Thyrotropin-Releasing Hormone (TRH) Stimulation Test


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Subject: Thyrotropin-Releasing Hormone (TRH) Stimulation Test

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  • TRH is a hormone produced in the hypothalamus; it can stimulate the release of TSH from the pituitary gland. TSH then further stimulates the production and the release of T3 and T4 from the thyroid gland. Therefore, the TRH stimulation test can evaluate the thyroid function status. However, TRH also stimulate the release of growth hormone (GH) as well as prolactin. Three blood specimens are collected for serum TSH testing: one immediately prior to TRH injection, and one 15 minutes and one 30 minutes after TRH injection. TRH is administrated IV (200–500 μg). Pharmacy consultation for TRH dosage is recommended (see Fig. 16.4).

Figure 16–4
Sample curves of serum thyroid-stimulating hormone (TSH) response to administration of thyrotropin-releasing hormone (TRH) in various conditions.


  • Rarely used clinically for diagnosis of the thyroid diseases. Measurements of serum TSH and T3 and T4 levels are informative in evaluating thyroid function in most clinical situations. However, when the diagnosis is still unclear, the TRH stimulation test can be of help.

  • May be particularly useful in T3 toxicosis in which the other test results are normal or in patients clinically suspicious for hyperthyroidism with borderline serum T3 levels. TRH stimulation test is superior to the T3 suppression test of RAIU. Abnormal TSH response to TRH administration does not definitely establish the diagnosis of hyperthyroidism (because autonomous production of normal or slightly increased amounts of thyroid hormones causes pituitary suppression). TRH test may remain abnormal even after successful therapy of Graves disease.

  • Helps differentiate two forms of thyrotropin-induced hyperthyroidism (whether or not due to tumor).

  • May help differentiate hypothalamic from pituitary hypothyroidism.


  • Normally, a significant rise in serum TSH occurs from a basal level of 2–3 μU/mL, and this then returns to normal by 120 minutes. Response is usually greater in women than in men. A blunted response indicates hyperthyroidism but may occur in other conditions (e.g., uremia, Cushing syndrome, starvation, elevated levels of glucocorticoids, depression, some elderly patients). Largely replaced by sensitive TSH assays.

    • Hyperthyroidism: ruled out by a normal increase of >2–3 μU/mL after TRH administration

    • Primary hypothyroidism: an exaggerated prolonged rise of an already increased TSH level

    • Secondary (pituitary) hypothyroidism: no rise in the decreased TSH level

    • Hypothalamic hypothyroidism: low serum T3, T4, and TSH levels, with a TRH response that may be exaggerated or normal or (most characteristically) with a peak delay 45–60 minutes

  • TSH high sensitivity, <0.1 mU/L, obviates need for TRH, except for TSH-secreting tumor and thyroid hormone resistance (in which case TSH thyroxine is high).

  • Interpretation must be based on clinical studies that exclude the pituitary gland as the site of the disease.

  • Lack of response shows adequate therapy in patients receiving thyroid hormones to shrink thyroid nodules and goiters and during long-term treatment of thyroid carcinoma.

  • In patients with euthyroid Graves disease who have only exophthalmos (unilateral or bilateral), the TRH stimulation test may sometimes be normal. A T3 suppression test may be required.

  • Elderly patients with or without symptoms of hyperthyroidism may have serum T4 and T3 in upper normal range.

  • Euthyroid sick syndrome—response varies. Some patients respond normally, whereas many have less than normal response.


  • Contraindicated in pregnancy.

  • No T4 or T3 should be given for 3 weeks prior to test.

  • TRH can cause smooth muscle spasm; use with caution in asthma and ischemic heart disease.

  • The TSH response to TRH is modified by antithyroid drugs, corticosteroids, estrogens, large amounts of salicylates, and levodopa.