What is the approach to a patient with a normal Thyroid-Stimulating Hormone (TSH) level and low Free Triiodothyronine (FT3)?

Approach to Normal TSH with Low FT3

In most cases, a normal TSH with isolated low FT3 represents nonthyroidal illness syndrome (NTIS) or "low T3 syndrome" and does not require thyroid hormone replacement. This pattern is an adaptive physiological response to acute or chronic illness, not true hypothyroidism 1, 2.

Diagnostic Algorithm

Step 1: Confirm the Clinical Context

• Assess for acute or chronic illness - The low T3 syndrome occurs in approximately 70% of hospitalized patients and is associated with infectious disease, cardiovascular disease, malignancy, or any severe systemic illness 1, 2, 3.
• Review medication list - Dopamine, high-dose glucocorticoids, amiodarone, and beta-blockers can all decrease peripheral T4 to T3 conversion while maintaining normal TSH 2.
• Evaluate nutritional status - Caloric deprivation and starvation states decrease T3 production as an adaptive mechanism to conserve protein 1, 2.

Step 2: Measure Free T4

• If free T4 is normal - This confirms NTIS/low T3 syndrome, which represents decreased peripheral conversion of T4 to T3 rather than thyroid gland failure 1, 2.
• If free T4 is low with normal TSH - Consider central (secondary) hypothyroidism and immediately check morning cortisol and ACTH before any thyroid hormone treatment 4.
• If free T4 is elevated with low FT3 - This pattern in hospitalized patients typically represents nonthyroidal illness combined with drug effects and usually does not require treatment 3.

Step 3: Assess TSH Reliability

• TSH remains the most sensitive screening test with sensitivity above 98% and specificity greater than 92% for detecting thyroid dysfunction 5.
• However, TSH may be transiently suppressed by acute illness, dopamine infusions, or high-dose glucocorticoids, even in the absence of true hyperthyroidism 2.
• In critically ill patients, TSH regulation may not be entirely normal, but an elevated TSH still reliably indicates thyroid failure 1.

Management Recommendations

Do NOT Treat If:

• Patient has acute or chronic nonthyroidal illness with normal TSH and normal/low-normal FT4 - The low T3 represents an adaptive change that enables the sick patient to conserve protein 1.
• Patient is hospitalized with infectious or cardiovascular disease and FT3 is below the middle of the normal range - Treatment is probably unnecessary 3.
• Free T4 is normal or elevated - This excludes thyroid gland failure and confirms the low T3 is from decreased peripheral conversion 1, 2.

Consider Further Evaluation If:

• Free T4 is also low with normal TSH - This suggests central hypothyroidism requiring immediate evaluation for hypopituitarism:

  • Check morning cortisol and ACTH levels urgently 4
  • Never start thyroid hormone before ruling out adrenal insufficiency, as this can precipitate life-threatening adrenal crisis 4
  • If cortisol is low, start hydrocortisone 10-20 mg in the morning and 5-10 mg in early afternoon, then wait several days before initiating levothyroxine 4
  • Obtain endocrinology consultation for comprehensive pituitary evaluation 4

• Patient has persistent symptoms after recovery from acute illness - Recheck TSH and free T4 after 3-6 weeks following resolution of the acute illness 5.

Critical Pitfalls to Avoid

• Do not initiate levothyroxine based solely on low FT3 with normal TSH and normal FT4 - This represents physiologic adaptation, not hypothyroidism requiring treatment 1, 2.
• Do not assume hypothyroidism in hospitalized patients - The combination of low TSH and high FT4 in hospitalized patients is usually caused by nonthyroidal illness combined with drug effects, not thyrotoxicosis 3.
• Do not overlook central hypothyroidism - If both FT4 and FT3 are low with normal or low-normal TSH, immediately evaluate for pituitary/hypothalamic disease and concurrent adrenal insufficiency before any treatment 4.
• Do not treat to normalize T3 levels during acute illness - Treatment with levothyroxine to restore serum thyroid concentrations to the normal range is not indicated and may be harmful 1.

Monitoring Strategy

• For patients with nonthyroidal illness - Recheck thyroid function tests 4-6 weeks after resolution of the acute illness to confirm normalization 5.
• For suspected central hypothyroidism - Monitor free T4 and free T3 levels (not TSH) to assess adequacy of treatment, targeting FT4 in the upper half of the normal range 4.
• Avoid frequent retesting - Do not recheck thyroid function tests before 6-8 weeks, as this leads to inappropriate interventions before steady state is reached 5.