receiving glucocorticoids or dopamine 1
Relying solely on TSH or FT4 measurements without clinical correlation can lead to inappropriate treatment decisions 2