We here described a 39-year-old woman with a severe chronic mood disorder, 
refractory to antidepressive therapy who showed a significant improvement after 
a self-prescription of high doses of liothyronine (T(3)). A modified Refetoff 
protocol was carried out to study the role of thyroid hormones on her clinical 
and biochemical responses. Depression severity was assessed by the HAM-D and 
MADRS Depression Rating Scales. Sequencing of Thyroid Receptors (TR) alpha1 and 
beta1 genes was done. At the final stage of the study, plasma T3 and free T3 
were >800 ng/dl (80-180) and 1409 pg/dl (230-420), respectively. No changes in 
the cardiovascular parameters, alkaline phosphatase isoenzymes, creatinine 
kinase, or ferritin were observed. However, an improvement in mood was detected 
by specific scores (HAM-D 24 to 8; MADRS 40 to 11). No mutations in DNA- and 
hormone-binding-domains of TRbeta1 and TRalpha1 genes were found in proband, 
suggesting that the defect could be due to an unknown mutation in either the TR 
gene or a post receptor abnormality. These results support the existence of a 
peripheral RTH manifestation as a refractory chronic depression reverted by high 
doses of T(3). Screening for RTH in refractory chronic depression may provide an 
alternative treatment for this psychiatric condition.