The Role of Testosterone in Spermatogenesis: lessons from proteome profiling of human spermatozoa in testosterone deficiency

Testosterone is essential to maintain qualitative spermatogenesis. Nonetheless, no studies have been yet performed in humans to analyze the testosterone-mediated expression of sperm proteins and their importance in reproduction. Thus, this study aimed to identify sperm protein alterations in male hypogonadism using proteomic profiling. We have performed a comparative proteomic analysis comparing sperm from fertile controls (a pool of 5 normogonadic normozoospermic fertile men) versus sperm from patients with secondary hypogonadism (a pool of 5 oligozoospermic hypogonadic patients due to isolated LH deficiency). Sperm protein composition was analyzed, after peptide labelling with Isobaric Tags, via liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) on an LTQ Velos-Orbitrap mass spectrometer. LC-MS/MS data were analyzed using Proteome Discoverer. Criteria used to accept protein identification included a false discovery rate (FDR) of 1% and at least 1 peptide match per protein. Up to 986 proteins were identified and, of those, 43 proteins were differentially expressed: 32 proteins were under-expressed and 11 were over-expressed in the pool of hypogonadic patients compared to the controls. Bioinformatic analyses were performed using UniProt Knowledgebase, and the Gene Ontology Consortium database based on PANTHER. Notably, 13 of these 43 differentially expressed proteins have been previously reported to be related to sperm function and spermatogenesis. Western blot analyses for A-Kinase Anchoring Protein 3 (AKAP3) and the Prolactin Inducible Protein (PIP) were used to confirm the proteomics data. In summary, a high-resolution mass spectrometry-based proteomic approach was used for the first time to describe alterations of the sperm proteome in secondary male hypogonadism. Some of the differential sperm proteins described in this study, which include Prosaposin, SMOC-1, SERPINA5, SPANXB1, GSG1, ELSPBP1, fibronectin, 5-oxoprolinase, AKAP3, AKAP4, HYDIN, ROPN1B, ß-Microseminoprotein and Protein S100-A8, could represent new targets for the design of infertility treatments due to androgen deficiency

Dalla cardiochirurgia alla neurochirurgia: un caso di apoplessia ipofisaria dopo bypass aorto-coronarico con chiara evidenza RMN

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Partial response to first generation SSA guides the choice and predict the outcome of second line therapy in acromegaly

Treatment of acromegaly resistant to first generation somatostatin analogues (first gen-SSA) is often difficult. We aimed to investigate the role of partial response and resistance to first gen-SSA in the choice of second line treatments and their outcomes

L'immagine medico-nucleare recettoriale guida la terapia del residuo post-chirurgico degli adenomi ipofisari non secernenti

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Psychological complications in patients with acromegaly: relationships with sex, arthropathy, and quality of life

Current treatment of acromegaly restores a normal life expectancy in most cases. So, the study of persistent complications affecting patients' quality of life (QoL) is of paramount importance, especially motor disability and depression. In a large cohort of acromegalic patients we aimed at establishing the prevalence of depression, to look for clinical and sociodemographic factors associated with it, and to investigate the respective roles (and interactions) of depression and arthropathy in influencing QoL

Molecular and Genetic Immune Biomarkers of Primary and Immune-Therapy Induced Hypophysitis: From Laboratories to the Clinical Practice

Hypophysitis is a rare and potentially life-threatening disease, characterized by an elevated risk of complications, such as the occurrence of acute central hypoadrenalism, persistent hypopituitarism, or the extension of the inflammatory process to the neighboring neurological structures. In recent years, a large number of cases has been described. The diagnosis of hypophysitis is complex because it is based on clinical and radiological criteria. Due to this, the integration of molecular and genetic biomarkers can help physicians in the diagnosis of hypophysitis and play a role in predicting disease outcome. In this paper, we review current knowledge about molecular and genetic biomarkers of hypophysitis with the aim of suggesting a possible integration of these biomarkers in clinical practice

Clinical management of teratoma, a rare hypothalamic-pituitary neoplasia

Intracranial teratomas are rare and comprise about 0.5 % of all intracranial tumours. Actually, a total of 15 cases of sellar-suprasellar teratoma have been described in the last 24 years. Although rare, hypothalamic-pituitary teratomas should be taken into account in the differential diagnosis of hypothalamic-pituitary region tumours. The current review focuses on the clinical and therapeutic management of pituitary region teratomas. Teratomas occur more frequently in children and young adults than in the older population and in males as compared to females. Symptoms at diagnosis are usually neurological defects, diabetes insipidus and hypopituitarism. Teratoma diagnosis can be suggested though neuroimaging findings. Magnetic resonance imaging remains the preferred modality for assessment of teratoma. Neuro-radiological findings of mixed-density mass, usually with mixed cystic and solid components or inclusions of teeth, fat and calcification can be suggestive. Tumour markers as beta-HCG and alpha-FP can be useful at teratoma diagnosis for distinguishing immature teratomas, mixed GCTs and mature teratomas with immature or malignant components. Optimal treatment for mature teratoma is neurosurgical excision. Radical excision is advocated as recurrence rate for a mature teratoma is extremely low in cases of complete resection and long-term outcome is excellent. During post-treatment follow-up, in cases of healing, according to tumour marker evaluation and contrasted MRI findings, hormone replacement therapy should be considered, also for secondary hypogonadism and GH deficit, with a more intense follow-up. However, as actually few evidence are available, safety data have to be confirmed also trough a surveillance study

Reappraising the Role of Trans-Sphenoidal Surgery in Prolactin-Secreting Pituitary Tumors

Background: Prolactinomas represent a unique challenge for endocrinologists and neurosurgeons. Considering recent innovations in surgical practice, the authors aimed to investigate the best management for prolactinomas. Methods: A retrospective, cross-sectional and monocentric study was designed. Consecutive patients affected by prolactinomas were enrolled if treated with a first-line treatment with a dopamine agonist (DA) or trans-sphenoidal surgery (TSS). Patients carried giant prolactinomas, and those with a follow-up <12 months were excluded. Results: Two hundred and fifty-nine patients were enrolled. The first treatment was DA for 140 patients and TS for 119 cases. One hundred and forty-six of 249 patients (58.6%) needed a second therapy. The mean follow-up was 102.2 months (12–438 months). Surgery highly impacted on the cure rate—in particular, in females (p = 0.0021) and in microprolactinomas (p = 0.0020). Considering the multivariate analysis, the female gender and surgical treatment in the course of the clinical history were the only independent positive predictors of a cure at the end of 5 years follow-up (p = 0.0016, p = 0.0005). The evaluation of serum prolactin (24 hours after TSS) revealed that 86.4% of patients with postoperative prolactin (PRL) ≤10 ng/mL were cured at the end of the follow-up (p < 0.0001). Conclusions: According to our experience, surgery allows a high cure rate of prolactinomas, particularly in females with microadenoma, with a good safety profile. TSS for prolactinomas should be considered as a concrete option, during the multidisciplinary evaluation, in centers of reference for pituitary diseases