They also noted that oxidative stress is one of the causes of chronic diseases and cancer.The study looked at the prevalence of breast, colorectal, gastric and lung cancer in 18 Italian Regions during 2010 and correlated this data with sales of LT4 in 2009, focusing on women aged 30-84. (They noted that this age range corresponds to more than 80% of the consumers of the drug and to about 99% of all malignant cancers). They then correlated drug sales with cancers, eliminating the contribution of age and smoking for lung cancer risk.
They found no significant correlation between T4 sales and breast, colorectal and gastric cancers, but did find a significant correlation for lung cancer(p < 0.05) corrected for smoking and age.In discussing their findings, the authors noted that they could not exclude the possibility that the condition of hypothyroidism could favor the development of lung cancer. However, they pointed out that the opposite was recently described, and that “…hypothyroidism reduces the aggressiveness of some cancers because of the presence of thyroid hormone receptors on cancer cells, and spontaneous hypothyroidism may delay onset or reduce aggressiveness of cancers.”Other research indicating that increased thyroid activity (hyperthyroidism) contributes to lung cancer pathogenesis was presented, including.
● Recently T4 has been reported as one of the several endogenous factors capable of supporting proliferation of lung cancer cells.
● The observation that patients with small cell carcinoma of the lung often present symptoms suggestive of hyperthyroidism (i.e. weight loss, anorexia) was made many years ago together with an over production of both T4 and T3.
● An old clinical observation on the relationship between lung cancer and thyroid function reported that patients were characterized by a low concentration of T3 and an increased T4/T3 ratio due to a decrease of 5′-monodeiodination (DI).
● More recently DI activity in lung cancer was found to be lower than in peripheral lung tissue.
The authors also cite animal experimental research which has shown that T4 increases the oxidative stress and spontaneous pulmonary metastases in mice. They also elaborate on a mechanism of T4-induced lung tissue toxicity:rats lung the deiodination of LT4 is the lowest compared to all the other tissues.This means that the amount of LT4 reaching the lungs following an external supplementation cannot to be transformed into LT3 as in the other tissues, and make lungs very vulnerable to possible toxic effects of LT4.
The authors delved deeper into the reason why oxidative stress taking place during T4 treatment is particularly linked to lung cancer only:The hypothesis could be that in lungs the increase of hypoxia-induced factor (HIF-1) which is determined by T4 can make oxygen much more available, increasing locally the oxidative stress together with a dangerous angiogenesis stimulation.   Although we should never forget that LT4 is a life-saving thyroid hormone replacement, and that one should not exclude that the pathological reason that leads to the prescription of LT4 could favor the lung cancer development also.The authors expanded on their findings further:”However, the impression we get from our experience in epidemiological studies monitoring is that this drug should be prescribed more cautiously.
Considering that the population in Italy is about 60 million people and the sales of LT4 in the country in 2010 were 17.69 million boxes (+ 6% Vs 2009), hypothyroidism, which is the main reason for the prescription, should be a real national concern (almost 0.7 boxes/women/year). Most of the time, doctors tell patients treated with LT4 that any side effects will be temporary and almost ineluctable, and are usually dealt with through dose reduction. Assessment of oxidative stress and its balance has not been taken into consideration up to now as it should be.”Finally, they pointed out that T4, which is a synthetic form of thyroid hormone, might be avoided if T3 or the desiccated pig-derived form known as Armour Thyroid was used to control the oxidative-stress producing hydroperoxides.