Dopamine agonist resistant prolactinomas: any alternative medical treatment?

Consensus guidelines recommend dopamine agonists (DAs) as the mainstay treatment for prolactinomas. In most patients, DAs achieve tumor shrinkage and normoprolactinemia at well tolerated doses. However, primary or, less often, secondary resistance to DAs may be also encountered representing challenging clinical scenarios. This is particularly true for aggressive prolactinomas in which surgery and radiotherapy may not achieve tumor control. In these cases, alternative medical treatments have been considered but data on their efficacy should be interpreted within the constraints of publication bias and of lack of relevant clinical trials. The limited reports on somatostatin analogues have shown conflicting results, but cases with optimal outcomes have been documented. Data on estrogen modulators and metformin are scarce and their usefulness remains to be evaluated. In many aggressive lactotroph tumors, temozolomide has demonstrated optimal outcomes, whereas for other cytotoxic agents, tyrosine kinase inhibitors and for inhibitors of mammalian target of rapamycin (mTOR), higher quality evidence is needed. Finally, promising preliminary results from in vitro and animal reports need to be further assessed and, if appropriate, translated in human studies.

Impact of Bariatric Surgery on Long-term Cardiovascular Risk: Comparative Effectiveness of Different Surgical Procedures.

INTRODUCTION: Several reports highlight bariatric surgery as an efficient and long-lasting strategy for weight loss. Herein, we aimed to evaluate the impact of bariatric surgery on 10-year cardiovascular disease (CVD) risk and to compare the effectiveness of different surgical procedures, employing the Framingham Risk Score (FRS). METHODS: Retrospective longitudinal observational study of patients undergoing bariatric surgery. Data was assessed preoperatively and during a 4-year follow-up period. RESULTS: We evaluated 1449 individuals, 85.2% female, age of 42.4 ± 10.6 years, and preoperative BMI of 44.3 ± 5.8 kg/m2; 58.0% underwent Roux-en-Y gastric bypass (RYGB), 23.4% sleeve gastrectomy (SG), and 18.6% adjustable gastric band (AGB). The 10-year CVD risk decreased 43.6% in the first postoperative year. The decrease in FRS was more pronounced in the RYGB group (50.5% in the first postoperative year) (p < 0.001). Although there was a subsequent slight increase in FRS during the follow-up period, the cardiovascular benefits were maintained when compared with baseline. For all surgical procedures, CVD risk showed a quadratic trend with a J-shaped curve. A negative interaction between the RYGB group CVD risk and time was observed (ß = - 0.072 (95% CI, - 0.109; - 0.035)). In the RYGB group, FRS decreased more when compared with the SG and AGB groups and, from the second postoperative year onwards, increased more slowly, regardless of gender. The SG group showed similar trend as that of the AGB (ß = - 0.002 (95% CI, - 0.049; 0.053)). CONCLUSION: Our study showed a significant reduction of 10-year CVD risk after bariatric surgery. This decrease was more pronounced in the first postoperative year, and RYGB was the procedure with the greatest decrease of the 10-year CVD risk.

Insulin resistance and sex hormone-binding globulin are independently correlated with low free testosterone levels in obese males.

Male obesity is associated with decreased testosterone levels but the pathophysiological mechanisms behind this association are not completely understood. This study aimed to investigate the impact of hyperglycaemia/insulin resistance and sex hormone-binding globulin (SHBG) levels on testosterone levels in a population of obese men. We investigated the impact of several clinical, anthropometric and analytic measures on testosterone levels in 150 obese males. Testosterone deficiency was present in 52.0% of the enrolled patients. This percentage dropped to 17.6% when only calculated free testosterone (FT) was accounted, as SHBG levels were correlated negatively with body mass index (r = -.20; p < .05). Older age (p < .05) and higher homoeostasis model assessment of insulin resistance (HOMA-IR) (p < .01) and lower SHBG levels (p < .05) were independently correlated with lower FT. Weight and fasting plasma glucose lost their statistical significance after multivariate adjustment. Patients with type 2 diabetes mellitus and pre-diabetes had lower FT than those with normal glucose tolerance (p < .05 and p < .01 respectively). Insulin resistance, and not hyperglycaemia and weight per se, seems to be the main determinant of low testosterone levels in obese males. Low SHBG levels are correlated with low FT even after HOMA-IR adjustment. This suggests that SHBG can be associated with testosterone deficiency beyond the influence of insulin resistance unlike previously reported.