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If the distribution is extrapolated to be Gaussian, then the upper limit for the 97.5th percentile will be 2.5 mIU/L. The serum TSH distribution curve is not Gaussian there is a tail end at the upper limits of normal. 9 After exclusion of persons with goiter, antithyroid antibodies, and a family history of thyroid disease, the mean serum TSH is 1.5 mIU/L. 6, 8 The strongest argument in favor of lowering the upper limit of normal for the serum TSH level is the higher level of antithyroid antibodies detected in persons with a serum TSH level between 3.0 and 5.0 mIU/L and the higher rate of progression to clinical thyroid disease. 0 or even 2.5 mIU/L has been proposed, 7, 9 but such proposals have been met with substantial critique. Lowering the upper limit of normal for the serum TSH level from 5.0 to 3. WHAT IS THE UPPER LIMIT OF NORMAL FOR THE SERUM TSH LEVEL? Some evidence indicates that levothyroxine replacement improves some parameters of lipid profiles and left ventricular function. Data on health-related quality of life and symptoms did not show significant differences between intervention groups. 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. 11 Some authors argue for routine 10 and some for selective 5 therapy. 5, 10 However, management of patients with a serum TSH level of less than 10 mIU/L is controversial. 6- 9 When the TSH level is above 10 mIU/L, levothyroxine therapy is generally agreed to be appropriate. The clinical importance of and therapy for mild elevation of serum TSH (<10 mIU/L) 5 and the exact upper limit of normal for the serum TSH level remain subjects of debate. Transient SCH may occur after episodes of postpartum, silent, and granulomatous thyroiditis. 1 Previous radioiodine therapy, thyroid surgery, and external radiation therapy can also result in mild thyroid failure. However, the most common cause of elevated TSH is autoimmune thyroid disease. 2 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.īefore 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. 2 After the sixth decade of life, the prevalence in men approaches that of women, with a combined prevalence of 10%. 2, 3 The prevalence increases with age and is higher in women. Subclinical hypothyroidism or mild thyroid failure is a common problem, with a prevalence of 3% to 8% in the population without known thyroid disease.

1 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. 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.

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1 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). 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.

SCH = subclinical hypothyroidism TPO = thyroperoxidase TSH = thyroid-stimulating hormone

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