This is the only retrospective study reported to use long-term (mean 27 months) thyroid replacements with combination therapy and to compare between the two forms of therapy: synthetic and natural.
For patients undergoing either therapy, the study did not identify additional risks of atrial fibrillation, cardiovascular disease, or mortality in patients of all ages with hypothyroidism.
None of the patients who had abnormally low TSH or elevated FT3 or FT4 levels had hospitalizations for arrhythmias or thyrotoxicosis.
On the Medical Outcomes Study Short Form-20 questionnaire, >92% answered feeling "excellent, very good, or good" when questioned about their health while undergoing thyroid replacement compared with levothyroxine alone.
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Tariq A, Wert Y, Cheriyath P, Joshi R. Effects of Long-Term Combination LT4 and LT3 Therapy for Improving Hypothyroidism and Overall Quality of Life. South Med J. 2018 Jun;111(6):363-369. doi: 10.14423/SMJ.0000000000000823. PMID: 29863229; PMCID: PMC5965938.