TSH (Thyroid Stimulating Hormone) Reference Range Wars

And What Does It All Mean For You and Your Health?

Doctor taking blood sample of a man
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A battle over the reference range for the Thyroid Stimulating Hormone (TSH) test was waged in the early 2000s. The controversy was important for patients and practitioners as this test is relied upon for diagnosis and management of thyroid disease.

There is ongoing controversy about whether reliance on the TSH test -- and excluding clinical symptoms and other tests such as Free T4, Free T3, and antibodies tests -- is medically sound.

That is a controversy that is unlikely to be decided for years. Most physicians rely almost exclusively on the TSH test to detect thyroid disease, and monitor the effectiveness of treatment.

Surprisingly, there is complete disagreement within the community as to what constitutes the "normal range" for TSH.

Stay up-to-date with evolving reference ranges. MedlinePlus from the U.S.National Library of Medicine is kept updated with the current normal values.

What is a Reference Range?

Reference range is a critical component, and the validity of the entire TSH test as diagnostic tool depends on it. A TSH reference range is obtained by taking a large group of people in the population, measuring their TSH levels, and calculating a mean value. Supposedly, these people should be free of thyroid disease, so that the level represents the mean TSH of a typical thyroid disease-free person in the population.

The reference range is what determines whether or not thyroid disease is even diagnosed at all, much less treated, and when it is diagnosed, how it is treated.

Currently, at most laboratories in the U.S., the reference range for TSH tests is approximately 0.5 to 5.0. Depending on the lab, you may seem some variations, i.e., 0.4 to 5.5, or 0.6 to 5.7, etc., but generally, 0.5 to 5.0 is considered typical of many labs.

Typically, doctors interpret levels below 0.5 as indicative of hyperthyroidism (an overactive thyroid), and levels above 5.0 as indicative of hypothyroidism (an underactive thyroid.)

Changing the Reference Range

After noticing that patients who had TSH levels in the higher end of the normal range tended to go on to develop hypothyroidism more often than those in the lower end of the spectrum, researchers delved more fully into understanding how valid were the reference ranges in use. They found that the upper TSH normal range has traditionally included people who have mild thyroid disease, and their higher TSH levels skewed the standard curve, potentially making the reference range wider than it should be, and excluding some people who legitimately had a thyroid condition.

These findings led to the recommendation in January 2003 by the American Association of Clinical Endocrinologists (AACE) that doctors "consider treatment for patients who test outside the boundaries of a narrower margin based on a target TSH level of 0.3 to 3.0.

AACE believes the new range will result in proper diagnosis for millions of Americans who suffer from a mild thyroid disorder, but have gone untreated until now."

In a statement from the AACE, Hossein Gharib, MD, FACE, and president of AACE at the time, said, "The prevalence of undiagnosed thyroid disease in the United States is shockingly high...The new TSH range from the AACE guidelines gives physicians the information they need to diagnose mild thyroid disease before it can lead to more serious effects on a patient's health - such as elevated cholesterol, heart disease, osteoporosis, infertility, and depression."

AACE cited as evidence the guidelines issued by the National Academy of Clinical Biochemistry, part of the Academy of the American Association for Clinical Chemistry (AACC), and presented in their Laboratory Medicine Practice Guidelines for the Diagnosis and Monitoring of Thyroid Disease. Late in 2002, the group concluded that "it is likely that the current upper limit of the population reference range is skewed by the inclusion of persons with occult thyroid dysfunction." In their guidelines, the National Academy of Clinical Biochemistry reported that: "In the future, it is likely that the upper limit of the serum TSH euthyroid reference range will be reduced to 2.5 mIU/L because 95% of rigorously screened normal euthyroid volunteers have serum TSH values between 0.4 and 2.5 mIU/L." They also stated that "a serum TSH result between 0.5 and 2.0 mIU/L is generally considered the therapeutic target for a standard L-T4 replacement dose for primary hypothyroidism."

What Would a Narrower Range Mean for Patients?

At the time of the announcement, almost three years ago, AACE estimated that the new guidelines would double the number of people who have abnormal thyroid function, bringing the total to as many as 27 million, up from 13 million thought to have the condition under the old guidelines. These new estimates would make thyroid disease the most common endocrine disorder in North America, far outpacing diabetes.

The announcement from AACE was seen by many as a long-overdue and much-needed improvement in the level of awareness of endocrinologists. After decades of denying that patients within the normal range of TSH could in fact have a thyroid condition, they were acknowledging what patients and advocates had been saying quite vocally for years: that the high and low end of the TSH normal range were not, in fact, normal for most people.

"...using a TSH upper normal range of 5.0, approximately 5% of the population is hypothyroid. However, if the upper portion of the normal range was lowered to 3.0, approximately 20% of the population would be hypothyroid..."

More recently, researchers have looked at an important question: If the normal TSH range were narrowed, as has been recommended by AACE and the National Academy of Clinical Biochemistry, what are the implications? One 2005 study found that using a TSH upper normal range of 5.0, approximately 5% of the population is hypothyroid. However, if the upper portion of the normal range was lowered to 3.0, approximately 20% of the population would be hypothyroid! According to another study, an additional 12.8 to 16 million people would be diagnosed with hypothyroidism if the TSH upper limit was 3.0, and an additional 5.4% to 6.3% of the population --- 10.8 to 12.6 million -- would be diagnosed as hypothyroid if the upper range for TSH was 2.5.

Clearly, these narrower ranges have huge implications for millions of people who are not being diagnosed or treated, because their test results are being evaluated according to the old reference range.

Untreated thyroid disease can severely compromise quality of life, and in some cases even be fatal. Untreated thyroid disease can cause or contribute to numerous debilitating symptoms and conditions, including, among others:

  • weight problems and obesity
  • exhaustion and fatigue
  • depression and anxiety disorders
  • heart disease
  • stroke
  • infertility
  • miscarriage
  • birth defects

Some Experts Adopt the New Range

Interestingly, however, in the past three years, most laboratories in the U.S., despite what are clear communications from both AACE and the Laboratory Medicine Practice Guidelines, have not revised their TSH reference range, and remain with the 0.5 to 5.0 range as their "normal range."

Some practitioners have adopted the new range for diagnostic and treatment purposes. Some physicians, who are aware of the new guidelines, have, however, chosen not to follow them, and remain with the older reference range. Some of them have made this decision because they do not agree with the new range, medically. Others are attempting to "play it safe" and protect themselves because the laboratories have not yet gone with the change, and these doctors are reluctant to diagnose a thyroid condition unless the printed lab report flags a TSH test result as "high" or "low."

There are also many doctors, general practitioners and even endocrinologists who are still routinely diagnosing and treating patients according to the old reference range simply because they aren't even aware of the new reference range guidelines.

Interestingly, some patients who have asked for physicians to diagnose and treat them by the new reference range have been turned down, told off, or even fired by their physicians. This has led to even greater controversy in the medical community, as doctors are taking sides in the debate over the old and new reference ranges.

The Debate Goes Public

In September of 2005, two articles appeared in the Journal of Clinical Endocrinology and Metabolism, presenting the two sides of the argument.

Martin Surks, Gayotri Goswami and Gilbert Daniels argued that the reference range should remain the same in their article "Controversy in Clinical Endocrinology: The Thyrotropin Reference Range Should Remain Unchanged," while Leonard Wartofsky and Richard Dickey argued that "The Evidence for a Narrower Thyrotropin Reference Range is Compelling."

Surks, Goswami and Daniels base their argument on their assertion that "because routine levothyroxine treatment is not recommended for subclinical hypothyroidism, it is certainly not warranted in individuals with upper reference range TSH [TSH 2.5 to 4.5]."

Drs. Wartofsky and Dickey argue that the previously accepted reference ranges are no longer valid because the reference populations previously considered normal were "contaminated" with individuals with various levels of thyroid disease. They argue that the benefits of treatment far outweigh any minimal risks.

Surks, Goswami and Daniels -- Don't Change the TSH Reference Range

How these researchers could come to such a definitive conclusion that treatment is not warranted for subclinical hypothyroidism is inexplicable, given that in the same journal where their research is published, an article appeared just a few years earlier that demonstrated that treatment of patients with subclinical hypothyroidism could help with cholesterol levels and potentially reduce cardiovascular mortality risk by 31%. ["TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study)," Journal of Clinical Endocrinology and Metabolism, 2001 Oct;86(10):4860-6]

There is also evidence in the literature that levels above 2.0 during pregnancy can potentially complicate pregnancy, and that upper level normal TSH levels can inhibit fertility. For example, in early 2005, Drs. Casey and colleague wrote in the journal Obstetrics and Gynecology that "Pregnancies in women with subclinical hypothyroidism were 3 times more likely to be complicated by placental abruption."

There is also a Norwegian study just published in the International Journal of Obesity that found that there is a positive association between serum TSH within the normal range and body mass index, and the higher the TSH level, the higher the body mass index and likelihood of overweight or obesity.

These are just a few of the many examples of peer-reviewed literature in respected medical journals that discredit the argument that treatment is not recommended or warranted for subclinical hypothyroidism. The authors also state "The only documented adverse health outcome for individuals with TSH levels between 3.0 and 5.0 is progression to overt hypothyroidismLevothyroxine treatment would clearly prevent that outcome, but at what price?"

However, it must be asked, why is preventing progression to overt hypothyroidism not a desired health objective, given that overt hypothyroidism most definitely can contribute to obesity, heart disease, depression, infertility, and host of other health problems?

Prevention of disease is a major focus of much of today's medicine, with exercise, diet and medications to prevent heart disease, obesity, stroke, and many other conditions. Some of these preventative approaches, particularly drug therapies, come with some risk factors, but the risks are presented along with benefits, so patients can make an informed choice.

Even if there is a small risk to treatment of subclinical hypothyroidism (and the existence of such a risk is a theory, not a proven fact) then why is this same approach not used for thyroid patients, who could be given the opportunity to prevent overt hypothyroidism, realizing that the prevention also comes with some risk?

Wartofsky and Dickey: The New Range is More Accurate

Drs. Wartofsky and Dickey defend the shift to the new range, with some caveats. They say: "We will probably never have an absolutely cutoff value for TSH distinguishing normal from abnormal, but recognition that the mean of normal TSH values is only between 1.18 and 1.4 mU/liter and that more than 95% of the normal population will have a TSH level less than 2.5 mU/liter clearly imply that anyone with a higher value should be carefully assessed for early thyroid failure."

"...the decision as to whether to initiate a trial of levothyroxine therapy is based more upon the 'art of medicine' at this time than the science."

In their article, they point to some key facts, including:

  • In an iodine-sufficient population, the mean TSH is 1.5
  • In African-Americans with low incidence of Hashimoto's thyroiditis, the mean TSH is 1.18, which suggests that "this is close to the true normal mean for a normal population"
  • When people with positive antithyroid antibodies or family history of autoimmune thyroid disease are excluded from the "reference range" cohort, the normal reference range becomes .4 to 2.5

They argue that physicians are practicing a double standard -- considering one level the "normal" for treatment, but another for diagnosis. The authors write:

We are also befuddled by the practice of supporters of the recommendations of the consensus panel [the panel that recommended that the reference range not be changed] who promote a target TSH range of 1.0-1.5 mU/liter in patients already receiving T4 therapy, whereas they refuse to accept TSH levels of 3-10 mU/liter as abnormal in patients not receiving T4 therapy.

According to Wartofsky and Dickey, opponents of the new range argue against treatment for subclinical thyroid problems because they are concerned about risks of subclinical hyperthyroidism due to overtreatment. Wartofsky and Dickey argue, however, that there is an equivalent risk of undertreatment, and that all of these risks can be minimized by educating doctors about the desirable TSH target and teaching them how to use various dosages to reach those targets in patients. They write:

To us, individual failure on the part of physicians to appropriately monitor levothyroxine therapy and adjust doses is not a rationale to withhold the indicated therapy. We find the reluctance of the consensus panel to consider treatment for mild TSH elevations puzzling when it is most likely that they would not argue with the wisdom and rationale for early therapeutic intervention to mild diabetes mellitus with slight, but definite, elevations in blood glucose, mild elevations in low-density lipoprotein cholesterol, or mild elevations in blood pressure. After all, few endocrine disease states appear suddenly in an "on or off" or "black and white" manner. Rather, the disordered physiology must start at sub-intense level and then will have the potential to progress from mild to moderate to overt or severe. Just as we have revised downward our concept of normal range blood pressure and cholesterol, we new now should consider the evidence for doing so with TSH. Given the wealth of data on the abnormalities present in untreated subclinical hypothyroidism or hyperthyroidism and the demonstrated benefits of therapy to date, we are not disposed to have our hands tied by the deficiencies inherent in analyses of this issue by evidence-based medicine and allow our patients to continue to be at risk as a consequence."

They also conclude their article with what may be the most sensible statement of both arguments:

"...the decision as to whether to initiate a trial of levothyroxine therapy is based more upon the 'art of medicine' at this time than the science."

What's Normal, Anyway?

There is also an argument regarding whether or not fluctuations with the normal range -- by whichever standard, old or new -- represent thyroid dysfunction on an individual basis. Danish researchers found that each person tends to have what's known as a "set point," a particular level of T4, T3 and TSH that their body wants to return to automatically. We then tend to maintain thyroid levels around that set point, within a narrow range -- a range much narrower than the "reference range" for normal used by laboratories for testing.

Because each of us has a distinct set point for TSH, T3 and T4 levels, the general population references ranges are in fact too broad to detect changes to thyroid function that may represent disease in an individual.

The Danish researchers concluded that:

The distinction between subclinical and overt thyroid disease is somewhat arbitrary because it depends to a considerable extent on the position of the patient's normal set point for T3 and T4 within the laboratory reference range...In conclusion, we found that individual reference ranges for serum T3 and T4 are about half the width of population-based reference ranges. Hence, a test result within the laboratory reference limits is not necessarily normal for the individual.

What This All Means for You

1. Your doctor probably is still using the old reference range of 0.5 to 5.0 for diagnosis and management of your thyroid disease

2. You should not accept the answers "normal," "high" or "low" as a report of your blood tests. Instead, ask for the actual numbers and ask for the lab's normal range. Better yet, ask that a copy of your blood test report be faxed or mailed or given to you.

3. If your TSH test levels come in below 0.5, or above 2.5-3.0, and your doctor is saying these levels are normal, make him or her aware of the AACE and American Association for Clinical Chemistry Laboratory Medicine Practice Guidelines and their 0.3 to 3.0 new reference range. Ask the doctor if he or she will consider a different diagnosis and treatment based on this new information.

4. If your doctor refuses to consider your results according to the new range, you may want to look for a new doctor who is more accepting of change and new evidence, and who will in fact be practicing according to the American Association of Clinical Endocrinologists new guidelines.

5. Stay up-to-date with evolving reference ranges. MedlinePlus from the U.S.National Library of Medicine is kept updated with the current normal values.


Anderson et. al., "Narrow Individual Variations in the Serum T4 and T3 in Normal Subjects: A Clue to the Understanding of Subclinical Thyroid Disease," Journal of Clinical Endocrinology and Metabolism, 87(3): 1068-1072

Garber J, Cobin R, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American association of clinical endocrinologists and the American thyroid association. Endocrine Practice. 2012;18(6):988–1028. doi:10.4158/ep12280.gl.

Guber HA, Farag AF. Evaluation of endocrine function. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 24.

NACB Laboratory Medicine Practice Guidelines, Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease, 2002.

Surks, et.al. "Controversy in Clinical Endocrinology: The Thyrotropin Reference Range Should Remain Unchanged," Journal of Clinical Endocrinology and Metabolism 90(9)/5489-5496

Wartofsky & Dickey, "Controversy in Clinical Endocrinology: The Evidence for a Narrower Thyrotropin Reference Range is Compelling," Journal of Clinical Endocrinology and Metabolism 90(9)/5483-5488

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