From the Guidelines
Thyroid-stimulating hormone (TSH) levels typically decrease during acute illness, a phenomenon known as "non-thyroidal illness syndrome" or "euthyroid sick syndrome". During acute illness, the body suppresses TSH production in the pituitary gland, leading to lower circulating TSH levels, as noted in a study published in the Annals of Internal Medicine 1. This occurs as part of the body's stress response, mediated by increased cortisol and cytokines that directly inhibit the hypothalamic-pituitary-thyroid axis. The severity of illness often correlates with the degree of TSH suppression, with more critically ill patients showing more pronounced decreases. Some key points to consider when evaluating TSH levels in the context of illness include:
- TSH levels can vary by as much as 50% of mean values on a day-to-day basis, with up to 40% variation of values obtained from serial TSH measurements performed at the same time of day, as reported in the study 1.
- Factors other than thyroid disorders, such as the administration of certain drugs or substances, adrenal insufficiency, pregnancy, anorexia nervosa, and pituitary adenomas, can also interfere with normal circulating levels of TSH, as discussed in the study 1.
- Because of these illness-induced alterations, thyroid function tests should be interpreted cautiously in acutely ill patients, and definitive diagnosis of thyroid disorders should generally be postponed until after recovery from acute illness. It is essential to consider these factors when interpreting TSH levels in the context of illness to avoid misdiagnosis or inappropriate treatment, as highlighted in the study 1.
From the Research
TSH Changes in Illness
- In nonthyroidal illness, TSH levels can remain normal despite changes in thyroid hormone levels 2, 3
- Certain drugs, such as dopamine and high-dose glucocorticoids, can suppress TSH secretion from the pituitary, leading to central hypothyroidism 2
- In primary hypothyroidism, TSH levels are high and decrease with thyroid hormone replacement, indicating a preserved thyroid axis inhibitory feedback system 4
- Non-thyroidal illness syndrome (NTIS) is characterized by low thyroid hormone levels and normal TSH levels, which may be due to sustained thyroid hormone supply to TRH neurons 4
- The mechanisms underlying TSH regulation in nonthyroidal illness are not fully understood and require further study 3, 5
Factors Influencing TSH Levels
- Severity of illness: critically ill patients may have decreased T4 levels, but normal free T4 concentrations 3
- Caloric deprivation: can lead to decreased T3 production and altered thyroid hormone binding 2, 3
- Inflammatory pathways: may play a role in non-systemic changes in thyroid hormone metabolism, but the evidence is limited 5
- Drug interactions: certain medications can affect TSH levels and thyroid function tests 2
Clinical Implications
- TSH measurement is a useful diagnostic tool for hypothyroidism, but may not always reflect the thyroid state in nonthyroidal illness 6
- Treatment with L-thyroxine may not be indicated in nonthyroidal illness, as the changes in thyroid hormone metabolism may be adaptive 3, 5
- Further research is needed to understand the mechanisms underlying TSH regulation in nonthyroidal illness and to determine the optimal treatment approach 5