Adrenocortical Crisis Triggered by Levothyroxine in an Unrecognized Autoimmune Polyglandular Syndrome Type-2: A Case Report with Review of the Literature

Author(s): Dhruvkumar M. Patel, Jayanti K. Gurumikhani, Mukundkumar V. Patel*, Maitri M. Patel, Suyog Y. Patel, Prathna N. Patel

Journal Name: Current Drug Safety

Volume 16 , Issue 1 , 2021

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Graphical Abstract:


Background: Autoimmune polyglandular syndrometype-2 (APS-2) is an uncommon endocrine disorder of Addison’s disease with an autoimmune thyroid disorder and/or type 1 diabetes mellitus. The diagnosis is more challenging when a patient presents with nonspecific neuropsychiatric features with hypothyroidism in the setting of unrecognized Addison’s disease.

Case Report: We report a case of subclinical autoimmune hypothyroidism presented with nonspecific neuropsychiatric symptoms precipitated by stress. Despite levothyroxine treatment, her symptoms deteriorated and she was admitted with persistent vomiting and hypovolemic shock. Clinical features and laboratory parameters were suggestive of underlying adrenocortical insufficiency. Preexisting autoimmune hypothyroidism combined with Addison's disease confirmed the diagnosis of unrecognized APS-2. She remarkably improved and her thyroid function tests also normalized with the treatment of corticosteroids only.

Review of the Literature: We identified only five published case reports of our title by searching the database. Neufeld and Betterle have reported their data of APS-2 and concluded that a full- blown clinical picture of two or more components of the syndrome is like the tip of the iceberg.

Conclusion: The patients of one major component of APS-2 should be screened for other components of the disease to pick up latent cases. Addison’s disease should be ruled out in patients of hypothyroidism who are intolerant to levothyroxine.

Keywords: Autoimmune polyglandular syndrome type-2, autoimmune thyroiditis, hypothyroidism, levothyroxine, addison’s crisis, adrenocortical insufficiency, Schmidt’s syndrome.

Husebye ES, Anderson MS, Kämpe O. Autoimmune Polyendocrine Syndromes. N Engl J Med 2018; 378(12): 1132-41.
[] [PMID: 29562162]
Betterle C, Greggio NA, Volpato M. Clinical review 93: Autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 1998; 83(4): 1049-55.
[] [PMID: 9543115]
Betterle C, Lazzarotto F, Presotto F. Autoimmune polyglandular syndrome Type 2: The tip of an iceberg? Clin Exp Immunol 2004; 137(2): 225-33.
[] [PMID: 15270837]
Harold E. Lebovitz. autoimmune polyglandular syndromes: interplay between the immune and the endocrine systems leading to a diverse set of clinical diseasesandnewinsightsintoimmuneregulation. DiabetesTechno&The 2013; 15(S2): 21-8.
Akil H, Bulus AD, Andiran N, Veber PS, Keskin S. A case of autoimmune polyendocrine syndrome type 1 with ocular findings and unique AIRE gene defect. J Clin Ophthalmol Res 2016; 4: 37-9.
Wang X, Ping F, Qi C, Xiao X. Delayed diagnosis with autoimmune polyglandular syndrome type 2 causing acute adrenal crisis: A case report. Medicine (Baltimore) 2016; 95(42)e5062
[] [PMID: 27759634]
Majeroni BA, Patel P. Autoimmune polyglandular syndrome, type II. Am Fam Physician 2007; 75(5): 667-70.
[PMID: 17375512]
Anyfantakis D, Symvoulakis EK, Vourliotaki I, Kastanakis S. Schmidt’s syndrome presenting as a generalised anxiety disorder: A case report. J Med Life 2013; 6(4): 451-3.
[PMID: 24868260]
Anglin RE, Rosebush PI, Mazurek MF. The neuropsychiatric profile of Addison’s disease: Revisiting a forgotten phenomenon. J Neuropsychiatry Clin Neurosci 2006; 18(4): 450-9.
[] [PMID: 17135373]
Kaushik ML, Sharma RC. Addison’s disease presenting as depression. Indian J Med Sci 2003; 57(6): 249-51.
[PMID: 14510342]
Virtanen R, Viikari J. Depression as a first symptom of Addison disease. Duodecim 1998; 114(14): 1420-1.
[PMID: 11552251]
Lakhotia M, Pahadia HR, Kumar H, Singh J, Tak S. A case of autoimmune polyglandular syndrome (APS) type ii with hypothyroidism, hypoadrenalism, and celiac disease - a rare combination. J Clin Diagn Res 2015; 9(4): OD01-3.
[] [PMID: 26023582]
Franco JS, Amaya-Amaya J, Anaya JM. Thyroid Disease and Autoimmune Diseases.Autoimmunity: From Bench to Bedside Chapter 30. Bogota, Colombia: El Rosario University Press 2013. [Internet]
Gupta AN, Nagri SK. Schmidt’s syndrome - Case report. Australas Med J 2012; 5(6): 292-5.
[] [PMID: 22848326]
Prylutskyi O, Prylutska O, Degonskyi A, Tkachenko K. A Case of Autoimmune Polyglandular Syndrome. Type 2 associated with atypical form of Scleromyxedema. Ethiop J Health Sci 2016; 26(5): 503-7.
[PMID: 28446858]
Huecker MR, Dominique E. Adrenal Insufficiency.StatPearls. Treasure Island, FL: StatPearls Publishing 2020. Updated 2020 Mar 2 Internet
Hoener K, Sharma T. Type II polyglandular autoimmune syndrome: A case of Addison’s disease precipitated by use of levothyroxine. BMJ Case Rep 2019; 12(8)e230760
[] [PMID: 31439557]
Lakhani OJ, Tripathi S, Indu KC, Desai M. Levothyroxine replacement before glucocorticoid replacement leading to adrenal crisis in a case of autoimmune polyendocrine syndrome type II (Schmidt syndrome). Thyroid Res Pract 2015; 12: 116-8.
Vallianou N, Gounari P, Skourtis A. A case of autoimmune polyglandular syndrome type II presenting with adrenal crisis. Hippokratia 2013; 17(2): 191.
[PMID: 24376335]
Graves L III, Klein RM, Walling AD. Addisonian crisis precipitated by thyroxine therapy: A complication of type 2 autoimmune polyglandular syndrome. South Med J 2003; 96(8): 824-7.
[] [PMID: 14515930]
Upala S, Yong WC, Sanguankeo A. Primary adrenal insufficiency misdiagnosed as hypothyroidism in a patient with polyglandular syndrome. N Am J Med Sci 2016; 8(5): 226-8.
[] [PMID: 27298818]
Michels A, Michels N. Addison disease: Early detection and treatment principles. Am Fam Physician 2014; 89(7): 563-8.
[PMID: 24695602]
Attaye I, van Andel M, Kooter AJ. More, less or both? BMJ Case Rep 2018; 2018bcr-2017-222355
[] [PMID: 29507013]
Sonthalia N, Ray S, Maiti A, Maitra S. Autoimmune polyglandular syndrome type ii presenting as an endocrine emergency: a case report. Oman Med J 2013; 28(3)e048
[] [PMID: 31440356]
William F. Paolo Jr, Joshua D. Nosanchuk. Adrenal infections. Int J Infect Dis 2006; 10: 343-53.
Laureti S, Vecchi L, Santeusanio F, Falorni A. Is the prevalence of Addison’s disease underestimated? J Clin Endocrinol Metab 1999; 84(5): 1762.
[PMID: 10323417]
Ten S, New M, Maclaren N. Clinical review 130: Addison’s disease 2001. J Clin Endocrinol Metab 2001; 86(7): 2909-22.
[PMID: 11443143]
Davis J, Sheppard M. Acute adrenal crisis precipitated by thyroxine. Br Med J (Clin Res Ed) 1986; 292(6535): 1595.
[] [PMID: 3087527]
Bleicken B, Hahner S, Ventz M, Quinkler M. Delayed diagnosis of adrenal insufficiency is common: A cross-sectional study in 216 patients. Am J Med Sci 2010; 339(6): 525-31.
[] [PMID: 20400889]

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Article Details

Year: 2021
Published on: 25 August, 2020
Page: [101 - 106]
Pages: 6
DOI: 10.2174/1574886315666200826095842
Price: $65

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