Abstract
Hypothyroidism is common throughout the world and readily diagnosed with thyroid function tests. Management should be straightforward but appears not to be the case. Thyroid hormone replacement with levothyroxine monotherapy is the standard treatment which is effective in the majority of cases. However, 10–15% of patients established on levothyroxine do not feel their health is entirely restored and some patients prefer the addition of liothyronine. Proponents of liothyronine argue that the ratio of T3 and T4 hormones is substantially altered on T4 monotherapy and therefore both hormones may be needed for optimal health. This remains controversial as clinical trials have not demonstrated superiority of combination therapy (levothyroxine and liothyronine) over levothyroxine monotherapy. There is now a pressing need for further studies and in particular randomized controlled trials in this area. To help design and facilitate dedicated trials and better understand thyroid hormone replacement, this review summarizes the evidence where there is established knowledge and agreement (knowns) and areas where research is lacking (unknowns). Agreements include the extent of dissatisfaction with levothyroxine monotherapy, biases in testing for hypothyroidism and prescribing levothyroxine, as well as variable thresholds for prescribing levothyroxine and challenges in liothyronine dosing. The review will also highlight and summarize the unknowns including the long-term safety profile of liothyronine, and potential biomarkers to identify individuals who might benefit most from combination therapy.
Highlights
Hypothyroidism is common throughout the world and affects females [1]
There is recent evidence that T4 inhibits the deiodinase that converts T4 to T3 in target tissues, with the potential to result in paradoxically reduced levels of intracellular T3 when there is a high circulating T4/T3 ratio [25]. Based on this uncertainty regarding the benefit of LT3, current European Thyroid Association guidance [26] recognizes that LT4 is the treatment of choice but recommends that a 3-months trial of LT3 could be considered in patients with persistent unexplained symptoms despite good compliance
In a small number of patients with goiter who received levothyroxine before thyroidectomy, a 33% increase in LT4 dose was required after thyroidectomy to maintain pre-surgical TSH levels [51] but a clear reduction in FT3 was not observed in the same patient before and after thyroidectomy
Summary
Hypothyroidism is common throughout the world and affects females [1]. It is readily identifiable and treatable, but if untreated or poorly managed can have profound adverse effects [1, 2]. Levothyroxine (LT4) is the current standard treatment liothyronine (LT3) and desiccated thyroid extract (DTE) are used [2, 3]. Prior to the 1970’s both combination thyroid hormone replacement (LT3 + LT4) and DTE were widely prescribed [4]. Thyroid hormone replacement is an important global public health issue and as at present, LT4 is the most commonly prescribed medication in the USA and the third most commonly prescribed in the UK [2]
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