Clinical respiratory and radiographic abnormalities in dogs with spontaneous hypercortisolism.

The objective of this study was to characterize respiratory clinical signs, other than panting and respiratory distress, as well as thoracic radiographic abnormalities, in dogs with hypercortisolism. Although there have been case reports and studies evaluating the results of pulmonary scintigraphy, no studies have yet reviewed respiratory clinical signs and radiograph results in dogs with hypercortisolism. This study addresses this gap. A case series was evaluated and the dogs' clinical histories were obtained, including clinical signs and physical examination. Digital thoracic radiographs were analyzed to consider such parameters as the diameter of the main bronchi, lung patterns, and the size of the pulmonary trunk. The most common respiratory symptoms were snoring (61.9%), coughing (57.1%), and fatigue (52.4%). Physical examination revealed a high frequency of changes on lung auscultation (95.2%). The body condition score (BCS) was high in 95% of dogs and a significant correlation was observed between the presence of cyanosis and changes in lung auscultation, both of which present similar risk factors. Furthermore, body weight showed a moderate correlation with respiratory rate (RR = 0.571). Radiographic changes were evident in 47.5% of dogs, with the bronchial pattern being the most common (70%). Based on these results, it was observed that respiratory and radiographic abnormalities are frequent in dogs with spontaneous hypercortisolism and a high body condition score was relevant for exacerbating clinical respiratory signs, such as cyanosis and tachypnea.

L'objectif de cette étude était de caractériser les signes cliniques respiratoires, autres que le halètement et la détresse respiratoire, ainsi que les anomalies radiographiques thoraciques, chez les chiens atteints d'hypercortisolisme. Bien qu'il existe des rapports de cas et des études évaluant les résultats de la scintigraphie pulmonaire, aucune étude n'a encore examiné les signes cliniques respiratoires et les résultats radiographiques chez les chiens atteints d'hypercortisolisme. Cette étude comble cette lacune. Une série de cas a été évaluée et les antécédents cliniques des chiens ont été obtenus, incluant les signes cliniques et l'examen physique. Des radiographies thoraciques numériques ont été analysées pour prendre en compte des paramètres tels que le diamètre des bronches principales, les schémas pulmonaires et la taille du tronc pulmonaire. Les symptômes respiratoires les plus courants étaient le ronflement (61,9 %), la toux (57,1 %) et la fatigue (52,4 %). L'examen physique a révélé une fréquence élevée de changements à l'auscultation pulmonaire (95,2 %). Le score d'état corporel (BCS) était élevé chez 95 % des chiens et une corrélation significative a été observée entre la présence de cyanose et les modifications de l'auscultation pulmonaire, qui présentent toutes deux des facteurs de risque similaires. De plus, le poids corporel a montré une corrélation modérée avec la fréquence respiratoire (RR = 0,571). Des changements radiographiques étaient évidents chez 47,5 % des chiens, le schéma bronchique étant le plus courant (70 %). Sur la base de ces résultats, il a été observé que les anomalies respiratoires et radiographiques sont fréquentes chez les chiens atteints d'hypercortisolisme spontané, et qu'un score d'état corporel élevé était pertinent pour l'exacerbation des signes respiratoires cliniques, tels que la cyanose et la tachypnée.(Traduit par Docteur Serge Messier).

Ectopic Cushing Syndrome Localized by 68 Ga-DOTA-LM3 PET/CT.

ABSTRACT: A 53-year-old woman presented with signs of Cushing syndrome with challenges in diagnosis and localization. A novel somatostatin receptor (SSTR)-targeted PET/CT with 68 Ga-DOTA-LM3, an SSTR antagonist, revealed a suspicious focal finding in the pancreatic head, proven to be ectopic Cushing syndrome after surgical resection. This interesting image clearly shows the potential of PET imaging with SSTR antagonists as 68 Ga-DOTA-LM3 in the diagnosis of ectopic Cushing syndrome.

Left ventricular subclinical systolic myocardial dysfunction assessed by speckle-tracking in patients with Cushing's syndrome.

PURPOSE: Two-dimensional speckle tracking echocardiography is a novel ultrasound technique, which can detect early subclinical myocardial dysfunction with high sensitivity. The purpose of this study was to explore the value of speckle tracking echocardiography in the evaluation of subclinical myocardial injury in patients with Cushing's syndrome. METHODS: 35 patients with Cushing's syndrome and 29 healthy controls matched for age, sex, BMI, and systolic blood pressure were included in the study. All subjects were assessed using both conventional Doppler echocardiography and speckle tracking echocardiography. Among patients, they were further divided into inactive group (n = 7) and active group (n = 28) based on cortisol levels. Trend analysis was used among patients in different disease activity. Correlation analysis and linear regression analysis were used to explore influence factors related to subclinical myocardial dysfunction. RESULTS: Left ventricular ejection fraction value showed no statistical difference between patients Cushing's syndrome and control group. However, GLS and LVSD, show significant differences in Cushing's syndrome group. Also, among active Cushing's syndrome group, inactive Cushing's syndrome group and control group, GLS (-15.4 ± 3.0 vs -18.1 ± 3.1 vs-19.4 ± 2.4, P < 0001) and LVSD (48.9 ± 21.5 vs 43.5 ± 17.9 vs 28.5 ± 8.3, P < 0001) changed significantly with the disease activity status. In addition, GLS and LVSD were both linearly corrected with 24-hour urinary cortisol level. CONCLUSION: GLS and LVSD are sensitive parameters in detecting and monitoring subclinical myocardial systolic dysfunction in patients with Cushing's syndrome. Myocardial injury is linearly correlated with cortisol level, which can be partially reversed after the biochemical control of cortisol.

68Ga-pentixafor PET/CT in the localization diagnosis of primary aldosteronism concurrent subclinical cushing's syndrsome: two case reports.

PURPOSE: Adrenal venous sampling (AVS) is recommended for subtyping primary aldosteronism (PA). However, in cases of PA, concurrent subclinical Cushing's syndrome (SCS) has the potential to confound AVS results. Pentixafor, a CXC chemokine receptor type 4-specific ligand, has been reported as a promising marker to evaluate functional nature of adrenal adenomas. This study aims to investigate the clinical value of Gallium-68 Pentixafor Positron Emission Tomography-Computed Tomography (68Ga-Pentixafor PET/CT) in the localization diagnosis of patients with PA plus SCS. METHODS: Two patients with a confirmed diagnosis of PA plus SCS underwent AVS and 68Ga-Pentixafor PET/CT. RESULTS: AVS results revealed no lateralization for both patients while 68Ga-Pentixafor PET/CT showed a unilateral adrenal nodule with increased uptake of 68Ga-Pentixafor. Unilateral adrenalectomy was performed based on the results of 68Ga-Pentixafor PET/CT. Subsequently, complete biochemical remission of autonomous aldosterone and cortisol secretion were achieved in both cases. CONCLUSIONS: 68Ga-Pentixafor PET/CT shows promising potential for the localization of aldosterone and cortisol co-secreting adrenal adenoma in patients with PA plus SCS.

Clinical and imaging presentations are associated with function in incidental adrenocortical adenomas: a retrospective cohort study.

OBJECTIVE: The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs). DESIGN: This is a single-center cohort study. METHODS: Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016. RESULTS: Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 µg/dL, P = .002). CONCLUSIONS: Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.

Cardiac magnetic resonance reveals biventricular impairment in Cushing's syndrome: a multicentre case-control study.

PURPOSE: Cushing's syndrome (CS) is associated with severe cardiovascular (CV) morbidity and mortality. Cardiac magnetic resonance (CMR) is the non-invasive gold standard for assessing cardiac structure and function; however, few CMR studies explore cardiac remodeling in patients exposed to chronic glucocorticoid (GC) excess. We aimed to describe the CMR features directly attributable to previous GC exposure in patients with cured or treated endogenous CS. METHODS: This was a prospective, multicentre, case-control study enrolling consecutive patients with cured or treated CS and patients harboring non-functioning adrenal incidentalomas (NFAI), comparable in terms of sex, age, CV risk factors, and BMI. All patients were in stable condition and had a minimum 24-month follow-up. RESULTS: Sixteen patients with CS and 15 NFAI were enrolled. Indexed left ventricle (LV) end-systolic volume and LV mass were higher in patients with CS (p = 0.027; p = 0.013); similarly, indexed right ventricle (RV) end-diastolic and end-systolic volumes were higher in patients with CS compared to NFAI (p = 0.035; p = 0.006). Morphological alterations also affected cardiac function, as LV and RV ejection fractions decreased in patients with CS (p = 0.056; p = 0.044). CMR features were independent of metabolic status or other CV risk factors, with fasting glucose significantly lower in CS remission than NFAI (p < 0.001) and no differences in lipid levels or blood pressure. CONCLUSION: CS is associated with biventricular cardiac structural and functional impairment at CMR, likely attributable to chronic exposure to cortisol excess independently of known traditional risk factors.

Cushing's syndrome diagnosed incidentally on CT imaging.

In this case report, we describe an uncommon presentation of Cushing's syndrome in a patient in their 60s who presented to the emergency department with left-sided chest pain. The initial workup for the patient was unremarkable except for an elevated blood pressure and elevated fasting plasma glucose. A CT scan of the chest, abdomen and pelvis was performed, demonstrating a splenic artery thrombus with multiple splenic infarcts, in addition to a combination of macronodular adrenal hyperplasia, bilateral gynecomastia, centripetal fat distribution and suspected mild bone demineralisation. Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia, a rare aetiology responsible for Cushing's syndrome, was raised as a potential unifying diagnosis for the patient's hypercoagulable status, which was subsequently confirmed on an endocrinological investigation. The case report underscores the importance of communicating clinically relevant details to the imaging specialist in combination with considering a broad differential, including endocrine disorders, when evaluating an undifferentiated patient with atypical imaging findings.

[Diagnostic value of bilateral inferior petrosal sinus sampling in various modifications and methods of radiation and radionuclide imaging in the diagnosis and differential diagnosis of ACTH-dependent endogenous hypercortisolism].

AIM: To analyze the diagnostic performance of bilateral inferior petrosal sinus sampling (BIPSS) with desmopressin as a stimulation agent and prolactin measurements to control catheter position with or without the ACTH/prolactin normalized ratio calculation in the differential diagnosis of ACTH-dependent endogenous hypercortisolism, and the diagnostics performance of ectopic ACTH-syndrome (EAS) visualization. MATERIALS AND METHODS: A single-center diagnostic study with a retrospective analysis of the data was carried out. The study included patients with ACTH-dependent endogenous hypercorticism with no visualization of pituitary adenoma on MRI or adenoma sizes less than 6 mm. All patients underwent BIPSS with and without calculation of the ACTH/prolactin normalized ratio. Visualization of an EAS included pituitary MRI (to exclude EAS), whole-body CT scan with contrast, and somatostatin receptor scintigraphy with 99mTc-Tectrotide and CT (99mTc-Tectrotide SPECT). The final verification was based on immunohistochemical confirmation of the tumor or stable remission of Cushing's disease (CD) after surgical treatment. Statistical data processing was carried out by using IBM SPSS Statistics 23. Confidence intervals were calculated using the JavaStat online calculator. RESULTS: 230 BIPSS were performed in 228 patients (166 women, 62 men), of which 178 patients were verified as CD and 50 cases were EAS of various localization. The effectiveness of catheterization of petrosal sinuses was 96.9%. The sensitivity of BIPSS without ACTH/prolactin ratio calculation (n=70) was 95.9% (95% CI 86.3-98.9), specificity was 92% (95% CI 75.0-97.8), for the BIPSS with additional determination of ACTH/prolactin-normalized ratio (n=51) - 97.3% (95% CI 86.2-99.5) and 93.8% (95% CI 71.7-98.9), respectively. The use of the MRI method for this sample of patients had a sensitivity of 60.2% (95% CI 52.6-67.5), specificity of 59.2% (95% CI 44.2-73.0), the total body CT with contrast has a sensitivity of 74% (95% CI 59.7-85.4), specificity of 100% (95% CI 97.95-100). The diagnostic accuracy for 99mTc-Tectrotide SPECT in NET visualization has a sensitivity of 73.3% (95% CI 44.9-92.2), specificity of 100% (95% CI 95.3-100). CONCLUSION: BIPSS with desmopressin stimulation and prolactin measurements to control catheter position, as well as the additional calculation of the ACTH/prolactin-normalized ratio, is an optimal method for the differential diagnosis of EAS. Patients who are identified an EAS on BIPSS may be further referred for 99mTc-Tectrotide SPECT and CT for tumor visualization.

Evaluation of bone-related mechanical properties in female patients with long-term remission of Cushing's syndrome using quantitative computed tomography-based finite element analysis.

BACKGROUND: Hypercortisolism in Cushing's syndrome (CS) is associated with bone loss, skeletal fragility, and altered bone quality. No studies evaluated bone geometric and strain-stress values in CS patients after remission thus far. PATIENTS AND METHODS: Thirty-two women with CS in remission (mean age [±SD] 51 ± 11; body mass index [BMI], 27 ± 4 kg/m2; mean time of remission, 120 ± 90 months) and 32 age-, BMI-, and gonadal status-matched female controls. Quantitative computed tomography (QCT) was used to assess volumetric bone mineral density (vBMD) and buckling ratio, cross-sectional area, and average cortical thickness at the level of the proximal femur. Finite element (FE) models were generated from QCT to calculate strain and stress values (maximum principal strain [MPE], maximum strain energy density [SED], maximum Von Mises [VM], and maximum principal stress [MPS]). Areal BMD (aBMD) and trabecular bone score (TBS) were assessed by dual-energy X-ray absorptiometry (2D DXA). RESULTS: Trabecular vBMD at total hip and trochanter were lower in CS as compared with controls (P < .05). Average cortical thickness was lower, and buckling ratio was greater in CS vs controls (P < .01). All strain and stress values were higher in CS patients vs controls (P < .05). 2D DXA-derived measures were similar between patients and controls (P > .05). Prior hypercortisolism predicted both VM (ß .30, P = .014) and MPS (ß .30, P = .015), after adjusting for age, BMI, menopause, delay to diagnosis, and duration of remission. CONCLUSIONS: Women with prior hypercortisolism have reduced trabecular vBMD and impaired bone geometrical and mechanical properties, which may contribute to an elevated fracture risk despite long-term remission.

An Overlooked Manifestation of Hypercortisolism: Cerebral Cortical Atrophy and Challenges in Identifying the Etiology of Hypercortisolism - A Report of 2 Pediatric Cases.

INTRODUCTION: Endogenous Cushing's syndrome (CS) is a rare, severe disease that can cause multiple systemic involvements and behavioral problems due to excessive cortisol production. Structural changes can be noted in the brain magnetic resonance imaging (MRI) scans of these cases. CASES: A 9-year-old girl and a 13-year-old boy were admitted with hypercortisolism. In the female patient, altered consciousness was prominent along with cerebral and cerebellar brain atrophy, and findings indicating posterior reversible encephalopathy syndrome were detected in the brain MRI. Although the male patient's neurological examination was normal, significant cerebral atrophy was seen in the brain MRI. Case 1 was diagnosed as having ectopic ACTH syndrome (EAS) due to a thymic carcinoid tumor. Case 2 underwent a pulmonary lobectomy upon detection of a bronchial lesion in the Ga-68 DOTATATE PET/CT scan while being examined for EAS due to a lack of suppression in the high-dose dexamethasone suppression test. However, hypercortisolism persisted despite the removal of the bronchial lesion, and subsequently, a diagnosis of Cushing's disease was established following bilateral inferior petrosal sinus sampling. DISCUSSION: Endogenous hypercortisolism may cause brain atrophy of varying severity. The central nervous system findings can be overlooked in children with CS. More comprehensive studies are needed to better understand the behavioral changes caused by the effects on the brain and to evaluate whether these changes are reversible. In addition, identifying the source of hypercortisolism can be difficult due to a lack of experience related to the rarity of the disease in children.

Cardiac disease in Cushing's syndrome. Emphasis on the role of cardiovascular magnetic resonance imaging.

BACKGROUND: Cushing's Syndrome (CS) is associated with increased cardiovascular morbidity and mortality. In endogenous CS, cardiovascular mortality remains increased for up to 15 years post remission of hypercortisolism. Similarly, patients with exogenous CS have 4-fold increased incidence of cardiovascular events, regardless of pre-existing cardiovascular disease (CVD). OBJECTIVE: To present the pathophysiology, prognosis, clinical and imaging phenotype of cardiac disease in CS. METHODS: A Pubmed search for cardiac disease in CS over the last 20 years was conducted using combinations of relevant terms. Preclinical and clinical studies, as well as review papers reporting on subclinical heart failure (HF), cardiomyopathy, coronary heart disease (CHD), and cardiovascular imaging were selected. RESULTS: Cardiac disease in CS is associated with direct mineralocorticoid and glucocorticoid receptor activation, increased responsiveness to angiotensin II, ectopic epicardial adiposity, arterial stiffness and endothelial dysfunction, as well as with diabetes mellitus, hypertension, hyperlipidemia, obesity and prothrombotic diathesis. Subclinical HF and cardiomyopathy are principally related to direct glucocorticoid (GC) effects and markedly improve or regress post hypercortisolism remission. In contrast, CHD is related to both direct GC effects and CS comorbidities and persists post cure. In patients without clinical evidence of CVD, echocardiography and cardiac magnetic resonance (CMR) imaging reveal left ventricular hypertrophy, fibrosis, diastolic and systolic dysfunction, with the latter being underestimated by echocardiography. Finally, coronary microvascular disease is encountered in one third of cases. CONCLUSION: Cardiovascular imaging is crucial in evaluation of cardiac involvement in CS. CMR superiority in terms of reproducibility, operator independency, unrestricted field of view and capability of tissue characterisation makes this modality ideal for future studies.

Emerging diagnostic methods and imaging modalities in cushing's syndrome.

Endogenous Cushing's syndrome (CS) is a rare disease characterized by prolonged glucocorticoid excess. Timely diagnosis is critical to allow prompt treatment and limit long-term disease morbidity and risk for mortality. Traditional biochemical diagnostic modalities each have limitations and sensitivities and specificities that vary significantly with diagnostic cutoff values. Biochemical evaluation is particularly complex in patients whose hypercortisolemia fluctuates daily, often requiring repetition of tests to confirm or exclude disease, and when delineating CS from physiologic, nonneoplastic states of hypercortisolism. Lastly, traditional pituitary MRI may be negative in up to 60% of patients with adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (termed "Cushing's disease" [CD]) whereas false positive pituitary MRI findings may exist in patients with ectopic ACTH secretion. Thus, differentiating CD from ectopic ACTH secretion may necessitate dynamic testing or even invasive procedures such as bilateral inferior petrosal sinus sampling. Newer methods may relieve some of the diagnostic uncertainty in CS, providing a more definitive diagnosis prior to subjecting patients to additional imaging or invasive procedures. For example, a novel method of cortisol measurement in patients with CS is scalp hair analysis, a non-invasive method yielding cortisol and cortisone values representing long-term glucocorticoid exposure of the past months. Hair cortisol and cortisone have both shown to differentiate between CS patients and controls with a high sensitivity and specificity. Moreover, advances in imaging techniques may enhance detection of ACTH-secreting pituitary adenomas. While conventional pituitary MRI may fail to identify microadenomas in patients with CD, high-resolution 3T-MRI with 3D-spoiled gradient-echo sequence has thinner sections and superior soft-tissue contrast that can detect adenomas as small as 2 mm. Similarly, functional imaging may improve the identification of ACTH-secreting adenomas noninvasively; Gallium-68-tagged corticotropin-releasing hormone (CRH) combined with PET-CT can be used to detect CRH receptors, which are upregulated on corticotroph adenomas. This technique can delineate functionality of adenomas in patients with CD from patients with ectopic ACTH secretion and false positive pituitary lesions on MRI. Here, we review emerging methods and imaging modalities for the diagnosis of CS, discussing their diagnostic accuracy, strengths and limitations, and applicability to clinical practice.

Iliopsoas muscle to visceral fat ratio on CT predicts Cushing's syndrome in elderly females with adrenal tumors.

There is no computed tomography (CT)-based numerical index for predicting Cushing's syndrome (CS) in patients with adrenal incidentalomas. We tested the hypothesis that the iliopsoas muscle (Ip-M) to visceral fat (V-fat) ratio (IVR) on CT may predict CS in elderly female patients with adrenal tumors. We examined the V-fat area, subcutaneous fat (S-fat) area, Ip-M area, V-fat/S-fat ratio, and IVR at the third lumbar vertebra (L3) level using abdominal CT in female patients aged ≥50 years with cortisol-producing adrenal tumor diagnosed with CS or non-functioning adrenal tumor (NFT) in the derivation cohort. We performed receiver operating characteristic (ROC) analysis to evaluate the diagnostic value of the V-fat/S-fat ratio and IVR for predicting CS. We assessed the usefulness of the IVR in a separate validation cohort. In the derivation cohort, the IVR was significantly lower in the 9 patients with CS than in the 15 patients with NFT (p < 0.001). In ROC analysis with a cut-off value of 0.067, the IVR showed a sensitivity of 100%, specificity of 80.0%, positive likelihood ratio (PLR) of 5.000, and negative likelihood ratio (NLR) of 0.000. The area under the curve was significantly higher for the IVR than for the V-fat/S-fat ratio (0.933 vs. 0.704, respectively, p = 0.036). In 23 patients in the validation cohort, the IVR demonstrated a PLR of 5.714 and an NLR of 0.327. The novel IVR index, based on single-slice CT at the L3 level, predicted CS in elderly female patients with adrenal tumors.

High-resolution contrast-enhanced MRI with three-dimensional fast spin echo improved the diagnostic performance for identifying pituitary microadenomas in Cushing's syndrome.

OBJECTIVES: To assess the diagnostic performance of high-resolution contrast-enhanced MRI (hrMRI) with three-dimensional (3D) fast spin echo (FSE) sequence by comparison with conventional contrast-enhanced MRI (cMRI) and dynamic contrast-enhanced MRI (dMRI) with 2D FSE sequence for identifying pituitary microadenomas. METHODS: This single-institutional retrospective study included 69 consecutive patients with Cushing's syndrome who underwent preoperative pituitary MRI, including cMRI, dMRI, and hrMRI, between January 2016 to December 2020. Reference standards were established by using all available imaging, clinical, surgical, and pathological resources. The diagnostic performance of cMRI, dMRI, and hrMRI for identifying pituitary microadenomas was independently evaluated by two experienced neuroradiologists. The area under the receiver operating characteristics curves (AUCs) were compared between protocols for each reader by using the DeLong test to assess the diagnostic performance for identifying pituitary microadenomas. The inter-observer agreement was assessed by using the κ analysis. RESULTS: The diagnostic performance of hrMRI (AUC, 0.95-0.97) was higher than cMRI (AUC, 0.74-0.75; p ≤ .002) and dMRI (AUC, 0.59-0.68; p ≤ .001) for identifying pituitary microadenomas. The sensitivity and specificity of hrMRI were 90-93% and 100%, respectively. There were 78% (18/23) to 82% (14/17) of the patients, who were misdiagnosed on cMRI and dMRI and correctly diagnosed on hrMRI. The inter-observer agreement for identifying pituitary microadenomas was moderate on cMRI (κ = 0.50), moderate on dMRI (κ = 0.57), and almost perfect on hrMRI (κ = 0.91), respectively. CONCLUSIONS: The hrMRI showed higher diagnostic performance than cMRI and dMRI for identifying pituitary microadenomas in patients with Cushing's syndrome. KEY POINTS: • The diagnostic performance of hrMRI was higher than cMRI and dMRI for identifying pituitary microadenomas in Cushing's syndrome. • About 80% of patients, who were misdiagnosed on cMRI and dMRI, were correctly diagnosed on hrMRI. • The inter-observer agreement for identifying pituitary microadenomas was almost perfect on hrMRI.

Osteoporotic vertebral compression fractures caused by Cushing's syndrome in young women: case report and literature review.

BACKGROUND: Cushing's syndrome is known as an important cause of secondary osteoporosis, characterized by reduction of bone mineral density and potential occurrence of fragility fractures before diagnosis in young population. Therefore, for young patients with fragility fractures, especially in young women, more attention should be paid on glucocorticoid excess caused by Cushing's syndrome, due to relatively higher rate of misdiagnosis, distinct pathological characteristics and different treatment strategies compared with violent fractures and primary osteoporosis related fractures. CASE PRESENTATION: We presented an unusual case of a 26-year-old woman with multiple vertebral compression fractures and pelvis fractures, subsequently diagnosed as Cushing's syndrome. On admission, the radiographic results showed fresh second lumbar vertebra fracture, and old fourth lumbar vertebra and pelvic fractures. The dual energy X-ray absorptiometry of lumbar spine revealed marked osteoporosis, and her plasm cortisol was extremely high. Then, Cushing's syndrome, caused by left adrenal adenoma, was diagnosed by further endocrinological and radiographic examinations. After receiving left adrenalectomy, her plasma ACTH and cortisol values returned to normal level. In term of OVCF, we adopted conservative treatments, including pain management, brace treatment, and anti-osteoporosis measures. Three months after discharge, the patient's low back pain was in complete remission without new onset of pain, and returned to normal life and work. Furthermore, we reviewed the literatures on advancements in the treatment of OVCF caused by Cushing's syndrome, and based on our experiences, proposed some additional perspectives to guide treatment. CONCLUSION: In term of OVCF secondary to Cushing's syndrome without neurological damage, we prefer systematic conservative treatments, including pain management, brace treatment, and anti-osteoporosis measures, to surgical treatment. Among them, anti-osteoporosis treatment has the highest priority because of the reversibility of osteoporosis caused by Cushing's syndrome.

Irreversible Alterations of Susceptibility in Cushing's Disease: A Longitudinal QSM Study.

OBJECTIVES: Chronic exposure to hypercortisolism is associated with accelerated aging and neurodegenerative diseases, while Cushing's disease (CD) is the most common form of endogenous hypercortisolism exposure. This study aimed to assess longitudinal susceptibility changes in CD using quantitative susceptibility mapping (QSM) before and after resolution of hypercortisolism. METHODS: In this study, 24 CD patients and 24 healthy controls underwent magnetic resonance imaging (MRI) with QSM. All CD patients underwent MRI scans before and after the curative operation. RESULTS: After resolution of hypercortisolism, irreversibly altered susceptibility values were found in the anterior cingulate cortex, frontal lobe, caudate, and red nucleus. These alterations were significantly correlated with the changes in gray matter/white matter volumes and clinical features. Additionally, decreased susceptibility was found in several regions in CD patients. CONCLUSION: Chronic exposure to hypercortisolism may be related to susceptibility alterations and significantly correlated with altered brain volumes and clinical features. in CD patients. The decrease of susceptibility might suggest the involvement of the calcium deregulation in these alterations.

Trabecular bone score, bone marrow fat and vertebral fractures in cushing syndrome.

OBJECTIVE: Prediction of fragility fractures in Cushing syndrome (CS) is a challenge since dual energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) does not capture all the alterations in bone microstructure induced by glucocorticoid excess. In this study we investigated the relationship between trabecular bone score (TBS), bone marrow fat (BMF) and vertebral fractures (VFs) in endogenous CS. DESIGN: Cross-sectional. METHODS: Thirty subjects (7 M and 23 F, mean age 44.8 ± 13.4 yrs, range: 25-71) with active hypercortisolism were evaluated for VFs by quantitative morphometry, BMD and TBS by lumbar spine DXA and BMF by single-voxel magnetic resonance spectroscopy of vertebral body of L3. RESULTS: Subjects with VFs (17 cases; 56.7%) had higher BMF (P = 0.014) and lower BMD T-score (P = 0.012) and TBS (P = 0.004) as compared to those without VFs. Prevalence of VFs resulted to be significantly higher in individuals with impaired TBS as compared to those with normal TBS (77.8% vs. 25.0%; P = 0.008). Among patients with VFs, only 6 (35.3%) had either osteoporosis or "low BMD for age". In logistic regression analysis, impaired TBS maintained the significant association with VFs [odds ratio (OR) 6.60, 95% C.I. 1.07-40.61; P = 0.042] independently of BMF (OR 1.03, 95% C.I. 0.99-1.08; P = 0.152). CONCLUSIONS: TBS might be more accurate than BMF in identifying subjects with active CS and skeletal fragility at risk of VFs. SIGNIFICANCE STATEMENT: Excess in glucocorticoids is associated with alterations in bone remodeling and metabolism, leading to fragility fractures regardless of bone mineral density, making more challenging for the clinician the identification of high-risk population and the definition of preventing strategies. In this context, instrumental parameters suggestive of bone quality alterations and predictive of increased fracture risk are needed. In this study, we found CS patients to have bone quality alterations as indicated by the decreased trabecular bone score and increased bone marrow fat, as measured by DEXA and MRI respectively. Both parameters were associated with high risk of VFs, and were inversely correlated, although TBS seems to be more accurate than BMF in fractures prediction in this clinical setting.

68Ga-DOTATATE PET/CT of ACTH-Independent Cushing Syndrome Due to Ectopic Adrenocortical Adenoma.

ABSTRACT: Adrenocorticotropic hormone-independent Cushing syndrome due to ectopic adrenocortical adenoma is a very rare entity. We herein present a case of a 57-year-old woman who was referred to our hospital with persistent Cushing syndrome after undergoing unnecessary laparoscopic left adrenalectomy. 68Ga-DOTATATE PET/CT revealed increased uptake in the nodule in the right hilum, which was histologically confirmed to be ectopic adrenocortical adenoma. Removal of the tumor was followed by the disappearance of clinical symptoms of Cushing syndrome. In this case, 68Ga-DOTATATE PET/CT contributed to the diagnosis of ectopic adrenocortical adenoma.

Central venous sampling and magnetic resonance imaging in the diagnosis of ACTH-dependent Cushing's syndrome.

OBJECTIVES: Central venous sampling (CVS) with corticotropin-releasing hormone (CRH) stimulation is a crucial technique in evaluating adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS). We evaluated central venous sampling (CVS) and magnetic resonance imaging (MRI) findings in predicting the localization and lateralization of pituitary microadenomas. METHODS: We analyzed 29 patients with CS who underwent CVS with CRH stimulation and examined with MRI retrospectively. Catheterization to central sinuses was successfully performed in 26 patients. Three patients with variant anatomy or inability to cannulate were diagnosed with CD after examination of pathology. RESULTS: After CVS, among 26 patients, 23 patients were determined to have CD (88.4%) and 2 (7.7%) patients were diagnosed with ectopic ACTH syndrome. One patient was diagnosed with CD postoperatively. While the sensitivity of the CVS was 95.6%, sensitivity of the preoperative pituitary MRI was lower (69.5%). Also, the negative predictive value ratio was higher in CVS than in MRI (66% versus 22%). Diagnostic accuracy in the lateralization of the tumor was high as in CVS as in MRI (76.4% versus 73.9%). CONCLUSION: Central venous sampling with higher sensitivity in the localization of pituitary microadenoma, also has approximately similar diagnostic accuracy in lateralizing the tumor with MRI.