SDHx and Non-Chromaffin Tumors: A Mediastinal Germ Cell Tumor Occurring in a Young Man with Germline SDHB Mutation.

Background: Mutations in genes encoding one of the subunits of succinate dehydrogenase (SDH) are involved in pheochromocytoma (PHEO) and paraganglioma (PGL) development. Over the last few years, such mutations have also been associated with non-chromaffin tumors. However, immunohistochemistry (IHC) on the tumor tissue and a study on the loss of heterozygosity (LOH) aimed at demonstrating the pathogenic role of SDHx genes have only been employed in a few cases. Case report: We describe the case of a 19-year-old Caucasian man with a germline SDHB mutation, who presented with acne vulgaris resistant to medical treatment. His follow-up for chromaffin tumors was negative, while hormonal tests revealed suppressed gonadotropins with testosterone in the upper range of normality and elevated ß-human chorionic gonadotropin (ß-hCG). At the whole-body enhanced CT scan, a mediastinal lesion suggestive of a germ cell tumor (GCT) was detected. 18FDG-PET (fluorodeoxyglucose-positron emission tomography) imaging showed low glucose metabolism at the mediastinal site. Surgical removal of the mass was uneventful. Pathology confirmed the diagnosis of GCT consisting of cystic teratoma (95%) and seminoma (5%). IHC for SDHB showed normal protein expression, and genetic analysis of the tumor tissue revealed the absence of SDHB LOH. Normalization of the hormonal tests and acne attenuation were achieved after surgery. Conclusion: We report an incidental association of a germinal SDHB mutation and mediastinal GCT in a young Caucasian man. Our paper highlights the importance of IHC and genetic analysis in confirming the etiologic role of SDHx genes in nonchromaffin tumors, thus excluding incidental associations.

Female sexual dysfunction and hormonal status in multiple sclerosis patients.

INTRODUCTION: Literature holds no information on a correlation between blood hormonal levels, in particular sex hormones and the sexual response of women with multiple sclerosis (MS). AIM: To investigate a possible correlation between hormonal status and the sexual response of females with MS. MAIN OUTCOME MEASURES: The Female Sexual Function Index (FSFI) questionnaire was used to determine sexual dysfunctions (SDs). Methods for measuring blood hormones were chemiluminescence immunoassay, electrochemiluminescence immunoassay, enzyme immunoassay, and radioimmunoassay. METHODS: During the screening phase, 55 women of reproductive age were recruited and completed the FSFI. In the first phase of the study females underwent a hematic hormonal evaluation on the third day of their menstrual cycle. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH), cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstenedione, 17[alpha]-hydroxyprogesterone, total and free testosterone, 17 beta estradiol, inhibin and sex hormone binding globulin (SHBG), and thyroid hormones (fT3 and fT4) were checked. On the day 20-21 into their menstrual cycle the progesterone hematic value was noted. Patients with amenorrhea had all hormones tested once with a random blood drawing. After a 3-month period patients began phase 2, completing the FSFI again. The same blood hormones were investigated. RESULTS: Fifty-four females completed the study. Thirty-one continued to manifest at least one SD: desire (57.4%) was the most common. Overall, 36.4% showed abnormal hormonal alterations. The most frequent was 40% for 17 beta-estradiol. None of the FSFI domains, including the total score, revealed any statistically significant correlation to the hormones investigated. No statistically significant clinical predictive factors for blood hormone abnormalities were detected; comparing females with and without SD, P = 0.250 using chi-squared test was reached. CONCLUSIONS: Notable percentages of blood hormonal alterations and SD were documented, but no significant statistical correlations were detected between hormonal status and sexual function.

Male osteoporosis and androgenic therapy: from testosterone to SARMs.

As in the women, male osteoporosis represents an important social problem, amplified by the increasing life expectance.Differently from women, 50% of male osteoporosis is secondary to treatments and/or diseases that make mandatory their search through an accurate clinical investigations in every newly diagnosed osteoporotic men. Male osteoporosis is frequently underdiagnosed and consequently undertreated, and too often it is revealed only after the occurrence of a fragility fracture. Androgens may prevent the loss of cancellous bone and stimulate periosteal cortical bone apposition. The anabolic effect of testosterone on both bone and muscle, is limited by the high incidence of androgenic side effects. Hypogonadism is the only situation where the benefits of the use of testosterone formulations exceed the side effects. Selective androgen receptor modulators can dissociate androgenic and anabolic effect on different tissues with various strategies. Many compounds have been studied with positive results in vivo and in clinical trials.

Clinical female sexual outcome after sacral neuromodulation implant for lower urinary tract symptom (LUTS).

INTRODUCTION: Over the last few years, sacral neuromodulation (SNM) has become an established treatment option for lower urinary tract symptoms (LUTS). AIM: To evaluate if SNM improves sexual function in females treated with SNM for LUTS. MAIN OUTCOME MEASURES: Improvement in sexuality by the Female Sexual Function Index (FSFI) and the Female Sexual Distress Score (FSDS). MATERIALS AND METHODS: We included 31 women, 17 of whom were neurogenic with permanent SNM. Prior to the neuromodulation screening, we assessed sexual function through blood sexual hormones, the FSFI and the FSDS questionnaires. Significant enhancement in sexuality meant an increase of 60% of the total score or of one FSFI domain, or 50% improvement on the FSDS. Only females who showed significant benefits in the first visit post-permanent SNM repeated the questionnaires in follow-up. All these women had their final visit by July 2007. RESULTS: Both questionnaires indicated a clinically significant improvement in sexuality that was maintained up to the final visit for 4 out of 11 neurogenics with sexual dysfunctions: one showed arousal and desire disorders, one showed arousal disorder and lubrication impairment, one showed arousal disorder and pain, and one showed desire and orgasm deficits. Mean duration of sexual improvement was 23 months. Notable clinical improvement in sexuality was observed in two out of eight idiopathics (one suffering from arousal and desire disorders, and one from lubrication impairment) with a median follow-up of 22 months. CONCLUSIONS: The positive effects regarding sexuality may be due either to enhancement of LUTS or to the direct stimulation of the sacral roots (S3).

A patient with MEN1-associated hyperparathyroidism, responsive to cinacalcet.

BACKGROUND: A 30-year-old woman with suspected multiple endocrine neoplasia type 1 (MEN1) was referred to our center in 2001 with primary hyperparathyroidism caused by a multiglandular parathyroid adenoma. The patient also had hyperprolactinemia caused by an anterior pituitary macroadenoma. The patient underwent a parathyroidectomy with autotransplantation of parathyroid fragments into the nondominant forearm, resulting in resolution of the primary hyperparathyroidism. MEN1 was confirmed by analysis of the MEN1 gene, which revealed a 1555insG frameshift mutation. In 2006 serum calcium and parathyroid hormone (PTH) levels were again found to be high. INVESTIGATIONS: After parathyroidectomy in 2001, the patient underwent regular measurements of PTH levels from both forearms, of serum calcium, prolactin and phosphate levels, and of urinary calcium and phosphate levels. When serum calcium and PTH levels were found to be elevated in 2006, circulating PTH levels were similar in both forearms. Ultrasound scan and technetium-99m-labeled hexakis-2-methoxyisobutylisonitrile ((99m)Tc MIBI) scintigraphy evidenced a metabolically active parathyroid nodule in the neck. DIAGNOSIS: Local recurrence of a parathyroid adenoma associated with MEN1. MANAGEMENT: Because the patient refused a further operation, we decided to initiate pharmacological treatment with cinacalcet. After 1 month of therapy, serum calcium and PTH levels returned to normal. The patient has now been closely monitored for 1 year. During this time calcium and PTH levels remained normal, morphologically the parathyroid nodular lesion remained unchanged and cinacalcet was well tolerated without the occurrence of adverse events. Cinacalcet could represent an important pharmacological intervention in MEN1-associated primary hyperparathyroidism before surgery and in postsurgical recurrences.

Psychobiologic correlates of the metabolic syndrome and associated sexual dysfunction.

OBJECTIVES: The association of low testosterone level and erectile dysfunction (ED) with metabolic syndrome (MS) is receiving increasing attention. The present study determined the psychobiologic characteristics of sexual dysfunction (SD) associated with MS (as defined by the National Cholesterol Education Program's Adult Treatment Panel III criteria) in a series of 803 consecutive male outpatients. METHODS: Several hormonal, biochemical, and instrumental (penile Doppler ultrasound [PDU]) parameters were studied, along with general psychopathology scores (Middlesex Hospital Questionnaire modified [MHQ]). The Structured Interview on Erectile Dysfunction (SIEDY) was also applied. RESULTS: Among the 236 patients (29.4%) diagnosed as having a MS, 96.5% reported ED, 39.6% hypoactive sexual desire (HSD), 22.7% premature ejaculation, and 4.8% delayed ejaculation. Patients with MS were characterised by greater subjective (as assessed by SIEDY) and objective (as assessed by PDU) ED and by greater somatised anxiety than the rest of the sample. The prevalence of overt hypogonadism (total testosterone <8 nM) was significantly higher in patients with MS. Among MS components, waist circumference and hyperglycaemia were the best predictors of hypogonadism. Hypogonadal patients with MS showed higher gonadotropin and lower free testosterone levels, suggesting a primary hypogonadism. Among patients with MS, hypogonadism was present in 11.9% and 3.8% in the rest of the sample (p<0.0001) and was associated with typical hypogonadism-related symptoms, such as hypoactive sexual desire, low frequency of sexual intercourse, and depressive symptoms. CONCLUSIONS: Our data suggest that MS is associated with a more severe ED and induces somatisation. Furthermore, MS is associated with a higher prevalence of hypogonadism in patients with SD. The presence of hypogonadism can further exacerbate the MS-associated sexual dysfunction, adding the typical hypogonadism-related symptoms (including HSD, 66.7%). Recognising MS associated with hypogonadism is important for both sexual and general health and its serious potential associated risks.