E. Menini

Impairment of lymphocyte activities in depressed aged subjects

Lymphocyte activities were determined in a population of 26 institutionalized aged subjects, selected as healthy according to the SENIEUR protocol and previously reported to display immunological and endocrinological abnormalities correlated with depressive disorders. The lymphocyte mitotic response to PHA, which was reduced in aged as compared to adult subjects, was found to be significantly lower and negatively correlated with the depression score in the elderly subjects. In supernatants of PHA-stimulated lymphocyte culture from aged subjects, IL-2, IL-4 and gamma-IFN levels were very low and more severely affected in the depressed aged group. Each cytokine production was negatively correlated with age and depression score. NK activity was lower in the aged and it could be augmented by the addition of IL-2 or alpha-IFN, even though to a lesser extent than in the adult subjects. The nondepressed aged displayed higher levels of IL-2 inducible NK activity than the depressed aged subjects. IL-2 and alpha-IFN stimulated NK activities were negatively correlated with depression score. The present work indicates that the psychological status could affect lymphocyte reactivity in the aged. Given the relatively high frequency of affective disorders in these subjects, the psychological status should be considered in studies of immune senescence.

Neuropeptide Y plasma levels and immunological changes during academic Stress

Academic stress is a good model of psychological stress in humans for studying psychoneuroimmune correlations. We looked for correlations between psychological scores, immune tests and plasma levels of cortisol and neuropeptide Y (NPY). A group of medical students were evaluated at the beginning of the academic year (Baseline) and the day before an examination (Stress). They underwent evaluation by The Profile of Mood States (POMS), The Malaise Inventory, The Self Efficacy Scale and A Global Assessment of Recent Stress (GARS). The lymphocyte subsets, the lymphocyte proliferative response and the cytokine production were also evaluated. We detected modifications of some psychological test scores between the Baseline and Stress evaluation, a significant reduction of lymphocyte proliferation, IL-2 production and percentage of the lymphocyte CD19, and an increase in plasma cortisol levels during stress. The lymphocyte proliferation negatively correlated with the POMS score as well as the percentage of CD16+ cells with NPY plasma levels. NPY levels were not different from Baseline. The emotional and mood states seem to influence immunity.

Relationships between Intracranial Pressure and Diurnal Prolactin Secretion in Primary Empty Sella

The role of the intracranial pressure (ICP) in the development and/or maintenance of the primary empty sella has been evaluated by recording the ICP during sleeping and waking periods in 11 women who had this syndrome. Concomitantly, plasma PRL levels, measured at 2-hour intervals during a 24-hour period, were compared with the changes in ICP. Daily PRL variations were also measured in 5 normally cycling and 5 postmenopausal women. ICP was abnormally increased in 8 patients with PES. In 3 of them, increased values were recorded during waking and sleeping periods, while in 5 subjects abnormal values were observed only during sleep. In the remaining 3 patients the ICP was normal in all conditions tested. 8 patients with elevated ICP presented an absent or blunted nocturnal PRL increase. In 3 patients with normal ICP, the circadian periodicity of PRL was preserved. The normalization of ICP obtained in 4 patients by a surgical shunting procedure was accompanied by the return to normal of the circadian PRL periodicity. Our observations demonstrate that the finding of a normal ICP during wakefulness is not sufficient to rule out an actual increase in ICP, since a rise in the CRF pressure can occur during sleep. Our data also demonstrated a correlation between an abnormal rise in ICP and an absent or blunted nocturnal increment in PRL secretion.

Hormonal profile in benign breast disease. Endocrine status of cyclical mastalgia patients

Plasma levels of prolactin, before and after TRH stimulation, progesterone, estradiol, sex-hormone-binding-globulin, androstenedione, testosterone and dehydroepiandrosterone-sulphate were determined in a group of women with benign breast disease and in control group, in order to correlate a possible hormonal disorder to breast pathology. The hormonal pattern in the patients with benign breast disease was characterized by an increased responsiveness of lactotrophes to TRH stimulation and by higher levels of sex hormone binding globulin, probably sustained by an underlying hyperestrogenism.

Immune parameters in a populatio of institutionalized elderly subjects: influence of depressive disorders and endocrinological correlations

Twenty-six institutionalized elderly subjects, selected as healthy according to the SENIEUR protocol, were compared to adult controls to establish correlations between affective disorders and immune abnormalities and to investigate underlying neuroendocrine mechanisms. After an extensive psychodiagnostic examination, 35% of the aged subjects were classified as depressed. Cutaneous delayed hypersensitivity tests showed reduced responses in the aged, but no correlation was found with the psychological status. Examination of the peripheral blood lymphocyte subsets revealed no imbalance in the percentages of CD3+, CD4+, CD8+ cells in the aged. A slight reduction in the CD4+/CD8+ cell ratio could however be detected in the non-depressed aged, as compared to adult controls. The CD4+/CD45R+ cell subset was reduced in non-depressed aged. The percentage of B lymphocytes was reduced in the aged, mostly in the non-depressed subjects. No changes were detected in the percent of OKDR+ cells. The percentage of CD16+ cells was found unchanged, while that of Leu7+ cells was significantly higher in the aged than in the adults and in the non-depressed than in the depressed aged. Leu7+ cell levels were negatively correlated with the depression score. On double labelling, the percent of CD16+/Leu7+ cells appears increased in the subgroup of depressed aged and positively correlated with age. Plasmatic and urinary cortisol levels were both positively correlated with depression score. Urinary cortisol level was higher in the depressed aged. These parameters, as well as plasmatic ACTH, beta-endorphin and urinary catecholamines, were not correlated with immune responses. Based on these findings, we recommend that the neuroendocrinological conditions should be taken into account when healthy subjects are examined in studies of immune senescence.

Effects of ovary suppression by a long-acting GnRH-agonist on circulating GH, insulin-like growth factor I and insulin levels in women with polycystic ovary syndrome

Our aim was to investigate the effect of GnRH-agonist (GnRH-a) induced suppression of plasma sex steroids on serum GH, insulin like growth factor-l (IGF-I) and insulin levels after an oral glucose load (OGTT) in women with polycystic ovary syndrome (PCOS). Serum insulin, GH and IGF-I levels during a 75-g 4-h OGTT were measured in 3 nonobese and 7 obese hyperandrogenic women with PCOS and normal glucose tolerance before and after 10 weeks of treatment with the GnRH-a triptorelin (3, 75 mg im every 28 days). Basal estrogen and androgen levels were also measured at time 0 of the first and the second OGTT. After the therapy serum estrogens and androgens were significantly suppressed. Body weight remained unchanged. Basal GH significantly increased after the treatment while fasting IGF-I and insulin levels decreased from (mean±SE) 349.3±31.8 to 278.7±33.2 ng/mL and from 22.4±4.1 to 18.8±4.4 µU/mL, respectively. The insulin response to OGTT (area under curve) was also reduced (from 16017±2598 to 11736±2317 µU/mL/240 min). Our results suggest that the GnRH-a induced suppression of ovary secretion may modify the serum GH and IGF-I levels and the insulin response to an OGTT in women with PCOS.

Gonadotropin levels in women with polycystic ovary syndrome: Their relationship to body weight and insulin levels

The purpose of this work was to investigate the relationship of gonadotropin levels to body weight and insulin levels in women with polycystic ovary syndrome (PCOS). Specifically, we wished to test the hypothesis that circulating luteinizing hormone (LH) and insulin levels are different in obese and normal weight patients with PCOS. The basal plasma levels of gonadotropins, estrogens, androgens and sex hormone-binding globulin, the gonadotropin responses to gonadotropin releasing hormone (GnRH) and the insulin and C-peptide responses to a 3-hour oral glucose tolerance test (OGTT) were measured in 19 obese and 19 normal weight patients with PCOS and 7 obese and 8 normal weight ovulatory controls. Data of the patients were evaluated according to body weight (obese vs normal weight) and basal LH (high vs normal). There was no significant difference in basal LH and androgen levels and in the insulin response to oral glucose between obese and normal weight patients with PCOS. Compared to the weight matched controls, both obese and non obese patients showed significantly higher LH responses to GnRH and C-peptide responses to OGTT. When the high LH patients (no=18) were compared those with normal LH (no=20), the high LH subjects exhibited significantly higher androstenedione levels. Both obese (no=10) and normal weight (no=8) patients with high LH showed significantly greater C-peptide responses to OGTT than obese (no=9) and non obese (no=11) patients with normal LH. However, as compared with the weight matched controls, both the high LH and normal LH patients had significantly greater C-peptide responses to OGTT. We conclude that obese and non obese patients with PCOS do not seem to differ in the prevalence of elevated LH levels or in the LH secretory pattern. Insulin resistance, expressed by an enhanced pancreatic sensitivity to oral glucose, is present in both the high LH and the normal LH subjects, even though the PCOS patients with elevated LH tend to be more insulin resistant and hyperandrogenic than the normal LH patients.

A case of mucinous cystadenocarcinoma of the ovary associated with virilization: pre and post-operative steroid plasma levels

A premenopausal woman with a mucinous carcinoma of one ovary, and a mucinous adenoma of the other, together with secondary virilization, is reported. Preoperative ievels of androstenedione, testosterone and dehydroepiandrosterone sulphate were high, suggesting the presence of a virilizing tumor. Preoperative plasma estrone (E1), but not estradiol (E2), was elevated along with inversion of the E2/E1 ratio, suggesting a peripheral origin of the estrogens. FSH and LH plasma concentrations were low. After bilateral ovariectomy, levels of all steroids measured significantly decreased and gonadotropins rose to the postmenopausal range.

Ovarian and peripheral steroid hormones in a case of Sertoli-Leydig cell tumor.

The clinical course, histology, and steroid secretion of a 59-year-old postmenopausal woman with a 4-yr history of virilizing well-differentiated Sertoli-Leydig cell tumor of the right ovary are reported. Hormone secretion was examined by measuring peripheral and ovarian venous gradients and pre- and postoperative levels of some A 4 and A 5 steroids, estrogens, gonadotropins and Sex Hormone Binding Globulin levels. The preoperative responsiveness to ACTH, dexamethasone and hCG is also reported. The results are consistent with a Sertoli-Leydig cell tumor producing mainly testosterone and, to a lesser degree, androstenedione, progesterone, estrone and 17α-hydroxypro-gesterone. The tumor hormone secretion may be in part responsive to hCG.

Endocrine status in patients with mammary gland diseases: correlation between steroid hormones and sex steroid binding globulin

We have studied 131 women affected by benign or malignant breast disease, in order to explore their endocrine status. We evaluated basal concentrations of the following hormones: FSH, LH, PRL, estrone (E1), estradiol (E2), testosterone (T), androstenedione (A), DHEAS and SHBG. Basal hormone levels in these patients were not significantly different from those in normal age-matched subjects. However, in premenopausal women, 31% of patients with benign disease and 34.4% with malignant lumps exhibited an elevated FSH/LH ratio (greater than 1) and lower T levels, compared to those having a normal FSH/LH ratio. The difference in T levels was not coupled with the expected specular variations in SHBG levels. Moreover, in none of the group considered, T concentrations or E2/T were significantly correlated with SHBG levels. These data seem to suggest an altered regulation of SHBG in these patients, in whom the modulation of SHBG by circulating sexual steroids appears to be different when compared with normal subjects.