Subclinical Hypothyroidism: An Update for Primary Care Physicians

Subclinical hypothyroidism (SCH) is defined as a serum thyroid-stimulating hormone (TSH) level above the upper limit of normal despite normal levels of serum free thyroxine. Serum TSH has a log-linear relationship with circulating thyroid hormone levels (a 2-fold change in free thyroxine will produce a 100-fold change in TSH). Thus, serum TSH measurement is the necessary test for diagnosis of mild thyroid failure when the peripheral thyroid hormone levels are within normal laboratory range. The individual range for peripheral thyroid hormones is narrower than the population reference laboratory range; therefore, a slight reduction within the normal range will result in elevation of serum TSH above the normal range.

Subclinical hypothyroidism or mild thyroid failure is a common problem, with a prevalence of 3% to 8% in the population without known thyroid disease. The prevalence increases with age and is higher in women. After the sixth decade of life, the prevalence in men approaches that of women, with a combined prevalence of 10%. Antithyroid antibodies can be detected in 80% of patients with SCH, and 80% of patients with SCH have a serum TSH of less than 10 mIU/L.

Before diagnosis of SCH, other causes of an elevated TSH level, such as recovery from nonthyroidal illness, assay variability, presence of heterophile antibodies interfering with the TSH assay, and certain cases of central hypothyroidism with biologically inactive TSH and thyroid hormone resistance, should be excluded. However, the most common cause of elevated TSH is autoimmune thyroid disease. Previous radioiodine therapy, thyroid surgery, and external radiation therapy can also result in mild thyroid failure. Transient SCH may occur after episodes of postpartum, silent, and granulomatous thyroiditis.

The clinical importance of and therapy for mild elevation of serum TSH (<10 mIU/L) and the exact upper limit of normal for the serum TSH level remain subjects of debate. When the TSH level is above 10 mIU/L, levothyroxine therapy is generally agreed to be appropriate. However, management of patients with a serum TSH level of less than 10 mIU/L is controversial. Some authors argue for routine and some for selective therapy. A recent 2007 meta-analysis of 14 randomized clinical trials enrolling a total of 350 patients concluded that levothyroxine replacement therapy for SCH does not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not show significant differences between intervention groups. Some evidence indicates that levothyroxine replacement improves some parameters of lipid profiles and left ventricular function.