Low-T3 syndrome

The low T3 syndrome is induced by a decrease in the production of plasma T3 as well as the clearance of plasma rT3 and is observed in several clinical situations such as starvation, systemic illness and the use of certain drugs [115]. In fasting [70] and illness [108] the abnormal thyroid hormone metabolism appears to result from a defective liver uptake and, therefore, a decreased supply of T4 and rT3 for intracellular deiodination. In other conditions such as treatment with PTU or propranolol [116], the defect appears localized in the type I deiodinase itself leading to a decline in T3 formation and rT3 breakdown. 

Raciti, M., Ripoli, A., Scarlattini, M., L Abbate, A. and Donato, L. (2003) Low-T3 syndrome a strong prognostic predictor of death in patients with heart disease. Circulation, 107, 708—713. 

Patients with severe non-thyroidal illness may show apparent abnormalities in thyroid hormone resuits, known as the low T3 syndrome or non-thyroidal illness pattern of results. 

L0W-T3 syndrome is the principal and most common alteration ofTH metabolism found in patients known to have another (i.e., non thyroidal) disease. Regarding cardiac disorders, low-T3 syndrome has been documented in patients with various heart diseases including congestive HF (Hamilton et al., 1990) and acute myocardial infarction (Friberg et al, 2002), as well as after cardiac surgery in both adults and children (Holland et al., 1991 Murzi et al, 1995). The incidence of low-T3 syndrome increases with the severity of the disease and afflicts up to 20—30% of the total cardiac population (Hamilton et al., 1990 lervasi et al, 2003). Several factors contribute to thyroid abnormalities (1) inhibition of the activity of Type 1 deiodinase (2) decreased transport of T4 into tissues and probably (3) reduced activity of Type 2 deiodinase, believed to be responsible for local cellular demand for T3. 

Figure 110.3 Survival curves in euthyroid cardiac patients and in cardiac patients with subclinical hypothyroidism. Kaplan-Meier survival curves of cardiac patients with normal thyroid function and of cardiac patients with low-T3 syndrome. Events considered cardiac and overall death. Modified from lervasi et al., (2007). Reprinted with permission.

Figure 110.7 Effects of L-T3 IV administration on systo-diastolic function assessed by cardiac magnetic resonance in a patient with heart failure. An example of cardiac magnetic resonance performed in a patient with dilated cardiomyopathy and low-T3 syndrome before and early after 3-day continuous administration of IV L-T3. The images show the traced endocardial (internal line) and epicardial (external line) borders of the left ventricle for calculating volumes of the left ventricle. Histograms show the values of the end-diastolic left ventricular volume and of the stroke volume before and early after 3-day continuous administration of IV L-T3 (unpublished data from the authors). Mean value SD.

Thyroid function tests are often altered by somatropin because of increased conversion of T4 to T3, but this is clinically insignificant at low doses (SEDA-21, 453). One child with Prader-Willi syndrome had a fall in serum thyroxine concentration during somatropin therapy and needed thyroxine replacement (33). Hypothyroidism developed in 11 of 46 growth hormone-deficient children treated with somatropin (34). Prior abnormalities in hypothalamic-pituitary function and alterations in thyroid hormone metabolism, probably both, contributed to the high incidence of hypothyroidism, which was similar to that in previous studies. 

A progressive spectrum of thyroid test result anomalies accompanies NTIs in euthyroid patients (the euthyroid sick syndrome )(Figure 52-6 and Box 52-5). The earliest and most common changes that occur are a reduction in the serum concentrations of total and free Tj, sometimes to extremely low concentrations, and an elevation in the serum concentration of rT (the lowTj state ). These changes have been ascribed to a block in the 5 deiodinases that convert T4 to T3 in peripheral tissue. Acute and chronic nutritional problems, poorly controlled diabetes meUitus, and drugs such as hydrocortisone and beta blockers can also inhibit this conversion. 

Reverse T3 in serum is present almost entirely as a result of its generation from T4 in peripheral tissues by 5-deiodinases. The concentration of serum rT3 is lower than that of Ts because of the faster metabolic clearance of rTs. Serum rT3 concentrations are elevated at birth, but decrease to stable values by about the fifth day of life. Reverse T3 in amniotic fluid decreases with increasing gestational age. The use of reverse Ts in patients with the euthyroid sick syndrome has fallen out of favor with the recognition that rTs is not always elevated in iUness. Specifically, renal failure is associated with low rTs concentrations. 

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