Two patients with atypical low triiodothyronine syndrome: primary deiodinase abnormalities?

Low triiodothyronine (T(3)) concentrations in the presence of normal thyroxine (T(4)) and TSH levels, referred to as the low T(3) syndrome (LT(3)S), are common. LT(3)S may be caused by starvation, various non-thyroidal illnesses (NTIs) and some medications. Reverse T(3) (rT(3)) concentrations are elevated in the more severely ill, and they characteristically fail to respond to exogenous levothyroxine (l-T(4)) therapy. The biochemical abnormalities have been explained on the basis of altered peripheral deiodinase activities. Herein, we report on two patients with hypothyroid symptoms who on testing were found to have LT(3)S. They were atypical clinically in not having LT(3)S due to any of the usual causes, had no increased rT(3) concentrations, and had a normal negative TSH feedback response to l-T(4). One (patient 1) had previously been diagnosed with Hashimoto's autoimmune primary hypothyroidism and was on l-T(4) therapy. Both had T(4) concentrations in the reference range. TSH levels were elevated in patient 1 and in the reference range in patient 2. Starting or increasing l-T(4) doses resulted in no clinical improvement and no increase in T(3) levels in spite of a marked increase in T(4) levels. It is suggested that in the absence of the usual causes, lack of elevated rT(3) levels, response to treatment and intact negative TSH feedback these two patients differ from the usual secondary causes of decreases in deiodinase activity. It is speculated that they may represent primary alterations in deiodinase enzymes possibly due to genetic variations in the deiodinase-encoding genes. LEARNING POINTS: LT(3)S is commonly found secondary to starvation, NTIs and use of some medications. Low T(3) levels are the result of alterations in the activity of deiodinase enzymes. LT(3)S without the usual causes may represent a primary disturbance in deiodinase activity.