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.     

Delayed TSH release in anorexia nervosa following injection of thyrotropin-releasing hormone (TRH)

We studied plasma concentrations of thyrotropin (TSH), prolactin and growth hormone (GH) after injection of 500 microgram of thyrotropin-releasing hormone (TRH) in 10 patients with acute anorexia nervosa, subsequent to initial nutritional stabilization and again after weight recovery. Plasma thyroxine levels were normal throughout, whereas plasma triiodothyronine levels were low initially but rose with weight gain. The TSH secretory response to TRH was delayed and prolonged during the initial study but showed a normal overall quantitative response, except for two patients who showed no TSH rise. Following weight gain the TSH response was more rapid, and positive correlations were found between body weight and peak TSH levels and rapidity of TSH response. Six of 10 patients, however, continued to exhibit a delayed TSH peak response, the average response was markedly increased in comparison with that in normal females. The prolactin response curves were normal at both times. Rises in GH following TRH were observed in two patients prior to and in one patient after weight gain. We conclude that acute anorexia nervosa, with its concomitant profound weight loss, is accompanied by abnormalities in the hypothalamo-pituitary-thyroid axis, which are reversed only in part with improvement in the illness and weight gain, suggesting the persistence of disordered neuroendocrine function in this illness.     

Growth hormone releasing factor increases growth hormone release from MtTW15 pituitary tumors

The MtTW15 pituitary tumor secretes growth hormone and prolactin. Perifusion of these dispersed MtTW15 tumor cells with 10 nM growth hormone releasing factor (GRF) increases growth hormone release without affecting prolactin release. This effect is dose-dependent between 0.001 and 0.1 nM and is blocked by 100 nM somatostatin. These findings suggest that this tumor and clones derived from it may be valuable tools in studying the cellular mechanisms of action of GRF and somatostatin.     

Diurnal secretion profiles of growth hormone, thyrotrophin and prolactin in Parkinson's disease

Recently, a massive loss of both hypocretin and melanin‐concentrating hormone (MCH) neurones was found in the hypothalamus of Parkinson’s disease (PD) patients. Because both hypocretin and MCH play a key role in the regulation of sleep, energy homeostasis and autonomic function, partly by modulation of the somatotrophic, thyrotrophic and lactotrophic axes, neuroendocrine dysregulation may contribute to some of the non‐motor features of PD. In eight de novo, medication‐free PD patients and eight age‐, sex‐ and body mass index‐matched controls, we measured serum levels of growth hormone (GH), thyroid‐stimulating hormone (TSH) and prolactin every 10 min for 24 h. Auto‐deconvolution, cosinor and approximate entropy analysis were applied to quantify GH, TSH and prolactin secretion rates, diurnal rhythmicity, as well as regularity of hormone release. Sleep was polygraphically‐recorded throughout the night. Total 24‐h secretion of GH (191 ± 31 versus 130 ± 39 mU/l/24 h), TSH (38 ± 9 versus 36 ± 2 mU/l/24 h) and prolactin (102 ± 14 versus 116 ± 17 μg/l/24 h), as well as their diurnal rhythmicity and regularity of release, were not significantly different between PD patients and controls (all P ≥ 0.12). Fasting levels of insulin‐like growth factor‐1 were also unaltered in PD patients. However, free thyroxine (T₄) levels were significantly higher in PD patients compared to controls (16.19 ± 0.80 versus 13.88 ± 0.40 pmol/l; P = 0.031). In PD patients, prolactin levels were related to disease duration (r = 0.76, P = 0.028), whereas both GH (r = ?0.91, P = 0.002) and free T₄ (r = ?0.71, P = 0.050) levels correlated inversely with body fat content. Apart from a mild increase in free T₄ levels, we found no indications for altered somatotrophic, thyrotrophic and lactotrophic axes activity in early‐stage PD patients.     

Lithium effects on neuroendocrine function

1. We studied growth hormone and prolactin responses to insulin hypoglycemia and TSH responses to TRH in symptom-free bipolar patients and healthy controls.

2. There were no significant differences in prolactia and growth hormone responses to hypoglycemia between stabilized bipolar patients and healthy controls, both tested medication-free. When lithium was administered to both groups, only bipolar patients showed a dramatic reduction in prolactin and growth hormone responses.

3. Both bipolar patients in remission and healthy controls showed an increase of TSH response to TRH when treated with lithium in comparison with the testings before lithium administration.

4. The subjects, both patients and volunteers, showed a comparable degree of hypoglycemia on and off lithium.

5. The observed difference in responsivenes s of bipolar patients warrants further systematic investigation and offers interesting possibilities for practical utilization.     

Thyroid stimulating hormone response after thyrotropin releasing hormone in depressed, schizophrenic and normal women.

(1) Thyroid stimulating hormone (TSH) response after injection of thyrotropin releasing hormone (TRH) was studied in 23 depressed, 9 schizophrenic and 40 normal women. (2) In no group was TSH response correlated with age. (3) In the depressed patients, no relationship was found between TSH response and (i) severity of illness, (ii) clinical subtypes (unipolar/bipolar) and (iii) clinical remission. (4) There were no statistically significant differences in TSH baseline values between the groups. (5) Neither of the two patient groups showed reliable differences from controls regarding TSH response. However, depressed patients tended to show lower values than controls, while schizophrenic patients tended to show higher values than normal controls. (6) Significant differences were found between depressed and schizophrenic patients in regard to TSH response. In three depressed patients a TSH response below 5 μU/ml was found. This deficient TSH response occurred in unipolar depressed patients and was not seen in bipolar depressed patients, schizophrenic patients or normal controls. (7) These data provide evidence for a fault in hypothalamic pituitary regulation in some depressed patients but not in schizophrenic patients.     

Parallel changes of the responses of thyrotropin, growth hormone and prolactin to thyrotropin-releasing hormone in endogenous depression

The responses of growth hormone (GH) and prolactin (Prl) to thyrotropin releasing hormone (TRH) were studied in two selected groups of patients with endogenous depression (ED). One group, ED 1, was characterized by an increased thyrotropin (TSH) response to TRH after recovery from depression and by a good prognosis, whereas the other group, ED 2, was characterized by an unaltered TSH response and relapse within six months after stopping the antidepressive treatment. (1) After treatment significantly increased responses of GH (p <0.01) and Prl (p <0.05) to TRH were found in group ED 1, whereas those in group ED 2 were unchanged. (2) Using an increase of the GH response after treatment of 0.5 mg/ml compared to that before treatment, and an increase of 8.0 ng/ml of the Prl response, a correct prediction of the prognosis was possible in 74 and 72% of the patients, respectively. Using the TSH response to TRH we have previously reported correct prediction in 91% of patients with ED. This value is significantly higher than those obtained with the GH and Prl responses (p <0.05). (3) GH and Prl responses in ED were compared to those obtained in healthy and psychiatric controls, but they were found to be of no diagnostic value.     

Growth hormone (GH) response to clonidine and growth hormone releasing factor (GRF) in normal controls

To investigate the relationship between the plasma growth hormone (GH) response to provocative challenge with the hypothalamic peptide growth hormone-releasing factor (GRF) and the alpha 2-adrenergic agonist clonidine, we administered GRF (1 microgram/kg), clonidine (2 micrograms/kg), and placebo to 21 healthy normal controls (13 men and eight women). Both clonidine and GRF caused significant increases in plasma GH levels over baseline. The peak GH-responses to GRF and clonidine were similar (GRF = 8.7 +/- 6.7 ng/ml; clonidine = 6.5 +/- 5.9 ng/ml; Wilcoxon test: s = 361, z = -1.31, p = NS). The GH responses to GRF and clonidine were significantly correlated (rs = 0.62, n = 20, p = 0.004). Unexpectedly, we found that five of the 21 (26%) normal controls had no GH secretory response to either GRF or clonidine. There was a modest gender effect with clonidine (men greater than women; p less than 0.06) and a negative correlation between GH secretion and age with both GRF and clonidine. Neither GRF nor clonidine had an effect on cortisol levels (DRUG x TIME interaction: F(8,152) = 0.60, p = NS). These findings are consistent with animal studies suggesting that the GH response to clonidine is mediated by GRF. The age and gender effects underscore the importance of careful matching for these factors in studies measuring the GH secretory response.     

Thyroid status in senile dementia of the Alzheimer type (SDAT)

Thyroid function was investigated in a group of 21 patients with severe senile dementia of the Alzheimer type (SDAT) and in a group of 17 age and sex matched normal controls. Free thyroid hormone levels (triiodothyronine (T3) and thyroxine (T4) were measured, as were also the thyrotrophin (TSH), prolactin (PRL) and growth hormone (GH) responses to thyrotrophin releasing hormone (TRH)). When compared to controls, patients demonstrated a significantly lower free T3 value (but not free T4), a blunted TSH response to TRH, slightly elevated basal PRL and GH values and a small GH response to TRH. However, all differences were small in biological terms and were within the laboratory's normal range. This emphasizes the relative normality of neuroendocrine function, particularly thyroid status, in SDAT.     

Thyrotropin, prolactin, and growth hormone responses to thyrotropin-releasing hormone in anorexia nervosa and bulimia

Serum thyrotropin (TSH), prolactin (PRL), and growth hormone (GH) levels were measured before and after stimulation with thyrotropin-releasing hormone (TRH) in 10 patients with bulimia, 7 with features of the restricting subtype of anorexia nervosa, and 6 with bulimic subtype of anorexia nervosa. The mean basal levels of TSH, PRL, and GH did not differ among the three groups. A delayed TSH response was found in 86% of the restricting anorectics, 80% of the bulimic anorectics, and 22% of the bulimics. The PRL response was normal in all patients, with no significant difference among the three groups. Elevated basal GH levels were found in 29% of the restricting anorectics, 33% of the bulimic anorectics, and 33% of the bulimics. An abnormal GH increase after TRH stimulation was observed in 50% of the restricting anorectics, 20% of the bulimic anorectics, and 13% of the bulimics. These results suggest that some patients with bulimia, and some with anorexia nervosa, have a hypothalamic dysfunction. These neuroendocrine abnormalities do not appear to be due solely to low weight or to metabolic changes resulting from binge eating and are not associated with depressive symptoms.     

Effects of antidepressant treatment on thyrotropin-releasing hormone stimulation, growth hormone response to L-DOPA, and dexamethasone suppression tests in major depressive patients

Dexamethasone suppression (DST), thyroid-stimulating hormone (TSH) and prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) and growth hormone (GH) response to L-DOPA tests were evaluated in 19 depressed inpatients before the commencement of the antidepressant treatment and after the clinical response to examine: (i) the functional relationships among the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axis and dopaminergic system in depression, (ii) any alterations in these hormonal functions with the antidepressant treatment. TSH responses to TRH showed a tendency to increase from pre- to posttreatment period, while TRH-induced PRL and L-DOPA-induced GH responses did not change with treatment in depressed patients who responded to the treatment. Females showed significantly higher TSH and PRL responses to TRH compared to males. No interconnections were found among the responses in DST, TRH stimulation test and L-DOPA-induced GH test in the patients. The results do not support the interrelations between the abnormalities in the HPT and HPA axes and central dopaminergic activity in 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.     

Studies on the prolactin response induced by electroconvulsive therapy in schizophrenics

Electroconvulsive therapy (ECT) and simulated ECT (SECT)-induced prolactin response has been studied in 14 schizophrenic males. Cortisol, growth hormone, and thyroid stimulating hormone (TSH) changes have been measured simultaneously. The prolactin rise was significantly higher after ECT than after SECT. Cortisol increase after ECT did not exceed significantly the elevation after SECT. Changes in growth hormone and TSH concentrations were inconsistent and non-significant. On the basis of the results it may be assumed that ECT-induced prolactin response is a consequence of specific transmitter changes in the CNS and not a result of stress reaction or generalized neuronal discharge. ECT-induced prolactin response was negligible in two cases. Both patients were chronically hospitalized schizophrenics resistant to therapy. Whether the prolactin response or its absence is of predictive value with respect to prognosis or effect of ECT remains to be seen.     

Multiple hormone responses to clonidine administration in depressed patients and healthy volunteers

Abnormalities in several hypothalamic-pituitary-target organ axes in depression may reflect alterations in central neurotransmitter receptor function. As the alpha 2-adrenergic receptor has been implicated in a variety of neuroendocrine abnormalities in depression, we assessed the role of alpha 2-adrenoceptor dysfunction in mediating response abnormalities of growth hormone, cortisol, and prolactin after intravenous clonidine administration (an alpha 2-adrenergic receptor agonist) in 18 patients with major depression (12 with melancholic features, 6 without melancholic symptoms) and 9 healthy volunteers. In particular, we examined the hypothesis that these abnormalities might be more evident in patients with DSM-III melancholic depression. After clonidine, the mean growth hormone response was significantly lower in melancholic depressives compared to controls (p = 0.02), and the shape of the growth hormone response profile was also significantly different in melancholic patients (p = 0.04). There was an overall decrease in the mean cortisol concentration after clonidine in melancholic patients and control subjects (p = 0.02), as well as a larger cumulative prolactin response in melancholic patients compared to those without melancholic features (p = 0.02). The present results confirm prior observations of a blunted growth hormone response after clonidine and suggest that alterations in alpha 2-adrenergic receptor activity might also contribute to several neuroendocrine abnormalities in patients with melancholic depression.     

Effect of hypothalamic ventromedial lesions on plasma growth hormone response to growth hormone-releasing factor in rats

The effect of ventromedial-arcuate (VMH-ARC) nuclei lesions on plasma growth hormone (GH) response to human growth hormone-releasing factor (GRF, 1 microgram/kg b.wt., i.v.) was studied in conscious rats after they had received chlorpromazine (CPZ) or CPZ plus antiserum against somatostatin (ASS). When rats were pretreated with CPZ alone, there was no difference in basal plasma GH level between VMH-ARC lesioned rats and controls. The magnitude of plasma GH response to GRF in 5 out of 6 VMH-ARC lesioned rats exceeded that of controls. When the same observation was repeated using the same rats after they had received ASS and CPZ, basal plasma GH levels of controls were significantly higher than those of VMH-ARC lesioned rats, and the magnitude of the plasma GH response to GRF was augmented in both groups of rats. The plasma GH response to GRF was comparable between two groups, though the peak plasma GH response to GRF was slightly but significantly lower in VMH-ARC lesioned rats as compared to controls. Pituitary GH content was reduced significantly in VMH-ARC lesioned rats as compared to controls. The results demonstrate that the pituitary responsiveness to GRF does not appear to be altered significantly in rats bearing bilateral VMH-ARC lesions. In addition, the placement of electrolytic lesions in VMH-ARC regions causes reduced SS secretion into the hypophyseal portal vessels and leads to an augmentation of plasma GH response to GRF.     

Hormonal response to thyrotropin-releasing hormone following rest-activity reversal in normal men

The prolactin (PRL) and thyrotropin (TSH) response to an intravenous dose (400 micrograms) of thyrotropin-releasing hormone (TRH) was studied in eight healthy young men in the morning (0800 hr), in the evening (2000 hr), and after an acute 12-hr shift of the rest-activity cycle. The PRL and TSH response to TRH was significantly greater in the evening than the morning. The increased PRL and TSH responses observed in the evening were significantly reduced following rest-activity reversal. Our findings underscore the importance of temporal factors in determining response to TRH. These factors may be relevant in clarifying the mechanisms underlying abnormal hormonal responses to TRH in patients with affective disorders.     

Effect of hypthalamic ventromedial lesions on plasma growth hormone response to growth hormone-releasing factor in rats

The effect of ventromedial-arcuate (VMH-ARC) nuclei lesions on plasma growth hormone (GH) response to human growth hormone-releasing factor (GRF, 1 μg/kg b.wt., i.v.) was studied in conscious rats after they had received chlorpromazine (CPZ) or CPZ plus antiserum against somatostatin (ASS). When rats were pretreated with CPZ alone, there was no difference in basal plasma GH level between VMH-ARC lesioned rats and controls. The magnitude of plasma GH response to GRF in 5 out of 6 VMH-ARC lesioned rats exceeded that of controls. When the same observation was repeated using the same rats after they had received ASS and CPZ, basal plasma GH levels of controls were significantly higher than those of VMH-ARC lesioned rats, and the magnitude of the plasma GH response to GRF was augmented in both groups of rats. The plasma GH response to GRF was comparable between two groups, though the peak plasma GH response to GRF was slightly but significantly lower in VMH-ARC lesioned rats as compared to controls. Pituitary GH content was reduced significantly in VMH-ARC lesioned rats as compared to controls. The results demonstrate that the pituitary responsiveness to GRF does not appear to be altered significantly in rats bearing bilateral VMH-ARC lesions. In addition, the placement of electrolytic lesions in VMH-ARC regions causes reduced SS secretion into the hypophyseal portal vessels and leads to an augmentation of plasma GH response to GRF.     

Multiple hormonal responses to morphine: relationship to diagnosis and dexamethasone suppression

Plasma cortisol, prolactin (PRL), growth hormone (GH), and thyroid stimulating hormone (TSH) responses to intravenous morphine (0.1 mg/kg body weight) were investigated in five healthy women and 22 female psychiatric inpatients (eight with major depression, 12 with schizophrenia and two with personality disorders) during a 120 min period. The results were also related to a subsequent dexamethasone suppression test (DST). Morphine caused a strong and progressive decline in plasma cortisol which was uniform in controls, depressed, and nondepressed patients. DST nonsuppressors had significantly higher cortisol levels during the entire period, but the same response to morphine. Morphine strongly stimulated PRL secretion, which was found to be significantly smaller in patients than in controls, but no difference was seen between depressed and nondepressed subjects. GH and TSH showed only minor and variable changes after morphine, with no overall significant differences. The data in this study do not support the assumption of a major alteration in opiate receptor responsivity either in depression or in DST nonsuppressor patients insofar as the regulation of the adrenal, thyroid, GH and PRL hormone secretion is concerned.     

Central action of interleukin-1 in altering the release of TSH, growth hormone, and prolactin in the male rat

In order to determine the possible effects of interleukin-1 on the release of pituitary hormones by direct action on the brain, the peptide was injected into the third brain ventricle of conscious, unrestrained male rats and the effects on hormone release were compared with effects on rectal temperature. The procedure of blood sampling and intraventricular injection resulted in a significant decline in body temperature and a decrease in plasma growth hormone without alteration in the plasma level of thyroid stimulating hormone (TSH) and prolactin. Interleukin-1 injected intraventricularly at a dose of 5 ng (0.3 pmol) prevented the decline in body temperature that occurred in the saline-injected controls and resulted in a significant elevation of plasma growth hormone levels that became apparent within 15 min of injection, as well as a highly variable but significant elevation of plasma prolactin and a significant decline in plasma TSH that was observed at 30 min. The results were similar when areas under the release curves for the various hormones were calculated. On the other hand, the higher dose of 25 ng (1.5 pmole) of interleukin-1, although producing a frank pyrexia, was associated with smaller changes in hormone values, which were no longer significant for any of the three hormones. The results indicate that interleukin-1 can act in minute doses, presumably on structures near the third ventricle, to stimulate growth hormone and prolactin release and to inhibit TSH release. Apparently when frank febrile responses occur, these hormonal responses are muted for reasons that are yet to be determined. In view of the minute doses injected we favor a hypothalamic site for these effects.     

Plasma profiles of adrenocorticotropic hormone,cortisol, growth hormone and prolactin in patients with untreated parkinson's disease

Summary Plasma profiles of prolactin, growth hormone, adrenocorticotropic hormone (ACTH) and cortisol were evaluated in a group of untreated patients with idiopathic Parkinson's disease and a group of healthy age-matched controls. Plasma integrated concentrations of all hormones except prolactin were significantly lower in the patients as compared with the controls; however, prolactin nocturnal peak concentration was significantly elevated in the patients; nocturnal growth hormone levels were significantly reduced in the Parkinson group; ACTH and cortisol plasma concentrations were also consistently lower during most of the day in the patients with Parkinson's disease. These data confirm the presence of a hypothalamic disturbance in patients with idopathic Parkinson's disease, which can affect pituitary function.