The TRH stimulation test and the dexamethasone suppression test in depression

The thyrotropin-releasing hormone (TRH) stimulation test and the dexamethasone suppression test (DST) were performed in 40 depressive patients. More endogenously depressed patients than nonendogenously depressed patients showed a blunted response to TRH. No difference was found in delta max thyroid-stimulating hormone (TSH) between patients who responded to dexamethasone administration with a normal suppression of cortisol and those who responded with nonsuppression.     

Dexamethasone suppression test and TRH test in endogenous depression

Dexamethasone suppression test (DST) and thyrotropin releasing hormone (TRH) stimulation test were performed in 34 patients with endogenous depression. Compared with 33 psychiatric controls (limit of discrimination for serum cortisol of 275 nmol/l = 10 micrograms/100 ml) the specificity of the DST was 91% and the sensitivity was 65%. Compared with 24 healthy subjects the sensitivity of the TRH test was 24%, and the combined sensitivity for the DST and the TRH test was 76%. In contrast to the TRH test the DST showed a significant relationship (r = 0.54, P less than 0.01) to the Hamilton Rating Score. Repeating the tests after clinical recovery parallel changes of the two tests were found in 14 of 19 patients with abnormal DST in the depressed phase. In the remaining five patients the DST normalized, while the TRH test remained unchanged. It is suggested that both the apparent higher diagnostic sensitivity and the higher rate of normalization after clinical recovery of the DST is due to the dependency of the severity of depression.     

TRH stimulation test in obsessive-compulsive patients

Serum thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) levels were measured before and after stimulation with 200 micrograms of thyrotropin releasing hormone (TRH) in 10 patients with obsessive-compulsive disorder (OCD) and in 10 control subjects. There were significantly more blunted TSH responses among OCD patients than control subjects. PRL and GH responses to TRH challenge did not differ between OCD patients and controls. These results may indicate dysregulation of the hypothalamic-pituitary-thyroid axis in OCD.     

The TRH stimulation test in Alzheimer's disease and major depression: relationship to clinical and CSF measures

A blunted thyroid-stimulating hormone (TSH) response to exogenous thyrotropin-releasing hormone (TRH) has been reported to occur consistently in patients with major depression and less consistently in patients with Alzheimer's disease (AD). In this study we compared the TSH response to TRH in a large group (n = 40) of AD patients, elderly patients with major depression (n = 17), and age-matched controls (n = 14) to further characterize how it may relate to clinical variables, baseline thyroid function tests, and cerebrospinal fluid measures. Comparisons of TRH stimulation test response across all three groups revealed that patients with major depression had lower stimulated TSH levels (delta maxTSH) (p less than 0.02) and higher (though still within normal limits) mean thyroxine (T4) levels (p less than 0.05) than the AD patients or controls. AD patients with a blunted TSH response had a significantly higher mean free T4 (FT4) level (p less than 0.03) and tended to be more severely demented (p less than 0.01) than those with a nonblunted response.     

DST and TRH stimulation test in mood disorder subtypes

Both the dexamethasone suppression test (DST) and the thyrotropin-releasing hormone (TRH) stimulation test have been reported to be useful in subtyping some depression diagnoses. Whether the DST discriminates delusional from nondelusional depression remains controversial, but this possibility has not been studied for the TRH test. The authors evaluated DST and TRH test results in 29 depressed hospitalized patients; both tests significantly discriminated patients with nonendogenous depression from those with endogenous depression. Furthermore, postdexamethasone cortisol levels but not the change in thyroid-stimulating hormone discriminated the patients with endogenous delusional depression from those with endogenous nondelusional depression.     

Effects of ECT on the TRH stimulation test

The prognostic value of the TRH stimulation test was evaluated in 23 inpatients with major depressive disorder before and after a trial of ECT. In contrast to previous reports, the peak TSH response to TRH was significantly decreased after treatment compared with before treatment. This effect was consistent across individuals and subgroups (responders/nonresponders; unilateral/bilateral ECT). The particular ECT technique used in the study may account for the discrepancies between these findings and those previously reported by other authors.     

The TRH test in the diagnosis of major and minor depression

(1) The effect of TRH on TSH and GH release was studied in 144 consecutive psychiatric admissions. The magnitude of the TSH response to TRH differentiated unipolar from clinically similar and dissimilar groups. (2) Of 41 patients with unipolar depression, 31 had a ΔTSH of ≤7 μI.U./ml while only 1 of 12 bipolar and 0 of 10 minor depressive patients had a ΔTSH of ≤7 μI.U./ml. (3) A ΔTSH of ≤7 μI.U./ml is a frequent finding in unipolar depression and infrequently associated with other psychiatric diagnoses. (4) The data reported support the hypothesis that patients with a ΔTSH of ≤7 are unipolar depressives. (5) Six of 12 bipolar and 17 of 41 unipolar depressives had a GH response to TRH while none of the patients with a minor depression had a significant GH response. These data suggest that major and minor depressions can be separated on the basis of the TRH-induced GH response test. (6) The magnitude of the TRH-induced TSH response and the presence of a pathological GH response may be extremely useful in differentiating manics from schizophrenics and other similarly appearing patient groups. (7) The TRH test is useful in clinical differential diagnosis of dysphoric states and as a confirmatory laboratory test for major depressive disease and unipolar depression.     

Clinical correlates of the TRH infusion test in primary depression

Relationships between clinical measures, diagnosis and neuroendocrine findings were examined in a group of 25 primary depressives maintained drug free on a Neuropsychiatric Evaluation Unit. The TSH response to TRH infusion curves for unipolar and bipolar depressives were significantly different. Agitated patients but not psychomotor retarded patients demonstrated a blunted TSH response curve. No relationships were noted for cortisol hypersecretion and/or loss of diurnality and either diagnosis or psychomotor activity levels in depression. Biochemical and diagnostic implications of these findings are discussed.     

Thyrotrophin-releasing hormone (TRH) stimulation test in psychiatric patients

The thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TRH) 300 micrograms intravenously was studied in 25 patients with schizophrenia, 14 with depression, and 8 with mania. The rate of blunted TRH test results was zero in healthy controls, 64.3% in depression, 62.5% in mania, and 28.0% in schizophrenia. These differences of the rates between depression or mania patients and controls were significant, whereas the difference of rates between schizophrenias and healthy controls was not significant by X2 test. These results seemed to support the view that TRH stimulation test can be used as a biological marker to distinguish affective disorder and that both depression and mania is correlated with the decreased function of serotonin.     

The effect of diagnostic methodology on the sensitivity of the TRH stimulation test for depression: a literature review

The authors review over 50 reports comparing test sensitivity of the thyrotropin-releasing hormone (TRH) stimulation test using either DSM-III or Research Diagnostic Criteria (RDC) criteria for depression. Ten reports with a total of 410 patients and 458 test results were analyzed that met specific criteria for diagnosis for the TRH test. The sensitivity for depression with the TRH test in the DSM-III reports was 34.8% compared with six RDC reports in which the sensitivity was 51% (chi 2 10.41, p less than 0.001). The authors discuss possible endocrine and psychiatric implications of this finding and encourage researchers to use two methods for diagnosis in future clinical research in order that this type of comparison can be undertaken in the same patients. This will help in future modifications and revisions of the DSM.     

TRH stimulation test in dementia of the Alzheimer type and elderly controls

Dementia of the Alzheimer type (DAT) is known to be a heterogeneous syndrome with many clinical manifestations, including depression. In the present study, the thyrotropin-releasing hormone (TRH) stimulation test, previously used as a possible biological marker of depression, was administered to 15 DAT patients and 10 elderly controls. Seven out of 15 (47%) of the patients but none of the controls showed a blunted response with maximal changes of thyroid-stimulating hormone (TSH) from baseline of less than or equal to 7 microIU/ml following injection of 500 micrograms of TRH. The degree of blunting did not correlate with concurrent depression ratings.     

Thyrotrophin-releasing hormone (TRH) stimulation test in manic-depressive illness.

The thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TRH 200 microgram intravenously was studied in 19 patients with unipolar depression, 12 with bipolar depression, 14 with mania, and 5 with mixed manic-depressive illness. The TSH responses were decreased in all of these affective disorders compared to those found in 10 patients with reactive depression, 5 with reactive paranoid psychosis, 14 with neurotic depression, and 60 controls. The decrease of the TSH response in manics could not be accounted for by the effects of neuroleptic drugs. The TSH response in the groups with reactive depression, reactive paranoid psychosis, and neurotic depression, respectively, did not differ significantly from that found in controls. With the exception of a decrease in serum T3 level and free T3 index in the manics, no significant differences in serum T3 level or in free T3 and T4 indexes were found between the groups. Changes found in serum T4 level were due to changes in the thyroxine-binding proteins.     

Specificity of the DST and the TRH test for major depression in alcoholics

The authors examined dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) test results in 32 chronic alcoholics without depression or hepatic disease to see if alcoholism alone might lead to positive test results. After 3 weeks of sobriety there were no DST abnormalities, but blunted TRH test results were observed in eight of the 32 alcoholics. More of the 15 patients also tested during alcohol withdrawal than of the 20 normal subjects or the 32 alcoholics without alcohol withdrawal had DST and TRH test abnormalities. When performed after 3 weeks of sobriety, the DST but not the TRH test has potential as a specific laboratory adjunct in the diagnosis of depression in alcoholics.     

Growth hormone-releasing factor stimulation test in depression

The authors administered the growth hormone-releasing factor (GRF) stimulation test to 19 patients with major depression and 19 age- and sex-matched control subjects to test the hypothesis that a blunted growth hormone (GH) response to clonidine reflects a central alpha 2-adrenergic receptor subsensitivity in depression. GH response to GRF was significantly higher in patients with depression than in control subjects. This group difference was mainly attributable to three of the 19 depressed patients who exhibited markedly high GH responses to GRF. These results suggest that the blunted GH response to clonidine seen in patients with depression is not due to a pituitary defect in GH secretion.