NACB - Scientific Shorts
NACB - Scientific Shorts (formerly NACB Blog)
By Martin Kroll, MD, FACB

Most clinicians rely on TSH to screen for thyroid disease, especially hypothyroidism (1). As the methods for TSH have improved, the number of cases with abnormal TSH values, but minimal symptoms has increased (2). Most physicians have relied on a TSH range of 0.3 to 5.0 mU/L; but the American Association of Clinical Endocrinologists (AACE) has recently advocated tightening up this range (0.4 to 2.5 mU/L), reasoning that many patients have subclinical hypothyroidism (3). The proposal has stirred some controversy in the endocrine community.

We all know what will happen if we move the upper end of the reference interval for TSH from 5.0 to 2.5 mU/L. We will increase the sensitivity of the test, but decrease its specificity, because there is overlap between normal patients and those who are hypothyroid. Biological Variation complicates this picture by spreading a patient’s values over a range and making the values bounce around the patient’s true value. While the CV for FT4 is only 3.5%, TSH has a one-week CV of 19.3%. If a patient had a true TSH of 3.0 mU/L, their 95% confidence interval would range from 1.4 to 4.6 mU/L, thus confusing the issue. A central two-thirds confidence interval would range from 2.2 to 3.8 mU/L, which could still be misinterpreted. Luckily TSH has a positively skewed distribution with its tail pointing towards higher values among euthyroid patients, so many patients would have values not straddling the 3.0 value. But still relying on one value could result in misinterpretation. It is not a common practice to obtain three TSH values and average them, but that might be a much better approach. Should we try to influence our clinicians that an average is better than one result? We would have to persuade insurers that obtaining multiple samples is the correct course.

In addition, if we had adequate baselines on our patients, we could detect individual changes over time, which would be a convenient way to personalize medicine. Is this a good time to ask for more testing, given the current high cost of healthcare?


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Posted by
On 5/19/2011

What happend to diagnostic skills? Lab testing should be used to help confirm a diagnosis. If a patient has a TSH of 4.0 the clinician needs to decide if it is normal or subclinical Hypothyroidism. How many normal patients in the 2.5 to 5.0 range will be referred to Endocrinologists for expensive evaluations? 20% of the population moves from normal to abnormal with the new range. What percent is now misdiagnosed verus what percent is possibly misdiagnosed now? Maybe you need 3 reporting criteria: 0.4 - 2.5 Normal; 2.6 - 5.0 possible sub clinical Hypothyroidism; >5.0 Abnormal This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!

Posted by
On 5/19/2011

According to US preventative medicine the US ranks last among 19 industrialized countries in preventative care. So what? So perhaps testing TSH and establishing a personalized range per patient with a relatively inexpensive test would prevent the downstream excessive, expensive and often non-specific testing going on now. So spend a few more"pennies" on TSH and target more efficient use of "dollars" later on in the diagnostic algorithm.... This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!

About the Author
Martin Kroll, MD, FACB
Martin Kroll, MD, FACB 


1. Demers LM, Spencer CA. Laboratory support for the diagnosis and monitoring of thyoid disease. Laboratory Medicine Practice Guidelines. NACB vol. 13, 2002.

2. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease. Scientific review and guidelines for diagnosis and management. JAMA 2004;291:228-238.

3. Mariotti S. Solving the dilemma: what to do as a simple clinician. Endocrine Abstracts 2010;22:S13.4.