Increased Infection Risk in Addison's Disease and Congenital Adrenal Hyperplasia

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2019 Sep 19

PMID 31532828

Citations 40

Authors

Alberto S Tresoldi

Dana Sumilo

Mary Perrins

Konstantinos A Toulis

Alessandro Prete

Narendra Reddy

John A H Wass

Wiebke Arlt

Krishnarajah Nirantharakumar

Affiliations

Soon will be listed here.

Abstract

Context: Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI). However, the risk of primary care-managed infections in patients with PAI is unknown.

Objective: To estimate infection risk in PAI due to Addison's disease (AD) and congenital adrenal hyperplasia (CAH) in a primary care setting.

Design: Retrospective cohort study using UK data collected from 1995 to 2018.

Main Outcome Measures: Incidence of lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), gastrointestinal infections (GIIs), and prescription counts of antimicrobials in adult PAI patients compared to unexposed controls.

Results: A diagnosis of PAI was established in 1580 AD patients (mean age 51.7 years) and 602 CAH patients (mean age 35.4 years). All AD patients and 42% of CAH patients were prescribed glucocorticoids, most frequently hydrocortisone in AD (82%) and prednisolone in CAH (50%). AD and CAH patients exposed to glucocorticoids, but not CAH patients without glucocorticoid treatment, had a significantly increased risk of LRTIs (adjusted incidence rate ratio AD 2.11 [95% confidence interval (CI) 1.64-2.69], CAH 3.23 [95% CI 1.21-8.61]), UTIs (AD 1.51 [95% CI 1.29-1.77], CAH 2.20 [95% CI 1.43-3.34]), and GIIs (AD 3.80 [95% CI 2.99-4.84], CAH 1.93 [95% CI 1.06-3.52]). This was mirrored by increased prescription of antibiotics (AD 1.73 [95% CI 1.69-1.77], CAH 1.77 [95% CI 1.66-1.89]) and antifungals (AD 1.89 [95% CI 1.74-2.05], CAH 1.91 [95% CI 1.50-2.43]).

Conclusions: There is an increased risk of infections and antimicrobial use in PAI in the primary care setting at least partially linked to glucocorticoid treatment. Future studies will need to address whether more physiological glucocorticoid replacement modes could reduce this risk.

Citing Articles

Infections and gender: clues for diagnosis of adrenal insufficiency-a case report and a review of the literature.

Grandi G, Di Stefano M, Cebrelli C, Mengoli C, Di Sabatino A Intern Emerg Med. 2024; 19(7):1821-1828.

PMID: 38888722 PMC: 11466904. DOI: 10.1007/s11739-024-03613-8.

Current Challenges and Future Directions in the Assessment of Glucocorticoid Status.

Clarke S, Eng P, Comninos A, Lazarus K, Choudhury S, Tsang C Endocr Rev. 2024; 45(6):795-817.

PMID: 38795365 PMC: 11581704. DOI: 10.1210/endrev/bnae016.

Course of COVID-19 infection in patients with congenital adrenal hyperplasia.

Javaid R, Sinaii N, Kollender S, Desai J, Moon A, Merke D Front Endocrinol (Lausanne). 2024; 15:1348130.

PMID: 38405151 PMC: 10884314. DOI: 10.3389/fendo.2024.1348130.

Major immunophenotypic abnormalities in patients with primary adrenal insufficiency of different etiology.

Nowotny H, Seiter T, Ju J, Gottschlich A, Schneider H, Zopp S Front Immunol. 2023; 14:1275828.

PMID: 38045693 PMC: 10690587. DOI: 10.3389/fimmu.2023.1275828.

From Emergence to Endemicity: A Comprehensive Review of COVID-19.

Naik R, Avula S, Palleti S, Gummadi J, Ramachandran R, Chandramohan D Cureus. 2023; 15(10):e48046.

PMID: 37916248 PMC: 10617653. DOI: 10.7759/cureus.48046.

References

Lewis J, Schinnar R, Bilker W, Wang X, Strom B . Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf. 2006; 16(4):393-401. DOI: 10.1002/pds.1335. View

Betterle C, Dal Pra C, Mantero F, Zanchetta R . Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev. 2002; 23(3):327-64. DOI: 10.1210/edrv.23.3.0466. View

. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012; 61(40):816-9. View

Arlt W, Willis D, Wild S, Krone N, Doherty E, Hahner S . Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J Clin Endocrinol Metab. 2010; 95(11):5110-21. PMC: 3066446. DOI: 10.1210/jc.2010-0917. View

Erichsen M, Lovas K, Fougner K, Svartberg J, R Hauge E, Bollerslev J . Normal overall mortality rate in Addison's disease, but young patients are at risk of premature death. Eur J Endocrinol. 2008; 160(2):233-7. DOI: 10.1530/EJE-08-0550. View

Isidori A, Venneri M, Graziadio C, Simeoli C, Fiore D, Hasenmajer V . Effect of once-daily, modified-release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): a single-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 2017; 6(3):173-185. DOI: 10.1016/S2213-8587(17)30398-4. View

Murray R, Ekman B, Uddin S, Marelli C, Quinkler M, Zelissen P . Management of glucocorticoid replacement in adrenal insufficiency shows notable heterogeneity - data from the EU-AIR. Clin Endocrinol (Oxf). 2016; 86(3):340-346. DOI: 10.1111/cen.13267. View

Charlson M, Pompei P, Ales K, MacKenzie C . A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987; 40(5):373-83. DOI: 10.1016/0021-9681(87)90171-8. View

Crooks C, West J, Card T . A comparison of the recording of comorbidity in primary and secondary care by using the Charlson Index to predict short-term and long-term survival in a routine linked data cohort. BMJ Open. 2015; 5(6):e007974. PMC: 4458584. DOI: 10.1136/bmjopen-2015-007974. View

10.

Muller L, Quinkler M . Adrenal disease: Imitating the cortisol profile improves the immune system. Nat Rev Endocrinol. 2018; 14(3):137-139. DOI: 10.1038/nrendo.2018.5. View

11.

Gagliardi L, Nenke M, Thynne T, von der Borch J, Rankin W, Henley D . Continuous subcutaneous hydrocortisone infusion therapy in Addison's disease: a randomized, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2014; 99(11):4149-57. DOI: 10.1210/jc.2014-2433. View

12.

Smans L, Souverein P, Leufkens H, Hoepelman A, Zelissen P . Increased use of antimicrobial agents and hospital admission for infections in patients with primary adrenal insufficiency: a cohort study. Eur J Endocrinol. 2013; 168(4):609-14. DOI: 10.1530/EJE-12-0879. View

13.

Stoupa A, Gonzalez-Briceno L, Pinto G, Samara-Boustani D, Thalassinos C, Flechtner I . Inadequate cortisol response to the tetracosactide (Synacthen®) test in non-classic congenital adrenal hyperplasia: an exception to the rule?. Horm Res Paediatr. 2015; 83(4):262-7. DOI: 10.1159/000369901. View

14.

Hak E, Rovers M, Kuyvenhoven M, Schellevis F, Verheij T . Incidence of GP-diagnosed respiratory tract infections according to age, gender and high-risk co-morbidity: the Second Dutch National Survey of General Practice. Fam Pract. 2006; 23(3):291-4. DOI: 10.1093/fampra/cmi121. View

15.

Blak B, Thompson M, Dattani H, Bourke A . Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates. Inform Prim Care. 2012; 19(4):251-5. DOI: 10.14236/jhi.v19i4.820. View

16.

Maguire A, Blak B, Thompson M . The importance of defining periods of complete mortality reporting for research using automated data from primary care. Pharmacoepidemiol Drug Saf. 2008; 18(1):76-83. DOI: 10.1002/pds.1688. View

17.

Jenkins-Jones S, Parviainen L, Porter J, Withe M, Whitaker M, Holden S . Poor compliance and increased mortality, depression and healthcare costs in patients with congenital adrenal hyperplasia. Eur J Endocrinol. 2018; 178(4):309-320. DOI: 10.1530/EJE-17-0895. View

18.

Bancos I, Hazeldine J, Chortis V, Hampson P, Taylor A, Lord J . Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality. Eur J Endocrinol. 2017; 176(4):471-480. PMC: 5425935. DOI: 10.1530/EJE-16-0969. View

19.

Bjornsdottir S, Sundstrom A, Ludvigsson J, Blomqvist P, Kampe O, Bensing S . Drug prescription patterns in patients with Addison's disease: a Swedish population-based cohort study. J Clin Endocrinol Metab. 2013; 98(5):2009-18. DOI: 10.1210/jc.2012-3561. View

20.

Fleming D, Cross K, Barley M . Recent changes in the prevalence of diseases presenting for health care. Br J Gen Pract. 2005; 55(517):589-95. PMC: 1463227. View