Corticotroph cell hyperplasia as a rare cause of ACTH-dependent Cushing syndrome.

OBJECTIVE: Our aim was to characterise a cohort of patients with Cushing's disease (CD) who did not present pituitary adenoma in magnetic resonance imaging (MRI), needing a catheterisation of the inferior petrosal sinus (CIPS), and to study the pathological findings of the pituitary gland in these subjects after transsphenoidal surgery in order to establish the aetiology of CD. Furthermore, we evaluated possible differences in the features of the diagnosis between hyperplasia and adenoma. SUBJECTS AND METHODS: We included 16 subjects. 17 CIPS were done. Hormonal parameters were measured using standard methods. A microscopic histochemical study following standard procedures and immunohistochemical analysis was performed. The diagnostic criteria for adenoma and hyperplasia were based on the WHO classification. RESULTS: One patient was excluded for presenting an ACTH-producing bronchial neuroendocrine tumour. The 15 subjects with CD have a positive CIPS test indicating hypophyseal ACTH production. After transsphenoidal surgery, 12 patients showed a microadenoma and three (20%) a corticotroph cell hyperplasia. We found four recurrences after the transsphenoidal surgery (26%), with a mean time for recurrence of 105 months. We found that recurrence was more frequent in subjects with hyperplasia, and in those subjects with lower right/left ACTH ratio. CONCLUSION: Our study, which was focused on patients with CD with no pituitary adenoma detected by MRI and a positive CRH test after CIPS, has found that 20% showed corticotroph cell hyperplasia as the cause of CD. Right/left ACTH ratio after CIPS was useful to differentiate adenoma from hyperplasia. This finding may have important prognostic and treatment implications. More studies are necessary to confirm our result.

Anthropometric parameters and permanent remission of comorbidities 10 years after open gastric bypass in a cohort with high prevalence of super-obesity.

BACKGROUND AND AIM: Roux-en-Y gastric bypass (RYGB) is an effective treatment for weight loss in patients with morbid obesity. However, few studies have assessed its long-term efficacy in super-obese patients. The study objective was to analyse the long-term effectiveness of RYGB and its effect on improvement of comorbidities after 10 years of follow-up, and to compare the results depending on baseline BMI (<50kg/m2 vs ≥50kg/m2). PATIENTS AND METHODS: A retrospective study was conducted in 63 patients referred for RYGB with a 10-year or longer follow-up period. Mean BMI before surgery was 55kg/m2. RESULTS: Mean BMI decreased to 38.1kg/m2 at 10 years of follow-up. The success rates according to Reinhold criteria modified by Christou and to Biron's criteria were 30.2% and 54% respectively. The corresponding rates in super-obese patients were 21.4% and 57.1%. Significant, stable improvement was seen in diabetes, dyslipidemia, hypertension, and sleep apnea. CONCLUSIONS: Sustained weight loss was achieved after gastric bypass, with a mean excess weight loss of 50.6% after 10 years despite the high prevalence of super-obesity. Comorbidity improvement was maintained.

Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages.

The quantity and activation state of adipose tissue macrophages (ATMs) impact the development of obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding of their effects on ATMs is limited. Here, we have shown that human and mouse ATMs express NPFFR2, a receptor for the appetite-reducing neuropeptide FF (NPFF), and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine. Plasma levels of NPFF decreased in obese patients and high-fat diet-fed mice and increased following caloric restriction. NPFF promoted M2 activation and increased the proliferation of murine and human ATMs. Both M2 activation and increased ATM proliferation were abolished in NPFFR2-deficient ATMs. Mechanistically, the effects of NPFF involved the suppression of E3 ubiquitin ligase RNF128 expression, resulting in enhanced stability of phosphorylated STAT6 and increased transcription of the M2 macrophage-associated genes IL-4 receptor α (Il4ra), arginase 1 (Arg1), IL-10 (Il10), and alkylglycerol monooxygenase (Agmo). NPFF induced ATM proliferation concomitantly with the increase in N-Myc downstream-regulated gene 2 (Ndrg2) expression and suppressed the transcription of Ifi200 cell-cycle inhibitor family members and MAF bZIP transcription factor B (Mafb), a negative regulator of macrophage proliferation. NPFF thus plays an important role in supporting healthy adipose tissue via the maintenance of metabolically beneficial ATMs.

Increased thioredoxin levels are related to insulin resistance in familial combined hyperlipidaemia.

BACKGROUND: Thioredoxins (TRX) are major cellular protein disulphide reductases that are critical for redox regulation. Oxidative stress and inflammation play promoting roles in the genesis and progression of atherosclerosis, but until now scarce data are available considering the influence of TRX activity in familial combined hyperlipidaemia (FCH). Since FCH is associated with high risk of cardiovascular disease, the objective of the present study was to assess oxidative stress status in FCH patients, and evaluate the influence of insulin resistance (IR). MATERIALS AND METHODS: A cohort of 35 control subjects and 35 non-related FCH patients were included, all of them nondiabetic, normotensive and nonsmokers. We measured lipid profile, glucose and insulin levels in plasma, and markers of oxidative stress and inflammation such as oxidized glutathione (GSSG), reduced glutathione (GSH) and TRX. RESULTS: Familial combined hyperlipidaemia subjects showed significantly higher levels of GSSG, GSSG/GSH ratio and TRX than controls. In addition, FCH individuals with IR showed the worst profile of oxidative stress status compared to controls and FCH patients without IR (P < 0·01). TRX levels correlated with higher insulin resistance. CONCLUSION: Familial combined hyperlipidaemia patients showed increased TRX levels. TRX was positively correlated with IR. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients.