{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:35:11Z","timestamp":1791477311178,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Secondary hypertension and resistant hypertension may result from potentially treatable acquired or hereditary diseases. Inherited Metabolic Disorders are not routinely included in the differential diagnosis of these contexts associated with hypertension, despite the key importance of diagnosis for several of them which enable the early treatment of them. We aim to discuss the current evidence that indicates that a significant portion of cases of unknown resistant hypertension or suspected secondary hypertension may result from unrecognized Acute Hepatic Porphyria (AHP). Diagnostic work-up for AHP is not routinely performed during the evaluation of patients with resistant or refractory hypertension nor in the investigation of secondary hypertension. AHP may present both with neurological and systemic involvement, and hypertension may be observed as part of acute dysautonomia during acute neurovisceral attacks and as a chronic complication during disease course. As AHP represent a potentially treatable group of metabolic disorders, clinicians should consider the inclusion of this group in the diagnostic evaluation of patients with secondary or resistant hypertension.<\/jats:p>","DOI":"10.3390\/medsci13010014","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T11:32:32Z","timestamp":1738841552000},"page":"14","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Acute Hepatic Porphyria Should Be Included in the Diagnostic Work-Up of Patients with Resistant Hypertension or Suspected Secondary Hypertension"],"prefix":"10.3390","volume":"13","author":[{"given":"Paulo","family":"de Lima Serrano","sequence":"first","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7360-0494","authenticated-orcid":false,"given":"Bruno","family":"de Mattos Lombardi Badia","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Paulo","family":"Barile","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Marques","family":"Mendes","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renan Brand\u00e3o Rambaldi","family":"Cavalheiro","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaliny Oliveira","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor Braga","family":"Farias","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Ismael Lacerda","family":"Machado","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Delgado","family":"Seneor","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0150-525X","authenticated-orcid":false,"given":"Wladimir Bocca Vieira","family":"de Rezende Pinto","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6986-4937","authenticated-orcid":false,"given":"Acary Souza Bulle","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7416-7108","authenticated-orcid":false,"given":"Paulo","family":"Sgobbi","sequence":"additional","affiliation":[{"name":"Porphyria Unit, Division of Neuromuscular Diseases, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04039-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.mcna.2021.11.004","article-title":"Evaluation and management of secondary hypertension","volume":"106","author":"Sarathy","year":"2022","journal-title":"Med. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","article-title":"2024 ESC Guidelines for the management of elevated blood pressure and hypertension","volume":"45","author":"McEvoy","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1097\/HJH.0000000000003480","article-title":"2023 ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA)","volume":"41","author":"Mancia","year":"2023","journal-title":"J. Hypertens."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1210\/er.2018-00071","article-title":"Genetics of human primary hypertension: Focus on hormonal mechanisms","volume":"40","author":"Manosroi","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2224898","DOI":"10.1080\/08037051.2023.2224898","article-title":"Secondary hypertension as a cause of treatment resistance","volume":"32","author":"Sudano","year":"2023","journal-title":"Blood Press."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/s41371-024-00922-5","article-title":"Investigation and management of young-onset hypertension: British and Irish hypertension society position statement","volume":"38","author":"Kulkarni","year":"2024","journal-title":"J. Hum. Hypertens."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1161\/CIRCRESAHA.118.312156","article-title":"Treatment of resistant and refractory hypertension","volume":"124","author":"Acelajado","year":"2019","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.jacc.2024.02.037","article-title":"Malignant hypertension: A systemic cardiovascular disease: JACC review topic of the week","volume":"83","author":"Boulestreau","year":"2024","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ymgme.2019.04.008","article-title":"Heme biosynthesis and the porphyrias","volume":"128","author":"Phillips","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/s13023-022-02463-x","article-title":"Disease burden in patients with acute hepatic porphyria: Experience from the phase 3 ENVISION study","volume":"17","author":"Wang","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1590\/0004-282x20200096","article-title":"Acute hepatic porphyria for the neurologist: Current concepts and perspectives","volume":"79","author":"Souza","year":"2021","journal-title":"Arq. Neuropsiquiatr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Souza, P.V.S., Badia, B.M.L., Farias, I.B., Pinto, W.B.V.R., and Oliveira, A.S.B. (2021). Acute Hepatic Porphyria: Pathophysiological basis of neuromuscular manifestations. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.715523"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1053\/j.gastro.2022.11.034","article-title":"AGA Clinical Practice update on diagnosis and management of Acute Hepatic Porphyrias: Expert Review","volume":"164","author":"Wang","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1139\/y95-234","article-title":"Cytochrome P450 and its interactions with the heme biosynthetic pathway","volume":"74","author":"Marks","year":"1996","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s13023-022-02314-9","article-title":"Challenges in diagnosis and management of acute hepatic porphyrias: From an uncommon pediatric onset to innovative treatments and perspectives","volume":"17","author":"Marcacci","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1365-2796.1994.tb01279.x","article-title":"Hypertension and renal disease in patients with acute intermittent porphyria","volume":"236","author":"Andersson","year":"1994","journal-title":"J. Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1046\/j.1365-2796.2000.00743.x","article-title":"Renal symptomatology in patients with acute intermittent porphyria. A population-based study","volume":"248","author":"Andersson","year":"2000","journal-title":"J. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/ki.2015.97","article-title":"High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria","volume":"88","author":"Pallet","year":"2015","journal-title":"Kidney Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1136\/jclinpath-2012-200791","article-title":"Review of hepatocellular cancer, hypertension and renal impairment as late complications of acute porphyria and recommendations for patient follow-up","volume":"65","author":"Stewart","year":"2012","journal-title":"J. Clin. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ymgme.2020.12.290","article-title":"Clinical and biochemical footprints of inherited metabolic diseases. IV. Metabolic cardiovascular disease","volume":"132","author":"Ferreira","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ricci, A., Sandri, G., Marcacci, M., Di Pierro, E., Granata, F., Cuoghi, C., Marchini, S., Pietrangelo, A., and Ventura, P. (2022). Endothelial dysfunction in Acute Hepatic Porphyrias. Diagnostics, 12.","DOI":"10.3390\/diagnostics12061303"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ricci, A., Guida, C.C., Manzini, P., Cuoghi, C., and Ventura, P. (2021). Kidney involvement in Acute Hepatic Porphyrias: Pathophysiology and diagnostic implications. Diagnostics, 11.","DOI":"10.3390\/diagnostics11122324"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2478\/sjecr-2017-0039","article-title":"Hypertensive crisis in patients with Acute Intermittent Porphyria","volume":"23","author":"Andrejic","year":"2022","journal-title":"Serb. J. Exp. Clin. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/S0140-6736(89)91599-7","article-title":"Acute hypertension mimicking phaeochromocytoma as main presenting feature of acute intermittent porphyria","volume":"2","author":"Bravenboer","year":"1989","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1002\/jimd.12551","article-title":"EXPLORE B: A prospective, long-term natural history study of patients with acute hepatic porphyria with chronic symptoms","volume":"45","author":"Cassiman","year":"2022","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1002\/hep.30936","article-title":"EXPLORE: A prospective, multinational, natural history study of patients with Acute Hepatic Porphyria with recurrent attacks","volume":"71","author":"Gouya","year":"2019","journal-title":"Hepatology"},{"key":"ref_27","first-page":"986","article-title":"Hypertension and renal impairment as complications of acute porphyria","volume":"7","author":"Church","year":"1992","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/qjmed\/89.2.161","article-title":"Hypertension in porphyria\u2014An understated problem","volume":"89","author":"Wathen","year":"1996","journal-title":"QJM"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1136\/jcp.2005.032722","article-title":"Acute intermittent porphyria and phaeochromocytoma: Shared features","volume":"60","author":"Stewart","year":"2007","journal-title":"J. Clin. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ijcard.2016.01.035","article-title":"Takotsubo syndrome triggered by acute intermittent porphyria attack: An unusual stressor for catecholamine-induced cardiomyopathy","volume":"207","author":"Messas","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16820","DOI":"10.20452\/pamw.16820","article-title":"Cardiovascular abnormalities in patients with acute intermittent porphyria: The AIPRACUS study","volume":"134","author":"Jaworski","year":"2024","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_32","first-page":"84","article-title":"Acute intermittent porphyria and arterial hypertension","volume":"86","author":"Kostrzewska","year":"1991","journal-title":"Pol. Arch. Med. Wewn."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13023-023-02653-1","article-title":"Brazilian registry of patients with porphyria: REBRAPPO study","volume":"18","author":"Souza","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_34","first-page":"339","article-title":"Drug treatment of hypertension in acute intermittent porphyria: Doxazosin and amlodipine","volume":"43","author":"Gorchein","year":"1997","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1161\/HYPERTENSIONAHA.115.06271","article-title":"Unusual case of severe hypertension in a 20-year-old woman","volume":"66","author":"Pichler","year":"2015","journal-title":"Hypertension"},{"key":"ref_36","first-page":"225","article-title":"Acute intermittent porphyria: An unusual cause of malignant hypertension","volume":"51","author":"Singh","year":"2003","journal-title":"J. Assoc. Physicians India"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejim.2024.05.033","article-title":"2024 European Society of Hypertension clinical practice guidelines for the management of arterial hypertension","volume":"126","author":"Kreutz","year":"2024","journal-title":"Eur. J. Intern. Med."},{"key":"ref_38","first-page":"71","article-title":"Clinical features of Japanese patients with acute hepatic porphyria","volume":"64","author":"Horie","year":"2022","journal-title":"JIMD Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1186\/s13023-023-02913-0","article-title":"Clinical features of acute attacks, chronic symptoms, and long-term complications among patients with acute hepatic porphyria in Japan: A real-world claims database study","volume":"18","author":"Horie","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2147\/TACG.S48605","article-title":"An update of clinical management of acute intermittent porphyria","volume":"8","author":"Pischik","year":"2015","journal-title":"Appl. Clin. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.pharmthera.2011.06.001","article-title":"Drugs in porphyria: From observation to a modern algorithm-based system for the prediction of porphyrogenicity","volume":"132","author":"Hift","year":"2011","journal-title":"Pharmacol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1177\/106002809703100223","article-title":"Amlodipine-induced acute intermittent porphyria exacerbation","volume":"31","author":"Kepple","year":"1997","journal-title":"Ann. Pharmacother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1097\/FAD.0000000000000011","article-title":"Safe prescribing in the autosomal dominant acute porphyrias: A practical approach: Part I","volume":"293","author":"Lockett","year":"2015","journal-title":"Adv. Drug React. Bull."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3810\/pgm.2014.11.2839","article-title":"Drugs and acute porphyria: Reasons for a hazardous relationship","volume":"126","author":"Roveri","year":"2014","journal-title":"Postgrad. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/j.0306-5251.2007.02955.x","article-title":"Guide to drug porphyrinogenicity prediction and drug prescription in the acute porphyrias","volume":"64","author":"Thunell","year":"2007","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_46","unstructured":"(2025, January 10). Drug Database from the American Porphyria Foundation (APF). Available online: https:\/\/porphyriafoundation.org\/drugdatabase\/."},{"key":"ref_47","unstructured":"(2025, January 10). Acute Porphyria Drug Database, The Norwegian Porphyria Centre (NAPOS), from the Haukeland University Hospital, in Norway. Available online: https:\/\/drugsporphyria.net\/clear\/1."},{"key":"ref_48","unstructured":"(2025, January 10). Safe List from the United Kingdom Porphyria Medicines Information Service (UKPMIS) and Cardiff Porphyria Service (at the University Hospital of Wales), Supported by the National Acute Porphyria Service (NAPS). Available online: https:\/\/www.wmic.wales.nhs.uk\/specialist-services\/drugs-in-porphyria\/."},{"key":"ref_49","unstructured":"(2025, January 10). The Porphyria Information Centre at the University of Cape Town. Porphyria for Professionals, Porphyria South Africa. Available online: https:\/\/porphyria.uct.ac.za\/porphyria-professionals\/further-information\/porphyria-information-centre-uct."}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/1\/14\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:28:21Z","timestamp":1760027301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/1\/14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["medsci13010014"],"URL":"https:\/\/doi.org\/10.3390\/medsci13010014","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,6]]}}}