From the Guidelines
Thyrotropin-releasing hormone (TRH) testing is primarily indicated for diagnosing central hypothyroidism and differentiating between hypothalamic and pituitary causes of thyroid dysfunction. The test is most useful when evaluating patients with low or low-normal thyroid-stimulating hormone (TSH) levels accompanied by low free T4 levels, suggesting central rather than primary hypothyroidism. TRH testing involves administering 200-500 mcg of synthetic TRH intravenously and measuring TSH levels at baseline and at intervals (usually 15,30, and 60 minutes) afterward. In healthy individuals, TSH typically increases by 5-30 mIU/L within 30 minutes. A blunted response (minimal or no TSH increase) suggests pituitary dysfunction, while an exaggerated or delayed response may indicate hypothalamic dysfunction. TRH testing can also help evaluate hyperprolactinemia, as TRH normally stimulates prolactin release. However, the clinical use of TRH testing has declined with improvements in sensitive TSH assays and advanced imaging techniques. The test is contraindicated in pregnancy, uncontrolled hypertension, and recent myocardial infarction due to potential side effects including nausea, flushing, urinary urgency, and transient blood pressure changes. These physiological responses occur because TRH stimulates the anterior pituitary to release TSH, which then acts on the thyroid gland to regulate thyroid hormone production.
Key Points
- TRH testing is used to diagnose central hypothyroidism and differentiate between hypothalamic and pituitary causes of thyroid dysfunction.
- The test involves administering synthetic TRH intravenously and measuring TSH levels at baseline and at intervals afterward.
- A blunted response suggests pituitary dysfunction, while an exaggerated or delayed response may indicate hypothalamic dysfunction.
- TRH testing can also help evaluate hyperprolactinemia.
- The test is contraindicated in pregnancy, uncontrolled hypertension, and recent myocardial infarction.
Indications for TRH Testing
- Low or low-normal TSH levels accompanied by low free T4 levels.
- Evaluation of hyperprolactinemia.
- Differentiation between hypothalamic and pituitary causes of thyroid dysfunction.
Contraindications for TRH Testing
- Pregnancy.
- Uncontrolled hypertension.
- Recent myocardial infarction.
According to the study by 1, the American College of Radiology (ACR) Appropriateness Criteria for neuroendocrine imaging recommends that TRH testing be used to evaluate patients with suspected central hypothyroidism or hyperprolactinemia. The study by 1 also notes that TRH testing can be used to diagnose and differentiate between hypothalamic and pituitary causes of thyroid dysfunction. However, the clinical use of TRH testing has declined with improvements in sensitive TSH assays and advanced imaging techniques, as noted in the study by 1.
From the Research
Indications for Thyrotropin-Releasing Hormone (TRH) Testing
The indications for TRH testing include:
- Evaluation of pituitary TSH and prolactin reserve in patients with pituitary lesions 2
- Differentiation of pituitary and hypothalamic causes of hypothyroidism 2
- Diagnosis of euthyroid Graves' disease 2
- Evaluation of the adequacy of TSH suppression in thyroid hormone therapy of nodular goiter 2
- Possible diagnosis of mild primary hypothyroidism 2
- Diagnosis of central hypothyroidism, which can be complicated by concomitant affection of other hypothalamus-pituitary-hormone axes 3
- Assessment of pituitary and thyroid function, as TRH testing is a safe, convenient, and rapid method 2
Use of TRH in Diagnostic Testing
TRH testing is used to assess the function of the hypothalamic-pituitary-thyroid axis, which is regulated by the hypothalamic paraventricular nucleus 4. The test can help diagnose various conditions, including hypothyroidism, hyperthyroidism, and pituitary disorders. The results of TRH testing can be influenced by other hypothalamus-pituitary-hormone axes, and clinicians should be aware of these interactions when interpreting test results 3.
Regulation of the Hypothalamic-Pituitary-Thyroid Axis
The hypothalamic-pituitary-thyroid axis is regulated by a complex interplay of hormones, including TRH, TSH, and thyroid hormones 5, 6. TRH stimulates the release of TSH from the anterior pituitary, which in turn stimulates the synthesis and release of thyroid hormones from the thyroid gland. The axis is also regulated by negative feedback from thyroid hormones, which inhibit the release of TRH and TSH. The dominant role of TRH in regulating the axis has been demonstrated in studies using mouse models 5.