Mechanisms of non-thyroidal illness syndrome elucidated
A study in rats has suggested that non-thyroidal illness syndrome (NTIS), a generalized response to any serious illness, might be treatable by forced expression of steroid receptor co-activator (SRC-1).
The research team, led by Ronald Koenig, from the University of Michigan in Ann Arbor, USA, explains that NTIS is characterized by a decreased level of circulating triiodothyronine (T3).
They comment: "The current standard of care is not to treat the NTIS, but the data that guide this practice are sparse. There is currently no way to identify which, if any, patients might benefit from treatment, nor what the treatment might be."
It is known, however, that cytokines produced during illness, such as interleukin (IL)-1, induce a decrease in the hepatic type 1 iodothyronine deiodinase (D1) enzyme that, in healthy individuals, converts thyroxine (T4) to T3.
In turn, D1 is also induced by T3, and so decreased T3 levels also result in a further decline in D1 expression.
To examine these processes further, the scientists infected primary rat hepatocyte cultures with an adenoviral SRC-1 expression vector while exposing the cells to IL-1.
They found that in the control adenovirus-treated cells, T3 increased D1 messenger (m)RNA production by about six times. IL-1 inhibited T3 induction, reducing it to a two-fold increase.
In contrast, infection of cells with an SRC-1 expressing adenovirus prevented this effect of IL-1, whereas T3 still induced D1 mRNA about six times.
"Our results confirm the prior finding that cytokines such as IL-1 impair hepatic T3 production from a euthyroid to a hypothyroid level, which further serves to decrease D1 expression and T3 levels," Koenig and co-workers write in the journal Endocrinology.
Importantly, they stress that the current data "suggest that the low circulating T3 is at least in part due to a defect in nuclear receptor co-activator function, and that this defect can be overcome by forced expression of SRC-1."
The researchers conclude: "Further research will be required to better understand the underlying defect and to address if, what, and when therapy of the NTIS should be instituted."