Background: Hypercortisolism has been implicated in the development of venous thromboembolic events (VTE). We aimed to characterize VTE risk in endogenous Cushing's syndrome (CS) patients, compare that risk to other pathologies, and determine if there are any associated coagulation factor changes. Methods: Medline and Scopus search for "hypercortisolism" and "thromboembolic disease" from January 1980 to April 2017 to include studies that reported VTE rates and/or coagulation profile of CS patients. A systematic review and meta-analysis were performed. Results: Forty-eight studies met inclusion criteria. There were 7,142 CS patients, average age was 42 years and 77.7% female. Odds ratio of spontaneous VTE in CS is 17.82 (95%CI 15.24-20.85, p < 0.00001) when comparing to a healthy population. For CS patients undergoing surgery, the odds ratio (both with / without anticoagulation) of spontaneous VTE is 0.26 (95%CI 0.07-0.11, p < 0.00001)/0.34 (0.19-0.36, p < 0.00001) when compared to patients undergoing hip fracture surgery who were not treated with anticoagulants. Coagulation profiles in patients with CS showed statistically significant differences compared to controls, as reflected by increases in von Willebrand factor (180.11 vs. 112.53 IU/dL, p < 0.01), as well as decreases in activated partial thromboplastin time (aPTT; 26.91 vs. 30.65, p < 0.001) and increases in factor VIII (169 vs. 137 IU/dL, p < 0.05). Conclusion: CS is associated with significantly increased VTE odds vs. general population, but lower than in patients undergoing major orthopedic surgery. Although exact timing, type, and dose of anticoagulation medication remains to be established, clinicians might consider monitoring vWF, PTT, and factor VIII when evaluating CS patients and balance advantages of thromboprophylaxis with risk of bleeding.

Ectopic Cushing Syndrome (EAS) is a rare condition responsible for about 5-20% of all Cushing syndrome cases. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The aim of this study is to present a 20-year experience in the diagnosis and clinical course of patients with EAS in a single Clinical Centre in Southern Poland as well as a comparison of clinical course and outcomes depending on the source of ectopic ACTH production-especially neuroendocrine tumors with other neoplasms.

The objective of this systematic literature review (SLR) was to summarize the latest studies evaluating the burden of illness in endogenous Cushing's syndrome (CS), including the impact of CS on overall and domain-specific health-related quality of life (HRQoL) and the economic burden of CS to provide a holistic understanding of disease and treatment burden.

In patients with Cushing's syndrome, development of Pneumocystis pneumonia (PCP) is associated with extreme cortisol production levels. In this setting, immune reconstitution after abrogation of cortisol excess appears to induce development of symptomatic PCP. The high mortality rate warrants timely initiation of chemoprophylaxis or even preemptive treatment of PCP.

Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development.

Neoplasms that secrete ectopic adrenocorticotropin (ACTH) may cause severe, life-threatening hypercortisolism. These tumors are often difficult to localize and treat, requiring a comprehensive and systematic management plan orchestrated by a multidisciplinary team. The Mount Sinai Adrenal Center hosted an interdisciplinary retreat of experts in adrenal disorders and neuroendocrine tumors (NETs) with the aim of developing a clinical pathway for the management of Cushing syndrome due to ectopic ACTH production. The result was institutional recommendations for the diagnosis, localization, surgical approaches to intrathoracic tumors and bilateral adrenalectomy, and perioperative and postoperative medical management of hypercortisolism and its sequelae. Specific recommendations were made regarding the timing and selection of therapies based on the considerations of our team as well as a review of the current literature. Our clinical pathway can be applied by other institutions directly or serve as a guide for institution-specific management.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder and is characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Obesity, low-grade chronic inflammatory status, and insulin-resistance (IR) often coexist in PCOS. The Mediterranean diet (MD) is an anti-inflammatory dietary pattern, which is rich in complex carbohydrates and fiber, and high in monounsaturated fat. There is a close association among obesity, low-grade chronic inflammation, IR, and hormonal derangements in PCOS. The main aim of the present study was to evaluate the adherence to MD, the dietary intake, and the body composition and their association with PCOS clinical severity in a cohort of treatment-naïve women with PCOS when compared with a control group of healthy women matched for age and body mass index (BMI). In this case-controlled, cross-sectional study, we enrolled 112 patients with PCOS and 112 controls. PREvención con DIetaMEDiterránea (PREDIMED) and seven-day food records were used to evaluate the degree of adherence to the MD and dietary pattern, respectively. Body composition was evaluated by bioelectrical impedance analysis (BIA) phase-sensitive system. Testosterone levels and Ferriman-Gallwey score assessed the clinical severity of PCOS. C-reactive protein (CRP) levels were determined with a nephelometric assay with CardioPhase high sensitivity. PCOS women showed higher testosterone levels, Ferriman-Gallwey score, fasting insulin and glucose levels, and Homeostatic Model Assessment (HoMA)-IR when compared with the control group (p < 0.001). In addition, we found that the PCOS women consumed less extra-virgin olive oil, legumes, fish/seafood, and nuts compared with control group. Despite no differences in energy intake between the two groups, the PCOS women consumed a lower quantity of complex carbohydrate, fiber, monounsaturated fatty acids (MUFA), and n-3 polyunsaturated fatty acid (PUFA), and higher quantity of simple carbohydrate, total fat, saturated fatty acid (SFA), PUFA and n-6 PUFA than the control group. The PCOS women have an adverse body composition when compared with controls, with the lowest values of phase angle (PhA) and fat-free mass (p < 0.001). Additionally, after adjusting for BMI and total energy intake, testosterone levels showed significant negative correlations with PREDIMED score (p < 0.001) and consumption of protein (p = 0.005), complex carbohydrate (p < 0.001), fiber (p < 0.001), MUFA (p < 0.001), n-3 PUFA (p = 0.001), and positive associations with CRP levels, simple carbohydrate, SFA, n-6 PUFA (p < 0.001, respectively), and PUFA (p = 0.002). The cut-off for PREDIMED score ≤ 6 (p < 0.001, area under the curve (AUC) 0.848, standard error 0.036, 95% confidence interval (CI) 0.768 to 0.909) could serve as a threshold for significantly increased risk of high value of testosterone levels. In conclusion, a novel direct association between the adherence to MD and the clinical severity of the disease was reported in women with PCOS. This association could support a therapeutic role of foods and nutrients of the Mediterranean dietary pattern in the PCOS pathogenesis likely involving their inflammatory status, IR, and hyperandrogenemia. In addition, we reported a different body composition that is characterized by lower PhA and fat-free mass than controls. These data suggested a role of PhA as a useful marker of the clinical severity of this syndrome and provided strong evidence regarding the strategic relevance of the nutritional assessment in the management of women with PCOS.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the cause of a worldwide pandemic. Many commercial SARS-CoV-2 reverse transcription-PCR (RT-PCR) assays have received Emergency Use Authorization from the U.S. Food and Drug Administration. However, there are limited data describing their performance, in particular the performance of high-throughput SARS-CoV-2 RT-PCR systems. We analyzed the diagnostic performance of two high-throughput systems: cobas 6800 and Panther Fusion, and their associated RT-PCR assays, with a collection of 389 nasopharyngeal specimens. The overall agreement between the platforms was 96.4% (375/389). Cohen's kappa analysis rated the strength of agreement between the two platforms as "almost perfect" (κ = 0.922; standard error, 0.051). Furthermore, there was no significant difference between corresponding cycle threshold values generated on the two systems (P value = 0.88; Student's t test). Taken together, these data imply that the two platforms can be considered comparable in terms of their clinical performance. We believe that this information will be useful for those who have already adopted these platforms or are seeking to implement high-throughput RT-PCR testing to stem the SARS-CoV-2 pandemic.

We report a consanguineous couple that has experienced three consecutive pregnancy losses following the foetal ultrasound finding of short limbs. Post-termination examination revealed no skeletal dysplasia, but some subtle proximal limb shortening in two foetuses, and a spectrum of mildly dysmorphic features. Karyotype was normal in all three foetuses (46, XX) and comparative genomic hybridization microarray analysis detected no pathogenic copy number variants.

An epidemic caused by an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in December 2019 has since rapidly spread internationally, requiring urgent response from the clinical diagnostics community. We present a detailed overview of the clinical validation and implementation of the first laboratory-developed real-time RT-PCR test offered in the NewYork-Presbyterian Hospital system following the Emergency Use Authorization issued by the US Food and Drug Administration. Nasopharyngeal and sputum specimens (n = 174) were validated using newly designed dual-target real-time RT-PCR (altona RealStar SARS-CoV-2 Reagent) for detecting SARS-CoV-2 in upper respiratory tract and lower respiratory tract specimens. Accuracy testing demonstrated excellent assay agreement between expected and observed values and comparable diagnostic performance to reference tests. The limit of detection was 2.7 and 23.0 gene copies per reaction for nasopharyngeal and sputum specimens, respectively. Retrospective analysis of 1694 upper respiratory tract specimens from 1571 patients revealed increased positivity in older patients and males compared with females, and an increasing positivity rate from approximately 20% at the start of testing to 50% at the end of testing 3 weeks later. Herein, we demonstrate that the assay accurately and sensitively identifies SARS-CoV-2 in multiple specimen types in the clinical setting and summarize clinical data from early in the epidemic in New York City.

Cushing's disease caused due to adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (ACTHomas) leads to hypercortisolemia, resulting in increased morbidity and mortality. Autonomous ACTH secretion is attributed to the impaired glucocorticoid negative feedback (glucocorticoid resistance) response. Interestingly, other conditions, such as ectopic ACTH syndrome (EAS) and non-neoplastic hypercortisolemia (NNH, also known as pseudo-Cushing's syndrome) also exhibit glucocorticoid resistance. Therefore, to differentiate between these conditions, several dynamic tests, including those with desmopressin (DDAVP), corticotrophin-releasing hormone (CRH), and Dex/CRH have been developed. In normal pituitary corticotrophs, ACTH synthesis and secretion are regulated mainly by CRH and glucocorticoids, which are the ACTH secretion-stimulating and -suppressing factors, respectively. These factors regulate ACTH synthesis and secretion through genomic and non-genomic mechanisms. Conversely, glucocorticoid negative feedback is impaired in ACTHomas, which could be due to the overexpression of 11β-HSD2, HSP90, or TR4, or loss of expression of CABLES1 or nuclear BRG1 proteins. Genetic analysis has indicated the involvement of several genes in the etiology of ACTHomas, including USP8, USP48, BRAF, and TP53. However, the association between glucocorticoid resistance and these genes remains unclear. Here, we review the clinical aspects and molecular mechanisms of ACTHomas and compare them to those of other related conditions.

Coronavirus disease 2019 (COVID-19) infection primarily involves the respiratory system but has many noteworthy extra pulmonary manifestations as well. We write this review to highlight the basis of some pathophysiological mechanisms of COVID-19 infection-induced endocrine dysfunction. Different scientific databases and institutional websites were searched to collect and consolidate the most up-to-date data relating to COVID-19 infection and endocrine systems. Hypopituitarism, central diabetes insipidus, SIADH, thyroid abnormalities, hyperglycemia, adrenal insufficiency, orchitis and alteration in sperm morphology have been reported in case reports of patients with COVID-19 infection. Data focusing on COVID-19 vaccination was also searched to summarize the effect, if any, on the endocrine system. Endocrinopathies noted post COVID-19 vaccination, including cases of adrenal hemorrhage, new onset Type II Diabetes Mellitus and subacute thyroiditis, are also discussed in this review. This review calls attention to the misinformation relating to COVID-19 vaccination with supposed endocrine effects such as infertility and problems with pregnancy. Rebutting these misconceptions can help increase compliance and maximize COVID-19 vaccination to the public.

Some authors consider adrenal lesions size of less than 4 cm as a positive cut-off limit to set the indications for minimally invasive surgery due to a lower risk of malignancy. Aim of this study is to report the risk of cancer for adrenal lesions measuring 4 cm or more in diameter, assessed as benign at preoperative workup (primary outcome), and to evaluate the feasibility and safety of laparoscopic adrenalectomy (LA) in these cases (secondary outcome).

Objective To explore stable and functional microRNA (miRNA)-disease relationships using a genome-wide expression profile pattern matching strategy. Methods We applied the ranked microarray pattern matching strategy Gene Set Enrichment Analysis to identify miRNA permutations with similar expression patterns to diseases. We also used quantitative reverse transcription PCR to validate the predicted expression levels of miRNAs in three diseases: inflammatory bowel disease (IBD), oesophageal cancer, and colorectal cancer. Results We found that hsa-miR-200 c was upregulated more than 40-fold in oesophageal cancer. The expression of miR-16 and miR-124 was not consistently upregulated in IBD or colorectal cancer. Conclusions Our results suggest that this expression profile matching strategy can be used to identify functional miRNA-disease relationships.

Primary macronodular adrenal hyperplasia (PMAH) is a rare type of Cushing or subclinical Cushing syndrome and is associated with bilateral multinodular formation. ARMC5 is one of the responsible genes for PMAH.

Mifepristone is a glucocorticoid and progesterone receptor blocker that can be used for patients with hyperglycemia and Cushing syndrome in whom surgery failed to achieve remission or who were ineligible for surgery. We report a case series of patients with Cushing disease (CD) and central hypothyroidism that presented with increased levothyroxine requirements during mifepristone therapy.

cAMP and cGMP are important secondary messengers involved in cell regulation and metabolism driven by the G protein‑coupled receptor. cAMP is converted via adenylyl cyclase (AC) and activates protein kinase A to phosphorylate intracellular proteins that mediate specific responses. cAMP signaling serves a role at multiple steps in tumorigenesis. The level of cAMP is increased in association with cancer cell formation through activation of AC‑stimulatory G protein by mutation. Phosphodiesterases (PDEs) hydrolyze cAMP and cGMP to AMP and GMP. PDEs are composed of 11 families, and each can hydrolyze cAMP and cGMP or both cAMP and cGMP. PDEs perform various roles depending on their location and expression site, and are involved in several diseases, including male erectile dysfunction, pulmonary hypertension, Alzheimer's disease and schizophrenia. PDE11A is the 11th member of the PDE family and is characterized by four splice variants with varying tissue expression and N‑terminal regulatory regions. Among tissues, the expression of PDE11A was highest in the prostate, and it was also expressed in hepatic skeletal muscle, pituitary, pancreas and kidney. PDE11A is the first PDE associated with an adrenocortical tumor associated genetic condition. In several studies, three PDE11A mutations have been reported in patients with Cushing syndrome with primary pigmented nodular adrenocortical disease or isolated micronodular adrenocortical disease without other genetic defects. It has been reported that an increase in PDE11A expression affects the proliferation of glioblastoma and worsens patient prognosis. The present mini‑review summarizes the location of PDE11A expression, the impact of structural differences and disease relevance.

Adrenal insufficiency and Cushing syndrome are known adverse events of glucocorticoids. However, no population estimates of dose-related risks are available.

The proper clinical evaluation of pituitary and adrenal disorders depends on the accurate measurement of plasma ACTH. The modern two-site sandwich ACTH immunoassay is a great improvement compared with older methods but still has the potential for interferences such as heterophile antibodies and pro-opiomelanocortin (POMC) and ACTH fragments. We report the cases of five patients in whom the diagnosis or differential diagnosis of Cushing syndrome was confounded by erroneously elevated results from the Siemens ACTH Immulite assay [ACTH(Immulite)] that were resolved using the Roche Cobas or Tosoh AIA [ACTH(Cobas) and ACTH(AIA), respectively]. In one case, falsely elevated ACTH(Immulite) results owing to interfering antibodies resulted in several invasive differential diagnostic procedures (including inferior petrosal sinus sampling), MRI, and unnecessary pituitary surgery. ACTH(Cobas) measurements were normal, and further studies excluded the diagnosis of Cushing syndrome. In three cases, either Cushing disease or occult ectopic ACTH were suspected owing to elevated ACTH(Immulite) results. However, adrenal (ACTH-independent) Cushing syndrome was established using ACTH(AIA) or ACTH(Cobas) and proved surgically. In one case, ectopic ACTH was suspected owing to elevated ACTH(Immulite) results; however, the ACTH(Cobas) findings led to the diagnosis of alcohol-induced hypercortisolism that resolved with abstinence. We have concluded that ACTH(Immulite) results can be falsely increased and alternate ACTH assays should be used in the diagnosis or differential diagnosis of clinical disorders of the hypothalamic-pituitary-adrenal axis.

This study aimed to investigate the characteristics and extent of glycometabolism impairment in patients with adrenal diseases, including Cushing syndrome, primary aldosteronism, pheochromocytoma, and nonfunctional adrenal incidentaloma.