A 38-year-old female with no previous history of any thyroid problem is admitted in the ICU with septic shock. Avoid doing TFT in a sick patient unless indicated. Patient is on ventilator for past 3 days and has thyroid profile as below: • T3–66 ng/dL (75–200 ng/dL) • T4–3 μg/dL (4.5–11.5 μg/dL) • TSH 0.2 μIU/L (0.45–4.5 μIU/L) A consultation is sent to endocrinology department for treatment of probable hypothyroidism? What is the interpretation of these results? The patient’s differential diagnosis could be: • Secondary hypothyroidism • Sick euthyroid syndrome or nonthyroid illness syndrome (NTIS) The diagnosis of sick euthyroid syndrome is kept as the first possibility in this case because she has no prior history of thyroid problem and has no history of being treated for hypothyroidism in the past. Prior history of deranged TFT can be helpful in reaching a diagnosis. The secondary hypothyroidism is also kept as a possibility so to evaluate for any other pituitary hormone deficiency a random serum cortisol is done along with prolactin, FSH and LH. There is no prior history of pituitary problem in this patient. The FT4 and FT3 are also ordered in this patient. The patient’s FT4 is 1 ng/L (0.8–2 ng/L) and FT3 is 2 pg/mL (2.3–4.2 pg/mL). The serum cortisol is elevated and it is 52 μg/dL because of the stress state and during severe stress serum cortisol can be more than 50 μg/dL and it should be at least more than 25 μg/dL and prolactin is also in the high normal range (36 ng/mL) which is also probably a stress response. Rest of the pituitary hormones are in the normal range. The patient was normally menstruating till the last month so it was also an indirect evidence that the gonadotropic axis is intact. The patient improves over a period of time in the next 2 weeks and thyroid profile is repeated after 2 weeks where it shows the following results:
• FT4—1.2 ng/mL
• T4—5 ug/dL
• T3—78 ng/dL
• TSH—5.6 μ IU/mL
What is the pathophysiology of sick euthyroid syndrome?
Medicine
It is postulated that in sick euthyroid syndrome inhibition of 5’-deiodinase enzyme is the main mechanism. The initial pathophysiology is acute inhibition of the enzyme type 1, 5’-deiodinase which leads to decreased conversion of T4 to T3 in extrathyroidal tissue. The sick state causes a reduced activity of 5’ monodeiodinases and increase in the activity of 5’ deiodinase which results in reduced conversion of T4 to T3 and increased conversion of T4 to rT3 which is also called the inactivating pathway. The changes in serum FT3 and FT4 may be modest compared to the changes seen in the levels of T3 and T4. The deiodination of inner ring T4 is not affected at all so the concentration of reverse T3 increases while the breakdown of rT3 is decreased as the type 1, 5’-deiodinase is inhibited during acute illness. It has been shown in knockout mice that the fall of T3 in sick state may occur independently of the DI and D2 enzymes and the fall in T3 levels precede the onset of hepatic D1 inhibition. The thyrotropin levels decrease possibly secondary to decrease in leptin caused by malnutrition and there is a localized increase in hypothalamic T3 catalyzed by altered expression of hypothalamic iodothyronine deiodinases D2 and D3. 5’-deiodinase converts rT3 to T2 and its reduced activity slows the clearance of rT3 and thus its level rises in the blood. Deiodinases play a role in thyroid hormone metabolism not only in the periphery but also in the hypothalamus and the pituitary and thus in the alterations accompanying NTIS.
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