Dall'Asta C

Sexual Dysfunction Is Frequent in Premenopausal Women with Diabetes, Obesity, and Hypothyroidism, and Correlates with Markers of Increased Cardiovascular Risk. A Preliminary Report

INTRODUCTION Female sexual dysfunction (FSD) is characterized by reduced sexual appetite and altered psychologic and physiologic response to sexual intercourse; it is reported to be frequent in diabetes mellitus, but no data have been reported in thyroid disorders. AIMS To compare the prevalence of FSD in diabetic, in obese, and in hypothyroid women vs. healthy women, and to correlate FSD with endocrine and metabolic profiles. METHODS We evaluated, through a questionnaire (Female Sexual Function Index [FSFI]), the prevalence of FSD in 91 women affected by diabetes mellitus, obesity, or hypothyroidism, and in 36 healthy women, all aged 22-51 years and in premenopausal state. MAIN OUTCOME MEASURES FSFI score, endocrine and metabolic parameters (triglycerides, high-density lipoprotein [HDL] and low-density lipoprotein [LDL] cholesterol, free-triiodothyronine (FT3), free-thyroxine (FT4), thyroid stimulating hormone [TSH], 17-beta-estradiol, testosterone, glycated hemoglobin 1c (HbA1c), thyroid autoantibodies, E-selectin, P-selectin, intercellular adhesion molecule-1 [ICAM-1], plasminogen-activator inhibitor-1 [PAI-1]), and anthropometric parameters (body mass index, waist, blood pressure [BP]). RESULTS A reduced FSFI score was more frequent in diabetic, obese, and hypothyroid women vs. healthy women (P < 0.01). In the different groups of women, FSFI score was inversely correlated (pairwise correlation) with at least one of the following: HbA1c, TSH, LDL-cholesterol, PAI-1, diastolic BP, presence of thyroid Ab, and directly correlated with HDL-cholesterol (always P < 0.05 or less). At stepwise regression analysis, HDL-cholesterol (protective) and HbA1c, LDL-cholesterol, PAI-1, and diastolic BP (negatively) predicted reduced FSFI score. CONCLUSION These data indicate an increased prevalence of sexual dysfunction in diabetic, in obese, and in hypothyroid women, associated with markers of cardiovascular risk.

Effect of weight loss through laparoscopic gastric banding on blood pressure, plasma renin activity and aldosterone levels in morbid obesity

BACKGROUND AND AIMS Several mechanisms are probably involved in obesity-related hypertension. This study was aimed to investigate the effect of significant weight loss on blood pressure and plasma renin activity (PRA) and aldosterone levels, other then on metabolic profile, in normotensive and hypertensive obese subjects. METHODS AND RESULTS Forty hypertensive and 55 normotensive obese subjects were studied under basal conditions and again 1 year after significant weight loss obtained through laparoscopic adjustable gastric banding (LAGB). Weight, waist circumference, blood glucose, insulin, electrolytes (Na and K), lipids and supine and upright PRA and aldosterone were evaluated. All parameters evaluated improved, except for total cholesterol, and electrolytes that did not change. Blood pressure decreased in hypertensive subjects, with a concordant decrease in PRA and supine aldosterone levels, not observed in normotensive patients. CONCLUSION Weight loss is associated with reduction of blood pressure and of PRA and aldosterone levels in obese hypertensive subjects.

Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism

Oral DHEA administration to patients with hypoadrenalism, in addition to glucocorticoid and mineralcorticoid replacement, may improve both well-being and hormonal/metabolic parameters. Twenty patients (13 men, 7 women, 26276 yr, 11 with Addison’s disease, 9 with central hypoadrenalism) were recruited in a placebocontrolled, randomized study. Hormone levels, carbohydrate and lipid parameters, bone metabolism, body composition and psychological parameters were evaluated at baseline and after treatment with DHEA 50 mg/day or placebo for 4 months. After 4 months of DHEA administration, serum DHEAS levels raised both in men (from 0.71±0.18 to 8.28±1.66 μmol/l, p<0.005) and in women (from 0.25±0.07 to 5.65±1.93 μmol/l, p<0.05). Only in hypoadrenal women an increase in testosterone (T; from 0.4±0.1 to 1.45±0.26 nmol/l, p<0.05) and androstenedione (A; from 0.86±0.34 to 2.05±0.29 nmol/l, p<0.05) levels was observed. In men no significant modifications in T and 17-hydroxyprogesterone (17-OHP) levels were found, whereas serum SHBG significantly decreased. As far as the metabolic parameters are concerned, only in patients with Addison’s disease a significant decrease in total cholesterol and in low-density lipoproteins after 4 months of DHEA administration was found. No changes in glucose metabolism and insulin sensitivity were observed. In basal conditions, mean serum osteocalcin (OC) was normal and significantly decreased after DHEA treatment. A significant reduction in body fat mass percentage (BF%) after DHEA administration was observed. As far as well-being is concerned, DHEA replacement did not cause any relevant variation of subjective health scales and sexuality in both sexes. Our study confirms that DHEA may be beneficial for female patients with hypoadrenalism, mainly in restoring androgen levels. Concerning the health status, more sensitive and specific instruments to measure the effects of DHEA treatment could be necessary.

Weight Loss Through Gastric Banding: Effects on TSH and Thyroid Hormones in Obese Subjects With Normal Thyroid Function

Studies on thyroid function in obesity yielded inconsistent results; high thyroid‐stimulating hormone (TSH) levels were generally shown; high free triiodothyronine (fT)‐3 or fT4 levels were described in some, but not in other studies. After weight loss, TSH and thyroid hormones have been described to either increase or decrease. Our aim was to describe TSH, fT3, and fT4 in obese subjects with normal thyroid function before and after durable and significant weight loss, obtained through laparoscopic gastric banding (LAGB), in comparison with nonobese subjects. TSH, fT3, fT4, and fT3/fT4 ratio (an index of D1 and D2 deiodinase activity), were evaluated in 99 healthy controls and in 258 obese subjects, at baseline and 6 months, 1 year, and 2 years after LAGB, together with indexes of glucose (glucose, insulin, homeostasis model assessment of insulin resistance index) and lipid (triglycerides, total and high‐density lipoprotein–cholesterol) metabolism, and anthropometric measures (BMI and waist circumference). Under basal conditions, TSH, fT3, and fT4 were all in the normal range, but higher in obese than in nonobese subjects, and fT3/fT4 ratio was normal; with weight loss, fT3 and fT3/fT4 ratio decreased in obese subjects, while fT4 increased and TSH remained steady; all values were again within the normal range. Albumin and cholesterol levels remained steady, while triglycerides, insulin, and homeostasis model assessment of insulin resistance decreased, and high‐density lipoprotein–cholesterol increased. These changes, however, do not modify TSH, letting us to hypothesize that the changes are due to a decrease of D1 and D2 deiodinase activities.

MRI in identifying hepatic steatosis in obese children and relation to ultrasonography and metabolic findings.

Objectives: The aim of this study was to identify nonalcoholic fatty liver in obese children by magnetic resonance imaging (MRI) and to compare the findings with the data from ultrasonography and from clinical and laboratory testing. Patients and Methods: Sixty obese children, 6 to 14 years old, underwent hepatic MRI and abdominal ultrasonography. Biochemistry determinations included serum aminotransferases, lipid profile, glucose, and insulin. Anthropometry included body mass index, total and trunk fat, and fat-free mass obtained by dual-energy radiographic absorptiometry. Hepatic steatosis, judged as hepatic fat fraction by MRI, was ≥9%. Results: By MRI, 14 (23%) children had hepatic steatosis; of those, 5 had a fat fraction of 9% to 18%, and 9 had a fat fraction >18%. At univariate analysis, fat fraction was positively associated with being male, serum alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase, body mass index z score, insulin, systolic pressure, and total and trunk fat mass. Hepatic steatosis was independently associated with alanine aminotransferase (P < 0.01). Overall, liver echogenicity on ultrasonography correlated well with fat fraction by MRI (correlation coefficient 0.527, P < 0.0001). Among the 27 children with increased liver echogenicity, 13 (48%) had hepatic fat fraction ≥9%, and 89% of children with echogenicity graded 2 or 3 had fat fraction >18%. All of the children (n = 9) with fat fraction >18% had increased liver echogenicity, and in 8 of them it was graded 2 or 3, but the MRI fat fraction ranged greatly (28%–45%). Conclusions: In obese children, nonalcoholic hepatic steatosis may be associated with the metabolic syndrome. Ultrasonography may be valuable in identifying high hepatic fat accumulation, but its ability to identify lower fat accumulation in the liver is scanty compared with MRI.

Comparison of different regimens of glucocorticoid replacement therapy in patients with hypoadrenalism

Since the optimal glucocorticoid replacement needs to avoid over and under treatment, the adequacy of different daily cortisone acetate (CA) doses was assessed in 34 patients with primary and central hypoadrenalism. The conventional twice CA 37.5 mg/day dose was administered to all patients (A regimen: 25 mg at 07:00 h, 12.5 mg at 15:00 h), while in 2 subgroups of 12 patients the dose was shifted on 2 thrice daily regimens (B: 25 mg at 07:00, 6.25 mg at 12: 00, 6.25 mg at 17:00; C: 12.5 mg, 12.5 mg, 12.5 mg). In other 12 patients the conventional dose was reduced to a thrice 25 mg/day administration (D regimen: 12.5 mg, 6.25 mg, 6.25 mg). In all patients, urinary free cortisol (UFC) excretion and cortisol day curves were evaluated. During the CA 37.5 mg administration, nadir cortisol levels were significantly higher with the thrice daily regimens (143±31 on B and 151±34 nmol/l on C) than with the conventional twice (85±16 nmol/l). Moreover, UFC, morning cortisol levels and mean cortisol day curves were similar in each group. Finally, during D regimen nadir cortisol levels were higher than in A and similar to B and C regimens. No difference in UFC and in cortisol day curves by reducing the CA dose was found. In conclusion, the thrice daily cortisone regimens, in which more physiological cortisol levels are achieved, perform better as replacement therapy. The administration of 25 mg/day CA confirms that replacement therapy is more adequate with a lower dose, particularly in patients with central hypoadrenalism.

Baseline and CRH-stimulated ACTH and cortisol levels after administration of the peroxisome proliferator-activated receptor-γ ligand, rosiglitazone, in Cushing’s disease

The ability of acute rosiglitazone administration in influencing ACTH/cortisol secretion in basal conditions and after CRH stimulation was studied in patients with Cushing’s disease. Ten patients (8 women and 2 men, aged 18–65 yr) with Cushing’s disease were enrolled in the study: 6 of them had previously undergone unsuccessful surgery and 4 were untreated. Plasma ACTH and serum cortisol levels were evaluated at serial time points for 3 h during saline infusion and after the administration of rosiglitazone (8 mg, po) and for 1 h after the injection of CRH (1 μg/kg iv) given alone or 30 min following rosiglitazone administration. The 4 tests were performed in all subjects in randomized order on different days. No significant difference was observed between the pattern of hormone secretion during saline alone and after rosiglitazone, as evaluated by two-way analysis of variance (ANOVA). The integrated areas under the curves (AUCs) were also not significantly different (ACTH: 5683±1038 vs 6111±1007 pg/ml/180 min; cortisol: 2333±267 vs 2902±486 μg/dl/180 min). In addition, there was no difference for ACTH and cortisol responses to CRH given either alone or after rosiglitazone, when evaluated as peak, increment or AUC; the pattern of the responses analyzed by two-way ANOVA was also similar. In conclusion: 1) the administration of a single dose of rosiglitazone did not decrease ACTH/cortisol levels or blunt their response after CRH injection; 2) the activation of PPAR-γ receptors by rosiglitazone seems unable to affect ACTH and cortisol secretion, at least in acute conditions, in patients with ACTH-secreting pituitary adenomas.

Echocardiographic alterations in patients with non-functioning adrenal incidentaloma.

Objective: While left ventricular (LV) dysfunction has been described in patients with Cushing’s syndrome (CS), data concerning morphologic and functional cardiac alterations in patients with incidentally discovered adrenal masses [adrenal “incidentaloma” (AI)], without overt hypercortisolism, are lacking. In this study the echocardiographic characteristics of patients with AI were evaluated and then compared with those of lean and obese normotensive subjects. Subjects and methods: Twenty-one patients with AI, without clinical or subclinical hypercortisolism, 18 normotensive obese subjects matched for gender and body mass index (BMI) and 20 normotensive lean subjects were studied. Echocardiography was performed in all subjects. In all patients plasma ACTH, serum cortisol, and DHEA-S levels were measured. Results: Patients with AI showed greater impairment of several echocardiographic indices of LV hypertrophy and diastolic dysfunction compared to normotensive lean subjects (p<0.05), but did not differ from those in obese subjects. Hypertensive AI patients showed a greater alteration of echocardiographic parameters (p<0.05) and higher BMI (p<0.01) and cortisol values (p<0.05) than normotensive ones. Plasma ACTH and serum cortisol were similar in AI patients and in obese controls, while DHEA-S levels were lower in AI (p<0.05). No correlations between cortisol secretion and echocardiographic parameters were found. Conclusion: In patients with non-functioning AI there is an impairment of cardiac morphology and function. These data suggest that patients with AI should be carefully screened also by means of echocardiographic studies.

Effectiveness of long‐term rosiglitazone administration in patients with Cushing's disease

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Difficulties in diagnosis and treatment of ectopic ACTH-producing tumors of the chest

It is widely accepted that surgery is the first choice treatment for ACTH-secreting tumors, most of them being lung or bronchial tumors. However, the localization of such lesions is rather difficult and it needs a compelling work-up. Here we present the results of different hormonal and imaging investigations and the surgical outcome of three patients with ectopic Cushings syndrome.