Diabetes Mellitus-Associated Functional Hypercortisolism Impairs Sexual Function in Male Late-Onset Hypogonadism.

Functional hypercortisolism is generated by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and has been proven to have a negative role in several complications. However, no study has evaluated the possible influence of diabetes mellitus-associated functional hypercortisolism on male hypogonadism and sexual function. We aimed to identify any association of hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and sexual function in men simultaneously affected by diabetes mellitus and late-onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism subjects suffering from functional hypercortisolism and fifteen diabetes mellitus and late-onset hypogonadism subjects who were free of functional hypercortisolism were retrospectively reviewed. Clinical, hormonal, and sexual parameters were considered. Hypercortisolemic subjects showed higher values of body mass index, waist, and glycated hemoglobin and lower ones of testosterone compared to normocortisolemic ones. All sexual parameters, except for orgasmic function, were significantly worse in hypercortisolemic than in normocortisolemic subjects. Hypercortisolemic patients showed higher values of cortisol after dexamethasone and urinary free cortisol as well as a lesser ACTH response after corticotropin releasing hormone test (ACTH area under curve) compared to normocortisolemic ones. No significant association was found at Poisson regression analysis between hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic subjects, negative and significant associations of cortisol response after corticotropin releasing hormone (cortisol area under curve) with erectile function (ß: -0.0008; p: 0.015) and total international index of erectile function score (ß: -0.0006; p: 0.001) were evident. This study suggests for the first time the impairing influence of the dysregulated hypothalamic-pituitary-adrenal axis on sexual function in diabetes mellitus-associated late-onset hypogonadism.

Diabetes mellitus and late-onset hypogonadism: the role of Glu298Asp endothelial nitric oxide synthase polymorphism.

Nitric oxide has been associated with insulin resistance and type 2 diabetes mellitus (DM). An association has been suggested between a single nucleotide polymorphism (Glu298Asp variant) of the endothelial nitric oxide synthase (eNOS) gene and increased risk of DM. However, the role of this polymorphism in favouring DM has not been investigated in hypogonadism, in which low testosterone and obesity are believed to play the major role. We aimed to evaluate whether eNOS gene single nucleotide polymorphism (Glu298Asp variant) might give a relevant contribution also to the onset of hypogonadism-associated DM. 110 men affected by late-onset hypogonadism were retrospectively reviewed. Patients were clinically and biochemically evaluated. Detection of eNOS Glu298Asp polymorphism was performed. After splitting the sample according to the three genetic variants (i.e. eNOSGG , eNOSGT , eNOSTT ), no difference was evident in age, body mass index (BMI) and total testosterone. Conversely, DM prevalence, glycaemia and glycated haemoglobin were significantly higher in eNOSTT than in eNOSGT and eNOSGG . Logistic regression analysis showed that, after adjustment for age, BMI and total testosterone, eNOSTT was positively and significantly associated with DM. Our study suggests that Glu298Asp single nucleotide polymorphism of the eNOS gene may be an independent risk factor for hypogonadism-associated type 2 DM.

Percutaneous therapy of varicocele: effects on semen parameters in young adults.

BACKGROUND: In spite of many years of debate, the impact of varicocele on male infertility is still controversial since its pathogenetic role on the impairment of semen quality has never been fully demonstrated. METHODS: In the present work, a series of 426 young adult males undergoing percutaneous treatment of varicocele were studied and semen parameters were evaluated at baseline and 12 months of follow-up. RESULTS: A significant increase in sperm cell concentration and a decrease in immotile spermatozoa were found after varicocele repair, but we failed to detect any significant positive change in progressive motility as well in sperm morphology after treatment. Similar results were also obtained when semen parameters were correlated with the degree of varicocele. CONCLUSION: Since a spontaneous improvement in semen quality has been mathematically established as a model of regression toward the mean, we conclude that the correction of varicocele in young adults is not a major indication when semen alteration is the only clinical problem.

Coenzyme Q10 levels in idiopathic and varicocele-associated asthenozoospermia.

Levels of coenzyme Q10 (CoQ10) and of its reduced and oxidized forms (ubiquinol, QH2, and ubiquinone, Qox) have been determined in sperm cells and seminal plasma of idiopathic (IDA) and varicocele-associated (VARA) asthenozoospermic patients and of controls. The results have shown significantly lower levels of coenzyme Q10 and of its reduced form, QH2, in semen samples from patients with asthenospermia; furthermore, the coenzyme Q10 content was mainly associated with spermatozoa. Interestingly, sperm cells from IDA patients exhibited significantly lower levels of CoQ10 and QH2 when compared to VARA ones. The QH2/Qox ratio was significantly lower in sperm cells from IDA patients and in seminal plasma from IDA and VARA patients when compared with the control group. The present data suggest that the QH2/Qox ratio may be an index of oxidative stress and its reduction, a risk factor for semen quality. Therefore, the present data could suggest that sperm cells, characterized by low motility and abnormal morphology, have low levels of coenzyme Q10. As a consequence, they could be less capable in dealing with oxidative stress which could lead to a reduced QH2/Qox ratio. Furthermore, the significantly lower levels of CoQ10 and QH2 levels in sperm cells from IDA patients, when compared to VARA ones, enable us to hypothesize a pathogenetic role of antioxidant impairment, at least as a cofactor, in idiopathic forms of asthenozoospermia.

Metal imidazolato complexes: synthesis, characterization, and X-ray powder diffraction studies of group 10 coordination polymers.

Binary metal imidazolates of the group 10 metals have been prepared and typically found amorphous. However, the intermediacy of a number of (poly)crystalline species during their formation has been evidenced; their selective preparation and characterization, by chemical, spectroscopic, and thermal methods and their structure solution by the ab initio X-ray powder diffraction technique lead to the discovery of new interesting structural features, such as those of polymeric Ni(Him)(2)(im)(CH(3)COO) (Him = imidazole) and of the hydrogen-bonded polymers of general Pd(x)Pt(1-x)(Him)(2)(im)(2) formula (x = 0, 0.5, 1). The latter are built upon 2D frameworks of (pseudo)square meshes, which, in the pure Pd derivative, form an entangled structure based upon interpenetrating 2D layers, coupled in pairs. The different structures are discussed in terms of different conformations of the new "im-H-im" ligand, which acts as monoanionic exobidentate fragment, similar to im, pyrazolate (pz), "pz-H-pz", and pyrimidin-2-olate.

Positron emission tomography with fluorine-18 fluorodeoxyglucose to evaluate response of early breast carcinoma treated with stereotaxic interstitial laser therapy.

Stereotaxic interstitial laser therapy is a promising new alternative to surgery to treat early-stage breast cancer. With this, laser energy coagulates the tumor with controlled heat, leading to fibrosis. Fluorodeoxyglucose positron emission tomography (FDG PET) scanning was performed in four patients treated by this technique to determine the degree of necrosis after interstitial laser therapy. The results showed that FDG PET scanning was in close agreement with histopathologic findings, confirming complete necrosis in one patient and variable response in the other three patients. Uptake of FDG appears to be a reliable means to monitor treatment response after interstitial laser therapy and may be useful in the management of breast cancer when used with this new procedure.

Response of Osteosarcoma to Chemotherapy. Evaluation with F-18 FDG-PET Scans.

Objective: Positron emission tomography (PET) using fluorine-18-fluoro-2-D-deoxyglucose (FDG) is increasingly being used to evaluate and manage oncology patients. Several reports have documented its utility in diagnosis, staging, response to treatment, and tumor viability assessment. There is, however, a paucity of literature on PET scanning in patients with osteosarcoma. We report results of serial F-18 FDG-PET scans in 16 untreated patients with osteosarcoma who underwent chemotherapy prior to surgical resection of the primary tumor site.Procedure: Changes in tumor fluoro-2-D-deoxyglucose (FDG) uptake were correlated with percent tumor necrosis on histopathology. PET studies were analyzed by visual assessment of tumor uptake of FDG by 3 independent observers, calculating a tumor to normal background activity ratio (TBR) by drawing regions of interest (ROIs) around the tumor and background activity in the contralateral normal limb, and percent change in TBR values between baseline and presurgical study.Results: All patients had positive baseline scans. Baseline TBRs ranged between 2.5-8.7 and visual assessment of intensity of FDG uptake was 2-3 on a scale of 0-3. At histopathologic examination, 8 patients were classified as good responses with more than 90% tumor necrosis and 8 patients as poor responses with less than 90% necrosis. Tumor necrosis was accurately predicted on PET scan in 15/16 patients by visual assessment, 14/15 patients by final TBR value on presurgery scans, and 7/15 patients using percent change of TBR on serial scans.Conclusions: The results of this small series suggest that FDG-PET scanning is fairly accurate in evaluating the response of osteosarcoma to chemotherapy. Visual assessment and TBR are more accurate in predicting tumor necrosis than percent change in TBR on serial scans.

Normal thymic uptake of 2-deoxy-2[F-18]fluoro-D-glucose.

Whole-body 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) positron emission tomography (PET) of a 54-year-old woman with a history of recurrent thyroid follicular cancer and an elevated thyroglobulin level showed significant FDG uptake in the thyroid bed and anterior mediastinum. A previous scan after high-dose I-131 therapy also showed iodine uptake in these regions. Because of a lack of response to iodine therapy, the patient had surgery. Recurrent thyroid cancer was found in the neck, but the mediastinal lesion was shown to consist of normal thymus tissue. In repeated examinations performed after surgery, there was no uptake of FDG or I-131 in the anterior mediastinum. Previous treatment with a high dose of radioiodine may have contributed to visualization of a normal adult thymus with FDG PET.

Hematopoietic cytokine-mediated FDG uptake simulates the appearance of diffuse metastatic disease on whole-body PET imaging.

FDG-PET is increasingly being used to assess malignant tumors. However, leukocyte colony-stimulating factors (CSFs), which promote the expansion of hematopoietic bone marrow, have also been demonstrated to cause increased bone-marrow FDG uptake. Three hundred FDG-PET studies conducted over a 1-year period were reviewed for diffuse bone-marrow uptake. Elevated bone-marrow uptake on PET was correlated with pathological findings and courses of granulocyte-CSF (G-CSF) therapy. These results demonstrate that G-CSF mediated FDG uptake in bone marrow is often indistinguishable from that caused by disseminated metastatic disease. However, the bone-marrow response to G-CSF decreases rapidly following the last CSF administration. Therefore, FDG-PET in patients receiving G-CSF should be delayed, when possible, until 5 days after the end of G-CSF therapy.

Normal thymic uptake of FDG on PET imaging.

Assessment and characterization of the thymus by various imaging methods have been extensively described. The authors report increased uptake of 2-(18)Fluoro-2-deoxy-D-glucose (FDG) in the normal thymus gland of patients between the ages of 2 and 13 years. Most of these patients had PET scans for various oncologic conditions and had no clinical problems referable to the thymus gland. This uptake assumes an important role when evaluating mediastinal uptake in whole-body PET scans in pediatric oncology patients to avoid false-positive interpretation.

Combined chemoradiation therapy for anal cancer. A report of 56 cases.

Fifty-six consecutive patients with primary epidermoid cancer of the anus were treated with combined chemoradiotherapy (CRT). No patient had been previously treated. There were 44 women and 12 men, with an age range of 25 to 88 years (median, 62 years). Cancer was located at the anal verge in five and at the anal canal in 51 patients. The tumor extended from the canal to adjacent sites in 37 cases. All patients had their tumors histologically assessed: 54 were squamous cell and two were basaloid carcinoma. Twelve patients had T1, 27 had T2, and 17 had T3 primaries, and eight had inguinal metastatic nodes. The protocol treatment consisted of three cycles of 5-fluorouracil (FU) (750 mg/m2/day x 5 days continuous infusion) and mitomycin C (MMC) (15 mg/m2 intravenous (I.V.) bolus on day 1 of each course) given every 6 weeks. Radiotherapy (RT) was started simultaneously: 36 Gy was given in 4 weeks to the anal region with perineum and the lower and middle pelvis, including inguinal and external iliac nodes. After 2 weeks of rest, a boost of 18 Gy was delivered to the anoperineal region in 10 fractions. Because of toxicity, the planned treatment was performed in 50% of patients: 28 patients received less than three cycles of chemotherapy, and seven patients received less than 49 Gy radiation therapy. Toxicities were mild to moderate, and no patients needed hospitalization. A complete response (CR) was observed in 49 patients (87%), eight of whom had metastatic nodes. A partial response (PR) was assessed in five patients (9%) and stable and progressive disease in 2 patients (4%). Objective response (OR) had no evident relationship with extent of primary, presence of metastatic nodes, number of cycles of chemotherapy, and doses of radiotherapy. Of 49 patients who achieved CR, 12 (24%) developed a local recurrence after a median interval of 8 months (range, 2 to 45 months); 11 of them were submitted to surgical rescue and 8 are alive without evidence of disease. Local recurrence was correlated with the main characteristics of patient and tumor and with treatment, but no clear correlation was observed. Actuarial survival rate at 5 years was 81%. Results of present study are compared with those reported by others, and crucial questions concerning combined chemoradiationtherapy are discussed. The authors conclude that chemoradiotherapy is a highly effective treatment of anal cancer, which should be employed as primary approach regardless of different characteristics of patient and tumor.