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Thyroid hormone receptor expression in the "sick euthyroid" syndrome
G R Williams1, J A Franklyn, J M Neuberger
1Department of Medicine and Liver Unit, University of Birmingham, Queen Elizabeth Hospital, Edgbaston.
Abstract:
To explore the hypothesis that alteration of T3 receptor expression may be an important mechanism controlling the tissue effects of thyroid hormones in the "sick euthyroid" syndrome, specific triiodothyronine (T3) receptor mRNAs were measured in tissues from normal subjects and from patients with liver disease, chronic renal failure, or with multiple organ failure on an intensive care unit (ICU). In all patient groups circulating free thyroxine and free T3 were reduced, while thyroid stimulating hormone remained normal. In patients with liver or renal disease, there were significant increases in levels of both alpha and beta T3 receptor mRNAs in peripheral mononuclear cells (PMNCs); in ICU patients there was a significant increase in beta mRNA. In patients with liver disease increases in T3 receptor mRNAs were not confined to PMNCs but were also found in liver biopsy specimens when levels were compared with those in normal donor liver. After liver transplantation, receptor mRNAs in PMNCs were similar to those in controls; likewise beta mRNA was similar in liver tissue to normal liver. There was, however, persistent elevation in alpha receptor mRNA. Increases in T3 receptor expression in non-thyroidal illness may be responsible for the maintenance of euthyroidism in the face of reduced levels of circulating thyroid hormones.
Insights
Altered thyroid hormone receptor expression, specifically increased T3 receptor mRNAs, may explain normal thyroid status in non-thyroidal illness. This finding is crucial for understanding the "sick euthyroid" syndrome.
Area of Science:
- Endocrinology
- Molecular Biology
- Critical Care Medicine
Background:
- The
- sick euthyroid
- syndrome involves altered thyroid hormone levels during critical illness.
Purpose of the Study:
- To investigate if changes in triiodothyronine (T3) receptor mRNA levels explain the tissue effects of thyroid hormones in non-thyroidal illness.
Main Methods:
- Measured T3 receptor alpha and beta mRNAs in peripheral mononuclear cells (PMNCs) and tissues from normal subjects and patients with liver disease, renal failure, or multiple organ failure (ICU).
Main Results:
- Reduced circulating free thyroxine and T3 observed in all patient groups. Significant increases in T3 receptor mRNAs (alpha and beta) found in PMNCs of liver/renal patients and beta mRNA in ICU patients. Liver disease patients showed increased receptor mRNAs in liver biopsies. Alpha receptor mRNA remained elevated post-liver transplant.
Conclusions:
- Increased T3 receptor expression in non-thyroidal illness may maintain euthyroidism despite reduced circulating thyroid hormones.
- Persistent elevation of alpha receptor mRNA post-transplant suggests long-term alterations.