Thyrotropin-releasing hormone (TRH) stimulation test

From Cat

The TRH test is an alternative to the T3-suppression test for detecting feline hyperthyroidism. This test measures the serum T4 response to administration of TRH. In clinically normal cats, the administration of TRH causes an increase in TSH secretion and serum T4 concentrations, whereas in cats with hyperthyroidism, the TSH and serum T4 response to TRH is blunted or totally absent[1]. The lack of response is due to chronic suppression of TSH secretion in cats with hyperthyroidism that cannot be overcome by a single injection of TRH.

To perform a TRH stimulation test, blood is collected for serum T4 determination before and 4 hrs after intravenous administration of 0.1 mg/kg TRH (Relefact)[2]. Cats with hyperthyroidism show little, if any, rise in serum T4 concentrations after administration of TRH, whereas a consistent rise of serum T4 concentrations (approximately twofold increase) occurs after TRH administration in clinically normal cats and cats with non-thyroidal disease. The serum T3 response to TRH is less helpful in separating normal from hyperthyroid cats, because many normal cats have only a small and inconsistent rise in serum T3 concentrations after TRH administration. Therefore, although basal T3 concentration might be helpful in diagnosis of hyperthyroidism in soem cats, it is not recommended to determine the serum T3 response as part of the TRH stimulation test[3].

Regarding interpretation of the TRH stimulation test results, the relative rise in serum T4 concentration after administration of TRH is the best (most sensitive) criterion for predicting whether or not cats are hyperthyroid. A per cent rise in serum T4 of less than 50% is consistent with hyperthyroidism, whereas a value of greater than 60% is seen in normal cats and cat with non-thyroidal illness; values between 50 and 60% are equivocal or borderline responses[4].

Both the TRH stimulation test and T3-suppression test are best for diagnosing cats with mild or early hyperthyroidism that do not have any concurrent illnesses. In hyperthyroid cats that have developed marked suppression of the circulating T4 concentrations into the normal (or subnormal) range because of the effects of concurrent moderate to severe non-thyroidal illness, the diagnostic accuracy of both these tests will decrease[5]. The advantages of the TRH stimulation test over the T3-suppression test include the shorter time needed to perform the test (4 hours instead of 3 days), and the fact that the TRH stimulation test is not dependent upon the owner's ability to administer oral medication. The major disadvantage of the TRH test in cats is that side effects (e.g. salivation, vomiting, tachypnoea and defecation) occur commonly immediately after administration of the TRH[6]. Fortunaely, all the adverse effects are transient and resolve after 4 hours.

T3-suppression test Thyrotropin-releasing hormone (TRH) stimulation test TSH stimulation test TSH stimulation test
Drug Liothyronine (Cytomel) TRH Bovine TSH Human TSH
Dose 25 µg q 8hr for 7 doses 0.1 µg/kg 0.5 IU/kg 0.025 - 0.20 mg/cat
Route Oral Intravenous Intravenous Intravenous
Sampling time Before and 2-4 hrs after last dose Before and at 4 hrs Before and at 6 hrs Before and at 6-8 hrs
Assay Total T4 and T3 Total T4 Total T4 Total T4
Interpretation:
Euthyroidism T4 <20 nmol/L with >50% suppression >60% increase in T4 >100% increase in T4 >100% increase in T4
Hyperthyroidism T4 >20 nmol/L with <3% suppression <50% rise in T4 Minimal to no increase Not determined

References

  1. Utiger, RD (1986) Tests of thyroregulatory mechanisms. In Ingbar, SH & Braverman, LE (Eds): The thyroid: a fundamental and clinical text. Lippincott, Philadelphia. pp:511-523
  2. Peterson, ME (1995) Hyperthyroid diseases. In Ettinger, SJ (Ed): Textbook of veterinary internal medicine: diseases of the dog and cat. 4th edn. WB Saunders, Philadelphia. pp:1466-1487
  3. August, JR (2006) Consultations in feline internal medicine. Vol 5. Elsevier Saunders, USA
  4. Peterson, ME Broussard, JD & Gamble, DA (1994) Use of the thyrotropin releasing hormone stimulation test to diagnose mild hyperthyroidism. J Vet Intern Med 8:279-286
  5. Tomsa, K ;;et al (2001) Thyrotropin-releasing hormone stimulation test to assess thyroid function in severely sick cats. J Vet Intern Med 15:89-93
  6. Holtman, JR et al (1986) Central respiratory stimulation produced by thyrotropin-releasing hormone in the cat. Peptides 7:207-212