Euthyroid sick syndrome
1. What is euthyroid sick syndrome?
Euthyroid sick syndrome refers to changes in serum thyroid-stimulating hormone (TSH), serum thyroid hormone, and tissue thyroid hormone levels that occur in patients with various nonthyroidal illnesses and starvation. It is not a primary thyroid disorder but instead results from changes in thyroid hormone secretion, transport, and metabolism induced by the nonthyroidal illness.
2. What hormone changes occur in patients with mild to moderate nonthyroidal illnesses?
Serum total triiodothyronine (T3) and free T3 and tissue T3 levels decrease as a result of reduced conversion of thyroxine (T4) to T3 in peripheral tissues, predominantly the liver, where hepatic deiodinase type I (D1) activity is decreased. Serum free T4 and TSH levels usually remain within the reference range in the mildest form of this condition.
3. Describe the hormone changes in patients with moderate to severe nonthyroidal illnesses.
Serum total T3 and free T3 levels decrease further; total T4 also decreases, and the T3 resin uptake (T3RU) increases. The latter changes result from reduced binding of thyroid hormones to their transport proteins because of both impaired protein synthesis and the presence of circulating inhibitors of protein binding. Serum TSH levels remain normal or become decreased at this stage. Free T4 may be normal, decreased, or increased.
4. Describe the hormone changes associated with recovery from nonthyroidal illnesses.
Free T4 decreases, and TSH increases. As hepatic protein synthesis improves and circulating inhibitors of protein binding disappear, serum free T4 levels drop transiently with a compensatory increase in serum TSH levels before complete normalization occurs. Serum T3 levels also eventually normalize.
5. How can euthyroid sick syndrome be distinguished from hypothyroidism?
In euthyroid sick syndrome, serum T3 is decreased proportionately more than T4, the T3RU is high, and TSH is normal or mildly decreased and then mildly increased during recovery. In primary hypothyroidism, serum T4 is reduced proportionately more than T3, the T3RU is low, and TSH is increased. Other tests may also be helpful. In euthyroid sick syndrome, free T4 is usually normal and reverse T3 (rT3) is increased; in hypothyroidism, both free T4 and rT3 are decreased.
6. What causes euthyroid sick syndrome?
Euthyroid sick syndrome is believed to be caused by increased circulating cytokines and other inflammation mediators resulting from the underlying nonthyroidal illness. These mediators inhibit the thyroid axis at multiple levels, including the pituitary (decreased TSH secretion), the thyroid (decreased T4 and T3 responses to TSH), transport proteins (decreased thyroid hormone binding), and peripheral tissues (decreased conversion of T4 to T3).
7. What is the function of the deiodinase enzymes?
Deiodinases are selenocysteine enzymes that activate and deactivate thyroid hormones by removing iodine molecules. Deiodinase enzymes have three known subtypes: D1, deiodinase 2 (D2), and deiodinase 3 (D3) (Table 39-1 and Fig. 39-1). D1 converts T4 to T3 in the liver and kidneys, thus producing the majority of circulating T3, and converts reverse T3 (rT3
