Thyroid function tests are often requested in acutely ill patients. Awareness of the alterations in serum thyroid hormone levels that accompany acute illness will facilitate management.
CASE HISTORY
A woman of 71 was admitted after 24 hours of fever, headache and confusion. Two weeks previously she had consulted her general practitioner because of palpitations and weight loss of 10 kg, and thyroid function tests had been arranged. On admission she was thin, confused, pyrexial (38.7°C), tachycardic, tachypnoeic and hypotensive, with a moderate diffuse goitre and bilateral periorbital oedema. Chest X-ray showed bilateral basal bronchopneumonia. Arterial blood gases pointed to type 2 respiratory failure and serum creatinine was 224 μmol/L (reference range 40-125). On transfer to the intensive care unit she received physiotherapy, oxygen and intravenous antibiotics. She improved and was discharged home after 7 days.
Thyroid function tests on admission (day 1) did not confirm the clinical impression of hyperthyroidism. Serum thyroid stimulating hormone, < 0.03 mU/L (0.4-4.0), was suppressed but free thyroxine and free triiodothyronine, 7 pmol/L (12-26) and 1.4 pmol/L (< 5.5) respectively, were low. Investigations were repeated on days 2 and 14. After review of these results and of thyroid function tests arranged before admission (day — 14), Graves' hyperthyroidism was diagnosed. Carbimazole 20 mg twice daily was started on day 14 and thyroid function was monitored over the next four weeks (Table 1). Six weeks after admissions and taking carbimazole, the patient was well with normal thyroid function tests and chest X-ray.
Table 1.
Serial thyroid function tests. Day 1 is the day of admission. Treatment with carbimazole from day 14
|
Day
|
||||||
|---|---|---|---|---|---|---|
| -14 | 1 | 2 | 14 | 28 | 42 | |
| FT4 (pmol/L) | 31 | 7 | 8 | 29 | 25 | 10 |
| FT3 (pmol/L) | 7.7 | 1.4 | 2.5 | 7.3 | 4.6 | 4.0 |
| TSH (mU/L) | <0.03 | <0.03 | <0.03 | <0.03 | <0.03 | 0.19 |
COMMENT
The alteration in serum thyroid hormone concentrations that accompanies illness and starvation is known as nonthyroidal illness syndrome, or NTIS. Almost any severe illness or trauma or short-term episode of starvation causes a fall in serum triiodothyronine (T3) and most acutely ill patients in hospital have a low serum T3.1 T3 is largely derived from the conversion of thyroxine (T4) in peripheral tissues and this conversion is suppressed. Patients who only show a low serum T3 have the mildest form of NTIS and do not have signs of hypothyroidism. The hyperthyroid patient described here was critically ill on admission to the intensive care unit with bronchopneumonia and had low levels of both T3 and T4. This picture is due to reduced hormone production by the thyroid gland in addition to suppressed peripheral conversion of T4 to T3. Thyroid hormone entry into target cells is also impaired2 and less T3 is formed locally, with low tissue concentrations of T3 and T4.3
There was difficulty in interpreting thyroid function tests in this patient, who had symptoms and signs of hyperthyroidism before becoming acutely ill. Thyroid hormone concentrations, previously high, fell during the acute illness to an extent that made free T3 and free T4 measurement unreliable. There is one published report of a similar case.4
Interest in NTIS goes beyond the physiology. Although there is no evidence that small decreases in T3 increase the probability of death, large changes in thyroid hormone concentrations are associated with excess morbidity. In very ill patients both T3 and T4 are low and T4 concentrations reflect the severity of the illness. Patients with the lowest T4 have the worst prognosis.5,8 In a prospective study of 84 patients admitted to intensive care and coronary care units 22% had a low T4. Probability of death was approximately 50% when serum T4 fell below normal and 80% when it was more than 40% below normal.6 Would thyroid hormone treatment have been beneficial to some of these patients? A large prospective study would be needed to answer this question.
Although a slight increase in serum thyroid stimulating hormone (TSH) may be seen during recovery, TSH in severe NTIS is generally low or normal.7 The TSH is inappropriately low for the observed T3 and T4. There is therefore reason to believe that hypothalamic function is impaired in NTIS, with a low TSH depressing output of hormones by the thyroid gland. In intensive care, matters are often complicated by use of drugs such as dopamine8 and glucocorticoids,9 which reduce thyroid hormone concentrations by suppressing TSH production. Hypothyroidism as well as hyperthyroidism can be missed through the effect of fasting, critical illness or drugs on TSH secretion.10
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