{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:38:21Z","timestamp":1760143101677,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Graves\u2019 disease (GD) and primary aldosteronism (PA) are two pathologies that can cause significant morbidity and mortality. GD is mediated by autoantibodies, and recent studies have shown autoantibody involvement in the pathophysiology behind both PA and pre-eclampsia. The coexistence of GD and PA, however, is reportedly rare. This report describes a unique case of Graves\u2019 hyperthyroidism and concomitant PA in a patient with a history of pre-eclampsia with severe features. Case Presentation: The patient presented at 17 weeks pregnancy with mild hyperthyroidism, negative TSH receptor antibodies, and a low level of thyroid-stimulating immunoglobulins (TSI). Her TSH became detectable with normal thyroid hormone levels, and therefore, no anti-thyroid medication was administered. At 34 weeks she developed pre-eclampsia with severe features, and a healthy child was delivered; her TSH returned to normal. Seven months after delivery, she presented emergently with severe hyperthyroidism, hypertensive crisis, and a serum potassium of 2.5 mmol\/L. Her hypertension was uncontrolled on multiple anti-hypertensives. Both TSI and TSH receptor antibodies were negative. The aldosterone(ng\/dL)\/renin(ng\/mL\/h ratio was (13\/0.06) = 216.7, and abdominal CT imaging demonstrated normal adrenal glands; thus, a diagnosis of PA was made. Her blood pressure was subsequently controlled with only spironolactone at 50 mg 2xday. Methimazole was started but discontinued because of an allergic reaction. Consequently, a thyroidectomy was performed, and pathology revealed Graves\u2019 disease. The patient remained well on levothyroxine at 125 mcg\/day and spironolactone at 50 mg 2xday three months after the thyroidectomy. Conclusions: This patient manifested severe GD with antibodies undetectable by conventional TSI and TSH receptor assays and accelerated hypertension from PA simultaneously. These conditions were successfully treated separately by spironolactone and thyroidectomy. Autoimmune PA was considered likely given the clinical picture. The diagnosis of PA should be considered in hypertension with GD.<\/jats:p>","DOI":"10.3390\/medicina60010170","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T04:16:56Z","timestamp":1705465016000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autoimmune Implications in a Patient with Graves\u2019 Hyperthyroidism, Pre-eclampsia with Severe Features, and Primary Aldosteronism"],"prefix":"10.3390","volume":"60","author":[{"given":"Benjamin","family":"Lin","sequence":"first","affiliation":[{"name":"School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Robinson","sequence":"additional","affiliation":[{"name":"School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basem","family":"Soliman","sequence":"additional","affiliation":[{"name":"Department of Surgery, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Gulizia","sequence":"additional","affiliation":[{"name":"Women\u2019s Healthcare Associates, Obstetrics and Gynecology, Amarillo, TX 79106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-6492","authenticated-orcid":false,"given":"Stephen","family":"Usala","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101387","DOI":"10.1016\/j.beem.2020.101387","article-title":"Graves\u2019 disease: Epidemiology, genetic and environmental risk factors and viruses","volume":"34","author":"Antonelli","year":"2020","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41572-020-0184-y","article-title":"Graves\u2019 disease","volume":"6","author":"Davies","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1056\/NEJMra1510030","article-title":"Graves\u2019 Disease","volume":"375","author":"Smith","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1586\/eci.11.56","article-title":"Receptor-activating autoantibodies and disease: Preeclampsia and beyond","volume":"7","author":"Xia","year":"2011","journal-title":"Expert. Rev. Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1161\/HYPERTENSIONAHA.115.05643","article-title":"Genetic and potential autoimmune triggers of primary aldosteronism","volume":"66","author":"Williams","year":"2015","journal-title":"Hypertension"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-0031-1295438","article-title":"Prevalence of primary aldosteronism in patient\u2019s cohorts and in population-based studies--A review of the current literature","volume":"44","author":"Hannemann","year":"2012","journal-title":"Horm. Metab. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1161\/HYPERTENSIONAHA.113.01060","article-title":"Cardiovascular complications associated with primary aldosteronism: A controlled cross-sectional study","volume":"62","author":"Savard","year":"2013","journal-title":"Hypertension"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev-pathol-121808-102149","article-title":"Pathogenesis of preeclampsia","volume":"5","author":"Young","year":"2010","journal-title":"Annu. Rev. Pathol."},{"doi-asserted-by":"crossref","unstructured":"(2020). Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet. Gynecol., 135, e237\u2013e260.","key":"ref_9","DOI":"10.1097\/AOG.0000000000003891"},{"key":"ref_10","first-page":"4050458","article-title":"Coexistence of Primary Hyperaldosteronism and Graves\u2019 Disease, a Rare Combination of Endocrine Disorders: Is It beyond a Coincidence-A Case Report and Review of the Literature","volume":"2017","author":"Gunatilake","year":"2017","journal-title":"Case Rep. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1055\/s-2002-20170","article-title":"Diagnosis and management of primary aldosteronism in pregnancy: Case report and review of the literature","volume":"19","author":"Okawa","year":"2002","journal-title":"Am. J. Perinatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1210\/jc.2015-4061","article-title":"The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline","volume":"101","author":"Funder","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1161\/CIRCULATIONAHA.118.033597","article-title":"Primary Aldosteronism: Practical Approach to Diagnosis and Management","volume":"138","author":"Byrd","year":"2018","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1038\/ajh.2011.144","article-title":"Blood pressure, thyroid-stimulating hormone, and thyroid disease prevalence in primary aldosteronism and essential hypertension","volume":"24","author":"Turchi","year":"2011","journal-title":"Am. J. Hypertens."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1385\/ENDO:22:2:155","article-title":"High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism","volume":"22","author":"Armanini","year":"2003","journal-title":"Endocrine"},{"key":"ref_16","first-page":"352","article-title":"High prevalence of thyroid disfunction in primary hyperaldosteronism","volume":"96","author":"Santori","year":"2005","journal-title":"Recenti Prog. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s12020-016-0880-2","article-title":"Association of primary aldosteronism with chronic thyroiditis","volume":"55","author":"Sabbadin","year":"2017","journal-title":"Endocrine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"967","DOI":"10.2169\/internalmedicine.41.967","article-title":"Combined primary aldosteronism and Cushing\u2019s syndrome due to a single adrenocortical adenoma complicated by Hashimoto\u2019s thyroiditis","volume":"41","author":"Tanaka","year":"2002","journal-title":"Intern Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1007\/s00296-011-2032-6","article-title":"Coexistence of primary aldosteronism and Hashimoto\u2019s thyroiditis","volume":"32","author":"Krysiak","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_20","first-page":"150087","article-title":"Iatrogenic myxoedema madness following radioactive iodine ablation for Graves\u2019 disease, with a concurrent diagnosis of primary hyperaldosteronism","volume":"2015","author":"Larouche","year":"2015","journal-title":"Endocrinol. Diabetes Metab. Case Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"219","DOI":"10.2169\/internalmedicine1962.30.219","article-title":"Thyrotoxic periodic paralysis complicated with primary aldosteronism","volume":"30","author":"Yokota","year":"1991","journal-title":"Jpn. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/j.1365-2362.2009.02159.x","article-title":"Hypokalemic paralysis: The interplay between primary aldosteronism and hyperthyroidism","volume":"39","author":"Kuo","year":"2009","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1055\/a-1120-8647","article-title":"Angiotensin II Type 1 Receptor Autoantibodies in Primary Aldosteronism","volume":"52","author":"Meyer","year":"2020","journal-title":"Horm. Metab. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1136\/ard.2010.135772","article-title":"Involvement of functional autoantibodies against vascular receptors in systemic sclerosis","volume":"70","author":"Riemekasten","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1161\/HYPERTENSIONAHA.112.202945","article-title":"Elevation of angiotensin-II type-1-receptor autoantibodies titer in primary aldosteronism as a result of aldosterone-producing adenoma","volume":"61","author":"Rossitto","year":"2013","journal-title":"Hypertension"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jash.2014.10.009","article-title":"Prevalence of angiotensin II type 1 receptor (AT1R)-activating autoantibodies in primary aldosteronism","volume":"9","author":"Li","year":"2015","journal-title":"J. Am. Soc. Hypertens."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1210\/jc.2013-3282","article-title":"Autoimmune mechanisms activating the angiotensin AT1 receptor in \u2018primary\u2019 aldosteronism","volume":"99","author":"Kem","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1530\/ERC-21-0287","article-title":"Aldosterone-producing nodules and CYP11B1 signaling correlate in primary aldosteronism","volume":"29","author":"Lin","year":"2022","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1210\/clinem\/dgaa952","article-title":"Approach to the Patient with Primary Aldosteronism: Utility and Limitations of Adrenal Vein Sampling","volume":"106","author":"Turcu","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1055\/a-1128-0421","article-title":"The Potential Role of Aldosterone-Producing Cell Clusters in Adrenal Disease","volume":"52","author":"Lim","year":"2020","journal-title":"Horm. Metab. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1210\/js.2017-00134","article-title":"Aldosterone-Producing Cell Clusters Frequently Harbor Somatic Mutations and Accumulate With Age in Normal Adrenals","volume":"1","author":"Omata","year":"2017","journal-title":"J. Endocr. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1172\/JCI4106","article-title":"Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor","volume":"103","author":"Wallukat","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1161\/01.HYP.0000190040.66563.04","article-title":"Angiotensin II type 1 receptor agonistic antibodies reflect fundamental alterations in the uteroplacental vasculature","volume":"46","author":"Walther","year":"2005","journal-title":"Hypertension"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1161\/HYPERTENSIONAHA.109.140061","article-title":"Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia: Correlation with disease severity","volume":"55","author":"Siddiqui","year":"2010","journal-title":"Hypertension"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1161\/01.HYP.0000256565.20983.d4","article-title":"Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsia","volume":"49","author":"Hubel","year":"2007","journal-title":"Hypertension"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/nm.1856","article-title":"Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice","volume":"14","author":"Zhou","year":"2008","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1161\/HYPERTENSIONAHA.109.137935","article-title":"Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats: Role of endothelin-1","volume":"54","author":"LaMarca","year":"2009","journal-title":"Hypertension"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1161\/HYPERTENSIONAHA.113.01648","article-title":"Endothelin-1, oxidative stress, and endogenous angiotensin II: Mechanisms of angiotensin II type I receptor autoantibody-enhanced renal and blood pressure response during pregnancy","volume":"62","author":"Brewer","year":"2013","journal-title":"Hypertension"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1161\/HYPERTENSIONAHA.111.171348","article-title":"Angiotensin II type 1 receptor antibodies and increased angiotensin II sensitivity in pregnant rats","volume":"58","author":"Wenzel","year":"2011","journal-title":"Hypertension"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1210\/jc.2012-4309","article-title":"Clinical review: Clinical utility of TSH receptor antibodies","volume":"98","author":"Barbesino","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.eprac.2022.01.007","article-title":"Performance of Thyroid-Stimulating Immunoglobulin Bioassay and Thyrotropin-Binding Inhibitory Immunoglobulin Assay for the Diagnosis of Graves\u2019 Disease in Patients With Active Thyrotoxicosis","volume":"28","author":"Angell","year":"2022","journal-title":"Endocr. Pract."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.ando.2018.08.002","article-title":"Diagnostic procedure in suspected Graves\u2019 disease","volume":"79","author":"Goichot","year":"2018","journal-title":"Ann. Endocrinol."},{"key":"ref_43","first-page":"716","article-title":"Thyroid histology of hyperthyroid Graves\u2019 disease with undetectable thyrotropin receptor antibodies","volume":"77","author":"Kawai","year":"1993","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/ncpendmet0430","article-title":"Primary aldosteronism: Current knowledge and controversies in Conn\u2019s syndrome","volume":"3","author":"Schirpenbach","year":"2007","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/1\/170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:48:36Z","timestamp":1760104116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/1\/170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,17]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["medicina60010170"],"URL":"https:\/\/doi.org\/10.3390\/medicina60010170","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2024,1,17]]}}}