Increased fT4 concentrations in patients using levothyroxine without complete suppression of TSH

Area of Science:

• Clinical Chemistry
• Endocrinology
• Laboratory Medicine

Background:

• Physicians observed elevated free thyroxine (fT4) with non-suppressed thyroid-stimulating hormone (TSH) post-new immunoassay introduction.
• This discordance prompted investigation into reference intervals, analytical issues, and patient factors.

Purpose of the Study:

• To determine the causes of high fT4 concentrations without TSH suppression.
• To assess the impact of levothyroxine (L-T4) intake timing on fT4 levels.

Main Methods:

• Re-evaluated fT4 immunoassay reference intervals using healthy volunteers.
• Assessed immunoassay performance via quality controls and external rounds.
• Retrospectively analyzed discordant fT4/TSH results from Delfia and Cobas assays.
• Conducted a literature search on L-T4 intake timing and fT4 levels.

Main Results:

• Confirmed original reference intervals; no analytical issues identified.
• Discordance frequencies were similar between Delfia (5.5%) and Cobas (8.7%) assays.
• 72-81% of discordant results were from levothyroxine (L-T4) users.
• Literature suggests L-T4 intake timing influences fT4 concentrations.

Conclusions:

• Elevated fT4 without suppressed TSH is primarily associated with L-T4 intake.
• Awareness of this phenomenon is crucial for physicians and lab specialists.
• Prevents unnecessary questioning of assay performance or L-T4 dose adjustments.