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“While levothyroxine remains the golden standard of care, its inability to resolve persistent symptoms in a subset of patients highlights the need for alternative approaches.” (Ditshego et al, 2025)
Hypothyroidism affects millions of people, with symptoms ranging from mildly unpleasant to severe and debilitating. The standard of care calls for measuring thyroid stimulating hormone (TSH) and treating with levothyroxine (T4) to normalize the TSH level. However, as highlighted in previous articles, the TSH test is not always sufficient for identifying hypothyroidism, and T4 monotherapy doesn’t always resolve symptoms, even when TSH is normalized. A recent review view adds additional support for using a combination of T4 and T3 (liothyronine) in patients for whom the standard approach fails to resolve symptoms and improve quality of life.
The researchers note that as much as 20 percent of patients remain symptomatic despite normalization of TSH, and that T4 monotherapy may induce “a relative and sometimes absolute deficiency” of T3. This undesired outcome may occur because T4 normalizes TSH in the pituitary gland, but it does “not consistently restore T3 levels in peripheral tissues.” So even when TSH is normal, the concentration of T3 – the active form of thyroid hormone – may be inadequate for supporting a healthy metabolic rate, proper body temperature, and other critical physiological functions.
The authors also acknowledge that there may be a role for T3 monotherapy in patients who don’t absorb T4 well or in those in whom the conversion of T4 to T3 doesn’t happen optimally. T3 monotherapy – including supraphysiological doses – is unconventional but not unprecedented.
Dosing T3 or combinations of T4 and T3 is not as straightforward as dosing T4 alone, owing to the shorter half-life and potential unpredictability of T3, but divided dosing, use of slow- or sustained-release thyroid medication, and careful monitoring of symptoms can help to reduce the potential for adverse effects.
The standard treatment for low thyroid has left millions of patients with lingering symptoms. Employing T4 + T3 combination therapy, or, when warranted, T3 alone, may be more effective for these individuals. As the authors stated, “By addressing the shortcomings of traditional therapies, these innovative approaches aim to improve the quality of life and clinical outcomes for patients with hypothyroidism, especially when the golden standard fails.”
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