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Biomedical subjects

R Pasquali

Publications and source records attributed to R Pasquali.

At least 37 records · Page 2Linked to original sources
PubMed2002

Obesity and the polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is a condition characterized by hyperandrogenism and chronic oligo-anovulation. However, many features of the metabolic syndrome are inconsistently present in the majority of women with PCOS. Approximately 50% of PCOS women are overweight or obese and most of them have the abdominal phenotype. Obesity may play a pathogenetic role in the development of the syndrome in susceptible individuals. In fact, insulin possesses true gonadotrophic function and an increased insulin availability at the level of ovarian tissue may favour excess androgen synthesis. Obesity, particularly the abdominal phenotype, may be partly responsible for insulin resistance and associated hyperinsulinemia in women with PCOS. Therefore, obesity-related hyperinsulinemia may play a key role in favouring hyperandrogenism in these women. Other factors such as increased estrogen production rate, increased activity of the opioid system and of the hypothalamic-pituitary-adrenal axis, decreased sex hormone binding globulin synthesis and, possibly, high dietary lipid intake, may be additional mechanisms by which obesity favours the development of hyperandrogenism in PCOS. Irrespective of the pathogenetic mechanism involved, obese PCOS women have more severe hyperandrogenism and related clinical features (such as hirsutism, menstrual abnormalities and anovulation) than normal-weight PCOS women. This picture tends to be more pronounced in obese PCOS women with the abdominal phenotype. Body weight loss is associated with beneficial effects on hormones, metabolism and clinical features. A further clinical and endocrinological improvement can also be achieved by adding insulin-sensitizing agents and/or antiandrogens to weight reduction programmes. These obviously emphasize the role of obesity in the pathophysiology of PCOS.

Androgens↗
PubMed2001

Relationship between socio-economic and cultural status, psychological factors and body fat distribution in middle-aged women living in Northern Italy.

This study analyses the relationships between body fat distribution and socioeconomic and psychological factors in a cohort of 426 healthy middle-aged women living in Virgilio, Mantua (Northern Italy). The information concerning their occupational, social and psychological conditions and smoking habits were obtained by means of questionnaires. Psychological factors were investigated using the Italian version of the Illness Behaviour Questionnaire and the Symptom Questionnaire. Anthropometric measurements, body mass index (BMI) (kg/m2), waist/hip ratio (WHR) and clinical/hormonal menopausal status were also collected for each subject. The women reported significantly higher or lower psychological factor scores (symptoms of conversion: p=0.005; perception of disease: p=-0.018; denial: p=0.021; hostility: p=0.57; and laxity: p=0.047) as their WHR increased, thus indicating some concern about their health. In a multiple regression model, their WHR and waist circumference (W) significantly correlated with symptoms of conversion (p=0.005 and p=0.029), and W was also significantly related to the perception of disease (p=0.043). There was a significant inverse correlation between the WHR and educational level (p<0.001). The prevalence of partners who were entrepreneurs or self-employed also decreased as WHR increased (p<0.001). Furthermore, the number of women living in the centre of town significantly diminished, whereas those living in the suburbs or in the country significantly increased (p=0.005). However, using age, BMI and menopausal status as covariates, only the partner's work significantly and negatively correlated with the WHR (p=0.029). These results are consistent with the hypothesis that psychological and socio-economic handicaps are associated with a higher prevalence of abdominal fatness in middle-aged women living in Northern Italy

Adult↗
PubMed2001

Testosterone in ageing men.

A progressive decline in androgen levels is a common finding in men after middle age. The resulting clinical picture may be characterised by alterations in the physical and psychological domains, which have been demonstrated to correlate positively with testosterone serum levels. This clinical picture closely resembles the features of primary or secondary hypogonadism. Testosterone is the more convenient hormone for substitution therapy in classic hypogonadism as well as in age-related hypoandrogenism. Different choices of testosterone preparations are currently available, which are characterised by different routes of administration and by various pharmacokinetic profiles. Two major achievements urgently need to be investigated in the near future: the ability of the new formulations to reach more physiological and sustained hormone levels with the concomitant amelioration of their tolerability and the evidence of long-term prospective studies aimed at demonstrating the benefits and the possible complications of this therapy.

Aged↗
PubMed2000

Testosterone therapy in men: clinical and pharmacological perspectives.

There is increasing evidence that androgen therapy in men may be effectively applied in several conditions to improve well being and health. Classical indications for androgen therapy in males are represented by primary or secondary hypogonadism, delayed puberty, aplastic anemia and that secondary to chronic renal failure, protein wasting diseases such as trauma, burns, tumors and infectious diseases. Androgen innovating applications in men are represented by aging and visceral obesity associated with the metabolic syndrome. In addition, it is clear that appropriate testosterone treatment can be adequately used in male contraception, provided spermatogenesis is abolished and tolerability is adequate. Due to unphysiological hormone levels achieved by currently available testosterone preparations, new delivery systems have been produced to achieve more physiological and sustained hormone levels and improve tolerability and action at the levels of target tissues. Some of them are now available in several countries and new formulas are under development.

Aging↗
PubMed2000

alpha2-adrenoceptor regulation of the hypothalamic-pituitary-adrenocortical axis in obesity.

BACKGROUND: Abdominal obesity is associated with hyper-responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) axis to stimulatory neuropeptides and to stress. Catecholamines are involved in the regulation of the HPA axis, particularly during stress, via alpha-adrenoceptor modulation. DESIGN: In this study, we investigated the effects of pre-treatment with an alpha2-adrenoceptor agonist, clonidine (2 microg/kg over 10 minutes) and antagonist, yohimbine (0.125 mg/kg bolus, followed by 0. 001 mg/kg/minutes per 90 minutes infusion) on the HPA axis, measured by ACTH and cortisol response to combined CRH (human, 100 microg) plus AVP (0.3 IU) administration, and on noradrenalin (NA) and adrenalin (A) blood levels, in a group of obese women with abdominal (A-BFD) or peripheral (P-BFD) body fat distribution and in nonobese controls. RESULTS: During the control CRH + AVP test the ACTH but not the cortisol response was higher (P < 0.05) in obese A-BFD women than in controls, with minor and transient variations of NA levels. Neither the control test nor clonidine or yohimbine influenced basal or post CRH + AVP A concentrations. Clonidine pretreatment similarly and significantly decreased NA levels in all women and, compared to the control test, marginally influenced the ACTH response to CRH + AVP. Conversely, during yohimbine infusion NA levels steadily and similarly increased to values more or less double baseline values in all groups. Compared to the control test, however, the ACTH response to the CRH + AVP test performed during yohimbine infusion significantly decreased in the control subjects whereas a tendency to a further increase occurred in the obese groups and, specifically, in the A-BFD group significantly (P < 0.05) more than in the P-BFD group. CONCLUSIONS: This study shows that alpha2-adrenoceptor regulation of the HPA axis is different in obese and nonobese women, particularly in stressed conditions. We suggest that the abnormal ACTH response to CRH + AVP challenge with increased noradrenergic tone may represent a specific pathophysiological aspect of the abnormal response to stress or to other specific stimulatory factors in obese women, particularly those with abdominal body fat distribution.

Adrenergic alpha-Agonists↗
PubMed2000

Abnormalities of the hypothalamic-pituitary-adrenal axis in nondepressed women with abdominal obesity and relations with insulin resistance: evidence for a central and a peripheral alteration.

We have previously shown that women with abdominal body fat distribution (A-BFD) have a hyperactive hypothalamic-pituitary-adrenal (HPA) axis. However, we did not consider the presence of anxiety and/or depression, common manifestations in obese subjects. Anxiety and depression may be associated with oversecretion of cortisol and could represent a confounding factor in the evaluation of the HPA axis in different obesity phenotypes. In this study nondepressed obese women with abdominal and peripheral (P-BFD) body fat distribution and a control lean group underwent a CRH/AVP stimulation test for ACTH and cortisol determinations. Moreover, all women underwent metabolic evaluation and had their urinary free cortisol (UFC) excretion measured. After the stimuli, ACTH and cortisol responded more in the A-BFD than in the P-BFD and control groups. A positive correlation was found between either ACTH area under the curve (r2 = 0.366; P = 0.003) or cortisol area under the curve (r2 = 0.378; P = 0.043) and the homeostasis insulin resistance index in all obese patients. Unexpectedly, A-BFD had significantly lower UFC per m2 values than P-BFD (P < 0.05). Lowered UFC excretion in the A-BFD group is in keeping with an increased cortisol clearance, which, in turn, may lead to HPA axis hyperactivity as an appropriate compensatory mechanism. On the other hand, other mechanisms, possibly central in origin, such as overdriving of the CRH-ACTH system to chronic environmental stress factors, may be involved in determining HPA overresponsiveness in abdominal obesity. In conclusion, this study suggests that women with the abdominal obesity phenotype are characterized by both central and peripheral alterations of the HPA axis activity.

Abdomen↗
PubMed2000

Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome.

Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was well tolerated. In the PCOS group, metformin therapy improved hirsutism and menstrual cycles significantly more than placebo. Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups, without any significant effect on CT scan parameters. In both PCOS and control women, however, metformin treatment reduced body weight and BMI significantly more than placebo. Changes in the waist-to-hip ratio values were similar in PCOS women and controls, regardless of pharmacological treatment. Metformin treatment significantly decreased SAT values in both PCOS and control groups, although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment. On the contrary, visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups, but only in the former was the effect of metformin treatment significantly higher than that of placebo. Fasting insulin significantly decreased in both PCOS women and controls, regardless of treatment, whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin. Neither metformin or placebo significantly modified the levels of LH, FSH, dehydroepiandrosterone sulphate, and progesterone in any group, whereas testosterone concentrations decreased only in PCOS women treated with metformin. SHBG concentrations remained unchanged in all PCOS women; whereas in the control group, they significantly increased after both metformin and placebo. Leptin levels decreased only during metformin treatment in both PCOS and control groups. (ABSTRACT TRUNCATED)

Abdomen↗
PubMed2000

Activity of the hypothalamic-pituitary-adrenal axis in different obesity phenotypes.

Subjects with abdominal obesity are characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which leads to a condition of 'functional hypercortisolism'. This appears to be the result of two distinct mechanisms. The first, which appears to be central in origin, is characterized by altered ACTH pulsatile secretory dynamics and by hyper-responsiveness of the HPA axis to different neuropeptides and acute or chronic stress events and, possibly, to selected dietary factors. The other appears to be located in the periphery, specifically the liver and visceral adipose tissue, and is characterized by supranormal cortisol production, whose paracrine and systemic effects remain unclear. It is suggested that increased exposure to cortisol of the body may play a fundamental role not only in the development of increased fat in abdominal/visceral depots, but also in determining all metabolic abnormalities closely related to the abdominal obesity phenotype.

Abdomen↗
PubMed2000

[Steroid therapy and adrenal function].

Glucocorticoids are frequently used for both diagnostic and therapeutic purposes. Their action mimics endogenous glucocorticoid actions by altering the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, they can be responsible for iatrogenic diseases, particularly if used at high doses and for a long time. The aim of this brief review is to show the main pharmacological characteristics and the endocrine effects of glucocorticoids. The HPA axis insufficiency, related to acute glucocorticoid withdrawal, is also discussed.

Adrenal Insufficiency↗
PubMed2000

[Pseudo-Cushing syndrome. Physiopathologic aspects and differential diagnosis].

Pseudo-Cushing Syndromes (PCS) are a heterogeneous group of disorders, including alcoholism and depression, that share many of the clinical and biochemical features of Cushing's Syndrome (CS). It has been suggested that hypercortisolism of PCS may be the result of increased hypothalamic corticotropin-releasing hormone secretion in the context of a hypothalamic-pituitary-adrenal axis that is otherwise normally constituted. The substantial overlap in clinical features and daily urinary free cortisol levels between several patients with CS and those with PCS can make the differential diagnosis difficult. The most accurate tests in the distinction of CS from alcohol-induced PCS are dexamethasone-CRH and a midnight serum cortisol measurement. In depressed patients, the insulin tolerance test may be useful, although some overlap may exist. This brief review summarises the principal pathophysiological events of PCS and provides a useful strategy for differential diagnosis.

Adrenocorticotropic Hormone↗
PubMed1999

ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome.

OBJECTIVES: To investigate the activity of the hypothalamic-pituitary-adrenal (HPA) axis in male obesity and its relationship with several prominent parameters of the metabolic syndrome. DESIGN: A cross-sectional clinical study of the activity of the HPA axis in groups of obese males and normal-weight controls. SUBJECTS: Seventeen obese non-diabetic males with a body mass index (BMI) >28 and eight normal-weight controls were examined. MEASUREMENTS: Fat free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance, and the waist-to-hip circumference ratio (WHR) was calculated in all subjects. Baseline samples were taken for sex hormone and lipid determination, and an oral glucose tolerance test (OGTT) was performed for glucose and insulin determination. The activity of the HPA axis was determined by the combined administration of human corticotropin releasing hormone (CRH) (100 microg) and arginine vasopressin (AVP) (0.3 IU). RESULTS: As expected, FFM and FM and the WHR were higher in obese men than in controls, as were fasting insulin and stimulated (as area under the curve (AUC)) glucose and insulin concentrations. Baseline adrenocorticotropin (ACTH) and cortisol concentrations were similar in both groups, but stimulated (as AUC), ACTH was higher (P < 0.05) in obese subjects than in controls, whereas no significant difference in cortisolAUC was present. Since the main differences between obese subjects and controls were present during the early 30 min of the test, the correlation coefficients between total and incremental ACTH(AUC 0-30 min) and CortisolAUC 0-30 min and all other variables were analyzed. A significant correlation coefficient was present between them and all anthropometric parameters, fasting insulin and insulinAUC, but not with androgens and gonadotrophins. In addition, a significant correlation was present between total and incremental ACTH(AUC 0-30 min) and triglyceride concentrations. However, after adjusting for BMI or FM values, all correlation coefficients became non-significant, except the one between incremental ACTH(AUC 0-30 min) and insulinAUC (P < 0.05). CONCLUSION: These findings indicate that obese men may also have an altered pituitary response to combined CRH/AVP stimulation, which appears to be predominantly related to body size and total body fat. ACTH hyperresponsiveness after CRH/AVP stimulation also appears to be related to hyperinsulinaemia, but underlying mechanisms of this relationship remain to be elucidated.

Adipose Tissue↗
PubMed1999

The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long-term oestrogen-progestagen treatment.

OBJECTIVE: Little is known about the natural history of polycystic ovary syndrome (PCOS), although preliminary data indicate that affected women are more susceptible than the general population to diabetes and cardiovascular diseases at post-menopausal ages. The aim of this study was to follow-up all main features of the metabolic syndrome in a group of young women with PCOS and to investigate the long-term effects on metabolism and body composition of oestrogen-progestagen (OP) compounds, which are frequently used in these women to treat hyperandrogenism and related clinical features. DESIGN: Long-term follow-up study. SUBJECTS AND METHODS: Thirty-seven women with PCOS were re-evaluated 10.3 +/- 0.8 years (range 6-18 years) after their first assessments (age: before 19.8 +/- 4.9 years; after 29.9 +/- 4.4 years). When first examined, women were instructed to follow a hypocaloric diet if they were obese plus OP, if they agreed to such treatment. Main anthropometric parameters, basal sex hormones and lipids, fasting and glucose-stimulated glucose and insulin levels and several clinical data were recorded before and after follow-up. RESULTS: In the whole group of women with PCOS we found no changes in body weight and fat mass, whereas both the waist-to-hip ratio and the waist-to-thigh ratio were significantly reduced. No significant changes occurred in mean fasting and glucose-stimulated glucose and insulin concentrations, whereas a significant increase in high-density lipoprotein-cholesterol was found. No significant changes occurred in testosterone levels. During the follow-up period 16 women took OP for an average of 97 +/- 18 months (range 12-180 months) (OP-users) whereas 21 women never took OP (non-OP-users). All OP-users were still taking OP when re-evaluated at the follow-up examination. With respect to baseline values, body mass index was higher in non-OP-users than in their counterparts. Waist circumference (P < 0.025), the waist-to-hip (P < 0.05) and the waist-to-thigh (P < 0.01) ratios decreased significantly only in the OP-users. In addition, percentage changes in waist circumference (P < 0.05) and waist-to-hip ratio (P < 0.05) during the follow-up period were significantly different between the groups. Glucose tolerance (as area under the curve (AUC)) improved (P < 0.05) in OP-users but not in non-OP-users. Moreover, compared to baseline values, basal insulin levels were significantly (P < 0.01) reduced in OP-users but not in non-OP-users. On the contrary, no significant change was found in insulinAUC in the former, whereas it significantly increased (P < 0.05) in the latter. Accordingly, fasting C-peptide decreased (P < 0.05) in OP-users, whereas both fasting (P < 0.01) and stimulated (P < 0.01) C-peptide significantly increased in non-OP-users. Changes in fasting or stimulated insulin and C-peptide in non-OP-users were not associated with parallel changes in testosterone levels. Total cholesterol and triglycerides did not change in either group, but HDL-cholesterol increased (P < 0.05) only in OP-users. Sex hormone-binding globulin concentrations increased significantly (P < 0.01) in OP-users, without any significant change in non-OP-users. Testosterone concentrations did not change significantly in either group, but the testosterone: SHBG ratio significantly decreased in OP-users (P < 0.05) but not in the non-OP-users. Among the clinical features, acanthosis nigricans significantly (P < 0.01) worsened in non-OP-users but not in the OP-users, without any significant change in the hirsutism and acne scores. Pregnancy rates during the follow-up were similar in both groups. CONCLUSIONS: These data indicate that hyperinsulinaemia and insulin resistance tended to worsen spontaneously in women with PCOS, without any worsening of the hyperandrogenism. Long-term oestrogen-progestagen treatment countered this tendency, probably because it improved the pattern of body fat distribution, by reducing abdominal fat depots.

Adolescent↗
PubMed1999

Tubercular involvement of the thyroid gland: a report of two cases.

Thyroid tuberculosis is rare. In the last decade, however, the incidence of extrapulmonary forms of tuberculosis has increased. We report on 2 cases of thyroid tuberculosis. In case 1, a tubercular abscess mimicking acute thyroiditis was found which was correctly diagnosed by fine-needle aspiration biopsy (FNAb). No evidence of active disease was noticed. Pleural thickening on chest X-ray was the only sign compatible with a previous infection. In case 2, tubercular thyroiditis with lymph node enlargement was also diagnosed by FNAb in a reevaluation setting. In both cases treatment with antitubercular drugs resulted in complete recovery. Thyroid tuberculosis should be kept in mind in the differential diagnosis of thyroid nodules, notably in patients with a history of tuberculous disease. FNAb represents the main approach to making the diagnosis.

Abscess↗
PubMed1998

Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.

BACKGROUND: Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene. We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene. METHODS: We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome. Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo. Serum progesterone was measured on days 14, 28, 35, 44, and 53, and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter (26 nmol per liter) on any of these days. RESULTS: Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study. Among the 21 women given metformin plus clomiphene, the mean (+/-SE) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute (40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute, P=0.03), but it did not change significantly in the 25 women given placebo plus clomiphene. Nineteen of the 21 women (90 percent) who received metformin plus clomiphene ovulated (mean peak serum progesterone concentration, 23.8+/-3.4 ng per milliliter [7.6+/-10.9 nmol per liter]). Two of the 25 women (8 percent) who received placebo plus clomiphene ovulated (P<0.001). Overall, 31 of the 35 women (89 percent) treated with metformin ovulated spontaneously or in response to clomiphene, as compared with 3 of the 26 women (12 percent) treated with placebo. CONCLUSIONS: The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin.

Adult↗
PubMed1998

Serum leptin in obese women with polycystic ovary syndrome is correlated with body weight and fat distribution but not with androgen and insulin levels.

Leptin is a hormone produced in the adipose tissue and its concentrations in peripheral blood are significantly correlated with the amount of body fat. Whether other factors, including the pattern of body fat distribution and several hormones (such as insulin, sex steroids, and glucocorticoids), may be involved in the regulation of circulating blood leptin levels is controversial. Women with the polycystic ovary syndrome (PCOS) are hyperandrogenic and most of them are characterized by hyperinsulinemia, insulin resistance, and obesity, particularly the visceral phenotype. To assess the potential contribution of anthropometric factors, androgens, and insulin in determining leptin levels, we examined their relationship with body-mass index (BMI), visceral (VAT) and subcutaneous (SAT) adipose tissue areas, basal androgen levels, and fasting and glucose-stimulated (AUC) insulin in different groups of obese women with PCOS (n = 23) and of age-matched obese (n = 16) and non-obese (n = 10) otherwise healthy controls. The VAT/SAT ratio was measured as a parameter of body fat distribution. Serum leptin levels were significantly higher in obese PCOS women than in obese and normal-weight healthy controls and, within the controls, in the obese than in the non-obese group. In all women considered together, and in each group separately, leptin concentrations were highly significantly correlated with BMI. In addition, after adjusting for BMI, both VAT and the VAT/SAT ratio were positively and significantly correlated with leptin. Partial correlations with the VAT/SAT ratio remained significant in both the obese PCOS group and in controls considered separately, whereas the correlation with the SAT value was significant only in the control group. After adjusting for BMI, no correlation between leptin, androgens and fasting or stimulated (like AUC) insulin was found. These findings indicate that leptin levels in obese women with PCOS are higher than those observed in obese and non-obese controls. Moreover, they suggest that, other than BMI, the pattern of body fat distribution may be an independent factor related to circulating leptin levels, which, on the contrary, do not appear to be related to either androgen or insulin concentrations.

Adipose Tissue↗
PubMed1998

Pulsatile secretion of ACTH and cortisol in premenopausal women: effect of obesity and body fat distribution.

OBJECTIVE: There is emerging evidence that women with visceral obesity may have hyper-responsiveness of the hypothalamic-pituitary-adrenal axis. There are no studies on basal daily secretory pattern of ACTH and cortisol in subjects with different obesity phenotypes. DESIGN AND PATIENTS: In this study we examined daytime pulsatile secretion of ACTH and cortisol in two groups of premenopausal obese women with visceral (V-BFD) (BMI 37.1 +/- 1.7) and subcutaneous (S-BFD) (BMI 38.8 +/- 1.5) body fat distribution (measured by CT scan) and in a group of normal weight healthy controls (BMI 21.1 +/- 0.5). After an overnight fast, blood samples were taken at 15-minute intervals for 12 h (49 samples, from 0800 h until 2000 h). All women avoided breakfast but had a normal lunch and dinner, both containing similar food, energy and nutrient composition. ACTH and cortisol responses to mixed meals at noon and in the evening were also investigated. RESULTS: Mean values of ACTH and cortisol did not differ between the groups. However, ACTH pulse frequency was significantly higher in V-BFD (P < 0.06) and S-BFD (P < 0.02) obese women than in controls, without any significant differences between the two obese subgroups. Mean ACTH pulse amplitude was lower in the V-BFD than in S-BFD obese (P < 0.02) and control (P < 0.05) groups. Cortisol episodic characteristics did not differ between V-BFD and S-BFD obese and controls. All differences in ACTH pulsatile parameters between obese and controls and between the two obese subgroups were evident only in the morning, with no further significant differences during the early and late afternoon. There were no significant differences in cortisol parameters during the three periods of the day between the various groups, apart from late afternoon cortisol pulse frequencies, which were significantly lower in V-BFD than in controls. After lunch, ACTH and cortisol levels significantly increased in all groups, but the cortisol increase tended to be more rapid in V-BFD than in the other two groups. After dinner, ACTH significantly increased in V-BFD and controls but not in the S-BFD group, whereas cortisol rose significantly in all groups, but significantly less in S-BFD than in V-BFD and controls. CortisolAUC (but not ACTHAUC) after lunch was significantly higher than after dinner in all groups. ACTH response after each meal was similar in all groups, but cortisolAUC after dinner was significantly lower in S-BFD than in V-BFD women. CONCLUSION: This study demonstrates that in premenopausal women, obesity, particularly the visceral phenotype, is associated with several abnormalities of ACTH pulsatile secretion, particularly in the morning. On the contrary, no major differences were present in either blood concentrations, diurnal rhythm or secretory pattern of cortisol between obese and controls. The responses to meals seem to indicate a much more rapid cortisol response after lunch in women with visceral obesity and a reduced activation of the hypothalamic-pituitary-adrenal axis after dinner in women with subcutaneous obesity.

Adrenocorticotropic Hormone↗