Normal Thyroid Stimulating Hormone (TSH) Values

Subject: The Normal Range used for interpreting thyroid tests misses many cases of hypothyroid disease.

Hypothyroid disease is a frequently missed diagnosis. The symptoms associated with full blown disease may not be present or be overlooked when the disease is in its early stages. Laboratory testing misses many people with the disease. There are many different causes of hypothyroid disease. Typical tests screen for only the most common causes.

The most common test to run to screen for thyroid problems is the Thyroid Stimulating Hormone (TSH) test. This hormone is made in the brain and regulates how much thyroid hormone the thyroid gland makes and releases into the body. If the thyroid gland is under active and not producing enough thyroid hormone the brain tells it to pick up the pace and it does so by increasing how much TSH it secretes into the blood. Thus an elevated TSH is an indication that someone is hypothyroid.

The guidelines for interpreting TSH values have changed over the years. There is a daily fluctuation in TSH: nighttime values may be 200% higher than mid-afternoon values. The problem is further compounded because it has been difficult to find a group of healthy subjects with which to set the “normal range” for the test. Individuals with undiagnosed thyroid disease have been included in the groups of people tested to set these “normal ranges.”

In the last 20 years the accepted normal upper limit for TSH has officially dropped from around 20 to about 4.5. Even this limit is too high. A TSH of over 2.0 puts someone at increased risk of developing overt disease.

Most of our local labs still classify a TSH under 5.5 as normal. Current medical science does not support this. In 2002 the American Association of Clinical Endocrinologists suggested that the upper range for a normal TSH be lowered to 3.0. According to the National Association of Clinical Biochemistry, “ In the future, it is likely that the upper limit of the serum TSH euthyroid reference range will be reduced to 2.5 because >95% of rigorously screened normal euthyroid volunteers have serum TSH values between 0.4 and 2.5 ”

I write this because all too often I hear from patients who we suspect have hypothyroid disease that they contacted their medical doctor, “had the thyroid test done and the doctor's office said the results were normal” only to find after requesting the records that the TSH was elevated according to these current guidelines.

Pasted below are two excerpts. First a few paragraphs from the National Association of Clinical Biochemists on the correct upper limit for the TSH test and second an article written for the general public and published on the website of The American Academy of Clinical Endocrinologists

From the NACB : (NACB: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease by Laurence M. Demers, Ph.D., F.A.C.B.and Carole A. Spencer Ph.D., F.A.C.B.)

Free download: http://www.nacb.org/lmpg/thyroid_LMPG_Word.stm

TSH Reference Intervals

Despite some gender, age and ethnicity-related differences in TSH levels revealed by the recently published NHANES III US survey, it is not considered necessary to adjust the reference interval for these factors in clinical practice (18 ) . Serum TSH levels exhibit a diurnal variation with the peak occurring during the night and the nadir, which approximates to 50% of the peak value, occurring between 1000 and 1600 hours (123,124) . This biologic variation does not influence the diagnostic interpretation of the test result since most clinical TSH measurements are performed on ambulatory patients between 0800 and 1800 hours and TSH reference intervals are more commonly established from specimens collected during this time period. Serum TSH reference intervals should be established using specimens from TPOAb-negative, ambulatory, euthyroid subjects who have no personal or family history of thyroid dysfunction and no visible goiter. The variation in the reference intervals for different methods reflects differences in antibody epitope recognition by the different kit reagents and the rigor applied to the selection of appropriate normal subjects.

Serum TSH concentrations determined in normal euthyroid subjects are skewed with a relatively long "tail" towards the higher values of the distribution. The values become more normally distributed when log-transformed. For reference range calculations, it is customary to log-transform the TSH results to calculate the 95% reference interval (typical population mean value ~1.5 mIU/L, range 0.4 to 4.0 mIU/L in iodide-sufficient populations) (202,206) . However, given the high prevalence of mild (subclinical) hypothyroidism in the general population, it is likely that the current upper limit of the population reference range is skewed by the inclusion of persons with occult thyroid dysfunction (18).

(a) TSH Upper Reference Limits

Over the last two decades, the upper reference limit for TSH has steadily declined from ~10 to approximately ~4.0-4.5 mIU/L . This decrease reflects a number of factors including the improved sensitivity and specificity of current monoclonal antibody based immunometric assays, the recognition that normal TSH values are log-distributed and importantly, improvements in the sensitivity and specificity of the thyroid antibody tests that are used to pre-screen subjects. The recent follow-up study of the Whickham cohort has found that individuals with a serum TSH >2.0 mIU/L at their primary evaluation had an increased odds ratio of developing hypothyroidism over the next 20 years , especially if thyroid antibodies were elevated (35) . An increased odds-ratio for hypothyroidism was even seen in antibody-negative subjects. It is likely that such subjects had low levels of thyroid antibodies that could not be detected by the insensitive microsomal antibody agglutination tests used in the initial study (207) . Even the current sensitive TPOAb immunoassays may not identify all individuals with occult thyroid insufficiency. 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.

The following article is from the website of The American Academy of Clinical Endocrinologists http://www.aace.com/pub/tam2003/tsh.php

DETECTING MILD THYROID FAILURE
WITH A SENSITIVE TSH TEST

The sensitive thyroid stimulating hormone (TSH) test is generally considered to provide the most accurate measure of the appropriateness of thyroid gland activity. In the past, physicians were unable to detect thyroid hormone excess or deficiency until a patient's symptoms were fairly advanced. With the sensitive TSH test, however, physicians are able to diagnose thyroid disorders at an earlier stage -- in many cases, even before patients begin to experience symptoms.

TSH tests, due to their high degree of sensitivity, enable physicians to detect even the mildest abnormalities of thyroid function. Early detection and treatment of thyroid disorder allows physicians to prevent the onset of symptoms and long-term complications.

How the Thyroid Functions
The thyroid gland operates as part of a feedback mechanism involving the hypothalamus and the pituitary gland. First, the hypothalamus sends a signal to the pituitary gland through a hormone called TRH (thyrotropin releasing hormone). When the pituitary gland receives this signal, it releases TSH (thyroid stimulating hormone) into the bloodstream, where it is carried to the thyroid gland. Upon receiving TSH, the thyroid responds by releasing two hormones, thyroxine (T4) and triodothyronine (T3), which then enter the bloodstream and affect the metabolism of the heart, liver, muscles and other organs. Finally, the pituitary “monitors” the level of thyroid hormone in the blood and increases or decreases the amount of TSH released, which then regulates the amount of thyroid hormone in the blood.

A “Measurable” Improvement in Thyroid Tests
Prior to the introduction of the TSH test, the standard blood tests for thyroid disorders measured only T4 and T3 levels in the blood. Research has shown, however, that these hormone levels can appear relatively normal even when the thyroid is not functioning normally, because the pituitary gland will under- or over-compensate for thyroid function. When the thyroid gland begins to fail (leading to hypothyroidism or an underactive thyroid), the pituitary gland produces higher levels of TSH in an attempt to simulate the gland to produce more T4 and T3. On the other hand, when the thyroid gland begins to produce too much thyroid hormone (seen with hyperthyroidism or an overactive thyroid), the pituitary gland decreases or completely stops producing TSH.

TSH testing offers a marked improvement over simply measuring T4 and T3 by taking advantage of the “wisdom” of the pituitary gland, the organ that first recognizes thyroid dysfunction, and therefore provides a more exact measure of thyroid function.

Beyond disease diagnosis, TSH testing plays a critical role in helping physicians manage thyroid disorders. In this capacity, TSH tests are used to determine the optimal medication dosages for patients with hypothyroidism and hyperthyroidism, as well as to monitor changes in dosage requirements over time.

Interpreting a TSH Test
A TSH test is done by drawing a small blood sample and sending it to a laboratory for analysis. The laboratory will measure the level of TSH, and based on a reported normal value range, it will determine whether the level is below normal (hyperthyroid), above normal (hypothyroid) or within the normal range (euthyroid).

People who believe they may have a thyroid disorder should ask their physician to have their TSH level checked. Ultimately, periodic screening may lead to early recognition and treatment of thyroid dysfunction. Without treatment, mild thyroid failure may develop into overt hypothyroidism at a rate of 5 to 26 percent per year. Furthermore, mild thyroid underactivity, while not necessarily producing any symptoms, may be associated with increased cholesterol levels. Sensitive TSH tests, with their unique ability to detect mild thyroid failure, can help prevent this undesirable result. Another reason why TSH testing is more accurate than simply measuring T4 and T3 is that most T3 is actually made in peripheral tissues rather than being directly secreted by the thyroid and the body can preferentially make T3 even if the thyroid is not working as well as it should. This is why a person who is hypothyroid can take only thyroxine (T4) and still make adequate amounts of T3 for proper body function.

In November 2002, AACE published revised guidelines that provided a new range for normal thyroid function. Until this time, doctors had relied on a normal TSH level ranging from 0.5 to 5.0 to diagnose and treat patients with a thyroid disorder who tested outside the boundaries of that range. AACE encouraged doctors to consider treatment for patients who test outside the boundaries of a narrower margin based on a target TSH level of 0.3 to 3.04 . AACE believes the new range will result in improved accuracy of diagnosis for millions of Americans who suffer from a mild thyroid disorder, but have gone untreated.

In order to develop the new range, an AACE task force reviewed available data and current trends in practice, and updated the AACE Guidelines for Clinical Practice for the Evaluation and Treatment of Hyperthyroidism and Hypothyroidism. The task force also suggested that, in patients on thyroxine replacement therapy, "The target TSH level should be between 0.3 and 3.0 uIU/mL." By inference, any patient with TSH outside this range has an "abnormal" level which should be carefully followed but not necessarily treated. Some authors, however, treat marginally abnormal TSH when coupled with positive antithyroid antibody titers because of high progression rates to clinical hypothyroidism. This area remains very controversial but other endocrine organizations such as The Endocrine Society and the American Thyroid