A 66-year-old man with abnormal thyroid function tests

Cleveland Clinic Journal of Medicine. 2019 October;86(10):666-675 | 10.3949/ccjm.86a.19024
October 1, 2019|Cleveland Clinic Journal of Medicine
Yazan N. Alhalaseh, MD;Zaid A. Abdulelah, MD;Ahmad O. Armouti, MD;Ayman A. Zayed, MD, MSc, FACE, FACP
Author and Disclosure Information

Yazan N. Alhalaseh, MD
Department of Internal Medicine, King Hussein Cancer Center, Amman, Jordan

Zaid A. Abdulelah, MD
Istishari Hospital, Amman, Jordan

Ahmad O. Armouti, MD
King Hussein Medical Center, Amman, Jordan

Ayman A. Zayed, MD, MSc, FACE, FACP
Professor of Medicine and Chief, Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, Jordan University Hospital, Amman, Jordan

Address: Ayman A. Zayed, MD, MSc, FACE, FACP, Department of Internal Medicine, Jordan University Hospital, Queen Rania Street, Amman, Jordan, 11942; baraaayman@gmail.com

Release date: October 1, 2019
Expiration date: September 30, 2020
Estimated time of completion: 1 hour

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BETA-BLOCKERS, BETA-AGONISTS AND THYROID FUNCTION

While there is general agreement that beta-adrenergic antagonists (beta-blockers) do not affect the serum TSH concentration, conflicting data have been reported concerning their effect on other thyroid function tests. This may be due to several factors, including dose, duration of therapy, the patient’s thyroid status, and differences in laboratory methodology.30

In studies of propranolol, serum total T4 concentrations did not change or were increased with daily doses of 160 mg or more in both euthyroid participants and hyperthyroid patients31–33; serum total T3 concentrations did not change or were decreased with 40 mg or more daily34; and serum reverse T3 concentrations were increased with daily doses of 80 mg or more.31 It is most likely that propranolol exerts these changes by inhibiting D1 activity in peripheral tissues.

Furthermore, a significant decrease in serum total T3 concentrations was observed in hyperthyroid patients treated with atenolol 100 mg daily, metoprolol 100 mg daily, and alprenolol 100 mg daily, but not with sotalol 80 mg daily or nadolol (up to 240 mg daily).35,36

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On the other hand, beta-adrenergic agonists have not been reported to cause significant changes in thyroid function tests.37

SUBCLINICAL THYROTOXICOSIS OR HASHIMOTO THYROIDITIS?

Our patient’s thyroid function test results are more likely due to his nonthyroidal illness and glucocorticoid therapy, as there is no clinical evidence to point to a hypothalamic-pituitary disorder accounting for true central hypothyroidism.

The other options mentioned in question 2 are unlikely to explain our patient’s thyroid function test results.

Subclinical thyrotoxicosis is characterized by suppressed serum TSH, but both serum free T4 and total T3 remain within the normal reference ranges. In addition, the serum TSH level may help to differentiate between thyrotoxicosis and nonthyroidal illness. In the former, serum TSH is usually suppressed (< 0.01 mU/L), whereas in the latter it is usually low but detectable (0.05– 0.3 mU/L).38,39

Hashimoto thyroiditis is a chronic autoimmune thyroid disease characterized by diffuse lymphocytic infiltration of the thyroid gland. Almost all patients with Hashimoto thyroiditis have elevated levels of antibodies to thyroid peroxidase or thyroglobulin.40 Clinically, patients with Hashimoto thyroiditis can either be hypothyroid or have normal thyroid function, which is not the case in our patient.

CASE CONTINUED

An endocrinologist, consulted for a second opinion, agreed that the patient’s thyroid function test results were most likely due to his nonthyroidal illness and glucocorticoid therapy.

3. In view of the endocrinologist’s opinion, which should be the next step in the management of the patient’s thyroid condition?

  • Start levothyroxine (T4) therapy
  • Start liothyronine (T3) therapy
  • Start N-acetylcysteine therapy
  • Start thyrotropin-releasing hormone therapy
  • Remeasure thyroid hormones after full recovery from his acute illness

It is not clear whether the changes in thyroid hormone levels during an acute illness are a pathologic alteration for which thyroid hormone therapy may be beneficial, or a physiologic adaptation for which such therapy would not be indicated.41

However, current data argue against thyroid hormone therapy using T4 or T3 for patients with nonthyroidal illness syndrome (also called euthyroid sick syndrome).42 Indeed, several randomized controlled trials showed that thyroid hormone therapy is not beneficial in such patients and may be detrimental.41,43

Therapies other than thyroid hormone have been investigated to ameliorate thyroid hormone abnormalities in patients with nonthyroidal illness. These include N-acetylcysteine, thyrotropin-releasing hormone therapy, and nutritional support.

Some studies showed that giving N-acetyl­cysteine, an antioxidant, increased serum T3 and decreased serum reverse T3 concentrations in patients with acute myocardial infarction.44 Nevertheless, the mortality rate and length of hospitalization were not affected. Further studies are needed to know whether N-acetylcysteine therapy is beneficial for such patients.

Similarly, a study using a thyrotropin-releasing hormone analogue along with growth hormone-releasing peptide 2 showed an increase in serum TSH, T4, and T3 levels in critically ill patients.45 The benefit of this therapy has yet to be determined. On the other hand, early nutritional support was reported to prevent thyroid hormonal changes in patients postoperatively.46

Measuring thyroid hormone levels after full recovery is the most appropriate next step in our patient, as the changes in thyroid hormone concentrations subside as the acute illness resolves.47