Concomitant pheochromocytoma and hyperaldosteronism in a 47-year-old man: A case report

Concomitant pheochromocytoma and hyperaldosteronism in a 47-year-old man: A case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Concomitant pheochromocytoma and hyperaldosteronism in a 47-year-old man: A case report Fatemeh Majidi, Ali Shabbak, Shadi Nazarizadeh, Aryan Madady This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4596371/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The coexistence of pheochromocytoma and hyperaldosteronism is a rare and clinically significant finding with diagnostic challenges that need to be considered in the workup of patients with hypertension. Case Presentation: This case report describes a 47-year-old man who initially presented with cold symptoms, chills, and headaches. Despite being diagnosed with panic disorder, his symptoms worsened, leading to a systolic blood pressure crisis. The results indicated elevated levels of 24-hour urine vanillylmandelic acid (VMA), metanephrine, and normetanephrine, suggesting increased catecholamine levels. An increase in serum aldosterone was also observed. Further evaluation revealed a 4 cm left adrenal mass and subsequent tests confirmed the diagnosis of pheochromocytoma and hyperaldosteronism. The patient underwent left adrenal gland resection, resulting in complete resolution of symptoms and normalization of test results. Conclusions: This case highlights the importance of considering rare coexisting endocrine disorders in patients presenting with hypertension. Appropriate diagnosis and management of concomitant pheochromocytoma and hyperaldosteronism are crucial for favorable outcomes and may offer insights into potential overlaps in disease pathways. pheochromocytoma hyperaldosteronism hypertension Figures Figure 1 Figure 2 Introduction In terms of etiology, hypertension can be primary without a known cause or secondary (with a known cause). Despite the higher prevalence of the primary type (90–95%), evaluating the secondary type is particularly important due to differences in treatment approaches and variable prognoses ( 1 , 2 ). Although factors such as renovascular disease, renal parenchymal disease, and obstructive sleep apnea can cause secondary hypertension, the most common cause of secondary hypertension is endocrine disorders ( 3 ). Approximately 63% of secondary hypertension cases are caused by primary hyperalderonism ( 4 ). Aldosterone is a hormone secreted from the cortical part of the adrenal gland that plays a role in regulating blood pressure by controlling sodium stored in the bloodstream and potassium output. Hyperalderonism can be primary (disorder in the adrenal glands) or secondary (disorder in other parts of the body). Primary hyperalderonism can cause serious cardiovascular complications such as atrial fibrillation, stroke, and myocardial infarction ( 5 ). The treatment of choice for unilateral disease is surgery, while mineralocorticoid receptor antagonists (MRAs) are available for treating bilateral lesions ( 6 ). Pheochromocytoma is an adrenal medulla tumor that occurs in 0.2–0.6% of hypertensive individuals and can arise from nonadrenal tissue in 10–15% of patients ( 7 ). Approximately 95% of patients with pheochromocytoma develop hypertension due to elevated levels of catecholamines, which can be either short-term or long-term. Hypertensive paroxysms (episodic hypertension) may occur in individuals despite the presence of constant hypertension ( 8 ). Other symptoms of this disease include headache, sweating, palpitations, abdominal discomfort, vomiting, extreme fatigue, indigestion, right hypochondrial pain, and increased liver enzymes ( 9 – 11 ). Screening for pheochromocytoma is performed by measuring 24-hour urine levels of catecholamines, total and fractionated metanephrine, and vanillyl-mandelic acid (VMA). Visualization of the mass by imaging with Computed Tomography scan (CT scan) or Magnetic Resonance Imaging (MRI) can also be used for diagnostic evaluation ( 7 ). A review of studies revealed that the simultaneous presence of two causes of secondary hypertension is not as rare as expected ( 12 , 13 ). However, the coexistence of pheochromocytoma and hyperalderonism is still rare. We present a patient with pheochromocytoma and hyperalderonism. Case report A 47-year-old man with a history of cold symptoms from four days ago, including fever, chills, sweating, and headache, was referred to the neurology unit with a headache complaint. Following a medical evaluation with a brain MRI, which did not show any pathological findings, he was diagnosed with panic attack disorder and received appropriate medication. The next day, he presented with worsening headache, agitation, and sweating without fever, nausea, or vomiting. A systolic blood pressure crisis of up to 250 mm Hg was reported. The patient's blood pressure did not improve with nitroglycerin (TNG) but decreased with labetalol. His 12-lead Electrocardiogram (ECG) revealed a normal sinus rhythm, no axis deviation, and no significant ST-segment or T-wave changes. (Fig. 1, Fig. 1 title: ECG, Fig. 1 legend: first day ECG, which showed normal findings without any rhythm disorder, axis deviation, ST-segment, or T-wave changes) He then underwent echocardiography to exclude the possibility of coarctation of the aorta. His blood sugar was 400 mg/dL. Serum electrolyte assessment revealed that the sodium (141.3 mmol/L), potassium (4.20 mmol/L), and chloride (102 mmol/L) concentrations were within normal limits. He was a smoker (one pack per year for ten years) without any other past medical history, such as diabetes mellitus or hypertension. The patient’s family history revealed left adrenal gland cancer in his aunt, which resulted in her death at a young age, and a history of diabetes mellitus in his family members. An abdominal CT scan was requested due to the suspicion of an adrenal tumor, and a 4 cm left adrenal mass was observed without any other pathological findings, such as pancreatic lesions. (Fig. 2, Fig. 2 title: abdominopelvic CT scan with and without contrast, Fig. 2 legend: (A): axial view of Pre-contrast abdominopelvic CT scan, (B): axial view of abdominopelvic CT with contrast. (C): coronal view of Pre-contrast abdominopelvic CT scan, (D): coronal view of abdominopelvic CT with contrast; (A) and (C) demonstrated a 4 cm mass in the left adrenal (arrow), (B) and (D) showed mass enhancement with contrast (arrow)) Following the observation of the adrenal mass, additional tests were conducted, revealing the following results: a 24-hour urine cortisol level of 172.5 g/24 hrs (within the normal range of 50–190 g/24 hrs), a 24-hour urine vanillylmandelic acid (VMA) concentration of 18.35 mg/24 hrs (elevated compared to the normal limit of 13.6 mg/24 hrs), 24-hour urine metanephrine levels exceeding 2000 µg/24 hrs, and a 24-hour urine normetanephrine level of 1731.9 µg/24 hrs. The findings revealed an increase in catecholamine levels in the 24-hour urine sample. Regarding microalbuminuria and creatinine, the test findings indicated normal results; however, the 24-hour urine volume was 2500 ml, which is considered elevated. The notably high serum aldosterone level of 24.70 ng/dL was of particular significance. Subsequent assessment was conducted to investigate the presence of multiple endocrine neoplasia (MEN) syndromes. The results of his thyroid and parathyroid ultrasound were found to be normal, and his brain MRI did not show any abnormal findings, such as pituitary gland adenoma. Additionally, normal thyroid function tests ruled out the possibility of MEN syndrome and thyroiditis. Based on these results, the diagnosis of pheochromocytoma combined with hyperaldosteronism was confirmed. Following the management of blood pressure with alpha-blockers, the patient underwent surgical resection of the left adrenal gland. The renin levels were not measured to determine the classification of hyperaldosteronism (primary or secondary), as the decision to proceed with adrenal gland resection had already been made, and it would not have altered the treatment plan. Following surgery, the patient's symptoms completely resolved, and all test results returned to within normal ranges. Discussion The patient in question initially presented to a neurologist with a chief complaint of headaches, leading to a consideration of panic attack as a potential diagnosis. In cases of pheochromocytoma, the presence of palpitations, often described as "my heart is coming out of the chest," and feelings of anxiety may lead the neurologist to initially suspect panic and anxiety disorders. These symptoms can be attributed to elevated levels of catecholamines in the patient's serum, which are also elevated in individuals experiencing panic and anxiety ( 14 ). However, persistent headaches and elevated blood pressure prompted further investigation into potential endocrine disruptions. Therefore, it is crucial to be mindful of these two manifestations in patients who are initially suspected of having panic and anxiety disorders. While there was no laboratory confirmation specifically indicating primary hyperaldosteronism, the normalization of all relevant parameters subsequent to the resection of the adrenal gland, coupled with the absence of symptom recurrence or hypertension for a duration of one year, allows for the inference that the elevated secretion of aldosterone was indeed attributable to the excised adrenal gland. This increased secretion may have resulted from either an excessive release of aldosterone from the adrenal cortex or the release of an aldosterone-stimulating factor originating from the pheochromocytoma. Furthermore, based on the patient's response following surgical intervention, the possibility of a contralateral adenoma or bilateral adrenal hyperplasia can be effectively discounted. Cases of simultaneous pheochromocytoma and primary aldosteronism are rare, and in a case series and literature review by Mao et al. in 2021, only 15 patients were identified and described ( 15 ). Among these patients, high blood pressure emerged as the prevailing symptom, with 13 out of the 15 patients exhibiting this manifestation, according to the study. Notably, the prevalence of hypokalemia mirrors that of hypertension among patients presenting with pheochromocytoma and primary aldosteronism. Hypokalemia, attributable to the direct impact of aldosterone on serum potassium levels, constitutes one of the diagnostic findings of aldosteronism. While its prevalence remains relatively modest in primary aldosteronism cases (below 40% in the absence of concurrent conditions) ( 16 ), an approximate incidence of 87% has been reported in simultaneous cases of pheochromocytoma and aldosteronism ( 15 ). However, in the specific patient under investigation, the patient's potassium level before any intervention was measured at 4.20 mmol/L, denoting a state of complete normalcy. Research has demonstrated that in patients with concurrent pheochromocytoma and primary aldosteronism, the failure to administer adrenergic blockers prior to surgery can potentially lead to life-threatening blood pressure crises ( 17 ). In our patient, upon suspicion of pheochromocytoma, standard diagnostic tests were conducted to confirm the presence of the tumor. Additionally, aldosterone level testing was requested, and based on the elevated aldosterone levels and the absence of contralateral adrenal masses, the proposed course of action involved unilateral adrenal gland resection following pretreatment with alpha-blockers. After surgery, the patient experienced remarkable improvement, and his symptoms disappeared. This highlights the favorable prognosis associated with adrenal gland resection in such cases. Conclusion The concurrent occurrence of pheochromocytoma and primary aldosteronism represents an infrequent yet manageable medical condition that necessitates prompt identification by physicians. Failure to detect pheochromocytoma in such patients may lead to unfavorable outcomes if surgical intervention targeting hyperaldosteronism is pursued without prior pretreatment. Notably, despite markedly elevated blood pressure in affected individuals, their potassium levels can remain within the normal range. Abbreviations VMA vanillylmandelic acid MRAs mineralocorticoid receptor antagonists CT scan Computed Tomography scan MRI Magnetic Resonance Imaging ECG Electrocardiogram MEN multiple endocrine neoplasia Declarations Ethics approval and consent to participate: ethical approval is Not applicable, and patients’ Written informed consent to participate is present. Consent for publication: patients’ Written informed consent is present and available upon request Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests Funding: none Authors' contributions: FM Conceptualized the study, collected data, and revised the manuscript. AS collected data, drafted the manuscript, and ensured the completion of the final draft. SN drafted the manuscript and participated in the Review & Editing of the manuscript. AM Reviewed the literature and drafted the manuscript. All authors read and approved the final manuscript Acknowledgements: Not applicable References Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2018;71(19):e127-e248. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). European heart journal. 2018;39(33):3021-104. Daly PL, Goodwin ET, Kipnis CM, Smith DK. Hypertensive Conditions: Secondary Causes of Hypertension in Adults. FP essentials. 2022;522:13-7. Morganti A, Rosei EA, Mantero F. Secondary hypertension: Springer; 2020. Cohen JB, Bancos I, Brown JM, Sarathy H, Turcu AF, Cohen DL. Primary Aldosteronism and the Role of Mineralocorticoid Receptor Antagonists for the Heart and Kidneys. Annual Review of Medicine. 2023;74:217-30. Takeda Y, Demura M, Yoneda T. Medical Treatment of Primary Aldosteronism. Primary Aldosteronism: Molecular Genetics, Endocrinology, and Translational Medicine. 2014:209-14. Farrugia F, Martikos G, Tzanetis P, Charalampopoulos A, Misiakos E, Zavras N, et al. Pheochromocytoma, diagnosis and treatment: Review of the literature. Endocr Regul. 2017;51(3):168-81. Wang X, Zhao Q, Sang H, Dong J, Bai M. Research on the damage of adrenal pheochromocytoma to patients’ cardiovascular vessels and its correlation with hypertension. Journal of Oncology. 2022;2022. Baig M, Khan SW, Shakeel Z, Ahmad A, Khan KJ. Pheochromocytoma Presenting with Upper GI Symptoms: A Case Report. Pakistan Journal of Medical & Health Sciences. 2023;17(02):268-. Choi Y, Lee J-H, Song H-K, Bae JS, Kim Y. Pheochromocytoma-related Headache and Symptoms that Should Not be Overlooked: A Case Report. Journal of Neurosonology and Neuroimaging. 2023;15(1):54-6. Habib MB, Abdelrazek M, Alatasi S, Mohamed MF, Ali H, Hamad MK. Pheochromocytoma presenting with severe abdominal pain and abnormal liver enzymes. Clinical Case Reports. 2021;9(8):e04640. Vallejo-Vaz AJ, Grilo A, Villar J, Domínguez-Hidalgo L, Stiefel P. Coexistence of two causes of secondary hypertension in a single patient. Revista Clínica Española. 2013;213(8):e81-e3. Wang L, Li N, Yao X, Chang G, Zhang D, Heizhati M, et al. Detection of secondary causes and coexisting diseases in hypertensive patients: OSA and PA are the common causes associated with hypertension. BioMed Research International. 2017;2017. Alguire C, Chbat J, Forest I, Godbout A, Bourdeau I. Unusual presentation of pheochromocytoma: thirteen years of anxiety requiring psychiatric treatment. Endocrinology, Diabetes & Metabolism Case Reports. 2018;2018(1). Mao JJ, Baker JE, Rainey WE, Young Jr WF, Bancos I. Concomitant pheochromocytoma and primary aldosteronism: a case series and literature review. Journal of the Endocrine Society. 2021;5(8):bvab107. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism. 2016;101(5):1889-916. Myklejord DJ. Undiagnosed pheochromocytoma: the anesthesiologist nightmare. Clinical Medicine & Research. 2004;2(1):59-62. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4596371","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":316697412,"identity":"a31f5a8d-0f20-426b-a878-9e584417b4bf","order_by":0,"name":"Fatemeh Majidi","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Fatemeh","middleName":"","lastName":"Majidi","suffix":""},{"id":316697413,"identity":"74e7276f-5bcb-4857-b246-6b7b0c3ce525","order_by":1,"name":"Ali Shabbak","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYDACCQY2ZgaGBAY+ZuYDIK4M8VrYmNkSQFweErQw8BiA+IS1yM9ufva4oCZNno2d5/OrGzUWPAzsh49uwKfF4M4xc+MZx3IM25h5t1nnHAM6jCct7QZeLRIJZtI8bBWMIC3GOWxALRI8Zni1yM9I/ybN86/Cvo2Z55lxzj8itDDcyDGT5m3LSQRqYX6c20aEFoMbOeXGM/vSktuY2cyYc/skeNgI+QXosG2PC74l2/bzH378OedbnRw/++Fj+B2GBNgkwCSxykGA+QMpqkfBKBgFo2DkAAB06z+CoZAdGAAAAABJRU5ErkJggg==","orcid":"","institution":"Guilan University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Ali","middleName":"","lastName":"Shabbak","suffix":""},{"id":316697414,"identity":"de5df0b5-70bf-4dca-b72c-17c987ed674b","order_by":2,"name":"Shadi Nazarizadeh","email":"","orcid":"","institution":"Shahid Chamran University of Ahvaz","correspondingAuthor":false,"prefix":"","firstName":"Shadi","middleName":"","lastName":"Nazarizadeh","suffix":""},{"id":316697415,"identity":"d8a86a65-39ed-408b-a6d3-5e80201783bb","order_by":3,"name":"Aryan Madady","email":"","orcid":"","institution":"Alborz University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Aryan","middleName":"","lastName":"Madady","suffix":""}],"badges":[],"createdAt":"2024-06-18 00:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4596371/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4596371/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59030205,"identity":"12761755-c033-4f8f-90fb-5606891ed11c","added_by":"auto","created_at":"2024-06-25 14:03:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1656981,"visible":true,"origin":"","legend":"\u003cp\u003eECG\u003c/p\u003e\n\u003cp\u003efirst day ECG, which showed normal findings without any rhythm disorder, axis deviation, ST-segment, or T-wave changes\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4596371/v1/b4a443c8d23ca3880de379d5.png"},{"id":59030206,"identity":"40e21d50-9ad8-48ca-8cec-4396721b96fc","added_by":"auto","created_at":"2024-06-25 14:03:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":707138,"visible":true,"origin":"","legend":"\u003cp\u003eAbdominopelvic CT scan\u003cstrong\u003e \u003c/strong\u003ewith and without contrast\u003c/p\u003e\n\u003cp\u003e(A): axial view of Pre-contrast abdominopelvic CT scan, (B): axial view of abdominopelvic CT with contrast. (C): coronal view of Pre-contrast abdominopelvic CT scan, (D): coronal view of abdominopelvic CT with contrast; (A) and (C) demonstrated\u003cstrong\u003e \u003c/strong\u003ea 4 cm mass in the left adrenal (arrow), (B) and (D) showed mass enhancement with contrast (arrow)\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4596371/v1/b48276144b98ad60b17ff16f.png"},{"id":59030215,"identity":"af2a7ac6-f835-4d8d-8ad8-b60f43e0d7f0","added_by":"auto","created_at":"2024-06-25 14:03:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2711472,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4596371/v1/15c0ac5d-e89e-4820-bb72-e1bdead109fa.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Concomitant pheochromocytoma and hyperaldosteronism in a 47-year-old man: A case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn terms of etiology, hypertension can be primary without a known cause or secondary (with a known cause). Despite the higher prevalence of the primary type (90\u0026ndash;95%), evaluating the secondary type is particularly important due to differences in treatment approaches and variable prognoses (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Although factors such as renovascular disease, renal parenchymal disease, and obstructive sleep apnea can cause secondary hypertension, the most common cause of secondary hypertension is endocrine disorders (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Approximately 63% of secondary hypertension cases are caused by primary hyperalderonism (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Aldosterone is a hormone secreted from the cortical part of the adrenal gland that plays a role in regulating blood pressure by controlling sodium stored in the bloodstream and potassium output. Hyperalderonism can be primary (disorder in the adrenal glands) or secondary (disorder in other parts of the body). Primary hyperalderonism can cause serious cardiovascular complications such as atrial fibrillation, stroke, and myocardial infarction (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The treatment of choice for unilateral disease is surgery, while mineralocorticoid receptor antagonists (MRAs) are available for treating bilateral lesions (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePheochromocytoma is an adrenal medulla tumor that occurs in 0.2\u0026ndash;0.6% of hypertensive individuals and can arise from nonadrenal tissue in 10\u0026ndash;15% of patients (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Approximately 95% of patients with pheochromocytoma develop hypertension due to elevated levels of catecholamines, which can be either short-term or long-term. Hypertensive paroxysms (episodic hypertension) may occur in individuals despite the presence of constant hypertension (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Other symptoms of this disease include headache, sweating, palpitations, abdominal discomfort, vomiting, extreme fatigue, indigestion, right hypochondrial pain, and increased liver enzymes (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Screening for pheochromocytoma is performed by measuring 24-hour urine levels of catecholamines, total and fractionated metanephrine, and vanillyl-mandelic acid (VMA). Visualization of the mass by imaging with Computed Tomography scan (CT scan) or Magnetic Resonance Imaging (MRI) can also be used for diagnostic evaluation (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). A review of studies revealed that the simultaneous presence of two causes of secondary hypertension is not as rare as expected (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). However, the coexistence of pheochromocytoma and hyperalderonism is still rare. We present a patient with pheochromocytoma and hyperalderonism.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 47-year-old man with a history of cold symptoms from four days ago, including fever, chills, sweating, and headache, was referred to the neurology unit with a headache complaint.\u003c/p\u003e \u003cp\u003eFollowing a medical evaluation with a brain MRI, which did not show any pathological findings, he was diagnosed with panic attack disorder and received appropriate medication.\u003c/p\u003e \u003cp\u003eThe next day, he presented with worsening headache, agitation, and sweating without fever, nausea, or vomiting. A systolic blood pressure crisis of up to 250 mm Hg was reported. The patient's blood pressure did not improve with nitroglycerin (TNG) but decreased with labetalol.\u003c/p\u003e \u003cp\u003eHis 12-lead Electrocardiogram (ECG) revealed a normal sinus rhythm, no axis deviation, and no significant ST-segment or T-wave changes. (Fig.\u0026nbsp;1, Fig.\u0026nbsp;1 title: ECG, Fig.\u0026nbsp;1 legend: first day ECG, which showed normal findings without any rhythm disorder, axis deviation, ST-segment, or T-wave changes) He then underwent echocardiography to exclude the possibility of coarctation of the aorta.\u003c/p\u003e \u003cp\u003eHis blood sugar was 400 mg/dL. Serum electrolyte assessment revealed that the sodium (141.3 mmol/L), potassium (4.20 mmol/L), and chloride (102 mmol/L) concentrations were within normal limits. He was a smoker (one pack per year for ten years) without any other past medical history, such as diabetes mellitus or hypertension. The patient\u0026rsquo;s family history revealed left adrenal gland cancer in his aunt, which resulted in her death at a young age, and a history of diabetes mellitus in his family members. An abdominal CT scan was requested due to the suspicion of an adrenal tumor, and a 4 cm left adrenal mass was observed without any other pathological findings, such as pancreatic lesions. (Fig.\u0026nbsp;2, Fig.\u0026nbsp;2 title: abdominopelvic CT scan with and without contrast, Fig.\u0026nbsp;2 legend: (A): axial view of Pre-contrast abdominopelvic CT scan, (B): axial view of abdominopelvic CT with contrast. (C): coronal view of Pre-contrast abdominopelvic CT scan, (D): coronal view of abdominopelvic CT with contrast; (A) and (C) demonstrated a 4 cm mass in the left adrenal (arrow), (B) and (D) showed mass enhancement with contrast (arrow))\u003c/p\u003e \u003cp\u003eFollowing the observation of the adrenal mass, additional tests were conducted, revealing the following results: a 24-hour urine cortisol level of 172.5 g/24 hrs (within the normal range of 50\u0026ndash;190 g/24 hrs), a 24-hour urine vanillylmandelic acid (VMA) concentration of 18.35 mg/24 hrs (elevated compared to the normal limit of 13.6 mg/24 hrs), 24-hour urine metanephrine levels exceeding 2000 \u0026micro;g/24 hrs, and a 24-hour urine normetanephrine level of 1731.9 \u0026micro;g/24 hrs. The findings revealed an increase in catecholamine levels in the 24-hour urine sample. Regarding microalbuminuria and creatinine, the test findings indicated normal results; however, the 24-hour urine volume was 2500 ml, which is considered elevated. The notably high serum aldosterone level of 24.70 ng/dL was of particular significance. Subsequent assessment was conducted to investigate the presence of multiple endocrine neoplasia (MEN) syndromes. The results of his thyroid and parathyroid ultrasound were found to be normal, and his brain MRI did not show any abnormal findings, such as pituitary gland adenoma. Additionally, normal thyroid function tests ruled out the possibility of MEN syndrome and thyroiditis.\u003c/p\u003e \u003cp\u003eBased on these results, the diagnosis of pheochromocytoma combined with hyperaldosteronism was confirmed. Following the management of blood pressure with alpha-blockers, the patient underwent surgical resection of the left adrenal gland. The renin levels were not measured to determine the classification of hyperaldosteronism (primary or secondary), as the decision to proceed with adrenal gland resection had already been made, and it would not have altered the treatment plan. Following surgery, the patient's symptoms completely resolved, and all test results returned to within normal ranges.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe patient in question initially presented to a neurologist with a chief complaint of headaches, leading to a consideration of panic attack as a potential diagnosis. In cases of pheochromocytoma, the presence of palpitations, often described as \"my heart is coming out of the chest,\" and feelings of anxiety may lead the neurologist to initially suspect panic and anxiety disorders. These symptoms can be attributed to elevated levels of catecholamines in the patient's serum, which are also elevated in individuals experiencing panic and anxiety (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). However, persistent headaches and elevated blood pressure prompted further investigation into potential endocrine disruptions. Therefore, it is crucial to be mindful of these two manifestations in patients who are initially suspected of having panic and anxiety disorders.\u003c/p\u003e \u003cp\u003eWhile there was no laboratory confirmation specifically indicating primary hyperaldosteronism, the normalization of all relevant parameters subsequent to the resection of the adrenal gland, coupled with the absence of symptom recurrence or hypertension for a duration of one year, allows for the inference that the elevated secretion of aldosterone was indeed attributable to the excised adrenal gland. This increased secretion may have resulted from either an excessive release of aldosterone from the adrenal cortex or the release of an aldosterone-stimulating factor originating from the pheochromocytoma. Furthermore, based on the patient's response following surgical intervention, the possibility of a contralateral adenoma or bilateral adrenal hyperplasia can be effectively discounted.\u003c/p\u003e \u003cp\u003eCases of simultaneous pheochromocytoma and primary aldosteronism are rare, and in a case series and literature review by Mao et al. in 2021, only 15 patients were identified and described (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Among these patients, high blood pressure emerged as the prevailing symptom, with 13 out of the 15 patients exhibiting this manifestation, according to the study. Notably, the prevalence of hypokalemia mirrors that of hypertension among patients presenting with pheochromocytoma and primary aldosteronism. Hypokalemia, attributable to the direct impact of aldosterone on serum potassium levels, constitutes one of the diagnostic findings of aldosteronism. While its prevalence remains relatively modest in primary aldosteronism cases (below 40% in the absence of concurrent conditions) (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), an approximate incidence of 87% has been reported in simultaneous cases of pheochromocytoma and aldosteronism (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). However, in the specific patient under investigation, the patient's potassium level before any intervention was measured at 4.20 mmol/L, denoting a state of complete normalcy. Research has demonstrated that in patients with concurrent pheochromocytoma and primary aldosteronism, the failure to administer adrenergic blockers prior to surgery can potentially lead to life-threatening blood pressure crises (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In our patient, upon suspicion of pheochromocytoma, standard diagnostic tests were conducted to confirm the presence of the tumor.\u003c/p\u003e \u003cp\u003eAdditionally, aldosterone level testing was requested, and based on the elevated aldosterone levels and the absence of contralateral adrenal masses, the proposed course of action involved unilateral adrenal gland resection following pretreatment with alpha-blockers. After surgery, the patient experienced remarkable improvement, and his symptoms disappeared. This highlights the favorable prognosis associated with adrenal gland resection in such cases.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe concurrent occurrence of pheochromocytoma and primary aldosteronism represents an infrequent yet manageable medical condition that necessitates prompt identification by physicians. Failure to detect pheochromocytoma in such patients may lead to unfavorable outcomes if surgical intervention targeting hyperaldosteronism is pursued without prior pretreatment. Notably, despite markedly elevated blood pressure in affected individuals, their potassium levels can remain within the normal range.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eVMA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evanillylmandelic acid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMRAs\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emineralocorticoid receptor antagonists\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCT scan\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComputed Tomography scan\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMRI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic Resonance Imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eECG\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectrocardiogram\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMEN\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emultiple endocrine neoplasia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eethical approval is Not applicable, and patients’ Written informed consent to participate is present.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003epatients’ Written informed consent is present and available upon request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003enone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFM Conceptualized the study, collected data, and revised the manuscript. AS collected data, drafted the manuscript, and ensured the completion of the final draft. SN drafted the manuscript and participated in the Review \u0026amp; Editing of the manuscript. AM Reviewed the literature and drafted the manuscript. All authors read and approved the final manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWhelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2018;71(19):e127-e248.\u003c/li\u003e\n\u003cli\u003eWilliams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). European heart journal. 2018;39(33):3021-104.\u003c/li\u003e\n\u003cli\u003eDaly PL, Goodwin ET, Kipnis CM, Smith DK. Hypertensive Conditions: Secondary Causes of Hypertension in Adults. FP essentials. 2022;522:13-7.\u003c/li\u003e\n\u003cli\u003eMorganti A, Rosei EA, Mantero F. Secondary hypertension: Springer; 2020.\u003c/li\u003e\n\u003cli\u003eCohen JB, Bancos I, Brown JM, Sarathy H, Turcu AF, Cohen DL. Primary Aldosteronism and the Role of Mineralocorticoid Receptor Antagonists for the Heart and Kidneys. Annual Review of Medicine. 2023;74:217-30.\u003c/li\u003e\n\u003cli\u003eTakeda Y, Demura M, Yoneda T. Medical Treatment of Primary Aldosteronism. Primary Aldosteronism: Molecular Genetics, Endocrinology, and Translational Medicine. 2014:209-14.\u003c/li\u003e\n\u003cli\u003eFarrugia F, Martikos G, Tzanetis P, Charalampopoulos A, Misiakos E, Zavras N, et al. Pheochromocytoma, diagnosis and treatment: Review of the literature. Endocr Regul. 2017;51(3):168-81.\u003c/li\u003e\n\u003cli\u003eWang X, Zhao Q, Sang H, Dong J, Bai M. Research on the damage of adrenal pheochromocytoma to patients\u0026rsquo; cardiovascular vessels and its correlation with hypertension. Journal of Oncology. 2022;2022.\u003c/li\u003e\n\u003cli\u003eBaig M, Khan SW, Shakeel Z, Ahmad A, Khan KJ. Pheochromocytoma Presenting with Upper GI Symptoms: A Case Report. Pakistan Journal of Medical \u0026amp; Health Sciences. 2023;17(02):268-.\u003c/li\u003e\n\u003cli\u003eChoi Y, Lee J-H, Song H-K, Bae JS, Kim Y. Pheochromocytoma-related Headache and Symptoms that Should Not be Overlooked: A Case Report. Journal of Neurosonology and Neuroimaging. 2023;15(1):54-6.\u003c/li\u003e\n\u003cli\u003eHabib MB, Abdelrazek M, Alatasi S, Mohamed MF, Ali H, Hamad MK. Pheochromocytoma presenting with severe abdominal pain and abnormal liver enzymes. Clinical Case Reports. 2021;9(8):e04640.\u003c/li\u003e\n\u003cli\u003eVallejo-Vaz AJ, Grilo A, Villar J, Dom\u0026iacute;nguez-Hidalgo L, Stiefel P. Coexistence of two causes of secondary hypertension in a single patient. Revista Cl\u0026iacute;nica Espa\u0026ntilde;ola. 2013;213(8):e81-e3.\u003c/li\u003e\n\u003cli\u003eWang L, Li N, Yao X, Chang G, Zhang D, Heizhati M, et al. Detection of secondary causes and coexisting diseases in hypertensive patients: OSA and PA are the common causes associated with hypertension. BioMed Research International. 2017;2017.\u003c/li\u003e\n\u003cli\u003eAlguire C, Chbat J, Forest I, Godbout A, Bourdeau I. Unusual presentation of pheochromocytoma: thirteen years of anxiety requiring psychiatric treatment. Endocrinology, Diabetes \u0026amp; Metabolism Case Reports. 2018;2018(1).\u003c/li\u003e\n\u003cli\u003eMao JJ, Baker JE, Rainey WE, Young Jr WF, Bancos I. Concomitant pheochromocytoma and primary aldosteronism: a case series and literature review. Journal of the Endocrine Society. 2021;5(8):bvab107.\u003c/li\u003e\n\u003cli\u003eFunder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. The Journal of Clinical Endocrinology \u0026amp; Metabolism. 2016;101(5):1889-916.\u003c/li\u003e\n\u003cli\u003eMyklejord DJ. Undiagnosed pheochromocytoma: the anesthesiologist nightmare. Clinical Medicine \u0026amp; Research. 2004;2(1):59-62.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"pheochromocytoma, hyperaldosteronism, hypertension","lastPublishedDoi":"10.21203/rs.3.rs-4596371/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4596371/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e The coexistence of pheochromocytoma and hyperaldosteronism is a rare and clinically significant finding with diagnostic challenges that need to be considered in the workup of patients with hypertension.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation:\u003c/strong\u003e This case report describes a 47-year-old man who initially presented with cold symptoms, chills, and headaches. Despite being diagnosed with panic disorder, his symptoms worsened, leading to a systolic blood pressure crisis. The results indicated elevated levels of 24-hour urine vanillylmandelic acid (VMA), metanephrine, and normetanephrine, suggesting increased catecholamine levels. An increase in serum aldosterone was also observed. Further evaluation revealed a 4 cm left adrenal mass and subsequent tests confirmed the diagnosis of pheochromocytoma and hyperaldosteronism. The patient underwent left adrenal gland resection, resulting in complete resolution of symptoms and normalization of test results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThis case highlights the importance of considering rare coexisting endocrine disorders in patients presenting with hypertension. Appropriate diagnosis and management of concomitant pheochromocytoma and hyperaldosteronism are crucial for favorable outcomes and may offer insights into potential overlaps in disease pathways.\u003c/p\u003e","manuscriptTitle":"Concomitant pheochromocytoma and hyperaldosteronism in a 47-year-old man: A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-25 14:03:42","doi":"10.21203/rs.3.rs-4596371/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8f73fce1-8dac-4cba-aaeb-66c41ee24335","owner":[],"postedDate":"June 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-25T14:03:42+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-25 14:03:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4596371","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4596371","identity":"rs-4596371","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}