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Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency

Pleased to see this paper has now hit PubMed. :-)

Endocr Connect. 2015 Dec;4(4):196-205.

Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency.

Midgley JE1, Larisch R1, Dietrich JW2, Hoermann R3.


Several influences modulate biochemical responses to a weight-adjusted levothyroxine (l-T4) replacement dose. We conducted a secondary analysis of the relationship of l-T4 dose to TSH and free T3 (FT3), using a prospective observational study examining the interacting equilibria between thyroid parameters. We studied 353 patients on steady-state l-T4 replacement for autoimmune thyroiditis or after surgery for malignant or benign thyroid disease. Peripheral deiodinase activity was calculated as a measure of T4-T3 conversion efficiency. In euthyroid subjects, the median l-T4 dose was 1.3 μg/kg per day (interquartile range (IQR) 0.94,1.60). The dose was independently associated with gender, age, aetiology and deiodinase activity (all P<0.001). Comparable FT3 levels required higher l-T4 doses in the carcinoma group (n=143), even after adjusting for different TSH levels. Euthyroid athyreotic thyroid carcinoma patients (n=50) received 1.57 μg/kg per day l-T4 (IQR 1.40, 1.69), compared to 1.19 μg/kg per day (0.85,1.47) in autoimmune thyroiditis (P<0.01, n=76) and 1.08 μg/kg per day (0.82, 1.44) in patients operated on for benign disease (P< 0.01, n=80). Stratifying patients by deiodinase activity categories of <23, 23-29 and >29 nmol/s revealed an increasing FT3-FT4 dissociation; the poorest converters showed the lowest FT3 levels in spite of the highest dose and circulating FT4 (P<0.001). An l-T4-related FT3-TSH disjoint was also apparent; some patients with fully suppressed TSH failed to raise FT3 above the median level. These findings imply that thyroid hormone conversion efficiency is an important modulator of the biochemical response to l-T4; FT3 measurement may be an additional treatment target; and l-T4 dose escalation may have limited success to raise FT3 appropriately in some cases.

© 2015 The authors.


TSH; conversion; deiodinase; l-T4 therapy; levothyroxine; thyroid hormone replacement; triiodothyronine

2 Replies

Helvella, that's good news, a much wider readership. Wonder how long it will take before the findings are adopted?


It sounds like a good additional measurement to achieve that perfect conversion we spend our whole hypothyroid life seeking......but if endos struggle to read our test results as they are ...what hope can we have of them understanding yet another set of equations?

Unless they passed then straight onto that's another story..! !


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