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Diagnosis and Management of Adrenal Insufficiency in Children and Adults

  • Sofia LlahanaEmail author
  • Irene Mitchelhill
  • Phillip Yeoh
  • Marcus Quinkler
Chapter

Abstract

Adrenal insufficiency (AI) is a common life-threatening endocrine condition. It is caused by the inability of the adrenal glands to produce cortisol, a hormone essential for life, either due to failure of the adrenals (primary AI), or due to diseases affecting the hypothalamus or the pituitary which control the adrenals (secondary AI). Patients with AI require lifelong glucocorticoid (GC) replacement therapy and increased GC doses during periods of intercurrent illness or other major psychological and physical stress to mimic the normal increase in physiological cortisol response to such situations. Inadequate GC replacement for daily maintenance and increased doses during illness, can precipitate an adrenal crisis (AC) an adrenal crisis which can be fatal if the immediate administration of parenteral hydrocortisone is delayed.

The prevalence of primary AI is 93–140 patients/million population and of secondary AI is 150–280/per million. Standard mortality rate for patients with AI is more than twofold compared to the general population according to retrospective hospital data. AI has significant impact on patients’ quality of life, and suboptimal GC replacement (over- or under-replacement) can lead to acute and long term complications such as osteoporosis and type 2 diabetes.

AI encompasses a wide variety of medical diagnoses and can be an unrecognised underlying condition masked by another diagnosis in both paediatrics and adults. There should be a heightened sense of suspicion in the presentation of any seriously unwell neonate, child or adult where an unexplained presentation, deterioration of an intercurrent illness or other stress (e.g. surgery or significant trauma) may have precipitate an AC.

The diagnosis of AI brings many challenges for children, parents, adult patients and their families with the impact of a multiple daily medication routine, and the need for sick day surveillance and management, and for vigilance to detect potential illness and possible events which may be life threatening. Health professionals need to provide adequate ongoing psychological support and education for patients and families long term as they adapt to their health needs of their condition and incorporate treatment plans into their daily lives. Understanding of the education process is crucial and one of the most one important aspects of the role of the endocrine nurse.

Keywords

Adrenal insufficiency Adrenal crisis Hydrocortisone Glucocorticoids Fludrocortisone Patient education Primary adrenal insufficiency Secondary adrenal insufficiency Quality of life 

Abbreviations

AC

Adrenal crisis

ACTH

Adrenocorticotropic hormone

AD

Addison’s disease

AI

Adrenal insufficiency

CA

Cortisone acetate

CAH

Congenital adrenal hyperplasia

CRH

Corticotropin-releasing hormone

CSHI

Continuous subcutaneous hydrocortisone infusion

DHEA

Dehydroepiandrosterone

GC

Glucocorticoids

HPA

Hypothalamic-pituitary-adrenal axis

ITT

Insulin tolerance test

PAI

Primary adrenal insufficiency

QoL

Quality of life

SAI

Secondary adrenal insufficiency

SST

Short synacthen test

Notes

Acknowledgments

With special thanks to our patients for their case studies and to Grahame Collier from the Australian Addison’s Disease Association Inc (http://addisons.org.au; email: ) for the information on their Patient Advocacy Group.

References

  1. Arlt W. Chapter 8: Disorders of the adrenal cortex. In: Jameson JL, editor. Harrison’s endocrinology. 4th ed. New York: McGraw Hill Education; 2017. p. 107–35.Google Scholar
  2. Arlt W, Allolio B. Adrenal insufficiency. Lancet (London, England). 2003;361(9372):1881–93.CrossRefGoogle Scholar
  3. Aulinas A, Casanueva F, Goni F, Monereo S, Moreno B, Pico A, et al. Adrenal insufficiency and adrenal replacement therapy. Current status in Spain. Endocrinol Nutr. 2013;60(3):136–43.PubMedCrossRefGoogle Scholar
  4. Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol. 2015;3(3):216–26.PubMedCrossRefGoogle Scholar
  5. Barthel A, Willenberg HS, Gruber M, Bornstein SR. Chapter 102—Adrenal insufficiency. In: Jameson JL, De Groot LJ, de Kretser DM, Giudice LC, Grossman AB, Melmed S, et al., editors. Endocrinology: adult and pediatric. 7th ed. Philadelphia: W.B. Saunders; 2016. p. 1763–74.e4.CrossRefGoogle Scholar
  6. Bergthorsdottir R, Leonsson-Zachrisson M, Oden A, Johannsson G. Premature mortality in patients with Addison’s disease: a population-based study. J Clin Endocrinol Metab. 2006;91(12):4849–53.PubMedCrossRefGoogle Scholar
  7. Betman JEM. Parental grief when a child is diagnosed with a life threatening chronic illness: impact of gender, perceptions and coping strategies. University of Canterbury NZ. Thesis submitted for Doctor of Philosophy degree; 2006.Google Scholar
  8. Bjornsdottir S, Saaf M, Bensing S, Kampe O, Michaelsson K, Ludvigsson JF. Risk of hip fracture in Addison’s disease: a population-based cohort study. J Intern Med. 2011;270(2):187–95.PubMedCrossRefGoogle Scholar
  9. Bleicken B, Hahner S, Loeffler M, Ventz M, Decker O, Allolio B, et al. Influence of hydrocortisone dosage scheme on health-related quality of life in patients with adrenal insufficiency. Clin Endocrinol. 2010a;72(3):297–304.CrossRefGoogle Scholar
  10. 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. 2010b;339(6):525–31.PubMedCrossRefGoogle Scholar
  11. Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364–89.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Broersen LHA, Pereira AM, Jørgensen JOL, Dekkers OM. Adrenal insufficiency in corticosteroids use: systematic review and meta-analysis. J Clin Endocrinol Metabol. 2015;100(6):2171–80.CrossRefGoogle Scholar
  13. Brooke AM, Kalingag LA, Miraki-Moud F, Camacho-Hubner C, Maher KT, Walker DM, et al. Dehydroepiandrosterone improves psychological well-being in male and female hypopituitary patients on maintenance growth hormone replacement. J Clin Endocrinol Metab. 2006;91(10):3773–9.PubMedCrossRefGoogle Scholar
  14. Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int. 2007;18(10):1319–28.PubMedCrossRefGoogle Scholar
  15. Chapman SC, Llahana S, Carroll P, Horne R. Glucocorticoid therapy for adrenal insufficiency: nonadherence, concerns and dissatisfaction with information. Clin Endocrinol. 2016;84(5):664–71.CrossRefGoogle Scholar
  16. Chihaoui M, Chaker F, Yazidi M, Grira W, Ben Amor Z, Rejeb O, et al. Ramadan fasting in patients with adrenal insufficiency. Endocrine. 2017;55(1):289–95.PubMedCrossRefGoogle Scholar
  17. Cooper V, Metcalf L, Versnel J, Upton J, Walker S, Horne R. Patient-reported side effects, concerns and adherence to corticosteroid treatment for asthma, and comparison with physician estimates of side-effect prevalence: a UK-wide, cross-sectional study. NPJ Prim Care Res Med. 2015;25:15026.CrossRefGoogle Scholar
  18. Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med. 2003;139(3):194–204.PubMedCrossRefGoogle Scholar
  19. El-Farhan N, Pickett A, Ducroq D, Bailey C, Mitchem K, Morgan N, et al. Method-specific serum cortisol responses to the adrenocorticotrophin test: comparison of gas chromatography-mass spectrometry and five automated immunoassays. Clin Endocrinol. 2013;78(5):673–80.CrossRefGoogle Scholar
  20. Erichsen MM, Lovas K, Fougner KJ, Svartberg J, Hauge ER, Bollerslev J, et al. Normal overall mortality rate in Addison’s disease, but young patients are at risk of premature death. Eur J Endocrinol. 2009;160(2):233–7.PubMedCrossRefGoogle Scholar
  21. Fardet L, Petersen I, Nazareth I. Prevalence of long-term oral glucocorticoid prescriptions in the UK over the past 20 years. Rheumatology (Oxford, England). 2011;50(11):1982–90.CrossRefGoogle Scholar
  22. Filipsson H, Johannsson G. GH replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies. Eur J Endocrinol. 2009;161(Suppl 1):S85–95.PubMedCrossRefGoogle Scholar
  23. Filipsson H, Monson JP, Koltowska-Haggstrom 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(10):3954–61.PubMedCrossRefGoogle Scholar
  24. Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R, et al. Hormonal replacement in hypopituitarism in adults: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(11):3888–921.PubMedCrossRefGoogle Scholar
  25. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Frey KR, Kienitz T, Schulz J, Ventz M, Zopf K, Quinkler M. Prednisolone is associated with a worse bone mineral density in primary adrenal insufficiency. Endocr Connect. 2018;7(6):811–8.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Giavoli C, Libé R, Corbetta S, Ferrante E, Lania A, Arosio M, et al. Effect of recombinant human growth hormone (GH) replacement on the hypothalamic-pituitary-adrenal axis in adult GH-deficient patients. J Clin Endocrinol Metabol. 2004;89(11):5397–401.CrossRefGoogle Scholar
  28. Grossman AB. Clinical review: the diagnosis and management of central hypoadrenalism. J Clin Endocrinol Metab. 2010;95(11):4855–63.PubMedCrossRefGoogle Scholar
  29. Grossman A, Johannsson G, Quinkler M, Zelissen P. Therapy of endocrine disease: perspectives on the management of adrenal insufficiency: clinical insights from across Europe. Eur J Endocrinol. 2013;169(6):R165–75.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Hahner S, Loeffler M, Fassnacht M, Weismann D, Koschker AC, Quinkler M, et al. Impaired subjective health status in 256 patients with adrenal insufficiency on standard therapy based on cross-sectional analysis. J Clin Endocrinol Metab. 2007;92(10):3912–22.PubMedCrossRefGoogle Scholar
  31. Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010;162(3):597–602.PubMedCrossRefGoogle Scholar
  32. Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, et al. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015;100(2):407–16.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Henselmans I, Heijmans M, Rademakers J, van Dulmen S. Participation of chronic patients in medical consultations: patients’ perceived efficacy, barriers and interest in support. Health Expect. 2015;18(6):2375–88.PubMedCrossRefGoogle Scholar
  34. Horne R. Compliance, adherence, and concordance: implications for asthma treatment. Chest J. 2006;130(Suppl 1):65S–72S.CrossRefGoogle Scholar
  35. Horne R, Weinman J, Barber N, Elliot R, Morgan M. Concordance, adherence and compliance in medicine taking: a conceptual map and research priorities. London: National Institute for Health Research (NIHR) Service Delivery and Organisation (SDO) Programme; 2005.Google Scholar
  36. Husebye ES, Allolio B, Arlt W, Badenhoop K, Bensing S, Betterle C, et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med. 2014;275(2):104–15.PubMedCrossRefGoogle Scholar
  37. Isidori AM, Venneri MA, Graziadio C, Simeoli C, Fiore D, Hasenmajer V, et al. 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. 2018;6(3):173–85.PubMedCrossRefGoogle Scholar
  38. Johannsson G, Bergthorsdottir R, Nilsson AG, Lennernas H, Hedner T, Skrtic S. Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study. Eur J Endocrinol. 2009;161(1):119–30.PubMedCrossRefGoogle Scholar
  39. Johannsson G, Nilsson AG, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, et al. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metabol. 2012;97(2):473–81.CrossRefGoogle Scholar
  40. Johannsson G, Falorni A, Skrtic S, Lennernas H, Quinkler M, Monson JP, et al. Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy. Clin Endocrinol. 2015;82(1):2–11.CrossRefGoogle Scholar
  41. Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Semin Arthritis Rheum. 2016;46(1):133–41.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Koyama Y, Homma K, Hasegawa T. Urinary steroid profiling: a powerful method for the diagnosis of abnormal steroidogenesis. Endocrinol Metab. 2014;9(3):273–82.Google Scholar
  43. Kwok MY, Scanlon MC, Slyper AH. Atypical presentation of shock from acute adrenal insufficiency in an adolescent male. Paediatr Emerg Care. 2005;21(6):380–3.CrossRefGoogle Scholar
  44. Lee AS, Twigg SM. Opioid-induced secondary adrenal insufficiency presenting as hypercalcaemia. Endocrinol Diabetes Metab Case Rep. 2015;2015:150035.PubMedPubMedCentralGoogle Scholar
  45. Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Llahana S, Philips D, Webber J, Chapman S, Carroll P, McBride P, et al., editors. Development and evaluation of the acceptability of new materials to address individualised needs to support self-management for patients with adrenal insufficiency Society for Endocrinology. Brighton: BES; 2016.Google Scholar
  47. Lovas K, Loge JH, Husebye ES. Subjective health status in Norwegian patients with Addison’s disease. Clin Endocrinol. 2002;56(5):581–8.CrossRefGoogle Scholar
  48. Lovas K, Gjesdal CG, Christensen M, Wolff AB, Almas B, Svartberg J, et al. Glucocorticoid replacement therapy and pharmacogenetics in Addison’s disease: effects on bone. Eur J Endocrinol. 2009;160(6):993–1002.PubMedCrossRefGoogle Scholar
  49. Lovas K, Curran S, Oksnes M, Husebye ES, Huppert FA, Chatterjee VK. Development of a disease-specific quality of life questionnaire in Addison’s disease. J Clin Endocrinol Metab. 2010;95(2):545–51.PubMedCrossRefGoogle Scholar
  50. Mah PM, Jenkins RC, Rostami-Hodjegan A, Newell-Price J, Doane A, Ibbotson V, et al. Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clin Endocrinol. 2004;61(3):367–75.CrossRefGoogle Scholar
  51. Mendoza-Cruz AC, Wargon O, Adams S, Tran H, Verge CF. HPA axis recovered within 6-12 weeks of infant prednisolone therapy. J Clin Endocrinol Metab. 2013;98(12):E1936–40.  https://doi.org/10.1210/jc.2013-2649.PubMedCrossRefGoogle Scholar
  52. Methlie P, Husebye EE, Hustad S, Lien EA, Lovas K. Grapefruit juice and licorice increase cortisol availability in patients with Addison’s disease. Eur J Endocrinol. 2011;165(5):761–9.PubMedCrossRefGoogle Scholar
  53. Migeon CJ, Lanes R. Adrenal cortex: hypofunction and hyperfunction (Chpater 8). In: Lifshitz F, editor. Pediatric endocrinology. Growth, adrenal, sexual, thyroid, calcium and fluid balance disorders, vol. 2. 5th ed. New York: Informa Healthcare; 2009.Google Scholar
  54. Miller W, Achermann JC, Fluck CE. The adrenal cortex and its disorders (Chapter 12). In: Sperling MA, editor. Pediatric Endocrinology. 3rd ed. Philadelphia, PA: Saunders Elsevier; 2008.Google Scholar
  55. Muller L, Quinkler M. Adrenal disease: imitating the cortisol profile improves the immune system. Nat Rev Endocrinol. 2018;14(3):137–9.PubMedCrossRefGoogle Scholar
  56. Murray RD, Ekman B, Uddin S, Marelli C, Quinkler M, Zelissen PM. Management of glucocorticoid replacement in adrenal insufficiency shows notable heterogeneity—data from the EU-AIR. Clin Endocrinol. 2017;86(3):340–6.CrossRefGoogle Scholar
  57. Neary N, Nieman L. Adrenal insufficiency: etiology, diagnosis and treatment. Curr Opin Endocrinol Diabetes Obes. 2010;17(3):217–23.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Neumann U, Whitaker MJ, Wiegand S, Krude H, Porter J, Davies M, et al. Absorption and tolerability of taste-masked hydrocortisone granules in neonates, infants and children under 6 years of age with adrenal insufficiency. Clin Endocrinol. 2018;88(1):21–9.CrossRefGoogle Scholar
  59. Nunes V, Neilson J, O’Flynn N, Calvert N, Kuntze S, Smithson H, et al. Clinical Guidelines and Evidence Review for Medicines Adherence: involving patients in decisions about prescribed medicines and supporting adherence. London: National Collaborating Centre for Primary Care and Royal College of General Practitioners; 2009.Google Scholar
  60. Oksnes M, Bjornsdottir S, Isaksson M, Methlie P, Carlsen S, Nilsen RM, et al. Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone replacement for treatment of Addison’s disease: a randomized clinical trial. J Clin Endocrinol Metab. 2014;99(5):1665–74.PubMedCrossRefGoogle Scholar
  61. Oksnes M, Ross R, Lovas K. Optimal glucocorticoid replacement in adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2015;29(1):3–15.PubMedCrossRefGoogle Scholar
  62. Policola C, Stokes V, Karavitaki N, Grossman A. Adrenal insufficiency in acute oral opiate therapy. Endocrinol Diabetes Metab Case Rep. 2014;2014:130071.PubMedPubMedCentralGoogle Scholar
  63. Quinkler M, Hahner S. What is the best long-term management strategy for patients with primary adrenal insufficiency? Clin Endocrinol. 2012;76(1):21–5.CrossRefGoogle Scholar
  64. Quinkler M, Beuschlein F, Hahner S, Meyer G, Schofl C, Stalla GK. Adrenal cortical insufficiency—a life threatening illness with multiple etiologies. Dtsch Arztebl Int. 2013;110(51–52):882–8.PubMedPubMedCentralGoogle Scholar
  65. Quinkler M, Oelkers W, Remde H, Allolio B. Mineralocorticoid substitution and monitoring in primary adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2015;29(1):17–24.PubMedCrossRefGoogle Scholar
  66. Quinkler M, Ekman B, Marelli C, Uddin S, Zelissen P, Murray RD, et al. Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency. Endocr Connect. 2016;6(1):1–8.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Qureshi AC, Bahri A, Breen LA, Barnes SC, Powrie JK, Thomas SM, et al. The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol. Clin Endocrinol. 2007;66(5):632–5.CrossRefGoogle Scholar
  68. Rushworth RL, Chrisp GL, Dean B, Falhammar H, Thorpy DJ. Hospitalisation in children with adrenal insufficiency and hypopituitarism: is there a differential burden between boys and girls and between age groups? Horm Res Paediatr. 2017;88(5):339–46.  https://doi.org/10.1159/000479370.PubMedCrossRefGoogle Scholar
  69. Salprietro V, Polizzi A, Di Rosa G, Romeo AC, Dipasqualw V, Morabito P, Chirico V, Arrigo T, Ruffieri M. Adrenal disorders and the paediatric brain: pathophysiological considerations and clinical implications. Int J Endocrinol. 2014.  https://doi.org/10.1155/2014/282489. 15 pages.CrossRefGoogle Scholar
  70. Schulz J, Frey KR, Cooper M, Zopf K, Ventz M, Diederich S, et al. Reduction in daily hydrocortisone dose improves bone health in primary adrenal insufficiency. Eur J Endocrinol. 2016;174(4):531–8.  https://doi.org/10.1530/eje-15-1096.PubMedCrossRefGoogle Scholar
  71. Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol. 2016;84(1):17–22.CrossRefGoogle Scholar
  72. Stewart PM. Chapter 14: The adrenal cortex. In: Kronemberg HM, Melmed S, Polonsky KS, Larsen PR, editors. Williams textbook of endocrinology. 11th ed. Philadelphia: Saunders Elsevier; 2008. p. 445–503.Google Scholar
  73. Tomlinson JW, Holden N, Hills RK, Wheatley K, Clayton RN, Bates AS, et al. Association between premature mortality and hypopituitarism. Lancet (London, England). 2001;357(9254):425–31.CrossRefGoogle Scholar
  74. Uta N, WM J, Susanna W, Heiko K, John P, Madhu D, et al. Absorption and tolerability of taste-masked hydrocortisone granules in neonates, infants and children under 6 years of age with adrenal insufficiency. Clin Endocrinol. 2018;88(1):21–9.CrossRefGoogle Scholar
  75. Wass JA, Arlt W. How to avoid precipitating an acute adrenal crisis. BMJ (Clin Res Ed). 2012;345:e6333.Google Scholar
  76. Whitaker M, Digweed D, Huatan H, Eckland D, Spielmann S, Johnson T, et al. Infacort, oral hydrocortisone granules with taste masking for the treatment of neonates and infants with adrenal insufficiency. Endocr Rev. 2014;35.Google Scholar
  77. White K, Arlt W. Adrenal crisis in treated Addison’s disease: a predictable but under-managed event. Eur J Endocrinol. 2010;162(1):115–20.PubMedCrossRefGoogle Scholar
  78. Zelissen PM, Croughs RJ, van Rijk PP, Raymakers JA. Effect of glucocorticoid replacement therapy on bone mineral density in patients with Addison disease. Ann Intern Med. 1994;120(3):207–10.PubMedCrossRefGoogle Scholar

Key Reading

  1. 1.
    Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol. 2015;3(3):216–26.PubMedCrossRefGoogle Scholar
  2. 2.
    Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364–89.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Grossman AB. Clinical review: the diagnosis and management of central hypoadrenalism. J Clin Endocrinol Metab. 2010;95(11):4855–63.PubMedCrossRefGoogle Scholar
  4. 4.
    Migeon CJ, Lanes R. Adrenal cortex: hypofunction and hyperfunction (Chapter 8). In: Lifshitz F, editor. Pediatric endocrinology. Growth, adrenal, sexual, thyroid, calcium and fluid balance disorders, vol. 2. 5th ed. New York: Informa Healthcare; 2009.Google Scholar
  5. 5.
    Arlt W. Disorders of the adrenal cortex (Chapter 8). In: Jameson JL, editor. Harrison’s endocrinology. 4th ed. New York: McGraw Hill Education; 2017. p. 107–35.Google Scholar
  6. 6.
    Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003;361(9372):1881–93.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sofia Llahana
    • 1
    Email author
  • Irene Mitchelhill
    • 2
  • Phillip Yeoh
    • 3
  • Marcus Quinkler
    • 4
  1. 1.School of Health Sciences, City, University of LondonLondonUK
  2. 2.Department of EndocrinologySydney Children’s Hospital (SCHN)RandwickAustralia
  3. 3.The London ClinicLondonUK
  4. 4.Endocrinology in Charlottenburg Stuttgarter Platz 1BerlinGermany

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