Exploration of Endocrine and Metabolic Diseases

Table 1. Major endocrine causes of HT and their hormonal profiles.

Disorder	Principal hormone	Source	Mechanism of HT	Biochemical findings	Ref. No.
Primary aldosteronism	Aldosterone	Adrenal cortex (zona glomerulosa)	Sodium retention, potassium loss, plasma volume expansion	↑ Aldosterone, ↓ renin, ↑ ARR	[1–4, 8]
Pheochromocytoma/Paraganglioma	Catecholamines (epinephrine, norepinephrine, dopamine)	Adrenal medulla/extra-adrenal paraganglia	α/β-Adrenergic overstimulation	↑ Plasma/Urinary metanephrines	[6, 23–28]
CS	Cortisol	Adrenal cortex (zona fasciculata)	Mineralocorticoid receptor activation, insulin resistance	↑ Cortisol, loss of diurnal rhythm	[41–44]

Return to article view

ARR: aldosterone-to-renin ratio; HT: hypertension; CS: Cushing syndrome.

Declarations

Author contributions

MMŞ: Conceptualization, Investigation, Writing—original draft. MK: Conceptualization, Writing—review & editing. MY: Writing—review & editing. MCÇ: Conceptualization, Investigation, Writing—original draft. LB: Supervision, Validation. YK: Supervision, Validation. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

No financial funding was received for this study.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Carey RM, Calhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-Himmelfarb CR, et al.; American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; Stroke Council. Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association. Hypertension. 2018;72:e53–90. [DOI] [PubMed] [PMC]

Reincke M, Bancos I, Mulatero P, Scholl UI, Stowasser M, Williams TA. Diagnosis and treatment of primary aldosteronism. Lancet Diabetes Endocrinol. 2021;9:876–92. [DOI] [PubMed]

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. J Clin Endocrinol Metab. 2016;101:1889–916. [DOI] [PubMed]

Buonafine M, Bonnard B, Jaisser F. Mineralocorticoid Receptor and Cardiovascular Disease. Am J Hypertens. 2018;31:1165–74. [DOI] [PubMed]

Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study. Lancet Diabetes Endocrinol. 2018;6:51–9. [DOI] [PubMed] [PMC]

Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, et al.; Endocrine Society. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:1915–42. [DOI] [PubMed]

Fallo F, Di Dalmazi G, Beuschlein F, Biermasz NR, Castinetti F, Elenkova A, et al. Diagnosis and management of hypertension in patients with Cushing's syndrome: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension. J Hypertens. 2022;40:2085–101. [DOI] [PubMed]

Monticone S, D’Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018;6:41–50. [DOI] [PubMed]

Dekkers OM, Horváth-Puhó E, Jørgensen JO, Cannegieter SC, Ehrenstein V, Vandenbroucke JP, et al. Multisystem morbidity and mortality in Cushing’s syndrome: a cohort study. J Clin Endocrinol Metab. 2013;98:2277–84. [DOI] [PubMed]

10.

Pappachan JM, Fernandez CJ, editors. Endocrine Hypertension: From Basic Science to Clinical Practice. Academic Press; 2023. [DOI]

11.

Young WF Jr. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J Intern Med. 2019;285:126–48. [DOI] [PubMed]

12.

Chilton RJ, Silva-Cardoso J. Mineralocorticoid receptor antagonists in cardiovascular translational biology. Cardiovasc Endocrinol Metab. 2023;12:e0289. [DOI] [PubMed] [PMC]

13.

Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EA, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol. 2002;283:H1802–10. [DOI] [PubMed]

14.

Brilla CG, Matsubara LS, Weber KT. Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. Am J Cardiol. 1993;71:12A–6A. [DOI] [PubMed]

15.

Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45:1243–8. [DOI] [PubMed]

16.

Pan CT, Liao CW, Tsai CH, Chen ZW, Chen L, Hung CS, et al.; TAIPAI study group. Influence of Different Treatment Strategies on New-Onset Atrial Fibrillation Among Patients With Primary Aldosteronism: A Nationwide Longitudinal Cohort-Based Study. J Am Heart Assoc. 2020;9:e013699. [DOI] [PubMed] [PMC]

17.

Rossi GP, Maiolino G, Flego A, Belfiore A, Bernini G, Fabris B, et al.; PAPY Study Investigators. Adrenalectomy Lowers Incident Atrial Fibrillation in Primary Aldosteronism Patients at Long Term. Hypertension. 2018;71:585–91. [DOI] [PubMed]

18.

Nishimoto K, Seki T, Hayashi Y, Mikami S, Al-Eyd G, Nakagawa K, et al. Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation. Int J Endocrinol. 2016;2016:7834356. [DOI] [PubMed] [PMC]

19.

Catena C, Colussi G, Lapenna R, Nadalini E, Chiuch A, Gianfagna P, et al. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension. 2007;50:911–8. [DOI] [PubMed]

20.

Chen SY, Chen JY, Huang WC, Puar THK, Chin Kek P, Chueh JS, et al. Cardiovascular outcomes and all-cause mortality in primary aldosteronism after adrenalectomy or mineralocorticoid receptor antagonist treatment: a meta-analysis. Eur J Endocrinol. 2022;187:S47–58. [DOI] [PubMed]

21.

Fernandes-Rosa FL, Williams TA, Riester A, Steichen O, Beuschlein F, Boulkroun S, et al. Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma. Hypertension. 2014;64:354–61. [DOI] [PubMed]

22.

Marzano L, Zoccatelli F, Pizzolo F, Friso S. Adrenalectomy Versus Medical Therapy in Primary Aldosteronism: A Meta-Analysis of Long-Term Cardiac Remodeling and Function: Medical versus Adrenalectomy Treatment Compared in Hyperaldosteronism (MATCH) Study. Hypertension. 2025;82:e142–53. [DOI] [PubMed]

23.

Nayak SS, Amini-Salehi E, Joukar F, Biswas P, Nobakht S, Letafatkar N, et al. Cardiovascular and all-cause mortality outcomes of adrenalectomy versus medical treatment in primary aldosteronism: an umbrella review. Int J Surg. 2024;110:7367–80. [DOI] [PubMed] [PMC]

24.

Petrák O, Krátká Z, Holaj R, Zítek M, Nguyen Nikrýnová T, Klímová J, et al. Cardiovascular Complications in Pheochromocytoma and Paraganglioma: Does Phenotype Matter? Hypertension. 2024;81:595–603. [DOI] [PubMed]

25.

Kassim TA, Clarke DD, Mai VQ, Clyde PW, Mohamed Shakir KM. Catecholamine-induced cardiomyopathy. Endocr Pract. 2008;14:1137–49. [DOI] [PubMed]

26.

Y-Hassan S, Falhammar H. Cardiovascular Manifestations and Complications of Pheochromocytomas and Paragangliomas. J Clin Med. 2020;9:2435. [DOI] [PubMed] [PMC]

27.

Nazari MA, Hasan R, Haigney M, Maghsoudi A, Lenders JWM, Carey RM, et al. Catecholamine-induced hypertensive crises: current insights and management. Lancet Diabetes Endocrinol. 2023;11:942–54. [DOI] [PubMed]

28.

Nazari MA, Rosenblum JS, Haigney MC, Rosing DR, Pacak K. Pathophysiology and Acute Management of Tachyarrhythmias in Pheochromocytoma: JACC Review Topic of the Week. J Am Coll Cardiol. 2020;76:451–64. [DOI] [PubMed] [PMC]

29.

Agarwal V, Kant G, Hans N, Messerli FH. Takotsubo-like cardiomyopathy in pheochromocytoma. Int J Cardiol. 2011;153:241–8. [DOI] [PubMed]

30.

Menke-van der Houven van Oordt CW, Twickler TB, van Asperdt FG, Ackermans P, Timmers HJ, Hermus AR. Pheochromocytoma mimicking an acute myocardial infarction. Neth Heart J. 2007;15:248–51. [DOI] [PubMed] [PMC]

31.

Bansal R, Dhirawani B, Rathi C, Lokhandwala Y. Pheochromocytoma presenting with recurrent syncope, prolonged QT interval and macroscopic T-wave alternans. Ann Pediatr Cardiol. 2024;17:455–8. [DOI] [PubMed] [PMC]

32.

Saavedra T JS, Nati-Castillo HA, Valderrama Cometa LA, Rivera-Martínez WA, Asprilla J, Castaño-Giraldo CM, et al. Pheochromocytoma: an updated scoping review from clinical presentation to management and treatment. Front Endocrinol (Lausanne). 2024;15:1433582. [DOI] [PubMed] [PMC]

33.

Li G, Xu S, Shi S, Ouyang X, Mai P, Zhang H, et al. Acute myocardial injury induced by pheochromocytoma: a case report. BMC Cardiovasc Disord. 2025;25:682. [DOI] [PubMed] [PMC]

34.

Timmers HJLM, Taïeb D, Pacak K, Lenders JWM. Imaging of Pheochromocytomas and Paragangliomas. Endocr Rev. 2024;45:414–34. [DOI] [PubMed] [PMC]

35.

Cascón A, Calsina B, Monteagudo M, Mellid S, Díaz-Talavera A, Currás-Freixes M, et al. Genetic bases of pheochromocytoma and paraganglioma. J Mol Endocrinol. 2023;70:e220167. [DOI] [PubMed]

36.

Garrison PG, East L, Wanna C, Paudel B, Tallaj J, McElwee S, et al. Pheochromocytoma-Induced Cardiomyopathy Requiring Mechanical Circulatory Support With Cardiac Recovery Following Surgical Resection. JACC Case Rep. 2025;30:104564. [DOI] [PubMed] [PMC]

37.

Torresan F, Beber A, Schiavone D, Zovato S, Galuppini F, Crimì F, et al. Long-Term Outcomes after Surgery for Pheochromocytoma and Sympathetic Paraganglioma. Cancers (Basel). 2023;15:2890. [DOI] [PubMed] [PMC]

38.

Zelinka T, Petrák O, Turková H, Holaj R, Strauch B, Kršek M, et al. High incidence of cardiovascular complications in pheochromocytoma. Horm Metab Res. 2012;44:379–84. [DOI] [PubMed]

39.

Guo N, Liu T, Zhao P, Bai S. Long-Term Cardiovascular Complications in Patients With Pheochromocytomas and Paragangliomas After Surgery: A Large Multi-Center Study. Clin Endocrinol (Oxf). 2025;102:273–80. [DOI] [PubMed]

40.

Çoner A, Özyıldız AG. Pheochromocytoma: An overlooked reversible cause of heart failure with reduced ejection fraction. Turk Kardiyol Dern Ars. 2021;49:501–5. [DOI] [PubMed]

41.

Crawford RM, Anderson EJ. Not ‘Inactive’ After All: Cardiotoxic Mechanisms of Catecholamine Metabolism by Monoamine Oxidase. Cardiovasc Toxicol. 2025;25:1202–21. [DOI] [PubMed] [PMC]

42.

Cicala MV, Mantero F. Hypertension in Cushing’s syndrome: from pathogenesis to treatment. Neuroendocrinology. 2010;92 Suppl 1:44–9. [DOI] [PubMed]

43.

Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO, et al.; Endocrine Society. Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100:2807–31. [DOI] [PubMed] [PMC]

44.

Pivonello R, Isidori AM, De Martino MC, Newell-Price J, Biller BM, Colao A. Complications of Cushing’s syndrome: state of the art. Lancet Diabetes Endocrinol. 2016;4:611–29. [DOI] [PubMed]

45.

Whitworth JA, Williamson PM, Mangos G, Kelly JJ. Cardiovascular consequences of cortisol excess. Vasc Health Risk Manag. 2005;1:291–9. [DOI] [PubMed] [PMC]

46.

Muiesan ML, Lupia M, Salvetti M, Grigoletto C, Sonino N, Boscaro M, et al. Left ventricular structural and functional characteristics in Cushing's syndrome. J Am Coll Cardiol. 2003;41:2275–9. [DOI] [PubMed]

47.

Colao A, Pivonello R, Spiezia S, Faggiano A, Ferone D, Filippella M, et al. Persistence of increased cardiovascular risk in patients with Cushing’s disease after five years of successful cure. J Clin Endocrinol Metab. 1999;84:2664–72. [DOI] [PubMed]

48.

Faggiano A, Pivonello R, Spiezia S, De Martino MC, Filippella M, Di Somma C, et al. Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing's disease during active disease and 1 year after disease remission. J Clin Endocrinol Metab. 2003;88:2527–33. [DOI] [PubMed]

49.

Hacioglu A, Firat ST, Caglar AS, Karaca Z, Kalay N, Taheri S, et al. Cardiovascular evaluation and endothelial dysfunction in Cushing syndrome following remission: a prospective study. J Endocrinol Invest. 2024;47:645–53. [DOI] [PubMed]

50.

Frustaci A, Letizia C, Verardo R, Grande C, Petramala L, Russo MA, et al. Cushing Syndrome Cardiomyopathy: Clinicopathologic Impact of Cortisol Normalization. Circ Cardiovasc Imaging. 2016;9:e004569. [DOI] [PubMed]

51.

Mazziotti G, Gazzaruso C, Giustina A. Diabetes in Cushing syndrome: basic and clinical aspects. Trends Endocrinol Metab. 2011;22:499–506. [DOI] [PubMed]

52.

Terzolo M, Pia A, Reimondo G. Subclinical Cushing’s syndrome: definition and management. Clin Endocrinol (Oxf). 2012;76:12–8. [DOI] [PubMed]

53.

Khadembashiri MM, Mohseni S, Harandi H, Pejman Sani M, Khadembashiri MA, Atlasi R, et al. Comparison of adrenalectomy with conservative treatment on mild autonomous cortisol secretion: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2024;15:1374711. [DOI] [PubMed] [PMC]

54.

Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, et al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023;189:G1–42. [DOI] [PubMed]

55.

Constantinescu G, Preda C, Constantinescu V, Siepmann T, Bornstein SR, Lenders JWM, et al. Silent pheochromocytoma and paraganglioma: Systematic review and proposed definitions for standardized terminology. Front Endocrinol (Lausanne). 2022;13:1021420. [DOI] [PubMed] [PMC]

56.

Brown JM, Robinson-Cohen C, Luque-Fernandez MA, Allison MA, Baudrand R, Ix JH, et al. The Spectrum of Subclinical Primary Aldosteronism and Incident Hypertension: A Cohort Study. Ann Intern Med. 2017;167:630–41. [DOI] [PubMed] [PMC]

57.

Chen Y, Xu T, Xu J, Zhu L, Wang D, Li Y, et al. Strain Imaging for the Early Detection of Cardiac Remodeling and Dysfunction in Primary Aldosteronism. Diagnostics (Basel). 2022;12:543. [DOI] [PubMed] [PMC]

58.

Wu T, Ren Y, Wang W, Cheng W, Zhou F, He S, et al. Left Ventricular Remodeling in Patients with Primary Aldosteronism: A Prospective Cardiac Magnetic Resonance Imaging Study. Korean J Radiol. 2021;22:1619–27. [DOI] [PubMed] [PMC]

59.

Ito S, Itoh H, Rakugi H, Okuda Y, Yoshimura M, Yamakawa S. Double-Blind Randomized Phase 3 Study Comparing Esaxerenone (CS-3150) and Eplerenone in Patients With Essential Hypertension (ESAX-HTN Study). Hypertension. 2020;75:51–8. [DOI] [PubMed]

60.

Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, et al.; FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020;383:2219–29. [DOI] [PubMed]

61.

Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Renal Outcomes in Medically and Surgically Treated Primary Aldosteronism. Hypertension. 2018;72:658–66. [DOI] [PubMed] [PMC]

62.

Fernandes-Rosa FL, Boulkroun S, Fedlaoui B, Hureaux M, Travers-Allard S, Drossart T, et al. New advances in endocrine hypertension: from genes to biomarkers. Kidney Int. 2023;103:485–500. [DOI] [PubMed]

63.

Gasior T. Advances in Cardiac Imaging and Genetic Testing for Diagnosis and Risk Stratification in Cardiomyopathies: 2024 Update. J Clin Med. 2024;13:7166. [DOI] [PubMed] [PMC]

64.

Sade LE, Hazirolan T, Kozan H, Ozdemir H, Hayran M, Eroglu S, et al. T1 Mapping by Cardiac Magnetic Resonance and Multidimensional Speckle-Tracking Strain by Echocardiography for the Detection of Acute Cellular Rejection in Cardiac Allograft Recipients. JACC Cardiovasc Imaging. 2019;12:1601–14. [DOI] [PubMed]

65.

Dahia PL. Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity. Nat Rev Cancer. 2014;14:108–19. [DOI] [PubMed]

66.

Nanba K, Omata K, Else T, Beck PCC, Nanba AT, Turcu AF, et al. Targeted Molecular Characterization of Aldosterone-Producing Adenomas in White Americans. J Clin Endocrinol Metab. 2018;103:3869–76. [DOI] [PubMed] [PMC]

67.

Fernandez CJ, Nagendra L, Alkhalifah M, Pappachan JM. Endocrine Hypertension: The Urgent Need for Greater Global Awareness. touchREV Endocrinol. 2023;19:31–41. [DOI] [PubMed] [PMC]