Dabigatran Etexilate Related Unilateral Adrenal Hemorrhage.

A 63-year-old male presented to our clinic with computed tomography data of a large tumor of the left adrenal gland. The formation is highly suspicious for malignancy with central necrosis and hemorrhage, and a total size of 197/183/201 mm. Due to elevated D-dimer values of 7.17 mg/l (reference range <0.5 mg/l), treatment with dabigatran etexilate 2x150 mg was prescribed following a cardiology consult. On the third day of therapy, the patient noticed a large swelling in the left abdominal flank, which caused discomfort. No additional symptoms were reported. No previous abdominal surgical interventions or trauma were reported. Following a thorough physical examination, the patient was referred for a computer tomography that reported a diagnosis of a tumor of the left adrenal gland. Due to the size of the neoplasm, the suspicion of malignancy, compression of adjacent structures, and significant anemia with an Hb of 112 g/L, operative treatment was chosen as the best treatment modality. The mass was reported as a large organizing adrenal hematoma with no suspicion of malignancy on histology. Following a review of available literature, no other cases of unilateral adrenal hematoma with a size of 201x197 mm, following oral anticoagulant therapy with dabigatran etexilate, without any prior surgery or trauma have been reported. Most clinical cases report bilateral adrenal hemorrhage during the postoperative period, following prophylaxis with heparin and the development of heparin-induced thrombocytopenia. The patient underwent operative treatment, after which the patient recovered normally and was discharged from the clinic without complications.

Impact of endocrine-active compounds on adrenal androgen production in pigs during neonatal period.

This study investigated the impact of neonatal exposure to endocrine-active compounds (EACs): flutamide (antiandrogen), 4-tert-octylphenol (an estrogenic compound), and methoxychlor (an organochlorine insecticide exhibiting estrogenic, antiestrogenic and antiandrogenic activities) on androgen production within porcine adrenal glands. The expression of genes related to androgen synthesis and the level of androgen production were analyzed (i) in the adrenal glands of piglets exposed to EACs during the first 10 days of life (in vivo study), and (ii) in adrenal explants from sow-fed or formula-fed 10-day-old piglets incubated with EACs (ex vivo study). EACs affected the expression of genes linked to adrenal androgen biosynthesis. The prominent effect of methoxychlor on downregulation of StAR, CYP11A1 and HSD3B and upregulation of CYP17A1 and SULT2A1 were demonstrated. Furthermore, our study revealed divergent response to EACs between sow-fed and formula-fed piglets, suggesting that natural feeding may provide protection against adverse EACs effects, particularly those interfering with estrogens action.

Anatomical Variations Encountered during Adrenal Venous Sampling: A Report of Three Case Series and Review of Literature.

Primary aldosteronism is a group of disorders in which the autonomous secretion of aldosterone is associated with hypertension and hypokalemia. It is crucial to determine the laterality of aldosterone hypersecretion because treatment options differ accordingly. Adrenal venous sampling (AVS) is considered the most reliable method for assessing the laterality of primary aldosteronism. This procedure is often technically challenging because of the small size and varied locations of the adrenal veins. A better understanding of anatomical variations and careful review of imaging studies would improve sampling success. This report presents three cases of anatomical variations encountered during AVS.

Ultrasonographic measurements of the normal adrenal glands in guinea pigs (Cavia Porcellus).

Hyperadrenocorticism is an uncommon but important endocrine disease in guinea pigs, but due to its subtle clinical signs and the limited information in veterinary literature, it can be underdiagnosed or misdiagnosed. Ultrasound of the adrenal glands in patients with suspected hyperadrenocorticism can help in identifying adrenomegaly. The purpose of this prospective study was to identify ultrasonographic adrenal gland dimensions in presumed healthy guinea pigs using the same standardized method described for dogs and cats. A conscious ultrasound scan was conducted on twenty client-owned, presumed healthy guinea pigs, and their adrenal glands were measured. A possible correlation between adrenal dimensions with age, sex, and body weight was investigated. The mean length, cranial and caudal pole thickness for the left and right adrenal glands were, respectively, 12.64 ± 2.11 mm and 11.55 ± 1.52 mm; 4.83 mm ± 1.03 mm and 4.69 ± 1.34 mm; 4.8 ± 1.23 mm and 4.04 ± 0.75 mm. The thickness of the left caudal pole was significantly higher than the right (P = 0.02). A significant positive correlation was found between the length of the left adrenal gland and both age (r = 0.46; P = .03) and weight (r = 0.59; P = .01). Statistical correlation between the thickness of each cranial and caudal pole, with age, sex, or weight, was not found. The dimensions provided could prove a useful tool in the clinical evaluation of guinea pigs with suspected hyperadrenocorticism.

Effect of resuscitation of cryopreserved porcine adrenal glands at 26 °C on their recovery and functioning under xenotransplantation.

The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO2, DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro, and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice.

Bilateral Adrenal Myelolipoma and Breast Cancer in a Patient With Congenital Adrenal Hyperplasia.

Adrenal myelolipoma is a rare, benign tumor of the adrenal gland, typically non-functional, asymptomatic and unilateral. With the increased use of radiological imaging, it has been discovered more frequently as incidental mass. It is common to occur concurrently with hormonal dysfunction conditions like congenital adrenal hyperplasia. However, there are few previous reported cases of malignancy concomitant with adrenal myelolipoma. We present a case of a 33-year-old patient diagnosed with congenital adrenal hyperplasia since birth. She was diagnosed with giant bilateral adrenal myelolipoma incidentally during the investigation done for staging her breast cancer. To the best of our knowledge, this is the second reported case of breast cancer concomitant with adrenal myelolipoma. Although this entity is very rare, physicians should be familiar with such rare adrenal masses and their associations in order to manage them appropriately.

Phaeochromocytoma and paraganglioma.

Phaeochromocytomas and paragangliomas are rare catecholamine-producing neuroendocrine tumours which can potentially cause catastrophic crises with high morbidity and mortality. This best practice article considers the causes and presentation of such tumours, screening and diagnostic tests, management of these patients and consideration of family members at risk.

Validation of the modified CT criteria for identifying non-adenomas.

PURPOSE: Although adrenal computed tomography (CT) percentage washout is a potentially powerful imaging technique for differentiating adrenal adenomas from non-adenomas, its application to non-adenomas can be problematic. Recently, modified criteria for diagnosing pheochromocytomas using adrenal CT were developed based on data from 199 patients with surgically proven pheochromocytomas and adenomas. However, these criteria have not been thoroughly validated. The purpose of this study was to validate the performance of the modified criteria for diagnosing non-adenomas including pheochromocytomas. METHODS: The conventional and modified criteria were applied to 266 patients from two cohorts who had surgically proven lipid-poor adenomas (155/266, 58.3%) and non-adenomas (111/266, 41.7%) and underwent adrenal CT. Two radiologists calculated the attenuation on each dynamic phase and percentage washout of adrenal masses. The final assessments based on the conventional and modified criteria were categorized into adenomas or non-adenomas. The diagnostic performance of each criterion for diagnosing non-adenomas was evaluated using the area under the receiver operating characteristic curve (AUC). False negatives and positives were also compared. RESULTS: The AUC for the diagnosis of non-adenomas was 0.806 for conventional criteria and 0.858 for modified criteria (p = 0.047). The false-negative rate of conventional criteria for the diagnosis of non-adenomas was 29.7%. Use of modified criteria could have reduced the false-negative rate by to 7.2%. The false-positive rate increased from 9% to 21.3% when using the modified criteria. CONCLUSION: The utilization of modified criteria has the potential to identify additional non-adenomas that would otherwise be misdiagnosed as adenomas using conventional criteria alone.

Deregulated Transcriptome as a Platform for Adrenal Huntington's Disease-Related Pathology.

Huntington's disease (HD) is a neurodegenerative disorder that affects mainly the central nervous system (CNS) by inducing progressive deterioration in both its structure and function. In recent years, there has been growing interest in the impact of HD on peripheral tissue function. Herein, we used the R6/2 mouse model of HD to investigate the influence of the disease on adrenal gland functioning. A transcriptomic analysis conducted using a well-established quantitative method, an Affymetrix array, revealed changes in gene expression in the R6/2 model compared to genetic background controls. For the first time, we identified disruptions in cholesterol and sterol metabolism, blood coagulation, and xenobiotic metabolism in HD adrenal glands. This study showed that the disrupted expression of these genes may contribute to the underlying mechanisms of Huntington's disease. Our findings may contribute to developing a better understanding of Huntington's disease progression and aid in the development of novel diagnostic or therapeutic approaches.

Brain tissue heterotopic in the adrenal gland in a child: a scarce case report.

Heterotopic brain tissue is rare and has not been reported. Our center made the first report. 4 years and 2 months old Girl presented with a cystic mass in the right adrenal gland 2 weeks after right upper abdominal pain. The operation was successful, and the diagnosis was confirmed by postoperative pathology. 6 months after the procedure, the incision healed well without recurrence. This case report has a detailed diagnosis and treatment process and satisfactory examination results. It can provide a reference for diagnosing and treating clinical HBT and reduce the risk of misdiagnosis and mistreatment.

Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study.

BACKGROUND: Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy. METHODS: We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue. RESULTS: The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein CACNA1D mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45-17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00-26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20-6.31]). CONCLUSIONS: Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.

Adrenal limb thickness is associated with metabolism profiles in patients with diabetes: A cross-sectional study.

BACKGROUND: The association between adrenal size and metabolic profiles in patients with diabetes mellitus (DM) is unclear. This study was conducted to determine whether the adrenal thickness measured by computed tomography (CT) is correlated with the metabolic profiles of patients with DM. METHODS: This was a cross-sectional study including 588 Chinese hospitalized patients with DM without comorbidities or medications known to affect adrenal morphology or hormone secretion. Adrenal limb thickness was measured on unenhanced chest CT. Participants were stratified into tertiles according to their total adrenal limb thickness. Linear and logistic regression models were used to estimate the correlations. RESULTS: After adjustment for sex and age, the adrenal thickness was positively associated with body mass index (BMI), waist circumference (WC), urinary albumin/creatinine ratio, and 24-h urinary free cortisol (UFC) and negatively correlated with high-density lipoprotein cholesterol. The sequential equation model (SEM) suggested UFC partially mediated the effect of adrenal limb thickness on WC by 12%. Adrenal thickness, but not UFC, was associated with a higher risk of existing hypertension (odds ratio [OR] = 3.78, 95% confidence interval [CI] 1.58, 9.02) and hyperlipidemia (OR = 2.76, 95% CI 1.03, 7.38), independent of age, gender, BMI, and WC. CONCLUSIONS: The adrenal thickness is independently associated with BMI, WC, cortisol levels, urinary albumin/creatinine ratio, hypertension, and dyslipidemia but not glycemic parameters in patients with diabetes. Our study encourages further studies to investigate the role of adrenal physiology in patients with diabetes.

Relationship Between Overnight Dexamethasone Suppression Test and Aging.

Background This study aims to investigate the relationship between suppressed cortisol levels measured after the 1-mg dexamethasone suppression test (DST) and age based on the hypothesis that aging can alter the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Methodology Data obtained by the retrospective evaluation of suppressed 1-mg overnight DST results of adults aged ≥18 years with adrenal incidentaloma or suspected endogenous hypercortisolemia between December 2021 and March 2023 were subjected to age-dependent correlation analysis. Individuals aged between 18 and 90 years (n = 1111) were classified into the following four groups: <30 years, 30-49 years, 50-69 years, and >70 years. DST results were compared according to age groups. Results Median post-DST cortisol was 18.49 nmol/L, with a level of 17.9 nmol/L in females and 20.7 nmol/L in males. The overall rate of DST suppression was 62.7%, with a rate of 63.8% in females and 59.7% in males. On pairwise comparisons of all age groups, there was a difference in post-DST cortisol levels (p = 0.000). Our statistical analysis revealed a strong positive correlation between age and cortisol levels after DST. Conclusions The negative feedback mechanism for cortisol may be altered in older patients. Therefore, the 1-mg DST may yield a higher rate of false positives in the elderly.

Beyond Binary: Gender Reassignment in a Case of 11ß-Hydroxylase Deficiency.

Congenital adrenal hyperplasia (CAH) encompasses a spectrum of disorders characterized by enzyme deficiencies in the hormone biosynthesis pathways of the adrenal glands, resulting in impaired cortisol synthesis. These disorders are typically inherited in an autosomal recessive pattern. Numerous enzymes participate in the hormonal synthesis within the adrenal glands, and the clinical presentation of affected individuals exhibits significant variability, contingent upon the specific enzyme deficiency and its severity. In this case, we present a compelling instance of 11ß-hydroxylase deficiency (11ßOHD). The patient initially presented as a male, with complaints of early-onset hypertension and intermittent hematuria. He had a history of precocious puberty and had experienced a progressive increase in breast size. Subsequently, the patient was found to have an XX karyotype, and a pelvic ultrasound revealed the presence of a uterus, two ovaries, and a rudimentary vagina. Gender reassignment surgery was done to this patient. This intricate case underscores the critical importance of promptly recognizing and effectively managing CAH. Timely and appropriate treatment is pivotal in ensuring the well-being of affected individuals.

Recurrent Post-Traumatic Adrenal Bleeding after Transcatheter Arterial Embolization: A Case Report.

Adrenal gland trauma is uncommon and is diagnosed at an increasing frequency using CT scans. However, owing to the rarity of this injury and its diverse clinical presentations and prognoses, there is no consensus on its management. In this case report, a 73-year-old male patient experienced recurrent bleeding in the right adrenal gland due to an in-car traffic accident, which was treated with repeated transcatheter arterial embolization.

Asymmetries of Left and Right Adrenal Glands in Neural Innervation and Glucocorticoids Production.

The adrenal gland is paired peripheral end organs of the neuroendocrine system and is responsible for producing crucial stress hormones from its two functional compartments, the adrenal cortex, and the adrenal medulla under stimuli. Left-right asymmetry in vertebrates exists from the central nervous system to peripheral paired endocrine glands. The sided difference in the cerebral cortex is extensively investigated, while the knowledge of asymmetry of paired endocrine glands is still poor. The present study aims to investigate the asymmetries of bilateral adrenal glands, which play important roles in stress adaptation and energy homeostasis via steroid hormones produced from the distinct functional zones. Left and right adrenal glands from male C57BL/6J mice were initially histologically analyzed, and high-throughput RNA sequencing was then used to detect the gene transcriptional difference between left and right adrenal glands. Subsequently, the enrichment of functional pathways and ceRNA regulatory work was validated. The results demonstrated that the left adrenal gland had higher tissue mass and levels of energy expenditure, whereas the right adrenal gland appeared to be more potent in glucocorticoid secretion. Further analysis of adrenal stem/progenitor cell markers predicted that Shh signaling might play an important role in the left-right asymmetry of adrenal glands. Of the hub miRNAs, miRNA-466i-5p was identified in the left-right differential innervation of the adrenal glands. Therefore, the present study provides evidence that there are asymmetries between the left and right adrenal glands in glucocorticoid production and neural innervation, in which Shh signaling and miRNA-466i-5p play an important role.

Malignant Pheochromocytoma With Intravascular Extension to the Heart.

Background: Malignant pheochromocytomas are rare and aggressive tumors that arise from the adrenal medulla and secrete catecholamines. Patients exhibit episodic symptoms of hypertension, headaches, sweating, and palpitations. The diagnosis is supported by elevated levels of urinary metanephrines, and imaging is used to determine the stage. Treatment involves surgical resection when possible. Case Report: A 57-year-old male presented with hematemesis and melena, and endoscopy revealed upper gastrointestinal bleeding. Imaging showed a malignant pheochromocytoma that had infiltrated the upper lobe of the right kidney and the right lobe of the liver, with a tumor thrombus extending into the hepatic inferior vena cava, the right atrium, and the right ventricle. The patient denied surgery and was treated with palliative medical therapy until he died 3 months later. Conclusion: Although rare, malignant pheochromocytomas may present with upper gastrointestinal bleeding. While metastasis to the liver is a typical manifestation of malignant pheochromocytomas, invasion of the inferior vena cava with infiltration to the right ventricle resulting in tricuspid valve malfunction is a rare finding.

Thyroid and adrenal incidentalomas on chest CT: Prevalence, diagnostic work-up and outcomes in a cohort of COVID-19 suspected patients.

OBJECTIVE: Due to increased use of computed tomography (CT), prevalence of thyroid and adrenal incidentalomas is rising. Yet, previous studies on the outcomes of diagnostic work-up of incidentalomas are subjected to inclusion bias. Therefore, we aimed to investigate prevalence and outcomes of diagnostic work-up of thyroid and adrenal incidentalomas detected on chest CT in a less selected population of COVID-19 suspected patients. DESIGN: A retrospective, observational cohort study. METHODS: We included all COVID-19 suspected patients who underwent chest CT between March 2020 and March 2021. Radiology reports and medical records were reviewed for the presence and subsequent diagnostic work-up of thyroid and adrenal incidentalomas. RESULTS: A total of 1,992 consecutive COVID-19 patients were included (59.4% male, median age 71 years [IQR: 71-80]). Thyroid and adrenal incidentalomas were identified in 95 (4.8%) and 133 (6.7%) patients, respectively. Higher prevalence was observed with increasing age, among female patients and in patients with malignancy. Forty-four incidentalomas were further analyzed, but no malignancies were found. Only three lesions were hormonally active (1 thyrotoxicosis and 2 mild autonomous cortisol secretion). Diagnostic work-up did not lead to any change in clinical management in 97.7% of the analyzed patients. CONCLUSION: Prevalence rates of thyroid and adrenal incidentalomas on chest CT in a less selected COVID-19 cohort were 4.8% and 6.7%, respectively. Yet, as all incidentalomas turned out to be benign and only three lesions were (mildly) hormonally active, this raises the question whether intensive diagnostic work-up of incidentalomas is necessary in all patients.

Differentiating adrenal metastases from benign lesions with multiphase CT imaging: Deep learning could play an active role in assisting radiologists.

OBJECTIVES: To develop and externally validate multiphase CT-based deep learning (DL) models for differentiating adrenal metastases from benign lesions. MATERIALS AND METHODS: This retrospective two-center study included 1146 adrenal lesions from 1059 patients who underwent multiphase CT scanning between January 2008 and March 2021. The study encompassed 564 surgically confirmed adenomas, along with 135 benign lesions and 447 metastases confirmed by observation. DL models based on multiphase CT images were developed, validated and tested. The diagnostic performance of the classification models, imaging phases and radiologists with or without DL were compared using accuracy (ACC) and receiver operating characteristic (ROC) curves. Integrated discrimination improvement (IDI) analysis and the DeLong test were used to compare the area under the curve (AUC) among models. Decision curve analysis (DCA) was used to assess the clinical usefulness of the predictive models. RESULTS: The DL signature based on LASSO (DLSL) had a higher AUC than that of the other classification models (IDI > 0, P < 0.05). Furthermore, the precontrast phase (PCP)-based DLSL performed best in the independent external validation (AUC = 0.881, ACC = 82.9 %) and clinical test cohorts (AUC = 0.790, ACC = 70.4 %), outperforming DLSL based on the other single-phase or three-phase images (IDI > 0, P < 0.05). DCA demonstrated that PCP-based DLSL provided a higher net benefit (0.01-0.95). The diagnostic performance led to statistically significant improvements when radiologists incorporated the DL model, with the AUC improving by 0.056-0.159 and the ACC improving by 0.069-0.178 (P < 0.05). CONCLUSION: The DL model based on PCP CT images performed acceptably in differentiating adrenal metastases from benign lesions, and it may assist radiologists in accurate tumor staging for patients with a history of extra-adrenal malignancy.