Thyrotropin-releasing Hormone Test Research Articles

Endocrine effects of testosterone undecanoate as a supplementary treatment to menopausal gonadotropins or tamoxifen citrate in idiopathic oligozoospermia

To evaluate the effects of T undecanoate given as a supplementary treatment with tamoxifen citrate (TAM) or hMG on pituitary and Leydig cell function in men with idiopathic oligozoospermia. A total of 48 normogonadotropic men with idiopathic oligozoospermia were allocated in to six groups (n = 8 per group) treated with placebo, 40 mg T undecanoate three times per day, 10 mg TAM two times per day, T undecanoate and TAM, 75 IU/d hMG, and T undecanoate and hMG. All groups were evaluated with standard GnRH, thyrotropin-releasing hormone, and hCG tests before and on the final day of 3 months on treatment with measurements of FSH, LH, thyroid-stimulating hormone (TSH), PRL, T, E2, 17-hydroxyprogesterone, sex hormone-binding globulin, and seminal analyses (at least twice each time). Basal and stimulated concentrations and incremental FSH and LH values showed no differences among TAM or hMG and TAM + T undecanoate or hMG + T undecanoate treated groups. Basal, stimulated, and incremental values for TSH and PRL were elevated markedly during treatment in most groups in comparison to placebo. Basal, stimulated, and incremental T and E2 values were similar in active treatment groups except that higher T concentration was found in TAM + T undecanoate as compared with T undecanoate only treated men. Finally, significant improvements were noted in important seminal parameters and particularly in the functional sperm fraction of the TAM + T undecanoate group as compared with single treatment with TAM. These results indicate that T undecanoate in combination with TAM or hMG not only had no adverse effects on pituitary and Leydig cell activity but also seemed to improve important seminal parameters and signify that androgens may be tried as a supplementary treatment to conventional regimes in idiopathic oligozoospermia.

Combined pyridostigmine–thyrotrophin-releasing hormone test for the evaluation of hypothalamic somatostatinergic activity in healthy normal men

Pyridostigmine (PST), a cholinesterase inhibitor, induces a clear growth hormone (GH) release in man by suppression of hypothalamic somatostatin (SRIH). Somatostatin suppresses thyrotrophin (TSH) release in rats and men. Earlier studies showed that the thryotrophin-releasing hormone (TRH)-induced TSH response was not altered by 60-120 mg of PST. We studied whether a larger dose (180 mg) of PST can increase the TSH response to TRH. Six healthy young men were studied with the following six tests: (Test 1) 200 micrograms of TRH i.v.; (Test 2) 180 mg of PST po; (Test 3) three different doses of PST (60, 120, 180 mg) + TRH; (Test 4) 100 micrograms of octreotide (SMS) i.v.; (Test 5) SMS + TRH; (Test 6) PST + SMS + TRH. A large dose of PST (180 mg) significantly augmented GH, TSH and prolactin responses to TRH, while smaller doses of PST (60 and 120 mg) did not significantly increase the responses of GH and TSH. While the increased TRH-induced prolactin response by PST was not suppressed by SMS, the increased responses of GH and TSH were suppressed remarkably by SMS. Most of the subjects noticed a mild to moderate abdominal pain, nausea and muscular fasciculation after the administration of a large dose of PST administration. These data suggest that suppression of hypothalamic SRIH secretion by 180 mg of PST can augment the TSH response to TRH. However, the considerable side effects should be minimized before clinical application of the combined PST-TRH test.

Hormonal Regulation of the Thyrotropin Releasing Hormone (TRH) Gene

Significant advances in understanding the function, distribution, and hormonal regulation of TRH gene expression have occurred since the cloning of the TRH gene. TRH gene expression is widespread in the CNS and peripheral sites but only TRH mRNA located in the paraventricular nucleus is under negative regulation by thyroid hormone. Molecular biological experiments using gene transfer of TRH promoter-reporter mini' genes reproduce the in vivo transcriptional repression by thyroid hormones. In vitro binding studies using the TRH promoter demonstrate binding sites for transcriptional trans-acting factors including thyroid hormone receptor, CREB, and c-jun. The divergent hormonal response of the TRH gene in the thyrotropic area of the hypo-thalamus compared to peripheral sites illustrate the importance in hormonal regulation of the distribution of cell-specific factors including nuclear hormone receptors and transcription factors.The TRH stimulation test has been replaced by second and third generation TSH assays in the diagnosis of hypothyroidism. The paradoxical response of some pituitary adenomas to exogenous TRH administration allows the use of the TRH test as a marker for these tumors. The studies demonstrating the widespread distribution and function of TRH have provided information that has led to the new and exciting field of the therapeutic use of TRH in a wide array of clinical disorders.

Thyroid antoantibodies and the response to thyrotropin releasing hormone in patients with subclinical hypothyroidism.

To evaluate the clinical usefulness of the thyrotropin releasing hormone (TRH) test and estimation of thyroid autoantibody concentrations in patients with borderline raised thyroid stimulating hormone (TSH). The records of 34 consecutive patients with persistent borderline increased TSH (4.4-9.9 mU/l) referred to the Medical Investigation Unit were reviewed. The response of patients with thyroid autoantibodies to the TRH test was compared with that of patients with a negative antibody screen. Eleven (44%) of 25 patients with positive anti-thyroid microsomal and/or thyroglobulin antibody tests and three (33%) of nine patients with a negative antibody screen had hypothyroid responses to TRH. Neither age nor sex affected the response to TRH. Basal TSH alone was poorly correlated with these indices. Twelve (35%) patients who had elevated basal TSH had a normal response to the TRH test. Patients with positive or negative thyroid autoantibodies and an exaggerated response to the TRH test should be regarded as hypothyroid and treated with thyroxine. Patients with positive thyroid autoantibodies and normal TSH response may subsequently develop hypothyroidism and should be given long term follow up.

The hypothalamo-hypophyseal system in patients with multinodular colloid euthyroid goiter

Eighty patients with multinodular colloidal euthyroid goiter were examined. Thyrotropin-releasing hormone (TRH) test was carried out in 22 patients and 7 healthy women. The results of the test indicate a clear-cut tendency to reduction of hypophyseal TTH reserve in patients with multinodular euthyroid goiter with enlarged thyroid. In other words, clinical diagnosis of an euthyroid condition in the examinees appears to be groundless, particularly in patients with stage IV multinodular euthyroid goiter who may be referred to latent hyperthyrosis group on the basis of TRH test results. Three types of STH reaction were revealed by TRH test in these patients. The authors put forward a hypothesis on STH contribution as a growth factor to the pathogenesis of multinodular colloid euthyroid goiter.

Mechanism of anovulation in hyperprolactinemic amenorrhea determined by pulsatile gonadotropin-releasing hormone injection combined with human chorionic gonadotropin

To clarify the mechanism of anovulation in hyperprolactinemic anovulatory women by subcutaneous (SC) pulsatile GnRH injection. Prospective clinical study. Studies were made on at the Department of Obstetrics and Gynecology, the University of Tokushima, School of Medicine. Six hyperprolactinemic (group 1) and 7 normoprolactinemic (group 2) anovulatory patients were studied. After examinations of pulsatile secretion of LH, the GnRH test, thyrotropin-releasing hormone test and estrogen test, pulsatile GnRH treatment (20 micrograms/2 hours SC) was performed. Two protocols were tested on each patient. In the non-hCG protocol, GnRH treatment was continued until ovulation. In the hCG protocol, 5,000 IU of hCG was injected to induce ovulation when follicles were fully mature. The rates of follicular maturation and ovulation, serum E2 and P in the two groups. Pulsatile LH secretion was impaired in both groups. LH release 48 hours after estrogen injection was impaired in group 1 but not in group 2. Follicles matured on pulsatile GnRH treatment in all cycles in both groups. However, with the non-hCG protocol, ovulation occurred in only 17% of group 1, but in 89% of group 2. With the hCG protocol ovulation occurred in all cycles in both groups. The main cause of anovulation is impaired gonadotropin pulsatility and derangement of the estrogen-positive feedback effect on LH secretion in hyperprolactinemic patients, their ovarian response to gonadotropin being well maintained. Subcutaneous pulsatile GnRH therapy combined with hCG can be used as an alternative to bromocriptine treatment for induction of ovulation in these patients.

Diagnosis and treatment of thyrotoxicosis in childhood. A European questionnaire study.

A covering letter and a questionnaire covering the diagnosis and treatment of thyrotoxicosis in childhood was circulated between October 1992 and February 1993 amongst 672 European members of the European Thyroid Association (ETA) and members of the European Society for Pediatric Endocrinology (ESPE). Almost 50% replied to the letter and 99 individuals or groups from 22 countries completed the questionnaire. A consensus was reached on the use of total thyroxine (T4) and/or free T4 and thyrotropin as routine diagnostic tools. Two-thirds included total triiodothyronine (T3) and/or free T3 and 32% used a thyrotropin-releasing hormone test. Surprisingly, thyroglobulin autoantibodies were used as a routine test by 78%; 63% included thyrotropin receptor antibodies and 60% microsomal antibodies, whereas only 50% measured thyroperoxidase antibodies. For thyroid imaging, 40% performed a thyroid scintigram and 56% measured the size of the thyroid gland by ultrasound. Antithyroid drugs (ATD) were the basic initial treatment of choice given by 99% of the respondents for children with uncomplicated Graves' disease. Carbimazole, methimazole and thiamazole were the most frequently used drugs, with a median initial dose of 0.8 mg.kg-1.day-1. Two-thirds added beta-blockers and a few used sedatives. The ATD dose was adjusted for each patient by 39%, whereas 56% combined ATD with T4 for long-term treatment; 84% gave treatment for a fixed period (44% for 1-2 years). Surgery was considered the treatment of choice in children with an adenoma (83%), with a nodular (53%) or large goiter (16%) and recurrence after ATD (14%).(ABSTRACT TRUNCATED AT 250 WORDS)

A case of familial thyroxine binding globulin excess associated with growth hormone deficiency

A 7 years 3 months old Japanese boy with familial thyroxine binding globulin (TBG) excess associated with growth hormone (GH) deficiency is reported. The patients height was 106.4 cm (-2.86 s.d.) and his bone age was 5 years and 3 months. He had no goiter and his developmental milestones were normal. The serum thyroid stimulating hormone (TSH) was 2.8 microU/mL, triiodothyronine (T3) 3.1 ng/mL, thyroxine (T4) 23.4 micrograms/dL and free T4 1.8 ng/dL. The serum TBG level was beyond 80.0 micrograms/mL, with normal TSH response to the thyrotropin-releasing hormone (TRH) test. Familial study revealed that his grandmother, mother, uncle, younger sister and younger brother had high TBG and T3 levels, thus an X-linked co-dominant transmission was suggested. The peak GH responses to insulin and clonidine hydrochloride were 5.8 and 8.2 ng/mL, respectively. The mean nocturnal GH concentration was 2.5 ng/mL. His growth velocity increased from 4.8 to 8.4 cm/year and his serum TBG levels decreased gradually after human growth hormone (hGH) treatment.

Growth hormone secretion in children and adolescents with familial tall stature

Sixty-five patients (22 boys and 43 girls) presenting with familial tall stature were investigated with regard to growth hormone (GH) secretion, both physiological and after stimulation with thyrotropin releasing hormone (TRH) and growth hormone releasing hormone (GHRH). Plasma insulin-like growth factor-I (IGF-I) was also measured. Two groups of patients were distinguished according to their physiological secretion of GH: a high secretory group (n = 49) with a mean 24 h integrated concentration of GH (IC-GH) of 5.4 +/- 2.3 micrograms/l per minute and a large number of peaks (5.1 +/- 1.6 in 24 h), and a low secretory group (n = 16) with a mean 24 h IC-GH of 2.1 +/- 0.5 micrograms/l per minute and few peaks (3.3 +/- 1.3 in 24 h). Plasma IGF-I levels and GH peak values after the TRH test were significantly higher in the high secretory group. These results indicate that familial tall stature is the consequence either of hypersecretion of GH or of hypersensitivity to this hormone (IGF-I levels being normal in spite of low GH levels).

Influence of thyroid status on the paradoxical growth hormone response to thyrotropin-releasing hormone in human obesity

Thyrotropin-releasing hormone (TRH) tests were performed in 38 age- and weight-matched obese but otherwise healthy men. In all subjects, total thyroxine (T 4) and triiodothyronine (T 3) concentrations were in the normal range. According to basal and TRH-stimulated serum thyrotropin (TSH) levels, subjects were divided into the following three groups: group I (n = 14), euthyroid subjects; group II (n = 11), euthyroid subjects with normal basal but abnormally elevated TSH responses to TRH; group III (n = 13), subjects with elevated basal and TRH-induced TSH levels (subclinical hypothroidism). Basal TSH levels were 1.8 ± 0.4 mU/L in group I, 1.7 ± 0.3 in group II, and 6.0 ± 0.7 in group III. In both groups II and III, TRH-induced TSH increments were above the normal range (maximal increment >14 mU/L) and were significantly higher than in group I. The definition of euthyroidism for groups I and II and of subclinical hypothyroidism for group III according to the basal levels of TSH was confirmed by clinical (Billewicz index), hormonal (serum free-T 4 levels), and metabolic (serum apoprotein [apo] AI levels) parameters. Basal concentrations of growth hormone (GH) were similar in all groups. When GH levels after TRH stimulation were measured, significant increments (peak minus baseline >5 μg/L) were observed in nine of 13 hypothyroid obese men. The overall mean peak GH increase in group III was 4.5 times higher than baseline and was observed at 45 minutes. None of the euthyroid obese subjects of groups I and II showed any significant change in GH levels in response to TRH. These data show a paradoxical GH response to TRH in most obese men when they are affected by subclinical hypothyroidism, suggesting that this abnormality is related to hypothyroidism and not to obesity. The finding of an abnormal GH responsiveness to TRH in obese men with subclinical hypothyroidism but not in euthyroid obese men with elevated TSH responses to TRH suggests that these subjects are affected by different neuroendocrine alterations. The GH response to TRH may contribute to distinguish clinical conditions that are similar but require different therapeutic attention.

Do acute diseases transiently impair anterior pituitary function in patients over the age of 75? A longitudinal study of the TRH test and basal gonadotrophin levels.

Several studies have shown that anterior pituitary function is affected by the ageing process. Little is known, however, about the effect acute diseases have on the anterior pituitary. Should they be associated with a disturbance of anterior pituitary hormone production, they might make anterior pituitary function tests difficult to interpret when they are most needed. To test this hypothesis, we studied the thyrotrophin (TSH) releasing hormone (TRH) test and basal plasma gonadotrophins, taken as indicators of anterior pituitary function and reserve, in 74 consecutive patients (49 women) mean age 82 +/- 5.1 suffering from acute diseases soon after admission to hospital. A total of 44 (30 women) were followed up and retested after 3 disease-free months following recovery and discharge home. Seventy-one age- and sex-matched healthy controls (47 women), mean age 82 +/- 5.0 living in the community were also studied. The mean peak TSH increment after TRH (mean delta max TSH) increased from 5.7 soon after admission, to 7.7 U/l at follow-up (P = 0.01). The mean plasma LH increased from 25 to 35 U/l in women (P = 0.0004) and from 9.7 to 14 U/l in men (P = 0.03). The mean plasma FSH increased from 21 to 25 U/l in women (P = 0.04) and from 7.5 to 9.4 U/l in men (P = 0.01). Controls had greater TSH responses to TRH and higher plasma gonadotrophins levels when compared with acute patients (LH women P = 0.17, for all other tests P < 0.05). We conclude that a transient reduction of anterior pituitary function is a common occurrence in patients over the age of 75 suffering from acute diseases. This has diagnostic relevance and therapeutic implications.

Usefulness of thyrotropin-releasing hormone test, SMS 201-995, and bromocriptine in the diagnosis and treatment of gonadotropin-secreting pituitary adenomas.

Five patients with gonadotropin-secreting pituitary adenomas were studied. The utility of gonadotropin response to TRH stimulation in the diagnosis and follow-up of these tumors was evaluated, as well as the effects of somatostatin analogue SMS 201-995 and bromocriptine on gonadotropin release. Three patients had FSH and LH secreting adenomas while the other two tumors secreted FSH and alpha-subunit. Transsphenoidal resection of the pituitary adenomas were performed in all patients. Following preoperative TRH administration (400 micrograms i.v.), marked increases were observed in FSH levels in two cases, in LH levels in three and in alpha-subunit in one. The FSH and LH responses to t.his stimulus persisted in the same patients after surgery. Following acute bromocriptine administration (5 mg orally), FSH was reduced in all cases by 19% to 46%, LH in three cases by 50-67% and alpha-subunit in one by 33%. In patient no. 5, with persistent high FSH levels in the immediate postoperative period, long-term bromocriptine treatment was administered (15 mg/d orally), resulting in normalization of FSH levels 6 months later, although the size of the tumor was not reduced. After acute SMS 201-995 administration (100 micrograms sc) FSH decreased in two cases by 38% and 76%, LH in three by 30-56% and alpha-subunit in one by 20%. We conclude that gonadotropin response to TRH stimulation is useful in the diagnosis and follow-up of patients with gonadotroph adenoma. Bromocriptine and SMS 201-995 may be effective as coadjuvant treatment following surgery and radiotherapy in these patients, although long-term studies will be necessary to confirm these proposals.

Biochemical predictors of response to somatic antidepressant treatment

Ten years after the appearance of the first tricyclic antidepressant, a survey showed that only about two-thirds of depressed inpatients benefit from somatic treatment. The second-generation drugs and the selective reuptake inhibitors do not appear clinically more efficacious than the traditional tricyclic antidepressants. Along with the development of new drugs with alternative profiles of action, there have been many attempts to identify biologic tests and markers of affective disorders which could be useful in clarifying diagnosis and planning its treatment. This paper has reviewed studies of 11 biochemical predictor's - that is, dexa-methasone suppression test, thyrotropin-releasing hormone test, intravenous L-tryptophan test, 3-methoxy-4-hydroxyphenyl glycol, 5-hydroxyindoleacetic acid, precursor amino acids, amino acid transport into erythrocytes, platelet serotonin, platelet imipramine binding, platelet monoamine oxidase, and tyramine sulfate excretion - of antidepressant response and their application for clinical practice. Although some biochemical markers may be associated with antidepressant response in patient samples a reliable prediction of antidepressant response in individual patients is not available at present. On the basis of the state of knowledge of the biology of depression and the availability of treatments with various profiles of action, it is unsatisfactory that depression is not better treated. Improved and standardized methods for clinical description and diagnosis and for creating meaningful biochemical measures are needed.

The influence of DST and TRH test administration on depression assessments: A controlled study

Significant antidepressant effects have been reported after administration of dexamethasone and thyrotropin-releasing hormone (TRH). The purpose of this study was to evaluate whether or not the administration of the dexamethasone suppression test (DST) and TRH test in depressed patients, just before their entering clinical trials, has any impact on their symptoms. The Hamilton Rating Scale for Depression was administered to 166 subjects at screen visit, 1 week later (baseline visit), and 1 week after beginning treatment with fluoxetine 20 mg/day (week-1). Between screen and baseline visits, 62 patients were administered the DST alone, 6 underwent the TRH test alone, and 26 received both the DST and the TRH test. Seventy-two patients were not administered either test. No statistically significant differences in depression scores were found at screen, baseline and week-1 visits between patients who underwent neuroendocrine tests and those who did not. Our data suggest that the administration of neuroendocrine tests such as the DST and the TRH test does not have a statistically significant effect on depressive symptons and, therefore, does not interfere with study results and interpretation.

Thyroid function in elderly people. Thyrotrophin releasing hormone test is useful.

Thyroid function in elderly people. Thyrotrophin releasing hormone test is useful.

Anger attacks in unipolar depression, Part 2: Neuroendocrine correlates and changes following fluoxetine treatment.

Neuroendocrine derangements have been reported in both depression and aggressive behavior. The purpose of this study was to evaluate whether the subset of depressed patients with anger attacks have a distinctive neuroendocrine abnormality. The thyrotropin-releasing hormone (TRH) test was administered to 25 patients with major depression, 12 of whom reported having anger attacks, at the Depression Research Program of the Clinical Psychopharmacology Unit at the Massachusetts General Hospital. Twenty-two subjects underwent the TRH test again after 8 weeks of treatment with fluoxetine, a relatively selective serotonin uptake inhibitor. The depressed patients with anger attacks had a blunted prolactin response to TRH stimulation compared to the depressed patients without anger attacks. Treatment with fluoxetine was followed by an overall increase in the prolactin response to TRH among the depressed patients with anger attacks. The prolactin response to TRH also tended to predict the degree of response to treatment. These results suggest that the subset of depressed patients with anger attacks may have a greater central serotonergic dysregulation than depressed patients without such attacks.

Factors Affecting the Serum Free Thyroxine Levels in Hospitalized Chronic Geriatric Patients

Determination of whether nonthyroidal factors affect the diagnostic value of free thyroxine estimation in geriatric patients. Survey. A convenience sample of 381 non-selected, chronic, hospitalized geriatric patients over 60 years of age (I = relatively good health; II = relatively poor health; III = bad health; subgroups "sine therapia," ie, patients receiving no drugs that affect FT4) and 180 20-40 year old healthy persons. Thyrotropin-releasing hormone test; thyrotropin (TSH); free thyroxine (FT4, measured in part by two parallel methods) estimation in a screening study; and thyroxine-binding globulin and thyroxine-binding-inhibitor activity measurements. The normal FT4 ranges of the euthyroid geriatric (n = 210) and healthy young groups were similar. In the "sine therapia" euthyroid patients, FT4 decreased with age but increase with the severity of illness. High FT4 levels with non-suppressed TSH were more frequent in patients in poor and bad health. (I = 6/112; II = 14/140; III = 13/74; P < 0.01). The serum thyroxine-binding-inhibitor activity of euthyroid geriatric patients correlated with the severity of their clinical state (I = 6.22 +/- 5.65 (13); II = 7.40 +/- 4.33 (23); III = 10.04 +/- 5.50 (16) micrograms merthiolate equivalent/microL; ANOVA with log-transformed values: F(2.51) = 3.50, P < 0.05). The mean FT4 was higher in 36 heparin-treated patients (22.81 +/- 4.67 pmol/L) than in the 193 "sine therapia" patients (19.03 +/- 4.23 pmol/L; -P < 0.001). In a convenience subsample of 240 patients, a weak inverse correlation was found between FT4 and the thyroxine-binding globulin (r = -0.14, P < 0.02). Only 5/11 patients with low free thyroxine had hypothyroidism, while 11/46 patients with elevated free thyroxine had hyperthyroidism. There is no need to modify the normal free thyroxine range for hospitalized geriatric patients. Clinical condition, drug treatment, and, to a lesser extent, age are factors that significantly affect the diagnostic value of FT4 in hospitalized chronic geriatric patients, decreasing the specificity of the test in diagnosing clinical hyper- and hypothyroidism.

Pituitary-testicular and pituitary-thyroid axes in spinal cord-injured males

Thirty spinal cord-injured (SCI) males were studied for evaluation of their pituitary-testicular and pituitary-thyroid axes using combined luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) tests and electroejaculated semen analyses. Thirty age-matched normal male volunteers served as controls. There were four subjects with low serum triiodothyronine (T 3) levels, one with elevated serum follicle-stimulating hormone (FSH) level, eight with elevated serum testosterone levels, and 11 with elevated serum prolactin levels. There were significantly elevated luteinizing hormone (LH) responses to LHRH in SCI subjects when compared with normal controls. There were 16 (53.3%) SCI subjects who had exaggerated and/or prolonged LH responses. Among them, six subjects also had elevated FSH responses. There were eight and four subjects whose thyrotropin (TSH) and prolactin responses to TRH were exaggerated, respectively. Marked impaired motility was observed in 56 electroejaculated semen samples from 16 SCI subjects. There was a significant correlation between LH and total sperm count. Our data suggest that there is a reduced central dopaminergic tone in SCI subjects.

Thyrotropin response to thyrotropin-releasing hormone in patients with dementia of the Alzheimer type

Eleven patients with senile dementia of the Alzheimer type and 11 age-matched control subjects were given the thyrotropin-releasing hormone (TRH) test. The two groups did not differ with respect to peak thyrotropin (TSH) response or TSH levels at baseline, 20, 30, and 45 min after TRH injection. There were significant differences between the groups on Hamilton Depression Rating Scale scores (p < 0.03), although neither group met clinical criteria for depression. Items that were significantly different pertained to depressed mood, loss of interest, loss of insight, suicidal ideation, and obsessional symptoms.

An evaluation of basal hypothalamic-pituitary-thyroid axis function in depression: Results of a large-scaled and controlled study

In order to evaluate the function of the hypothalamic-pituitary-thyroid (HPT)-axis in unipolar depression, the authors measured basal 0800h plasma levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) by means of the new, ultrasensitive assays (TSH-IRMA) in 69 healthy controls, 62 minor, 101 simple major, and 57 melancholic depressed subjects. Basal HPT-axis hormone levels of almost all (96.8%) unipolar depressed patients fell within the normal, euthyroid range. None of the major depressed subjects showed subclinical hypothyroidism. It was found that 8.8% of the melancholic subjects exhibited some degree of subclinical hyperthyroidism. Basal TSH-IRMA values were significantly lower in melancholic patients than in healthy controls, minor and simple major depressed patients, and in major vs. minor depressed subjects. FT4 circulating levels were significantly higher in melancholic patients than in all other subjects. Basal TSH-IRMA and FT4 levels were significantly correlated with severity of illness. In depression, there was a significant and negative correlation between basal TSH-IRMA values and FT4 concentrations. No significant gender- or age-related differences in TSH-IRMA or thyroid hormones were detected in depression. It is argued that—in depression research—the assays of basal TSH-IRMA should replace thyrotropin releasing hormone tests.