The Scale of the Problem
Each year there are about 375,000 cases of cancer in the UK with 166,000 deaths (Cancer Research UK). Lung Cancer accounts for around 48,500 cases and 35,100 deaths per year, only 10% of lung cancer patients survive for 10 years. If we assume 2% of the population are on levothyroxine monotherapy this would equate to 7,500 cases of cancer (IF these patients have the same cancer risk as the general population). The actual number of cases will be higher because both hypothyroidism and cancer are more common in later life.
The Integrin αvβ3 Receptor and Thyroxine
T4 acting at the integrin αvβ3 receptor promotes cancer growth, metastasis and angiogenesis. It inhibits apoptosis and enhances radioresistance.
Studies of T4 and cancer in the general population have conflicting results. Baseline T4 levels are likely to change over time and abnormal levels may be treated.
Levothyroxine Monotherapy and Cancer
Levothyroxine monotherapy raises the T4/T3 ratio and is associated with an increased cancer risk linked to the duration of therapy. Combined L-T3/L-T4 therapy reduces cancer incidence and lowers cancer and all-cause mortality.
Assume a conservative estimate of 3,320 annual hypothyroid patient cancer deaths (2% of 166,000). If we apply the 0.776 hazard ratio then substituting combination therapy for levothyroxine therapy will save about 740 lives each year. Estimating the number of lives lost to levothyroxine monotherapy is difficult because of a lack of data as only a small percentage of patients are receiving combination therapy at present.
A decision should not wait for more precise figures, the exact number of lives saved each year should not affect the treatment strategy. Patients are entitled to the safer option now.
An additional consideration is that post COVID cancer care resources are severely overstretched, any opportunity to reduce the burden of cancer should be taken.
Conclusion and Recommendations
There is strong evidence that T4 promotes cancer via its action at the integrin αvβ3 receptor. Studies show levothyroxine monotherapy increases overall cancer risk and mortality compared to liothyronine / levothyroxine combination therapy. Except for special cases levothyroxine monotherapy should not be prescribed.
It has been recommended that: ‘T3 be considered alternative replacement treatment for patients with primary hypothyroidism who also have cancer‘. A better approach would be to amend the ‘Warnings and precautions Talk to your doctor‘ section of the Levothyroxine Patient Information Leaflet (PIL) to add ‘if you are diagnosed with cancer‘. This would enable specialists to adjust thyroid hormone therapy on a case-by-case basis depending on the nature of the cancer.