Case Reports in Neurology
Case Rep Neurol 2025;17:204-210
DOI: 10.1159/000549473
Received: May 20, 2025 Accepted: October 31, 2025 Published online: November 21, 2025
@ 2025 The Author(s). OPEN ACCESS
Published by S. Karger AG, Basel www.karger.com/crn
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Single Case - Cerebrovascular Diseases and Stroke
New Diagnosis of Adrenocortical Carcinoma with Stroke Workup
Ruoyan Zhuª Tshibambe Nathanael Tshimbombuª Monica C. Rodriguezb Mercedes Martinez Gil” Kevin C.J. Yuenb Paige Banyasa
aDepartment of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center Phoenix, Phoenix, AZ, USA; bBarrow Pituitary Center and Neuroendocrinology Clinic, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton University School of Medicine, Phoenix, AZ, USA; “Department of Internal Medicine, Creighton University School of Medicine, Omaha, NE, USA
Keywords
Stroke . Adrenocortical carcinoma . Cushing syndrome
Abstract
Introduction: Ischemic stroke has well-established risk factors such as hypertension, diabetes, hyperlipidemia, and atrial fibrillation. However, strokes can also occur in the context of less common etiologies such as malignancies, particularly as certain malignancies are associated with hypercoagulable states. Adrenocortical carcinoma (ACC) is a malignancy that can present with a hypercortisolemic state, which can further exacerbate cancer coagulopathy and the traditional metabolic risk factors of stroke. Case Presentation: A 60-year-old woman presented with expressive aphasia and was found to have multifocal acute infarcts on magnetic resonance imaging. She underwent a thorough cardiac, coagulopathy, and paraneoplastic workup and was found to have a right adrenal mass and was biochemically hypercortisolemic. The patient underwent surgical resection of the adrenal mass and pathology confirmed the diagnosis of ACC. Conclusion: The discovery of this rare malignancy underscores the complex interplay between malignancy, hormonal imbalances, hypercoagulability in stroke and the importance of a comprehensive clinical diagnostic evaluation.
@ 2025 The Author(s). Published by S. Karger AG, Basel
Introduction
Stroke is recognized as one of the leading causes of morbidity and mortality worldwide, impacting millions of individuals each year [1]. The global burden of stroke is expected to increase in the coming decades, primarily due to demographic changes and healthcare
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| Case Reports in | Case Rep Neurol 2025;17:204-210 | |
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| DOI: 10.1159/000549473 | @ 2025 The Author(s). Published by S. Karger AG, Basel www.karger.com/crn | |
| Neurology | Zhu et al .: Diagnosis of Adrenocortical Carcinoma with Stroke Workup | |
challenges, especially in developing nations. Thus, effective stroke management requires a comprehensive approach, addressing immediate neurological care and including thorough evaluations for underlying conditions such as cancer and endocrine disorders.
The association between cancer and stroke is well-documented. In an autopsy study of patients with systemic cancer, 14.6% were found to have cerebral vascular disease [2]. Common mechanism of ischemic stroke in cancer patients includes paradoxical embolism from deep vein thrombosis, nonbacterial thrombotic endocarditis, and in- travascular coagulopathy [3]. Different types of malignancies also show a propensity to induce or exacerbate cerebrovascular events [4]. Among these, adrenocortical carci- noma (ACC) is a rare malignancy that can lead to a state of hypercortisolemia resulting in Cushing syndrome (CS) - a condition characterized by chronic hypercortisolemia that impacts multiple organ systems and heightens cardiovascular risk [5]. Elevated cortisol levels can lead to increased blood pressure, altered vascular reactivity, and throm- bophilia, all of which contribute to an increased risk of ischemic stroke. Furthermore, patients with CS often present with manifestations of metabolic syndrome, such as hypertension and dyslipidemia, notable independent risk factors for stroke development [6].
This case report discusses a patient who initially presented with expressive aphasia secondary to multifocal acute infarcts that was ultimately diagnosed with ACC and CS. The discovery of this unusual malignancy underscores the complex interplay between malig- nancy, hormonal imbalances, hypercoagulability, and the importance of a comprehensive clinical diagnostic evaluation.
Case Report
A 60-year-old woman with a previous history of hypothyroidism and primary hy- perparathyroidism status post parathyroidectomy presented to the emergency department for evaluation of 4 days of new onset nonfluent aphasia characterized by word-finding difficulty and loss of verbal fluency. The patient had no motor, sensory, or visual deficits and denied any headache, vomiting or vertigo. However, she endorsed 6 months of intermittent confusion, fatigue, bloating, constipation, bilateral lower extremity edema and approxi- mately 18 kg unintentional weight gain. The presenting National Institute of Health Stroke Scale was 1 for mild aphasia.
Given the patient’s medical history and symptoms, a broad workup was initiated to evaluate for a primary neurological condition that could explain her aphasia and cognitive changes as well as an assessment of her underlying endocrine conditions.
The patient underwent magnetic resonance imaging of the brain that revealed multiple small acute infarcts predominantly located in the left parietal and temporal cortices, with additional involvement in the bilateral frontoparietal subcortical white matter, the left occipital lobe, and the left cerebellum (shown in Fig. 1, 2). These findings were accompanied by evidence of chronic microvascular ischemic changes and a chronic lacunar infarcts, suggesting a preexisting disposition to ischemic events.
To assess the integrity of the cerebral vasculature, a magnetic resonance angiography of the head and neck was performed, which revealed no significant stenosis or occlusion. Given the absence of arterial abnormalities on magnetic resonance angiography and presence of acute infarcts involving multiple vascular territories, the diagnostic focus shifted toward searching for a central embolic source. A venous ultrasound of the bilateral lower ex- tremities identified a chronic, nonocclusive deep venous thrombosis (DVT) in the right femoral vein. To evaluate the possibility of paradoxical embolism, a transthoracic
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DOI: 10.1159/000549473
@ 2025 The Author(s). Published by S. Karger AG, Basel www.karger.com/crn
Zhu et al .: Diagnosis of Adrenocortical Carcinoma with Stroke Workup
echocardiogram with bubble study was conducted and failed to reveal an atrial septal defect or patent foramen ovale. Standard stroke risk factors were evaluated. Her hemoglobin A1c was 6.8% and thyroid stimulating hormone was elevated at 7.8 uIU/mL, though the patient had just recently resumed levothyroxine after a period of noncompliance. Fasting lipid panel showed a mildly elevated low-density lipoprotein of 105 mg/dl and a total cholesterol of 171 mg/dL. The patient denies any cardiac history and electrocardiogram and inpatient telemetry were negative for cardiac arrhythmias.
Blood work to evaluate for inherited and acquired thrombophilias, including lupus anticoagulant, antiphospholipid antibody panel, factor V Leiden mutation, antithrombin III deficiency, prothrombin gene mutation, and protein C and S activity yielded normal results. Given the patient’s presentation and the absence of a clear embolic source, the clinical suspicion heightened for an unknown malignancy contributing to a hypercoagulable state. A computed tomography (CT) scan of the chest, abdomen, and pelvis was performed to screen for occult malignancy.
CT chest, abdomen, pelvis with and without contrast revealed a 7.1 cm heterogeneously enhancing mass in the right adrenal gland with a central necrotic component and associated mass effect on the inferior vena cava (shown in Fig. 3). These characteristics raised concern for adrenal malignancy. Plasma levels of metanephrine and normetanephrine were mea- sured to evaluate for pheochromocytoma and were within normal limits (metanephrine 0.24 nmol/L and normetanephrine <0.1 nmol/L). A 1 mg overnight dexamethasone sup- pression test was then performed, revealing failed cortisol suppression with a morning cortisol level of 383.64 nmol/L, confirming the diagnosis of CS. The patient’s ACTH level was <1.10 pmol/L, consistent with an adrenal origin for CS.
On discharge, the patient was started on atorvastatin for secondary stroke prevention and apixaban for the treatment of her DVT and thromboprophylaxis for secondary stroke prevention in the setting of presumed cancer. She was referred to outpatient speech therapy for her aphasia. Two months later, the patient underwent a right adrenalectomy and the pathology report revealed a low-grade ACC.
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Case Reports in Neurology
DOI: 10.1159/000549473
Zhu et al .: Diagnosis of Adrenocortical Carcinoma with Stroke Workup
a
b
c
d
At 8-month follow-up, she reported one hospitalization following her surgery for ad- renal insufficiency for which she was treated with glucocorticoid replacement therapy. The patient is currently undergoing long term cardiac monitoring to further rule out a cardiac arrhythmia and continues to follow-up with endocrinology and oncology.
Discussion
This case report outlines a case of a 60-year-old woman who presented with a chief complaint of subacute expressive aphasia who was found to have embolic-appearing is- chemic infarcts in the setting of a right ACC. While aphasia without hemiparesis is a clinical feature suggestive of cardioembolic infarcts [7], the absence of traditional stroke risk factors
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DOI: 10.1159/000549473
@ 2025 The Author(s). Published by S. Karger AG, Basel www.karger.com/crn
Zhu et al .: Diagnosis of Adrenocortical Carcinoma with Stroke Workup
70.7 mm
a
b
such as vascular disease and cardiac arrhythmia and the eventual identification of a rare unknown malignancy highlight the lesser known paraneoplastic and metabolic contributors of ischemic stroke.
Ischemic stroke is a prevalent condition with multiple well-established risk factors including hypertension, diabetes, hyperlipidemia, and atrial fibrillation [8]. However, it can also occur in the context of less common etiologies such as malignancies, particularly those associated with hypercoagulable states. Although this patient did not have a known history of traditional vascular risk factors, a more detailed interview elicited symptoms of which suggested an underlying metabolic abnormality.
The final diagnosis of low-grade ACC carries significant implications for understanding the underlying hypercoagulable state in this patient. Adrenal cortical carcinoma is an uncommon malignancy associated with hypercoagulability due to both direct tumor effects and paraneoplastic syndromes. Tumor-derived factors, such as extracellular vesicles and tissue factor, initiate, and amplify coagulation pathways, promoting intravascular thrombus formation [3]. Additionally, cytokine production by tumor cells can trigger a pro- inflammatory response and induce a prothrombotic endothelium [9]. Because of this pathophysiology, venous and arterial thromboses are leading causes of mortality in cancer patients [10]. While paradoxical embolism is unlikely in this patient given the absence of a patent foramen ovale or atrial septal defect, the finding of a nonocclusive DVT raises concern for an underlying hypercoagulable state.
In this case, the patient’s malignancy was complicated by the fact that she had con- current CS, putting her at even greater risk for thrombotic events. Hypercortisolism con- tributes to hypercoagulable state by inducing elevated levels of procoagulant factors and reducing fibrinolytic activity [11]. Studies have shown that up to 70% of CS patients have glucose metabolism impairments [12], 80% have hypertension [13] and 72% have dysli- pidemia [14]. Therefore, vigilant stroke monitoring may be a consideration for these patients.
It is important to acknowledge the limitations of this case. ACTH levels and throm- bophilia tests are best done outside the acute phase since stress and illness can sometimes affect results. In our case, ACTH was measured soon after presentation, but the significantly
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| Case Reports in | Case Rep Neurol 2025;17:204-210 | |
|---|---|---|
| DOI: 10.1159/000549473 | @ 2025 The Author(s). Published by S. Karger AG, Basel www.karger.com/crn | |
| Neurology | Zhu et al .: Diagnosis of Adrenocortical Carcinoma with Stroke Workup | |
lower levels still clearly supported an adrenal source, in line with the large adrenal mass on imaging. Thrombophilia testing was also performed during the admission to assist the work- up, but we recognize that repeating these tests later, once the patient is stable, would be more accurate and may have higher utility in select populations (young patient, patients with patent foramen ovale, etc.), though more research is still warranted [15]. Furthermore, there is currently limited data on the benefit of anticoagulation for recurrent stroke in cancer patients with ischemic stroke [16]. Therefore, individualized evaluation and careful re- flection on comorbidities and bleeding risk is recommended when considering anti- coagulation. In this case, given that the patient did not possess high-risk features for bleeding (intracranial metastasis, thrombocytopenia) and was believed to have an underlying hy- percoagulable state that would predispose her to reoccurrence, the decision was made to cautiously initiate anticoagulation with the plan to reevaluate her antithrombotic regimen shortly after she underwent surgical treatment and consulted with her oncologist. Addi- tional research is needed to investigate the impact of anticoagulation on stroke recurrence in cancer patients.
This case not only emphasizes the need for thorough diagnostic measures when evaluating new neurological symptoms in patients with complex metabolic conditions but also highlights the importance of considering malignancy in patients presenting with acute stroke symptoms to avoid overlooking a potential underlying cause. It showcases how neurological presentations may precede the diagnosis of an endocrine malignancy.
In conclusion, this case is a compelling example of the intersection of endocrine dys- function, stroke, and malignancy, highlighting the potential for atypical presentations of stroke. Our key takeaway is that strokes of unclear etiology warrant a step-wise investi- gation and thorough review of systems as clinical outcomes can be impacted by timely diagnosis and management of the underlying pathology.
Acknowledgments
We would like to acknowledge and thank Dr. David Wang for providing feedback on the early conception of this paper.
Statement of Ethics
Ethical approval is not required for this case report in accordance with local or national guidelines. Written informed consent was obtained from the individual for publication of the details of their medical case and any accompanying images. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000549473).
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
This case report was not supported by any sponsor or funder.
Karger’s
Case Rep Neurol 2025;17:204-210
DOI: 10.1159/000549473
@ 2025 The Author(s). Published by S. Karger AG, Basel www.karger.com/crn
Zhu et al .: Diagnosis of Adrenocortical Carcinoma with Stroke Workup
Case Reports in Neurology
Author Contributions
P.B. and K.C.J.Y. supervised the work, reviewed the content, and edited the text in regard to their respective fields of expertise. M.C.R. was responsible for the diagnosis and man- agement of the case. R.Z. and T.N.T. wrote the manuscript with the support of M.M.G. on the endocrinological perspective.
Data Availability Statement
All data discussed or analyzed during this study are included in this article (and its online supplementary material files). Further inquiries can be directed to the corresponding author.
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