Physiologic combinations of synthetic thyroid hormones in myxedema

Physicians in the United Kingdom and the United States concluded in the 1960s that only treatment with LT4+LT3 was able to resolve symptoms and restore thyroid hormone levels as assessed through protein-bound iodine levels.

“Indeed, physicians in the United Kingdom and the United States concluded back in the 1960s that only treatment with LT4+LT3 was able to resolve symptoms and restore TH levels (as assessed through protein-bound iodine levels) (12–14).”

DTE preparations could not be standardized from lot to lot to provide uniform hormonal activity because standardization was based on iodine levels and not on T4 and T3 content.

“they could not be standardized from lot to lot to provide uniform hormonal activity (67,78,79) given that standardization was based on iodine levels and not on T4 and T3 content (80,81).”

One of the first clinical trials of combination therapy concluded that 175-200 mcg/day LT4 combined with 25-50 mcg/day LT3 maintained an athyreotic patient in clinical euthyroidism.

“Using clinical parameters to define euthyroidism, the crossover study of 21 hypothyroid patients who were treated with different LT4/LT3 combinations for periods of 6–8 weeks concluded that 175–200 mcg/day LT4 combined with 25–50 mcg/day LT3 maintained an athyreotic patient in clinical euthyroidism (78).”

Dampened enthusiasm for DTE over standardization concerns led physicians to progressively turn to synthetic LT4 and/or LT3 preparations that eventually became the standard of care.

“Dampened enthusiasm for DTE to treat hypothyroidism over-standardization concerns (78) led physicians to progressively turn to synthetic LT4 and/or LT3 preparations that eventually became the standard of care (78,79,86).”