Adrenal crises: perspectives and research directions
- 678 Downloads
Adrenal crises are life-threatening complications of adrenal insufficiency. These events have an estimated incidence of between 5 and 10 adrenal crises/100 patient years and are responsible for some of the increased morbidity and excess mortality experienced by patients with adrenal insufficiency. Treatment involves urgent administration of IV/IM hydrocortisone and IV fluids. Patient education regarding preventive measures, such as increasing the dose of replacement therapy (“stress dosing”) when sick, using parenteral hydrocortisone as necessary and accessing medical assistance promptly, is still considered the best approach to averting the onset of an adrenal crisis at times of physiological stress, most commonly an infection. However, recent evidence has demonstrated that patient education does not prevent many adrenal crisis events and the reasons for this are not fully understood. Furthermore, there is no widely accepted definition of an adrenal crisis. Without a validated adrenal crisis definition it is difficult to interpret variations in the incidence of adrenal crises and determine the effectiveness of preventive measures. This article aims to review the clinical aspects of adrenal crisis events, to explore the epidemiology, and to offer a definition of an adrenal crisis and to offer a perspective on future directions for research into adrenal crisis prevention.
KeywordsAdrenal insufficiency Incidence Risk factors Morbidity Mortality
HF is supported by the Magnus Bergvall Foundation, Karolinska Institutet, and the Stockholm County Council.
No funding was received for this review.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 3.P. Burman, A.F. Mattsson, G. Johannsson, C. Höybye, H. Holmer, P. Dahlqvist, K. Berinder, B.E. Engström, B. Ekman, E.M. Erfurth, J. Svensson, J. Wahlberg, F.A. Karlsson, Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality. J. Clin. Endocrinol. Metab. 98(4), 1466–1475 (2013)CrossRefPubMedGoogle Scholar
- 6.S. Bensing, L. Brandt, F. Tabaroj, O. Sjoberg, B. Nilsson, A. Ekbom, P. Blomqvist, O. Kampe, Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency. Clin. Endocrinol. (Oxf). 69, 697–704 (2008)CrossRefGoogle Scholar
- 7.S. Hahner, C. Spinnler, M. Fassnacht, S. Burger-Stritt, K. Lang, D. Milovanovic, F. Beuschlein, H.S. Willenberg, M. Quinkler, B. Allolio, High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J. Clin. Endocrinol. Metab. 100(2), 407–416 (2015)CrossRefPubMedGoogle Scholar
- 22.World Health Organisation: International statistical classification of diseases and health related problems, 10th Revision (ICD 10). Geneva: WHO (2011)Google Scholar
- 23.S.R. Bornstein, B. Allolio, W. Arlt, A. Barthel, A. Don-Wauchope, G.D. Hammer, E.S. Husebye, D.P. Merke, M.H. Murad, C.A. Stratakis, D.J. Torpy, Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 101(2), 364–389 (2016)CrossRefPubMedGoogle Scholar
- 30.A.A. Nofal, I. Bancos, K. Benkhadra, N.M. Ospina, A. Javed, Kapoor E, Muthusamy K, Brito JP, Turcu AF, Wang Z, Prokop L, Erickson DZ, Lteif AN, Natt N, Murad MH. Glucocorticoid replacement regimens in chronic adrenal insufficiency: a systematic review and meta-analysis. Endocr. Pract. (2016) Sep 15 [Epub ahead of print]Google Scholar
- 31.D.J. Torpy Glucocorticoid replacement in adrenal insufficiency; evaluating the evidence for optimal therapy. Endocr. Pract. (2016) On Line before print. doi: 10.4158/EP161591.CO
- 33.R.L. Rushworth, H. Falhammar, C.F. Munns, A.M. Maguire, D.J. Torpy, Hospitalisation in children with Congenital Adrenal Hyperplasia: the importance of younger age, viral infections and acute hypoadrenalism. Int. J. Endocrinol. (2016). doi: 10.1155/2016/5748264
- 38.R.L. Rushworth, C. Bischoff, D.J. Torpy, Preventing adrenal crises—home administered subcutaneous hydrocortisone is an option. Int. Med. Journal (in press)Google Scholar
- 40.D. Kampmeyer, H. Lehnert, H. Moenig, C.S. Haas, B. Harbeck, A strong need for improving the education of physicians on glucocorticoid replacement treatment in adrenal insufficiency: an interdisciplinary and multicentre evaluation. Eur. J. Intern. Med. S0953-6205(16), 30075–30079 (2016)Google Scholar
- 42.M.A. Nenke, W. Rankin, M.J. Chapman, N.E. Stevens, K.R. Diener, J.D. Hayball, J.G. Lewis, D.J. Torpy, Depletion of high-affinity corticosteroid-binding globulin corresponds to illness severity in sepsis and septic shock; clinical implications. Clin. Endocrinol. (Oxf). 82(6), 801–807 (2015)CrossRefPubMedGoogle Scholar
- 44.K. Betito, J. Diorio, M.J. Meaney, P. Boksa, Adrenal phenylethanolamine N-methyltransferase induction in relation to glucocorticoid receptor dynamics: evidence that acute exposure to high cortisol levels is sufficient to induce the enzyme. J. Neurochem. 58(5), 1853–1862 (1992)CrossRefPubMedGoogle Scholar
- 49.K.S. Petersen, R.L. Rushworth, P.M. Clifton, D.J. Torpy, Recurrent nocturnal hypoglycaemia as a cause of morning fatigue in treated Addison’s disease—favourable response to dietary management: a case report. BMC. Endocr. Disord. 15, 61 (2015). doi: 10.1186/s12902-015-0058-6 CrossRefPubMedPubMedCentralGoogle Scholar
- 51.M. Forss, G. Batcheller, S. Skrtic, G. Johannsson, Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency—a worldwide patient survey. BMC. Endocr. Disord. 12, 8 (2012). doi: 10.1186/1472-6823-12-8 CrossRefPubMedPubMedCentralGoogle Scholar