Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are non-functioning adrenocortical adenomas, but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas. We followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system and updated systematic reviews on four predefined clinical questions crucial for the management of incidentalomas: A) How to assess risk of malignancy? ; B) How to define and manage mild autonomous cortisol secretion? ; C) Who should have surgical treatment and how should it be performed? ; D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected Recommendations: 1) Each adrenal mass requires dedicated adrenal imaging. Recent advances now allow discrimination between risk categories: Homogeneous lesions with HU ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size. All other patients should be discussed in a multidisciplinary expert meeting, but only lesions >4 cm that are inhomogeneous or have HU >20 have sufficiently high risk of malignancy that surgery will be the usual management of choice. 2) Every patient needs a thorough clinical and endocrine work-up to exclude hormone excess including the measurement of plasma or urinary metanephrines and a 1-mg overnight dexamethasone suppression test (applying a cutoff value of serum cortisol ≤50 nmol/l (≤1.8 µg/dl)). Recent studies have provided evidence that most patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post dexamethasone >50 nmol/l (>1.8 µg/dl) harbor increased risk of morbidity and mortality. For this condition, we propose the term ‘mild autonomous cortisol secretion’ (MACS). 3) All patients with MACS should be screened for potential cortisol-related comorbidities that are potentially attributably to cortisol (e.g. hypertension and type 2 diabetes mellitus), to ensure these are appropriately treated. 4) In patients with MACS who also have relevant comorbidities surgical treatment should be considered in an individualized approach. 5) The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. 6) Surgery is not usually indicated in patients with an asymptomatic, non-functioning unilateral adrenal mass and obvious benign features on imaging studies. Furthermore, we offer recommendations for the follow-up of non-operated patients, management of patients with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses, and for young and elderly patients with adrenal incidentalomas. Finally, we suggest ten important research questions for the future.

Context Joint complaints in patients with acromegaly are common, although the long-term disease course is largely unknown. Objective To evaluate the long-term course of acromegalic arthropathy. Design and setting Prospective longitudinal cohort study of controlled acromegaly patients followed at a tertial referral center, with three study visits: baseline, and after a median of 2.6 and 9.1 years. Patients Thirty-one patients with biochemically controlled acromegaly for ≥2 years (49% female, median age 60 years) at baseline. Main outcome measures Radiographic arthropathy of the knee, hip, hand, and cervical and lumbar spine were evaluated using Kellgren and Lawrence (KL) scores, developed for assessment of primary osteoarthritis (OA). Radiographic progression was defined as a KL increase above the smallest detectable change (SDC). Joint symptoms were assessed using self-reported questionnaires. Progression was defined on existing clinically important cut-off values. Risk factors for progression were investigated using a multivariate model. Results All patients had definite radiographic OA at ≥1 joint at baseline. Radiographic progression was observed in 29%, 48%, 84%, and 94% of patients in the knees, hips, hands and axial joints, respectively. Deterioration in hand-related pain and function was observed in 10 (32.3%) and 11 patients (35.5%), respectively. Solely baseline KL scores of the hip were associated with hip OA progression (OR 1.88 (95% CI 1.09-3.16)). Conclusions Acromegalic arthropathy showed significant radiographic progression over 9.1 years of follow-up in patients in remission, whereas clinical progression was observed less frequently. Future studies should focus on adequate prevention and treatment strategies of acromegalic arthropathy.

Central venous catheters (CVCs) in neonates are associated with a risk of central line-associated bloodstream infections (CLABSI). Most reports on the incidence of CLABSI in neonates focus on umbilical venous catheters (UVCs) and peripherally inserted central catheters (PICCs). We evaluated the incidence and risk factors for CLABSI in a cohort of neonates with femoral venous catheters (FVCs), UVCs, and PICCs, with a gestational age ≥34 weeks born between January 1, 2006 and June 30, 2013. We included 2,986 neonates with a total of 656 catheters. The CLABSI incidence rate varied from 12.3 per 1,000 catheter-days in FVCs to 10.6 per 1,000 catheter-days in UVCs and 5.3 per 1,000 catheter-days in PICCs. In a Kaplan–Meier survival analysis, we did not find a difference in CLABSI risk between the catheter types (p = 0.29). The following factors were independently associated with an increased risk of CLABSI: parenteral nutrition [hazard ratio (HR) 2.60, 95% confidence interval (CI) 1.25–5.41], male gender (HR 2.63, 95% CI 1.17–5.90), and higher birth weight (HR 1.04, 95% CI 1.002–1.09), whereas antibiotic treatment at birth (HR 0.25, 95% CI 0.12–0.52) was associated with a decreased risk. Conclusion: In our cohort, we did not find a difference between the CLABSI incidence in FVCs, PICCs, and UVCs. Occurrence of CLABSI is associated with parenteral nutrition, male gender, and higher birth weight. Antibiotic treatment at birth was associated with a decreased risk of CLABSI.

Background: Small for gestational age (SGA) neonates are at increased risk of mortality and morbidity, including necrotizing enterocolitis (NEC), but detailed information on the incidence and risk factors of NEC in SGA neonates is lacking. Objective: This study aims to estimate the incidence of NEC in a large cohort of SGA neonates, compared to appropriate for gestational age (AGA) neonates. Methods: We included all SGA neonates without congenital malformations admitted to our neonatal nursery between 2004 and 2013. Neonates in the SGA group were matched for gestational age with a control group of AGA neonates admitted during the same study period. We recorded the occurrence of NEC and studied the association with SGA and other potential risk factors. Results: A total of 475 SGA neonates were matched for gestational age at birth to 475 control AGA neonates. The incidence of NEC in the SGA group was 3.2% (15/475) versus 1.3% (6/475) in the AGA group (OR 2.55, 95% CI 0.98-6.63, p = 0.047). The incidence of NEC in the subgroups with mild, moderate and severe SGA was 2.3% (5/215), 4.7% (5/1.07) and 3.2% (5/153), respectively (p = 0.531). Conclusions: The risk of development of NEC is more than twofold increased in SGA neonates compared to AGA neonates. We found no association between the severity of SGA and NEC.

Objective Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) excess results in both reversible and irreversible musculoskeletal damage, including increased vertebral fracture (VF) risk. The prevalence of VFs is approximately 60% in controlled acromegaly patients, and these VFs can progress in time. We aimed to identify the course of VFs in a cohort of acromegaly patients in long-term remission and their associated risk factors during prolonged follow-up. Methods Thirty-one patients with acromegaly (49% female, median age 60 years (IQR 53–66)), who were in remission for 2 years, were included in this longitudinal, prospective, follow-up study. Spine radiographs of vertebrae Th4 to L4 were assessed for VFs using the Genant score, at baseline, after 2.6 years and 9.1 years. Progression was defined as either a new fracture, or a 1-point increase in Genant score. Results The prevalence of VF at baseline was 87% (27/31 patients). Progression of VFs was observed in eleven patients (35.5%) during the 9.1-year follow-up period, with a total incidence rate of 65.5 per 1,000 PY (Males 59.8 per 1,000 PY vs. females 71.6 per 1,000 PY). Patients treated with surgery or radiotherapy had a higher risk of VF progression in this cohort (P=0.030). Conclusions In this cohort of long-term well-controlled acromegalic patients, the prevalence and progression of VFs was high, showing that the deleterious effects of GH and IGF-1 excess on bone persist despite achievement of longstanding remission.