The Potential of Thyroid Hormone Therapy in Severe COVID-19: Rationale and Preliminary Evidence.

Tissue hypoxia is one of the main pathophysiologic mechanisms in sepsis and particularly in COVID-19. Microvascular dysfunction, endothelialitis and alterations in red blood cell hemorheology are all implicated in severe COVID-19 hypoxia and multiorgan dysfunction. Tissue hypoxia results in tissue injury and remodeling with re-emergence of fetal programming via hypoxia-inducible factor-1α (HIF-1a)-dependent and -independent pathways. In this context, thyroid hormone (TH), a critical regulator of organ maturation, may be of relevance in preventing fetal-like hypoxia-induced remodeling in COVID-19 sepsis. Acute triiodothyronine (T3) treatment can prevent cardiac remodeling and improve recovery of function in clinical settings of hypoxic injury as acute myocardial infarction and by-pass cardiac surgery. Furthermore, T3 administration prevents tissue hypoxia in experimental sepsis. On the basis of this evidence, the use of T3 treatment was proposed for ICU (Intensive Care Unit) COVID-19 patients (Thy-Support, NCT04348513). The rationale for T3 therapy in severe COVID-19 and preliminary experimental and clinical evidence are discussed in this review.

Brain metastasis in renal cell cancer responding to sunitinib.

BACKGROUND: Sunitinib (SU011248; Sutent) is a new small molecule that inhibits members of the split-kinase domain family of receptor tyrosine kinases (RTKs), with established antitumor activity in renal cancer. In the current report, we describe a patient with a solitary brain metastasis from renal cell carcinoma who achieved partial response of the cerebral lesion following treatment with sunitinib. To the best of our knowledge, this is the first report of sunitinib activity in brain metastases from kidney cancer. A limited number of publications support the hypothesis that small tyrosine kinase inhibitors may cross the blood-brain barrier. Although the role of sunitinib in advanced renal carcinoma has been evaluated through prospective trials, the efficacy of the drug in patients with brain metastases has not been explored, since patients with cerebral lesions were excluded in those studies. Thus, we believe that accumulating evidence from personal experience or limited reports could be useful. Moreover, in our case, sunitinib was found to be safe, leading to considerable shrinkage of the brain metastasis without any serious adverse events or central nervous system toxicities. We consider this observation to be important, given the absence of data regarding the activity of the drug in this particular clinical setting.