Adrenocortical carcinoma (ACC) is a malignancy of the adrenal cortex with a high morbidity and mortality. More than half of the cases are functional tumors. As different hormones can be co-secreted above physiologic levels, it causes a very broad variety of symptoms and makes differentiating from more common entities hard. Here we present a case of a patient with a newly diagnosed ACC who initially presented with acute pulmonary embolism and recurrent deep vein thromboses (DVT) in the setting of hypercortisolism. Imaging showed a left adrenal mass invading adjacent structures including a nonocclusive thrombus in the left renal vein. Intravenous anticoagulation and thrombectomy were initially performed, followed by removal of the tumor and adjacent metastatic disease. Pathology confirmed ACC. The patient underwent left adrenalectomy, left nephrectomy, splenectomy, distal pancreatectomy, and caval thrombectomy with inferior vena cava (IVC) filter placement. Intravenous anticoagulation and glucocorticoid replacement were also administered as part of the treatment plan. Unfortunately, the patient had multiple episodes of bleeding and thrombosis and was eventually discharged to hospice care. DVT in the setting of ACC can be caused by increased hypercoagulability from hypercortisolism, direct venous thrombosis, or vascular invasion. Thrombosis, especially in the inferior vena cava, has been associated with poor prognosis and survival rates. Clinicians should be aware of this rare complication given its immediate therapeutic repercussions and prognostic value.

Osilodrostat is a novel potent oral steroidogenesis inhibitor with a non-steroidal chemical structure, recently approved for the treatment of adult patients with endogenous Cushing\'s syndrome, and Cushing\'s disease not cured bytab pituitary surgery or in whom pituitary surgery is not an option. Osilodrostat has been evaluated in different multicentre phase II and III clinical studies, and has shown to have notable effects, such as significant reductions in cortisol secretion, associated with significant improvement in body weight, blood pressure, glucose metabolism, lipid profile, psychological status and quality of life. The favourable safety profile, combined with the relevant efficacy, could make osilodrostat suitable as medical treatment in several phases of the Cushing\'s syndrome treatment journey: before surgery, as preoperative treatment, or instead of surgery, in cases where surgery is not an option or refused, as first-line treatment; after surgery, in cases of persistent or recurrent disease, as second-line treatment; after second surgery or radiotherapy following pituitary surgery as bridging treatment waiting for the definitive disease control, as third-line treatment. Further real-world clinical experience data are needed to confirm the current knowledge.

Cushing\'s syndrome (CS) arises from an excess of endogenous or exogenous cortisol, with Cushing\'s disease specifically implicating a pituitary adenoma and exaggerated adrenocorticotropic hormone (ACTH) production. Typically, Cushing\'s disease presents with characteristic symptoms such as weight gain, central obesity, moon face, and buffalo hump. This case report presents an unusual manifestation of CS in a 48-year-old male with a history of hypertension, where severe hypokalemia was the primary presentation. Initial complaints included bilateral leg swelling, muscle weakness, occasional shortness of breath, and a general feeling of not feeling well. Subsequent investigations revealed hypokalemia, metabolic alkalosis, and an abnormal response to dexamethasone suppression, raising concerns about hypercortisolism. Further tests, including 24-hour urinary free cortisol and ACTH testing, confirmed significant elevations. Brain magnetic resonance imaging (MRI) identified a pituitary macroadenoma, necessitating neurosurgical intervention. This case underscores the rarity of CS presenting with severe hypokalemia, highlighting the diagnostic challenges and the crucial role of a collaborative approach in managing such intricate cases.

BACKGROUND: The human adrenal cortex consists of three functionally and structurally distinct layers; zona glomerulosa, zona fasciculata (zF), and zona reticularis (zR), and produces adrenal steroid hormones in a layer-specific manner; aldosterone, cortisol, and adrenal androgens, respectively. Cortisol-producing adenomas (CPAs) occur mostly as a result of somatic mutations associated with the protein kinase A pathway. However, how CPAs develop after adrenocortical cells acquire genetic mutations, remains poorly understood.
METHODS: We conducted integrated approaches combining the detailed histopathologic studies with genetic, RNA-sequencing, and spatially resolved transcriptome (SRT) analyses for the adrenal cortices adjacent to human adrenocortical tumours.
RESULTS: Histopathological analysis revealed an adrenocortical nodular structure that exhibits the two-layered zF- and zR-like structure. The nodular structures harbour GNAS somatic mutations, known as a driver mutation of CPAs, and confer cell proliferative and autonomous steroidogenic capacities, which we termed steroids-producing nodules (SPNs). RNA-sequencing coupled with SRT analysis suggests that the expansion of the zF-like structure contributes to the formation of CPAs, whereas the zR-like structure is characterised by a macrophage-mediated immune response.
CONCLUSIONS: We postulate that CPAs arise from a precursor lesion, SPNs, where two distinct cell populations might contribute differently to adrenocortical tumorigenesis. Our data also provide clues to the molecular mechanisms underlying the layered structures of human adrenocortical tissues.
BACKGROUND: KAKENHI, The Uehara Memorial Foundation, Daiwa Securities Health Foundation, Kaibara Morikazu Medical Science Promotion Foundation, Secom Science and Technology Foundation, ONO Medical Research Foundation, and Japan Foundation for Applied Enzymology.

UNASSIGNED: Recently, it has been reported that there is a great diversity in strategies used for thromboprophylaxis in patients with Cushing\'s syndrome (CS). An aim of this review was to discuss these practices in light of the existing data on the thrombotic risk in patients with CS and guidelines for medically ill patients.
UNASSIGNED: The four relevant topics and questions on thrombotic risk in CS were identified. The current guidelines on prevention and diagnosis of venous thromboembolism (VTE) were reviewed for the answers. An algorithm to consider in the assessment of the thrombotic risk in patients with CS was proposed.
UNASSIGNED: To address both generic and CS-specific risk factors for VTE, the algorithm includes the stepwise approach consisting of Padua Score, urine free cortisol, and CS-VTE score, with no indication for routine thrombophilia testing in the prediction of an index VTE episode. Having confirmed VTE, selected patients require thrombophilia testing to aid the duration of anticoagulant treatment. The separate part of the algorithm is devoted to patients with ectopic adrenocorticotropic hormone syndrome in whom exclusion of VTE precedes introducing routine thromboprophylaxis to prevent VTE. The cancer-related VTE also prompts thromboprophylaxis, with the possible vessel invasion. The algorithm presents a unifactorial and multifactorial approach to exclude high-bleeding risks and safely introduce thromboprophylaxis with low-molecular-weight heparin.
UNASSIGNED: Our article is the first to present an algorithm to consider in the thrombotic risk assessment among patients with Cushing\'s syndrome as a starting point for a broader discussion in the environment. A plethora of factors affect the VTE risk in patients with CS, but no studies have conclusively evaluated the best thromboprophylaxis strategy so far. Future studies are needed to set standards of care.

OBJECTIVE: To present a case series of Cushing\'s syndrome (CS) during pregnancy caused by adrenocortical adenomas, highlighting clinical features, hormonal assessments and outcomes.
METHODS: We describe five pregnant women with CS, detailing clinical presentations and laboratory findings.
RESULTS: Common clinical features included a full moon face, buffalo back and severe hypertension. Elevated blood cortisol levels with circadian rhythm disruption and suppressed adrenocorticotrophic hormone (ACTH) levels were observed. Imaging revealed unilateral adrenal tumours. Two cases underwent laparoscopic adrenalectomies during the second trimester, while three had postpartum surgery. All required hormone replacement therapy, with postoperative pathological confirmation of adrenocortical adenomas.
CONCLUSIONS: Diagnosis of CS during pregnancy is challenging due to overlapping features with normal pregnancy: elevated blood cortisol levels and abnormal diurnal rhythm of blood cortisol, suppressed aid diagnosis. Treatment should be individualised due to a lack of explicit optimum therapeutic approaches. Laparoscopic adrenalectomy may be an optimal choice, along with multidisciplinary management including hormone replacement therapy.

Adrenal cortical eosinophilic adenoma usually presents as non-functional adrenal tumor but may lead to Cushing\'s syndrome in patients. The present article reports a patient with Cushing\'s syndrome caused by right adrenocortical oncocytoma. The patient was treated in Urology Department of Wuchuan People\'s Hospital (Zunyi, China) in November 2022 because of hirsutism, weight gain and hypertension. A laparoscopic right adrenal tumor resection was performed using an abdominal approach. Following surgery, blood pressure and heart rate of the patient fluctuated within a healthy range and menstruation returned to normal. Laparoscopic adrenalectomy has obvious advantages over open adrenalectomy, such as less trauma, shorter recovery time and fewer complications. Thus, this treatment for this rare disease is safe and feasible.

Adrenocortical carcinoma (ACC) is a very rare malignancy with a poor prognosis. It is predominantly noted in the fourth to fifth decades of life and is more common in White females. ACC is most commonly detected as an incidental finding but may have other presentations, such as rapid-onset Cushing\'s syndrome or pulmonary embolism. In the current case, ACC was incidentally observed in a 24-year-old female during imaging, and the patient later developed a pulmonary embolism. Lab investigations were suggestive of hypercortisolism along with hyperandrogenism. Following preoperative treatment with beta-blockers, metyrapone, and therapeutic anticoagulation, she underwent left radical nephrectomy with left open adrenalectomy and inferior vena cava (IVC) resection and reconstruction. Surgery was uncomplicated, and she was discharged with plans for outpatient adjuvant chemotherapy. This case highlights the fact that a seemingly unprovoked pulmonary embolism may point to the possibility of an underlying occult malignancy and undetected ACC should be included in the differential diagnosis of such cases.

BACKGROUND: The occurrence of hypercortisolism resulting from adrenocorticotropic hormone (ACTH)-secreting pheochromocytoma is exceedingly uncommon, with limited documented instances thus far.
METHODS: We present a case of ectopic ACTH-secreting pheochromocytoma in a patient who suffered from severe metabolic disorders. Our clinical case outlines the diagnostic history, preoperative correction of the patient\'s metabolic disturbances and surgical strategy for management of a rare ectopic ACTH producing pheochromocytoma.
CONCLUSIONS: Ectopic adrenocorticotropic hormone-secreting pheochromocytoma displays multifaceted clinical features and requires prompt diagnosis and multidisciplinary management in order to overcome the related severe clinical derangements.
CONCLUSIONS: The combination of biochemical and hormonal testing and imaging procedures is mandatory for the diagnosis of ectopic ACTH secretion, and in the presence of an adrenal mass, the possibility of an ACTH-secreting pheochromocytoma should be taken into account.

Hypertension affects about 1.28 billion adults globally, and significantly increases the risk of chronic morbidity and mortality among sufferers. About 15% of these individuals have secondary hypertension, the majority of whom have dysfunction of one or more endocrine systems as the cause of hypertension. Although adrenal disorders are often identified as the cause of endocrine hypertension, extra-adrenal disease and pituitary disorders also can cause the disease. Timely diagnosis is of paramount importance, because of the potential for a surgical cure or optimal disease control with pharmacotherapy to prevent hypertensive complications. Even with its relatively high prevalence compared with many other chronic illnesses, the diagnosis of endocrine hypertension is often delayed or never made because of poor awareness about the disease among physicians. This review attempts to provide an overview of the disease, with some practical aspects of diagnosis and management of a few of the important disorders causing endocrine hypertension.