Background: There have been controversial studies evaluating ventricular functions in patients with idiopathic hypogonadotropic hypogonadism (IHH). A recent study has demonstrated that low serum testosterone levels are associated with increased cardiovascular mortality. Aim: We aimed to investigate ventricular functions by standard echocardiography and examine the effects of substitutive therapy on right ventricular (RV) functions in patients with IHH by means of pulsed wave tissue Doppler imaging (PWTDI). Methods: Twenty-three patients with IHH and 31 controls were evaluated by standard echocardiography and PWTDI. Isovolumic acceleration (IVA), myocardial systolic wave (Sm) velocity, myocardial precontraction time (PCTm), and PCTm to contraction time (CTm) ratio were determined as systolic indices. Myocardial relaxation time (RTm), early (Em) velocity, late (Am) velocity, and Em to Am ratio were determined as diastolic indices. Results: Peak pulmonary artery pressure (PAP) was significantly higher in control subjects (p=0.008). IVA and Sm values were similar in patients and controls. Em, Am velocities, and their ratios did not differ. PCTm was significantly longer (p=0,001) and PCTm to CTm ratio was significantly higher in patients (p=0.001). These parameters also decreased after replacement therapy, albeit not statistically significantly (p>0.05). PAP was significantly higher after substitutive therapy (p=0.009). Conclusions: Ventricular functions are normal in patients with IHH. Substitutive therapy has no effects on RV functions. However, substitutive therapy may increase PAP in small amounts, which has no immediate clinical implication with short term use.

High parathyroid hormone (PTH) levels have been reported in patients with chronic heart failure (CHF). Similarly, its levels increases with ageing and are related to impaired survival in elderly adults. However, its relationships with neuroendocrine activation and endothelial dysfunction in CHF have not been previously studied. Seventy three CHF males with NYHA class II and III and 20 control subjects age >/= 55 years were recruited. PTH, 25-hydroxyvitamin D (25(OH)D), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), adiponectin, and osteoprotegerin were measured. Endothelial function (brachial flow mediated dilation), echocardiography, physical performance, and quality of life were assessed, as well. CHF patients had markedly increased serum PTH (77+/-33 vs. 40+/-11, P<0.0001), NT-pro-BNP [1809(2742) vs. 67(74), P<0.0001], adiponectin (17+/-9 vs. 10+/-2, P<0.0001), osteoprotegerin, whereas 25(OH)D levels were decreased compared to controls. Increased PTH is positively correlated with NT-pro-BNP (r=0.399, P<0.0001), adiponectin (r=0.398, P<0.0001), and osteoprotegerin, whereas negatively with 25(OH)D in CHF patients. Additionally, increased serum PTH was associated with endothelial dysfunction, echocardiographic variables of heart failure progression, impaired physical performance, and deteriorated quality of life. In a multivariate linear regression analysis, increased serum PTH was independently associated with neuroendocrine activation (NT-pro-BNP, adiponectin) and endothelial dysfunction in elderly CHF men (R2=0.455). Additionally, demonstrated relations with other well-established variables of heart failure severity suggest the potential role of serum PTH in the pathogenesis and non-invasive monitoring of heart failure progression. Future studies are welcome to evaluate the predictive value of serum PTH for clinical outcomes as well as beneficial potential of PTH suppression in CHF patients.

BACKGROUND. In contrast with maximal voluntary resistance exercise, which is allegedly considered a potent growth hormone (GH) stimulus in young subjects, evaluation of GH response to whole-body vibrations (WBV) has yielded conflicting results,. METHODS. The acute effects of WBV alone (test A), maximal voluntary isometric contractions (MVC, test B), and combination of WBV and MVC (test C) on serum GH and blood lactate (LA) levels were studied in 9 healthy adult males. Muscle soreness was assessed 24 and 48 hours after exercise by a visual analogue scale (VAS). RESULTS. GH responses were significantly higher after tests B and C than after test A (GH peaks: 18.8+/-9.5 ng/ml or 20.8+/-13.7 ng/ml, respectively, vs. 4.3+/-3.5 ng/ml; p<0.05), with no difference between tests B and C. LA concentrations significantly increased after test A, B and C, being significantly higher after tests B and C than test A (LA peaks: 2.0+/-0.5 mmol/l or 6.7+/-2.3 mmol/l, respectively, vs. 7.6+/-0.9 mmol/l; p<0.05). Peak LA values were significantly correlated to GH peaks in the three tests (r= 0.48; p<0.05). Muscle soreness was significantly higher 24-48 hour after tests B and C than after test A, no significant differences being present between tests B and C. CONCLUSIONS. WBV stimulates GH secretion and LA production, with no additive effect when combined with repeated isometric voluntary contractions. Optimization of protocols based on WBV seems important to maximize the positive effects of this intervention on the somatotropic function.

Background. With the increasing use of thyroid ultrasound, the recognition of thyroid nodules in a large proportion of apparently healthy subjects has become common. Because also the papillary thyroid microcarcinomas (PTMC) are being increasingly discovered, it is important to ascertain whether PTMC may exhibit heterogenous clinical features, associated with different aggressiveness. Aim. We retrospectively examined 122 subjects (98 female, 80.3%, and 24 males) with thyroid cancer to find potential clinical and pathological findings that could be predictive of clinically aggressive behavior. Results. 20 of the 31 patients with true incidental cancer (64.5%) in comparison to 20 of the 91 patients with non incidental cancer (21.9%) had a diameter <10 mm, and this difference was statistically significant (p <0.0001). There was a statistically significant association between size and invasiveness because 19.3% of invasive cancers were smaller than 10 mm whereas 44.6% of non invasive cancers were smaller than 10 mm (p=0.005). The relationship between incidental discovery and invasiveness was also evaluated, but the proportion of incidental invasive cancer (19.3%) was not significantly different than that of incidental non invasive cancer (30.8%). In the multivariate analysis, only size <10 mm (OR=0.35, p=0.013) and papillary vs. other histotypes (OR=0.35, p=0.04) were statistically significant protective factors against invasiveness. Conclusions. (i.) Incidentally discovered thyroid cancers are more frequently microcarcinomas; (ii.) there appears to be no difference in terms of invasive behavior between the incidental and non incidental thyroid cancer; (iii.) smaller tumor size emerges as a protective factor.

Aims: The purpose of the study was to assess energy expenditure and cardiovascular response to rhythmic activity with six machines exercising different arm and leg muscle groups in normal-weight (NW) and obese (OB) individuals. Methods: In 16 extremely OB subjects and 15 NW controls, oxygen uptake (VO2), heart rate (HR), blood lactate (LA) concentration and ratings of perceived exertion (RPE) were determined during submaximal rhythmic exercise at different intensities obtained by increasing the frequency of the movement (FOM) with each machine. Peak VO2 (VO2p) for each equipment was determined with incremental tests up to exhaustion, whereas maximal VO2 was estimated at cycle ergometer. Results: Net energy cost (Enet) of exercise increased (p<0.001) for effect of FOM, in both NW and OB with all equipments. Enet was higher in OB than NW during submaximal exercise with Chest/Back, Shoulder Press/Lat Pull and Leg Press. Higher VO2p were attained with lower limbs than with upper limbs, in both NW (p<0.001) and OB (p<0.001). At the same VO2 (relative to maximal), HR, LA and RPE were similar in NW and OB but higher during arm than leg activity (p<0.001), while at the same VO2 (relative to VO2p) no difference was detected. Conclusion: Enet of rhythmic exercise is higher in OB than NW with machines requiring wide displacement of large body segments. For both NW and OB, physiological responses and RPE are importantly affected by the relative activation of involved muscles. LA concentration is an important determinant of RPE, independent from the limb in activity.

Aim: Our objective was to report a single-center experience of the management of pituitary tumor apoplexy. Patients and Methods: We retrospectively analyzed a series of 44 patients hospitalized for pituitary apoplexy between January 1996 and March 2008 at the Timone Hospital, Marseille, France. Results: Most frequent presenting symptoms were headaches (93%), visual impairment (85%) and vomiting (59%). Hypopituitarism was present at diagnosis in 88% of patients, with a high incidence of corticotroph deficiency (70%). A risk factor was found in 52% of patients, mostly hypertension. Apoplexy occurred in a previously undiagnosed pituitary adenoma in 32/44 cases (73%). The apoplectic event concerned 12 secreting, 27 non-functioning, 4 uncharacterized adenomas and one Rathke's pouch cyst. Nineteen patients underwent surgery within the first month, and one patient had conventional radiotherapy. Twenty-four patients, who had no ophthalmic or neurological signs, were conservatively treated in first intention; among them, 6 received high dose corticosteroids. After a median follow-up of 21 months, there was no significant difference in terms of endocrine or visual recovery between the operated and the conservatively treated groups, nor between patients treated with corticosteroids or not. Panhypopituitarism was observed in 52% of patients, but partial or complete visual recovery was present in the majority of patients (91%), whatever the therapeutic approach. Conclusion: The outcome of patients treated with or without surgery for pituitary apoplexy without severe neuro-ophthalmic deficits seems to be identical, pleading for a conservative management of pituitary apoplexy in the absence of visual emergency.

Background: Subarachnoid hemorrhage (SAH) is a potential cause of hypopituitarism. Most of the studies regarding the relationship between SAH and anterior pituitary function were retrospective and hormonal assessment was performed several months after SAH. Aim: To prospectively evaluate the prevalence of anterior pituitary hormone deficiencies in the acute phase after spontaneous SAH and their possible correlation with clinical and radiological parameters. Methods: Pituitary function was tested in 60 patients within 72h after spontaneous SAH . Results: 56.9% of the patients showed at least one anterior pituitary hormone deficiency: gonadotropin and GH secretion failure represented the most prevalent hormonal deficiencies (33.3% and 22.0%, respectively), whereas ACTH and TSH deficiency were less frequent (7.1% and 1.8%, respectively). With the exception of secondary hypogonadism, the prevalence of other pituitary hormone deficiencies is in agreement with previous studies, which evaluated pituitary function on long-term follow up after SAH. No correlation was found between hypopituitarism and clinical status, as assessed with Hunt-Hess and Glascow Coma Scales. Moreover, no correlation was found between hypopituitarism and bleeding severity evaluated with Fisher's scale. Conclusions: We demonstrated a high prevalence of anterior pituitary hormone deficiencies acutely after SAH. Although part of GH and gonadotropin deficiencies might be a consequence of functional alteration due to SAH itself, the finding of low cortisol levels in this stressful condition strongly suggests the presence of true hypocortisolism. Therefore, an evaluation of pituitary function shortly after SAH might be useful to identify a subset of patients who deserve a more accurate follow up.

Few data are available regarding bone mineral density (BMD) and the risk of vertebral fracture among mainland Chinese women with type 2 diabetes mellitus (T2DM). A decrease in the bone projective area (BPA) can be an indirect marker reflecting compressed vertebral fracture. We investigated age-related BMD, BPA, and the prevalence of osteoporosis in women with T2DM in mainland China. BMD and BPA of the posteroanterior lumbar spine (L1-L4) and hip were measured by dual-energy X-ray absorptiometry in 1253 women with T2DM and 1194 control subjects without diabetes aged 40-80 years. BMD of the lumbar spine and hip decreased with age. BMD of the lumbar spine was higher in T2DM than controls (p<0.05-0.001), as was the same to BPA at some vertebral bodies (p<0.05-0.001), whereas, no significant intergroup differences in BPA were observed at the hip. The prevalence of osteoporosis in the women with T2DM increased with age: 0-2.58% at age 40-49 years; 6.94-28.4% at age 50-59 years; 32.7-76.7% at age 70-80 years, with the range reflecting differences between skeletal sites. In subjects over 60 years, the rates of osteoporosis at posteroanterior spine were significantly lower in T2DM than in controls (p<0.05-0.001). In conclusion, women with T2DM had higher BMD and lower risk of osteoporosis. Higher BPA of the vertebrae indicated that women with T2DM in mainland China would have a lower risk of vertebral fracture than non-diabetic women.

The objective was to investigate the effects of a 3-week weight-management program including moderate energy restriction and exercise training at two intensities (LI:40% and HI:70% V'O2max) on body composition, energy expenditure and fat oxidation rate in severely obese adolescents. Twenty obese adolescents, aged 15-17 years (BMI: 37.5 kg/m2 ; 38.2 % fat mass) participated in this study. Before starting (week 0, W0) and at the end of the weight-management period (week 3, W3), body composition was assessed by a multifrequency tetrapolar impedancemeter (BIA); basal metabolic rate (BMR), energy expenditure and substrate oxidation rate during exercise and post exercise recovery by indirect calorimetry. At W3, body mass and fat mass decreased significantly (p<0.005) in all groups, and the decreases were significantly greater in the LI than in the HI group (-8.1+/-1.6 vs -5.9+/-1.6 kg and -4.2+/-1.9 vs -2.3+/-1.7 kg, p< 0.05, respectively). Predicted V'O2max, expressed in relative values, changed significantly only in the HI group by +0.010+/-0.006 L/(kg FFM x min), (p=0.010). By contrast, no significant changes were observed at W3 in BMR, energy expenditure and substrate oxidation rate during exercise and post-exercise recovery. In conclusion, LI (40% of V'O2max) physical activity favours fat oxidation and it seems advisable to encourage obese adolescents to perform LI physical activity which is more feasible and acceptable than intense exercise.

Objective The aim of the study was to evaluate whether vitamin D [25-(OH) D3] status affects serum IGF1 concentrations in healthy subjects. Design and Patients Two hundred and forty one consecutive healthy subjects were included in the present study. Measurements Serum IGF1 and 25-(OH) D3 concentrations. Results As expected, serum IGF1 concentrations progressively decreased with age (r=-0.55, p<0.0001); on the contrary, gender was not related to serum IGF1 levels. A positive relationship was identified between serum 25-(OH) D3 and IGF1 concentrations (r=0.33, p<0.0001); the 25-(OH) D3 -dependent changes of serum IGF-1 concentrations were observed also when subjects were divided on the basis of vitamin D deficiency; in fact, those with severe 25-(OH) D3 deficiency (<20 ng/ml ) had lower (185+/-83 microg/l) IGF1 values than those with mild-to absent 25-(OH) D3 deficit (225+/-83 microg/l, p=0.0004). Conclusions 25-(OH) D3 status may contribute to determine serum IGF1 levels in healthy population.

Objective Current therapies for acromegaly are unsatisfactory for some patients. High dose thiazoledinediones have been reported to reduce serum GH levels in animal models of acromegaly. The objective of the study was to evaluate the effect of increasing doses of rosiglitazone on serum GH and IGF1 concentrations in acromegalic patients. Design Phase 2 clinical trial. Patients and Methods Five consecutive patients with active and uncontrolled acromegaly under conventional medical therapies were treated with increasing doses of rosiglitazone [4 mg/d every month, starting from 8 mg/d up to 20 mg/d] added to previous medical therapies for acromegaly. Results Mean serum IGF-1 concentrations decreased from 547+/-91 microg/liter to 265+/-126 microg/liter [p<0.001] during rosiglitazone treatment: 4 patients had normal serum IGF1 concentrations, and a patient had lowered serum IGF1 values, although still abnormal, at the end of the study. On the contrary, serum GH concentrations did not significantly changed during rosiglitazone therapy, as well as, other pituitary hormones. No relevant side effects of rosiglitazone were observed during the study period. Quantitative real time PCR and Western blotting showed that rosiglitazone lowered GH-dependent hepatic generation of IGF-1 in HepG2 cell line. Conclusions Rosiglitazone reduces serum IGF-1 concentrations in patients with uncontrolled acromegaly under conventional medical therapies, likely acting on the GH-dependent hepatic synthesis of IGF-1. Large studies are necessary to confirm the role of rosiglitazone as an adjunctive therapy for uncontrolled acromegalic patients under conventional medical therapies.

Background: The metabolic syndrome (MetS) has been found to be closely related with thrombotic diseases. The mechanism, however, is far from elucidated. Aim: This study was designed to investigate the relationship between endogenous resistin and thrombosis mediating factors, as well as its potential effects on the gene expression of cardiovascular diseases biomarkers. Methods: 90 patients satisfied the MetS criteria, and 55 healthy subjects were recruited as part of a single-center clinical study. Plasma levels of resistin, tissue factor (TF), tissue factor pathway inhibitor (TFPI), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) were measured by enzyme-linked immunosorbent assays. The effect of resistin on the expression of cardiovascular diseases biomarkers in human umbilical vessel endothelial cells (HUVEC) was assayed by gene microarray. Results: (1) The average levels of resistin in MetS patients with or without acute myocardial or cerebral infarction were significantly higher than that of the controls. (2) TF and TFPI levels were greatly increased in MetS with infarction patients than those of MetS patients. (3) In MetS with infarction patients, resistin was positively correlated with TF and PAI-1 (r=0.313, p=0.008; r=0.401, p=0.002, respectively). (4) In HUVEC, the microarray showed that apolipoprotein C-I (ApoC-I), angiotensin converting enzyme (ACE), tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and member 5 (CD40) genes expression were dramatically increased by resistin. Conclusion: In patients with MetS, resistin is strongly associated with hypercoagulative and hypofibrinolitic activities. Moreover, resistin may induce thrombotic complications via mediating the lipoprotein metabolism and stimulating inflammation.

Congenital Adrenal Hyperplasia, both in its classic (CCAH) and in non classic form (NCAH), is a morbid condition sustained by the absent or reduced function of one of the enzymes involved in cortisol biosynthesis - mainly 21 hydroxylase - associated with different levels of clinical androgenization. In a wide group of relatives of patients affected by CCAH and NCAH (N= 222) or healthy volunteers (N= 30) a clinical, hormonal and genetic evaluation had been performed in order to differentiate the condition of heterozygous mutation carrier or not of any among 21 hydroxylase gene (CYP 21) mutations. This study shows that clinical presentation and basal 17alpha-OHP are not able to differentiate between heterozygous carriers and non carriers whereas 17alpha-OHP value after ACTH bolus is significantly different between heterozygous carriers and non carriers: p<0.001 with a "cut-off" value of 3 ng/ml (90% sensitivity and 74,3% specificity). Moreover, our data indicate that 17alpha-OHP response to ACTH may be a useful tool to select subjects for genetic analysis.

Objective: The adjuvant radio/chemotherapy, usually employed after orchidectomy in patients with testicular tumors, allows a long term survival with a consequent increased request for fertility. However, little is known about the effects of the anti-neoplastic treatment on sperm cytogenetic. Therefore, this prospective, longitudinal study was designed to evaluate the effects of radio- and/or chemo-therapy on sperm chromosomal asset. Method: Eleven patients with testicular tumor were enrolled and underwent sperm aneuploidy rate evaluation before and after 3, 6, 9, 12, 18, 24 and 36 months from radio- and/or chemotherapy. A double and triple multicolor fluorescence in-situ hybridization for chromosomes 8, 12, 18, X and Y was used to evaluate the sperm aneuploidy rate. To define normal sperm aneuploidy rate, 18 healthy, normozoospermic men were selected as controls. Results: Before treatment, testicular tumor patients had a higher total sperm aneuploidy rate compared to normal men. Total sperm aneuploidy rate showed a slight, but statistically significant increase 6 months after anti-neoplastic treatment. This increase was mainly related to the high sperm aneuploidy rate found in 2 patients which remained elevated up to 12 months in both of them. Conclusion: These results showed that anti-neoplastic treatment caused only slight and transient sperm malsegregation events in patients with testicular tumor. However, since a subset of them had an elevated sperm aneuploidy rate for about one year, we suggest to counsel them to refrain from fatherhood for this length of time.

The alterations of sexual function known as the erectile dysfunction are quite frequent among patients affected by liver diseases and they tend to increase in advanced liver failure. This process is directly linked to cirrhosis or its treatments, such as liver transplantation, or to certain drugs (e.g. beta-blockers). Independent of cirrhosis, other factors may cause sexual problems in these patients. Alcohol itself seems to worsen sexual function in the absence of cirrhosis. Viral hepatitis has an uncertain influence on male gonadic function and even antiviral therapy itself can worsen some seminal and hormonal parameters, although it is reversible. Quality of life may be greatly decreased in cases of cirrhosis where these alterations are present, so it is important to value and care for them, if possible. This review investigates the major male sexual disturbances in liver diseases of various origins.