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Purpose The role of osteocalcin (OCN) in pubertal development, male hypogonadism, and the effect of testosterone (Te) replacement therapy (TRT) remains unclear. We aimed to investigate the total OCN (tOCN) concentrations in male patients with Klinefelter syndrome (KS), a model of adult hypergonadotropic hypogonadism. Methods This retrospective longitudinal study investigated 254 male patients with KS (47,XXY) between 2007 and 2021 at an academic referral center, categorized as (1) prepubertal, (2) pubertal, and (3) adults. All prepubertal patients were Te-naïve. Adult patients were subcategorized as (1) eugonadal, (2) hypogonadal, and (3) receiving TRT. We also analyzed 18 adult patients with available tOCN levels before and 3 months after TRT commencement. Results The tOCN levels varied throughout the lifespan according to pubertal status, were highest in eugonadal and significantly lower in TRT subjects, correlated with both LH ( p  = 0.017) and FSH levels ( p  = 0.004) in adults, and significantly declined after 3 months of TRT ( p  = 0.006) in the adult KS cohort. HPG-axis hormones levels demonstrated no correlation in prepubertal boys. Adjustment for age and body mass index confirmed previous results and revealed significant inverse correlations with total Te ( p  = 0.004), calculated free Te ( p  = 0.016), the Te/LH ( p  = 0.010), and calculated free Te/LH ratios ( p  = 0.031). Conclusion In KS, a model of male hypergonadotropic hypogonadism, tOCN levels were not associated with gonadal function during normal prepuberty and pubertal development but were associated with worse testicular function and a higher degree of HPG stimulation in adults. TRT acutely reduced tOCN levels in adults.

Purpose The immune environment represents a new, but little explored, tool for understanding neuroendocrine neoplasms (NENs) behavior. An immunosuppressed microenvironment is hypothesized to promote NENs progression. A missing profiling of circulating leukocyte and peripheral blood mononuclear cells (PBMCs) subpopulations would open new perspectives in the still limited diagnostic-therapeutic management of NENs. Methods A cross-sectional case-control pilot study was performed recruiting 30 consecutive subjects: 15 patients naïve to treatment, with histologically proven gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and 15 healthy controls, matched for age and sex. PBMCs subpopulations were studied by flow cytometry. Soluble Tie2 (sTie2), Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2) were evaluated by ELISA. Results Immune cell profiling revealed a significant lower CD3 − CD56 + natural killer (NK) cell count in NETs vs controls ( p  = 0.04). NK subset analysis showed a reduced relative count of CD56 + CD16 + NK cells ( p  =0.002) in NETs vs controls. Patients with NET showed a higher percentage of CD14 + CD16 ++ non-classical monocytes ( p  = 0.01), and a lower percentage of CD14 + CD16 + intermediate monocytes ( p  = 0.04). A decrease in percentage ( p  =  0.004 ) of CD4 + T-helper lymphocytes was found in NET patients. Evaluation of cellular and serum angiopoietin pathway mediators revealed in NET patients a higher relative count of Tie2-expressing monocytes (TEMs) ( p  < 0.001), and high levels of Ang-1 ( p  = 0.003) and Ang-2 ( p  = 0.002). Conclusions Patients with GEP-NET presented an immunosuppressed environment characterized by a low count of cytotoxic NK cells, a high count of anti-inflammatory non-classical monocytes, and a low count of T-helper lymphocytes. Higher levels of TEMs and angiopoietins suggest a crosstalk between innate immunity and angiogenic pathways in NETs.

Purpose Tall stature is defined as height greater than the threshold of more than 2 standard deviations above the average population height for age, sex, and ethnicity. Many studies have described the main aspects of this condition during puberty, but an analysis of the characteristics that the physician should consider in the differential diagnosis of gigantism—tall stature secondary to a pituitary tumour—during the transition age (15–25 years) is still lacking. Methods A comprehensive search of English-language original articles was conducted in the MEDLINE database (December 2021-March 2022). We selected all studies regarding epidemiology, genetic aspects, and the diagnosis of tall stature and gigantism during the transition age. Results Generally, referrals for tall stature are not as frequent as expected because most cases are familial and are usually unreported by parents and patients to endocrinologists. For this reason, lacking such experience of tall stature, familiarity with many rarer overgrowth syndromes is essential. In the transition age, it is important but challenging to distinguish adolescents with high constitutional stature from those with gigantism. Pituitary gigantism is a rare disease in the transition age, but its systemic complications are very relevant for future health. Endocrine evaluation is crucial for identifying conditions that require hormonal treatment so that they can be treated early to improve the quality of life and prevent comorbidities of individual patient in this age range. Conclusion The aim of our review is to provide a practical clinical approach to recognise adolescents, potentially affected by gigantism, as early as possible.

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.

TVT-O and TVT were compared in patients stratified according the severity of Stress Urinary Incontinence (SUI). Those patients with intrinsic sphincter deficiencies, overactive bladders, associated prolapses, neurovegetative disorders and recurrent SUI or under rehabilitative/medical therapies were all excluded. There were 208 women included. Operating times were longer, and postoperative pain greater for TVT ( p  < 0.001). TVT produced longer hospitalizations in severe SUI patients ( p  < 0.001). After 1 year of follow-up, incontinence was cured in all mild SUI patients with both techniques, in all severe SUI patients when treated with TVT and in 66% of them when treated with TVT-O ( p  < 0.001). Vaginal perforations occurred during the TVT-O ( p  = 0.01), bladder perforations during TVT ( p  = NS), bladder obstructions in mild SUI patients after TVT ( p  < 0.001). The severity of SUI is an important parameter that influences results after TVT-O and TVT, and could be used to guide surgeons in selecting the most effective intervention.

Background Isobaric gasless laparoscopy and minilaparotomy have been used as more recent minimally invasive approaches to myomectomy. This randomized trial aimed to compare the surgical and immediate postoperative outcomes for myomectomy performed by isobaric gasless laparoscopy with those for minilaparotomy. Methods A total of 100 patients with symptomatic uterine myomas requiring myomectomy were randomly allocated to the gasless laparoscopy group or the minilaparotomy group. The randomization procedure was based on a computer-generated list. The primary outcome was a comparison of the discharge times between the two procedures. A power calculation verified that more than 26 patients for each group was necessary to detect a difference of more than 24 h in discharge time with an alpha error level of 5% and a beta error of 80%. Continuous outcome variables were analyzed using the Student’s t -test. Discrete variables were analyzed with the chi-square test or Fisher’s exact test. A p value less than 0.05 was considered statistically significant. Results The mean discharge time was longer for minilaparotomy than for gasless laparoscopy (98.4 ± 1.4 vs 52.8 ± 1.6 h; p  < 0.001). Gasless laparoscopy resulted in shorter times for canalization (21.6 ± 1.1 vs 32 ± 1.3 h; p  < 0.05) and surgery (79.5 ± 25.1 vs 103.5 ± 24.9 min; p  < 0.001). The intraoperative blood loss was less with gasless laparoscopy (154.2 ± 1.2 vs 188.6 ± 1.3 ml; p  < 0.001). No intraoperative complications occurred, and no case was returned to the theater in either group. No conversion to standard laparotomy was necessary. Conclusions Isobaric gasless laparoscopy and minilaparotomy can be suitable options for uterine myomectomy. Several surgical and immediate postoperative outcomes were significantly better in the gasless laparoscopy group than in the minilaparotomy group. However, further controlled prospective studies are required to confirm the results.

Signal transduction through the IGF axis is implicated in proliferation, differentiation and survival during development and adult life. The IGF axis includes the IGF binding proteins (IGFBPs) that bind IGFs with high affinity and modulate their activity. In neuroblastoma (NB), a malignant childhood tumor, we found that IGFBP-5 is frequently expressed. Since NB is an IGF2-sensitive tumor, we investigated the relevance and the function of endogenous IGFBP-5 in LAN-5 and in SY5Y(N) cell lines transfected with micro and small interfering RNAs directed to IGFBP-5 mRNA. Cells in which IGFBP-5 expression was suppressed were growth-inhibited and more prone to apoptosis than the parental cell line and controls. Apoptosis was further enhanced by X-ray irradiation. The ability of these cells to undergo neuronal differentiation was impaired after IGFBP-5 inhibition but the effect was reversed by exposure to recombinant IGFBP-5. Together, these data demonstrate the importance of IGFBP-5 for NB cell functions and suggest that IGFBP-5 might serve as a novel therapeutic target in NB.

We present 1-year results obtained with Reemex for the cure of intrinsic sphincter deficiencies (ISDs). We recruited all patients with primary cases of stress urinary incontinence (SUI) due to an ISD (Valsalva leak-point pressure less than 60 cm or maximal urethral closure pressure less than 20 cm) who did not receive previous surgery. Thirty-eight patients were operated on. Postoperative pain was 3 (range, 1–5, visual analogue scale) at 24 h from surgery. Immediate regulation (the day after surgery) was necessary in three of 38 patients (7.9%), two for obstructive voiding difficulties and one for incontinence. Late regulation was necessary in three of 38 patients (7.9%), two for obstructive voiding difficulties (after 6 months) and one for incontinence (1 year). Symptoms resolved after the sling adjustment. Our results suggest that sling adjustments resolve postoperative failures and maintain the success rate of the Reemex system even in the midterm.