Is Low Total T4 with Normal TSH Caused by Testosterone?
Yes, testosterone therapy can directly cause a low total T4 level while maintaining a normal TSH, and this does not indicate true thyroid dysfunction. This occurs through a well-established mechanism where androgens decrease thyroxine-binding globulin (TBG) concentrations, resulting in lower total T4 measurements while free thyroid hormone levels remain normal 1.
Mechanism of Testosterone Effect on Thyroid Tests
Testosterone decreases thyroxine-binding globulin (TBG), which lowers total T4 measurements without affecting actual thyroid function. The FDA labeling for testosterone explicitly states: "Androgens, including testosterone gel, may decrease concentrations of thyroxine-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction" 1.
Key Laboratory Pattern with Testosterone Use:
- Total T4 is decreased (as in your case: 4.6 mcg/dL, below the 4.9-10.5 reference range) 1
- TSH remains normal (your 3.17 mIU/L is within the 0.40-4.50 reference range) 2
- Free T4 would be expected to remain normal (this is the critical test to order) 1
What You Need to Do Next
Order a free T4 level to confirm that your actual thyroid function is normal. Since total T4 can be artificially lowered by decreased binding proteins from testosterone, the free T4 (which measures the biologically active, unbound hormone) is the accurate indicator of thyroid status 1.
Interpretation Algorithm:
- If free T4 is normal: This confirms the low total T4 is simply due to testosterone's effect on binding proteins, not true hypothyroidism 1
- If free T4 is also low with normal TSH: This would suggest central hypothyroidism (pituitary/hypothalamic dysfunction) and requires further evaluation including morning ACTH, cortisol, and pituitary imaging 2
Ruling Out True Thyroid Dysfunction
Your normal TSH of 3.17 mIU/L makes primary hypothyroidism extremely unlikely, as primary hypothyroidism would cause an elevated TSH (typically >4.5 mIU/L, and often >10 mIU/L in overt cases) 2.
Central hypothyroidism would present with low TSH (or inappropriately normal TSH) combined with low free T4, not the pattern you have 2. In immune checkpoint inhibitor-induced hypophysitis, for example, patients show "low TSH with low free T4, suggestive of a central etiology" 2.
Common Pitfall to Avoid
Do not start thyroid hormone replacement based solely on a low total T4 when TSH is normal and you're on testosterone. This is a frequent error that leads to iatrogenic hyperthyroidism. The total T4 is misleading in the context of altered binding proteins 1. Always check free T4 first to assess actual thyroid hormone availability to tissues.
Additional Considerations:
- Nonthyroidal illness can also lower total T4 while maintaining normal free T4 and TSH, but this typically occurs in critically ill patients 3, 4
- Repeat testing in 3-6 months may be warranted if there's clinical concern, as thyroid function tests can show variability 2, 5
- Individual variation in thyroid parameters is actually quite narrow (coefficient of variation <10%), so significant changes from your baseline would be meaningful 6