Purpose: Since the term orthorexia nervosa (ON) was coined from the Greek (ὀρθός, right and ὄρεξις, appetite) in 1997 to describe an obsession with “correct” eating, it has been used worldwide without a consistent definition. Although multiple authors have proposed diagnostic criteria, and many theoretical papers have been published, no consensus definition of ON exists, empirical primary evidence is limited, and ON is not a standardized diagnosis. These gaps prevent research to identify risk and protective factors, pathophysiology, functional consequences, and evidence-based therapeutic treatments. The aims of the current study are to categorize the common observations and presentations of ON pathology among experts in the eating disorder field, propose tentative diagnostic criteria, and consider which DSM chapter and category would be most appropriate for ON should it be included. Methods: 47 eating disorder researchers and multidisciplinary treatment specialists from 14 different countries across four continents completed a three-phase modified Delphi process, with 75% agreement determined as the threshold for a statement to be included in the final consensus document. In phase I, participants were asked via online survey to agree or disagree with 67 statements about ON in four categories: A–Definition, Clinical Aspects, Duration; B–Consequences; C–Onset; D–Exclusion Criteria, and comment on their rationale. Responses were used to modify the statements which were then provided to the same participants for phase II, a second round of feedback, again in online survey form. Responses to phase II were used to modify and improve the statements for phase III, in which statements that met the predetermined 75% of agreement threshold were provided for review and commentary by all participants. Results: 27 statements met or exceeded the consensus threshold and were compiled into proposed diagnostic criteria for ON. Conclusions: This is the first time a standardized definition of ON has been developed from a worldwide, multidisciplinary cohort of experts. It represents a summary of observations, clinical expertise, and research findings from a wide base of knowledge. It may be used as a base for diagnosis, treatment protocols, and further research to answer the open questions that remain, particularly the functional consequences of ON and how it might be prevented or identified and intervened upon in its early stages. Although the participants encompass many countries and disciplines, further research will be needed to determine if these diagnostic criteria are applicable to the experience of ON in geographic areas not represented in the current expert panel. Level of evidence: Level V: opinions of expert committees

Glucocorticoids (GCs) target several components of the integrated system that preserves vascular integrity and free blood flow. Cohort studies on Cushing's syndrome (CS) have revealed increased thromboembolism, but the pathogenesis remains unclear. Lessons from epidemiological data and post-treatment normalisation time suggest a bimodal action with a rapid and reversible effect on coagulation factors and an indirect sustained effect on the vessel wall. The redundancy of the steps that are potentially involved requires a systematic comparison of data from patients with endogenous or exogenous hypercortisolism in the context of either inflammatory or non-inflammatory disorders. A predominant alteration in the intrinsic pathway that includes a remarkable rise in factor VIII and von Willebrand factor (vWF) levels and a reduction in activated partial thromboplastin time appears in the majority of studies on endogenous CS. There may also be a rise in platelets, thromboxane B2, thrombin–antithrombin complexes and fibrinogen (FBG) levels and, above all, impaired fibrinolytic capacity. The increased activation of coagulation inhibitors seems to be compensatory in order to counteract disseminated coagulation, but there remains a net change towards an increased risk of venous thromboembolism (VTE). Conversely, GC administered in the presence of inflammation lowers vWF and FBG, but fibrinolytic activity is also reduced. As a result, the overall risk of VTE is increased in long-term users. Finally, no studies have assessed haemostatic abnormalities in patients with Addison's disease, although these may present as a consequence of bilateral adrenal haemorrhage, especially in the presence of antiphospholipid antibodies or anticoagulant treatments. The present review aimed to provide a comprehensive overview of the complex alterations produced by GCs in order to develop better screening and prevention strategies against bleeding and thrombosis.

Background: Low-grade incomplete post-dexamethasone cortisol suppression in patients with adrenal incidentalomas – recently defined as possible autonomous cortisol secretion (pACS) – has been associated with increased cardiovascular events and mortality. However, prospective studies documenting cardiac abnormalities in these patients are lacking. Subjects and methods: Between July 2016 and September 2017, 71 consecutive patients with adrenal lesions were prospectively screened for hypercortisolism by dexamethasone suppression test (NCT 02611258). Complete anthropometric, metabolic and hormonal parameters were recorded along with full cardiac ultrasound assessment and noninvasive measurement of arterial stiffness. All patients underwent chemical-shift magnetic resonance imaging to characterize the lesions. Cardiovascular outcomes were recorded in blind. Results: According to post-dexamethasone suppression cortisol values (post-DST), 34 patients had pACS and 37 non-functioning adenomas (NFA). The two groups were similar in sex, BMI, age distribution, cardiovascular risk factors and comorbidities. Left ventricular mass index (LVMI^BSA) was increased in pACS compared to NFA (P = 0.006) and mildly correlated to the post-DST cortisol level (rho = 0.347; P = 0.004). The post-DST cortisol levels explained up to 13.7% of LVMI^BSA variance (P = 0.002). Compared to NFA, patients with pACS had a higher prevalence of diastolic dysfunction (35.1% vs 82.6%; P = 0.001) and worse arterial stiffness assessed by pulse wave velocity (P = 0.033). Conclusions: In apparently asymptomatic patients, mild autonomous cortisol secretion can sustain early cardiac and vascular remodeling, independently of other risk factors. The morphological and functional cardiovascular changes observed in pACS underline the need for further studies to correctly define the long-term management of this relatively common condition.

The circadian rhythm derives from the integration of many signals that shape the expression of clock-related genes in a 24-h cycle. Biological tasks, including cell proliferation, differentiation, energy storage, and immune regulation, are preferentially confined to specific periods. A gating system, supervised by the central and peripheral clocks, coordinates the endogenous and exogenous signals and prepares for transition to activities confined to periods of light or darkness. The fluctuations of cortisol and its receptor are crucial in modulating these signals. Glucocorticoids and the autonomous nervous system act as a bridge between the suprachiasmatic master clock and almost all peripheral clocks. Additional peripheral synchronizing mechanisms including metabolic fluxes and cytokines stabilize the network. The pacemaker is amplified by peaks and troughs in cortisol and their response to food, activity, and inflammation. However, when the glucocorticoid exposure pattern becomes chronically flattened at high- (as in Cushing’s syndrome) or low (as in adrenal insufficiency) levels, the system fails. While endocrinologists are well aware of cortisol rhythm, too little attention has been given to interventions aimed at restoring physiological cortisol fluctuations in adrenal disorders. However, acting on glucocorticoid levels may not be the only way to restore clock-related activities. First, a counterregulatory mechanism on the glucocorticoid receptor itself controls signal transduction, and second, melatonin and/or metabolically active drugs and nutrients could also be used to modulate the clock. All these aspects are described herein, providing some insights into the emerging role of chronopharmacology, focusing on glucocorticoid excess and deficiency disorders.