Predisposition to eating disorders in adults with type 1 diabetes: Comparison between multiple daily injections and continuous subcutaneous insulin infusion.

AIM: To evaluate predisposition to eating disorders (ED) or body dissatisfaction in adults with type 1 diabetes mellitus (T1DM); to further investigate any differences in ED predisposition between subjects with T1DM on multiple daily injections (MDI) or insulin pumps (CSII) and in respect to control healthy subjects. METHODS: We conducted a monocentric, cross-sectional, observational study. We enrolled subjects with T1DM, aged ≥ 18 years, and healthy subjects (HS) as control group. All participants completed two questionnaires to detect possible predisposition to ED: 34-items Body Shape Questionnaire (BSQ) and Eating Disorder Inventory-3 (EDI-3). HS only filled BSQ. For subjects with T1DM data about glycated hemoglobin and duration of disease were also collected. RESULTS: 162 subjects with T1DM (age 41 ± 12 years, 77 [47%] males) and 50 HS (age 38 ± 13 years, 18 (36%) males) were enrolled. 87 subjects with T1DM (54%) were on MDI and 75 (46%) were on CSII. No significant difference in the distribution of BSQ scores between subjects with T1DM and HS was observed (p = 0.551), although 16% of subjects with T1DM scored BSQ class 1 points while 8% of HS scored a BSQ class 1 points. No significant difference in BSQ scores was observed between subjects with T1DM on MDI or CSII. Between these two groups, no differences in EDI-3 scores were observed except for perfectionism score: subjects on MDI present more frequently a predisposition for perfectionism (p < 0.05) and, at a trend level, for bulimia. CONCLUSION: A non -significant higher percentage of BSQ class 1 was detected in subjects T1DM compared to healthy controls. Among subjects with T1DM, no differences between MDI and CSII were observed in ED predisposition. A more perfectionist personality has been detected among subjects on MDI.

Defense Mechanisms and Parenting Styles in Patients With Anorexia and Bulimia.

ABSTRACT: Dysfunctional parenting styles are risk factors for eating disorders (EDs). In this observational study, we examined 57 women with ED, a psychiatric control group (n = 26), and healthy participants (n = 60). Several instruments were administered: Defense Style Questionnaire (DSQ-40) to examine the type of defense mechanism used, Parental Bonding Instrument (PBI) to investigate the perception of the relationship with parents, Eating Disorder Examination Questionnaire and Eating Disorder Inventory-3 to assess the severity of the ED, and Body Shape Questionnaire to investigate the perception of their body shape. In patients with anorexia and bulimia, neurotic factor (p = 0.007) and immature factor (p = 0.002) are associated with perception of relationship with their own parents. In the PBI, maternal care was associated with higher scores in the DSQ-40 in the immature factor (p = 0.012), whereas paternal overprotection was associated with lower scores in the DSQ-40 in the mature factor (p = 0.016). Patients with anorexia and bulimia overutilize more neurotic and primitive defense mechanisms compared with nonclinical subjects, and this use is associated with greater severity of eating symptomatology. This can be related to diversified ego forces, can inform about the nature and severity of disease, and can characterize prognostic and psychotherapeutic value.

ENSAT registry-based randomized clinical trials for adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.

Expression of SOAT1 in Adrenocortical Carcinoma and Response to Mitotane Monotherapy: An ENSAT Multicenter Study.

CONTEXT: Objective response rate to mitotane in advanced adrenocortical carcinoma (ACC) is approximately 20%, and adverse drug effects are frequent. To date, there is no marker established that predicts treatment response. Mitotane has been shown to inhibit sterol-O-acyl transferase 1 (SOAT1), which leads to endoplasmic reticulum stress and cell death in ACC cells. OBJECTIVE: To investigate SOAT1 protein expression as a marker of treatment response to mitotane. PATIENTS: A total of 231 ACC patients treated with single-agent mitotane as adjuvant (n = 158) or advanced disease therapy (n = 73) from 12 ENSAT centers were included. SOAT1 protein expression was determined by immunohistochemistry on formalin-fixed paraffin-embedded specimens. SETTING: Retrospective study at 12 ACC referral centers. MAIN OUTCOME MEASURE: Recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). RESULTS: Sixty-one of 135 patients (45%) with adjuvant mitotane treatment had recurrences and 45/68 patients (66%) with mitotane treatment for advanced disease had progressive disease. After multivariate adjustment for sex, age, hormone secretion, tumor stage, and Ki67 index, RFS (hazard ratio [HR] = 1.07; 95% confidence interval [CI], 0.61-1.85; P = 0.82), and DSS (HR = 1.30; 95% CI, 0.58-2.93; P = 0.53) in adjuvantly treated ACC patients did not differ significantly between tumors with high and low SOAT1 expression. Similarly, in the advanced stage setting, PFS (HR = 1.34; 95% CI, 0.63-2.84; P = 0.45) and DSS (HR = 0.72; 95% CI, 0.31-1.70; P = 0.45) were comparable and response rates not significantly different. CONCLUSIONS: SOAT1 expression was not correlated with clinical endpoints RFS, PFS, and DSS in ACC patients with mitotane monotherapy. Other factors appear to be relevant for mitotane treatment response and ACC patient survival.

Mitotane Concentrations Influence Outcome in Patients with Advanced Adrenocortical Carcinoma.

Mitotane is the main option of treatment for advanced adrenocortical carcinoma (ACC). However, limited evidence is available regarding the impact of plasma mitotane levels on patient outcome. To address this question, we retrospectively analyzed patients with advanced ACC treated with mitotane for ≥3 months, with ≥3 measurements of plasma mitotane reported in the Lysosafe Online® database (HRA Pharma, France), followed at 12 tertiary centers in Italy from 2005 to 2017. We identified 80 patients, initially treated with mitotane alone (56.2%) or plus chemotherapy (43.8%). The preference toward combination therapy was given to de novo stage IV ACC and younger patients. After the first line of treatment, 25% of valid cases experienced clinical benefit (14.5% objective response, 10.5% stabilization of disease) and 75% progression, without differences between the groups of treatment. Patients with progression had a lower time in the target range (TTR) of plasma mitotane and an unfavorable outcome. Death occurred in 76.2% of cases and multivariate analysis showed that clinical benefit after first treatment and longer TTR were favorable predictors of overall survival (OS). In conclusion, the present findings support the importance of mitotane monitoring and strengthen the concept of a therapeutic window for mitotane.

Effects of Germline CYP2W1*6 and CYP2B6*6 Single Nucleotide Polymorphisms on Mitotane Treatment in Adrenocortical Carcinoma: A Multicenter ENSAT Study.

Mitotane is the only approved drug for advanced adrenocortical carcinoma (ACC) and no biomarkers are available to predict attainment of therapeutic plasma concentrations and clinical response. Aim of the study was to evaluate the suitability of cytochrome P450(CYP)2W1 and CYP2B6 single nucleotide polymorphisms (SNPs) as biomarkers. A multicenter cohort study including 182 ACC patients (F/M = 121/61) treated with mitotane monotherapy after radical resection (group A, n = 103) or in not completely resectable, recurrent or advanced disease (group B, n = 79) was performed. CYP2W1*2, CYP2W1*6, CYP2B6*6 and CYP2B6 rs4803419 were genotyped in germline DNA. Mitotane blood levels were measured regularly. Response to therapy was evaluated as time to progression (TTP) and disease control rate (DCR). Among investigated SNPs, CYP2W1*6 and CYP2B6*6 correlated with mitotane treatment only in group B. Patients with CYP2W1*6 (n = 21) achieved less frequently therapeutic mitotane levels (>14 mg/L) than those with wild type (WT) allele (76.2% vs 51.7%, p = 0.051) and experienced shorter TTP (HR = 2.10, p = 0.019) and lower DCR (chi-square = 6.948, p = 0.008). By contrast, 55% of patients with CYP2B6*6 vs. 28.2% WT (p = 0.016) achieved therapeutic range. Combined, a higher rate of patients with CYP2W1*6WT+CYP2B6*6 (60.6%) achieved mitotane therapeutic range (p = 0.034). In not completely resectable, recurrent or advanced ACC, CYP2W1*6 SNP was associated with a reduced probability to reach mitotane therapeutic range and lower response rates, whereas CYP2B6*6 correlated with higher mitotane levels. The association of these SNPs may predict individual response to mitotane.

Vitamin D testing: advantages and limits of the current assays.

Vitamin D deficiency and insufficiency has become a pandemic health problem with a consequent increase of requests for determining circulating levels of 25-hydroxyvitamin D [25(OH)D]. However, the analytical performance of these immunoassays, including radioimmunoassay and ELISA, is highly variable, and even mass spectrometric methods, which nowadays serves as the gold standard for the quantitatively determination of 25(OH)D, do not necessarily produce comparable results, creating limitations for the definition of normal vitamin D status ranges. To solve this problem, great efforts have been made to promote standardization of laboratory assays, which is important to achieve comparable results across different methods and manufacturers. In this review, we performed a systematic analysis evaluating critically the advantages and limits of the current assays available for the measure of vitamin D status, i.e., circulating 25(OH)D and its metabolites, making suggestions that could be used in the clinical practice. Moreover, we also suggest the use of alternatives to blood test, including standardized surveys that may be of value in alerting health-care professionals about the vitamin D status of their patients.

Mitotane Concentrations Influence the Risk of Recurrence in Adrenocortical Carcinoma Patients on Adjuvant Treatment.

Mitotane is used as a post-operative adjuvant treatment for patients with adrenocortical carcinoma. Monitoring of plasma mitotane concentrations is recommended, but we do not know what impact target concentrations have on patient outcome. To answer this question, we retrospectively analyzed patient records in the Lysosafe Online® database (HRA Pharma, France) for patients who were treated for ≥6 months and who had ≥3 measurements of plasma mitotane levels during follow-ups at 11 tertiary centers in Italy from 2005 to 2017. We identified 110 patients treated with adjuvant mitotane for a median of 46 months (IQR, interquartile range, 28-62) with a median maintenance dose of 2.0 g/day (IQR 1.5-2.5). Achievement of target mitotane concentrations (≥14 mg/L) required a median of 8 months (IQR 5-19). Female sex was associated inversely with the dose, while body mass index (BMI) was correlated positively. Multivariate analysis showed that the Ki67 index and time to achieve the target range of plasma mitotane were independent predictors of recurrence-free survival (RFS). In a separate multivariate model, considering only the maintenance phase (month 7 to month 36, M7-M36) of treatment, the time in the target range of plasma mitotane was associated with a significantly lower risk of recurrence (Hazard Ratio, HR = 0.93; 0.88-0.98, p < 0.01). The prognostic implications of the time in target range and the time needed to reach target mitotane concentrations support the use of mitotane monitoring and may inform practice.

Correction to: Adrenocortical incidentalomas and bone: from molecular insights to clinical perspectives.

The original version of this article unfortunately contained a mistake in Figure 1. There is a typo in the word "osteoclastogenesis" and the word "activity" is missing in the same entity. It should be "osteoclastogenesis" instead of "osteoclestogenesis".

Adrenocortical incidentalomas and bone: from molecular insights to clinical perspectives.

Adrenal incidentalomas constitute a common clinical problem with an overall prevalence of around 2-3%, but are more common with advancing age being present in 10% of those aged 70 years. The majority of these lesions are benign adrenocortical adenomas (80%), characterized in 10-40% of the cases by autonomous cortisol hypersecretion, and in 1-10% by aldosterone hypersecretion. Several observational studies have shown that autonomous cortisol and aldosterone hypersecretion are more prevalent than expected in patients with osteopenia and osteoporosis: these patients have accelerated bone loss and an increased incidence of vertebral fractures. In contrast to glucocorticoid action, the effects of aldosterone on bone are less well understood. Recent data, demonstrating a concomitant co-secretion of glucocorticoid metabolites in patients with primary aldosteronism, could explain some of the metabolic abnormalities seen in patients with aldosterone hypersecretion. In clinical practice, patients with unexplained osteoporosis, particularly when associated with other features such as impaired glucose tolerance or hypertension, should be investigated for the possible presence of autonomous cortisol or aldosterone secretion due to an adrenal adenoma. Randomized intervention studies are needed, however, to investigate the optimum interventions for osteoporosis and other co-morbidities in these patients.

Myoinositol combined with alpha-lipoic acid may improve the clinical and endocrine features of polycystic ovary syndrome through an insulin-independent action.

The aim of our study was to investigate the effects of a combined treatment with alpha-lipoic acid (ALA) and myoinositol (MYO) on clinical, endocrine and metabolic features of women affected by polycystic ovary syndrome (PCOS). In this pilot cohort study, forty women with PCOS were enrolled and clinical, hormonal and metabolic parameters were evaluated before and after a six-months combined treatment with ALA and MYO daily. Studied patients experienced a significant increase in the number of cycles in six months (p < 0.01). The free androgen index (FAI), the mean androstenedione and DHEAS levels significantly decreased after treatment (p < 0.05). Mean SHBG levels significantly raised (p < 0.01). A significant improvement in mean Ferriman-Gallwey (F-G) score (p < 0.01) and a significant reduction of BMI (p < 0.01) were also observed. A significant reduction of AMH levels, ovarian volume and total antral follicular count were observed in our studied women (p< 0.05). No significant changes occurred in gluco-insulinaemic and lipid parameters after treatment. The combined treatment of ALA and MYO is able to restore the menstrual pattern and to improve the hormonal milieu of PCOS women, even in the absence of apparent changes in insulin metabolism.

Current evidence on vitamin D deficiency and kidney transplant: What's new?

Kidney transplant is the treatment of choice for end-stage chronic kidney disease. Kidneys generate 1,25-dihydroxyvitamin D (calcitriol) from 25-hydroxyvitamin D (calcidiol) for circulation in the blood to regulate calcium levels. Transplant patients with low calcidiol levels have an increased risk of metabolic and endocrine problems, cardiovascular disease, type 2 diabetes mellitus, poor graft survival, bone disorders, cancer, and mortality rate. The recommended calcidiol level after transplant is at least 30 ng/mL (75 nmol/L), which could require 1000-3000 IU/d vitamin D3 to achieve. Vitamin D3 supplementation studies have found improved endothelial function and acute rejection episodes. However, since kidney function may still be impaired, raising calcidiol levels may not lead to normal calcitriol levels. Thus, supplementation with calcitriol or an analog, alfacalcidiol, is often employed. Some beneficial effects found include possible improved bone health and reduced risk of chronic allograft nephropathy and cancer.

Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

Vitamin D and pancreas: The role of sunshine vitamin in the pathogenesis of diabetes mellitus and pancreatic cancer.

Increasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin D's immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence ß-cell function, insulin sensitivity, and systematic inflammation-all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin D's role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.

Livin/BIRC7 expression as malignancy marker in adrenocortical tumors.

Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R.The mRNA expression of livin, its isoforms α and ß, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression.Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform ß more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability.In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.

Adrenal disorders: Is there Any role for vitamin D?

An emerging branch of research is examining the linkage between Vitamin D and nonskeletal disorders, including endocrine diseases. In this regard, a still little studied aspect concerns the involvement of vitamin D in adrenal gland disorders. Adrenal gland disorders, which might be theoretically affected by vitamin D unbalance, include adrenal insufficiency, Cushing's syndrome, adrenocortical tumors and hyperaldosteronism. In this review, we provide an updated document, which tries to collect and discuss the limited evidence to be found in the literature about the relationship between vitamin D and adrenal disorders. We conclude that there is insufficient evidence proving a causal relationship between vitamin D levels and adrenal disorders. Evidence coming from cross-sectional clinical studies can hardly clarify what comes first between vitamin D unbalance and adrenal disease. On the other hand, longitudinal studies monitoring the levels of vitamin D in patients with adrenal disorders or, conversely, the possible development of adrenal pathologies in subjects affected by impaired vitamin D levels would be able to elucidate this still unclear issue.

Prediction of Vertebral Fractures in Patients With Monolateral Adrenal Incidentalomas.

CONTEXT: Subtle hypercortisolism is associated with an increased risk of vertebral fracture (VFx). OBJECTIVE: The objective was to determine the best parameters of cortisol secretion for detecting the VFx risk in patients with adrenal incidentalomas (AI). DESIGN: This was a retrospective (cross-sectional arm) and prospective (longitudinal arm) design. In the cross-sectional arm, we assessed the accuracy of the cortisol secretion indexes in identifying the patients with VFx (prevalent VFx). In the longitudinal arm, we tested the cortisol secretion parameters, which were able to identify the prevalent VFx, for the prediction of the occurrence of a new VFx (incident VFx) in AI patients followed-up for at least 2 years. SETTING: Four referral Italian endocrinology units participated in this study. PATIENTS: A total of 444 and 126 AI patients without symptoms of hypercortisolism enrolled in the cross-sectional arm and longitudinal arm, respectively. MAIN OUTCOME MEASURES: Serum cortisol after a 1-mg dexamethasone suppression test (1 mg DST), urinary free cortisol, ACTH, bone mineral density at lumbar spine and femoral neck (by dual-energy x-ray absorptiometry), and the VFx presence (by x-ray). RESULTS: The cortisol levels after 1 mg DST that were greater than 2.0 µg/dl (55 nmol/liter) were the best criteria for detecting patients with both prevalent (73.6% sensitivity, 70.5% specificity) and incident VFx (80% sensitivity, 68.8% specificity) and were associated with a 10-fold increased risk of a new VFx (odds ratio,10.27; 95% confidence interval, 3.39-31.12; P < .0001), regardless of age, gender, bone mineral density at lumbar spine, and prevalent VFx. CONCLUSIONS: In AI patients without symptoms of overt hypercortisolism, the cortisol levels after 1 mg DST greater than 2.0 µg/dl (55 nmol/liter) represent the best criterion for detecting prevalent and incident VFx.

Adrenocortical tumors and insulin resistance: What is the first step?

The pathogenetic mechanisms underlying the onset of adrenocortical tumors (ACTs) are still largely unknown. Recently, more attention has been paid to the role of insulin and insulin-like growth factor (IGF) system on general tumor development and progression. Increased levels of insulin, IGF-1 and IGF-2 are associated with tumor cell growth and increased risk of cancer promotion and progression in patients with type 2 diabetes. Insulin resistance and compensatory hyperinsulinemia may play a role in adrenal tumor growth through the activation of insulin and IGF-1 receptors. Interestingly, apparently non-functioning ACTs are often associated with a high prevalence of insulin resistance and metabolic syndrome. However, it is unclear if ACT develops from a primary insulin resistance and compensatory hyperinsulinemia or if insulin resistance is only secondary to the slight cortisol hypersecretion by ACT. The aim of this review is to summarize the current evidence regarding the relationship between hyperinsulinemia and adrenocortical tumors.

Assessment of insulin resistance in lean women with polycystic ovary syndrome.

OBJECTIVE: To develop and validate a specific simple measure of insulin sensitivity using oral glucose tolerance test (OGTT) values for lean polycystic ovary syndrome (PCOS) women. DESIGN: Retrospective study. SETTING: Gynecologic Outpatient Clinic of University Hospital, affiliated with Unit of Gynecologic Endocrinology. PATIENT(S): Totals of 201 lean and 198 overweight/obese (ov-ob) nondiabetic PCOS patients were retrospectively selected. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): All patients underwent OGTT, euglycemic-hyperinsulinemic clamp, and androgenic and biochemical assays. The predictive performance of each insulin resistance (IR) index was analyzed with the use of receiver operating characteristic (ROC) curves. RESULT(S): Higher correlation coefficients with clamp studies were obtained with the Belfiore Area (RS=0.579) and the homeostasis-model assessment (HOMA)-M120 (RS=-0.576) in lean PCOS patients and with the Sib (RS=0.697) in ov-ob PCOS patients. The best predictive index of IR in lean PCOS was a HOMA-M120 value of ≥12.8 or more (area under the ROC curve [AUC] 92.4%). In the ov-ob PCOS population, the best predictive performance was obtained by a Sib of ≤10.2 or less (AUC 85.7%). CONCLUSION(S): IR should be assessed in all PCOS women, both lean and ov-ob subjects. The HOMA-M120 resulted as a very simple tool, validated specifically for the lean PCOS woman whose cardiometabolic impairment is more frequently misunderstood.

Long-term follow-up in adrenal incidentalomas: an Italian multicenter study.

CONTEXT: The long-term consequences of subclinical hypercortisolism (SH) in patients with adrenal incidentalomas (AIs) are unknown. SETTING AND PATIENTS: In this retrospective multicentric study, 206 AI patients with a ≥5-year follow-up (median, 72.3 mo; range, 60-186 mo) were enrolled. INTERVENTION AND MAIN OUTCOME MEASURES: Adrenocortical function, adenoma size, metabolic changes, and incident cardiovascular events (CVEs) were assessed. We diagnosed SH in 11.6% of patients in the presence of cortisol after a 1 mg-dexamethasone suppression test >5 µg/dL (138 nmol/L) or at least two of the following: low ACTH, increased urinary free cortisol, and 1 mg-dexamethasone suppression test >3 µg/dL (83 nmol/L). RESULTS: At baseline, age and the prevalence of CVEs and type 2 diabetes mellitus were higher in patients with SH than in patients without SH (62.2 ± 11 y vs 58.5 ± 10 y; 20.5 vs 6%; and 33.3 vs 16.8%, respectively; P < .05). SH and type 2 diabetes mellitus were associated with prevalent CVEs (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-9.0; and OR, 2.0; 95% CI, 1.2-3.3, respectively), regardless of age. At the end of the follow-up, SH was diagnosed in 15 patients who were without SH at baseline. An adenoma size >2.4 cm was associated with the risk of developing SH (sensitivity, 73.3%; specificity, 60.5%; P = .014). Weight, glycemic, lipidic, and blood pressure control worsened in 26, 25, 13, and 34% of patients, respectively. A new CVE occurred in 22 patients. SH was associated with the worsening of at least two metabolic parameters (OR, 3.32; 95% CI, 1.6-6.9) and with incident CVEs (OR, 2.7; 95% CI, 1.0-7.1), regardless of age and follow-up. CONCLUSION: SH is associated with the risk of incident CVEs. Besides the clinical follow-up, in patients with an AI >2.4 cm, a long-term biochemical follow-up is also required because of the risk of SH development.