Marco Faustini-Fustini

Effect of Testosterone and Estradiol in a Man with Aromatase Deficiency

Recent reports of disruptive mutations of the genes for the estrogen receptor or for cytochrome P-450 aromatase1–6 have shed new light on the role of estrogen. In females the lack of estrogen due to aromatase deficiency leads to pseudohermaphroditism and progressive virilization at puberty, whereas in males pubertal development is normal. In members of both sexes epiphyseal closure is delayed, resulting in a eunuchoid habitus, and osteopenia is present.6 These findings suggest a crucial role of estrogen in skeletal maturation.1–6 We describe the responses to androgen and estrogen in a man with a novel, homozygous inactivating mutation of .xa0.xa0.

Role of oestrogen in male sexual behaviour: insights from the natural model of aromatase deficiency

In order to evaluate the role of oestrogens on human male sexual behaviour, the gender‐identity, psychosexual orientation and sexual activity of a man with a congenital lack of oestradiol resulting from an inactivating mutation of the aromatase P450 gene was investigated. The psychosexual and sexual behavioural evaluations were performed before and during testosterone treatment and before oestradiol treatment, during three phases of different dosages of oestradiol treatment.

Predictors of morbidity and mortality in acromegaly: an Italian survey

OBJECTIVEnTo describe demographic and hormonal characteristics, comorbidities (diabetes mellitus and hypertension), therapeutic procedures and their effectiveness, as well as predictors of morbidity and mortality in a nationwide survey of Italian acromegalic patients.nnnDESIGNnRetrospective multicenter epidemiological study endorsed by the Italian Society of Endocrinology and performed in 24 tertiary referral Italian centers. The mean follow-up time was 120 months.nnnRESULTSnA total of 1512 patients, 41% male, mean age: 45±13 years, mean GH: 31±37 μg/l, IGF1: 744±318 ng/ml, were included. Diabetes mellitus was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1 levels at diagnosis were significant predictors of diabetes and hypertension. At the last follow-up, 65% of patients had a controlled disease, of whom 55% were off medical therapy. Observed deaths were 61, with a standardized mortality ratio of 1.13 95% (confidence interval (CI): 0.87-1.46). Mortality was significantly higher in the patients with persistently active disease (1.93; 95% CI: 1.34-2.70). Main causes of death were vascular diseases and malignancies with similar prevalence. A multivariate analysis showed that older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were independent predictors of mortality.nnnCONCLUSIONSnPretreatment IGF1 levels are important predictors of morbidity and mortality in acromegaly. The full hormonal control of the disease, nowadays reached in the majority of patients with modern management, reduces greatly the disease-related mortality.

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

CONTEXTnCushings 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.nnnOBJECTIVEnOur aim was to evaluate the prevalence of unsuspected Cushings syndrome among outpatients with type 2 diabetes.nnnDESIGN AND SETTINGnThis was a cross-sectional prospective study in 24 diabetes clinics across Italy.nnnPATIENTSnBetween 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.nnnRESULTSnForty 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.nnnCONCLUSIONSnThe 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.

Role of estrogen on bone in the human male: insights from the natural models of congenital estrogen deficiency

The reports of congenital estrogen deficiency - notably, estrogen resistance and aromatase deficiency - have completely changed our knowledge on the role of estrogen on bone in males. Particularly, the bone changes at puberty, which were classically considered androgen-dependent, are now considered to be induced at least in part by estrogen action. Clinical cases of congenital estrogen deficiency have clearly demonstrated that the role of estrogens in epiphyseal closure, skeletal proportions and bone mineralization is crucial not only in women but also in men. In addition progress have been made in the treatment of such a rare disease even though further studies are needed to a definitive understanding of this issue.

Silent corticotroph carcinoma of the adenohypophysis: a report of five cases.

We report five silent corticotroph carcinomas of the pituitary gland. They represent 0.05% of adenohypophyseal tumors surgically treated at Mayo Clinic during a 20-year period and about 5% of all reported pituitary carcinomas. The patients (three females and two males), ranging in age from 26 to 58 years (mean 39 years, median 35 years) presented with symptoms of mass effect; none had Cushings disease. All tumors were initially invasive macroadenomas, recurred locally, and metastasized, three outside the central nervous system. The follow-up period ranged from 2 to 23 years (mean 10.6 years). All patients died, four of disseminated tumor and one of myocardial infarction. Histologically, three of the primary lesions were indistinguishable from an ordinary benign adenoma. Two were initially diagnosed as atypical adenomas as they featured nuclear pleomorphism, prominent nucleoli, mitotic activity, high MIB-1 labeling indices, and p53 overexpression. For the purpose of comparison, 17 silent corticotroph adenomas were also investigated. In addition, the clinicopathologic features of the silent carcinomas were compared with those of a meta-analysis of published Cushings disease-associated pituitary carcinomas. The silent adrenocorticotropin carcinomas showed a propensity for extraneural dissemination and an outcome similar to those of the Cushings disease-associated carcinomas. The two patients with initial atypical tumors died with metastases outside the central nervous system at 2 and 4 years, whereas the three patients with tumors lacking atypia died 16, 18, and 23 years after initial sellar surgery.

Pituitary metastases: role of surgery.

OBJECTIVEnTo evaluate the clinical and radiographic manifestations of pituitary metastases (PM), discuss the role of surgery, and briefly review the pertinent literature.nnnMETHODSnAt a single institution between January 1992 and July 2011, 15 patients with PM were surgically treated (all cases were confirmed by histologic analysis). Of patients, 14 complained of visual impairment, 8 complained of headache, 4 complained of ophthalmoplegia, and 11 complained of endocrine disturbances manifesting as diabetes insipidus (7 patients) and anterior hypopituitarism (4 patients).nnnRESULTSnAfter transsphenoidal surgery, visual disturbances improved in 12 cases, headache improved in 5 cases, and ophthalmoplegia improved in 2 cases. Endocrinologic function remained unchanged in all cases. The mean survival time was 11.8 months (range, 3-43 months); one patient still survives after 33 months.nnnCONCLUSIONSnThe study cohort includes patients representing two clinical situations: (i) patients with a preoperative suspicion of PM and (ii) patients in whom the metastasis was an unexpected finding during surgery performed for a presumed pituitary adenoma. The former situation is indicative of the possibilities and limits of surgery, which may confirm the diagnosis but is only palliative, improving quality of life without improving life expectancy. The latter situation reveals how misleading clinical and radiographic features of PM can be. Considering these results, surgical treatment of PM should be specifically decided based on patient performance status, tumor staging, and patient preference.

Awareness and management of hyponatraemia: The Italian Hyponatraemia Survey

Background: Hyponatraemia is the most frequent electrolyte disorder in hospitalized patients and has been associated with increased morbidity, mortality and length of hospital stay. There is evidence that also mild chronic hyponatraemia may have clinical consequences, such as gait disturbances, attention deficits, falls, increased risk of fractures and reduced bone mineral density. Nevertheless, this condition appears to be rather often not taken into consideration, or inappropriately managed and treated, thus negatively affecting patients’ outcome. Aim: The aim of this study was to investigate the awareness and management of hyponatraemia secondary to SIAD, a common cause of hyponatraemia, among Italian physicians (endocrinologists, nephrologists, internists) commonly involved as consultants. Methods: A questionnaire, covering definition, diagnosis, management, treatment and prognosis of hyponatraemia secondary to SIAD, was developed with the support of the Italian Society of Endocrinology. Results: Among the respondents (n=275), the majority was aware of the negative implications of hyponatraemia or of an inappropriate treatment. Nevertheless, the answers indicated that SIAD is still underdiagnosed and incorrectly managed in clinical practice. In particular, only 47% of respondents used the validated biochemical parameters to diagnose hyponatraemia secondary to SIAD. The survey also indicated a rather satisfactory knowledge of the therapeutic options, including the currently available vasopressin receptor antagonists. Conclusions: One of the main findings of the survey was that the diagnostic work-up of hyponatraemia still represents a critical issue. Therefore, there is urgent need of educational programs in order to improve the management of this condition and reduce morbidity, mortality and costs.

Erectile Dysfunction Is Common among Men with Acromegaly and Is Associated with Morbidities Related to the Disease

INTRODUCTIONnThe prevalence of erectile dysfunction (ED) and its correlates in men with acromegaly has never been investigated.nnnAIMnThe aim of this study was to evaluate sexual function in men with acromegaly.nnnMETHODSnMulticenter-based, retrospective analysis of a nonselected series of 57 acromegalic subjects (mean age: 52.7u2009±u200914.2 years) was performed. Acromegalic subjects reporting ED (nu2009=u200924) were compared with matched ED patients without acromegaly or pituitary disease (controls), selected from a cohort of more than 4,000 subjects enrolled in the Florence Sexual Medicine and Andrology Unit.nnnMAIN OUTCOME MEASURESnPatients were interviewed using Structured Interview on Erectile Dysfunction (SIEDY) structured interview, a 13-item tool for the assessment of ED-related morbidities. Several clinical and biochemical parameters were taken. Penile color Doppler ultrasound (PCDU) was performed in a subgroup of 37 acromegalic subjects.nnnRESULTSnED was reported by 42.1% of acromegalic subjects. After adjusting for age and testosterone, acromegalic subjects with ED had a higher prevalence of hypertension and more often reported an impairment of sleep-related erections and a longer smoking habit. Accordingly, acromegaly-associated ED was characterized by a higher organic component and worse PCDU parameters. No relationship between ED and testosterone levels or other acromegaly-related parameters was found. However, acromegalic subjects with severe ED reported a longer disease duration. In a case-control analysis, comparing acromegalic subjects with ED-matched controls free from acromegaly (1:5 ratio), acromegalic men had a worse ED problem and a higher organic component of ED, as derived from SIEDY score. In line with these data, acromegalic patients with ED had a higher prevalence of major adverse cardiovascular events history at enrollment and lower PCDU parameters.nnnCONCLUSIONSnSubjects with complicated acromegaly are at an increased risk of developing ED, especially those with cardiovascular morbidities. Our data suggest including a sexual function evaluation in routine acromegaly follow-up.