Is There a Place For the TRH Stimulation Test?

Lab technician with blood samples and medical chart
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A test called the TRH stimulation test has gained some renewed interest from practitioners as a way to detect mild or sublinical hypothyroidism that is missed by the more common thyroid stimulating hormone (TSH) test.

The TRH test is considered outmoded by most practitioners, who consider the TSH test to be more sensitive.and accurate that the TRH. Still, a small number of practitioners continue to use the TRH test.


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 brain's pituitary gland 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 the reference 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 (Thyrel TRH).

Some practitioners feel that the TRH test can detect subtle thyroid problems and measure your thyroid's ability to respond in real time, compared to the TSH test, which is a snapshot of thyroid function at one point in time. 

How Does the TRH Test Differ from the TSH Test?

Comparing the TRH stimulation test and the TSH test is much like a cardiac stress test compared to a cardiogram, or a glucose tolerance test compared to fasting glucose level.

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

Still, most doctors consider the TSH test highly accurate, and it requires only one blood draw and no special supplies, and is inexpensive. In comparison, the labor-intensive TRH test requires two separate draws a half hour apart, availability of protirelin, and knowledge of how to accurately perform and interpret the test.

Benefits of the TRH 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.

One New York integrative physician, Rafael Kellman, uses the TRH test in his practice. According to Dr. 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.

A Word From Verywell 

If you are able to find a practitioner who does do the TRH stimulating test, keep in mind that the test should be used with caution if you:

  • Have asthma
  • Have chronic obstructive pulmonary disease
  • Have any form of heart disease caused by inadequate blood flow to the heart
  • Have shown evidence of reduced activity of the pituitary gland (hypopituitarism)
  • Are pregnant 

Ultimately, researchers have shown that the TRH stimulation test can detect dysfunction in the thyroid, despite otherwise normal TSH and other thyroid blood test levels. The TRH stimulation test can reveal what's referred to as "early sub-biochemical” hypothyroidism before it is reflected in the more common TSH test..

Hopefully, more studies will be conducted to determine the potential benefits to patients of more widespread use of the test. 


Doi SAR, et. al. "TRH Stimulation When Basal TSH is Within the Normal Range: Is There Sub-Biochemical Hypothyroidism?" Clinical Medicine & Research. 2007;5(3):145-148. doi:10.3121/cmr.2007.756.

Interview with Rafael Kellman, 2005 Thyrel/Protirelin Profile

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