Adrenal Insufficiency in Australia: Is it Possible that the Use of Lower Dose, Short-Acting Glucocorticoids has Increased the Risk of Adrenal Crises?

Abstract

Morbidity from adrenal insufficiency (AI) in Australia is poorly described. The objective of this study was to evaluate AI morbidity patterns in adults between 1999/2000 and 2011/2012 using national databases. A descriptive study of hospitalisations for AI and adrenal crises (AC) in adults and trends in prescriptions for 2 short-acting glucocorticoids (GC) was designed. The setting was the Australian healthcare system. Main outcome measures are the trends in hospitalisation and prescription rates. There were 7 378 hospital admissions for treatment of AI in adults between 1999/00 and 2011/12. Of these, 29.5% were for an AC. Admission rates for AC increased from 9.5 to 12.4 admissions/10⁶/year (p<0.05). There was a 5.8% decrease in admission rates for AI (excluding AC), from 27.0 to 25.5/10⁶/year (p=ns). Short-acting GC [hydrocortisone (HCT) and cortisone acetate (CA)] prescription rates increased significantly (p<0.001) from 3 176.1/10⁶ to 3 463.8/10⁶. Prescription rates for CA decreased by 22.4% (p<0.001) but HCT prescription rates increased to 77.1% (p<0.001). The increase in AC admission rates was positively correlated with the rise in both the total GC prescription rate (r=0.63, p<0.05) and the HCT prescription rate (r=0.74, p<0.01). Over the 13-year study period, there was a 30.8% increase in hospitalisation rates for ACs and a concomitant 77.1% increase in prescribing of HCT. The association between AC events and HCT use and/or reduced effective GC dose is plausibly causal, but confirmatory studies are required before suggesting any change to GC replacement in AI.

Key words

Addison’s disease - adrenal crisis - glucocorticoid replacement

• References

• 1 Mason AS, Meade TW, Lee JA, Morris JN. Epidemiological and clinical picture of Addison’s disease. Lancet 1968; 2: 744-747
• 2 Kong MF, Jeffcoate W. Eighty-six cases of Addison’s disease. Clin Endocrinol (Oxf) 1994; 41: 757-761
• 3 Willis AC, Vince FP. The prevalence of Addison’s disease in Coventry, UK. Postgrad Med J 1997; 73: 286-288
• 4 Laureti S, Vecchi L, Santeusanio F, Falorni A. Is the prevalence of Addison’s disease underestimated?. J Clin Endocrinol Metab 1999; 84: 1762
• 5 Løvås K, Husebye ES. High prevalence and increasing incidence of Addison’s disease in western Norway. Clin Endocrinol (Oxf) 2002; 56: 787-791
• 6 Regal M, Páramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol 2001; 55: 735-740
• 7 Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003; 361: 1881-1893
• 8 Fernandez-Rodriguez E, Lopez-Raton M, Andujar P, Martinez-Silva IM, Cadarso-Suarez C, Casanueva FF, Bernabeu I. Epidemiology, mortality rate and survival in a homogeneous population of hypopituitary patients. Clin Endocrinol 2013; 78: 278-284
• 9 Erichsen MM, Løvås K, Fougner KJ, Svartberg J, Hauge ER, Bollerslev J, Berg JP, Mella B, Husebye ES. Normal overall mortality rate in Addison’s disease, but young patients are at risk of premature death. Eur J Endocrinol 2009; 160: 233-237
• 10 White K, Arlt W. Adrenal crisis in treated Addison’s disease: A predictable but under-managed event. Eur J Endocrinol 2010; 162: 115-120
• 11 Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, Ventz M, Quinkler M, Allolio B. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol 2010; 162: 597-602
• 12 Meyer G, Neumann K, Badenhoop K, Linder R. Increasing prevalence of Addison’s disease in German females: health insurance data 2008–2012. Eur J Endocrinol 2014; 170: 367-373
• 13 Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC, Loriaux DL. Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. J Clin Endocrinol Metab 1991; 72: 39-45
• 14 Di Dalmazi G, Vicennati V, Rinaldi E, Morselli-Labate A, Giampalma E, Mosconi C, Pagotto U, Pasquali R. Progressively increased patterns of subclinical cortisol hypersecretion in adrenal incidentalomas differently predict major metabolic and cardiovascular outcomes: A large cross-sectional study. Eur J Endocrinol 2012; 166: 669-677
• 15 Løvås K, Gjesdal CG, Christensen M, Wolff AB, Almås B, Svartberg J, Fougner KJ, Syversen U, Bollerslev J, Falch JA, Hunt PJ, Chatterjee VK, Husebye ES. Glucocorticoid replacement therapy and pharmacogenetics in Addison’s disease: effects on bone. Eur J Endocrinol 2009; 160: 993-1002
• 16 Björnsdottir S, Sääf M, Bensing S, Kämpe O, Michaëlsson K, Ludvigsson JF. Risk of hip fracture in Addison’s disease: a population-based cohort study. J Intern Med 2011; 270: 187-195
• 17 Filipsson H, Monson JP, Koltowska-Häggström M, Mattsson A, Johannsson G. The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients. J Clin Endocrinol Metab 2006; 91: 3954-3961
• 18 Hahner S, Loeffler M, Fassnacht M, Weismann D, Koschker A, Quinkler M, Decker O, Arlt W, Allolio B. Impaired subjective health status in 256 patients with adrenal insufficiency on standard therapy based on cross-sectional analysis. J Clin Endocrinol Metab. 2007; 92: 3912-3922
• 19 Mah PM, Jenkins RC, Rostami-Hodjegan A, Newell-Price J, Doane A, Ibbotson V, Tucker GT, Ross RJ. Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clin Endocrinol (Oxf) 2004; 61: 367-375
• 20 Forss M, Batcheller G, Skrtic S, Johannsson G. Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency – a worldwide patient survey. BMC Endocr Disord 2012; 12: 8
• 21 Simon N, Castinetti F, Ouliac F, Lesavre N, Brue T, Oliver C. Pharmacokinetic evidence for suboptimal treatment of adrenal insufficiency with currently available hydrocortisone tablets. Clin Pharmacokinet 2010; 49: 455-463
• 22 Nieman LK. Treatment of adrenal insufficiency in adults. Up To Date 2013 Online subscription; www.uptodate.com
• 23 World Health Organisation . International Statistical Classification of Diseases and Related Health Problems, 10^th Revision (ICD-10). Geneva: WHO; 1992
• 24 Bergthorsdottir R, Leonsson-Zachrisson M, Odén A, Johannsson G. Premature mortality in patients with Addison’s disease: A population-based study. J Clin Endocrinol Metab 2006; 91: 4849-4853
• 25 Leelarathna L, Breen L, Powrie JK, Thomas SM, Guzder R, McGowan B, Carroll PV. Co-morbidities, management and clinical outcome of auto-immune Addison’s disease. Endocrine 2010; 38: 113-117
• 26 Smans LCCJ, Souverein PC, Leufkens HGM, Hoepelman AIM, Zelissen PMJ. Increased use of antimicrobial agents and hospital admission for infections in patients with primary adrenal insufficiency: A cohort study. Eur J Endocrinol 2013; 168: 609-614
• 27 Rushworth RL, Torpy DJ. 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
• 28 Repping-Wuts HJ, Stikkelbroeck NM, Noordzij A, Kerstens M, Hermus AR. A glucocorticoid education group meeting: an effective strategy for improving self-management to prevent adrenal crisis. Eur J Endocrinol 2013; 169: 17-22
• 29 Jacobson DL, Gange SJ, Rose NR, Graham NM. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol 1997; 84: 223-243
• 30 Betterle C, Scarpa R, Garelli S, Morlin L, Lazzarotto F, Presotto F, Coco G, Masiero S, Parolo A, Albergoni MP, Favero R, Barollo S, Salvà M, Basso D, Chen S, Rees Smith B, Furmaniak J, Mantero F. Addison’s disease: a survey on 633 patients in Padova. Eur J Endocrinol 2013; 169: 773-784
• 31 George MM, Bhangoo A. Human immune deficiency virus (HIV) infection and the hypothalamic pituitary adrenal axis. Rev Endocr Metab Disord 2013; 14: 105-112
• 32 Falorni A, Minarelli V, Morelli S. Therapy of adrenal insufficiency: an update. Endocrine 2013; 34: 514-528
• 33 Erichsen MM, Løvås K, Skinningsrud B, Wolff AB, Undlien DE, Svartberg J, Fougner KJ, Berg TJ, Bollerslev J, Mella B, Carlson JA, Erlich H, Husebye ES. Clinical, immunological, and genetic features of autoimmune primary adrenal insufficiency: observations from a Norwegian registry. J Clin Endocrinol Metab 2009; 94: 4882-4890
• 34 Arnold AC, Shibao C. Current concepts in orthostatic hypotension management. Curr Hypertens Rep 2013; 15: 304-312