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

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

Disclosures

South Med J. 2002;95(5) 

In This Article

Case 3

A 36-year-old man presented for evaluation of abnormal thyroid functions. He was first diagnosed with Hashimoto's thyroiditis 3 years before consultation, at which time he exhibited symptoms and signs of profound hypothyroidism. Since that time, he had been treated with increasing doses of levothyroxine, due to persistent symptoms of hypothyroidism and elevated TSH levels. His serum TSH level 8 months before consultation was 79 µU/mL (normal, 0.3 to 5.0 µU/mL). Physical examination revealed a man with no apparent thyroid eye disease, a firm thyroid with a palpable pyramidal lobe and isthmus, no cervical adenopathy, delayed deep tendon reflexes, and no tremor. His mental status was normal. Laboratory values were TSH 96.6 µU/mL, free T4 >8 ng/dL (normal, 0.60 to 5.00 ng/dL), and total T3 95 ng/dL (normal, 30 to 160 ng/dL).

Based on these clinical and laboratory findings, the free thyroxine level was measured by equilibrium dialysis and found to be low. The patient responded well to therapy with increased thyroxine and supplementation with triiodothyronine.

Discussion

This case illustrates one of the many caveats of serologic thyroid testing in patients with autoimmune thyroiditis. Autoimmune thyroid disease is common in western populations, and represents the most common cause of thyroid dysfunction in the United States.[14,15] Graves' disease and Hashimoto's thyroiditis are 2 forms of autoimmune thyroid disease that have different manifestations. While the autoimmune destruction characteristic of Hashimoto's thyroiditis generally leads to eventual hypothyroidism, hyperthyroidism characterizes Graves' disease. Although the genesis of autoimmunity remains incompletely understood, the advent of serum antibody assays has dramatically improved our ability to diagnose these disorders, and has also offered insight into other laboratory testing abnormalities.

A number of antibody studies are utilized to diagnose and classify autoimmune thyroid diseases and may help predict the long-term course of the disorders.[16,17] Antithyroglobulin antibodies and antithyroperoxidase antibodies have both been utilized to diagnose the presence of autoimmune thyroid disease or the likelihood of progression to autoimmune thyroiditis.[18] Antithyroglobulin antibodies are specifically directed against the thyroglobulin stored in thyroid follicles, which is endocytosed and lysed within the follicular cells of the thyroid to liberate thyroxine. Antithyroperoxidase (antimicrosomal) antibodies, however, likely target the thyroperoxidase enzyme present on the cell membrane of thyroid follicular cells.[19] These antibodies are present in 90% of patients with Hashimoto's disease and two thirds of patients with Graves' disease. Since the antimicrosomal antibodies fix complement and are directly cytotoxic, they may be responsible for the majority of autoimmune destruction in most autoimmune thyroid disease.

Thyroid-stimulating immunoglobulin (TSI) is the autoantibody believed to be responsible for Graves' disease. This immunoglobin binds to the TSH receptor of the thyroid follicular cell, and in doing so stimulates the TSH receptor, increases intracellular cyclic adenosine monophosphate (AMP) production, and leads to thyroid glandular hyperactivity.[16] Since the assay for TSI is readily available, detection of this antibody may help differentiate Graves' disease from other causes of hyperthyroidism.

Anti-thyroid-hormone antibodies may be present in any patient with autoimmune thyroiditis. In fact, as many as 40% of patients with Hashimoto's disease may have detectable levels of anti-thyroid-hormone antibodies.[20] Although the clinical implications probably vary based upon the affinity of a particular patient's antibodies for T4, the existence of these antibodies creates a potential pitfall in thyroid laboratory testing and treatment.[21] As shown by this case, anti-thyroid-hormone antibodies may interfere with measurements and thyroid hormone supplementation. When measured by radioimmunoassay, anti-thyroid-hormone antibodies may generate an artificially elevated free thyroxine measurement, as well as lead to increased rate of metabolic clearance of thyroid hormone itself. Patients often require doses of thyroxine far above the amount predicted for their weight. Free thryroxine, measured by equilibrium dialysis, avoids this laboratory testing inaccuracy. Administration of higher doses of T4 and/or T3 increases the effective hormone concentrations in the bloodstream and therefore should return the patient to a euthyroid state.

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