The Male Reproductive System and Endocrine Disruptors.

The male reproductive system is exposed to a great number of chemical substances which can interfere with the normal hormonal milieu and reproductive function; these are called endocrine disruptors (EDs). Despite a growing number of studies evaluating the negative effects of EDs, their production is continuously growing although some of them have been prohibited. The prevalence of poor semen quality, hypospadias, cryptorchidism, and testicular cancer has increased in the last decades, and recently, it has been postulated that these could all be part of a unique syndrome called testicular dysgenesis syndrome. This syndrome could be related to exposure to a number of EDs which cause imbalances in the hormonal milieu and oestrogenic over-exposure during the foetal stage. The same EDs can also impair spermatogenesis in offspring and have epigenetic effects. Although studies on animal and in vitro models have raised concerns, data are conflicting. However, these studies must be considered as the basis for future research to promote male reproductive health.

Impact of bariatric surgery-induced weight loss on circulating PCSK9 levels in obese patients.

BACKGROUND AND AIMS: To investigate the effect of obesity and bariatric-induced weight loss on circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) in severely obese patients. METHODS AND RESULTS: In this non-randomized interventional study, we enrolled 36 severely obese patients (BMI 43.7 ± 5.6 kg/m2), of which 20 underwent bariatric surgery, and 12 nonobese healthy controls. An oral glucose tolerance test (75-g OGTT) was performed in 31 of these obese patients at baseline (T0) and in 14 patients at 6 months after bariatric surgery (T6) to assess plasma glucose, insulin and PCSK9 levels. Plasma PCSK9 levels were also measured in 18 of these obese patients at T0 during a 2-h hyperinsulinemic-euglycemic clamp (HEC). At T0, PCSK9 levels were higher in obese patients than in controls (274.6 ± 76.7 ng/mL vs. 201.4 ± 53.3 ng/mL) and dropped after bariatric surgery (T6; 205.5 ± 51.7 ng/mL) along with BMI (from 44.1 ± 5.9 kg/m2 to 33.1 ± 5.6 kg/m2). At T6, there was also a decrease in plasma glucose (T0 vs. T6: 6.0 ± 1.8 vs. 5.0 ± 0.5 mmol/L) and insulin (15.7 ± 8.3 vs. 5.4 ± 2.1 mU/L) levels. At T0, plasma PCSK9 levels decreased during OGTT in obese patients, reaching a nadir of 262.0 ± 61.4 ng/mL at 120 min with a hyperinsulinemic peak of 75.1 ± 40.0 mU/L, at 60 min. Similarly, at T0 insulin infusion during 2-h HEC acutely reduced plasma PCSK9 levels in obese patients. The aforementioned OGTT-induced changes in plasma PCSK9 levels were not observed neither in nonobese healthy controls nor in obese patients after bariatric-surgery weight loss. CONCLUSIONS: These results suggest a pivotal role of adipose tissue and insulin resistance on PCSK9 homeostasis in severely obese patients.

A Case Report of Insulinoma Relapse on Background Nesidioblastosis: A Rare Cause of Adult Hypoglycemia.

Context: Nesidioblastosis is a rare cause of adult hypoglycemia. Current medical therapy can mitigate disease symptoms. However, side effects and limited efficacy may prevent long-term disease management. Case Description: A 63-year-old white woman presented at our institution on April 2017 with a history of distal spleno-pancreatectomy for well-differentiated insulinoma in 2013. Hypoglycemic events did not resolve after surgery, and residual nesidioblastosis near the pancreatic resection margins was identified. Hypoglycemic episodes increased in frequency and severity despite high-dose diazoxide (DZX) therapy. On April 2016, octreotide was introduced but soon discontinued for inefficacy. When the patient arrived at our attention, add-on pasireotide was started and glucose levels monitored by subcutaneous sensor. Compared with DZX, 225 mg/d alone, sensor glucose during pasireotide + DZX 75 mg/d showed occurrence of severe hypoglycemia. Pasireotide was discontinued, and the instrumental workup (68Ga-DOTATOC CT/positron emission tomography, 99mTc-nanocolloid scintigraphy and echo-endoscopy + fine-needle aspiration biopsy) identified an insulinoma relapse. Subtotal pancreatectomy was performed without further recurrence of hypoglycemia over 9 months of follow-up. Conclusions: Although insulinoma relapses on background nesidioblastosis rarely occur, they should be considered as an alternate diagnosis when medical therapy fails to prevent hypoglycemia. Further studies are warranted to test whether the immunophenotypic signature of nesidioblastosis/insulinoma may provide insights for a tailored use of pasireotide.