Most people thrive on levothyroxine. But a real minority — perhaps 1 in 10 — still feel unwell despite a 'perfect' TSH, and this is where medicine's most heated thyroid debate lives: whether to add T3, or switch to natural desiccated thyroid.
Around 10–15% of well-treated, biochemically-normal patients still have fatigue, brain fog, or low mood. One explanation: on T4-only therapy some people run a low-normal active T3, possibly converting T4→T3 poorly (sometimes linked to the DIO2 gene — plausible but genuinely disputed, and not a routine test). Real physiology for some; not the answer for everyone. Evidence ●●●○○
Adding synthetic T3 (liothyronine) to T4 hasn't shown an average benefit across ~14 trials — but a consistent finding is that a subset of patients, given a blinded choice, prefer it. The 2021 endocrine consensus says a supervised trial of combination therapy is reasonable for people who stay symptomatic on adequate levothyroxine — framed honestly as 'reasonable to try,' not 'proven to work,' with monitoring for over-treatment. Evidence ●●●○○
NDT (Armour, from pig thyroid) contains both T4 and T3 and is popular in patient and functional circles, with many reporting they feel better on it. Mainstream caution: its fixed ~4:1 T4:T3 ratio is far more T3-heavy than the human gland's (~14:1), giving T3 spikes, and trials show no average advantage. A real preference signal in some people; a real over-treatment concern in others. Evidence ●●○○○
Rule out the mimics first, then trial it — supervised
If you're symptomatic on a good levothyroxine dose with a normal TSH, first rule out the mimics (iron, B12, vitamin D, sleep, mood). If those are clear, a supervised trial of combination T4/T3 is a reasonable next step to discuss — with monitoring, not as a leap into NDT off the internet.
The Hashimoto’s Guide