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Gender- and sex- related differences represent a new frontier towards patient-tailored medicine, taking into account that theoretically every medical specialty can be influenced by both of them. Sex hormones define the differences between males and females, and the different endocrine environment promoted by estrogens, progesterone, testosterone, and their precursors might influence both human physiology and pathophysiology. With the term Gender we refer, instead, to behaviors, roles, expectations, and activities carried out by the individual in society. In other words, “gender” refers to a sociocultural sphere of the individual, whereas “sex” only defines the biological sex. In the last decade, increasing attention has been paid to understand the influence that gender can have on both the human physiology and pathogenesis of diseases. Even the clinical response to therapy may be influenced by sex hormones and gender, but further research is needed to investigate and clarify how they can affect the human pathophysiology. The path to a tailored medicine in which every patient is able to receive early diagnosis, risk assessments, and optimal treatments cannot exclude the importance of gender. In this review, we have focused our attention on the involvement of sex hormones and gender on different endocrine diseases.

Background The incidence of neuroendocrine neoplasm (NEN) and related carcinoid syndrome (CaS) has increased markedly in recent decades, and women appear to be more at risk than men. As per other tumors, gender may be relevant in influencing the clinical and prognostic characteristics of NEN-associated CS. However, specific data on carcinoid syndrome (CaS) are still lacking. Purpose To evaluate gender differences in clinical presentation and outcome of CaS. Methods Retrospective analysis of 144 CaS patients from 20 Italian high-volume centers was conducted. Clinical presentation, tumor characteristics, therapies, and outcomes (progression-free survival, PFS, overall survival, OS) were correlated to gender. Results Ninety (62.5%) CaS patients were male. There was no gender difference in the site of primary tumor, tumor grade and clinical stage, as well as in treatments. Men were more frequently smokers (37.2%) and alcohol drinkers (17.8%) than women (9.5%, p  = 0.002, and 3.7%, p  = 0.004, respectively). Concerning clinical presentation, women showed higher median number of symptoms ( p  = 0.0007), more frequent abdominal pain, tachycardia, and psychiatric disorders than men (53.3% vs 70.4%, p  = 0.044; 6.7% vs 31.5%, p  = 0.001; 50.9% vs . 26.7%, p  = 0.003, respectively). Lymph node metastases at diagnosis were more frequent in men than in women (80% vs 64.8%; p  = 0.04), but no differences in terms of PFS ( p  = 0.51) and OS ( p  = 0.64) were found between gender. Conclusions In this Italian cohort, CaS was slightly more frequent in males than females. Gender-related differences emerged in the clinical presentation of CaS, as well as gender-specific risk factors for CaS development. A gender-driven clinical management of these patients should be advisable.

Background Sellar/parasellar lesions have been studied in the adult and paediatric age range, but during the transition age their epidemiology, clinical manifestations, management and treatment outcomes have been poorly investigated. Materials and methods An Italian multicentre cohort study, in which hospital records of patients with diagnosis of sellar/parasellar lesions during the transition age and young adulthood (15–25 years), were reviewed in terms of prevalence, clinical and hormonal features at diagnosis, and outcomes where available. Both pituitary neuroendocrine tumours (pituitary tumours, Group A) and non-endocrine lesions (Group B) were included. Results Among Group A ( n  = 170, 46.5% macroadenomas), the most frequent were prolactin and GH-secreting tumours, with a female predominance. Among Group B ( n  = 28), germinomas and Rathke cells cysts were the most common. In Group A, the most frequent hormonal deficiency was gonadal dysfunction. Galactorrhoea and amenorrhoea were relatively common in female patients with prolactinomas. Pre-surgical diabetes insipidus was only seen in Group B, in which also hormone deficiencies were more frequent and numerous. Larger lesions were more likely to be seen in Group B. Patients in Group B were more frequently male, younger, and leaner than those of Group A, whereas at last follow-up they showed more obesity and dyslipidaemia. In our cohort, the percentage of patients with at least one pituitary deficiency increased slightly after surgery. Conclusions The management of sellar/parasellar lesions is challenging in the transition age, requiring an integrated and multidisciplinary approach. Hormone and metabolic disorders can occur many years after treatment, therefore long-term follow-up is mandatory.

Thyroid diseases and their treatment may influence the osseous system. The influence that prolonged suppressive L-thyroxine (LT4) therapy may have on inducing subclinical hyperthyroidism on bone metabolism is still a matter of debate. The aim of the present study was to assess the effects of chronic LT4 treatment at mildly inhibiting serum thyroid-stimulating hormone (TSH) doses on bone mineral density (BMD) and biochemical bone remodeling markers in a cohort of women with benign nodular goiter, and to verify the efficacy of the treatment on nodule size. A total of 200 euthyroid Caucasian women with nodular goiter (age 52.1 +/- 9; 80 pre- and 120 postmenopausal) were enrolled: 96 had been treated with LT4 for at least 3 years and a matched group of 104 had untreated goiter. LT4 therapy was given at a dose sufficient to reduce TSH under the lower limit of the normal range (0.27-4.20 microIU/ml) without suppressing it below the limit of assay sensitivity (0.005 microIU/ml) and maintaining normal serum values of free triiodothyronine (FT3) and free thyroxine (FT4). The adequacy of the dose was evaluated on the basis of serum TSH levels. The osteopenic effect of LT4 treatment was evaluated directly by total body and lumbar spine dual-energy X-ray absorptiometry (DEXA) and indirectly by biochemical parameters (alkaline phosphatase, osteocalcin, calcium, parathyroid hormone) at the baseline and throughout the follow-up. The efficacy of LT4 schedule on thyroid nodule size was assessed on the basis of the ultrasonographic evaluation. Mineralometric data showed no significant difference between BMD values for treated and untreated patients in both pre- and postmenopausal status. In all patients, serum markers of bone turnover were in the normal range, with no differences in the treated and control groups. The TSH concentrations were significantly lower in treated than in untreated patients (p < 0.0001); FT3 and FT4 were in the normal range for all patients. Evaluation of nodule size during follow-up showed a reduction of > or = 30% in 32 of 96 treated patients (33.3%) versus none in those untreated, whilst nodule size remained unmodified in 60 treated patients (62.5%) versus 35 (33.6%) in those untreated, and an increase in nodule size and/or development of new nodules was found in 4 treated patients (4.2%) versus 69 of the 104 untreated patients (66.3%). This study suggests that at slightly suppressing TSH doses, LT4 therapy has no adverse effects on BMD in both pre- and postmenopausal women, while having an efficacy on nodule size comparable with that reported using an LT4 schedule able to maintain TSH near or below the assay sensitivity limit.

In the present study, we compared the results of conventional ultrasonography (US) and colour flow Doppler sonography (CFDS) with those of US guided fine needle aspiration biopsy (FNAB) and of pathologic staging of resected thyroid nodules, to assess the relative importance of US and CFDS in discriminating malignant thyroid nodules. We retrospectively reviewed records of 230 patients submitted to US-guided FNAB before surgery for solitary, not hot thyroid nodules. Before US guided FNAB, they were examined with conventional US and CFDS. Conventional US evaluated nodule size, echogenicity, presence of halo sign and microcalcifications. CFDS evaluated the vascular pattern classified as types I, II and III. Twenty-seven patients with inadequate cytology were excluded from this study (11.7%). Two hundred and three patients underwent surgery. At histology a thyroid carcinoma was found in 36 patients (17.7%) and a benign nodule was observed in 167 patients (82.3%). We did not find any difference in cancer prevalence between nodules with a primary tumour size < or =1 cm and those >1 cm (17.6 vs. 17.7%; p = 0.99). A solid echo texture was not statistically significant to suggest malignancy (p = 0.32). Microcalcifications were seen in 83.3% (30/36) of malignant nodules and in 33.5% (56/167) of benign nodules. These results were statistically significant (p < 0.0001). The type III flow as determined by CFDS was a statistically significant criterion to suggest malignant disease (p < 0.005). The most predictive findings of malignancy on conventional US was the combination of microcalcifications plus the absence of halo sign (sensitivity 75%, specificity 71.9%, p < 0.0001). The combination of an absence of halo sign on conventional US and a type III pattern on CFDS presented the higher sensitivity (83.3%) for malignancy with a specificity of 43.7%. Microcalcifications on US in combination with a type III CFDS pattern showed a lesser sensitivity (80.6%) with an improved specificity (75.4%). In our opinion, the better balanced combination of US and CFDS features was the absence of halo sign plus microcalcifications and a type III CDFS pattern (sensitivity 72.2%, specificity 77.2%). The combination of conventional US and CFDS provides benefits in increasing the screening sensitivity and accuracy in distinguishing malignant thyroid nodules.