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Abstract Background While insulin resistance and diabetes shine as the central stars in the constellation of obesity-related conditions, other common endocrine diseases are also closely associated with obesity and high body mass index. Main body This review aims to illuminate the hormonal imbalances associated with obesity, beyond diabetes. It covers the prevalence, clinical presentation, screening, diagnosis, and treatment of some of these conditions. Conclusion In obese patients, physicians must pay attention to hormonal disorders that may be associated with obesity.

Mauriac syndrome (MS) is an exceptionally rare disorder occurring in poorly controlled Type-1 diabetic patients. The consequences include dwarfism, obesity, hepatomegaly, delayed puberty, growth failure and higher levels of transaminase enzyme. We report a case of an adolescent female with classical features of Mauriac syndrome.

Cushing Syndrome, a rare condition with increased glucocorticoid production can affect renal function directly by its effect on glomerular and tubular functions or indirectly through the cardiovascular system. The aim is to report a case of Cushing Syndrome complicated by End Stage Renal Failure. The authors present symptoms, clinical course and laboratory findings of a 16-year-old girl with a diagnosis of Cushing syndrome complicated by end stage renal failure. She presented with excessive weight gain of 7-years, recurrent abdominal pain of 1-year, vomiting of 3-weeks and headache of a day duration. She had moon face, striae, buffalo hump and hypertension.

Background/Objective: Ectopic cosecretion of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in silent (ie, non–catecholamine-secreting) pheochromocytoma is a rare cause of Cushing syndrome. Case Report: A 57-year-old woman rapidly developed hypercortisolism, clinically manifesting as fatigue, muscle weakness, weight gain, and worsening hypertension and biochemically characterized by hypokalemia and marked increases in the serum cortisol and plasma ACTH levels. This acute presentation suggested a diagnosis of ectopic ACTH syndrome (EAS). Imaging studies revealed a right adrenal mass that enhanced after administration of the radioisotope gallium-68-DOTATATE. Plasma metanephrines were normal in 2 separate measurements. The possibility of a silent pheochromocytoma was considered. After controlling her hypercortisolism with metyrapone and surgical preparation with alpha blockade, the patient underwent elective right adrenalectomy. Pathology revealed a pheochromocytoma that stained focally for ACTH and CRH. Postoperatively, the cortisol levels normalized, the hypothalamic-pituitary-adrenal axis was not suppressed, and clinical symptoms from hypercortisolism abated. Discussion: Patients who exhibit a rapid progression of ACTH-dependent hypercortisolism should be screened for EAS. The use of functional imaging radioisotopes (eg, gallium DOTA-peptides) improves the detection of ACTH-secreting tumors. Preoperative treatment with steroidogenesis inhibitors helps control clinical and metabolic derangements associated with severe hypercortisolemia, whereas alpha blockade prevents the onset of an adrenergic crisis. Conclusion: We present a rare case of EAS due to a silent pheochromocytoma that cosecreted ACTH and CRH. Pheochromocytoma should be considered in patients with EAS who have an adrenal mass even in the absence of excessive catecholamine secretion.

Background: Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE). Objective: The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis. Design and methods: A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG’s) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022. Results: Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3–30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Conclusion: Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed. Significance statement The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.

Background Subclinical Cushing's syndrome (SCS) is a common subtype of adrenal incidentaloma. There are few reports on the correlation between hyperglycemia and hypercortisone secretion and its postoperative change in SCS patients. Objective To assess the pre- and post-surgical prevalence of hyperglycemia in patients with SCS secondary to adrenal incidentaloma. Methods The data of 202 patients who consulted in respiratory department of endocrinology, renhe hospital affiliated to shanghai university (shanghai baoshan district renhe hospital). Participants included 36 SCS patients, 41 patients with Cushing's syndrome due to adrenal tumor (CSA), 47 with nonfunctional adrenal tumor (NAT), and 53 controls. OGTT was performed in all of them, and based on the results, HOMA-IR, the area under the curve of blood glucose (AUCGlu) and insulin (AUCIns) were calculated, and plasma cortisol and urinary free cortisol and plasma ACTH were measured, then the values of the parameters were compared between controls and patients. Surgical treatment was given to SCS and CSA patients. The association of hormone and glucose metabolism parameters was assessed using Pearson correlation analysis. Results The prevalence of hyperglycemia in SCS, CSA and NAT patients before surgery and in controls was 41.7%, 51.2%, 25.5%, and 24.5%, respectively. The HbA1c, 2-hour post-load insulin (2 hPIN), AUCGlu and AUCIns in SCS patients were higher than those of controls (P

Abstract Background Laparoscopic adrenalectomy is widely performed for a number of hormone-producing tumors and postoperative management depends on the hormones produced. In the present study, we conducted a retrospective analysis to clarify the risk factors for postoperative complications, particularly postoperative fever after laparoscopic adrenalectomy. Methods We analyzed 406 patients who underwent laparoscopic adrenalectomy at our hospital between 2003 and 2019. Postoperative fever was defined as a fever of 38 °C or higher within 72 h after surgery. We investigated the risk factors for postoperative fever after laparoscopic adrenalectomy. Results There were 188 males (46%) and 218 females (54%) with a median age of 52 years. Among these patients, tumor pathologies included 188 primary aldosteronism (46%), 75 Cushing syndrome (18%), and 80 pheochromocytoma (20%). Postoperative fever developed in 124 of all patients (31%), 30% of those with primary aldosteronism, 53% of those with pheochromocytoma, and 8% of those with Cushing syndrome. A multivariate logistic regression analysis identified pheochromocytoma and non-Cushing syndrome as independent predictors of postoperative fever. Postoperative fever was observed in 42 out of 80 cases of pheochromocytoma (53%), which was significantly higher than in cases of non-pheochromocytoma (82/326, 25%, p

IntroductionPatients with Cushing’s syndrome (CS) in remission show sustained fatigue, myopathy, and an increased prevalence of sarcopenia. The mechanisms that determine these persistent muscle problems are not well known. We aimed to identify circulating microRNAs (miRNAs) with differential expression that could be potential biomarkers for the diagnosis and/or prognosis in CS.Patients and methodsThirty-six women in sustained remission for 13 ± 7 years (mean ± SD) from CS, with a median age (IQ range) of 51 (45.2–60) years and mean ± SD BMI of 27 ± 4 Kg/m2, and 36 matched healthy controls were investigated. In 7 patients sarcopenia was present according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Small RNA libraries were generated and indexed using a modified Illumina TruSeq small RNA-sequencing protocol. MiRNAs were identified in plasma using bioinformatic analysis, and validation was carried out using RT-qPCR. For the validation, Taqman probes were performed on QuantStudio 5 equipment (Applied Biosystems).ResultsIn a first discovery group using RNA-sequencing, plasma samples of 18 CS patients and 18 healthy subjects were investigated; circulating miR-28-5p, miR-495-3p and miR-654-5p were upregulated in CS patients as compared with controls (p

Background: We previously reported that myocardial fibrosis may be one of the causes of left ventricular hypertrophy and cardiac dysfunction in dogs with hyperglucocorticism (HGC). The detailed mechanism by which myocardial fibrosis of the left ventricle occurs in dogs with hyperglucocorticism (HGC) remains unclear. Aim: This study investigated the mechanism by which HGC causes fibrosis of the left ventricle. Methods: The impacts of HGC on the heart by comparing samples obtained from high-dose glucocorticoid-treated (P) and untreated (C) dogs. The P group included healthy Beagle dogs (n=6) treated with prednisolone (2 mg/kg, bid, po) for 84 days, and the C group included healthy Beagle dogs (n=6) euthanized for unrelated reasons. In three of the P group dogs, serum was collected before the start of administration (Day 0) and on Day 84 to measure angiotensin II concentrations and oxidative stress markers (8-hydroxy-2'-deoxyguanosine (8OHdG), NADPH oxidase, and superoxide levels). Samples of the left ventricular free wall (LVFW), right ventricular free wall (RVFW), interventricular septum (IVS), and aortic root were harvested from both groups (n = 6 for each group). Using these tissue samples, angiotensin II type 1 receptor (AT1R), 8OHdG, and transforming growth factor β1 (TGFβ1) immunohistochemical stains were performed. Results: The blood NADPH oxidase concentration was significantly higher (P=0.027) in the P group 84 days after initiation of the medication compared to that before prednisolone treatment. By contrast, there was no significant difference in serum angiotensin II (P=0.450), 8OHdG (P=0.068), and superoxide (P=0.057) concentrations. The positive staining rates of AT1R, 8OHdG, and TGFβ1 in the heart (LVFW, RVFW, IVS, and aortic root) were significantly higher in the P group than those in the C group. Conclusion: Angiotensin II and oxidative stress in HGC may cause left ventricular fibrosis in dogs. [Open Vet J 2023; 13(12.000): 1708-1717]

Metabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The circulatory system facilitates metabolite exchange among organs, while the endocrine system finely tunes metabolism through hormone release. Endocrine disorders like obesity, diabetes, and Cushing’s syndrome disrupt this balance, contributing to systemic inflammation and global health burdens. They accompany metabolic changes on multiple levels from molecular interactions to individual organs to the whole body. Understanding how metabolic fluxes relate to endocrine disorders illuminates the underlying dysregulation. Cancer is increasingly considered a systemic disorder because it not only affects cells in localized tumors but also the whole body, especially in metastasis. In tumorigenesis, cancer-specific mutations and nutrient availability in the tumor microenvironment reprogram cellular metabolism to meet increased energy and biosynthesis needs. Cancer cachexia results in metabolic changes to other organs like muscle, adipose tissue, and liver. This review explores the interplay between the endocrine system and systems-level metabolism in health and disease. We highlight metabolic fluxes in conditions like obesity, diabetes, Cushing’s syndrome, and cancers. Recent advances in metabolomics, fluxomics, and systems biology promise new insights into dynamic metabolism, offering potential biomarkers, therapeutic targets, and personalized medicine.

ABSTRACT Objective Onset and exacerbation of autoimmune, inflammatory or steroid‐responsive conditions have been reported following the remission of Cushing syndrome, leading to challenges in distinguishing a new condition versus expected symptomatology following remission. We describe a case of a 42‐year‐old man presenting with new‐onset sarcoidosis diagnosed 12 months following the surgical cure of Cushing syndrome and synthesise existing literature reporting on de novo conditions presenting after Cushing syndrome remission. Methods A scoping review was conducted in Medline, Epub, Ovid and PubMed. Case reports and case series detailing adult patients presenting with new‐onset conditions following Cushing syndrome remission were included. Results In total, 1641 articles were screened, 138 full‐text studies were assessed for eligibility, and 43 studies were included, of which 84 cases (including our case) were identified. Most patients were female (85.7%), and the median reported age was 39.5 years old (IQR = 13). Thyroid diseases were the most commonly reported conditions (48.8%), followed by sarcoidosis (15.5%). Psoriasis, lymphocytic hypophysitis, idiopathic intracranial hypertension, multiple sclerosis, rheumatoid arthritis, lupus and seronegative arthritis were reported in more than one case. The median duration between Cushing remission and de novo condition diagnosis was 4.1 months (IQR = 3.75). Of those patients, 59.5% were receiving corticosteroid therapy at the time of onset. Conclusion Our scoping review identified several cases of de novo conditions emerging following the remission of Cushing syndrome. They occurred mostly in women and within the year following remission. Clinicians should remain aware that new symptoms, particularly in the first year following the treatment of Cushing syndrome, may be manifestations of a wide range of conditions aside from adrenal insufficiency or glucocorticoid withdrawal syndrome.

Glucocorticoid withdrawal syndrome is a challenging clinical phenomenon that can complicate the postsurgical recovery of Cushing syndrome. It is characterized by physical tolerance and dependence to supraphysiologic glucocorticoid exposure during active Cushing syndrome followed by the abrupt decline in cortisol levels after surgical treatment. The symptoms of glucocorticoid withdrawal often overlap with those of postoperative adrenal insufficiency and can be difficult for patients to cope with and for clinicians to treat. This mini review will discuss the clinical characteristics, pathophysiology, and management of glucocorticoid withdrawal syndrome while highlighting recent data in the field.

BackgroundCushing’s syndrome (CS) during pregnancy is a rare endocrine disorder characterized by hypercortisolism, which is significantly associated with maternal-fetal complications. Despite its rarity, CS during pregnancy may be related to a high risk of complications for both the mother and fetus.The aim of the present case study is to update the diagnostic approach to CS during pregnancy and the therapeutic strategies for this medical condition to minimize maternal-fetal complications.MethodsHere, we present two cases of CS in pregnant women, one of whom had twins. Typical clinical symptoms and signs of hypercortisolism developed at the beginning of pregnancy. The plasma cortisol diurnal rhythm of the pregnant patient was absent. CS was confirmed by cortisol and adrenocorticotropic hormone (ACTH) assessment, as well as imaging examination. We investigated the changes in the hypothalamic-pituitary-adrenal axis during normal pregnancy and the etiology, diagnosis and treatment of CS during pregnancy.ConclusionDue to the associated risks of laparoscopic adrenalectomy,it is uncertain whether this treatment significantly decreases overall maternal mortality. Additional observational research and validation through randomized controlled trials (RCTs) are required. We advise that CS in pregnant women be diagnosed and treated by experienced teams in relevant departments and medical centers.

Prolonged exposure to an excess of glucocorticosteroids (GCs), both endogenous and exogenous, leads to a wide range of comorbidities, including cardiovascular, metabolic, psychiatric, and musculoskeletal disorders. The latter comprise osteopenia and osteoporosis leading to skeletal fractures and myopathy. Although endogenous hypercortisolemia is a rare disorder, GCs are among the most frequently prescribed drugs, often administered chronically and despite multiple side effects, impossible to taper off due to therapeutic reasons. The pathophysiology of the effect of GC excess on bone often leads to fractures despite normal or low-normal bone mineral density and it includes direct (mainly disturbance in bone formation processes, through inactivation of the Wnt/β-catenin signalling pathway) and indirect mechanisms (through suppressing the gonadal and somatotrophic axis, and also through antagonizing vitamin D actions). Glucocorticosteroid-induced fast-twitch, glycolytic muscles atrophy occurs due to increased protein catabolism and impaired synthesis. Protein degradation is a result of activation of the ubiquitin proteasome and the lysosomes stimulated through overexpression of several atrogenes (such as FOXO-1 and atrogin-1). This review will discuss pathophysiology, clinical presentation, prevention, and management of GC- induced osteoporosis (including calcium and vitamin D supplementation, and bisphosphonates) and myopathy associated with GC excess.

Objective To screen risk factors related to visual acuity and visual field defects in patients with Cushing's disease, and based on risk factors to analyze health economics. Methods A total of 416 patients with Cushing's disease admitted to Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from August 1994 to December 2019 were included. Objective examination of visual acuity and visual field was used as the dependent variable, while gender, age, duration, blood glucose, blood pressure, hormone level, eye swelling, imaging features, and main complaint of visual acuity and visual field were used as independent variables. Univariate and multivariate Logistic regression analysis was used to screen the risk factors related to visual acuity and visual field defects, and cost ⁃ effectiveness ratio (CER) and cost ⁃ benefit ratio (CBR) were analyzed based on risk factors. Results Among 416 patients with Cushing's disease, 143 (34.38%) complained of abnormal visual acuity and visual field, including 59 cases of blurred vision, 11 cases of impaired visual field, 41 cases of blurred vision combined with impaired visual field, 13 cases of blurred vision combined with impaired visual field, 3 cases of impaired visual field combined with impaired visual field, and 16 cases of all three symptoms. There were 102 cases (24.52%) with abnormal visual acuity and visual field test, including 44 cases of visual loss, 39 cases of visual field defect, and 19 cases of visual loss combined with visual field defect. Logistic regression analysis showed the increased systolic blood pressure (OR = 1.016, 95%CI: 1.002-1.030; P = 0.025) and abnormal visual acuity and visual field complaints (OR = 14.000, 95%CI: 7.918-24.754; P = 0.000) were risk factors for visual acuity and visual field defects. According to the analysis of health economics, the CER of the whole group was 393 926.53, which was 6.56 times higher than that of the patients with abnormal visual acuity and visual field complaints (60 057.93). The CBR was 4.08, which was 2.25 times higher than that of patients with abnormal visual acuity and visual field complaints (1.81). Conclusions Cushing's disease patients with abnormal visual acuity and visual field complaints are more likely to have abnormal visual acuity and visual field. Therefore, taking abnormal visual acuity and visual field complaints as an indication for visual acuity and visual field test of Cushing's disease patients can improve the detection rate and reduce the waste of health and social resources, which is not only clinically feasible, but also can effectively prevent medical risks.

Cushing disease (CD) is the main cause of endogenous Cushing syndrome (CS) and is produced by an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma. Its relevance in pediatrics is due to the retardation of both growth and developmental processes because of hypercortisolism. In childhood, the main features of CS are facial changes, rapid or exaggerated weight gain, hirsutism, virilization, and acne. Endogenous hypercortisolism should be established after exogenous CS has been ruled out based on 24-hour urinary free cortisol, midnight serum or salivary cortisol, and dexamethasone suppression test; after that, ACTH dependence should be established. The diagnosis should be confirmed by pathology. The goal of treatment is to normalize cortisol level and reverse the signs and symptoms. Treatment options include surgery, medication, radiotherapy, or combined therapy. CD represents a challenge for physicians owing to its multiple associated conditions involving growth and pubertal development; thus, it is important to achieve an early diagnosis and treatment in order to control hypercortisolism and improve the prognosis. Its rarity in pediatric patients has led physicians to have limited experience in its management. The objective of this narrative review is to summarize the current knowledge about the pathophysiology, diagnosis, and treatment of CD in the pediatric population.

Abstract Background The diagnosis of Cushing’s syndrome is challenging; however, through the clinical picture and the search for secondary causes of osteoporosis, it was possible to reach the diagnosis of the case reported. There was an independent, symptomatic ACTH hypercortisolism manifested by typical phenotypic changes, severe secondary osteoporosis and arterial hypertension in a young patient. Case presentation A 20-year-old Brazilian man with low back pain for 8 months. Radiographs showed fragility fractures in the thoracolumbar spine, and bone densitometry showed osteoporosis, especially when evaluating the Z Score (− 5.6 in the lumbar spine). On physical examination, there were wide violaceous streaks on the upper limbs and abdomen, plethora and fat increase in the temporal facial region, hump, ecchymosis on limbs, hypotrophy of arms and thighs, central obesity and kyphoscoliosis. His blood pressure was 150 × 90 mmHg. Cortisol after 1 mg of dexamethasone (24.1 µg/dL) and after Liddle 1 (28 µg/dL) were not suppressed, despite normal cortisoluria. Tomography showed bilateral adrenal nodules with more severe characteristics. Unfortunately, through the catheterization of adrenal veins, it was not possible to differentiate the nodules due to the achievement of cortisol levels that exceeded the upper limit of the dilution method. Among the hypotheses for the differential diagnosis of bilateral adrenal hyperplasia are primary bilateral macronodular adrenal hyperplasia, McCune–Albright syndrome and isolated bilateral primary pigmented nodular hyperplasia or associated with Carney’s complex. In this case, primary pigmented nodular hyperplasia or carcinoma became important etiological hypotheses when comparing the epidemiology in a young man and the clinical-laboratory-imaging findings of the differential diagnoses. After 6 months of drug inhibition of steroidogenesis, blood pressure control and anti-osteoporotic therapy, the levels and deleterious metabolic effects of hypercortisolism, which could also impair adrenalectomy in the short and long term, were reduced. Left adrenalectomy was chosen, given the possibility of malignancy in a young patient and to avoid unnecessary definitive surgical adrenal insufficiency if the adrenalectomy was bilateral. Anatomopathology of the left gland revealed expansion of the zona fasciculate with multiple nonencapsulated nodules. Conclusion The early identification of Cushing’s syndrome, with measures based on the assessment of risks and benefits, remains the best way to prevent its progression and reduce the morbidity of the condition. Despite the unavailability of genetic analysis for a precise etiological definition, it is possible to take efficient measures to avoid future damage.

Two young girls, aged 11 and 12 years, presented with obesity and Acanthosis Nigricans. They were found to have severe insulin resistance and type-2 diabetes mellitus. Anti-glutamic acid decarboxylase and anti-islet cell antibodies were negative. Tests for hypothyroidism and Cushing’s syndrome were negative. They were managed with lifestyle modification and metformin.

We evaluated the accuracy of the 10 μg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome (EAS). A systematic review of studies on diagnostic test accuracy in patients with CD, NNH, or EAS subjected to the desmopressin test obtained from LILACS, PubMed, EMBASE, and CENTRAL databases was performed. Two reviewers independently selected the studies, assessed the risk of bias, and extracted the data. Hierarchical and bivariate models on Stata software were used for meta-analytical summaries. The certainty of evidence was measured using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation Working Group) approach. In total, 14 studies were included: 3 studies on differentiated CD versus NNH and 11 studies on differentiated CD versus EAS. Considering ΔACTH in 8 studies involving 429 patients, the pooled sensitivity for distinguishing CD from EAS was 0.85 (95% confidence interval [CI]: 0.80–0.89, I2 = 17.6%) and specificity was 0.64 (95% CI: 0.49–0.76, I2 = 9.46%). Regarding Δcortisol in 6 studies involving 233 participants, the sensitivity for distinguishing CD from EAS was 0.81 (95% CI: 0.74–0.87, I2 = 7.98%) and specificity was 0.80 (95% CI: 0.61–0.91, I2 = 12.89%). The sensitivity and specificity of the combination of ΔACTH > 35% and Δcortisol > 20% in 5 studies involving 511 participants were 0.88 (95% CI: 0.79–0.93, I2 = 35%) and 0.74 (95% CI: 0.55–0.87, I2 = 27%), respectively. The pooled sensitivity for distinguishing CD from NNH in 3 studies involving 170 participants was 0.88 (95% CI: 0.79–0.93) and the specificity was 0.94 (95% CI: 0.86–0.97). Based on the desmopressin test for differentiating CD from EAS, considering ΔACTH, Δcortisol, or both percent increments, 15%, 19%, or 20% of patients with CD, respectively, would be incorrectly classified as having EAS. For CD versus NNH, 11% of patients with CD would be falsely diagnosed as having NNH, whereas 7% of patients with NNH would be falsely diagnosed as having CD. However, in all hierarchical plots, the prediction intervals were considerably wider than the confidence intervals. This indicates low confidence in the estimated accuracy, and the true accuracy is likely to be different.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=85634, identifier CRD42018085634; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=68317, identifier CRD42017068317.

Abstract Background Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a highly heterogeneous disease with divergent manifestations ranging from asymptomatic subclinical Cushing syndrome (CS) to overt Cushing syndrome with severe complications. ARMC5 mutations occur in 20 to 55% PBMAH patients usually with more severe phenotypes. Different ARMC5 mutations might be associated with diverse phenotypes of PBMAH. Case presentation A 39-year-old man was admitted to our hospital with progressive weight gain and severe hypertension. He presented typical CS and its classical metabolic and bone complications like hypertension and osteoporosis. The laboratory results showed high levels of cortisol and low levels of ACTH. Low- and high-dosed dexamethasone suppression tests were negative. Contrast-enhanced computed tomography (CT) revealed multiple bilateral irregular macronodular adrenal masses. Adrenal venous sampling (AVS) confirmed that the right adrenal gland with larger nodules secreted more hormone that the left side did. Right adrenalectomy and subsequent contralateral subtotal resection were conducted. His blood pressure and CS symptoms as well as comorbidities including backache and muscle weakness improved. Whole exome sequencing identified one ARMC5 germline mutation (c.1855C > T, p. R619*), five ARMC5 somatic mutations (four novel mutations) in his right and left adrenal nodules. Conclusions This PBMAH patient was identified with one ARMC5 germline mutation and five different somatic ARMC5 mutations (four novel mutations) in the different nodules of the bilateral adrenal masses. AVS combined with CT imagine could be helpful to determine the dominant side for adrenalectomy. Genetic testing is important for the diagnosis and management of the patient with PBMAH.

Background: In recent years, left ventricular hypertrophy and cardiac dysfunction have been reported in human and canine patients with hypercortisolism (HAC) and in dogs treated experimentally with high-dose prednisolone. However, to our knowledge, there have been no reports on the effects of hyperglucocorticism (HGC) on the mitral valve (MV). Aim: This study aimed to compare the MV in dogs treated with high-dose prednisolone with that in healthy dogs to investigate the effects of HGC on the MV. Methods: We investigated the effects of HGC on the MV by comparing samples obtained from high-dose glucocorticoid-treated (P) and healthy (C) dogs. The P group included healthy Beagle dogs (n = 6) treated with prednisolone (2 mg/kg, bid, po) for 84 days and the C group included healthy Beagle dogs (n = 6) euthanized for unrelated reasons. The anterior and posterior mitral leaflets (AML and PML, respectively) from both groups were harvested and stained with hematoxylin–eosin, Alcian blue, and Masson trichome. Additionally, adiponectin (ADN) and glucocorticoid receptor immunohistochemistry were performed. Histological evaluation was performed in the atrialis, spongiosa, fibrosa, and all layers of the proximal, middle, and distal regions of the AML and PML. Results: The proportion of the spongiosa layer thickness to the total thickness was higher in the P than in the C group (proximal and middle AML). However, the proportion of the fibrosa layer thickness to the total thickness was lower in the P than in the C group (middle PML). Areas of acidic sulfated mucosubstance deposition were smaller in the fibrosa layer and all layers (middle AML), while those of collagen deposition were smaller in the spongiosa and total layers (proximal and middle AML), in the P than in the C group. Additionally, ADN expression in the spongiosa layer was higher in the P than in the C group (middle AML). Conclusion: These findings suggest that long-term administration of synthetic glucocorticoids induces histological changes in the MV. These changes may lead to MV dysfunction in dogs with HGC. [Open Vet J 2023; 13(2.000): 150-170]

Adrenocortical carcinomas are extremely rare in the paediatric population. Most of them are hormone-secretive lesions; therefore, they should be taken into consideration in a child with signs of precocious puberty and/or Cushing’s syndrome symptoms. Nonetheless, differentiation from benign adrenal tumours is necessary. We report a rare case of adrenocortical carcinoma in a girl and a literature review using the PubMed database. A four-year-old girl presented with rapidly progressing precocious puberty and signs of Cushing’s syndrome. Imaging of the abdomen revealed a large heterogeneous solid mass. Histopathologic evaluation confirmed adrenocortical carcinoma with high mitotic activity, atypical mitoses, pleomorphism, necrosis, and vascular invasion. After tumourectomy, a decrease of previously elevated hormonal blood parameters was observed. Genetic tests confirmed Li Fraumeni syndrome. Adrenocortical carcinoma should be suspected in children with premature pubarche and signs of Cushing’s syndrome. Diagnosis must be based on clinical presentation, hormonal tests, imaging, and histopathological evaluation. Complete surgical resection of the tumour is the gold standard. Oncological treatment in children is not yet well-studied and should be individually considered, especially in advanced, inoperable carcinomas with metastases. Genetic investigations are useful for determining the prognosis in patients and their siblings.

Background: Adrenocortical carcinoma accounts for less than 0.2% of all pediatric malignancies. Virilization is the most common revealing sign, whereas hyperaldosteronism and Cushing syndrome are less common.We report a case of adrenocortical carcinoma which was revealed by Cushing syndrome and successfully treated in an adolescent girl. Case presentation: A female patient of 14 years old was admitted with complaints of progressive abdominal mass. Clinical findings included arterial hypertension (180/110 mmHg), Cushing syndrome, and a left flank mass approximately 10 cm in length. Biologic tests revealed hypercortisolism and hyperandrogenism. Abdominal CT showed a large, well-circumscribed, polylobed left adrenal mass. After contrast injection, there was a heterogeneous enhancement and demarcated areas of liquefaction without visible calcifications. A complete resection of the adrenal gland with lymphadenectomy was performed. The anatomopathological conclusion was a Weisse 6 adrenocortical carcinoma.The ENSAT classification for adrenocortical carcinoma in children was T1N1MO.Post-adjuvant chemotherapy was administered according to the etoposide/doxorubicin/cisplatin + mitotan (EDP-M) protocol in combination with hydrocortisone replacement therapy. Conclusion: Adrenocortical carcinoma is a rare childhood cancer. Cushing syndrome is a rare but potentially serious manifestation. Early treatment with surgical resection and chemotherapy improves the prognosis.

Lung cancer is the deadliest type of cancer in the world, and small cell lung cancer (SCLC) is one of the most fatal types of relevant tumors. The aim of this report was to describe the status of a patient presenting with progressive weakness, who did not have a previous medical history. Clinical examination revealed bilateral edema of the lower limbs. Lab results exhibited severe hypokalemia and metabolic alkalosis. physical examination showed elevated blood pressure. Imaging revealed a large mass with necrosis. Bronchoscopy was done and biopsy pathology showed SCLC. The patient underwent chemotherapy with cisplatin and etoposide. Following SCLC, the patient developed a type of paraneoplastic syndrome called Cushing syndrome. He experienced a severe decrease in saturation in the second session of chemotherapy and eventually died. With respect to the fact that most paraneoplastic syndromes are associated with poor response to treatment, high clinical suspicion is essential for the rapid diagnosis of these syndromes to improve outcomes.

Ectopic adrenocorticotropic hormone syndrome (EAS) is a condition of hypercortisolism caused by non-pituitary tumors that secrete adrenocorticotropic hormone (ACTH). A rare occurrence of this syndrome is due to an ACTH-producing neuroendocrine tumor that originates from the gallbladder. One patient with severe hypokalemia and alkalosis was admitted to our hospital. Clinical presentations and radiographic findings confirmed the diagnosis of an aggressive ACTH-producing gallbladder malignancy with multiple liver metastases. The diagnosis was verified by pathological and immunohistochemical measurements from a biopsy of the hepatic metastasis. A literature review identified only four similar cases had been reported. Despite being rare and having a poor prognosis, hormone-producing neuroendocrine tumors that derive from the gallbladder should be considered in the differential diagnosis of ectopic ACTH syndrome.

Abstract Background Cushing disease (CD) arises due to a pituitary corticotroph adenoma, which is the most common cause of Cushing syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) is a safe method for differentiating CD from ectopic adrenocorticotropic hormone (ACTH)-dependent CS. Enhanced high-resolution magnetic resonance imaging (MRI) can localize tiny pituitary lesions. The aim of this study was to compare the preoperative diagnostic accuracy of BIPSS versus MRI for CD in CS patients. We performed a retrospective study of patients who underwent BIPSS and MRI between 2017 and 2021. Low- and high-dose dexamethasone suppression tests were performed. Blood samples were collected simultaneously from the right and left catheter and femoral vein before and after desmopressin stimulation. MRI images were obtained, and endoscopic endonasal transsphenoidal surgery (EETS) was performed in confirmed CD patients. Dominant sides of ACTH secretion during BIPSS and MRI were compared with surgical findings. Results Twenty-nine patients underwent BIPSS and MRI. CD was diagnosed in 28 patients, 27 of whom received EETS. Localizations of microadenomas by MRI and BIPSS agreed with the EETS findings in 96% and 93% of the cases, respectively. BIPSS and EETS were successfully performed on all patients. Conclusion BIPSS was the most accurate method (gold standard) for establishing a preoperative diagnosis of pituitary-dependent CD and was more sensitive than MRI in diagnosing microadenoma. High-resolution MRI with enhancement had an advantage over BIPSS in microadenoma lateralization diagnostics. The combined use of MRI and BIPSS could improve the preoperative diagnosis accuracy in ACTH-dependent CS patients.

Abstract Background Carney complex (CNC) is a rare multiple endocrine neoplasia syndrome characterized by mucocutaneous lentigines/ blue nevi, cardiac myxoma and endocrine overactivity. Here, we report a CNC case with PRKAR1A gene mutation characterized by left atrial adenomyxoma to explore the diagnosis and treatment of CNC. Case presentation A 42-year-old woman with a history of cardiac tumour surgery presented with typical features of Cushing syndrome, including central obesity, buffalo hump, mild facial plethora, purple striae on the lower abdomen, and spotty skin pigmentation. Left atrial adenomyxoma and thyroid papillary carcinoma were identified by postoperative histologic assays. Genetic screening revealed a pathogenic germline heterozygous mutation of c.682C > T (p.R228X) in exon 7 of the PRKAR1A gene. The clinical features and normal ACTH levels suggest this patient suffered the ACTH-independent primary pigmented nodular adrenocortical disease (PPNAD) with cyclic hypercortisolism or ACTH-dependent Cushing syndrome. Conclusion CNC is uncommon, however, if a patient develops clinical features involving multiple endocrine and non-endocrine tumors, especially Cushing syndrome and cardiac myxoma, CNC should be considered. Genetic analysis is recommended in patients with suspected CNC.

Background/Objective: Adrenal corticomedullary mixed tumor (CMMT) are extremely rare single adrenal tumor masses containing a mixture of adrenal cortical adenoma and pheochromocytoma cells. Case Report: A 52-year-old woman presented with clinical and biochemical evidence of cortisol and catecholamine excess and was found to have an adrenal CMMT with intermixed chromaffin, cortical adenoma, and ganglioneuroma components. She underwent a successful unilateral adrenalectomy with subsequent improvement in her symptoms. Discussion: We report the first case of a patient with a CMMT that had symptoms of both catecholamine and cortisol excess from her tumor. Typically, patients with similar tumors have signs of cortisol excess; however, the pheochromocytoma portion is clinically silent. Although most CMMT contain 2 distinct cell types, this is the third ever described case of a single adrenal CMMT containing 3 unique cellular components: (1) intermixed chromaffin, (2) cortical adenoma, and (3) ganglioneuroma cells. Conclusion: Our understanding of these rare tumors is limited, and this case serves to broaden our knowledge about their clinical, biochemical, and pathologic features.

Cushing's disease, the most common cause of endogenous Cushing's syndrome, is hypercortisolemia caused by adrenocorticotropic hormone-secreting pituitary adenoma. Patients may present clinical symptoms such as moon face, buffalo back, central obesity and metabolic disorders due to the persistence of hypercortisolemia. Accurate diagnosis, appropriate treatment and follow-up of Cushing's disease are vitally important. Based on recent evidence, the Pituitary Society published the Consensus on Diagnosis and Management of Cushing's Disease: a Guideline Update in December 2021, with updates in screening and diagnosis procedures, postoperative monitoring, medical therapies and radiotherapy, and complication management. This article interprets the medical therapies recommended in the consensus, which will be helpful for general practitioners and specialists to standardize the diagnosis and treatment of Cushing's disease.

Background/Objective: Cushing syndrome (CS) is a prothrombotic state associated with an increased risk of postoperative venous thrombosis. We aim to present the case of a patient with Cushing disease who underwent pituitary surgery and subsequently developed acute lower extremity deep venous thromboses after anticoagulation was stopped. Case Report: We present the case of a 57-year-old woman who was admitted for intra-abdominal abscesses after a gastric bypass surgery and was found to have evidence of severe CS. Her 24-hour urinary free cortisol level was 898.6 μg/24 h. She was diagnosed with Cushing disease and underwent transsphenoidal resection of a pituitary adenoma, with an appropriate postoperative drop in the cortisol level. She received thromboprophylaxis during hospitalization; however, this was discontinued upon discharge, on postoperative day 9, because she was ambulating. Five days after hospital discharge and 14 days after her surgery, she developed left lower extremity edema and was found to have 4 deep venous thromboses. Discussion: As previously described, thrombotic risk can be elevated for at least 1 month after surgery for CS, and thromboprophylaxis can decrease this risk. Conclusion: This case highlights the need for clear recommendations for the duration of postoperative thromboprophylaxis in patients with CS. Clinicians should consider continuing thromboprophylaxis for at least 1 month after surgery for CS.

Abstract Background Primary generalized glucocorticoid hypersensitivity (PGGH) is a very rare disease caused by terminal organ hypersensitivity to glucocorticoids for which the aetiology is unknown. The incidence of PGGH is extremely rare, especially in children. To date, the literatures about the etiology, prognosis and treatment of PGGH are scarce. Aim of the study is describing the cases of two Chinese children with infantile-onset PGGH in one family, one of whom died and one who was treated with mifepristone. They are the two youngest children with PGGH reported in the literature. Case presentation Two siblings with infantile-onset PGGH were affected in this family. The main manifestations of patient 1 were typical Cushing’s syndrome-like manifestations, significantly aggravated symptoms after physiological doses of glucocorticoids and very low levels of serum cortisol and adrenocorticotropin hormone (ACTH) during attacks. After being diagnosed with PGGH, he was given guidance to avoid glucocorticoids and took mifepristone therapy for 5 months, and his symptoms improved. Patient 2 was the younger brother of patient 1, with similar manifestations to his brother at the age of 4 months. Patient 2 ultimately died at the age of 9 months. Conclusion PGGH is a very rare disease that can lead to death if not diagnosed and treated in a timely manner. This article describes the cases of the two youngest children with PGGH reported in the literature, one of whom improved after mifepristone treatment, and increases the knowledge of the clinical manifestations of and the treatment experience in PGGH.

Introduction: Cushing's disease (CD) should always be suspected in a pediatric patient with growth delay, excessive weight gain and characteristic phenotype. It is suggested to start the diagnostic protocol sequence: verification of hypercortisolism, production site and images, to finally perform the definitive curative surgical treatment. Case reports: We report three (3) CD patients with altered growth velocity, weight gain and characteristic phenotype. The diagnostic sequence was performed to demonstrate hypercortisolism. CD was subsequently confirmed, and a pituitary nuclear magnetic resonance (NMR) was performed. All patients underwent curative surgery. Conclusion: CD in pediatrics continues to be a diagnostic challenge for the clinician. An approach with high initial clinical suspicion, associated with paraclinical studies and obtaining the adequate images, are necessary to make an accurate diagnosis and a definitive curative treatment.

Abstract Background McCune–Albright syndrome is a complex disorder encompassing multiple endocrinopathies. These manifestations are secondary to a mutation in the stimulatory G-protein alpha subunit. Cushing syndrome is due to autonomous secretory function of the adrenal gland and is present in 7.1% of patients with McCune–Albright syndrome. Cardiac newborn screenings assist in the identification of critical congenital heart disease. These screenings have become part of routine postnatal care nationwide. Case report A 6-week-old Caucasian male presented to a cardiologist at the University of Tennessee Health Science Center with left ventricular hypertrophy and poor feeding after a failed cardiac newborn screen. He had been previously seen at 2 weeks by a cardiologist on follow-up for abnormal critical congenital heart disease screening. Electrocardiogram and echocardiographic studies identified hypertrophic cardiomyopathy. Other examination findings revealed multiple characteristic café-au-lait lesions along with hypotonia and rounded facies. Given his cardiac disease, he was admitted to the hospital, where an evaluation was done for Cushing syndrome, showing elevated cortisol by immunoassay of 38 μg/dL (1.7–14.0 μg/dL, Vitros 5600) after a dexamethasone suppression test and urinary cortisol elevated to 35 μg/dL/24 hours (reference range 3–9 μg/dL/24 hours) (Esoterix; Calabasas, CA). He was started on metyrapone therapy to block synthesis of cortisol. His cortisol improved and was suppressed less than 2 μg/dL. His hypertension and clinical features of Cushing syndrome improved. Conclusions This case demonstrates a unique presentation of Cushing syndrome in a young infant. This is the first case to our knowledge showing significant left ventricular hypertrophy resulting from Cushing syndrome identified following a failure on a critical congenital heart disease screen. It highlights the importance of considering of McCune–Albright syndrome in patients with Cushing syndrome, especially if other clinical features are present. Medical therapy can be used to treat Cushing syndrome and can result in improvement in the cardiovascular pathology.

Abstract Dietary supplement use is common in the United States. Supplements are regulated by the US Food and Drug Administration (FDA) under a separate set of guidelines from typical food and drug products. This case report describes a patient who presented to the emergency department (ED) with abdominal pain, vomiting, and generalized weakness. On detailed history, we learned that he had been taking a supplement called Artri Ajo King for 18 months, followed by recent abrupt cessation before his ED presentation. He was subsequently found to have a low serum cortisol level and was diagnosed with secondary adrenal insufficiency by a cosyntropin stimulation test. Ultimately, he was started on hydrocortisone with resolution of his symptoms. This case illustrates the consequence of allowing dietary supplements to be sold before FDA evaluation as well as the importance of physicians eliciting history of supplement use and offering a culturally competent discussion with their patients regarding supplement use.

A rare condition called Cushing disease causes increased morbidity or mortality. Therapeutic methods such as anti-cortisol medications, bilateral adrenalectomy, or radiation procedures may therefore be required to prevent long-term dangers of hypercortisolism, such as hirsutism, moon face, facial plethora, and obesity. Endogenous hypercortisolism increases the risk of cardiovascular metabolic symptoms, osteoporosis, respiratory diseases, psychological difficulties, and infections while also having a high rate of morbidity or mortality. Significant fetal and mental complications during pregnancy are linked to Cushing syndrome. Early detection and treatment are essential. Except in the late trimester, surgery is the preferred method of treatment for Cushing syndrome during pregnancy, with medication therapy as a backup. Cushing syndrome is an endocrine illness that presents differently from other endocrine disorders, making it difficult for doctors to control.

IntroductionAlcohol-induced hypercortisolism (AIH) is underrecognized and may masquerade as neoplastic hypercortisolism [Cushing syndrome (CS)] obscuring its diagnosis.Objective and methodsIn order to characterize AIH, we performed a chart review of eight patients (4 males and 4 females; 2014-2022) referred for evaluation and treatment of neoplastic hypercortisolism — six for inferior petrosal sinus sampling, one due to persistent CS after unilateral adrenalectomy, and one for pituitary surgery for Cushing disease (CD). Five underwent dDAVP stimulation testing.ResultsAll eight patients had clinical features of hypercortisolism and plasma ACTH levels within or above the reference interval confirming hypothalamic-pituitary mediation. All had abnormal low-dose dexamethasone suppression test and increased late-night salivary cortisol. Only one had increased urine cortisol excretion. In contrast to CD, the 5 patients tested had blunted or absent ACTH and cortisol responses to desmopressin. Two had adrenal nodules and one had abnormal pituitary imaging. Most patients underreported their alcohol consumption and one denied alcohol use. Elevated blood phosphatidyl ethanol (PEth) was required in one patient to confirm excessive alcohol use. All patients had elevations of liver function tests (LFTs) with AST>ALT.ConclusionAIH is an under-appreciated, reversible cause of non-neoplastic hypercortisolism that is indistinguishable from neoplastic CS. Incidental pituitary and adrenal imaging abnormalities as well as under-reporting of alcohol consumption further confound the diagnosis. Measurement of PEth helps to confirm an alcohol use disorder. Elevations of LFTs (AST>ALT) and subnormal ACTH and cortisol responses to dDAVP help to distinguish AIH from neoplastic hypercortisolism.

Cushing disease, the most common cause of endogenous Cushing's syndrome characterized by hypercortisolemia, is a clinical syndrome caused by adrenocorticotropic hormone (ACTH) ——secreting pituitary adenomas. The excessive secretion of ACTH in Cushing's disease stimulates bilateral adrenal hyperplasia and causes hypercortisolemia, which can lead to a series of severe clinical syndromes such as electrolyte imbalance, glucose and lipid metabolism disorders, involving multiple organs and systems in the body. The clinical symptoms of Cushing's disease are complex and diverse, and its diagnosis and treatment are extremely challenging. In December 2021, the International Pituitary Society released the Consensus on Diagnosis and Management of Cushing's Disease: a Guideline Update, which focuses on the complications and comorbidities of Cushing's disease, such as hypercoagulability, cardiovascular disease, metabolic bone disease, growth hormone deficiency and infection, etc.; discusses the application of the latest evidence in clinical practice, with a particular focus on new treatment and screening options, diagnostic algorithms, and best practices for preventing disease recurrence. Based on the latest evidence-based medical evidence, this article focuses on the interpretation of Cushing's disease——related laboratory examinations, imaging examinations, diagnosis and treatment management procedures, and recurrence monitoring discussed in the Consensus on Diagnosis and Management of Cushing's Disease: a Guideline Update, in order to improve the general practitioners and specialists'understanding of this syndrome and improve the prognosis of patients with Cushing's disease.

Abstract Background Distinguishing between a pituitary adenoma and a pituicytoma can be challenging. Hormonal changes in pituicytomas are uncommon, and the tumor's mass effect has triggered most symptoms. There were only two reported cases of pituicytoma with elevated hormonal levels in patients who presented with Cushing syndrome as of 2017. Case presentation This report describes a rare case of a patient who had Cushing syndrome from a pituitary-related hypercortisolism, most likely a pituicytoma with neuroendocrine features with the benefit of early detection and surgical resection. Conclusions Pituicytomas have malignant tendencies while pituitary adenomas are mostly benign, hence the need to distinguish them accurately for prompt treatment and improved prognosis.

Abstract Background Ewing sarcoma/primitive neuroectodermal tumor (PNET) of the renal is extremely rare. The common cause of ectopic ACTH syndrome is pulmonary neuroendocrine tumors, such as small cell carcinomas and carcinoid tumors. Here, we present an unusual case of ectopic ACTH syndrome and hypothyroidism caused by Ewing sarcoma/PNET of the right kidney. Case presentation A 19-year-old girl presented with a history of right lumbar pain and discomfort for 2 months, aggravated for 2 days. Abdominal contrast-enhanced computed tomography and computed tomography angiography showed an upper pole occupancy of the right kidney occupancy with subepithelial hemorrhage. Preoperative hormone levels including plasma total cortisol (PTC), adrenocorticotrophic hormone (ACTH) and thyroid hormone measurements were abnormal, indicating that the patient had Cushing syndrome and hypothyroidism. The patient underwent right radical nephrectomy. Histopathological analysis revealed a renal small round blue cell tumor (consistent with a primitive neuroectodermal tumor), with positive immunohistochemistry for CD99 and Ki67 (about 10%) and molecular pathology for EWSR1 gene fusions. PTC, ACTH and thyroid hormone returned to normal after surgery. Conclusions We report a rare ectopic ACTH syndrome and hypothyroidism due to renal Ewing sarcoma/PNET. The clinical manifestation of renal Ewing sarcoma/PNET is non-specific and the diagnosis relies on pathological morphology, immunohistochemistry and fusion gene detection. At present, surgery combined with radiotherapy and chemotherapy is used in the treatment, but the prognosis is still not optimistic.

Amaç: Birçok hastalığın ve kanserlerin biyolojik mekanizmalarının incelenmesinde yaygın olarak kullanılan proteomik yaklaşımlar, hastalık sürecinin izlenmesinde, biyobelirteçlerin ve potansiyel terapötik hedeflerin tanımlanmasında kullanılagelmektedir. Proteomik alanında kullanılan biyolojik örnekler arasında serum gibi biyolojik sıvılar ve doku gibi katı örnekler sayılabilir. Bu bağlamda analiz edilen doku örneklerinin kalitesi, örneğin alındığı bölgenin doğruluğu ve hatta örneğin alınmasından sonra proteomik araştırma laboratuarına ulaşıncaya kadar geçen süre gibi pre-analitik süreçler çok önemlidir. Biz bu çalışmamızda, tümör dokusu içerisinde iki farklı bölgeden alınan örneklerin çözünür proteom profillerini karşılaştırmayı ve varsa tümör heterojenitesini göstermeyi amaçladık. Gereç ve Yöntemler: Cushing sendromu tanısı ile opere edilen bir hastanın adrenokortikal tümör dokusunun iki farklı bölgesinden (adenoma ve adenoma içi) ve sağlıklı dokusundan elde edilen proteinler 2DE yöntemi ile ayrıştırılarak karşılaştırmalı analize tabi tutulmuştur. Örnekler arasında regülasyon düzeyinde farklılık görülen protein sayısı belirlenmiş ve jellerden kesilerek MALDI-TOF/TOF kütle spektrometresi aracılığı ile tanımlanmıştır. Bulgular: Kontrol dokusuna göre adenom bölgesinde 17 protein, adenom içi bölgede ise 13 proteinin seviyelerinde regülasyon tespit edilmiştir. Bu proteinler çoğu enerji metabolizması, hücre iskeleti organizasyonu ve hücresel stres ile ilişkili proteinlerdir. Sonuç: Bu çalışma tümör dokusu içerisinde örneğin alındığı bölgenin proteom profilini ne ölçüde etkilediğini göstermiştir. Tümör dokusundan iki farklı bölgeden aldığımız örneklerde daha çok enerji metabolizması ile ilişkili proteinler olmak üzere bazı proteinlerin ifadelerinde ciddi farklılıklar görülmüştür. Bu durum özellikle biyobelirteç arayışlarının olduğu çalışmalarda proteomik bulgularının yorumlanmasında dikkat edilmesi gerektiği ve proteomik çalışmalarında örnek sayısının mümkün olduğunca fazla tutulması gerektiğini vurgulamaktadır.

Abstract Background Ectopic Cushing syndrome (ECS) is a sporadic condition. Even uncommon is an ECS that derives from a carcinoid tumor of the thymus. These tumors may pose several diagnostic and therapeutic conundrums. This report discusses the differential diagnosis, clinicopathological findings, and effective treatment of a rare case of ECS using a minimally invasive approach. Case presentation A 29-year-old woman with Cushing syndrome presented with facial flushing. Physical examination revealed hypertension (blood pressure: 141/100 mmHg). A mediastinal tumor was discovered to be the cause of the patient’s chronic hypokalemia and hypercortisolemia. Cortisol levels increased in the morning, reaching 47.7 ug/dL. The levels of the hormones ACTH, aldosterone, and renin were determined to be 281 pg/mL, 3.0 ng/dL, and 2.1 pg/mL, respectively. The presence of hypertension, hypokalemia, and alkalinity suggested Cushing’s syndrome, which was proven to be ACTH-dependent ECS by a dexamethasone suppression test. A chest CT scan revealed inflammation in the posterior basal region of the right lower lobe. The superior anterior mediastinum was characterized by round-shaped isodensity lesions with distinct borders. She underwent thoracoscopic anterior mediastinal tumor excision via the subxiphoid technique (R0 resection); following surgery, her blood pressure returned to normal, and the hypernatremia/hypopotassemia resolved. The tumor was determined to be a thymic carcinoid. Most notably, cortisol levels fell to half of their presurgical levels after one hour of surgery, and other abnormalities corrected substantially postoperatively. Conclusion Thoracoscopic excision of thymic tumors by subxiphoid incision may be a useful treatment option for ECS caused by neuroendocrine tumors of the thymus

BackgroundDifferentiating between adrenal Cushing syndrome (adrenal CS) and Cushing disease (CD) can be challenging if there are equivocal or falsely elevated adrenocorticotropic hormone (ACTH) values. We aim to investigate the diagnostic value of serum steroid profiles in differentiating adrenal CS from CD.MethodA total of 11 serum steroids in adrenal CS (n = 13) and CD (n = 15) were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Age- and gender-specific steroid ratios were generated by dividing the actual steroid concentration by the upper limit of the relevant reference range. A principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) were performed.ResultsThe PCA and OPLS-DA analyses showed distinct serum steroid profiles between adrenal CS and CD. Dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), and androstenedione ratios were identified as biomarkers for discrimination by variable importance in projection (VIP) in combination with t-tests. The sensitivity and specificity of DHEA-S ratios

Diagnosing and treating secondary psychiatric symptoms with accuracy can be challenging in clinical settings. In this case study, we report on a female patient with Cushing’s disease who was misdiagnosed with anxiety disorder during her first psychiatric visit. Following initial ineffective psychiatric intervention, unexplained hypokalemia, and hypothyroidism, the patient visited the endocrinology clinic and was diagnosed with Cushing’s disease. During the medical and surgical procedures that followed, high doses of psychotropic medication were continued to treat persisting anxiety. After discharge, the patient developed autonomic dysfunction and impaired consciousness. Upon readmission, serotonin syndrome due to inappropriate psychiatric medication was diagnosed. The management of secondary psychiatric syndromes must be adapted to changes in the patient’s primary condition, which necessitates interdisciplinary collaboration in general hospital settings.

Abstract Background To perform genetic screening for ARMC5 gene germline pathogenic variants in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH). Subjects and Methods In a group of 10 PBMAH patients, we performed complete sequencing of the coding region of the ARMC5 gene and MLPA analysis for large deletion detection. In subjects with the ARMC5 variant, we searched ARMC5 gene somatic variants on tumor samples. Results Among 10 PBMAH patients, we identified four ARMC5 germline variants (40%). One variant, c:174dupC p.Glu59Argfs*44, was already known; one variant p.Gly323Asp, was already reported and classified as likely disease‐causing VUS (class 3–4); two variants p.Leu596Arg and p.Arg811Pro, were never reported before. For p.Gly323Asp and p.Arg811Pro, we identified second deleterious variants at the somatic level, enforcing the possible pathogenic effect of germline variants. Conclusions Our results underscore the importance of performing genetic testing also in sporadic PBMAH patients and broaden the spectrum of molecular variants involved in PBMAH syndrome.

Cushing's disease is caused by excessive secretion of adrenocorticotropic hormone (ACTH) by hormone-secreting pituitary adenomas, the first-choice treatment for which is surgical resection of the pituitary adenoma. Medication therapy is the second-line treatment, and a necessary treatment for some patients with unsatisfactory surgical results or failing to use the surgery. With recent developments in pathogenesis studies of Cushing's disease, medications specifically targeting hormone-secreting pituitary adenomas have proven to be effective in controlling the tumor growth, and suppressing the tumor's secretion of ACTH, which may be a theoretical and practical basis for medical treatment of Cushing's disease. In this review, we discussed pituitary-directed medical therapies for Cushing's disease and their mechanisms of actions, aiming to increase medical workers' understanding of this disease, and to offer theoretical evidence for the development of appropriate treatment strategies.

Carney complex is a disease characterized by skin lesions, endocrine, cardiac, gonadal and other organ tumors, associated with mutations of the PRKAR1A gene. We present the clinical case of a patient with several of the most characteristic manifestations of this syndrome. Finally, there will be a review of the literature.

Cushing syndrome (CS) is a rare disease caused by hypercortisolemia. Although surgical treatment is the first-line treatment in CS, the appropriate medication for the patient's condition should be selected when medical treatment is needed. Etomidate is an adrenal-blocking drug used to treat CS and the most suitable for severe hypercortisolemia and adrenocortical carcinoma (ACC), due to cardiovascular stability and an anti-tumorigenic effect. However, its use and safe recommended dosage in infants with CS is unreported. Here we describe the case of a 2-month-old girl treated with etomidate for CS caused by ACC. Even though radical mass excision was performed, severe hypercortisolemia persisted, resulting from metastatic lesions in the liver, and medical treatment was considered. The etomidate doses, no bolus dose and infusion rate of 0.03 mg/kg/hour, may be an appropriate dose for severe hypercortisolemia in infants. This case will help determine future treatment strategies for similar cases in infants.