Is There a Place For the TRH Stimulation Test?

Lab technician with blood samples and medical chart
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Manhattan-based alternative practitioner Dr. Rafael Kellman is trying to revive interest in the TRH Stimulation Test, a test considered totally outmoded by most practitioners.

Understanding the TRH Test

To understand how the TRH Stimulation Test works, it's first helpful to quickly review how the various brain hormones interact with the thyroid.

  • Your hypothalamus is a gland in your brain that secretes thyrotropin-releasing hormone (TRH).
  • When TRH is released, it stimulates your pituitary gland -- also in the brain -- to release thyroid stimulating hormone (TSH).
  • TSH stimulates the thyroid itself to make thyroid hormones.

Most practitioners consider the best test of thyroid function to be the TSH test, which measures the circulating level of TSH in the bloodstream at one point in time. The TSH test results are then interpreted; levels higher or lower than a so-called normal range are considered evidence of potential thyroid disease.

The TRH test is different. A baseline TSH test is done. Then you are given an injection of TRH, which stimulates the pituitary to release TSH. A second blood sample is drawn 20 to 30 minutes later, and the TSH level is retested. TRH is known generically as protirelin (pronounced proe-TYE-re-lin). Its brand name used to be Thyrel, but production of Thyrel was discontinued several years ago.

Kellman believes that this test is the "best way to detect subtle thyroid problems..." and that it overcomes limitations of the TSH test.

According to Kellman:

The TSH test is a picture in time of circulating levels of thyroid hormone. But by challenging the thyroid, the TRH Stimulation Test evaluates the thyroid's actual ability to function in real life.

How Does the TRH Test Differ from the TSH Test?

One way to look at it is to consider the difference between the TRH Stimulation Test and the TSH test, much like a cardiac stress test is compared to a cardiogram, or a glucose tolerance test is compared to fasting glucose level.

In a stimulation test, the challenge may reveal an impairment in the thyroid.

With most practitioners, use of the TRH Stimulation Test was replaced by the TSH test. Conventional doctors consider the TSH test highly accurate, and it requires only one blood draw and no special supplies. In comparison, the TRH test requires two separate draws a half hour apart, availability of TRH, and knowledge of how to accurately perform and interpret the test.

The TRH test is occasionally used to help identify secondary hypothyroidism (hypothyroidism due to pituitary problems) and tertiary hypothyroidism (hypothyroidism due to hypothalamic disorder). But there are only a few doctors in the U.S. who know how to use the TRH Stimulation Test. These doctors believe the test is important when traditional TSH tests results are borderline, and when a patient has obvious thyroid symptoms but normal TSH results.

Says Kellman:

In some individuals (and depending on the physician's interpretation of the laboratory tests), outright hypothyroidism may take as long as 20 years to develop. With the help of measures such as the TRH stimulation test, I am able to diagnose hypothyroidism when the onset of symptoms (fatigue, weight gain, etc.) precedes abnormal laboratory values. Early intervention thus may save patients from years of needless suffering.

What Should You Do?

At present, it is almost impossible to get a TRH test. The drug needed for the test, protirelin, is no longer manufactured. The only protirelin that is apparently available is via compounding pharmacies. Whether or not that protirelin is of sufficient quality to conduct the test is a question that some practitioners have raised. If you find a practitioner who does do the TRH test, however, keep in mind that the TRH Stimulation Test and protirelin TRH should be used with caution in anyone with:

  • Asthma
  • Chronic obstructive pulmonary disease
  • Heart disease caused by inadequate blood flow to the heart
  • Reduced activity of the pituitary gland (hypopituitarism)
  • Pregnancy

Mary Shomon Interview with Rafael Kellman, 2005 Thyrel/Protirelin Profile

Mary Shomon,'s Thyroid Guide since 1997, is a nationally-known patient advocate and best-selling author of 10 books on health, including "The Thyroid Diet: Manage Your Metabolism for Lasting Weight Loss," "Living Well With Hypothyroidism: What Your Doctor Doesn't Tell You...That You Need to Know," "Living Well With Graves' Disease and Hyperthyroidism," "Living Well With Autoimmune Disease," "Living Well With Chronic Fatigue Syndrome and Fibromyalgia," and the "Thyroid Guide to Fertility, Pregnancy and Breastfeeding Success." Click here for more information on Mary Shomon.

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