Components of biological variation, including seasonality, in blood concentrations of TSH, TT3, FT4, PRL, cortisol and testosterone in healthy volunteers.

OBJECTIVE: There are few detailed studies of annual or seasonal variations in hormone concentrations in man. This study examines the components of biological variation, including seasonality, in plasma TSH, total T3 (TT3), free T4 (FT4), PRL, cortisol and testosterone in healthy volunteers. DESIGN: Monthly blood samplings for the assay of the above hormones were collected during one calendar year. SUBJECTS: Thirteen normal men and 13 normal women participated in the present study (mean age 38.7 +/- 13.4 years). MEASUREMENTS: Assays of TSH, TT3 and FT4 were carried out by means of immunoradiometric assays (IRMA), PRL by ELISA, cortisol by a fluorescence immunoassay, and testosterone with RIA. The time series were analysed by means of (bivariate or multivariate) spectral and cosinor analyses. RESULTS: Significant annual, four-monthly and biannual rhythms were detected in serum TSH; the lowest TSH values were observed in spring. A significant annual rhythm was detected in TT3, with lower values in spring and summer than in the other seasons. The peak-trough differences in the yearly variation expressed as a percentage of the mean were 29.1% and 8.2% for TSH and TT3, respectively. The yearly variation in plasma cortisol was significantly different between men and women: in men, 5.9% of the variation was explained by an annual rhythm, while in women 14.7% was explained by the fourth and seventh harmonical wave. The peak-trough differences in the yearly variation in plasma cortisol were 17.6% and 31.8% in men and women, respectively. There were no significant seasonal rhythms in PRL, FT4 or testosterone. The intraindividual/interindividual CV values were: TSH 29.3/48.4%, TT3 9.4/ 18.5%, FT4 7.1/9.1%, PRL 39.2/65.0%, cortisol 21.7/ 46.2%, and testosterone 12.6/40.8%. CONCLUSIONS: The degree of individuality measured in the plasma hormones is such that conventional population-based reference ranges may not correctly identify major alterations in these hormones in individual subjects.

Components of biological variation in serum soluble transferrin receptor: relationships to serum iron, transferrin and ferritin concentrations, and immune and haematological variables.

We investigated the components of biological variation in serum soluble transferrin receptor (TfR) in relation to serum iron, transferrin (Tf), ferritin, soluble interleukin-2 receptor (sIL-2R), sIL-6R, and number of erythrocytes, haemoglobin (Hb), haematocrit (Ht), mean corpuscular volume (MCV), mean cell haemoglobin (MCH), and erythrocyte distribution width (RDW). We took monthly blood samples during 1 calendar year from 26 healthy subjects for assay of the above variables. The estimated CVs for TfR were interindividual CVg = 20.8%, and intra-individual CVi = 13.6%; for Tf, CVg = 14.4% and CVi = 6.7%; for iron, CVg = 16.8% and CVi = 29.2%; and for ferritin, CVg = 71.1% and CVi = 26.5%. There was a statistically significant seasonal pattern in the four variables with significant annual, biannual and/or trimonthly rhythms, which were expressed as a group phenomenon. The peak-trough differences in the yearly variations, expressed as a percentage of the mean, were: for TfR, 11.7%; for iron, 39.2%; for Tf, 11.7%; and for ferritin, 29.3%. Up to 34.2% of the within-subject variability in TfR (which reflects changes over time) could be explained by the regression on iron, ferritin, Tf, sIL-2R, sIL-6R and MCH values. Up to 67.2% of the between-subject variability in TfR (which reflects differences in the homeostatic setpoint during the study year) could be explained by the regression on gender, iron, Tf, and ferritin values.

Seasonal variation in platelet [3H]paroxetine binding in healthy volunteers. Relationship to climatic variables.

Recently, our laboratory has reported significant seasonal differences in [3H]paroxetine binding to platelets in depressed subjects. This study aimed to examine the seasonal variation in [3H]paroxetine binding to platelets and the relationships between [3H]paroxetine binding and climatic variables in healthy volunteers. We took monthly blood samples during one calendar year from 26 healthy volunteers for assay of [3H]paroxetine binding and analyzed the data by means of univariate and multivariate spectral and cosinor analyses. There was a statistically highly significant seasonal pattern in [3H]paroxetine binding to platelets with significant annual, 4-monthly, and bimonthly rhythms, which were expressed as a group phenomenon. [3H]Paroxetine binding to platelets was significantly lower in fall and summer than in winter and spring; lows occurred in summer and peaks in spring. The peak-trough difference in this yearly variation, expressed as a percentage of the mean, was as large as 83.7%. A large part of the variance, that is, 32.5%, in [3H]paroxetine binding could be explained by weather variables, such as ambient temperature, relative humidity, and air pressure. Highly significant common annual rhythms were expressed in [3H]paroxetine binding and ambient temperature or humidity (both inversely related) and changes in temperature the 2 weeks preceding blood samplings (positively related).

Biochemical, metabolic and immune correlates of seasonal variation in violent suicide: a chronoepidemiologic study.

The purpose of this chronoepidemiologic study was to investigate the time-relationships between the yearly variations in occurrence of violent suicide in Belgium and the yearly variations in various biochemical, metabolic and immune variables in the Belgian population. The weekly mean number of deaths due to violent suicide for all of Belgium for the period 1979-1987 was computed. Twenty-six normal volunteers had monthly blood samplings during one calendar year for assays of plasma L-tryptophan (L-TRP), competing amino acids (CAA), and melatonin levels, maximal [3H]paroxetine binding to platelets, serum total cholesterol, calcium, magnesium, and soluble interleukin-2 receptor concentrations, and number of CD4+ T, CD8+ T and CD20+ B lymphocytes. The annual rhythm in violent suicide rate is highly significantly synchronized with the annual rhythms in L-TRP, [3H]paroxetine binding, cholesterol, calcium, magnesium, CD20+ B cells, and CD4+/CD8+ ratio; the mean peak (violent suicide, [3H]paroxetine binding) or nadir (all other variables) occurs around 3 May. There were significant inverse time-relationships between the time series of violent suicide rate and L-TRP, L-TRP/CAA ratio, total cholesterol, calcium and magnesium, CD4+/CD8+ T cell ratio and number of CD20+ B cells. Maximal [3H]paroxetine binding to platelets was significantly and positively related to the time series of violent suicide. An important part (56.4%) of the variance in mean weekly number of violent suicide rate was explained by the time series of L-TRP, cholesterol and melatonin.

Seasonal variation in plasma L-tryptophan availability in healthy volunteers. Relationships to violent suicide occurrence.

OBJECTIVE: To investigate the seasonal variation in levels of plasma L-tryptophan and competing amino acids (CAAs) in healthy humans in relation to climatic variables, total serum protein levels, and violent suicide occurrence. METHODS: Twenty-six healthy volunteers (13 men and 13 women; mean [+/- SD] age, 38.7 +/- 13.4 years) had monthly blood samplings for assays of L-tryptophan, valine, leucine, isoleucine, tyrosine, and phenylalanine during 1 calendar year. RESULTS: Significant annual rhythms were detected in L-tryptophan, the L-tryptophan/CAA ratio, phenylalanine, valine, and leucine, and semiannual rhythms in L-tryptophan values and in L-tryptophan/CAA ratios. Plasma L-tryptophan and the L-tryptophan/CAA ratio were significantly lower in the spring than in the other seasons. The peak-trough differences in the yearly variation expressed as a percentage of the mean were 17.1% and 16.1% for L-tryptophan values and L-tryptophan/CAA ratios, respectively. The amplitude of the yearly variation in all CAAs was low, ie, less than 7%. An important part of the variance in L-tryptophan availability (ie, 12% to 14%) could be explained by the composite effects of present and past climatic factors; higher ambient temperature and relative humidity in the face of lower air pressure are the most important predictors of low L-tryptophan availability. Important and positive time relationships were noted between total serum protein level and all amino acid concentrations, and a significant time relationship was also noted between the seasonal variation in L-tryptophan availability and the occurrence of violent suicide in Belgium. CONCLUSION: Our results show a bimodal seasonal pattern in the availability of plasma L-tryptophan that matches seasonal patterns in the prevalence of violent suicide in the local population and depression in other studies.

Components of biological variation in plasma haptoglobin: relationships to plasma fibrinogen and immune variables, including interleukin-6 and its receptor.

We investigated the components of biological variation, including seasonality, in plasma haptoglobin (Hp) levels and the relationships between plasma Hp and interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6), sIL-2R, fibrinogen (Fb) and absolute number of peripheral blood mononuclear cells, such as leukocytes, neutrophils, monocytes, lymphocytes, CD4+, CD8+, CD25+ T cells and CD20+ B cells. Monthly blood samples were taken from 26 normal volunteers during one calendar year. The estimated inter- and intra-individual C.V. values for plasma Hp were 27.9% and 20.0%, respectively; the index of individuality was 0.72. No significant seasonal rhythms could be detected in plasma Hp levels. The yearly mean values in plasma Hp were significantly and positively related to those in plasma Fb, absolute number of leukocytes, neutrophils, CD4+ T cells and the CD4+/CD8+ T cell ratio. 49.0% of the variance in the yearly mean values of plasma Hp could be explained by variances in serum IL-6 and number of CD4+ (positively related) and CD8+ (negatively related) T cells. There were significant and positive time relationships between plasma Hp, on the one hand, and plasma Fb, sIL-6R, sIL-2R and number of leukocytes, neutrophils and monocytes, on the other. A smaller part of the within-subject variability in plasma Hp (i.e. 6.0%) could be explained by serum sIL-6R and sIL-2R. It is concluded that there are (1) important between-subject differences in the homeostatic setpoints of plasma Hp, which are related to those in plasma Fb and in immune status and (2) significant within-subject, time relationships between plasma Hp and indicators of immune activation and plasma Fb.

Total serum protein and serum protein fractions in depression: relationships to depressive symptoms and glucocorticoid activity.

Recently, it has been reported that major depression is accompanied by changes in plasma protein concentrations indicative of an acute-phase protein (APP) response. The purpose of the present study was to examine total serum protein (TSP) and the electrophoretically separated major fractions of serum proteins (SP), i.e., albumin (Alb), alpha 1, alpha 2, beta and gamma globulin, in depression. Highly significant differences were found in TSP and the separated SP fractions between major depressed patients and normal controls and between melancholic and minor depressed patients. Major depressed subjects showed significantly lower TSP and Alb concentrations and a higher percentage of the alpha 1 globulin fraction than normal controls and minor depressed subjects. Major depressed subjects had significantly higher and lower percentages, respectively, of alpha 2 and gamma globulin fractions than normal controls. In depressed subjects, there were significant negative correlations between TSP or Alb concentrations and severity of illness. Psychomotor retardation and anorexia were psychopathological correlates of lower TSP and Alb concentrations while middle insomnia and psychomotor retardation were related to changes in the alpha 2 globulin fractions. Basal plasma cortisol values were significantly and positively related to serum alpha 2 globulin. The results support the view that major depression is accompanied by an APP response.

Components of biological, including seasonal, variation in hematological measurements and plasma fibrinogen concentrations in normal humans.

This study has been carried out in order to examine the components of biological and, in particular, seasonal variation in hematologic measurements in normal humans. Toward this end, 26 normal volunteers had monthly blood samplings during one calendar year for determination of number of red blood cells (RBC) and platelets, hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), MC Hb (MCH), MC Hb concentration (MCHC), RBC distribution width (RDW), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), and plasma fibrinogen concentrations. The data were analyzed by means of spectral analyses of a group of time series or a single time series, and by means of repeated measures analyses of variance. Most of the hematologic variables show seasonal rhythms, such as annual rhythms or harmonics, which are expressed as a group phenomenon. An important part of the variance ( > 15%) in Ht, MCV, MCH, MCHC, RDW, number of platelets, MPV and plasma fibrinogen was explained by a yearly variation. The peak-trough differences (expressed as a percentage of the mean) in the yearly variations in number of RBC, Ht, MCV, MCH, MCHC and RDW were very low (all < 8.5%). Number of platelets (14.4%) and plasma fibrinogen values (28%) showed a high-amplitude yearly variation. All hematological variables, except MCHC, show a high interindividual variability which exceeds by far the intraindividual variability.

Effects of serotonin precursors on the negative feedback effects of glucocorticoids on hypothalamic-pituitary-adrenal axis function in depression.

In order to investigate the relationships between brain serotonergic turnover and hypothalamic-pituitary-adrenal (HPA) axis function in unipolar depression, the authors measured intact adrenocorticotropic hormone (ACTH) and cortisol levels in baseline conditions and after combined dexamethasone (1 mg PO) and L-5-hydroxytryptophan (L-5-HTP, 200 mg PO) administration in 13 minor, 17 simple major, and 17 melancholic subjects. L-5-HTP significantly enhanced post-DST ACTH and cortisol secretion in major--but not in minor--depressed subjects. Major depressed subjects with or without melancholia exhibited significantly higher post-DST ACTH and cortisol responses to L-5-HTP than minor depressed subjects. L-5-HTP administration converted some major depressed ACTH or cortisol suppressors into nonsuppressors. L-5-HTP stimulated ACTH or cortisol secretion to the same extent in major depressed HPA-axis suppressors and nonsuppressors. It is concluded that L-5-HTP loading may augment ACTH and, consequently, cortisol escape from suppression by dexamethasone in major but not in minor depressed subjects. The findings show that serotonergic mechanisms modulate the negative feedback of glucocorticoids on central HPA-axis regulation. It is hypothesized that the higher L-5-HTP-induced post-DST HPA-axis hormone responses in major depression reflect upregulated 5-HT2 receptor-driven breakthrough secretion of pituitary ACTH from suppression by dexamethasone.

Plasma soluble interleukin-2-receptor in depression: relationships to plasma neopterin and serum IL-2 concentrations and HPA-axis activity.

The present study examined the plasma concentration of the soluble interleukin-2-receptor (sIL-2R) in depressed subjects in relation to hypothalamic pituitary adrenal (HPA) axis function and plasma neopterin and serum IL-2 concentrations. Plasma sIL-2R concentration was significantly higher in depressed patients (n = 47) than in controls (n = 19). There were no significant correlations between plasma sIL-2R and severity of illness. In the depressed subjects, there was a highly significant relationship between plasma sIL-2R and neopterin concentrations. Depressed patients with pathologically increased plasma neopterin levels had significantly higher plasma sIL-2R values than those with normal serum neopterin. There were no significant relationships between plasma sIL-2R and indices of HPA-axis function in depression. There was no significant effect of dexamethasone administration on sIL-2R levels. Significantly more depressed subjects had measurable serum IL-2 levels than normal controls. Our data support the notion that a moderate activation of cell-mediated immunity may play a role in the pathophysiology of depression.

Adrenocorticotropic hormone, beta-endorphin and cortisol responses to oCRH in unipolar depressed patients pretreated with dexamethasone.

1. Corticotropin-releasing hormone (ovine CRH, 100 micrograms intravenous bolus) was given to 63 unipolar depressed inpatients following the 1 mg overnight dexamethasone suppression test (DST). The depressed patients included 18 minor, 24 simple major and 21 melancholic subtypes. 2. Baseline or postdexamethasone plasma levels of intact adrenocorticotropic hormone (ACTH), beta-endorphin/beta-lipotropin (beta END/beta LPH), cortisol, and dexamethasone were measured, as well as the post DST+CRH hormone responses. 3. CRH administration 9.5 hr after dexamethasone resulted in a significant enhancement of ACTH, beta END/beta LPH and cortisol secretion. The post DST+CRH ACTH and beta END/beta LPH- but not cortisol-values exceeded their baseline hormone levels. The post DST+CRH ACTH--but not beta END/beta LPH or cortisol-levels were significantly higher in major depressives compared to minor depressives. The post DST+CRH ACTH and beta END/beta LPH--but not cortisol-levels were significantly higher in DST nonsuppressors than suppressors. The post DST+CRH ACTH levels were significantly and positively related to severity of illness. 4. The results provide evidence that the pathophysiology underlying the abnormal DST+CRH and DST tests in melancholia is localized at the pituitary level and may consist of a CRH-driven breakthrough of corticotropic cell secretion synergized by central and peripheral agents, in conjunction with a decrease in glucocorticoid feedback suppressibility.

Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response.

There is now some evidence that major depression may be accompanied by an immune response. The latter condition is suggested by elevated secretion of neopterin and interferon-gamma (IFN gamma) and by lower L-tryptophan (L-TRP) plasma levels. This study investigated the plasma levels of neopterin, L-TRP, and the L-TRP/competing amino acids (CAA) ratio in 30 normal control subjects and 47 depressed subjects (16 minor depressed, 13 simple major depressed, and 18 melancholic subjects), and IFN gamma secretion by mitogen-stimulated peripheral blood mononuclear cells in 7 normal control subjects and 13 major depressed subjects. Plasma neopterin levels were significantly higher in depressed subjects than in normal controls; 61% of melancholic patients had increased neopterin levels (> or = 7 nmol/l) with a specificity of 90%. Patients with major depression had significantly lower L-TRP and L-TRP/CAA values compared with normal control subjects. The amino acid values were significantly and negatively correlated with plasma neopterin levels. Major depressed subjects exhibited significantly higher IFN gamma secretion than did normal control subjects. The results further support the hypothesis that major depression is accompanied by an immune response and that the lower L-TRP availability in that illness may be an epiphenomenon of immune activation.

Lower degree of esterification of serum cholesterol in depression: relevance for depression and suicide research.

Previous studies have suggested that depression and suicide are related to alterations in total cholesterol serum concentrations, and that an altered distribution of haptoglobin (Hp) phenotypes in major depression indicates that variation on chromosome 16 may be associated with that illness. Lecithin:cholesterol acyl transferase (LCAT, EC 2.3.1.43), the enzyme that catalyzes the esterifying reaction of cholesterol in serum, is located close to the Hp gene. This study examined the serum concentrations of total and free cholesterol and the esterified cholesterol ratio in 26 healthy controls, 47 unipolar depressed subjects (16 minor, 14 simple major and 17 melancholic depressed subjects) and 12 relatives of melancholic subjects. Depressed subjects (regardless of subtype) and relatives of depressed subjects had a significantly lower esterified cholesterol ratio than normal controls. No significant differences in total or free cholesterol concentrations were found between the above study groups. In depressed subjects, there were no significant relationships between the esterified cholesterol ratio, total or free cholesterol and postdexamethasone adrenocorticotropic or cortisol values, Hp phenotypes, severity of illness or suicidal symptoms. It is hypothesized that lower esterification in serum cholesterol may constitute a vulnerability factor for depression through alterations in cell membrane microviscosity.

Binding of [3H]paroxetine to platelets of depressed patients: seasonal differences and effects of diagnostic classification.

[3H]Paroxetine is a more reliable ligand for studying the serotonin (5-HT) transporter complex than [3H]imipramine. The present study investigates [3H]paroxetine binding to platelets in 54 depressed in-patients (18 minor, 16 simple major and 20 melancholic depressed patients) and 16 healthy controls. There were no significant differences in maximal number of binding sites between depressed subjects and normal controls. There was no correlation between [3H]paroxetine binding to platelet membranes and severity of depression. [3H]Paroxetine binding to platelets was significantly higher in spring than in summer, fall and winter.

Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6, and soluble interleukin-2 and -6 receptor concentrations in normal volunteers.

This study has been carried out in order to investigate seasonal variation in peripheral blood immune cells, such as leukocytes, monocytes, neutrophils, lymphocytes, CD3+ T, CD4+ T, CD8+ T, CD25+ T, CD20+ B, and serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R levels in normal volunteers. Toward this end, 26 normal volunteers (13 men, 13 women) had monthly blood samplings during one calendar year for peripheral blood count, flow cytometric enumeration of peripheral leukocyte subsets and immunoassays of IL-6, sIL-6R and sIL-2R. It was found that most of the immune variables change rhythmically during the seasons as a group phenomenon. Statistically significant yearly variations with seasonal rhythms, i.e. annual rhythms or harmonics, such as semiannual, tetramensual and trimensual rhythms, were found in the number of leukocytes, neutrophils, monocytes, lymphocytes, CD4+ T, CD8+ T, CD25+ T, CD20+ B cells, in the CD4+/CD8+ ratio, and serum IL-6 and sIL-6R levels. It is concluded that the immune system is characterized by a multifrequency time-structure with significant high-amplitude yearly variations in the number of some peripheral blood leukocyte subsets.

Components of biological variation in prolyl endopeptidase and dipeptidyl-peptidase IV activity in plasma of healthy subjects.

We investigated the components of biological variation in plasma prolyl endopeptidase (PEP; EC 3.4.21.26) and dipeptidyl-peptidase IV (DPP IV; EC 3.4..14.5) activity in healthy individuals. We took monthly blood samples from 26 healthy volunteers for determination of plasma PEP and DPP IV activity during one calendar year. The estimated CVs for PEP activity were: total (CVt) = 25.0%, interindividual (CVg) = 13.9%, and intraindividual (CVi) = 16.8%. There was a statistically significant (P < 0.0001) seasonal pattern in plasma PEP activity, with significantly higher values in the fall than in the other seasons. The peak-trough difference in the yearly variation in PEP activity, expressed as a percentage of the mean, was as high as 56.8%. The estimated CVs for DPP IV activity were: CVt = 17.1%, CVg = 14.5%, and CVi = 8.2%. DPP IV activity was significantly (P < 0.0001) higher in summer than in the other seasons but the amplitude of the yearly variation was small.

Hypozincemia in depression.

This study investigates serum levels of zinc in 48 unipolar depressed subjects (16 minor, 14 simple major and 18 melancholic subjects) and 32 normal volunteers, and the relationships between zincemia and plasma neopterin levels, postdexamethasone adrenocorticotropic hormone and cortisol values, and anorexia-weight loss. Serum zinc levels were significantly lower in major depressed subjects than in normal controls, whereas minor depressed subjects showed intermediate values. There were significant negative correlations between serum zinc, and severity of depression and plasma neopterin concentrations. No significant relationships between zincemia and either postdexamethasone hormone values or anorexia/weight loss were found. The findings suggest that hypozincemia in major depression may be related to activation of cell-mediated immunity in that illness.

Lower serum prolyl endopeptidase enzyme activity in major depression: further evidence that peptidases play a role in the pathophysiology of depression.

Prolyl endopeptidase (PEP) is a serine proteinase, which may cleave peptides that are involved in the pathophysiology of major depression, such as arginine vasopressin, beta-endorphin, luteinizing hormone-releasing hormone, thyrotropin-releasing hormone, and maybe corticotropin-releasing hormone. PEP may be involved in activation of cell-mediated immunity, autoimmune and inflammatory responses, which repeatedly occur in severe depression. The present study investigates serum PEP activity in 33 normal controls, 16 minor, 14 simple major, and 18 melancholic depressed subjects. Pre-dexamethasone and post-dexamethasone (DST) intact adrenocorticotropic hormone (ACTH) and cortisol values were determined in 33 depressed subjects. Serum PEP activity was significantly lower in depressed subjects compared to normal controls and in melancholic depressed subjects compared to minor and simple major depressed subjects. Up to 61.1% of the melancholic patients had serum PEP activities below the mean PEP values of normal controls minus two SDs. In the depressed study group, significant negative correlations between serum PEP activity and severity of illness, post-DST cortisol, and ACTH values were observed. There was a trend toward higher serum PEP activity with increasing age. It is hypothesized that lower serum PEP activity, and lower serum activity of other peptidases, may play a role in the neuroendocrine and immune pathophysiology of major depression.

A further investigation of basal HPT axis function in unipolar depression: effects of diagnosis, hospitalization, and dexamethasone administration.

Hypothalamic-pituitary-thyroid (HPT) axis function was assessed in depressed subjects 1 and 8 days after hospital admission, and after the administration of 1 mg of dexamethasone. Plasma levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured by ultrasensitive assays in 16 patients with minor depression, 15 patients with simple major depression, and 13 patients with melancholia. The postdexamethasone adrenocorticotropic hormone (ACTH) (intact 1-39 molecule) and cortisol values were determined. Basal TSH values were significantly lower in melancholic patients than in patients with minor and simple major depression on the day after admission and 1 week later. Basal TSH values determined 1 week after admission were significantly and negatively related to FT4 values and severity of depression. There were no significant differences in basal TSH, FT3, and FT4 values obtained on day 1 and day 8 after hospital admission. Dexamethasone administration had a significant suppressant effect on basal TSH and FT3 values. Patients who failed to suppress cortisol after the dexamethasone suppression test (DST) exhibited significantly less suppression of basal TSH values than did DST cortisol suppressors.