DIAGNOSIS
The diagnosis of hypothyroidism is made on the basis of laboratory test results, but symptomatology can help guide the clinician to the appropriate laboratory workup. Symptoms alone, when laboratory values are within normal limits or even at the high end of the normal range, do not support a hypothyroidism diagnosis. In such a case, a differential diagnosis should be pursued.
Since overt symptoms of hypothyroidism are rare, clinicians may wonder if they should screen all their patients for hypothyroidism. Current recommendations, as set forth in the joint American Thyroid Association (ATA) and American Association of Clinical Endocrinologists (AACE) clinical practice guidelines, support “aggressive case finding” rather than universal screening because as yet, there is no consensus on screening guidelines.4 The ATA recommends screening all adults at age 35 and then every five years thereafter.6 In contrast, the AACE recommends routine TSH measurement in “older” patients, particularly women.7
There is, however, compelling evidence for testing patients with any of the following4
• An autoimmune disease
• Pernicious anemia
• A first-degree relative with autoimmune thyroid disease
• An abnormal thyroid examination
• Past radiation to the thyroid gland, including radioactive iodine therapy for hyperthyroidism
• Past external beam radiotherapy for head and neck malignancies
• History of thyroid surgery
• History of thyroid dysfunction
• One of the diagnoses listed in Table 1.
It is also suggested that patients with psychiatric disorders and patients taking amiodarone or lithium be screened.4
TREATMENT
The standard evidence-based treatment for hypothyroidism is hormone replacement with levothyroxine.4 This is a Grade A recommendation in the ATA/AACE joint guidelines. Levothyroxine is bioequivalent to T4 in the body and has a half-life of approximately six to seven days. It is stable and easily adjusted by monitoring TSH levels; adverse reactions or complications are minimal. The starting dose of levothyroxine is 1.6 µg/kg/d for both primary and secondary (central) hypothyroidism.
Dose increases are made in 12.5 or 25 µg increments. In primary hypothyroidism, TSH levels should be monitored to determine the need for dose adjustments. FT4 need not be checked unless there is a discrepancy in the TSH levels.4 In secondary hypothyroidism, TSH levels will always remain normal or low, and FT4 should be used to monitor therapy. Levels should be measured four to eight weeks after initiation of treatment or after subsequent dose adjustments.
Overt Hypothyroidism (Primary or Secondary)
All patients with symptomatic, overt hypothyroidism and an elevated TSH level should be treated. Treatment is lifelong, and the goal is to reduce patient symptomatology, improve well-being, and prevent complications. The treatment target is a TSH level in the normal range, approximately 0.45 to 4.5 mIU/L on most laboratory assays. However, NHANES III data revealed that the mean serum TSH level in the normal population is 1.5 mlU/L.2 Based on this fact and on their experience, many clinicians would argue that a more appropriate goal is a TSH target in the midnormal range, such as 0.5 to 2.5 mlU/L. There is little evidence to support a low- or subnormal TSH target in the treatment of hypothyroidism.4
Subclinical Hypothyroidism
For patients with the more common subclinical hypothyroidism (an elevated TSH level without symptoms), the benefits of treatment are less clear. It is suggested that if the TSH level is > 10 mIU/L, even patients without symptoms should be treated because risk for overt hypothyroidism is high.8 A TSH level > 10 mIU/L has also been shown to increase the patient’s coronary artery disease (CAD) risk.8 For individuals with TSH levels in the 4.5 to 10 mIU/L range who feel well and have no hypothyroid symptoms, the evidence is less clear. Treatment may be beneficial, but this has not been determined definitively.4 A watch-and-wait approach may be taken with these patients; if symptoms develop, treatment should be considered.
Patients with subclinical hypothyroidism generally do not require full replacement doses (ie, a starting dosage of 1.6 µg/kg/d). A dosage of 25 to 75 µg/d is typically sufficient to achieve goal TSH levels. For patients older than 60 with no CAD and for all patients with CAD, lower starting dosages of 50 µg/d and 12.5 to 25 µg/d, respectively, are recommended.4
Normal TSH, Positive TPO in Pregnancy
Current clinical evidence does not support treatment of patients who have normal TSH levels (2.5 to 4.5 mIU/L) but who are positive for TPO antibodies.4 The exception is pregnant women or those considering pregnancy. Research suggests that the rates of spontaneous miscarriage and preterm labor are higher in TPO-positive women in this TSH range, so treatment may reduce these risks.4
On the next page: Additional treatment considerations >>