Protirelin is the pharmaceutically available synthetic analogue of the endogenous peptide thyrotropin-releasing hormone (TRH). It is a tri-peptide tropic hormone, released by the hypothalamus, that stimulates the release of Thyroid Stimulating Hormone (TSH) and prolactin from the anterior pituitary.  >> Read More

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Thyroid levels were estimated in 15 patients with endogenous depressions. Before electroconvulsive treatment (ECT), serum thyroxine (T4) and free T4 index values were elevated (P less than .02). After recovery from depression, the levels were normal. Serum triiodothyronine (T3) and free T3 index were normal both before and after ECT. Serum thyrotropin (TSH) levels were also normal and not substantially altered by the ECT procedure. The mean maximal TSH response to protirelin (thyrotropin-releasing hormone) was diminished in the depressed patients and normal after recovery. In three patients, the increase in TSH response to protirelin after recovery did not occur and they relapsed within six months, while in seven patients with increased TSH response to protirelin after recovery only one relapse occurred. The disturbances in the free T4 index, T4, and the protirelin test may in some depressed patients resemble hyperthyroidism, but this condition can be excluded by means of serum, T3 and free T3 index.

Kirkegaard, C., Nørlem, N., Lauridsen, U. B., Bjørum, N., & Christiansen, C. (1975). Protirelin stimulation test and thyroid function during treatment of depression. Archives of general psychiatry, 32(9), 1115-1118.

To explore the possible utility of the protirelin test in differentiating manic and schizophrenic patients, we gave a test dose of protirelin to 30 consecutive euthyroid inpatients who met Research Diagnostic Criteria for mania, 30 who met criteria for schizophrenia, undifferentiated subtype, and 20 normal volunteer controls. The mean maximal thyroid-stimulating hormone (TSH) response (delta TSH) to protirelin in the manic patients was lower than in the schizophrenic patients and in the controls. This mean difference was not attributable to differences in age, sex, baseline thyroid functioning, cortisol levels, or medication, but there was a considerable overlap of values in the patient groups. However, with a delta TSH less than or equal to 7.0 I microunits/mL to identify manic patients in the overall group, the sensitivity of the protirelin test was 60% and the specificity was 84%.

Extein, I., Pottash, A. L. C., Gold, M. S., & Cowdry, R. W. (1982). Using the protirelin test to distinguish mania from schizophrenia. Archives of General Psychiatry, 39(1), 77-81.

Protirelin (thyrotropin-releasing hormone) appears to be a neuromodulator in the extrahypothalamic nervous system and has been suggested as an adjunct in the treatment of amyotrophic lateral sclerosis (ALS). Clinical studies have been divided on the efficacy of protirelin (TRH) despite strong experimental findings that are consistent with a role for the peptide in ALS. Recent findings provide evidence of a gender-related specificity in the ability of protirelin to potentiate the monosynaptic reflex. While castration in male neonatal rats lowered the sensitivity to protirelin, testosterone treatment restored that sensitivity. An examination of the clinical studies reveals a failure either to identify patients' sex or to separate the results on the basis of sex. These findings provide convincing evidence for the potential efficacy of protirelin in ALS if the patient's sex and underlying hormonal status are taken into account.

Miller, S. C., & Warnick, J. E. (1989). Protirelin (thyrotropin-releasing hormone) in amyotrophic lateral sclerosis: the role of androgens. Archives of neurology, 46(3), 330-335.