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Once-weekly levothyroxine therapy
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It is interesting how similar cases occasionally present in a series of pairs or triples. After not having seen hypothyroidism with persistently elevated thyroid-stimulating hormone levels while on high-dose levothyroxine therapy for several months, three cases came to see me in the same week. All had TSH >40 mIU/L despite being prescribed high-dose levothyroxine. The gentleman in my last post was not taking his levothyroxine daily because he could not afford to fill his prescription.
Later that same week, I saw a woman with mild dementia. She lives independently and has someone to help with cooking and cleaning. However, there is no one to assure that she takes her medications. Her TSH remains high because she cannot remember to take her levothyroxine and other medications every day.
Levothyroxine has an approximate seven-day half-life but the biologic effect may be longer. This means that it may be less important what exactly is taken on any particular day compared to what has been taken over the past week. Because of this, it is possible to give levothyroxine once or twice a week as directly observed therapy when necessary to ensure compliance.
There have only been a few case series with small numbers of patients reporting the safety and efficacy of once-weekly levothyroxine. Studies have shown that a single dose of as high as 3 mg of levothyroxine is well tolerated. Levels of free thyroxine are higher in the days immediately following the dose. However, as levels of T4 decrease before the next dose, peripheral conversion to active triiodothyronine becomes more efficient. Such autoregulatory mechanisms maintain euthyroidism. Patients on once-weekly therapy tolerate it well and without evidence of cardiac symptoms or toxicity. Some authors suggest that a slightly larger dose than seven times the normal daily dose may be necessary.
In the patient described above, we will first arrange to have pill boxes filled by her pharmacist. If she continues to be unable to remember to take her levothyroxine, family members have volunteered to witness her taking her levothyroxine as directly observed therapy twice a week. I rarely have to resort to once- or twice-weekly directly observed therapy. However, I have used it a few times in the past with success when all else failed.
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