Diagnostic performance of basal free cortisol/18-hydroxy-11-deoxycorticosterone (18-OH-DOC) ratio in endogenous depression: comparison with the dexamethasone suppression test.

We assessed the 8:00 AM ratio of free cortisol/18-hydroxy-11-deoxycorticosterone (18-OH-DOC) in 56 endogenous depressive inpatients and in 22 normal volunteers. A ratio higher than 40 was associated with a diagnostic sensitivity for endogenous depression of 75%, a specificity of 95.5%, and a diagnostic confidence of 97.7%. These diagnostic results were at least equivalent to the Dexamethasone Suppression Test (DST) using a cortisol cut-off limit of 5 micrograms/dl. This may thus represent a simpler procedure than the DST in the diagnostic analysis of endogenous depression.

Changes in fetal and maternal blood levels of prolactin, cortisol, and cortisone during eutocic and dystocic childbirth.

The changes in blood levels of prolactin, total and free cortisol, and cortisone were studied and compared in 51 mother-infant pairs, 30 with eutocic delivery and 21 with dystocic delivery. Regardless of the type of delivery, the newborn at term showed significantly higher prolactin and cortisone serum levels than their mothers, and significantly lower levels of free and total cortisol. In fetal distress of short duration, free cortisol levels were significantly raised in both the mother and the child, while prolactin and cortisone levels were significantly higher only in the child. In contrast to these observations, serum prolactin and cortisone levels in the mother were not altered by the occurrence of fetal distress. In the newborn at delivery there was a negative correlation between serum prolactin and the Apgar score at 1 min applied to the part of the graph between 8 and 2 Apgar scores. This study illustrates the utility of fetal prolactin measurements in evaluating the stress to which the fetus is subjected.

[The role of plasma alpha 1-glycoprotein acid in the binding of aminopyrine]. / Rôle de l' alpha 1-glycoprotéine acide plasmatique dans la fixation de l'aminopyrine.

Under certain pathological conditions the binding of various substances by serum proteins is altered. The plasma concentrations of alpha 1-acid glycoprotein, also known as orosomucoid are reported to be elevated in stressful situation and in certain disease states like acute myocardial infarction. The binding of aminopyrine to serum proteins and alpha 1-acid glycoprotein was determined using equilibrium dialysis. It appears that alpha 1-acid glycoprotein has specific binding sites for aminopyrine. Aminopyrine was also bound to other serum proteins. On addition the results indicate that an increase of alpha 1-acid glycoprotein to concentrations such as those seen in some pathological states does not really alter the percent of aminopyrine bind to serum proteins.

A simple, direct radioimmunoassay for salivary progesterone determination during the menstrual cycle.

We describe a direct radioimmunoassay for progesterone in saliva. Results for extracted and unextracted samples agree well, showing that extraction with petroleum ether is unnecessary. The direct assay is specific and accurate, and detects as little as 2 pg of progesterone per tube (12 pmol/L). Intra- and inter-assay CVs are less than 10%. The correlation between concentrations of progesterone in saliva and plasma is good during the luteal phase of the menstrual cycle (r = 0.78, p less than 0.001, n = 76) but not during the follicular phase. We present mean concentrations of progesterone in saliva and plasma for the whole cycle in 14 normal women. Although citric acid is an effective salivary-flow stimulant, its deleterious effect on the direct radioimmunoassay precludes its use with this assay for monitoring ovulation.

[Circadian and seasonal changes of the inducer:suppressor ratio (OKT4+:OKT8+) in venous blood of healthy adults]. / Variations circadienne et saisonnière du rapport inducteur:suppresseur (OKT4+:OKT8+) dans le sang veineux de l'homme adulte sain.

Circadian and seasonal variations in the T helper: T suppressor-cytotoxic ratio were investigated in peripheral blood from five healthy young men. Mononuclear cells were isolated on Ficoll-Paque gradient, then incubated with OKT4 and OKT8 monoclonal antibodies. Plasma cortisol was determined in four of these seven time series. Large interindividual differences were documented and statistically validated for the 24-hr.-means of total lymphocytes, OKT4+:OKT8+ ratio, and of plasma cortisol (both total and free). For a pooled data, a circadian rhythm was demonstrated by cosinor (p less than 0.001) for total lymphocytes (acrophase at 1.00 hr.), total plasma cortisol (acrophase at 10.30 hrs.) and free plasma cortisol (acrophase at 9.50 hrs.), but not for OKT4+:OKT8+ ratio. This index however exhibited a statistically significant circadian rhythm in April and August, but not in November. Its double-amplitude exceeded 80% of the 24-hour-mean and its acrophase was localized at 6.40 hrs. in April and at 22.30 hrs. in August. Its 24-hr-mean was higher in August as compared to April and November. The circadian rhythm in the OKT4+:OKT8+ ratio did not seem to be related to that of plasma cortisol. Both circadian and seasonal variations need to be taken into account when investigating the regulations of immune variables such as T helper: T suppressor-cytotoxic ratio.

[Free salivary steroids and plasma hormones in women]. / Stéroïdes salivaires et hormones plasmatiques libres chez la femme.

The use and limitations of steroid assay in saliva are presented and discussed. Salivary cortisol was well correlated with unbound cortisol plasma, the only biological active fraction of total cortisol. Assay of salivary cortisol is particularly useful in patients taking oral contraceptives or during pregnancy. Indeed, in these patients, because of the marked increase in plasma cortisol binding globulin concentration (from 41 to 100 mg% or more), plasma total cortisol concentration increases from 18 +/- 4 micrograms% to 40 +/- 10 micrograms% whereas plasma unbound cortisol usually remains within the normal range. During the menstrual cycle, salivary progesterone rises from 5.4 +/- 1.8 to 15.1 +/- 3.6 ng%. As it is well correlated with plasma unbound progesterone concentration, salivary progesterone may be considered as a convenient and reliable index of luteal function. Because of its very low concentration, salivary estradiol is difficult to assay with routinely available techniques and, at present, is of limited interest for clinical investigation.

Prediction of cortisol response to dexamethasone from age and basal cortisol in normal volunteers: a negative study.

The dexamethasone suppression test (1 mg at 23 h and 4 P.M. blood collection) was performed in 22 normal subjects. In contrast to a previous study using 0.5 mg dexamethasone and a 8-9 A.M. post-dexamethasone blood sample, age and basal cortisol level did not significantly predict postdexamethasone cortisol levels.

Diagnostic performance of the thirty-four hour dexamethasone suppression test.

The performance of the dexamethasone suppression test (DST) in the diagnostic confirmation of endogenous depression was compared according to two times of blood collection--1600 hr on day 2 (usual sample) and 0800 hr on day 3 (34 hr after dexamethasone intake)--in 14 endogenous depressives and in a control group of 17 psychiatric inpatients with other diagnoses. For the day 2 (1600 hr) sample, a 5 micrograms/dl cortisol concentration represented the best cut-off score, with sensitivity of 57% specificity of 88%, and diagnostic confidence of 80%. For the day 3 (0800 hr) sample, the best cut-off score was 20 micrograms/dl, with the same sensitivity (57%) but there was a decrease of both specificity (to 76%) and diagnostic confidence (to 67%). The mean cortisol levels were much higher on day 3 than on day 2, suggesting that the inhibitory activity of dexamethasone was no longer present.

Use of saliva cortisol in the dexamethasone suppression test.

In a sample of 26 inpatients (15 primary endogenous depressives and a heterogeneous comparison group of 11 psychiatric patients), results of the dexamethasone suppression test (DST) for endogenous depression were compared when cortisol was measured in plasma (total and free) and in saliva. Results showed a close linear relationship among plasma total and free cortisol, plasma total cortisol, and saliva cortisol, and between free plasma and saliva cortisol. A saliva cortisol cutoff point of 70 ng/dl achieved the same sensitivity (67%), specificity (91%), and diagnostic confidence (91%) as the best cutoff scores of plasma total cortisol (5 micrograms/dl) and plasma free cortisol (0.15 microgram/dl). These results suggest that saliva cortisol, which directly reflects the biologically active fraction of cortisol, can be used as a reliable and more practical index in the DST, especially in outpatients.

Plasma hormone levels in women receiving new oral contraceptives containing ethinyl estradiol plus levonorgestrel or desogestrel.

The changes in plasma hormone levels were evaluated in matched healthy female volunteers investigated before and after 6 months' use of three new oral contraceptives (OCs): TrigynonR (n = 13), a triphasic OC containing low doses of ethinylestradiol (EE) + levonorgestrel (LNg); MarvelonR (n = 14), a monophasic OC containing low doses of EE + desogestrel (DOG, a new progestogen derived from LNg); and OvidolR (n = 10), a sequential OC containing higher doses (50 micrograms) of EE + DOG. Serum levels of FSH, LH, estradiol and progesterone were decreased in all cases to levels incompatible with ovulation. Prolactin concentrations were unchanged. Sex hormone binding globulin (SHBG) and Transcortin (CBG) levels were significantly increased by all three OCs (Ovidol greater than Marvelon greater than Trigynon); free testosterone levels decreased significantly while free cortisol concentrations remained unchanged. Collectively, these data indicate that (a) all three OCs are effective ovulation inhibitors, (b) Ovidol and Marvelon have greater estrogenic effects than Trigynon, (c) LNg is more effective than DOG in reducing the EE-induced increase in SHBG levels, and (d) free testosterone levels are equally well suppressed by all three Ocs.

Adrenocortical hormones, ageing and mental condition: seasonal and circadian rhythms of plasma 18-hydroxy-11-deoxycorticosterone, total and free cortisol and urinary corticosteroids.

The circannual rhythms of plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), total and free cortisol have been documented on a circadian basis in January, March, June and October in seven young men (24 years old), six elderly men, six elderly women and six elderly demented subjects, both men and women, in their eighties. Blood samples were drawn every 4 h over a 24-h period at each sampling session and urine samples were collected at 4-h intervals only from the young men. A circadian rhythm of 17-hydroxy-corticosteroids (17-OH-CS), 17-ketosteroids (17-KS), urinary free cortisol and 18-OH-DOC was defined for each of the four seasons with stable acrophases throughout the year and the same excretory profiles. A circannual rhythm was validated in young men for 17-OH-CS, urinary free cortisol and 18-OH-DOC but not for 17-KS. A circadian rhythm of plasma free cortisol, the active form of the hormone, plasma total cortisol and plasma 18-OH-DOC was validated in all groups and at all the seasons at which samples were taken. The secretory profiles of 18-OH-DOC, free and total cortisol were very similar, with no differences attributable to age, sex or mental condition except for the levels of plasma free cortisol and 18-OH-DOC which were higher and lower respectively in the elderly subjects. Whereas a circannual rhythm of plasma 18-OH-DOC was validated for all groups, a circannual rhythm of both free and total cortisol in the plasma was validated in young men but not in any group of elderly subjects. This loss of the circannual rhythmicity of cortisol in the elderly may reflect the decrease with age of the capacity to adapt to seasonal external factors.

Inhibitory influence of exogenous oxytocin on adrenocorticotropin secretion in normal human subjects.

Oxytocin has been suggested to have behavioral effects opposite to those of vasopressin, and exogenous vasopressin is known to induce ACTH release in man. Thus, we tested the influence of exogenous oxytocin on blood levels of ACTH and cortisol during insulin-induced hypoglycemia and after vasopressin injection. Our results demonstrate an inhibitory effect of exogenous oxytocin on ACTH release and support the hypothesis of a reciprocal, balanced modulation of behavioral and neuroendocrine function by the two closely related neurohormones, vasopressin and oxytocin.

Adrenal circadian system in young and elderly human subjects: a comparative study.

Circadian changes in plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), total and unbound cortisol were studied in four groups: seven healthy young men, six elderly men, six elderly women and six elderly demented patients of both sexes. The daily activities of the subjects were synchronous; blood samples were taken every 4 h and 4 hourly urine samples were collected only from the young men. A circadian rhythm was defined for plasma 18-OH-DOC, total and unbound cortisol in all groups; the secretory patterns of these steroids were parallel, as were the profiles of urinary 18-OH-DOC and unconjugated cortisol. When compared with respect to sex, the 24-h mean level of total cortisol was higher in women; that of unbound cortisol was higher in the three groups of elderly patients than in the young men. No major changes in plasma steroids were observed between elderly demented patients (mainly women) and healthy elderly women. The phasing of total and unbound cortisol showed no major modifications with age, sex or senile dementia. Acrophases of 18-OH-DOC were earlier in elderly patients than in young men. Amplitudes were not modified with sex in elderly patients but were always lower in the demented patients. A circadian rhythm was defined for 18-OH-DOC, unconjugated cortisol, 17-hydroxycorticosteroids (17-OH-CS) and 17-ketosteroids in the urine of the young men. The acrophases of 18-OH-DOC and unbound cortisol were close, as were those of 17-OH-CS and 17-ketosteroids. The lag was short between the acrophases of 18-OH-DOC in plasma and urine and between those of plasma unbound cortisol and urinary unconjugated cortisol; it was much larger between the acrophases of plasma total cortisol and 17-OH-CS. Thus, the process of ageing, and the possible alterations in the central nervous system which are often seen in normal ageing, induced no major modifications in the temporal organization of adrenocortical function, even in subjects who were very advanced in age.

Serum CBG, free and total cortisol and circadian patterns of adrenal function in normal pregnancy.

Parameters of cortisol metabolism were studied in pregnancy and early post partum and in non pregnant women. Total serum cortisol was measured by a specific radioimmunoassay and its unbound- and CBG-bound fractions by equilibrium dialysis at 37 degrees C. CBG was measured directly, by an immunodiffusion method (true CBG) and indirectly, by the Scatchard analysis of its interaction with labelled cortisol (PT). During pregnancy the increases in true CBG and total cortisol concentrations were grossly parallel but the PT/true CBG ratio fell from almost 1 in non-pregnant and delivered women to 0.6 during the second half of pregnancy. At 6 p.m., unbound cortisol was significantly higher in outpatients during the 2d half of pregnancy than in non pregnant controls (0.017 vs 0.009 10(-6) mol/l). In hospitalized resting patients, unbound cortisol concentrations were the same in pregnant and non pregnant women except for a significantly higher level of unbound cortisol at midnight during the second half of pregnancy. Circadian variations of cortisol secretion persisted throughout pregnancy. It is concluded that in pregnancy (1) hypothalamic control of maternal adrenal secretion still prevails, (2) the increase in total cortisol is essentially due to that of CBG, (3) the unbound cortisol is normal or, at times, slightly increased and (4) variations in the PT/true CBG ratios may be explained by the presence of steroids (progesterone and 17-OH-progesterone) with a high affinity for CBG. The physiological significance of the mild hypercortisolism of pregnancy is discussed.