Screening and Treatment of Subclinical Hypothyroidism or Hyperthyroidism

A mildly elevated thyroid stimulating hormone (TSH - also called thyrotropin) concentration is the most common thyroid function test abnormality encountered in everyday practice. Most patients who have a mildly elevated TSH have a normal free thyroxine (T4) level. The treatment of such patients is controversial, particularly when they have few or no symptoms and no other clinical evidence of thyroid disease. Less frequently, clinicians encounter patients who have a low or undetectable serum TSH and normal triiodothyronine (T3) and free T4 levels. The management of these patients is also unclear. The main question addressed in this review was whether individuals who have mildly abnormal TSH values will either benefit from or be harmed by screening and potential subsequent treatment. We also addressed the question of whether the primary care clinician should screen for thyroid function in patients seen in general medical practice who have no specific indication for thyroid testing and who come to the clinician for other reasons. For the purposes of this review, we considered overt thyroid disease to be a well-defined clinical entity that has clear signs and symptoms, and thus, outside the scope of our review. In order for a condition to be a good candidate for screening in the general population, several conditions need to be met. First, the condition needs to be relatively prevalent, having a significant impact on the health of the population or an easily identified special population. Second, there needs to be a test that is readily available to the general population that is of reasonable cost and accuracy and is acceptable to individuals to undergo. Finally, there needs to be an intervention that is of reasonable cost and tolerability that when administered in a timely fashion will alter the disease state to prevent morbidity and/or morality. The Helfand (2004) review established that subclinical thyroid disease is quite prevalent; may be responsible for morbidity; and that the serum TSH test is a readily available, reliable, and acceptable test to detect the condition with a sensitivity above 98 percent and specificity greater than 92 percent. However, in 2004, it remained unclear whether, if detected, treating patients with subclinical thyroid disease would reduce morbidity. As evidence of prevalence, test yield, and test performance have already been adequately established,1 this current review focuses on whether new evidence demonstrates that treatment improves clinically important outcomes in adults with screen-detected thyroid disease. Key Questions include: Key Question 1. Does screening for subclinical thyroid dysfunction reduce morbidity or mortality? Key Question 2. What are the harms of screening? Specifically, how frequently and how severely do patients screened for subclinical thyroid dysfunction experience adverse psychological impacts or other harms of workup from screening? Key Question 3. Does treatment of patients with subclinical hypothyroidism or subclinical hyperthyroidism detected by screening affect outcomes? We were primarily interested in the comparative effectiveness of a strategy of routine treatment versus active surveillance to prevent the possible complications of untreated subclinical thyroid dysfunction. Key Question 4. What are the harms of treatment of subclinical hypothyroidism and subclinical hyperthyroidism? Specifically, what are the consequences of overtreatment, including effects on bone mineral density and incidence of atrial fibrillation, and how frequently do they occur?