Advertisement

Impact of underlying chronic adrenal insufficiency on clinical course of hospitalized patients with adrenal crisis: A nationwide cohort study

Published:April 10, 2019DOI:https://doi.org/10.1016/j.ejim.2019.04.001

      Highlights

      • Adrenal crisis may indicate underlying chronic adrenal insufficiency.
      • The proportions of newly- versus previously-diagnosed chronic AI cases were similar.
      • Pre-existing chronic AI is related to a favorable outcome.
      • AI-related symptoms are a significant risk factor for in-hospital death.

      Abstract

      Background

      Chronic adrenal insufficiency (AI) is an established risk factor for adrenal crisis (AC). However, the proportion of patients with newly diagnosed chronic AI during admission for AC is unclear.

      Methods

      This retrospective cohort study used a Japanese claims database involving 7.39 million patients at 145 acute care hospitals between 2003 and 2014. Study patients with AC met these criteria: 1) newly coded in claims as AI; 2) glucocorticoid therapy administered; 3) admission; and 4) age ≥ 18 years. We investigated the prevalence of underlying chronic AI and assessed in-hospital mortality. Additionally, we explored risk factors for in-hospital mortality through multivariate analysis using a Cox proportional hazards model.

      Results

      Among 504 patients with AC, chronic AI was diagnosed before and during admission in 73 (14.5%) and 86 (17.1%) patients, respectively. In-hospital mortality rates were 1.4% and 5.8%, respectively, lower than that of the total population (14.1%). Significant risk factors for increased mortality were: age (hazard ratio [HR] 1.45/10 years; 95% confidence interval [CI] 1.17–1.78), requiring mechanical ventilation (HR 3.81; 95% CI 1.88–7.72), vasopressor administration (HR 2.05; 95% CI 1.16–3.64), sepsis (HR 3.79; 95% CI 1.57–9.14), AI-related symptoms (HR 2.00; 95% CI 1.02–3.93), and liver disease (HR 3.24; 95% CI 1.10–9.58).

      Conclusions

      Relative to patients without chronic AI, those diagnosed before admission tended to survive to discharge; however, the difference with those diagnosed during admission was not significant. Hospital admission due to nonspecific AI-related symptoms was associated with an increased risk of in-hospital mortality.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Charmandari E.
        • Nicolaides N.C.
        • Chrousos G.P.
        Adrenal insufficiency.
        Lancet. 2014; 383 (doi): 2152-2167
        • Rushworth R.L.
        • Torpy D.J.
        • Falhammar H.
        Adrenal crises: perspectives and research directions.
        Endocrine. 2017; 55 (doi): 336-345
        • Hahner S.
        • Spinnler C.
        • Fassnacht M.
        • et al.
        High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study.
        J Clin Endocrinol Metab. 2015; 100 (doi): 407-416
        • Smans L.C.
        • Van der Valk E.S.
        • Hermus A.R.
        • Zelissen P.M.
        Incidence of adrenal crisis in patients with adrenal insufficiency.
        Clin Endocrinol (Oxf). 2016; 84 (doi): 17-22
        • Ono Y.
        • Ono S.
        • Yasunaga H.
        • Matsui H.
        • Fushimi K.
        • Tanaka Y.
        Clinical features and practice patterns of treatment for adrenal crisis: a nationwide cross-sectional study in Japan.
        Eur J Endocrinol. 2017; 176 (doi): 329-337
        • Mesotten D.
        • Vanhorebeek I.
        • Van den Berghe G.
        The altered adrenal axis and treatment with glucocorticoids during critical illness.
        Nat Clin Pract Endocrinol Metab. 2008; 4: 496-505https://doi.org/10.1038/ncpendmet0921
        • Annane D.
        • Pastores S.M.
        • Arlt W.
        • et al.
        Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a multispecialty task force of the society of critical care medicine (SCCM) and the european society of intensive care medicine (ESICM).
        Crit Care Med. 2017; 45 (doi): 2089-2098
        • Boonen E.
        • Vervenne H.
        • Meersseman P.
        • et al.
        Reduced cortisol metabolism during critical illness.
        N Engl J Med. 2013; 368: 1477-1488https://doi.org/10.1056/NEJMoa1214969
        • Ben-Shlomo A.
        • Mirocha J.
        • Gwin S.M.
        • et al.
        Clinical factors associated with biochemical adrenal-cortisol insufficiency in hospitalized patients.
        Am J Med. 2014; 127: 754-762https://doi.org/10.1016/j.amjmed.2014.03.002
        • Bornstein S.R.
        • Allolio B.
        • Arlt W.
        • et al.
        Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline.
        J Clin Endocrinol Metab. 2016; 101 (doi): 364-389
        • Annane D.
        • Pastores S.M.
        • Rochwerg B.
        • et al.
        Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (part I): society of critical care medicine (SCCM) and european society of intensive care medicine (ESICM) 2017.
        Crit Care Med. 2017; 45: 2078-2088https://doi.org/10.1097/CCM.0000000000002737
        • Yanase T.
        • Tajima T.
        • Katabami T.
        • et al.
        Diagnosis and treatment of adrenal insufficiency including adrenal crisis: a Japan endocrine society clinical practice guideline [opinion].
        Endocr J. 2016; 63: 765-784https://doi.org/10.1507/endocrj.EJ16-0242
        • Hahner S.
        • Hemmelmann N.
        • Quinkler M.
        • Beuschlein F.
        • Spinnler C.
        • Allolio B.
        Timelines in the management of adrenal crisis - targets, limits and reality.
        Clin Endocrinol (Oxf). 2015; 82: 497-502https://doi.org/10.1111/cen.12609
        • Papierska L.
        • Rabijewski M.
        Delay in diagnosis of adrenal insufficiency is a frequent cause of adrenal crisis.
        Int J Endocrinol. 2013; 2013482370https://doi.org/10.1155/2013/482370
        • Husebye E.S.
        • Allolio B.
        • Arlt W.
        • et al.
        Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency.
        J Intern Med. 2014; 275 (doi): 104-115
        • Wass J.A.
        • Arlt W.
        How to avoid precipitating an acute adrenal crisis.
        BMJ. 2012; 345: e6333https://doi.org/10.1136/bmj.e6333
        • Rushworth R.L.
        • Torpy D.J.
        A descriptive study of adrenal crises in adults with adrenal insufficiency: increased risk with age and in those with bacterial infections.
        BMC Endocr Disord. 2014; 14 (79-6823-14-79)https://doi.org/10.1186/1472-6823-14-79
        • Iwasaku M.
        • Shinzawa M.
        • Tanaka S.
        • Kimachi K.
        • Kawakami K.
        Clinical characteristics of adrenal crisis in adult population with and without predisposing chronic adrenal insufficiency: a retrospective cohort study.
        BMC Endocr Disord. 2017; 17 (58-017-0208-0)https://doi.org/10.1186/s12902-017-0208-0
        • Vincent J.L.
        • Moreno R.
        Clinical review: scoring systems in the critically ill.
        Crit Care. 2010; 14: 207https://doi.org/10.1186/cc8204
        • Bancos I.
        • Hahner S.
        • Tomlinson J.
        • Arlt W.
        Diagnosis and management of adrenal insufficiency.
        Lancet Diabetes Endocrinol. 2015; 3 (doi): 216-226
        • Freund Y.
        • Jabre P.
        • Mourad J.
        • et al.
        Relative adrenal insufficiency in critically ill patient after rapid sequence intubation: KETASED ancillary study.
        J Crit Care. 2014; 29 (doi): 386-389
        • Rhodes A.
        • Evans L.E.
        • Alhazzani W.
        • et al.
        Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016.
        Crit Care Med. 2017; 45: 486-552https://doi.org/10.1097/CCM.0000000000002255
        • van Vught L.A.
        • Klein Klouwenberg P.M.
        • Spitoni C.
        • et al.
        Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis.
        JAMA. 2016; 315 (doi): 1469-1479
        • Elsouri N.
        • Bander J.
        • Guzman J.A.
        Relative adrenal insufficiency in patients with septic shock; a close look to practice patterns.
        J Crit Care. 2006; 21 ([doi:S0883-9441(05)00191-7 [pii]): 73-77
        • Annane D.
        • Renault A.
        • Brun-Buisson C.
        • et al.
        Hydrocortisone plus fludrocortisone for adults with septic shock.
        N Engl J Med. 2018; 378: 809-818https://doi.org/10.1056/NEJMoa1705716