A 72-year-old man is hospitalized for cough, purulent sputum, and shortness of breath. His medical conditions include type 2 diabetes and hypertension. A chest x-ray reveals right lower lobe pneumonia, and treatment is started with supplemental oxygen and antibiotics. While hospitalized, the patient develops persistent sinus tachycardia. Thyroid function tests ordered during the subsequent work up reveal:
| Thyroid-stimulating hormone (TSH) | 1.3 mU/L (normal: 0.5-5.0 mU/L) |
| Free thyroxine (T4) | 1.2 ng/dL (normal: 0.9-2.4 ng/dL) |
| Triiodothyronine (T3), total | 60 ng/dL (normal: 115-190 ng/dL) |
Which of the following is the primary contributor to the decreased total T3 level in this patient?
Euthyroid sick syndrome (low T3 syndrome) | |
Clinical presentation |
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Pathophysiology |
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Diagnostic testing |
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IFN = interferon; IL = interleukin; TNF = tumor necrosis factor; TRH = thyrotropin-releasing hormone. | |
This patient has euthyroid sick syndrome (ESS) (also known as low T3 syndrome), characterized by a low T3 level, normal thyroid-stimulating hormone (TSH), and normal T4. Thyroid hormone is released primarily in the form of T4, with conversion to T3 (the more active form) by 5'-deiodinase (types I and II) in peripheral tissues. In severe illness, high levels of cortisol, inflammatory cytokines, and free fatty acids suppress deiodination of T4, resulting in lower circulating levels of T3. Concurrently, upregulation of 5'-deiodinase type III leads to increased conversion of T4 to reverse T3 (inactive form).
ESS is thought to be a form of mild, transient central hypothyroidism, intended to decrease maladaptive catabolism in severe illness; treatment with exogenous thyroid hormone does not improve outcomes and is not indicated. With increasing duration and severity of illness, central production of thyrotropin-releasing hormone (TRH) and TSH are also suppressed, leading to lower circulating TSH and T4 levels.
(Choice B) Thyroglobulin is iodinated by thyroperoxidase (TPO) in follicular colloid. TPO activity is increased by TSH and suppressed by thioamides (eg, methimazole, propylthiouracil). Although TSH (and therefore iodination of thyroglobulin) falls in later ESS, this patient's TSH is normal, and his normal T4 level suggests adequate iodination.
(Choice C) Although a small amount of T3 is produced in the thyroid (from T4 via 5'-deiodinase type II), most is produced in peripheral tissues. The fall in circulating T3 levels in ESS is primarily due to suppression of peripheral conversion.
(Choice D) Iodine deficiency is rare in developed countries. When it occurs, it presents chronically with goiter and primary hypothyroidism (ie, elevated TSH, low T4). This patient has a normal TSH level, making iodine deficiency unlikely.
(Choice E) Proinflammatory cytokines decrease TSH levels by reducing secretion of TRH in the hypothalamus. In patients with ESS, TSH increases normally following administration of exogenous TRH, suggesting an intact pituitary response to TRH.
Educational objective:
Euthyroid sick syndrome (ESS) is a common pattern of thyroid function markers seen in severely ill patients. It is characterized by decreased conversion of T4 to T3 in peripheral tissues. Initial findings include a low T3 level, but later, T4 and thyroid-stimulating hormone levels may also decrease. ESS may represent a mild central hypothyroid state, which functions to minimize catabolism in severe illness.