Effect of TRH on TSH and prolactin levels in affective disorders

The thyrotropin-releasing hormone (TRH) test was studied in 32 patients with acute major depressive disorder, 16 patients with recurrent unipolar (n = 8) or bipolar (n = 8) affective disorder in remission, and 22 healthy control subjects. Twenty-six of the 32 acutely ill patients were also studied when in remission. Outcome in these patients was correlated to serum levels of triiodothyronine (T3), 3,3',5'triiodothyronine (reverse T3), thyroxine (T4), thyroid-stimulating hormone (TSH), prolactin (PRL), melatonin, dexamethasone suppression test (DST) results, and clinical symptoms assessed by the Comprehensive Psychopathological Rating Scale (CPRS). The TSH response to TRH (delta TSH) was decreased in the acutely ill patients, but no difference was found between patients in remission and controls. The delta TSH was correlated to TSH but not to T3 and T4 levels in both acutely ill and control subjects. In the acutely ill group, delta TSH did not distinguish between patients with normal and abnormal DST results. Thus, abnormalities in the hypothalamic-pituitary-thyroid (HPT) axis are not correlated to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, delta TSH did not differentiate between melancholic (DSM-III) and nonmelancholic patients or between patients with primary and secondary depression. No correlation was found between delta TSH and CPRS scores. Patients with observable agitation greater than 0.25 points (item range 0-3) had higher levels of delta TSH than patients with lower levels. No significant correlation was found between delta TSH and seven specific symptom clusters on the CPRS. However, there was a possible relation between low delta TSH and violent suicide attempts or suicide. PRL levels did not distinguish acutely ill patients from controls. Finally, there was no significant regression between delta TSH and melatonin levels. The decrease in delta TSH seen in the acutely ill patients was too small to be of diagnostic value as a laboratory measure differentiating acutely ill and healthy subjects. The mechanism underlying the HPT alterations in acute major depressive disorder may be a desensitization of the TRH receptor in the thyrotrophs secondary to an increased endogenous TRH stimulation.     

Free-thyroxine index in schizophrenic patients before and after neuroleptic treatment

The mean values of serum thyroxine (T4), in vitro radioactive triiodothyronine uptake and free-thyroxine index (FTI) in 41 drug-free schizophrenic patients did not differ significantly from those of euthyroid controls. Following 6 weeks' treatment of 24 schizophrenics with chlorpromazine, trifluoperazine or clozapine, a significant decrease in serum T4 and FTI was noted after chlorpromazine and clozapine, whereas after trifluoperazine only serum T4 decreased, but not FTI. The questions arising from these findings are discussed and the need for a future investigation of serum triiodothyronine and serum TSH in schizophrenic patients before and after neuroleptic treatment is stressed.     

Serum dopamine-beta-hydroxylase activity in patients with major depressive disorders

The dopamine-beta-hydroxylase (DBH) activity in serum was assayed in 32 acutely ill inpatients with major disorder and in 33 healthy control subjects. Twenty-six of these patients were also studied in a state of remission. The DBH activity was compared to the serum levels (studied during a 24 h period) of T4, T3, TSH, prolactin and melatonin as well as to the outcome of the dexamethasone suppression and TRH test and to various clinical symptoms, as estimated by different rating procedures. No significant differences in DBH activity were found between the acutely ill patients, patients in remission, or normal subjects. Thus, the determination of the activity does not seem to be of practical importance as a laboratory diagnostic tool for major depressive disorder. A significant positive correlation was found between the DBH activity and the TSH levels, estimated by several parameters during the 24 h period, in the acutely ill patients, whereas no significant correlation was found in patients in remission or in the normal subjects. No significant correlation was found between the DBH activity in any group and the other laboratory or clinical parameters. The mechanism behind the significant correlation between the DBH activity and TSH levels remains to be clarified.     

The evaluation of thyroid functions, thyroid antibodies, and thyroid volumes in children with epilepsy during short-term administration of oxcarbazepine and valproate

PURPOSE: The aim of this study was to evaluate the effects of short-term oxcarbazepine (OXC) and valproate (VPA) monotherapy on thyroid functions in children. METHODS: Fifty-five newly diagnosed epileptic children with normal thyroid functions (confirmed with the thyrotropin releasing hormone stimulation test) participated in this study. VPA treatment was started in 30 patients and OXC in 25 patients. Serum thyroxine (T(4)), free thyroxine (fT(4)), triiodothyronine (T(3)), free triiodothyronine (fT(3)), reverse T3 (rT(3)), thyroid peroxidase antibodies (TPO-ab), and urine iodine levels were evaluated at baseline and at the third and sixth months of therapy. RESULTS: In the OXC group, serum T(4), fT(4), T(3), fT(3), and rT(3) levels were found to be decreased at the third and sixth months, the differences were significant compared to the baseline values except for fT(3) levels at the third month and fT(4) and rT(3) levels at the sixth month (p < 0.05). At the sixth month, serum T(4) level dropped below the normal reference value in 8 (32%), fT(4) in 5 (20%), T(3) in 4 (16%), and fT(3) in 3 (12%) patients. In the VPA group, mean T(4), fT(4), T(3), fT(3), and rT(3) levels at 3 and 6 months remained similar compared to the baseline values (p > 0.05). Mean serum thyroid stimulating hormone levels increased significantly at the sixth month compared to the baseline values in the VPA group (p < 0.05) while it remained unchanged in the OXC group (p > 0.05). There was no effect of either drug on urinary iodine excretion and serum TPO-ab levels remained in normal ranges throughout the study. CONCLUSIONS: In this prospective study, it is documented that children under short-term OXC or VPA therapy showed altered thyroid functions similar to the changes observed after long-term treatment. Although, the clinical significance of these results need to be evaluated with future studies, this observation of altered thyroid functions points out that thyroid functions may need to be monitored closely in children receiving antiepileptic treatment, even in the short-time interval.     

Neuroendocrinological investigations during sleep deprivation in depression. I. Early morning levels of thyrotropin, TH, cortisol, prolactin, LH, FSH, estradiol, and testosterone

Measurements of 12 hormones were conducted in patients with major depressive disorder at 8 AM on the morning before and at 8 AM on the morning after total sleep deprivation (SD). Thyrotropin (TSH), thyroxine (T4), triiodothyronine (T3), and free T3 (fT3) were measured in 50 patients, free T4 in 39 patients, reverse T3, cortisol, prolactin, luteinizing hormone, and follicle-stimulating hormone in 21, estradiol in 20 (women), and testosterone in 14 (men). After SD, there was a significant rise in TSH, T4, T3, and fT3 concentrations and a significant fall in testosterone levels. The increases in TSH levels were significantly correlated to clinical response. Responders to SD had higher T4, fT4, rT3, and testosterone concentrations before SD. Neither age, gender, polarity, nor antidepressant medication had a clearly significant effect on the response to SD.     

Schizophrenia, psychoticism, neuroleptics, and auditory evoked potentials

Auditory cortical evoked potentials of 20 schizophrenic patients with an acute exacerbation of the illness were investigated before neuroleptic medication and after remission of the acute symptoms, and compared with healthy controls matched for sex and age. Additionally, tests were conducted in 40 healthy volunteers to ascertain whether psychoticism or other personality factors were correlated with evoked potentials. The aim of the study was to test the overarousal hypothesis of schizophrenia and to control the effects of clinical state, neuroleptic medication and personality factors. Acutely ill schizophrenic patients had a shorter evoked potential N1 latency (Table 1). After remission of the symptoms under haloperidol N1 latency of the patients was no longer different from that of the controls. Patients after remission and on medication, however, had longer P2 and N2 latencies and a greater P2-N2 amplitude (Table 2). Psychoticism and extraversion were correlated negatively with amplitude data of components N1 and P2 in healthy volunteers. The results favor the overarousal hypothesis of schizophrenia. Haloperidol normalizes N1 latency in acutely ill patients. It's effect on later components of the evoked potentials seems comparable to a reduction in vigilance. Auditory evoked potentials might allow to follow up the effect of neuroleptics in acute schizophrenia. It seems necessary to consider personality factors when comparing patients with healthy controls in evoked potential studies.     

Altered interrelationship of dopamine,prolactin, thyrotropin and thyroid hormone in schizophrenic patients

Summary Increased dopaminergic activity has been postulated to be one of the main causes of schizophrenia. To evaluate this hypothesis further, the interrelation between dopamine, prolactin, thyrotropin (TSH) and l-thyroxine was studied by determining their concentrations in the serum of ten acutely ill schizophrenic patients exhibiting distinct stages of process activity and ten healthy subjects. The level of dopamine was elevated in the sera of schizophrenic patients, whereas the levels of prolactin, TSH and l-thyroxine were decreased. On the basis of these results we hypothesize that 1. increased dopaminergic activity affects pituitary secretory function, and 2. decreased -adrenergic activity may be a consequence of decreased thyroid hormone concentration in plasma.     

Twenty-four-hour serum levels of T4 and T3 in relation to decreased TSH serum levels and decreased TSH response to TRH in affective disorders

The serum levels of thyroxine and triiodothyronine (T4 and T3) were investigated at 10 different time points during a 24 h period in 31 inpatients meeting the RDC criteria for acute major depressive disorder. Twenty-three of these patients were also reinvestigated in a state of partial or complete remission. The results show that there was no significant difference in T4 or T3 levels during the 24 h period between depressed patients and 32 healthy controls despite significantly decreased TSH levels and TSH response to TRH administration (delta TSH) in the patient group. No indications were obtained that the patients' clinical presentation or depressive symptomatology as revealed by their CPRS scores, psychotropic medication, melatonin levels, or the outcome of the dexamethasone test, significantly influenced the T4 or T3 levels. The depressed patients who were studied longitudinally showed increased T4 levels in the acute phase compared to remission, whereas the T3 levels did not change. However, the levels of thyroid hormones were within the normal range in the acute phase as well as in remission. Furthermore, the changes in thyroid hormones between the state of relapse and remission were not significantly correlated to the corresponding increase in TSH levels and delta TSH between the two assessments. The present results are consistent with the hypothesis that the mechanism behind the impaired TSH response to TRH in acute major depressive disorder is a downregulation of the pituitary TRH receptors.     

Changes in thyroid hormones, thyroid stimulating hormone and cortisol in acute spinal cord injury.

To determine the hormonal response to acute spinal cord injury, serial serum samples were collected from 18 patients with acute spinal cord injury and from 14 control patients with spinal fractures without cord injury. The first sample was taken within 24 hours of injury, the second at 24-48 hours; and the third at 7 days for determination of thyroxine (T4), free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), T3 uptake (T3U), thyroid stimulating hormone (TSH), thyroxine binding globulin (TBG), growth hormone (GH), cortisol, and insulin. Significant increases were observed in rT3 levels and transient changes were observed in the T4 and T3 levels in the spinal cord injured group but not in the group with spinal fractures alone. The changes in the spinal cord injured patients are consistent with the 'low T3 syndrome'. However, the persisting rise of rT3 at 7 days was an unexpected finding. In addition to the cord injury, these changes may also be related to dexamthasone administration and nutritional factors.     

Neuroendocrinological investigations during sleep deprivation in depression. II. Longitudinal measurement of thyrotropin, TH, cortisol, prolactin, GH, and LH during sleep and sleep deprivation

Thyrotropin (TSH), thyroxin (T4), triiodothyronine (T3), free T3 (fT3), cortisol, prolactin, and human growth hormone (HGH) were measured every 2 hr during a night of sleep, the following day, and a night of sleep deprivation (SD) in 14 patients with major depressive disorder. In subgroups fT4 (n = 5), reverse T3 (rT3), and luteinizing hormone (LH) (n = 6) were also investigated. Significant increases in TSH, T4, fT4, T3, fT3, rT3, and cortisol and decreases in prolactin levels occurred during the night of SD, compared to the pattern during the night of sleep. The pre-SD T4 and T3 levels of the responders to SD were already higher than in the nonresponders, and increased less during SD. The cortisol and HGH concentrations of the responders rose higher during SD than those of the nonresponders. Changes in TSH and prolactin were not correlated to clinical response. Analysis of possible neurochemical mechanisms underlying this "pattern" of changes in different endocrine profiles suggests that enhanced noradrenergic activity might play a role in the changes in TSH, cortisol, thyroid hormones, and possibly HGH secretion during SD, and increased dopaminergic tone probably induced the decline in prolactin levels. Additional effects of the serotonergic system cannot be excluded at present. In conclusion, the data suggest that enhanced noradrenergic activity of the locus coeruleus stimulates alpha and/or beta adrenergic receptors in depressed patients during SD. This mechanism could well be involved in the antidepressant effect of this therapy.     

Effects of six weeks' neuroleptic treatment on the pituitary-thyroid axis in schizophrenic patients

In order to investigate the effects of 6 weeks' neuroleptic treatment on the pituitary-thyroid axis in 25 male schizophrenic patients, and the diurnal variation in the thyrotropin (TSH) and prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) in these patients, the TRH stimulation test was performed in each of them at 14.00 and 24.00 h of the same day, both before and after 6 weeks' treatment with neuroleptics (chlorpromazine or fluspirilene). Also, serum thyroxine (T4), in vitro radioactive triiodothyronine uptake (RT3 U) and free-thyroxine index (FTI) values were estimated from the pre-TRH blood sample. We found no evidence of diurnal variation in the TSH response to TRH in the schizophrenic patients, before or after 6 weeks' neuroleptic treatment. Only drug-free schizophrenic patients had significantly higher PRL responses to TRH at 14.00 h than those at 24.00 h. After 6 weeks' neuroleptic treatment, schizophrenic patients tended to have lower FTI values; also, they had significantly higher basal TSH and PRL values, as well as significantly augmented TSH and PRL responses to TRH, in comparison to their pretreatment values. These findings render possible the diagnosis of subclinical hypothyroidism in neuroleptic-treated schizophrenic patients.     

TSH response to TRH and haloperidol response latency in psychoses

Thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) was measured in 19 acutely psychotic (DSM-III schizophrenia, 7; schizophreniform, 2; schizoaffective, 3; affective, mood-incongruent psychosis, 5; manic, mood-congruent psychosis, 2) drug-free patients prior to systematic trials of lithium and/or haloperidol. TSH response was not associated with sex, age, baseline T4, or baseline TSH. A reduced TSH response was associated with affective diagnosis and was a significant predictor of a positive, rapid response to neuroleptic treatment.     

Zinc affects the metabolism of thyroid hormones in children with Down's syndrome: normalization of thyroid stimulating hormone and of reversal triiodothyronine plasmic levels by dietary zinc supplementation.

Levels of circulating thyroid stimulating hormone (TSH), tetraiodothyronine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5' triiodothyronine (reversal T3 or rT3) were measured in 25 children with trisomy of chromosome 21, also known as Down's syndrome (DS), and in 14 normal children. In subjects with DS TSH levels were increased, while plasmic levels of rT3 were decreased. No alteration in T3 and T4 levels was observed. Before zinc supplementation, plasmic levels of zinc and thymulin, a zinc dependent thymic hormone, were significantly decreased in DS children. After four months of dietary supplementation with zinc sulphate, a normalization of plasmic zinc, thymulin and TSH levels was observed. Plasmic levels of rT3 significantly increased, and after zinc treatment no difference was detectable between DS children and normal children. Clinical evaluation of the health status of DS children showed that zinc supplementation decreased the incidence of infectious diseases and improved school attendance. Thus, the increased efficiency of the immune system and the normalization of some endocrine parameters by zinc supplementation suggests that zinc deficiency may play a crucial role in some of the pathological manifestations associated with the syndrome, such as infections and malfunctioning of the thyroid gland.     

Prolactin levels in drug-naïve patients with schizophrenia and other psychotic disorders

Objective: Hyperprolactinaemia as a side effect of dopamine receptor blockers is common in patients with schizophrenia and other psychotic disorders and may lead to amenorrhoea, galactorrhoea, hypogonadism, subfertility and osteoporosis. The aim of our study was to determine whether hyperprolactinaemia occurs also in patients with schizophrenia and other psychotic disorders prior to any antipsychotic treatment.

Methods: Serum prolactin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), free tetraiodothyronine (FT4) and cortisol levels were measured in 40 newly diagnosed, drug naïve, patients with schizophrenia and other psychotic disorders and in 40 age and gender matched healthy subjects.

Results: The median prolactin value was 12.5?ng/ml (range: 2–38?ng/ml) for patients and 8.6?ng/ml (range: 4–17.6?ng/ml) for healthy subjects (p?=?0.011). Patients had lower levels of T3 compared to healthy controls (mean: 1.08?ng/ml, SD: 0.16 vs. 1.18?ng/ml, 0.18, respectively; p?=?0.008). Serum TSH, FT4 and cortisol levels were similar between the two groups. Multiple regression analysis revealed that the difference in serum prolactin values was independent of thyroid function (TSH, FT4, T3) and serum cortisol levels.

Conclusions: A higher serum prolactin level was found in drug naïve, newly diagnosed patients with schizophrenia and other psychotic disorders compared to healthy controls, prior to starting any antipsychotic treatment.     

Changes in thyroid function during ACTH therapy in patients with infantile spasms

Serum triiodothyronine (T3), free T3, thyroxine (T4) and free T4 levels were measured before and immediately after daily ACTH-Z therapy (0.01 mg/kg/day, 1-2 weeks) for patients with 9 cases of infantile spasms and one case of myoclonus epilepsy. In some of them, serum reverse T3 (rT3) and thyroxine binding globulin (TBG) levels were also measured. All patients became seizure free after ACTH-Z therapy. Before ACTH-Z therapy, all of the hormone levels were within normal limits. Serum T3 and free T3 levels were markedly decreased after daily ACTH-Z therapy, and serum T4, free T4 and TBG levels were moderately decreased after the therapy. 1-6 weeks after the daily treatment, all of these hormone levels returned to pretreatment levels. Serum rT3 levels did not change after ACTH-Z therapy. These results suggest that the effect of long-term daily ACTH-Z therapy is very critical to the immature brain, and conventional ACTH-Z therapy has to be reconsidered.     

Changes in the pituitary-thyroid axis accompanying major affective disorders

The reports tries to show the intercorrelations between the TRH-test and the peripheric thyroid function during the course of affective disorders. The sample comprised 22 manic (15 follow-up) and 24 depressive (13 follow-up) patients. As parameters serum thyroxine, triiodothyronine, T3-uptake, FT4-index, T3/T4-ratio, TSH basal and 30 min after 200 micrograms TRH i.v. were determined. In a smaller group of patients reverse-T3 was measured, too. During acute mania and depression there is an increase of thyroxine. We observed a stronger conversion of T4 to rT3 with less inactivation of T4 to T3 in mania than in depression. Both groups show attenuated TSH response to TRH stimulation in florid psychoses. Comprehensing all results we come to the conclusion that the changes in the pituitary-thyroid axis accompanying affective psychoses start from the thyroidea and not from the anterior pituitary gland.     

首发精神分裂症患者的血清甲状腺相关激素水平变化及其与临床关系对照研究

目的探讨首发精神分裂症患者血清甲状腺相关激素（Ｔ３、Ｔ４、ＴＳＨ、ＦＴ３及ＦＴ４）水平的动态变化及其与临床关系。方法４１例患者分别于疗前、疗后进行ＢＰＲＳ评定及血清Ｔ３、Ｔ４、ＴＳＨ、ＦＴ３、ＦＴ４测定，并与正常对照组作比较。结果研究组疗前血清甲状腺素（Ｔ４）显著高于对照组，并随治疗及病情改善而恢复正常。但游离甲状腺素（ＦＴ４）在疗前、疗后均低于正常对照组。患者的ＢＰＲＳ得分高低与其疗前血清Ｔ３、Ｔ４水平显著正相关（Ｐ＜０．０５）。结论精神分裂症患者血清Ｔ４、ＦＴ４水平变化可能与其疾病本身有关。血清Ｔ３，Ｔ４水平似乎可预测精神分裂症的严重度。     

Thyroglobulin and Thyroid Hormones in Patients on Long-Term Treatment with Phenytoin, Carbamazepine, and Valproic Acid

Serum concentrations of total triiodothyronine (T3) and thyroxine (T4) as well as serum thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) were measured in 24 patients with epilepsy taking anticonvulsants (either phenytoin, carbamazepine, or valproic acid as single treatment) and in a control group of 28 patients with scoliosis but without thyroid disease. The T4 as well as the TSH concentrations were depressed in patients on phenytoin or carbamazepine treatment. The T3 concentration was increased in the patients on carbamazepine or valproic acid treatment, whereas the Tg levels were unaffected by all three drugs. Thus, a slight depression of the TSH concentration within the normal range does not influence the Tg release. The lack of change in the Tg concentration also speaks against a direct effect of the antiepileptic drugs on the thyroid gland.     

Influence of carbamazepine on serum thyroxine and triiodothyronine in patients with epilepsy

Hypothyroidism induced by anti-epileptic drug treatment gave rise to thyroid function test studies in patients treated with carbamazepine (CBZ) only. In 42 patients on long-term CBZ treatment thyroxine (T4), free T4-index (FT4I), and triiodothyronine (T3) concentrations in serum were significantly lower than in controls, while triiodothyronine uptake (T3U) and thyrotropin (TSH) concentrations did not differ between patients and controls. In 12 patients starting on CBZ, means T4, calculated FT4 and thyroxine binding globulin (TBG) were 1-5 months later reduced compared to the initial levels. Thus, CBZ reduced thyroid hormones, TBG and FT4I. A CBZ-induced increase in conversion and metabolism of the thyroid hormones could explain this effect. The normal T3U values and decreased concentrations of TBG make a competitive CBZ binding to TBG less probable. Although the thyroid hormones levels were found lowered in the patients, all remained clinically euthyroid during the study.     

The role of NGF and IL-2 serum level in assisting the diagnosis in first episode schizophrenia

Development of reliable diagnostic bio-markers for schizophrenia remains a diagnostic challenge. Serum NGF and IL-2 were analyzed to examine the diagnostic efficiency and predictive capability of these two biomarkers in relation to schizophrenia diagnosis. Thirty neuroleptic naïve subjects with first-episode schizophrenia, thirty patients with major depressive disorder (MDD) and twenty-eight healthy control subjects participated in the study. One-way ANOVA demonstrated significantly lower serum IL-2 and NGF among schizophrenic patients and patients with MDD compared with healthy controls. Receiver operating characteristic (ROC) curve analysis was used to ascertain diagnostic efficiency of serum IL-2 and NGF levels. Area under the ROC curve (AUC) revealed a high level of differentiation between schizophrenic patients and healthy controls for both IL-2 and NGF serum concentrations. Diagnostic efficiency of combined NGF and IL-2 serum levels was also high in schizophrenic patients compared with healthy controls. Serum NGF and IL-2 are promising as potential screening or diagnostic biomarkers for schizophrenia and may be a useful adjunct for clinical assessment.