Thyrotropin and prolactin response to thyrotropin-releasing hormone in depressed and nondepressed alcoholic men

Thyrotropin-releasing hormone (TRH) stimulation tests were performed on 81 alcoholic men after at least 3 weeks of abstinence. Subjects were given 500 micrograms of TRH intravenously, and thyroid-stimulating hormone (TSH) and prolactin (PRL) were measured at baseline, and then 15 and 30 min later. Comparisons were made among alcoholics with (n = 27) and without (n = 54) a lifetime history of depression as determined by the Diagnostic Interview Schedule. Nine nondepressed, nonalcoholic subjects served as controls. Alcoholics with or without a depression history did not differ from each other or from control in TSH or PRL response area under the curve. Blunted TSH responses were present in 10 (12%) of the alcoholics and none of the controls when blunting was defined as a delta max TSH less than 5 microU/ml. When blunting was defined as a delta max TSH less than 7 microU/ml, 18 (22%) of the alcoholics and 1 (1%) of the controls were blunted. Conversely, 2 (2.5%) of the alcoholics had a delta max TSH greater than 32 microU/ml. All subjects were clinically euthyroid. Contrary to expectation, depressed subjects were slightly less likely to show blunted responses than nondepressed subjects. No relationship was found between neuroendocrine measurements and several measurements of alcoholism or depression. Some alcoholic subjects show a blunted TSH response to TRH injection, which may be a function primarily of the alcoholism itself. The precise mechanism remains unknown.     

Thyrotropin releasing hormone (TRH): a useful tool for psychoneuroendocrine investigation

(1) The hypothalamic tripeptide TRH was injected in normal controls and in schizophrenic, alcoholic and depressed patients. Behavioral and endocrine data were assessed and relationships between the two evaluated. (2) After TRH there was a brief and partial salutary behavioral change in all groups studied, suggesting that the behavioral effects of TRH are not disease specific. (3) A blunted TSH response after TRH was seen in some depressed and some alcoholic patients but not in schizophrenics, indicating that this fault is not simply a nonspecific attribute of mental illness. (4) In depression, but not in alcoholism, the blunting was accounted for by increased levels of serum cortisol. (5) In alcoholic patients, the TSH blunting was related to a favorable behavioral response to TRH. (6) While the relationship between ambient levels of serum cortisol and the TSH response was negative in normal subjects and depressed patients, it was positive in schizophrenic patients. The relative frequency of this finding in the various subtypes of schizophrenia is unknown. (7) The above data, taken together, suggest that both the behavioral and the endocrine effects of TRH render the tripeptide useful for psychoneuroendocrine investigation.     

Abnormal thyroid stimulating hormone, prolactin, and growth hormone responses to thyrotropin releasing hormone in abstinent alcoholic men with cerebral atrophy

The thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) responses to thyrotropin releasing hormone (TRH), the Wechsler Adult Intelligence Scale (WAIS) for cognitive impairment, and computed tomographic scans were evaluated in 15 nondepressed alcoholic men after 4 weeks of abstinence and in 10 normal controls. Both cognitive impairment and cerebral atrophy were found in 13 of the alcoholics. Eight alcoholics (seven with cerebral atrophy) had blunted TSH and PRL responses to TRH and a TRH-induced paradoxical increase of GH. This study demonstrates that besides affecting the TSH response to TRH, alcoholism often induces alterations of the PRL and GH secretory patterns in response to TRH. The severe brain damage caused by long-term alcoholism might be involved in the pathogenesis of these neuroendocrine alterations.     

The TRH-induced TSH response in psychiatric patients: a possible neuroendocrine marker

The finding of a diminished TSH response to exogenously administered TRH in a significant proportion of depressed patients has now been established as one of the most reproducible findings in biological psychiatry. More than 50 reports, in which more than 1000 patients have been studied, reveal that the TSH response is blunted in approximately 25% of patients with major depression. TSH blunting is clearly not specific for depression, because it also has been observed in mania, alcoholism, and borderline personality disorder. It is doubtful that TSH blunting represents a non-specific response to mental stress: it was found only rarely in schizophrenic patients, and the TSH response to in vivo flooding therapy in phobic patients was normal. In both depression and alcoholism, TSH blunting has been reported to be sometimes a state marker and sometimes a trait marker, i.e. the fault was found to persist into remission in more than half the patients. In both conditions, TSH blunting was unrelated to the patients' age, body weight, height, body surface, thyroid status, and serum cortisol concentrations. It also is unlikely that TSH blunting was due to increased dopaminergic inhibition of thyrotroph cells: serum prolactin concentrations in TSH blunters were found to be normal, and pretreatment with haloperidol had no effect on either basal TSH levels or TSH blunting. In depression, TSH blunting was not associated with previous drug intake, dexamethasone suppression test abnormalities, or variables of biogenic amine metabolism, nor did it usefully segregate between primary and secondary depression or between unipolar and bipolar subgroups. Preliminary evidence suggests that TSH blunting in depression may be related to duration of illness, history of violent suicide attempts, and a reduced 24 h TSH secretion. In alcoholism, TSH blunting was unrelated to family or personal history of depression and duration of abstinence. With reference to clinical utility, TSH blunting may aid in assessing the response to antidepressant treatment, predicting outcome to such treatment, assessing the risk for violent suicide attempts, and describing relationships between different psychiatric populations (e.g. depression and alcoholism).     

Effects of age and diagnosis on thyrotropin response to thyrotropin-releasing hormone in psychiatric patients

The thyrotropin (thyroid-stimulating hormone; TSH) response to thyrotropin-releasing hormone (TRH) was studied in 64 age-matched healthy volunteers, 44 patients with endogenous depression, and 21 patients with schizophrenia. A significant negative correlation between delta TSH and age was found both in healthy subjects and in depressed patients. We based our comparison on normal ranges for delta TSH calculated from the delta TSH values in the healthy subjects related to age. It was then seen that blunted TSH response to TRH does not occur significantly more often in depression (13.6%) than in healthy controls (4.7%). Blunted TRH test results were also found in a considerable number of severely ill schizophrenic patients (19%). Application of an improved radioimmunoassay revealed a highly significant correlation between TSH values at baseline and after stimulation, and showed decreased baseline TSH levels in subjects with blunted TRH test results.     

Thyroid stimulating hormone and prolactin responses to thyrotropin releasing hormone in nondepressed alcoholic inpatients.

Thyroid stimulating hormone (TSH) and prolactin (PRL) responses to thyrotropin releasing hormone (TRH) stimulation are sometimes blunted in alcoholic subjects; however, the mechanisms involved in these phenomena have not been established. We hypothesized that elevations in free thyroid concentrations might be related to these abnormal responses and then tested that hypothesis in a sample of nondepressed alcoholic inpatients (n = 21). Four alcoholic patients had delta max TSH responses that were < 7 mIU/l; three had PRL responses at or below 8 micrograms/l. Baseline TSH was the only significant predictor of peak TSH; however, free thyroxine (FT4) and baseline TSH both were significant predictors of peak PRL. The average baseline FT4 concentration in alcoholic patients was significantly higher than that in healthy control subjects (n = 10). Our data, thus, suggest that small elevations of FT4 play a role in the inhibition of TSH and PRL responses to TRH among nondepressed, abstinent alcoholic patients.     

Thyroid releasing hormone test in schizophrenic patients with post-psychotic depression

1. TSH response to TRH was assessed in 25 patients meeting operationalized criteria for the post-psychotic depression syndrome and in an age and sex matched control group of 34 primary depressed patients. 2. A blunted TSH response was observed in 36% of the patients with post-psychotic depression. 3. The rate of blunted TSH response was similar for patients with secondary post-psychotic depression to those patients with primary depressions. 4. Demographic and clinical parameters did not distinguish those post-psychotic depressed patients who had a blunted response from those who did not. 5. A blunted TSH response to TRH did not predict which patients were more likely to have a favorable response when adjunctive imipramine was added to their on-going fluphenazine decanoate and benztropine regimen.     

Violent suicidal behavior and the thyrotropin-releasing hormone-thyroid-stimulating hormone test: a clinical outcome study

A relation between abnormal response of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone (TRH) and a personal history of violent suicidal behavior was observed in a sample of 60 depressive women. Patients with a blunted TSH response to TRH were also at greater risk for subsequent suicide. There was no relationship between TSH response to TRH and age, severity of depression and polarity of the illness.     

TSH response to TRH and family history of alcoholism

The thyrotropin (TSH) response to intravenous thyrotropin-releasing hormone (TRH) was evaluated in 10 sons of alcoholic fathers (FHP group) and 10 matched controls (FHN group). No differences were observed between the two groups in basal TSH, peak TSH levels, on the incidence of TSH-blunting to TRH. Though there was a trend for a less intense TSH response over time after the TRH infusion, the difference between the family groups was not significant. These results are not consistent with some previous reports of an increased percentage of blunted TSH response to TRH for children of alcoholics. The clinical and research implications of these findings are discussed.     

Thyroid-stimulating hormone response to thyrotropin-releasing hormone in unipolar depression before and after clinical improvement

Fourteen patients with unipolar depression who had a blunted thyroid- stimulating hormone (TSH) response to infusion of 500 μg of thyrotropin- releasing hormone (TRH) and who showed marked clinical improvement after pharmacotherapy and/or electroconvulsive therapy had the TRH test repeated after improvement. The mean (± SD) maximal TSH response to TRH (Δ TSH) increased significantly from 4.0± 1.9 to 8.1± 3.5 μ IU/ml. The number of patients with Δ TSH ≤ 7.0 μIU/ml increased significantly from 0 to 9 of 14 after improvement. Eleven of the patients were followed for 5 to 19 months, and none showed clear relapse. The results suggest that the blunted TSH response to TRH has features of both a state marker for active unipolar depression and a trait marker for vulnerability to this illness, and support the suggestion that the TRH test may be useful in diagnosis and treatment planning.     

Evaluation of the diagnostic utility of the TRH-induced TSH response in psychiatric disorders

To evaluate the diagnostic utility of TSH blunting, the TRH-induced TSH response was measured in 168 normal subjects and 176 psychiatric patients. It was blunted in some acutely depressed, alcoholic, and borderline patients, but not in schizophrenic patients. In both depression and alcoholism the fault also occurred during symptomatic recovery, though with reduced frequency. Although TSH blunting was useful in distinguishing between borderline and schizophrenic patients, its diagnostic utility in identifying or confirming an existing psychiatric disorder appears to be limited. TSH blunting is not specific for any particular psychiatric diagnosis, and its sensitivity generally is low. However, the fault has promising research utility, particularly for study of the biologic interface between depression, alcoholism and borderline personality disorder. Beyond this, further study of the possible trait nature of TSH blunting in both depression and alcoholism appears warranted.     

Thyrotropin stimulating hormone response to thyrotropin releasing hormone in patients with panic disorder

OBJECTIVE: The aim of this study is to assess thyrotropin stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in patients with panic disorder (PD). METHOD: The effects of TRH administration on the release of TSH were examined in 15 patients who met DSM-III-R criteria for PD and compared their test results with those of 15 normal control subjects. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. RESULTS: delta max TSH values were lower in the panic disorder patients than in the control subjects. Using the criterion of delta max TSH < or = 7 mlU/l, nine of the 15 panic disorder patients and four of the 15 control subjects had a blunted TSH response to TRH. CONCLUSIONS: These results confirm the findings from earlier reports that patients with PD show blunted TSH response to TRH which is similar to that seen in depressed patients.     

Neuroendocrine abnormalities in affective disorders

The authors review neuroendocrine abnormalities in depression, and present data on the thyrotropin-releasing hormone (TRH) test in unipolar depression. Sixty of 105 patients who met Research Diagnostic Criteria for major unipolar depression had a blunted thyroid-stimulating hormone (TSH) response to TRH as defined as by delta TSH less than 7.0 micro IU/ml. Only 4 of 40 patients with non-major depression and 0 of 20 normal controls had a blunted TSH response to TRH by this criteria. Of 50 unipolar patients administered both the TRH test and the dexamethasone suppression test (DST), 34% were identified by the TRH test only, 20% by the DST only, 30% by either test, and 15 by neither test. The TRH test and DST seem to be complementary in the neuroendocrine evaluation of the patient with possible unipolar depression. The TRH test along with other neuroendocrine tests may be of help to the clinician in the diagnosis of depression and in treatment planning.     

Is there paradoxical growth hormone response to thyrotropin-releasing hormone in depression?

Several investigators have reported a paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) in depressed patients, but other studies have failed to confirm this. In the present study, the GH response to TRH was studied in depressed patients and normal subjects. The rate of paradoxical GH response to TRH in depression was no different than that observed in control subjects. This was the case whether the data was examined using mean values or using frequency of abnormal responses. Patients with blunted thyrotropin (TSH) responses did not differ in GH release from patients with normal TSH response. A variety of factors may have contributed to the earlier reports of a positive GH response to TRH, including the definition of paradoxical GH release and the fact that depressed patients exhibit more frequent spontaneous diurnal GH release than do normal subjects.     

Methodological issues in the measurement of serum TSH—implications for psychiatry

1. The TSH response to TRH has been reported to be blunted in endogenous depression. 2. We compared two radioimmunoassay (RIA) techniques of TSH in 21 subjects (7 psychiatric inpatients, 14 normal controls) to determine whether differences in assay could account for discrepancies in the reported prevalence rates of blunted TSH responses in depression. 3. A highly significant correlation (p < 0.001) was found between the Δ MAX TASH values of the two assays. 4. The mean Δ MAX TSH of one assay was significantly greater than the mean of the second assay. 5. One assay yielded 6 blunted TSH responses to TRH, while the other yielded 9 such responses. 6. Different TSH assay methods might account for discrepancies of the prevalence rates of blunted TSH response in depression.     

Effects of electroconvulsive therapy on the thyrotropin-releasing hormone test in patients with depression

We investigated the acute and lasting effects of electroconvulsive therapy (ECT) on the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in patients with depression. The TRH stimulation test was conducted (1) under basal conditions, after a first ECT, and at the end of a therapeutic course of 7 ECTs in 20 inpatients with depression; (2) before the initiation of antidepressant therapy and after the therapeutic response in 16 other inpatients with depression who responded to antidepressant drug treatment; and (3) in 20 healthy control subjects. Baseline TSH levels were lower in patients with depression, especially in those with more severe depression who were considered appropriate for ECT. Before the treatment, TSH response to TRH did not differ between the patients with depression and controls; however, more blunted TSH responses to TRH were observed in these patients compared with the controls. TSH response to TRH changed neither with one ECT nor throughout consecutive ECT sessions in patients with depression. Drug treatment also was found to have no impact on this response. These findings suggest that the therapeutic action of ECT in depression is not directly related to its effects on the hypothalamic-pituitary-thyroid axis. However, possible delayed effects of ECT on the HPT axis function should not be overlooked.     

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.     

Thyrotropin-releasing hormone test in recently abstinent alcoholics

Alcoholic men who had been abstinent from alcohol for more than 20 days were evaluated with the thyrotropin-releasing hormone (TRH) test. Abstinent alcoholics showed a blunted thyroid-stimulating hormone (TSH) response to TRH as compared with healthy controls. In the absence of any somatic illnesses, these data suggest that the TSH blunting in some alcoholics may be interpreted as a trait marker of being alcoholic.     

The dexamethasone suppression and thyrotropin-releasing hormone tests in depressed borderline patients

Borderline patients can be both a diagnostic and a therapeutic enigma. We investigated a group of 24 depressed women with borderline personality disorder or strong borderline features by DSM III criteria for the presence of either an abnormal dexamethasone suppression test (DST) or a blunted TSH response to TRH, abnormalities which have been reported in major depression. Thirteen of the 24 borderlines failed to suppress on the DST, compared with one of 14 normal women (p < 0.01). Nine of the 24 borderlines had a blunted TSH response to TRH, compared with one of 11 normal women. Neuroendocrine abnormalities were found in a total of 75% of the borderline women, independent of whether or not they met DSM III criteria for major depressive disorder. The results of this study support the notion that many borderline patients with depression have a genuine affective component to their illness, perhaps biologically similar to major depression in non-borderlines.