Introduction: Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence even after surgical resection. Surgery remains the mainstay of treatment, while adjuvant options are limited. Mitotane is the only approved systemic therapy. Current guidelines recommend stereotactic body radiotherapy (SBRT) alongside adjuvant mitotane therapy in Rx, R1, R2 resections and in locally advanced disease. Case: We present a case of a 40-year-old female who presented with abdominal pain and was found to have a large heterogeneous left adrenal mass measuring 8.2 × 8.5 × 9.5 cm (Hounsfield Unit 63) on computed tomography (CT) imaging. Clinically, she was obese with a body mass index of 33.7 kg/m². No discriminatory feature of Cushing’s was present. Hormonal evaluation demonstrated autonomous cortisol secretion with failure of suppression on both overnight and low-dose dexamethasone suppression tests at 301 nmol/L and 313.6 nmol/L, respectively. DHEA, testosterone, and urinary metanephrine were within range. Hemoglobin A1c was 6.6%. She underwent open left adrenalectomy. Intra-operatively, a 12 × 10 cm adrenal tumor was identified with multiple areas of tumor rupture and spillage during mobilization. HPE confirmed high-grade ACC with high Weiss score of 8, Ki-67 index 60–80%, and mitotic count 54/50 hpf (pT2Nx). Post-operative CT imaging demonstrated a residual soft tissue lesion in the left adrenal bed (largest diameter 3.8 cm) with fluorodeoxyglucose avidity. We commenced adjuvant mitotane therapy, titrated to 2 g TDS with supraphysiological hydrocortisone replacement. Mitotane level was within therapeutic range (16 mcg/mL). She was deemed unsuitable for repeat surgery due to the proximity of the residual mass to the adjacent vessel and was planned for SBRT therapy after a multidisciplinary team discussion. Conclusion High-risk ACC with suspected residual disease remains a therapeutic challenge. While mitotane remains the cornerstone of adjuvant therapy, SBRT may represent a promising adjunctive local treatment modality in carefully selected patients. Further studies are required to define its role in improving local control and outcomes in ACC.
Adrenocortical Carcinoma ; Mitotane

Introduction: Cushing’s syndrome is a multisystem disorder with significant cardiovascular morbidity, yet presentation as acute heart failure is uncommon. When driven by adrenocortical carcinoma (ACC), the clinical course is often aggressive and rapidly fatal, with particularly poor out-comes in resourcelimited settings where access to therapy is constrained. Case: A 39-year-old previously well female presented with acute decompensated heart failure, newly diagnosed hypertension, type 2 diabetes mellitus, and obesity, preceded by a 3-year history of secondary amenorrhea and progressive weight gain. On admission, she exhibited florid Cushingoid features. Biochemical evaluation confirmed severe adrenocorticotropic hormone (ACTH)-independent hypercortisolism: morning serum cortisol 1,950 nmol/L, failure of suppression on overnight dexamethasone suppression test (post-ODST cortisol 2022.9 nmol/L), and elevated 24-hour urinary free cortisol (2,069 nmol/24 hours, 2.56 × upper limit of normal). Androgen excess was evident, with elevated dehydroepiandrosterone sulfate (DHEAS more than 27 µmol/L) and testosterone (9.91 nmol/L). ACTH was suppressed, supporting an adrenal source, while aldosterone was normal. Contrast-enhanced computed tomography demonstrated a large left adrenal mass (12 cm) with tumor thrombus extending into the inferior vena cava and renal veins, with extensive hepatic and pulmonary metastases, consistent with advanced ACC. Management was limited by disease severity and resource constraints. Ketoconazole was contraindicated due to transaminitis, and alternative steroidogenesis inhibitors were unavailable, leaving metyrapone as the only feasible option. Oncological therapy was deferred due to sepsis and clinical instability. Her course was fulminant, complicated by recurrent heart failure, sepsis, and metabolic derangements, culminating in refractory cardiopulmonary failure. She died within 1 month of diagnosis, prior to definitive oncological intervention. Conclusion Fulminant cortisol-secreting ACC may present catastrophically as acute heart failure and progress rapidly. Early recognition and timely access to multimodal cortisollowering therapy are critical, particularly in resourcelimited settings. In fulminant hypercortisolism, the challenge is not diagnosis—but timing.
Adrenocortical Carcinoma ; Hydrocortisone ; Heart Failure

Introduction: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a predilection for metastasis to the liver, lungs, and lymph nodes. Bone involvement is less common and typically occurs alongside widespread disease. Isolated skeletal progression without visceral involvement is unusual and not well characterized. Case: A 60-year-old female underwent left adrenalectomy in 2019 for an incidentally detected adrenal mass, which was reported as a benign adrenal cortical adenoma (Ki67 <3%). In 2022, she presented with persistent low back pain. Imaging demonstrated fluorodeoxyglucoseavid lesions involving the T12 vertebra and right ilium, without evidence of local recurrence or visceral metastases. Histopathological evaluation of a bone biopsy initially suggested a neuroendocrine neoplasm based on synaptophysin positivity. Following multiple expert reviews and integration of clinical, radiological, and immunohistochemical findings, a consensus diagnosis of metastatic ACC was established. She received palliative radiotherapy to symptomatic skeletal sites and subsequently completed six cycles of etoposide, doxorubicin, and cisplatin chemotherapy in 2023, achieving disease stabilization. Surveillance imaging in May 2025 demonstrated progression confined to the axial and appendicular skeleton, with no involvement of the adrenal bed or visceral organs. Mitotane therapy was initiated in December 2025. Ongoing management focuses on systemic disease control, symptom palliation, and multidisciplinary supportive care. Conclusion This case illustrates an uncommon pattern of ACC progression characterized by bone-dominant metastases in the absence of visceral disease. It also highlights the importance of reconsidering the initial histopathological diagnosis when clinical behavior is discordant. Vigilance for atypical metastatic patterns is warranted, even years after resection of an adrenal lesion initially classified as benign.
Adrenocortical Carcinoma

Adrenal cortical carcinoma (ACC) is a rare malignancy, and oncocytic ACC (OAC) is a rare histopathologic variant of ACC, with <70 cases documented worldwide as of 2021. This is a case of a 64-year-old female initially presenting with epigastric-to-periumbilical pain, left flank pain, nausea, vomiting, and bloatedness. Computed tomography (CT) urogram revealed a 12.2 x 12.7 x 15 cm left adrenal mass, with pulmonary metastases on chest CT. The patient was clinically and biochemically unremarkable based on the hormonal panel. Left thoracoabdominal adrenalectomy was done, and the left adrenal mass was identified as a high-grade non-functioning OAC on histopathology and immunohistochemistry. The patient showed clinical improvement on chemotherapy with etoposide, cisplatin, doxorubicin (EDP), without mitotane, due to local unavailability. In conclusion, while EDP + mitotane is the standard therapy for metastatic cases, EDP alone showed promising outcomes in improving quality of life and resolving paraneoplastic neuropathy in the absence of mitotane. To date and to the best of our knowledge, this is the first documented case of non-functioning OAC in the Philippines. DS-related Kaposi sarcoma (KS) progresses rapidly with early mucosal and systemic involvement. Early diagnosis and treatment are crucial as they significantly impact the outcome. This is a case of disseminated cutaneous and gastrointestinal KS in a 24-year-old Filipino male living with HIV, presenting with hyperpigmented violaceous subcutaneous nodules, odynophagia, progressive dysphagia, and symptomatic anemia. Capsule endoscopy demonstrated utility in diagnosing gastrointestinal KS lesions, highlighting its crucial role when conventional upper endoscopy was challenging due to oropharyngeal involvement. Diagnostic limitations, mainly the unavailability of human herpesvirus-8 (HHV-8) immunohistochemical stain, were addressed through high clinical suspicion. Multidisciplinary approach including chemotherapy with liposomal doxorubicin, radiotherapy, and supportive care eventually yielded good clinical response. This case emphasizes the importance of early diagnosis, timely intervention, and long-term surveillance in achieving favorable outcomes for patients with KS despite some diagnostic limitations.
Human ; Adrenocortical Carcinoma ; Abdominal Pain

Adrenocortical carcinoma (ACC) is a rare malignant tumour originating from the adrenal cortex. Half of the cases are functional, with ACTH independent autonomous cortisol production being the most common. It is rare for ACC to present with markedly elevated metanephrine levels which is a typical characteristic of pheochromocytoma. We report a case of a large functioning adrenal tumour with overlapping biochemistry features of ACC and pheochromocytoma. Biopsy confirmed the histopathological diagnosis of metastatic ACC.
Adrenocortical Carcinoma ; Pheochromocytoma

Adrenocortical carcinoma (ACC) accounts for 0.05-2% of all malignant tumors. Forty-five percent of ACCs with secretory function have excess glucocorticoids alone and only less than 1% secrete aldosterone.

This is a case of a 44-year-old Filipino female with hypertension and a 12-year-history of an incidentaloma of the left adrenal gland, with recent-onset complaints of increasing abdominal girth, purple striae, amenorrhea, moon facies and a dorsocervical fat pad. Laboratory findings revealed low potassium levels, non-suppressed cortisol on dexamethasone test suggesting Cushing’s syndrome and elevated aldosterone-renin ratio and plasma aldosterone concentration pointing to primary hyperaldosteronism. A computed tomography scan revealed a left-sided adrenal mass measuring approximately 23 cm in largest diameter suggestive of carcinoma without metastasis or lymph node involvement. Complete resection via open adrenalectomy was performed and histopathologic assessment revealed Adrenocortical Carcinoma with Weiss score of 4. The Ki-67 proliferative index was found to be >20%. Radiotherapy was done as an adjuvant treatment.

Although rare, co-secretion of cortisol and aldosterone can occur in functional tumors of adrenocortical carcinoma. Malignancy should always be considered in patients who present with a history of a unilateral adrenal mass and/ or in those with signs and symptoms of adrenal hormone excess. Thus, a proper assessment derived from a thorough medical history, physical examination and laboratory work-up is warranted in patients with an adrenal mass to ascertain the diagnosis and provide adequate management.

OBJECTIVE: To report the clinical and genetic characteristics of a rare case of Gitelman syndrome with comorbid Graves disease and ACTH-independent adrenocortical adenoma. METHODS: A patient who had presented at the Nanchong Central Hospital on December 21, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole-exome sequencing was carried out on DNA extracted from peripheral venous blood samples from the patient and her family members. RESULTS: The patient, a 45-year-old woman, was found to have Graves disease, ACTH-independent Cushing syndrome, hypokalemia and hypomagnesemia following the discovery of an adrenal incidentaloma. MRI scan had revealed a 3.8 cm × 3.2 cm mass in the left adrenal gland. The mass was removed by surgery and confirmed as adrenocortical adenoma. DNA sequencing revealed that the patient and her sister have both harbored compound heterozygous variants of the SLC12A3 gene, namely c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M), which were respectively inherited from their father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M) were respectively classified as a variant of uncertain significance (PM2_Supporting+PP3) and a likely pathogenic variant (PM3_Strong+PM1+PP3). CONCLUSION The conjunction of Gitelman syndrome with Graves disease and adrenal cortex adenoma is rather rare. The newly discovered c.1444-10(IVS11)G>A variant of the SLC12A3 gene, together with the heterozygous variant of c.179(exon1)C>T (p.T60M), probably underlay the pathogenesis in this patient.
Humans ; Female ; Middle Aged ; Gitelman Syndrome/genetics* ; Adrenocortical Adenoma ; Hypokalemia ; Graves Disease/genetics* ; Mothers ; Mutation ; Solute Carrier Family 12, Member 3

OBJECTIVE: To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS). METHODS: In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups. RESULTS: In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05). CONCLUSION ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.
Humans ; Cushing Syndrome/complications* ; Adrenocortical Adenoma/complications* ; Adrenocorticotropic Hormone ; Hydrocortisone ; Retrospective Studies ; Glycated Hemoglobin ; Adrenal Cortex Neoplasms/diagnosis* ; Adenoma/diagnosis* ; Thrombophilia/complications*

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l^-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml^-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.
Abiraterone Acetate/therapeutic use* ; Adrenal Cortex Hormones/therapeutic use* ; Androstenes ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Dexamethasone/therapeutic use* ; Disease-Free Survival ; Humans ; Male ; Prednisone/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Retrospective Studies ; Treatment Outcome

Adenoma, Oxyphilic/surgery* ; Adrenal Cortex Neoplasms/surgery* ; Adrenocortical Adenoma/surgery* ; Humans