Pitfalls to Avoid While Interpreting Thyroid Function Tests: Five Illustrative Cases

Michael J. Fowler, MD, Aaron F. Pannone, BA, Lewis S. Blevins, Jr., MD


South Med J. 2002;95(5) 

In This Article

Case 5

A 56-year-old man was evaluated in the surgical intensive care unit for abnormal thyroid function tests. He was admitted 3 weeks previously for an elective 3-vessel coronary artery bypass grafting, but developed severe postoperative pneumonia for which he required intravenous antibiotic therapy and reintubation a week after the surgery. After extubation, the patient remained extremely somnolent 2 days after all sedatives were withdrawn. As part of an altered mental status evaluation, thyroid function tests were ordered. The serum TSH level was 0.7 µU/mL, free T4 level was 0.5 ng/mL, and total T3 level was 60 ng/dL. Endocrine consultation was sought to evaluate the possibility of central hypothyroidism. Physical examination revealed a middle-aged man who was arousable but somnolent. His thyroid was normal in consistency and size, and there were no palpable nodules. He could not cooperate with visual-field testing, but his skin was normal in texture and his reflexes were normal in amplitude and rate. The remainder of his physical examination was remarkable only for wounds consistent with his surgical procedure.

A decision was made to withhold treatment with levothyroxine, since the thyroid function test abnormalities were thought to be due to nonthyroidal illness (NTI). His mental status improved over the next 4 days, and he was subsequently discharged from the intensive care unit. Thyroid function tests at the conclusion of his hospitalization demonstrated a TSH level of 7.1 µU/mL and a free T4 level of 1.5 ng/mL. Six weeks later, the laboratory values were normal in the outpatient setting.


This case illustrates a classic example of the NTI syndrome. This syndrome may constitute an adaptive response of the neuroendocrine system to illness or trauma and is seen in as many as 70% of hospitalized patients. It has been described in patients with myocardial infarction,[26] surgery,[27] bone marrow transplantation,[28] and starvation.[29] There are 2 major subtypes of NTI: a low T3 state and a low T4 state. Although they are described separately, they are likely a continuum of the same pathophysiologic or adaptive process but correspond to differing severities of NTI.

The low T3 state is the most common type of NTI seen in clinical practice, and is accompanied by a high reverse T3 level. It may occur in virtually any illness, and the thyroid hormonal abnormalities may be striking. Serum total T3 concentrations may drop to as low as 60% of the normal value, while free T4 concentrations may fall to 40% of baseline.[30] These changes are believed to be due to inhibition of the type 1 iodothyronine deiodinase that converts T4 to T3. As a result, T3 levels fall and T4 levels may remain normal. Because the same enzyme also deiodinates reverse T3, reverse T3 levels rise.[30] As illness severity increases, reverse T3 levels remain stably elevated, while serum concentrations of T3 progressively decline. The low T3 state itself is not believed to be associated with any particular increased mortality, except in patients with end-stage human immunodeficiency virus disease.

The low T4 state, almost always in association with a low level of T3, represents the other major form of NTI. Down-regulation of TSH secretion by the anterior pituitary and/or a decrease in the sensitivity of the thyrotrophs to TRH may account for these changes.[31] Reverse T3 levels remain normal or elevated in this disorder, and T3 and T4 levels may decline even further. Detectable levels of TSH usually distinguish those with NTI from those with true hyperthyroidism, whose TSH levels are usually suppressed.[32] In addition to corresponding with worsening illness, low T4 and T3 levels correlate with increased mortality.[33]

Recovery from NTI has been well documented. Levels of T4 tend to normalize over a period of approximately 4 days, although some patients may recover more slowly. During the recovery phase, TSH concentrations may rise between twofold and 13-fold. Since the rise in TSH level typically occurs before elevations in T4 level, recovery from NTI is likely TSH-mediated.[34] This patient was clearly in the recovery phase of NTI at the conclusion of his hospitalization.

Treatment of low T4 and T3 levels during NTI does not appear to be necessary, but controversy over replacement therapy does exist among experts. Administration of T4 to severely ill patients further decreases TSH values, and yet neither increases T3 levels nor decreases mortality.[35] Administration of T3 to critically ill burn victims also did not affect mortality.[36,37,38] Close monitoring while treating the underlying disorders and reevaluation of thyroid functions 6 weeks after hospital discharge is recommended, since this approach usually permits one to differentiate those with NTI from those who have thyroid disease.

CME Information

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