Bruno Madeo

Congenital estrogen deficiency in men: a new syndrome with different phenotypes; clinical and therapeutic implications in men.

The report focuses on the role of estrogens in human male, dealing with two human models of congenital estrogen deficiency: estrogen resistance and aromatase deficiency. Similarities and differences of clinical phenotypes of these models are described and progresses of estrogen treatment of aromatase-deficient men are reported. Finally, the putative use of estrogen in men and the use of aromatase inhibitors and antiestrogen for male disorders are discussed.

Screening of Cushing's Syndrome in Outpatients with Type 2 Diabetes: Results of a Prospective Multicentric Study in Italy

CONTEXT Cushings syndrome may remain unrecognized among patients referred for metabolic syndrome; thus, a proactive screening has been suggested in certain patient populations with features of the disorder. However, conflicting data have been reported on the prevalence of Cushings syndrome in patients with type 2 diabetes. OBJECTIVE Our aim was to evaluate the prevalence of unsuspected Cushings syndrome among outpatients with type 2 diabetes. DESIGN AND SETTING This was a cross-sectional prospective study in 24 diabetes clinics across Italy. PATIENTS Between June 2006 and April 2008, 813 patients with known type 2 diabetes without clinically overt hypercortisolism were evaluated. Follow-up of the study was closed in September 2010. Patients were not selected for characteristics conferring a higher pretest probability of hypercortisolism. Patients underwent a first screening step with the 1-mg overnight dexamethasone suppression test. RESULTS Forty patients failed to suppress serum cortisol less than 5.0 μg/dl (138 nmol/liter) and underwent a standard 2-d, 2-mg dexamethasone suppression test, after which six patients (0.6% of the overall series) failed to suppress cortisol less than 1.8 μg/dl (50 nmol/liter), receiving a definitive diagnosis of Cushings syndrome that was adrenal dependent in five patients. Four patients were cured, being able to discontinue, or reduce, the glucose-lowering agents. CONCLUSIONS The present data do not support widespread screening of patients with type 2 diabetes for Cushings syndrome; however, the disorder is less rare than previously thought when considering epidemiology of type 2 diabetes. Our results support a case-finding approach in patients with uncontrolled diabetes and hypertension despite appropriate treatment.

Congenital estrogen deficiency: in search of the estrogen role in human male reproduction.

Recently, a remarkable progress has been made in our understanding about the role of sex steroids in male physiology. In this paper, we consider the clinical aspects of congenital estrogen deficiency - notably, estrogen resistance and aromatase deficiency - in men and we discuss both well-established and supposed estrogen roles in the human male reproductive function. These topics include the role of estrogens in the control of gonadotropin secretion, in male fertility determination and psychosexual behavior. Briefly, estrogens play a pivotal role in the control of serum gonadotropin concentrations in the human male. Furthermore, a possible role of estrogens on both human male fertility and sexuality has also been suggested by recent studies, even though the available data are far from being conclusive. Conversely, for what concern fertility and sexual behavior, a well-established effect of estrogens has been provided by recent studies on male rodents, which show impaired sexual behavior and fertility as a consequence of estrogen defect.

Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in men

Aims  The role of sex steroids in glucose and insulin metabolism in men remains unclear. To investigate the effects of sex steroids and oestrogen on insulin sensitivity in men, we studied two male adults with aromatase deficiency (subject 1 and subject 2).

Testosterone action on erythropoiesis does not require its aromatization to estrogen: Insights from the testosterone and estrogen treatment of two aromatase-deficient men.

Androgens act on erythropoiesis, but the relative role of testosterone (T) and estradiol (E(2)) on erythropoietic parameters in men is a poorly investigated issue. In order to evaluate separately the effects on erythropoiesis of high-dose T administration alone and of physiological dose of E(2) administration alone two adult men with aromatase deficiency were assessed before and during each treatment. Blood cell count, hemoglobin (Hb), hematocrit (Hct), erythrocyte mean cell volume (MCV), erythrocyte mean corpuscular hemoglobin (MCH), erythrocyte mean corpuscular hemoglobin concentration (MCHC), serum ferritin, iron and total iron-binding capacity (TIBC), serum erythropoietin, serum total testosterone and estradiol were evaluated. Hb, Hct and red cell count rose during testosterone treatment, consistently with the increase in circulating testosterone, but failed to increase during estradiol treatment. A decrease in Hb, Hct and red cell count was recorded in one of the two subjects during estradiol treatment, with a concomitant decrease in serum testosterone. Circulating T alone is capable of and sufficient to influence erythropoiesis, especially at supraphysiological dosage, while circulating E(2) have not the same effect on erythropoietic parameters, suggesting the hypothesis that the erythropoietic changes induced by androgens are not mediated via its aromatization to estrogens.

The Effects of Citalopram and Fluoxetine on Sexual Behavior in Healthy Men: Evidence of Delayed Ejaculation and Unaffected Sexual Desire. A Randomized, Placebo‐Controlled, Double‐Blind, Double‐Dummy, Parallel Group Study

INTRODUCTION Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and delayed ejaculation, while their effect on other aspects of sexual function, such as sexual motivation, arousal, and erectile function are unclear. AIM In order to evaluate the effect of chronic administration of two SSRIs, citalopram and fluoxetine, on normal sexual function, we studied the parameters of male sexual behavior, erectile function, and ejaculation on 48 healthy male volunteers, aged 29.5 +/- 4.9, in a randomized, placebo-controlled, double-blind, double-dummy study. Methods. The subjects were randomized to receive placebo (16 subjects), or fluoxetine (20 mg/day) (16 subjects) or citalopram (20 mg/day) for the first week, and 40 mg/day in the following 3 weeks (16 subjects). MAIN OUTCOME MEASURES Sexual function was investigated at the screening and at the end of the study by means of test of penile erection (TPE) and masturbation ejaculation latency time (MELT) performed during visual erotic stimulation, and at each visit by self-filled questionnaires (International Index Erectile Function [IIEF-15] and Golombock Rust Inventory of Sexual Satisfaction [GRISS]). RESULTS All the erectile parameters, evaluated by means of RigiScan Plus during TPE, were not significantly different when both fluoxetine and citalopram were compared with placebo. A delay in the ejaculation time was observed both during citalopram and during fluoxetine treatment when compared with placebo, reaching a statistical significance only with citalopram. During the treatment with citalopram and fluoxetine, the IIEF-15 score of all items decreased except for those items related to sexual desire; however, the scores were significantly lower only for the citalopram treatment. CONCLUSIONS The treatment with citalopram or with fluoxetine was confirmed to delay ejaculation, but was significant only for citalopram. Citalopram and fluoxetine did not affect sexual desire. Citalopram and fluoxetine did not directly affect penile erection as objectively assessed by RigiScan, although an impairment in the subjective assessment of erectile function was observed, but was significant only for citalopram, and it was thought to be a possible consequence of the delayed ejaculation perceived as a trouble.

Prevalence of Olfactory and Other Developmental Anomalies in Patients with Central Hypogonadotropic Hypogonadism

Introduction: Hypogonadotropic hypogonadism (HH) is a heterogeneous disease caused by mutations in several genes. Based on the presence of hyposmia/anosmia it is distinguished into Kallmann syndrome (KS) and isolated HH. The prevalence of other developmental anomalies is not well established. Methods: We studied 36 patients with HH (31 males, 5 females, mean age 41.5), 9 with familial and 27 with sporadic HH (33 congenital, 3 adult-onset), by physical examination, smell test (BSIT Sensonics), audiometry, renal ultrasound, and magnetic resonance imaging of the olfactory structures. Results: Based on the smell test, patients were classified as normosmic (n = 21, 58.3%) and hypo/anosmic (n = 15, 41.6%). Hypoplasia/agenesis of olfactory bulbs was found in 40% of patients (10/25; 75% hypo/anosmic, 7.6% normosmic, p < 0.01, Fisher’s test). Remarkably, olfactory structures were normal in two anosmic patients, while one normosmic patient presented a unilateral hypoplastic bulb. Fourteen of 33 patients (42.4%) presented neurosensorial hearing loss of various degrees (28.5% hypo/anosmic, 52.6% normosmic, p = NS). Renal ultrasound revealed 27.7% of cases with renal anomalies (26.6% hypo/anosmic, 28.5% normosmic, p = NS). At least one midline defect was found in 50% of the patients (53.3% hypo/anosmic, 47.6% normosmic, p = NS), including abnormal palate, dental anomalies, pectus excavatum, bimanual synkinesis, iris coloboma, and absent nasal cartilage. Anamnestically 4/31 patients reported cryptorchidism (25% hypo/anosmic, 5.2% normosmic, p = NS). Conclusion: Hypo/anosmia is significantly related to anatomical anomalies of the olfactory bulbs/tracts but the prevalence of other developmental anomalies, especially midline defects and neurosensorial hearing loss, is high both in HH and KS and independent of the presence of anosmia/hyposmia. From the clinical standpoint KS and normosmic HH should be considered as the same complex, developmental disease.

Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis

Treatment of osteoporosis is aimed to prevent fragility fractures and to stabilize or increase bone mineral density. Several drugs with different efficacy and safety profiles are available. The long-term therapeutic strategy should be planned, and the initial treatment should be selected according to the individual site-specific fracture risk and the need to give the maximal protection when the fracture risk is highest (i.e. in the late life). The present consensus focused on the strategies for the treatment of postmenopausal osteoporosis taking into consideration all the drugs available for this purpose. A short revision of the literature about treatment of secondary osteoporosis due both to androgen deprivation therapy for prostate cancer and to aromatase inhibitors for breast cancer was also performed. Also premenopausal females and males with osteoporosis are frequently seen in endocrine settings. Finally particular attention was paid to the tailoring of treatment as well as to its duration.

GH response to GHRH plus arginine is impaired in lipoatrophic women with human immunodeficiency virus compared with controls.

OBJECTIVE GH secretion is impaired in lipodystrophic human immunodeficiency virus (HIV) patients and inversely related to lipodystrophy-related fat redistribution in men. Less is known about the underlying mechanisms involved in reduced GH secretion in HIV-infected women. DESIGN A case-control, cross-sectional study comparing GH/IGF1 status, body composition, and metabolic parameters in 92 nonobese women with HIV-related lipodystrophy and 63 healthy controls matched for age, ethnicity, sex, and body mass index (BMI). METHODS GH, IGF1, IGF binding protein 3 (IGFBP3), GH after GHRH plus arginine (GHRH+Arg), several metabolic variables, and body composition were evaluated. RESULTS GH response to GHRH+Arg was lower in HIV-infected females than in controls. Using a cutoff of peak GH ≤ 7.5 μg/l, 20.6% of HIV-infected females demonstrated reduced peak GH response after GHRH+Arg. In contrast, none of the control subjects demonstrated a peak GH response ≤ 7.5 μg/l. Bone mineral density (BMD), quality of life, IGF1, and IGFBP3 were lowest in the HIV-infected females with a GH peak ≤ 7.5 μg/l. BMI was the main predictive factor of GH peak in stepwise multiregression analysis followed by age, with a less significant effect of visceral fat in the HIV-infected females. CONCLUSIONS This study establishes that i) GH response to GHRH+Arg is lower in lipoatrophic HIV-infected women than in healthy matched controls, ii) BMI more than visceral adipose tissue or trunk fat influences GH peak in this population, and iii) HIV-infected women with a GH peak below or equal to 7.5 μg/l demonstrate reduced IGF1, IGFBP3, BMD, and quality of life.

The Diagnostic Value of Calcitonin Measurement in Wash-Out Fluid from Fine-Needle Aspiration of Thyroid Nodules in the Diagnosis of Medullary Thyroid Cancer

OBJECTIVES The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy (FNAB) wash-out fluid (Ct-FNAB) for medullary thyroid cancer (MTC) remains to be determined. This prospective study aimed to assess the diagnostic value of Ct-FNAB in thyroid nodules in comparison with basal serum calcitonin (Ct), pentagastrin-stimulated Ct (Pg-sCt), and cytology. METHODS Among patients with goiter addressed with US-FNAB who had an initial clinical suggestion for thyroidectomy, 27 patients with thyroid nodule/s (n = 60) and normal, borderline, or increased Ct fulfilled the criteria for thyroidectomy. All 27 patients (enrolled according to exclusion/inclusion criteria) underwent ultrasonography (US), Ct, Pg-sCt, US-assisted FNAB of each patients nodule for both cytology, and Ct-FNAB before thyroidectomy. RESULTS Ct-FNAB always resulted in >1,000 pg/mL in MTC nodules at histology. For values between 36 and 1,000 pg/mL, MTCs and nodular or micronodular C-cell hyperplasia (CCH) results overlapped. Most of the nodules without MTC and/or CCH had Ct-FNAB ≤ 17 pg/mL. Ct-FNAB diagnostic power was superior to and similar to other diagnostic procedures (Ct, Pg-sCt, and cytology) in identifying both MTC and CCH, and MTC alone, respectively. CONCLUSION The diagnostic power of Ct-FNAB is valuable compared with other routine procedures. Ct-FNAB is highly reliable for the early detection and accurate localization of MTC in thyroid nodules, but it does not differentiate between MTC and CCH. Ct-FNAB is an extremely valuable diagnostic tool, especially considering that other diagnostic procedures do not provide a definitive diagnosis, and it can be included in the clinical work-up of thyroid nodules when MTC is suspected.