To Thyrotropin-releasing Hormone Test Research Articles

HPT axis, CSF monoamine metabolites, suicide intent and depression severity in male suicide attempters

A lower thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in depressed women has been associated with violent suicide attempts, suicidal intent, higher lethality and suicide risk. The cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) levels are related to suicidal behaviour. We studied the HPT axis function in twelve male suicide attempters and eight healthy volunteers submitted to lumbar puncture and to TRH test. Suicidal behaviour and depression severity were assessed. There was no association between deltamaxTSH and violent suicidality or subsequent suicide. The deltamaxTSH correlated with CSF HVA in suicide attempters. The plasma T3 showed a negative correlation with the Beck Suicide Intent Scale and the Montgomery Asberg Depression rating scale. Dopaminergic regulatory mechanisms on the thyroid hormone activity may be altered in male suicide attempters.

Effect of Dexamethasone on TSH Secretion Induced by TRH in Human Obesity

BackgroundThe presence of an abnormally high thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) makes it difficult to distinguish some euthyroid obese subjects from subclinically hypothyroid obese patients. Here, we...

Early postoperative growth hormone levels: high predictive value for long-term outcome after surgery for acromegaly.

To explore the prognostic value of early - within 1 week - postoperative growth hormone (GH) measurements with regard to outcome after surgery for acromegaly in a short- and a long-term perspective. Retrospective study of patients operated on between 1987 and 1998, including follow-up for up to 60 months. University hospital. Sixty-eight patients with acromegaly. Pituitary surgery aiming at adenomectomy with preservation of pituitary function. The effect of the operation was evaluated after 3 months, mostly by means of an oral glucose load or by insulin-like growth factor 1 (IGF-1). The specificity, sensitivity and the predictive values of an early postoperative mean GH concentration </= 4.8 mU L-1, as well as of the GH response to thyrotropin-releasing hormone (TRH) 3 months after surgery, were calculated with regard to outcome of the operation in both 3-month and long-term perspectives. Fifty patients (73.5%) showed a satisfactory effect at the evaluation 3 months postoperatively; 45 of these were followed between 12 and 60 months. Relapse was registered in five cases: 12, 12, 24, 24 and 48 months after surgery. In the long-term perspective, the predictive value of an early mean GH </= 4.8 mU L-1 was 93.6% with regard to a satisfactory effect of surgery, compared with 90.2% for a normalized somatomedin C (SmC)/IGF-1 and 90.0% for an absent GH response after TRH. An early mean GH > 4.8 mU L-1 had a 77.8% predictive value for persistent or recurrent disease, compared with 85.7% for persistently increased SmC/IGF-1 and 68.8% for an abnormal GH release after TRH 3 months after surgery. In the short-term perspective, the specificity and the predictive value of an early GH </= 4.8 mU L-1 were 77.3 and 97.1%, respectively. Early GH > 4.8 mU L-1 had a 94.4% sensitivity but a predicative value of only 63.0% for an unsatisfactory effect. Measurement of GH within 1 week after surgery is highly predictive for outcome of surgery for acromegaly. Specifically, an early mean GH </= 4.8 mU L-1 is as predictive for a satisfactory effect of treatment as a normalized IGF-1 3 months after surgery. Early postoperative GH values > 4.8 mU L-1 have a high sensitivity for persistent or recurrent disease in both the short- and long-term perspectives, but lower predictive value. The usefulness of the TRH test can be questioned.

Thyroid function in early pregnancy II: Paradoxical growth hormone response to thyrotropin-releasing hormone

A variant of growth hormone (GH) known as human placental growth hormone (hpGH) is found in maternal serum during pregnancy. It is well established that during the second half of normal pregnancy, pituitary GH secretion is suppressed; however, there are no data about maternal GH secretion during the first trimester of pregnancy, The present study reports the response of GH to thyrotropin-releasing hormone (TRH) in eight pregnant women in the first trimester of pregnancy (weeks 6-9) who had previously requested voluntary interruption of pregnancy. The TRH test induced a significant paradoxical GH response with a peak of 9.4 ± 0.5 ng/ml (mean ± SD) at 30 min and a higher thyroid-stimulating hormone (TSH) response in pregnant women. The increment was observed until 120 min and no response was observed in the control group.These data show the paradoxical response of GH to TRH, a releasing factor to which the hormone does not normally respond. This paradoxical secretion may be due to direct pituitary stimulation and can be explained on the basis of a state of gestational hypothyroidism.

THE THYROTROPIN RELEASING HORMONE STIMULATION TEST IN ALCOHOLISM

The mechanism for a blunted thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in alcoholics is not known. We performed a combined TRH and gonadoliberin stimulation test on three well-defined groups of nondepressed alcoholic men. Group A comprised patients with acute withdrawal symptoms (n = 28), group B patients abstinent for 5-8 weeks (n = 29) and group C patients who had been abstinent for > 2 years (n = 16). Twenty-two healthy male volunteers were used for comparison. A blunted TSH response to TRH (delta TSH < 5 microU/l) occurred only in groups A (39%) and B (17%). In group A delta TSH showed a significant negative correlation with the severity of withdrawal symptoms and a significant positive correlation with serum magnesium levels. In group B, patients with a family history of alcoholism had significantly lower delta TSH levels than those without such a family history. Groups did not differ with respect to basal and delta prolactin, and TSH responses were not significantly associated with vitamin deficiency, cortisol levels or free thyroid hormone levels. We conclude that TRH stimulation test blunting appears to be related to factors operating in the withdrawal state and improves with continued abstinence. A possible role of genetic factors and serum magnesium needs to be further explored.

Occult Hyperprolactinemia in Infertile Women

Objective To define the hypersensitive status of PRL secretion in normoprolactinemic infertile women and determine the incidence of occult hyperprolactinemia among them. Design The potential for PRL secretion was examined in 463 women. Setting Outpatient clinic in a university hospital. Patients Three hundred sixty-seven infertile women and 96 healthy volunteers. Interventions Patients were treated with bromocriptine, 2.5 or 5 mg/d for 3 months. Main Outcome Measures Prolactin response to thyrotropin-releasing hormone (TRH), circadian rhythm, and serum PRL changes during the menstrual cycle. Results Approximately 15% of infertile women showed an exaggerated response to TRH, and 95% among them had clinical disorders such as galactorrhea, luteal insufficiency, and menstrual disturbances. Bromocriptine proved effective in 90% of these women. Transient hyperprolactinemia was observed at night in 80% of normal PRL responders who had galactorrhea. Bromocriptine was effective in 75% of these women. Transient hyperprolactinemia during the menstrual cycle was observed in 43% of normal PRL responders with luteal insufficiency, 85% of whom responded to treatment with bromocriptine. Conclusion In infertile women, the TRH test helps in the selection of patients who may respond to bromocriptine. Among normal PRL responders, 60% of patients with galactorrhea and 47% of those with luteal insufficiency recovered after bromocriptine treatment. From these results, patients who exhibit clinical abnormalities such as galactorrhea and luteal insufficiency should undergo extensive PRL testing.

Lack of seasonal variation in abnormal TSH secretion in patients with seasonal affective disorder

The circadian variations in thyroid-stimulating hormone (TSH) secretion, with particular attention to the nocturnal serum TSH surge and the TSH response to thyrotropin releasing hormone (TRH), were measured in seven patients with seasonal affective disorder (SAD) and in eight normal controls. Both patients with SAD and normal controls were tested in fall/winter, when patients were suffering depressive symptoms, and in spring/summer, when patients were euthymic. The TRH tests were performed in the morning. In all tests, the mean peak TSH response to TRH was significantly lower in the patients with SAD than in the normal controls. No significant differences were observed in either group between spring/summer and fall/winter tests. At both periods, patients with SAD showed normal TSH levels in the morning, but did not experience a nocturnal TSH surge. In this group, morning and night TSH levels were similar. In contrast, normal controls showed significantly higher TSH levels at night than in the morning. Serum-free thyroid hormone levels were in the normal range in all subjects. Morning and night serum cortisol levels and 24-hour urinary cortisol concentrations were similar in all subjects. These data show that the secretion of TSH is impaired in SAD, regardless of the phase of the psychiatric disease. The low TSH response to TRH in the presence of normal serum thyroid hormone levels and the lack of the TSH nocturnal surge suggest that patients with SAD might be affected by mild central hypothyroidism.

Occult hyperprolactinemia in infertile women

To define the hypersensitive status of PRL secretion in normoprolactinemic infertile women and determine the incidence of occult hyperprolactinemia among them. The potential for PRL secretion was examined in 463 women. Outpatient clinic in a university hospital. Three hundred sixty-seven infertile women and 96 healthy volunteers. Patients were treated with bromocriptine, 2.5 or 5 mg/d for 3 months. Prolactin response to thyrotropin-releasing hormone (TRH), circadian rhythm, and serum PRL changes during the menstrual cycle. Approximately 15% of infertile women showed an exaggerated response to TRH, and 95% among them had clinical disorders such as galactorrhea, luteal insufficiency, and menstrual disturbances. Bromocriptine proved effective in 90% of these women. Transient hyperprolactinemia was observed at night in 80% of normal PRL responders who had galactorrhea. Bromocriptine was effective in 75% of these women. Transient hyperprolactinemia during the menstrual cycle was observed in 43% of normal PRL responders with luteal insufficiency, 85% of whom responded to treatment with bromocriptine. In infertile women, the TRH test helps in the selection of patients who may respond to bromocriptine. Among normal PRL responders, 60% of patients with galactorrhea and 47% of those with luteal insufficiency recovered after bromocriptine treatment. From these results, patients who exhibit clinical abnormalities such as galactorrhea and luteal insufficiency should undergo extensive PRL testing.

Screening for thyroid disorders in a working population

Subclinical thyroid disorders have received increasing attention in recent years due to refined laboratory methods and a stronger emphasis on the role of preventive medicine. We performed a screening for thyroid-stimulating hormone (TSH) on 6884 persons in a working population. In cases in which TSH was not within the normal range we also measured the levels of triiodothyronine (T3), thyroxine (T4), and thyroxine-binding globulin (TBG). All persons who did not present with exclusion criteria or other nonthyroidal illnesses (n = 59) and the controls (n = 39) were submitted to thyrotropin-releasing hormone (TRH)-testing. Additionally, sonography of the thyroid was performed on 120 persons (59 subjects with abnormal hormone levels and 61 controls) to determine thyroid size and rule out morphological abnormalities. Based on the TRH test and T3, T4, and TBG measurements we found a prevalence of 0.03% (2/6884) for overt hyperthyroidism, 0.33% (23/6884) for subclinical hypothyroidism, 0.09% (6/6884) for subclinical hypothyroidism, and 0.015% (1/6884) for overt hypothyroidism in the healthy population. In subjects with overt or subclinical hyperthyroidism the prevalence of goiters (thyroid volume > 18 ml in women, > 25 ml in men) was 28%. Of this group 48% had structural abnormalities. All persons with goiters and/or structural abnormalities were over 35 years of age. Among the euthyroid, 20% had thyroid enlargement, and the same proportion presented with structural abnormalities. There were no differences between the two age groups. In the group with overt/subclinical hypothyroidism 47% presented with structural abnormalities of the thyroid; however, none presented with thyroid enlargement. Thyroid nodules were found only in older persons (> 35 years) with euthyroidism or hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Blunted TSH and unaltered PRL responses to TRH following repeated administration of TRH in neurologic patients: A replication of neuroendocrine features of major depression

A blunted thyrotropin (TSH) and an unaltered prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) are widely recognized in neuroendocrinology of depression. We studied effects of repeated TRH administration of 1 mg/day for 10 days on the pituitary-thyroid axis function and PRL secretion in 16 euthyroid patients with neurological disorders. Although levels of serum thyroid hormones and of nonstimulated PRL were not affected by the treatment, baseline TSH levels were markedly inhibited. A blunted response of TSH to TRH was found without a significant effect on a PRL response to TRH after long-term treatment with TRH in four patients in whom a TRH test was performed. These changes are similar to those in depressed patients. TRH administration in this manner replicates a lowered sensitivity of thyrotrophs of the pituitary with a normal responsibility of lactotrophs in depression.

Panic, suicide, and agitation: Independent correlates of the TSH response to TRH in depression

We investigated the relationship between suicidality, agitation, panic attacks, and the thyrotropin-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH), and tested the hypothesis that panic would account for the association between a reduced TSH response and the other conditions. Twenty-seven euthyroid primary unipolar depressed inpatient women received a TRH test and systematic psychiatric assessment. Panic attacks were insufficient to explain the link between the TSH response and suicidal intent, lethality, and agitation; each condition was independently associated with a lower TSH response. In an additive fashion, copresence of conditions further reduced TSH response. The symptom constellation of panic, agitation, and suicidality in depression may correlate with the greatest reduction in TSH response.

Triiodothyronine administration reduces serum growth hormone levels and growth hormone responses to thyrotropin-releasing hormone in patients with anorexia nervosa

The aim of this study was to test the hypothesis that low serum T 3 concentrations may promote an abnormal growth hormone (GH) response to thyrotropin-releasing hormone (TRH) in patients with anorexia nervosa. Eight anorexic women and two anorexic men, ages 15–25 years, with low free T 3 circulating levels (mean ± SEM = 2.8 ± 0.3 pmol/l) were studied. A TRH test (200 μg IV) was carried out under basal conditions and repeated following treatment with oral T 3 (1.5 μg/kg BW/day) for eight days. Following T 3 administration, GH levels dropped significantly from a baseline of 7.1 ± 1.3 μg/l to 3.1 ± 0.7 μg/l ( p<0.02), as did GH peak responses to TRH (9.0±1.0 μg/l vs. 4.4 ± 0.8 μg/l, p<0.01). ANOVA and analysis of area under the curve (AUC) confirmed that after T 3 treatment there was a significant reduction in TRH-induced GH release in these patients (GH AUC: 902±132 μg/l vs. 456±91 μg/l, p<0.02). TSH responses to TRH, which were normal prior to T 3 treatment, completely disappeared following it, and PRL responses to TRH also were diminished. Although our experimental approach does not permit a conclusion that low T 3 levels were the primary reason for these changes, the data support the theory that low T 3 circulating levels may facilitate abnormal GH secretion and the GH-releasing activity of intravenous TRH.

TSH response to TRH in depression with and without panic attacks

Low thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) has been repeatedly described in approximately 25% of patients with major depression. Panic disorder appears related to depression along several dimensions, including prevalence of low TSH response to TRH. The authors divided 46 patients with primary unipolar depression by gender and by presence or absence of concurrent panic attacks and compared their TRH test results with those of 106 normal control subjects, controlling for confounding variables. Depressed patients with panic had higher prevalence of low TSH response and significantly lower mean TSH response than depressed patients without panic. The latter were indistinguishable from normal control subjects.

TRH test in schizophrenic patients and controls

The thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) is a neuroendocrine challenge test of the hypothalamic-pituitary-thyroid (HPT) axis. A blunted TSH response to TRH has been found to occur signi~cantly more often in depressed patients than controls (Loosen and Prange 1982). However, blunted TSH response to TRH have also been found in other neuropsychiatric disorders, including personality disorder, eating disorders, mania, ~~ho~srn, and cocaine abuse (reviewed in Extein et al. 1984). There have been relatively few studies of the TRH test among schizophrenic patients (reviewed in Braddock and Blake 1981). Of particular interest have been four studies that have reported abnormal growth hormone (GH) responses to TRH infusion in schizophrenic patients (Gil-Ad et al. 1981; Weizman et al. 1982; Ferrier et al. 1983; Demilio 1984). As part of a series of neurobiological studies in schizop~enia, we had performed the TRH test in 14 chronic schizop~nic patients and 14 ageand sex-matched controls. Thus, the purpose of this report is to compare schizophrenic patients and controls for their TSH, GH, and prolactin (PRL) responses on the TRH test.

Use of Sensitive Immunoradiometric Assay for Thyrotropin in Clinical Practice

Although measurement of thyrotropin (thyroid-stimulating hormone; TSH) by radioimmunoassay was a major advance in the laboratory diagnosis of thyroid failure--replacing the time-consuming TSH stimulation test--it was not sufficiently sensitive to discriminate reliably between euthyroid and hyperthyroid patients. Measurement of the TSH response to thyrotropin releasing hormone (TRH) served this purpose, however. The recent development of TSH assays that are severalfold more sensitive and more specific than conventional radioimmunoassays has allowed distinction of euthyroid from hyperthyroid patients and eliminated the need for the TRH test. Although undetectable levels of TSH, compatible with hyperthyroidism, are occasionally noted in euthyroid patients with severe nonthyroidal illness and during the first trimester of pregnancy, false-positive results are less often recorded for TSH than for free or total thyroid hormone measurements. Measurement of TSH by sensitive immunoradiometric assay is currently the most useful first-line test of thyroid function in patients with suspected thyroid disease and, in addition, has a valuable role in monitoring the dose of thyroxine replacement therapy.

Nodular goiter: Effects of surgery and thyroxine medication

AbstractIn a prospective investigation, thyroid function was studied in 43 patients before and after surgery on a nontoxic nodular goiter. Prior to surgery, 11 patients displayed a flat thyroid‐stimulating hormone (TSH) response to thyrotropin‐releasing hormone (TRH), suggesting subclinical hyperthyroidism. Thyroid autoantibodies (microsomal/thyroglobulin) were found in low titers in 7 of 43 patients, and in no patient were TSH‐receptor antibodies found. Three months following surgery, 32 patients were chemically euthyroid and 11 patients had elevated TSH values. Seven of the latter had additional signs of hypothyroidism and were given continuous thyroxine substitution. Starting 3 months after surgery, increasingly higher doses of thyroxine were administered to patients with a normal TRH test until an abnormal TSH response was observed. Four patients had a flat TSH response to TRH without administration of thyroxine and in 9 patients a daily dose of only 0.1 mg resulted in such a response. The 32 euthyroid patients developed flat TSH responses at an average dose of 123 μg of thyroxine. The data indicate that following surgery, the thyroid hormone production from the nonnodular thyroid remnant has low suppressibility, suggesting that, in nodular goiter, tissue with abnormal hormone production is widely distributed within the gland. It appears then that thyroxine medication in nodular goiter has a place mainly in patients developing hypothyroidism following surgery.

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 ΔTSH and age was found both in healthy subjects and in depressed patients. We based our comparison on normal ranges for ΔTSH calculated from the ΔTSH 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 radio-immunoassay 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.

Central thyroid stimulation in severely ill depressed, manic and schizophrenic patients

A blunted thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) has frequently been reported in endogenous depression and in other psychiatric diseases (Loosen and Prange 1982). Several studies have also reported an increased TSH response to TRH associated with low-normal thyroid hormone levels, particularly in depressed women (Targum et al. 1982; Calloway et al. 1984). Other authors have found abnormalities in thyroid hormone levels in different psychiatric disorders, with conflicting results on the possibilities of a relationship to blunted TRH test results (Prange et al. 1979; Kirkegaard and Faber 1981, Calloway et al. 1984). We evaluated the longitudinal pattern of TRH test results and thyroid hormone values in 35 patients with major depression and 15 control patients with schizophrenia and mania. Surprisingly, we found that four patients showed a simultaneous increase in the TSH response to TRH and all thyroid hormones during severe depressive, manic or psychotic crisis. Results with these four patients are presented.

Weight loss causes neuroendocrine disturbances: experimental study in healthy starving subjects

A variety of endocrine dysfunctions have been reported for anorexia nervosa, protein caloric malnutrition, and depression. The effect of reduced caloric intake and weight loss on endocrine functions was assessed in an experiment with five healthy female subjects during an initial baseline phase, a 3-week phase of complete food abstinence, weight gain to the original level, and a final baseline phase. During fasting, disturbances in hypothalamic-pituitary-adrenal function were observed, with elevated plasma cortisol levels, increase in the number of secretory episodes, increase in cortisol plasma half-life, and insufficient suppression following 1.5 mg dexamethasone. While all dexamethasone suppression tests (DSTs) were normal at baseline, 7 of 14 DSTs showed insufficient suppression in the fasting phase. During fasting, basal thyroid-stimulating hormone (TSH) values were lowered and the TSH response to thyrotropin-releasing hormone (TRH) was blunted. The plasma level of growth hormone (GH) over 24 hours was elevated during fasting and administration of the α 2-adrenergic receptor agonist clonidine resulted in a subnormal GH response after restoration of original body weight. One of the five subjects showed increased irritability, distress, anxiety, and depression as measured by various psychological scales. The results show that reduced caloric intake, weight loss, or catabolic state have powerful effects on several endocrine systems. The specificity of measures of endocrine disturbances (DST, TRH tests, and clonidine tests) as biological markers for certain types of depression must be questioned, and the metabolic state should be given more consideration in future studies.

Effect of amitriptyline on the thyrotropin response to thyrotropin-releasing hormone in endogenous depression

Patients with endogenous depression whose depressive episodes were clinically resolved after electroconvulsive therapy were divided into two groups: one in which patients remained well ( n = 16) and another in which patients relapsed within 6 months ( n = 11). Treatment with amitriptyline for 3 weeks did not affect the median thyrotropin (thyroid-stimulating hormone; TSH) response to thyrotropin-releasing hormone (TRH) in recovered patients, whereas that in relapsed patients was significantly enhanced. The data suggest that amitriptyline affects the TSH response to TRH differently in stably recovered and relapsed patients. If this effect is maintained beyond the 3-week period studied, treatment with amitriptyline will invalidate the predictive value of the TRH test.