Results from a number of clinical studies reported in the past several years have implications for the management of thyroid disorders. Woeber reviews the findings of some of these studies and their implications for clinical practice.

In 1998, the American College of Physicians published guidelines on screening for thyroid disease in patients seen by primary care physicians for reasons unrelated to thyroid disease. Screening can be useful to identify overt or subclinical hypothyroidism or hyperthyroidism. A sensitive thyroid-stimulating hormone (TSH) test is recommended as a screening test in women more than 50 years of age. If the TSH level is less than 0.3 to 0.4 μU per mL (0.3 to 0.4 mU per L) or greater than 10 μU per mL (10 mU per L), determination of the free thyroxine (T₄) level is recommended. Screening is not recommended in women less than age 50 or in men because the prevalence of unsuspected symptomatic thyroid dysfunction is low in these populations.

Persons found to have subclinical hyperthyroidism (TSH of less than 0.3 to 0.4 μU per mL and normal T₄ and free triiodothyronine [T₃] levels) are at increased risk for atrial fibrillation, osteoporosis and progression to overt disease. The optimal management of patients without goiter or ocular findings of Graves' disease is uncertain, but the author recommends repeat measurements of TSH, T₄ and T₃ every six to 12 months.

Persons with subclinical hypothyroidism (TSH level of greater than 5 μU per mL [5 mU per L] and a normal T₄ level) are at increased risk for hypercholesterolemia and progression to overt hypothyroidism. The effectiveness of treatment of subclinical hypothyroidism is uncertain; three small unrandomized trials yielded conflicting results. Observation is appropriate for persons with TSH levels between 5 and 10 μU per mL. A TSH of greater than 10 μU per mL or a high antithyroid antibody titer is associated with an increased risk of complications, and levothyroxine therapy may be appropriate.

The author notes that previous studies suggested that the addition of thyroid hormone to long-term methimazole or propylthiouracil therapy in patients with Graves' disease increased the likelihood of remission when antithyroid drug therapy was discontinued. More recently, several large randomized studies have failed to confirm that levothyroxine promotes remission in patients receiving antithyroid therapy. The author believes the concomitant use of thyroid hormone in these patients is unjustified, especially in light of the higher likelihood of serious adverse effects with higher doses of antithyroid drugs. Evidence supports the use of methimazole over propylthiouracil. Methimazole has been associated with higher cure rates, and this agent requires less frequent doses and may carry a lower risk for agranulocytosis.

With respect to the treatment of hypothyroidism, the author asserts that studies pointing to improved efficacy with the addition of levotriiodothyronine require further confirmation before this hormone is added to thyroid replacement therapy. Variations in the potency among compounds that contain both hormones limit the utility of this approach. Combined preparations may become the choice in the future when these preparations are more standardized. However, if an optimal state of well-being is not achieved with levothyroxine alone, the author believes consideration can be given to replacing 50 μg of the daily dose of levothyroxine with 5 μg of levotriiodothyronine twice daily.

Three studies found that the prevalence of thyroid carcinoma was similar (i.e., about 5 percent) in palpable and nonpalpable nodules. Ultrasonographically guided fine-needle aspiration biopsy of thyroid nodules should be performed if the patient has a history of radiation to the head, neck or upper chest, or a family history of thyroid carcinoma; if the diameter of the nodule is 1.0 cm or greater; or if suspicious ultrasonographic characteristics are present. In the absence of these findings, follow-up every six to 12 months is appropriate because most occult carcinomas are papillary and rarely aggressive.

TSH-suppressive therapy for benign solitary thyroid nodules is controversial. The effectiveness of such therapy in reducing nodule size is uncertain. Pooled data from seven trials show that nodule volume decreased by more than 50 percent in 25 percent of 242 patients who received levothyroxine and in 8 percent of the control group. In the author's opinion, a one-year course of TSH-suppressive therapy can be started in younger patients and continued only if nodule size has decreased. In older patients, in whom thyroid supplementation may decrease bone mineral density or increase the risk of atrial fibrillation and cardiac hypertrophy, the potential adverse effects of TSH suppression may outweigh any benefit.