Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study

Background: The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of comorbidities, and occurrence of cardiovascular events in uniformly stratified patients with adrenal incidentalomas and cortisol autonomy (defined as non-suppressible serum cortisol on dexamethasone suppression testing). Methods: We conducted an international, retrospective, cohort study (NAPACA Outcome) at 30 centres in 16 countries. Eligible patients were aged 18 years or older with an adrenal incidentaloma (diameter ≥1 cm) detected between Jan 1, 1996, and Dec 31, 2015, and availability of a 1 mg dexamethasone suppression test result from the time of the initial diagnosis. Patients with clinically apparent hormone excess, active malignancy, or follow-up of less than 36 months were excluded. Patients were stratified according to the 0800–0900 h serum cortisol values after an overnight 1 mg dexamethasone suppression test; less than 50 nmol/L was classed as non-functioning adenoma, 50–138 nmol/L as possible autonomous cortisol secretion, and greater than 138 nmol/L as autonomous cortisol secretion. The primary endpoint was all-cause mortality. Secondary endpoints were the prevalence of cardiometabolic comorbidities, cardiovascular events, and cause-specific mortality. The primary and secondary endpoints were assessed in all study participants. Findings: Of 4374 potentially eligible patients, 3656 (2089 [57·1%] with non-functioning adenoma, 1320 [36·1%] with possible autonomous cortisol secretion, and 247 [6·8%] with autonomous cortisol secretion) were included in the study cohort for mortality analysis (2350 [64·3%] women and 1306 [35·7%] men; median age 61 years [IQR 53–68]; median follow-up 7·0 years [IQR 4·7–10·2]). During follow-up, 352 (9·6%) patients died. All-cause mortality (adjusted for age, sex, comorbidities, and previous cardiovascular events) was significantly increased in patients with possible autonomous cortisol secretion (HR 1·52, 95% CI 1·19–1·94) and autonomous cortisol secretion (1·77, 1·20–2·62) compared with patients with non-functioning adenoma. In women younger than 65 years, autonomous cortisol secretion was associated with higher all-cause mortality than non-functioning adenoma (HR 4·39, 95% CI 1·93–9·96), although this was not observed in men. Cardiometabolic comorbidities were significantly less frequent with non-functioning adenoma than with possible autonomous cortisol secretion and autonomous cortisol secretion (hypertension occurred in 1186 [58·6%] of 2024 patients with non-functioning adenoma, 944 [74·0%] of 1275 with possible autonomous cortisol secretion, and 179 [75·2%] of 238 with autonomous cortisol secretion; dyslipidaemia occurred in 724 [36·2%] of 1999 patients, 547 [43·8%] of 1250, and 123 [51·9%] of 237; and any diabetes occurred in 365 [18·2%] of 2002, 288 [23·0%] of 1250, and 62 [26·7%] of 232; all p values <0·001). Interpretation: Cortisol autonomy is associated with increased all-cause mortality, particularly in women younger than 65 years. However, until results from randomised interventional trials are available, a conservative therapeutic approach seems to be justified in most patients with adrenal incidentaloma. Funding: Deutsche Forschungsgemeinschaft, Associazione Italiana per la Ricerca sul Cancro, Università di Torino

HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier?

The acquired immunodeficiency syndrome (AIDS) is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis

The effects of instrumental action on perceptual hand maps

Perceiving the external spatial location of body parts using position sense requires that immediate proprioceptive afferent signals be integrated with information about body size and shape. Longo and Haggard (Proc Natl Acad Sci USA 107:11727–11732, 2010) developed a method to measure perceptual hand maps reflecting this metric information about body size and shape. In this paradigm, participants indicate the perceived location of landmarks on their occluded hand by pointing with a long baton held in their other hand. By comparing the relative location of judgments of different hand landmarks, perceptual hand maps can be constructed and compared to actual hand structure. The maps show large and highly stereotyped distortions. Here, I investigated the potential effect of biases related to active motor control of the hand doing the pointing in these distortions. Participants localized the fingertip and knuckle of each finger on their occluded left hand either by actively pointing with a baton held in their right hand (pointing condition) or by giving verbal commands to an experimenter on how to move the baton (verbal condition). Similar distortions were clearly apparent in both conditions, suggesting that they are not an artifact of motor control biases related to the pointing hand

A single-centre experience of the implementation of adrenal vein sampling procedure: the impact on the diagnostic work-up in primary aldosteronism

BACKGROUND: Primary aldosteronism is one of the most common causes of secondary hypertension. Adrenal vein sampling (AVS) remains a "gold standard" procedure in differentiation between unilateral (adenoma) and bilateral (hyperplasia) disease. AIM: The aim of this study was to present our single-centre experience in establishing and implementating the AVS procedure. METHODS: All patients had primary aldosteronism confirmed in a salt-infusion test. AVS was performed sequentially during a continuous intravenous infusion of cosyntropin and was preceded by multislice contrast-enhanced computed tomography (CT) examination of adrenal glands performed a few weeks before AVS in the majority of patients. AVS was regarded as successful if the ratio of each adrenal vein cortisol to inferior vena cava cortisol levels (selectivity index [SI]) was higher than 3.0. In the case of failure, a second attempt was considered in a few weeks. Patients were divided into four groups according to the order of the procedure by quartiles. RESULTS: Between 31 May, 2012 and 5 May, 2016, AVS was performed in 124 patients (69% males, aged 55.3 +/- 10.3 years) and was successful in 120 (96.8%) patients. All failed cases were due to the failure of cannulation of the right adrenal vein. The first-attempt success rate was 94.3% (117 of 124 patients) and increased from 83.9% in the first 31 patients to 100% in the last 31 patients. Similarly, the overall success rate increased from 93.5% to 100%. The right SI was significantly higher than the left one (26.4 vs. 11.0, p < 0.0001). Both indices did not differ across quartiles of patients. No complications occurred during the procedure. CONCLUSIONS: The AVS procedure, preceded by adrenal CT, may be implemented into daily diagnostic practice safely with an excellent success rate