Management of a giant adrenal schwannoma.

In this case report, we present a man in his 60s who presented with an incidentally discovered right adrenal mass, which turned out to be an adrenal schwannoma. This is a very rare tumour that originates from Schwann cells and involves the peripheral nerves. The tumour was removed by open adrenalectomy, and this 15-cm adrenal schwannoma is one of the largest reported in the literature, with none >16 cm having ever been reported. This case highlights the importance of keeping an open mind about the cause of an incidentally discovered adrenal mass, which is an increasingly common way for adrenal tumours to present given the increased access to cross-sectional imaging. As well as presenting the case and the pathological basis behind adrenal schwannomas, we include a review of the literature and a general discussion about incidentally discovered adrenal masses.

Outcomes of Patients with Nelson's Syndrome after Primary Treatment: A Multicenter Study from 13 UK Pituitary Centers.

CONTEXT: Long-term outcomes of patients with Nelson's syndrome (NS) have been poorly explored, especially in the modern era. OBJECTIVE: To elucidate tumor control rates, effectiveness of various treatments, and markers of prognostic relevance in patients with NS. PATIENTS, DESIGN, AND SETTING: Retrospective cohort study of 68 patients from 13 UK pituitary centers with median imaging follow-up of 13 years (range 1-45) since NS diagnosis. RESULTS: Management of Cushing's disease (CD) prior to NS diagnosis included surgery+adrenalectomy (n = 30; eight patients had 2 and one had 3 pituitary operations), surgery+radiotherapy+adrenalectomy (n = 17; two received >1 courses of irradiation, two had ≥2 pituitary surgeries), radiotherapy+adrenalectomy (n = 2), and adrenalectomy (n = 19). Primary management of NS mainly included surgery, radiotherapy, surgery+radiotherapy, and observation; 10-year tumor progression-free survival was 62% (surgery 80%, radiotherapy 52%, surgery+radiotherapy 81%, observation 51%). Sex, age at CD or NS diagnosis, size of adenoma (micro-/macroadenoma) at CD diagnosis, presence of pituitary tumor on imaging prior adrenalectomy, and mode of NS primary management were not predictors of tumor progression. Mode of management of CD before NS diagnosis was a significant factor predicting progression, with the group treated by surgery+radiotherapy+adrenalectomy for their CD showing the highest risk (hazard ratio 4.6; 95% confidence interval, 1.6-13.5). During follow-up, 3% of patients had malignant transformation with spinal metastases and 4% died of aggressively enlarging tumor. CONCLUSIONS: At 10 years follow-up, 38% of the patients diagnosed with NS showed progression of their corticotroph tumor. Complexity of treatments for the CD prior to NS diagnosis, possibly reflecting corticotroph adenoma aggressiveness, predicts long-term tumor prognosis.

Intensive versus standard multifactorial cardiovascular risk factor control in screen-detected type 2 diabetes: 5-year and longer-term modelled outcomes of the ADDITION-Leicester study.

AIMS: Diabetes treatment algorithms recommend intensive intervention in those with a shorter duration of disease. Screening provides opportunities for earlier multifactorial cardiovascular risk factor control. Using data from the ADDITION-Leicester study (NCT00318032), we estimated the effects of this approach on modelled risk of diabetes-related complications in screen-detected patients. METHODS: A total of 345 (41% South Asian) people with screen-detected type 2 diabetes were cluster randomised to receive 5 years of (1) intensive multifactorial risk factor intervention or (2) standard treatment according to national guidance. Estimated 10 to 20-year risk of ischaemic heart disease, stroke, congestive cardiac failure, and death was calculated using UK-PDS risk equations. RESULTS: Compared with standard care, mean treatment differences for intensive management at 5 years were -11.7(95%CI: -15.0, -8.4) and -6.6(-8.8, -4.4) mmHg for systolic and diastolic blood pressure, respectively; -0.27 (-0.66, -0.26) % for HbA1c; and -0.46(-0.66; -0.26), -0.34 (-0.51; -0.18), and -0.19 (-0.28; -0.10) mmol/L for total cholesterol, LDL-cholesterol, and triglycerides, respectively. There was no significant weight gain in the intensive group despite additional medication use. Modelled risks were consistently lower for intensively managed patients. Absolute risk reduction associated with intensive treatment at 10 and 20 years were 3.5% and 6.2% for ischaemic heart disease and 6.3% and 8.8% for stroke. Risk reduction for congestive heart failure plateaued after 15 years at 5.3%. No differences were observed for blindness and all-cause death. CONCLUSION: Intensive multifactorial intervention in a multi-ethnic population with screen-detected type 2 diabetes results in sustained improvements in modelled ischaemic heart disease, stroke, and congestive cardiac failure.

Comparison of glucose-lowering agents after dual therapy failure in type 2 diabetes: A systematic review and network meta-analysis of randomized controlled trials.

AIMS: To assess the evidence supporting the choice of third-line agents in adults with inadequately controlled type 2 diabetes. MATERIALS AND METHODS: We searched randomized controlled trials (RCTs) published between January 2000 and July 2017 that reported data on cardiometabolic outcomes and hypoglycaemia for glucose-lowering agents added to metformin-based dual treatments. Data were stratified by background therapy and RCT duration, and synthesized, when possible, with network meta-analyses. RESULTS: A total of 43 RCTs (16 590 participants) were included, with metformin combined with: sulphonylureas (SUs) in 20 RCTs; thiazolidinediones (TZDs) in 10; basal or rapid-acting insulin in 6; dipeptidyl peptidase-4 (DPP-4) inhibitors in 3; glucagon-like peptide-1 receptor agonists (GLP-1RAs) in 2; and sodium-glucose co-transporter-2 (SGLT-2) inhibitors in 2. When added to metformin and SUs, after 24 to 36 weeks, rapid-acting insulin resulted in the largest reduction in glycated haemoglobin (HbA1c; 1.6% vs placebo), followed by GLP-1RAs (1.0%), basal insulin (0.8%) and SGLT-2 inhibitors (0.7%), with no difference between GLP-1RAs and SGLT-2 inhibitors; body weight increased with insulin treatment (~3 kg vs placebo), while the greatest reduction was observed for SGLT-2 inhibitors compared with all other therapies. Limited data for hypoglycaemia indicated a similar risk for SGLT-2 inhibitors and GLP-1RAs. Results for third-line agents added to metformin and TZDs were comparable, showing similar HbA1c reduction and risk of hypoglycaemia between SGLT-2 inhibitors and GLP-1RAs, and a slightly greater reduction in body weight with SGLT-2 inhibitors vs GLP-1RAs. Data for 52 to 54 weeks were more limited: added to metformin and a SU, TZDs, GLP-1RAs or SGLT-2 inhibitors reduced HbA1c to a similar extent but had different effects on body weight (7 kg and 5 kg more with TZDs vs SGLT-2 inhibitors and GLP-1RAs, respectively; 2 kg less when comparing SGLT-2 inhibitors with GLP-1RAs). Formal analyses could not be performed for any other dual therapy failure combinations because of the small number of available RCTs. CONCLUSIONS: Moderate-quality evidence supports the choice of a third-line agent only in patients on metformin combined with a SU or a TZD, with SGLT-2 inhibitors performing generally better than other drugs. In suggesting third-line agents, future guidelines should recognize the widely differing evidence on the various dual therapy failures.