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Diagnosis and management of secondary adrenal crisis

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Abstract

Adrenal crisis (AC) is a life threatening acute adrenal insufficiency (AI) episode which can occur in patients with primary AI but also secondary AI (SAI), tertiary AI (TAI) and iatrogenic AI (IAI). In SAI, TAI and IAI, AC may develop when the HPA axis is unable to mount an adequate glucocorticoid response to severe stress due to pituitary or hypothalamic disruption. It manifests as an acute deterioration in multi-organ homeostasis that, if untreated, leads to shock and death. Despite the availability of effective preventive strategies, its prevalence is increasing in patients with SAI, TAI and IAI due to more frequent exogenous steroid administration, pituitary immune-related effects of immune checkpoint inhibitors and opioid use in pain management. The delayed diagnosis of acute AI which remains infrequently suspected increases the risk of AC. Its main precipitating factors are infections, emotional distress, surgery, cessation or reduction in GC doses, pituitary infarction or surgical cure of endogenous Cushing's syndrome. In patients not known previously to have SAI/TAI/IAI, recognition of its symptoms, signs, and biochemical abnormalities can be challenging and cause delay in proper diagnosis and therapy. Effective therapy of AC is rapid intravenous administration of hydrocortisone (initial bolus of 100 mg followed by 200 mg/24 h as continuous infusion or bolus of 50 mg every 6 h) and 0.9% saline. In diagnosed patients, preventive education in sick-day rules adjustment of glucocorticoid replacement and hydrocortisone parenteral self-administration must be performed repeatedly by trained health care providers. Strategies to improve the adequate preventive education in patients at risk for secondary AI should be promoted in collaboration with various medical specialist societies and patients support associations.

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Abbreviations

AC:

Adrenal Crisis

ACTH:

Adrenocorticotropic Hormone

ADH:

Antidiuretic Hormone

AI:

Adrenal Insufficiency

CRH:

Corticotropin Releasing Hormone

CRP:

C-reactive protein

CYP3A4:

Cytochrome P450 3A4

GC:

Glucocorticoids

GH:

Growth Hormone

GIAI:

Glucocorticoid Induced Adrenal Insufficiency

GR:

Glucocorticoid Receptor

HESX1:

HES homeobox 1

HPA:

Hypothalamic–Pituitary–Adrenal Axis

ICU:

Intensive Care Unit

IAI:

Iatrogenic induced Adrenal Insufficiency

IV:

Intravenous

IL:

Interleukin

LHX3:

LIM homeobox 3

LHX4:

LIM homeobox 4

OTX2:

Orthodenticle homeobox 2

PAI:

Primary Adrenal Insufficiency

POMC:

Pro-opiomelanocortin

PROP-1:

Prophet of Pit1

SAI:

Secondary Adrenal Insufficiency

SIADH:

Syndrome of inappropriate antidiuretic hormone secretion

TAI:

Tertiary Adrenal Insufficiency

TNF:

Tumor Necrosis Factor

TBX19:

Tbox transcription factor 19

References

  1. Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, Husebye ES, Merke DP, Murad MH, Stratakis CA, et al. Diagnosis and treatment of primary adrenal insufficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364–89.

    Article  CAS  PubMed  Google Scholar 

  2. Woodcock T, Barker P, Daniel S, Fletcher S, Wass JAH, Tomlinson JW, Misra U, Dattani M, Arlt W, Vercueil A. Guidelines for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency: Guidelines from the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK. Anaesthesia. 2020;75(5):654–63.

    Article  CAS  PubMed  Google Scholar 

  3. Araujo Castro M, Currás Freixes M, de Miguel Novoa P, Gracia Gimeno P, Álvarez Escolá C, Hanzu FA. SEEN guidelines for the management and prevention of acute adrenal insufficiency. Endocrinol diabetes y Nutr. 2020 Jan 1 [cited 2023 Oct 3];67(1):53–60. Available from: https://pubmed.ncbi.nlm.nih.gov/31003863/.

  4. Pastores SM, Annane D, Rochwerg B. Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients (Part II): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Vol. 46, Critical Care Medicine. Lippincott Williams and Wilkins; 2018. p. 146–8.

  5. Rushworth RL, Torpy DJ. Adrenal Insufficiency in Australia: Is it Possible that the Use of Lower Dose, Short-Acting Glucocorticoids has Increased the Risk of Adrenal Crises? Horm Metab Res. 2015 Nov 18 [cited 2023 Aug 19];47(6):427–32. Available from: https://pubmed.ncbi.nlm.nih.gov/25738995/.

  6. 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 [cited 2023 Aug 19];162(3):597–602. Available from: https://pubmed.ncbi.nlm.nih.gov/19955259/.

  7. Rushworth RL, Torpy DJ, Falhammar H. Adrenal crises: perspectives and research directions. Endocrine. 2017 Feb 1 [cited 2023 Aug 19];55(2):336–45. Available from: https://pubmed.ncbi.nlm.nih.gov/27995500/.

  8. Smans LCCJ, Van Der Valk ES, Hermus ARMM, Zelissen PMJ. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2016 [cited 2023 Aug 19];84(1):17–22. Available from: https://pubmed.ncbi.nlm.nih.gov/26208266/.

  9. Rushworth RL, Chrisp GL, Torpy DJ. Glucocorticoid-induced Adrenal Insufficiency: A Study of the Incidence in Hospital Patients and a Review of Peri-operative Management. Endocr Pract. 2018 [cited 2023 Sep 27];24(5):437–45. Available from: https://pubmed.ncbi.nlm.nih.gov/29498915/.

  10. Li D, Genere N, Behnken E, Xhikola M, Abbondanza T, Vaidya A, Bancos I. Determinants of Self-reported Health Outcomes in Adrenal Insufficiency: A Multisite Survey Study. J Clin Endocrinol Metab. 2021 [cited 2023 Aug 24];106(3):E1408–19. Available from: https://pubmed.ncbi.nlm.nih.gov/32995875/.

  11. Rushworth RL, Torpy DJ. The Changing Epidemiology of Adrenal Insufficiency: Iatrogenic Factors Predominate. J Endocr Soc. 2023 Mar 1 [cited 2023 Oct 9];7(3). Available from: https://pubmed.ncbi.nlm.nih.gov/36777466/.

  12. Husebye ES, Pearce SH, Krone NP, Kämpe O. Adrenal insufficiency. Lancet Elsevier BV. 2021;397:613–29.

    Article  CAS  Google Scholar 

  13. Mebrahtu TF, Morgan AW, Keeley A, Baxter PD, Stewart PM, Pujades-Rodriguez M. Dose Dependency of Iatrogenic Glucocorticoid Excess and Adrenal Insufficiency and Mortality: A Cohort Study in England. J Clin Endocrinol Metab. 2019 [cited 2023 Sep 2];104(9):3757–67. Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/31009052/.

  14. Li T, Donegan D, Hooten WM, Bancos I. Clinical Presentation and Outcomes of Opioid-Induced Adrenal Insufficiency. Endocr Pract. 2020 Nov 1 [cited 2023 Aug 24];26(11):1291–7. Available from: https://pubmed.ncbi.nlm.nih.gov/33471659/.

  15. Woods CP, Argese N, Chapman M, Boot C, Webster R, Dabhi V, Grossman AB, Toogood AA, Arlt W, Stewart PM, et al. Adrenal suppression in patients taking inhaled glucocorticoids is highly prevalent and management can be guided by morning cortisol. Eur J Endocrinol. 2015 [cited 2023 Sep 2];173(5):633–42. Available from: https://pubmed.ncbi.nlm.nih.gov/26294794/.

  16. Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L. Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Endocr Rev. 2019 [cited 2023 Aug 22];40(1):17–65. Available from: https://pubmed.ncbi.nlm.nih.gov/30184160/.

  17. Tan MH, Iyengar R, Mizokami-Stout K, Yentz S, MacEachern MP, Shen LY, Redman B, Gianchandani R. Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports. Clin diabetes Endocrinol. 2019 [cited 2023 Aug 22];5(1). Available from: https://pubmed.ncbi.nlm.nih.gov/30693099/.

  18. Oelkers W. Adrenal insufficiency. N Engl J Med. 1996 [cited 2023 Aug 22];335(16):1206–12. Available from: https://pubmed.ncbi.nlm.nih.gov/8815944/.

  19. Allolio B. Extensive expertise in Endocrinology: Adrenal crisis. Eur J Endocrinol. 2015 [cited 2023 Aug 22];172(3):R115–24. Available from: https://doi.org/10.1530/EJE-14-0824.

  20. Rushworth RL, Torpy DJ, Falhammar H. Adrenal Crisis. Ingelfinger JR, editor. N Engl J Med. 2019;381(9):852–61. Available from: http://www.nejm. https://doi.org/10.1056/NEJMra1807486.

  21. Puar THK, Stikkelbroeck NMML, Smans LCCJ, Zelissen PMJ, Hermus ARMM. Adrenal Crisis: Still a Deadly Event in the 21st Century. Am J Med. 2016 [cited 2023 Aug 22];129(3):339.e1–339.e9. Available from: https://pubmed.ncbi.nlm.nih.gov/26363354/.

  22. Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015 [cited 2023 Aug 19];100(2):407–16. Available from: https://pubmed.ncbi.nlm.nih.gov/25419882/.

  23. Notter A, Jenni S, Christ E. Evaluation of the frequency of adrenal crises and preventive measures in patients with primary and secondary adrenal insufficiency in Switzerland. Swiss Med Wkly. 2018 [cited 2023 Aug 22];148:w14586. Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/29376554/.

  24. 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 [cited 2023 Aug 19];14(1). Available from: https://pubmed.ncbi.nlm.nih.gov/25273066/.

  25. 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 [cited 2023 Aug 22];176(3):329–37. Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/28130352/.

  26. Quinkler M, Ekman B, Zhang P, Isidori AM, Murray RD. Mortality data from the European Adrenal Insufficiency Registry-Patient characterization and associations. Clin Endocrinol (Oxf). 2018 [cited 2023 Aug 19];89(1):30–5. Available from: https://pubmed.ncbi.nlm.nih.gov/29682773/.

  27. Bollag WB. Regulation of aldosterone synthesis and secretion. Compr Physiol. 2014 [cited 2023 Oct 5];4(3):1017–55. Available from: https://pubmed.ncbi.nlm.nih.gov/24944029/.

  28. Erkut ZA, Pool C, Swaab DF. Glucocorticoids suppress corticotropin-releasing hormone and vasopressin expression in human hypothalamic neurons. J Clin Endocrinol Metab. 1998 [cited 2023 Oct 5];83(6):2066–73. Available from: https://pubmed.ncbi.nlm.nih.gov/9626140/.

  29. Kim JK, Summer SN, Wood WM, Schrier RW. Role of glucocorticoid hormones in arginine vasopressin gene regulation. Biochem Biophys Res Commun. 2001 [cited 2023 Oct 5];289(5):1252–6. Available from: https://pubmed.ncbi.nlm.nih.gov/11741329/.

  30. Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. lancet Diabetes Endocrinol. 2015 [cited 2023 Oct 9];3(3):216–26. Available from: https://pubmed.ncbi.nlm.nih.gov/25098712/.

  31. Malbon CC, Rapiejko PJ, Watkins DC. Permissive hormone regulation of hormone-sensitive effector systems. Trends Pharmacol Sci. 1988 [cited 2023 Oct 5];9(1):33–6. Available from: https://pubmed.ncbi.nlm.nih.gov/3072728/.

  32. Ueland T, Kristo C, Godang K, Aukrust P, Bollerslev J. Interleukin-1 Receptor Antagonist Is Associated with Fat Distribution in Endogenous Cushing’s Syndrome: A Longitudinal Study. J Clin Endocrinol Metab. 2003 [cited 2019 Sep 3];88(4):1492–6. Available from: https://academic.oup.com/jcem/article-abstract/88/4/1492/2845156.

  33. Bellavance MA, Rivest S. The HPA - Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain. Front Immunol. 2014 [cited 2023 Oct 5];5(MAR). Available from: https://pubmed.ncbi.nlm.nih.gov/24744759/.

  34. Pariante CM, Pearce BD, Pisell TL, Sanchez CI, Po C, Su C, Miller AH. The proinflammatory cytokine, interleukin-1alpha, reduces glucocorticoid receptor translocation and function. Endocrinology. 1999 [cited 2023 Oct 5];140(9):4359–66. Available from: https://pubmed.ncbi.nlm.nih.gov/10465310/.

  35. A E Barber 1, S M Coyle, M A Marano, E Fischer, S E Calvano, Y Fong, L L Moldawer SFL. Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man - PubMed. J Immunol. 1993 [cited 2024 Jan 16];150(5):1999–2006. Available from: https://pubmed.ncbi.nlm.nih.gov/8436830/.

  36. Morrow LE, McClellan JL, Conn CA, Kluger MJ. Glucocorticoids alter fever and IL-6 responses to psychological stress and to lipopolysaccharide. Am J Physiol. 1993 [cited 2024 Jan 16];264(5 Pt 2). Available from: https://pubmed.ncbi.nlm.nih.gov/8498588/.

  37. Kuo T, McQueen A, Chen TC, Wang JC. Regulation of Glucose Homeostasis by Glucocorticoids. Adv Exp Med Biol. 2015 [cited 2023 Oct 5];872:99. Available from: /pmc/articles/PMC6185996/

  38. DeVile CJ, Stanhope R. Hydrocortisone replacement therapy in children and adolescents with hypopituitarism. Clin Endocrinol (Oxf). 1997 [cited 2024 Jan 16];47(1):37–41. Available from: https://pubmed.ncbi.nlm.nih.gov/9302370/.

  39. Fischer JE, Stallmach T, Fanconi S. Adrenal crisis presenting as hypoglycemic coma. Intensive Care Med. 2000 [cited 2024 Jan 16];26(1):105–8. Available from: https://pubmed.ncbi.nlm.nih.gov/10663290/.

  40. Sominsky L, Spencer SJ. Eating behavior and stress: a pathway to obesity. Front Psychol. 2014 [cited 2023 Oct 5];5(MAY). Available from: https://pubmed.ncbi.nlm.nih.gov/24860541/.

  41. Samuels ME, Gallo-Payet N, Pinard S, Hasselmann C, Magne F, Patry L, Chouinard L, Schwartzentruber J, Patricia René, Sawyer N, et al. Bioinactive ACTH causing glucocorticoid deficiency. J Clin Endocrinol Metab. 2013 Feb [cited 2023 Sep 9];98(2):736–42. Available from: https://pubmed.ncbi.nlm.nih.gov/23293326/.

  42. Laugesen K, Lunde Jørgensen JO, Petersen I, Sørensen HT. Fifteen-year nationwide trends in systemic glucocorticoid drug use in Denmark. Eur J Endocrinol. 2019 [cited 2023 Aug 26];181(3):267–73. Available from: https://pubmed.ncbi.nlm.nih.gov/31269470/.

  43. Fardet L, Petersen I, Nazareth I. Prevalence of long-term oral glucocorticoid prescriptions in the UK over the past 20 years. Rheumatology (Oxford). 2011 [cited 2023 Aug 26];50(11):1982–90. Available from: https://pubmed.ncbi.nlm.nih.gov/21393338/.

  44. Van Staa TP, Leufkens HGM, Abenhaim L, Begaud B, Zhang B, Cooper C. Use of oral corticosteroids in the United Kingdom. QJM - Mon J Assoc Physicians. 2000;93(2):105–11.

    Article  Google Scholar 

  45. Overman RA, Yeh JY, Deal CL. Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Res (Hoboken). 2013 [cited 2023 Aug 19];65(2):294–8. Available from: https://pubmed.ncbi.nlm.nih.gov/22807233/.

  46. Meikle AW, Tyler FH. Potency and duration of action of glucocorticoids. Effects of hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function. Am J Med. 1977 [cited 2023 Sep 9];63(2):200–7. Available from: https://pubmed.ncbi.nlm.nih.gov/888843/.

  47. Einaudi S, Bertorello N, Masera N, Farinasso L, Barisone E, Rizzari C, Corrias A, Villa A, Riva F, Saracco P, et al. Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008 [cited 2023 Sep 9];50(3):537–41. Available from: https://pubmed.ncbi.nlm.nih.gov/17828747/.

  48. Kuperman H, Odone Filho V, Cristofani LM, Assis De Almeida MT, Setian N, Damiani D. Evaluation of adrenal reserve in children with acute lymphocytic leukemia treated with prednisone or dexamethasone. Horm Res Paediatr. 2012 [cited 2023 Sep 9];78(2):73–80. Available from: https://pubmed.ncbi.nlm.nih.gov/22922775/.

  49. Dinsen S, Baslund B, Klose M, Rasmussen AK, Friis-Hansen L, Hilsted L, Feldt-Rasmussen U. Why glucocorticoid withdrawal may sometimes be as dangerous as the treatment itself. Eur J Intern Med. 2013 [cited 2023 Sep 2];24(8):714–20. Available from: https://pubmed.ncbi.nlm.nih.gov/23806261/.

  50. Broersen LHA, Pereira AM, Jørgensen JOL, Dekkers OM. Adrenal Insufficiency in Corticosteroids Use: Systematic Review and Meta-Analysis. J Clin Endocrinol Metab. 2015 Jun 1 [cited 2023 Aug 26];100(6):2171–80. Available from: https://pubmed.ncbi.nlm.nih.gov/25844620/.

  51. Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: A systematic review. Semin Arthritis Rheum. 2016 [cited 2023 Aug 26];46(1):133–41. Available from: https://pubmed.ncbi.nlm.nih.gov/27105755/.

  52. Einarsdottir MJ, Bankvall M, Robledo-Sierra J, Rödström PO, Bergthorsdottir R, Trimpou P, Hasséus B, Ragnarsson O. Topical clobetasol treatment for oral lichen planus can cause adrenal insufficiency. Oral Dis. 2023 [cited 2024 Jan 19]; Available from: https://pubmed.ncbi.nlm.nih.gov/37103329/.

  53. Grossmann C, Scholz T, Rochel M, Bumke-Vogt C, Oelkers W, Pfeiffer AFH, Diederich S, Bähr V. Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties. Eur J Endocrinol. 2004 [cited 2023 Sep 9];151(3):397–406. Available from: https://pubmed.ncbi.nlm.nih.gov/15362971/.

  54. Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. Arch Intern Med. 1999 [cited 2024 Jan 16];159(9):941–55. Available from: https://pubmed.ncbi.nlm.nih.gov/10326936/.

  55. LaRochelle GE, LaRochelle AG, Ratner RE, Borenstein DG. Recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisone. Am J Med. 1993 [cited 2023 Sep 10];95(3):258–64. Available from: https://pubmed.ncbi.nlm.nih.gov/8368224/.

  56. Schlaghecke R, Kornely E, Santen RT, Ridderskamp P. The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. N Engl J Med. 1992 [cited 2023 Aug 26];326(4):226–30. Available from: https://pubmed.ncbi.nlm.nih.gov/1309389/.

  57. Borresen SW, Klose M, Baslund B, Rasmussen ÅK, Hilsted L, Friis-Hansen L, Locht H, Hansen A, Hetland ML, Lydolph MC, et al. Adrenal insufficiency is seen in more than one-third of patients during ongoing low-dose prednisolone treatment for rheumatoid arthritis. Eur J Endocrinol. 2017 [cited 2023 Aug 26];177(4):287–95. Available from: https://pubmed.ncbi.nlm.nih.gov/28877961/.

  58. Henzen C, Suter A, Lerch E, Urbinelli R, Schorno XH, Briner VA. Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment. Lancet (London, England). 2000 [cited 2023 Aug 26];355(9203):542–5. Available from: https://pubmed.ncbi.nlm.nih.gov/10683005/.

  59. Dineen R, Stewart PM, Sherlock M. Factors impacting on the action of glucocorticoids in patients receiving glucocorticoid therapy. Clin Endocrinol (Oxf). 2019 [cited 2023 Aug 26];90(1):3–14. Available from: https://pubmed.ncbi.nlm.nih.gov/30120786/.

  60. Nicolaides NC, Charmandari E, Chrousos GP, Kino T. Recent advances in the molecular mechanisms determining tissue sensitivity to glucocorticoids: novel mutations, circadian rhythm and ligand-induced repression of the human glucocorticoid receptor. BMC Endocr Disord. 2014 [cited 2023 Aug 26];14(1). Available from: https://pubmed.ncbi.nlm.nih.gov/25155432/.

  61. Quax RA, Manenschijn L, Koper JW, Hazes JM, Lamberts SWJ, Van Rossum EFC, Feelders RA. Glucocorticoid sensitivity in health and disease. Nat Rev Endocrinol. 2013 [cited 2023 Aug 26];9(11):670–86. Available from: https://pubmed.ncbi.nlm.nih.gov/24080732/.

  62. Huizenga NATM, Koper JW, de Lange P, Pols HAP, Stolk RP, Grobbee DE, de Jong FH, Lamberts SWJ. Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals. J Clin Endocrinol Metab. 1998 [cited 2023 Aug 26];83(1):47–54. Available from: https://pubmed.ncbi.nlm.nih.gov/9435415/.

  63. Neidert S, Schuetz P, Mueller B, Christ-Crain M. Dexamethasone suppression test predicts later development of an impaired adrenal function after a 14-day course of prednisone in healthy volunteers. Eur J Endocrinol. 2010 [cited 2023 Aug 26];162(5):943–9. Available from: https://pubmed.ncbi.nlm.nih.gov/20142368/.

  64. Bolton JL, Hayward C, Direk N, Lewis JG, Hammond GL, Hill LA, Anderson A, Huffman J, Wilson JF, Campbell H, et al. Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin. PLoS Genet. 2014 [cited 2023 Sep 2];10(7). Available from: https://pubmed.ncbi.nlm.nih.gov/25010111/.

  65. Hawcutt DB, Francis B, Carr DF, Jorgensen AL, Yin P, Wallin N, O’Hara N, Zhang EJ, Bloch KM, Ganguli A, et al. Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study. Lancet Respir Med. 2018 [cited 2023 Sep 2];6(6):442–50. Available from: https://pubmed.ncbi.nlm.nih.gov/29551627/.

  66. Van Keulen BJ, Dolan C V., Andrew R, Walker BR, Hulshoff Pol HE, Boomsma DI, Rotteveel J, Finken MJJ. Heritability of Cortisol Production and Metabolism Throughout Adolescence. J Clin Endocrinol Metab. 2020 [cited 2023 Sep 2];105(2). Available from: https://pubmed.ncbi.nlm.nih.gov/31608377/.

  67. Sagar R, Mackie S, W. Morgan A, Stewart P, Abbas A. Evaluating tertiary adrenal insufficiency in rheumatology patients on long-term systemic glucocorticoid treatment. Clin Endocrinol (Oxf). 2021 [cited 2023 Aug 26];94(3):361–70. Available from: https://pubmed.ncbi.nlm.nih.gov/33370485/.

  68. Borresen SW, Thorgrimsen TB, Jensen B, Hilsted L, Bartels EM, Feldt-Rasmussen U, Locht H. Adrenal insufficiency in prednisolone-treated patients with polymyalgia rheumatica or giant cell arteritis-prevalence and clinical approach. Rheumatology (Oxford). 2020 [cited 2023 Aug 26];59(10):2764–73. Available from: https://pubmed.ncbi.nlm.nih.gov/32031663/.

  69. Valentin A, Borresen SW, Rix M, Elung-Jensen T, Sørensen SS, Feldt-Rasmussen U. Adrenal insufficiency in kidney transplant patients during low-dose prednisolone therapy: a cross-sectional case-control study. Nephrol Dial Transplant. 2020 [cited 2023 Aug 26];35(12):2191–7. Available from: https://pubmed.ncbi.nlm.nih.gov/31539081/.

  70. Derendorf H. Pharmacokinetic and pharmacodynamic properties of inhaled corticosteroids in relation to efficacy and safety. Respir Med. 1997 [cited 2023 Aug 26];91 Suppl A(SUPPL. A):22–8. Available from: https://pubmed.ncbi.nlm.nih.gov/9474364/.

  71. Zöllner EW, Lombard CJ, Galal U, Hough FS, Irusen EM, Weinberg E. Hypothalamic-pituitary-adrenal axis suppression in asthmatic school children. Pediatrics. 2012 [cited 2023 Aug 26];130(6). Available from: https://pubmed.ncbi.nlm.nih.gov/23147980/.

  72. Czock D, Keller F, Rasche FM, Häussler U. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005 [cited 2023 Aug 26];44(1):61–98. Available from: https://pubmed.ncbi.nlm.nih.gov/15634032/.

  73. Jasani KM, Boyle JA, Dick WC, Williamson J, Taylor AK, Buchanan WW. Corticosteroid-induced hypothalamo-pituitary-adrenal axis suppression. Prospective study using two regimens of corticosteroid therapy. Ann Rheum Dis. 1968 [cited 2023 Aug 26];27(4):352–9. Available from: https://pubmed.ncbi.nlm.nih.gov/5666676/.

  74. Ekman B, Bachrach-Lindström M, Lindström T, Wahlberg J, Blomgren J, Arnqvist HJ. A randomized, double-blind, crossover study comparing two- and four-dose hydrocortisone regimen with regard to quality of life, cortisol and ACTH profiles in patients with primary adrenal insufficiency. Clin Endocrinol (Oxf). 2012 [cited 2023 Aug 26];77(1):18–25. Available from: https://pubmed.ncbi.nlm.nih.gov/22288685/.

  75. Li T, Cunningham JL, Gilliam WP, Loukianova L, Donegan DM, Bancos I. Prevalence of Opioid-Induced Adrenal Insufficiency in Patients Taking Chronic Opioids. J Clin Endocrinol Metab. 2020 [cited 2023 Aug 24];105(10):e3766. Available from: /pmc/articles/PMC7470471/.

  76. Nanus DE, Filer AD, Hughes B, Fisher BA, Taylor PC, Stewart PM, Buckley CD, McInnes I, Cooper MS, Raza K. TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis. Ann Rheum Dis. 2015 [cited 2023 Aug 26];74(2):464–9. Available from: https://pubmed.ncbi.nlm.nih.gov/24385202/.

  77. Einarsdottir MJ, Kristjansdottir HL, Bergthorsdottir R, Johannsson G, Trimpou P, Lewerin C, Ragnarsson O. Intermittent high-dose glucocorticoid treatment does not cause adrenal insufficiency in patients with diffuse large B-cell lymphoma - a prospective study. Acta Haematol. 2023 [cited 2024 Jan 19]; Available from: https://pubmed.ncbi.nlm.nih.gov/37757784/.

  78. Jespersen S, Nygaard B, Kristensen LØ. Methylprednisolone Pulse Treatment of Graves’ Ophthalmopathy Is Not Associated with Secondary Adrenocortical Insufficiency. Eur Thyroid J. 2015 [cited 2024 Jan 19];4(4):222–5. Available from: https://pubmed.ncbi.nlm.nih.gov/26835424/.

  79. Mehta P, Meeran K, Macphie E, Abbas A, Rippin J, Jeffery RC, Reddy V, Leandro MJ, Ciurtin C, Simpson HL, et al. Variability in counselling for adrenal insufficiency in COVID-19 and beyond: a survey of rheumatology practice. Lancet Rheumatol. 2021 [cited 2023 Aug 26];3(2):e92–4. Available from: https://pubmed.ncbi.nlm.nih.gov/33521672/.

  80. Gibb FW, Stewart A, Walker BR, Strachan MWJ. Adrenal insufficiency in patients on long-term opioid analgesia. Clin Endocrinol (Oxf). 2016 [cited 2023 Aug 24];85(6):831–5. Available from: https://pubmed.ncbi.nlm.nih.gov/27260138/.

  81. Tennant F, Hermann L. Normalization of serum cortisol concentration with opioid treatment of severe chronic pain. Pain Med. 2002 [cited 2023 Aug 24];3(2):132–4. Available from: https://pubmed.ncbi.nlm.nih.gov/15102160/.

  82. Demarest SP, Gill RS, Adler RA. Opioid endocrinopathy. Endocr Pract. 2015 [cited 2023 Aug 24];21(2):190–8. Available from: https://pubmed.ncbi.nlm.nih.gov/25536970/.

  83. de Vries F, Bruin M, Lobatto DJ, Dekkers OM, Schoones JW, van Furth WR, Pereira AM, Karavitaki N, Biermasz NR, Zamanipoor Najafabadi AH. Opioids and Their Endocrine Effects: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab. 2020 [cited 2023 Aug 26];105(3):1020–9. Available from: https://pubmed.ncbi.nlm.nih.gov/31511863/.

  84. Lamprecht A, Sorbello J, Jang C, Torpy DJ, Inder WJ. Secondary adrenal insufficiency and pituitary dysfunction in oral/transdermal opioid users with non-cancer pain. Eur J Endocrinol. 2018 [cited 2023 Aug 19];179(6):353–62. Available from: https://pubmed.ncbi.nlm.nih.gov/30324794/.

  85. Abs R, Verhelst J, Maeyaert J, Van Buyten JP, Opsomer F, Adriaensen H, Verlooy J, Van Havenbergh T, Smet M, Van Acker K. Endocrine Consequences of Long-Term Intrathecal Administration of Opioids. J Clin Endocrinol Metab. 2000 [cited 2023 Aug 26];85(6):2215–22. Available from: https://doi.org/10.1210/jcem.85.6.6615.

  86. Donegan D, Bancos I. Opioid-Induced Adrenal Insufficiency. Mayo Clin Proc. 2018 [cited 2023 Aug 26];93(7):937–44. Available from: https://pubmed.ncbi.nlm.nih.gov/29976376/.

  87. García García E, Ramírez Villar GL, Quiroga Cantero E. Megestrol-induced adrenal insufficiency in children and adolescents. Med Clin (Barc). 2022 [cited 2023 Oct 9];158(5):241–2. Available from: https://pubmed.ncbi.nlm.nih.gov/34074479/.

  88. Han HS, Shim YK, Kim JE, Jeon HJ, Lim SN, Oh TK, Lee KH, Kim ST. A pilot study of adrenal suppression after dexamethasone therapy as an antiemetic in cancer patients. Support Care Cancer. 2012 [cited 2023 Sep 2];20(7):1565–72. Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/21850416/.

  89. Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. Vol. 3, The Lancet Diabetes and Endocrinology. Lancet Publishing Group 2015:216–26.

  90. Crowley RK, Hamnvik OP, O’Sullivan EP, Behan LA, Smith D, Agha A, Thompson CJ. Morbidity and mortality in patients with craniopharyngioma after surgery. Clin Endocrinol (Oxf). 2010 [cited 2023 Sep 9];73(4):516–21. Available from: https://pubmed.ncbi.nlm.nih.gov/20550527/.

  91. O’Sullivan EP, Woods C, Glynn N, Behan LA, Crowley R, O’Kelly P, Smith D, Thompson CJ, Agha A. The natural history of surgically treated but radiotherapy-naïve nonfunctioning pituitary adenomas. Clin Endocrinol (Oxf). 2009 [cited 2023 Oct 9];71(5):709–14. Available from: https://pubmed.ncbi.nlm.nih.gov/19302582/.

  92. Faria M, Nascimento GC, Faria AM, Martins MRA. Hypopituitarism. Endocrinol Diabetes A Probl Oriented Approach Second Ed. 2022 [cited 2024 Jan 16];61–78. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278989/.

  93. Agha A, Thompson CJ. Anterior pituitary dysfunction following traumatic brain injury (TBI). Clin Endocrinol (Oxf). 2006 [cited 2023 Sep 9];64(5):481–8. Available from: https://pubmed.ncbi.nlm.nih.gov/16649964/.

  94. Agha A, Sherlock M, Brennan S, O’Connor SA, O’Sullivan E, Rogers B, Faul C, Rawluk D, Tormey W, Thompson CJ. Hypothalamic-pituitary dysfunction after irradiation of nonpituitary brain tumors in adults. J Clin Endocrinol Metab. 2005 [cited 2023 Sep 9];90(12):6355–60. Available from: https://pubmed.ncbi.nlm.nih.gov/16144946/.

  95. Hassan-Smith ZK, Sherlock M, Reulen RC, Arlt W, Ayuk J, Toogood AA, Cooper MS, Johnson AP, Stewart PM. Outcome of Cushing’s disease following transsphenoidal surgery in a single center over 20 years. J Clin Endocrinol Metab. 2012 [cited 2023 Sep 10];97(4):1194–201. Available from: https://pubmed.ncbi.nlm.nih.gov/22278423/.

  96. Abdelmannan D, Chaiban J, Selman WR, Arafah BM. Recurrences of ACTH-secreting adenomas after pituitary adenomectomy can be accurately predicted by perioperative measurements of plasma ACTH levels. J Clin Endocrinol Metab. 2013 [cited 2023 Sep 10];98(4):1458–65. Available from: https://pubmed.ncbi.nlm.nih.gov/23450054/.

  97. Biller BMK, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, Buchfelder M, Colao A, Hermus AR, Hofland LJ, et al. Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2008 [cited 2023 Sep 10];93(7):2454–62. Available from: https://pubmed.ncbi.nlm.nih.gov/18413427/.

  98. Heinrich DA, Adolf C, Holler F, Lechner B, Schneider H, Riester A, Nirschl N, Sturm L, Wang X, Ladurner R, et al. Adrenal Insufficiency After Unilateral Adrenalectomy in Primary Aldosteronism: Long-Term Outcome and Clinical Impact. J Clin Endocrinol Metab. 2019 [cited 2023 Aug 19];104(11):5658–64. Available from: https://pubmed.ncbi.nlm.nih.gov/31225874/.

  99. Glezer A, Bronstein MD. Pituitary autoimmune disease: nuances in clinical presentation. Endocrine. 2012 [cited 2023 Sep 9];42(1):74–9. Available from: https://pubmed.ncbi.nlm.nih.gov/22426958/.

  100. Suzuki K, Terakawa T, Furukawa J, Harada K, Hinata N, Nakano Y, Fujisawa M. Nivolumab-induced Adrenal Insufficiency in Patients With Renal Cell Carcinoma. J Immunother. 2020 [cited 2023 Aug 24];43(1):38–42. Available from: https://pubmed.ncbi.nlm.nih.gov/31567704/.

  101. Yamauchi I, Taura D, Hakata T, Fujita H, Okamoto K, Ueda Y, Fujii T, Inagaki N. Clinical features and thyroid dysfunction in adverse events involving the pituitary gland during PD-1 blockade therapy. Clin Endocrinol (Oxf). 2021 [cited 2023 Aug 24];94(2):258–68. Available from: https://pubmed.ncbi.nlm.nih.gov/33037658/.

  102. Levy M, Abeillon J, Dalle S, Assaad S, Borson-Chazot F, Disse E, Raverot G, Cugnet-Anceau C. Anti-PD1 and Anti-PDL1-Induced Hypophysitis: A Cohort Study of 17 Patients with Longitudinal Follow-Up. J Clin Med. 2020 [cited 2023 Aug 24];9(10):1–10. Available from: /pmc/articles/PMC7601962/.

  103. Zhai Y, Ye X, Hu F, Xu J, Guo X, Zhuang Y, He J. Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US Food and Drug Administration adverse events reporting system. J Immunother cancer. 2019 [cited 2023 Aug 26];7(1). Available from: https://pubmed.ncbi.nlm.nih.gov/31694698/.

  104. Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncol. 2018 [cited 2023 Aug 19];4(2):173–82. Available from: https://pubmed.ncbi.nlm.nih.gov/28973656/.

  105. Min L, Hodi FS, Giobbie-Hurder A, Ott PA, Luke JJ, Donahue H, Davis M, Carroll RS, Kaiser UB. Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study. Clin Cancer Res. 2015 [cited 2023 Aug 26];21(4):749–55. Available from: https://pubmed.ncbi.nlm.nih.gov/25538262/.

  106. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Grüters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998 [cited 2023 Sep 9];19(2):155–7. Available from: https://pubmed.ncbi.nlm.nih.gov/9620771/.

  107. Lamolet B, Pulichino AM, Lamonerie T, Gauthier Y, Brue T, Enjalbert A, Drouin J. A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins. Cell. 2001 [cited 2023 Sep 9];104(6):849–59. Available from: https://pubmed.ncbi.nlm.nih.gov/11290323/.

  108. Drouin J, Bilodeau S, Vallette S. Of old and new diseases: genetics of pituitary ACTH excess (Cushing) and deficiency. Clin Genet. 2007 [cited 2023 Sep 9];72(3):175–82. Available from: https://pubmed.ncbi.nlm.nih.gov/17718852/.

  109. Quentien MH, Delemer B, Papadimitriou DT, Souchon PF, Jaussaud R, Pagnier A, Munzer M, Jullien N, Reynaud R, Galon-Faure N, et al. Deficit in anterior pituitary function and variable immune deficiency (DAVID) in children presenting with adrenocorticotropin deficiency and severe infections. J Clin Endocrinol Metab. 2012 [cited 2023 Sep 9];97(1). Available from: https://pubmed.ncbi.nlm.nih.gov/22013103/.

  110. Vallette-Kasic S, Barlier A, Teinturier C, Diaz A, Manavela M, Berthezène F, Bouchard P, Chaussain JL, Brauner R, Pellegrini-Bouiller I, et al. PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency. J Clin Endocrinol Metab. 2001 [cited 2023 Sep 9];86(9):4529–35. Available from: https://pubmed.ncbi.nlm.nih.gov/11549703/.

  111. Rajab A, Kelberman D, De castro SCP, Biebermann H, Shaikh H, Pearce K, Hall CM, Shaikh G, Gerrelli D, Grueters A, et al. Novel mutations in LHX3 are associated with hypopituitarism and sensorineural hearing loss. Hum Mol Genet. 2008 [cited 2023 Sep 9];17(14):2150–9. Available from: https://pubmed.ncbi.nlm.nih.gov/18407919/.

  112. Tajima T, Hattori T, Nakajima T, Okuhara K, Tsubaki J, Fujieda K. A novel missense mutation (P366T) of the LHX4 gene causes severe combined pituitary hormone deficiency with pituitary hypoplasia, ectopic posterior lobe and a poorly developed sella turcica. Endocr J. 2007 [cited 2023 Sep 9];54(4):637–41. Available from: https://pubmed.ncbi.nlm.nih.gov/17527005/.

  113. Carvalho LR, Woods KS, Mendonca BB, Marcal N, Zamparini AL, Stifani S, Brickman JM, Arnhold IJP, Dattani MT. A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction. J Clin Invest. 2003 [cited 2023 Sep 9];112(8):1192–201. Available from: https://pubmed.ncbi.nlm.nih.gov/14561704/.

  114. Shimada A, Takagi M, Nagashima Y, Miyai K, Hasegawa Y. A Novel Mutation in OTX2 Causes Combined Pituitary Hormone Deficiency, Bilateral Microphthalmia, and Agenesis of the Left Internal Carotid Artery. Horm Res Paediatr. 2016 [cited 2023 Sep 9];86(1):62–9. Available from: https://pubmed.ncbi.nlm.nih.gov/27299576/.

  115. Maguire D, McLaren DS, Rasool I, Shah PM, Lynch J, Murray RD. ChAdOx1 SARS-CoV-2 vaccination: A putative precipitant of adrenal crises. Clin Endocrinol (Oxf). 2021 [cited 2023 Aug 22]; Available from: https://pubmed.ncbi.nlm.nih.gov/34358373/.

  116. Lewandowski KC, Marcinkowska M, Skowrońska-Jóźwiak E, Makarewicz J, Lewiński A. New onset Graves’ disease as a cause of an adrenal crisis in an individual with panhypopituitarism: brief report. Thyroid Res. 2008 [cited 2023 Sep 25];1(1). Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/19019235/.

  117. Sychev DA, Ashraf GM, Svistunov AA, Maksimov ML, Tarasov V V., Chubarev VN, Otdelenov VA, Denisenko NP, Barreto GE, Aliev G. The cytochrome P450 isoenzyme and some new opportunities for the prediction of negative drug interaction in vivo. Drug Des Devel Ther. 2018 [cited 2023 Sep 25];12:1147–56. Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/29780235/.

  118. Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet (London, England). 2014 [cited 2023 Aug 22];383(9935):2152–67. Available from: https://pubmed.ncbi.nlm.nih.gov/24503135/.

  119. Rushworth RL, Torpy DJ, Falhammar H. Adrenal crises in older patients. lancet Diabetes Endocrinol. 2020 [cited 2023 Aug 24];8(7):628–39. Available from: https://pubmed.ncbi.nlm.nih.gov/32559478/.

  120. Todd GRG, Acerini CL, Ross-Russell R, Zahra S, Warner JT, McCance D. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child. 2002 [cited 2023 Sep 2];87(6):457–61. Available from: https://pubmed.ncbi.nlm.nih.gov/12456538/.

  121. Kawahara T, Tsuji M, Tominaga N, Toyama N, Toda M. Frequency of Adrenal Insufficiency in Patients With Hypoglycemia in an Emergency Department: A Cross-sectional Study. J Endocr Soc. 2022 [cited 2023 Aug 22];6(10). Available from: https://pubmed.ncbi.nlm.nih.gov/36042975/.

  122. De Silva SDN, Aravinthan M, Katulanda P. Glucocorticoid-induced adrenal insufficiency: an uncommon cause of hypercalcaemia. Endocrinol diabetes Metab case reports. 2022 [cited 2023 Nov 3];2022(1). Available from: https://pubmed.ncbi.nlm.nih.gov/35510507/.

  123. Lee AS, Twigg SM. Opioid-induced secondary adrenal insufficiency presenting as hypercalcaemia. Endocrinol diabetes Metab case reports. 2015 [cited 2023 Nov 3];2015. Available from: https://pubmed.ncbi.nlm.nih.gov/26161260/.

  124. Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R, Samuels MH. Hormonal replacement in hypopituitarism in adults: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(11):3888–921.

    Article  CAS  PubMed  Google Scholar 

  125. Sbardella E, Isidori AM, Woods CP, Argese N, Tomlinson JW, Shine B, Jafar-Mohammadi B, Grossman AB. Baseline morning cortisol level as a predictor of pituitary-adrenal reserve: a comparison across three assays. Clin Endocrinol (Oxf). 2017 [cited 2023 Sep 2];86(2):177–84. Available from: https://pubmed.ncbi.nlm.nih.gov/27616279/.

  126. Grossman AB. Clinical Review#: The diagnosis and management of central hypoadrenalism. J Clin Endocrinol Metab. 2010 [cited 2023 Sep 2];95(11):4855–63. Available from: https://pubmed.ncbi.nlm.nih.gov/20719838/.

  127. Kazlauskaite R, Evans AT, Villabona C V., Abdu TAM, Ambrosi B, Atkinson AB, Cheung HC, Clayton RN, Courtney CH, Gonc EN, et al. Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab. 2008 [cited 2023 Sep 2];93(11):4245–53. Available from: https://pubmed.ncbi.nlm.nih.gov/18697868/.

  128. Kane KF, Emery P, Sheppard MCSP. Assessing the hypothalamo-pituitary-adrenal axis in patients on long-term glucocorticoid therapy: the short synacthen versus the insulin tolerance test. QJM. 1995;88(4):263–7.

    CAS  PubMed  Google Scholar 

  129. Agha A, Tomlinson JW, Clark PM, Holder G, Stewart PM. The long-term predictive accuracy of the short synacthen (corticotropin) stimulation test for assessment of the hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab. 2006 [cited 2023 Sep 2];91(1):43–7. Available from: https://pubmed.ncbi.nlm.nih.gov/16249286/.

  130. Ospina NS, Nofal A Al, Bancos I, Javed A, Benkhadra K, Kapoor E, Lteif AN, Natt N, Murad MH. ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis. J Clin Endocrinol Metab. 2016 [cited 2023 Oct 9];101(2):427–34. Available from: https://pubmed.ncbi.nlm.nih.gov/26649617/.

  131. Gruber LM, Nanda S, Nippoldt T, Chang AY, Bancos I. Secondary Adrenal Insufficiency and Growth Hormone Deficiency in Patients with Fibromyalgia. J Pain Res. 2021 [cited 2023 Oct 9];14:1323–9. Available from: https://pubmed.ncbi.nlm.nih.gov/34040435/.

  132. Plumpton, F.S. & Besser GM. The adrenocortical response to surgery and insulin-induced hypoglycemia in corticosteroid-treated and normal subjects. Br J Surg. 1969;(56):216–9.

  133. Ueland GA, Methlie P, Øksnes M, Thordarson HB, Sagen J, Kellmann R, Mellgren G, Ræder M, Dahlqvist P, Dahl SR, et al. The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS. J Clin Endocrinol Metab. 2018 [cited 2023 Sep 2];103(4):1696–703. Available from: https://pubmed.ncbi.nlm.nih.gov/29452421/.

  134. Raverot V, Richet C, Morel Y, Raverot G, Borson-Chazot F. Establishment of revised diagnostic cut-offs for adrenal laboratory investigation using the new Roche Diagnostics Elecsys® Cortisol II assay. Ann Endocrinol (Paris). 2016 [cited 2023 Sep 2];77(5):620–2. Available from: https://pubmed.ncbi.nlm.nih.gov/27449530/.

  135. Klose M, Hilsted L, Feldt-Rasmussen U. Method-specific serum cortisol responses to the ACTH test: comparison of two generations of Roche automated immunoassays using polyclonal vs MABs. Endocr Abstr. 2016 [cited 2023 Sep 2];41. Available from: https://www.endocrine-abstracts.org/ea/0041/ea0041ep22.

  136. Javorsky BR, Raff H, Carroll TB, Algeciras-Schimnich A, Singh RJ, Colón-Franco JM, Findling JW. New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency after ACTH Stimulation using Specific Cortisol Assays. J Endocr Soc. 2021 [cited 2023 Aug 24];5(4):1–11. Available from: https://academic.oup.com/jes1.

  137. Cho HY, Kim JH, Kim SW, Shin CS, Park KS, Kim SW, Jang HC, Kim SY. Different cut-off values of the insulin tolerance test, the high-dose short Synacthen test (250 μg) and the low-dose short Synacthen test (1 μg) in assessing central adrenal insufficiency. Clin Endocrinol (Oxf). 2014 [cited 2023 Sep 26];81(1):77–84. Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/24382108/.

  138. Verbeeten KC, Ahmet AH. The role of corticosteroid-binding globulin in the evaluation of adrenal insufficiency. J Pediatr Endocrinol Metab. 2018 [cited 2023 Sep 26];31(2):107–15. Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/29194043/.

  139. Ambroziak U, Kondracka A, Bartoszewicz Z, Krasnodębska-Kiljańska M, Bednarczuk T. The morning and late-night salivary cortisol ranges for healthy women may be used in pregnancy. Clin Endocrinol (Oxf). 2015;83(6):774–8.

    Article  CAS  PubMed  Google Scholar 

  140. Cornes MP, Ashby HL, Khalid Y, Buch HN, Ford C, Gama R. Salivary cortisol and cortisone responses to tetracosactrin (synacthen). Ann Clin Biochem. 2015 [cited 2024 Jan 20];52(Pt 5):606–10. Available from: https://pubmed.ncbi.nlm.nih.gov/25724424/.

  141. Lebbe M, Arlt W. What is the best diagnostic and therapeutic management strategy for an Addison patient during pregnancy? Clin Endocrinol (Oxf). 2013 Apr [cited 2023 Sep 2];78(4):497–502. Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/23153216/.

  142. Debono M, Elder CJ, Lewis J, Fearnside J, Caunt S, Dixon S, Jacques RM, Newell-Price J, Whitaker MJ, Keevil B, et al. Home Waking Salivary Cortisone to Screen for Adrenal Insufficiency. NEJM Evid. 2023 Jan 24;2(2).

  143. Krasowski MD, Drees D, Morris CS, Maakestad J, Blau JL, Ekins S. Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction. BMC Clin Pathol. 2014 [cited 2023 Sep 2];14(1). Available from: https://pubmed.ncbi.nlm.nih.gov/25071417/.

  144. Al-Aridi R, Abdelmannan D, Arafah BM. Biochemical diagnosis of adrenal insufficiency: the added value of dehydroepiandrosterone sulfate measurements. Endocr Pract. 2011 [cited 2023 Oct 9];17(2):261–70. Available from: https://pubmed.ncbi.nlm.nih.gov/21134877/.

  145. Arlt W. The approach to the adult with newly diagnosed adrenal insufficiency. J Clin Endocrinol Metab. 2009 [cited 2023 Aug 22];94(4):1059–67. Available from: https://pubmed.ncbi.nlm.nih.gov/19349469/.

  146. Hahner S, Allolio B. Therapeutic management of adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2009 [cited 2023 Aug 22];23(2):167–79. Available from: https://pubmed.ncbi.nlm.nih.gov/19500761/.

  147. Prete A, Taylor AE, Bancos I, Smith DJ, Foster MA, Kohler S, Fazal-Sanderson V, Komninos J, O’Neil DM, Vassiliadi DA, et al. Prevention of Adrenal Crisis: Cortisol Responses to Major Stress Compared to Stress Dose Hydrocortisone Delivery. J Clin Endocrinol Metab. 2020 [cited 2024 Jan 20];105(7). Available from: https://pubmed.ncbi.nlm.nih.gov/32170323/.

  148. Laugesen K, Broersen LHA, Hansen SB, Dekkers OM, Sørensen HT, Jorgensen JOL. Management of Endocrine Disease: Glucocorticoid-induced adrenal insufficiency: replace while we wait for evidence? Eur J Endocrinol. 2021 [cited 2023 Sep 2];184(4):R111–22. Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/33449912/.

  149. Braatvedt GD, Newrick PG, Corrall RJM. Patients’ self administration of hydrocortisone. BMJ Br Med J. 1990 [cited 2023 Sep 27];301(6764):1312. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664459/.

  150. 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 [cited 2023 Oct 9];82(4):497–502. Available from: https://pubmed.ncbi.nlm.nih.gov/25200922/.

  151. Hahner S, Burger-Stritt S, Allolio B. Subcutaneous hydrocortisone administration for emergency use in adrenal insufficiency. Eur J Endocrinol. 2013 [cited 2023 Oct 9];169(2):147–54. Available from: https://pubmed.ncbi.nlm.nih.gov/23672956/.

  152. Flemming TG, Østergaard Kristensen L. Quality of self-care in patients on replacement therapy with hydrocortisone. J Intern Med. 1999 [cited 2023 Sep 27];246(5):497–501. Available from: https://pubmed.ncbi.nlm.nih.gov/10583719/.

  153. Harsch IA, Schuller A, Hahn EG, Hensen J. Cortisone replacement therapy in endocrine disorders - quality of self-care. J Eval Clin Pract. 2010 [cited 2023 Sep 27];16(3):492–8. Available from: https://pubmed.ncbi.nlm.nih.gov/20210825/.

  154. Peacey SR, Pope RM, Naik KS, Hardern RD, Page MD, Belchetz PE. Corticosteroid therapy and intercurrent illness: the need for continuing patient education. Postgrad Med J. 1993 [cited 2023 Sep 27];69(810):282–4. Available from: https://pubmed.ncbi.nlm.nih.gov/8321791/.

  155. Repping-Wuts HJWJ, Stikkelbroeck NMML, Noordzij A, Kerstens M, Hermus ARMM. A glucocorticoid education group meeting: an effective strategy for improving self-management to prevent adrenal crisis. Eur J Endocrinol. 2013 [cited 2023 Sep 27];169(1):17–22. Available from: https://pubmed.ncbi.nlm.nih.gov/23636446/.

  156. White K, Arlt W. Adrenal crisis in treated Addison’s disease: a predictable but under-managed event. Eur J Endocrinol. 2010 [cited 2023 Aug 19];162(1):115–20. Available from: https://pubmed.ncbi.nlm.nih.gov/19776201/.

  157. 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 [cited 2023 Sep 27];12. Available from: https://pubmed.ncbi.nlm.nih.gov/22695167/.

  158. Chapman SCE, Llahana S, Carroll P, Horne R. Glucocorticoid therapy for adrenal insufficiency: nonadherence, concerns and dissatisfaction with information. Clin Endocrinol (Oxf). 2016 [cited 2023 Sep 27];84(5):664–71. Available from: https://pubmed.ncbi.nlm.nih.gov/26641418/.

  159. Løvås K, Loge JH, Husebye ES. Subjective health status in Norwegian patients with Addison’s disease. Clin Endocrinol (Oxf). 2002 [cited 2023 Sep 27];56(5):581–8. Available from: https://pubmed.ncbi.nlm.nih.gov/12030907/.

  160. Hahner S, Loeffler M, Fassnacht M, Weismann D, Koschker AC, 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 [cited 2023 Sep 27];92(10):3912–22. Available from: https://pubmed.ncbi.nlm.nih.gov/17684047/.

  161. Daae E, Feragen KB, Nermoen I, Falhammar H. Psychological adjustment, quality of life, and self-perceptions of reproductive health in males with congenital adrenal hyperplasia: a systematic review. Endocrine. 2018 [cited 2023 Sep 27];62(1):3–13. Available from: https://pubmed.ncbi.nlm.nih.gov/30128958/.

  162. Meyer G, Koch M, Herrmann E, Bojunga J, Badenhoop K. Longitudinal AddiQoL scores may identify higher risk for adrenal crises in Addison’s disease. Endocrine. 2018 [cited 2023 Sep 27];60(2):355–61. Available from: https://pubmed.ncbi.nlm.nih.gov/29388043/.

  163. Strandqvist A, Falhammar H, Lichtenstein P, Hirschberg AL, Wedell A, Norrby C, Nordenskjöld A, Frisén L, Nordenström A. Suboptimal psychosocial outcomes in patients with congenital adrenal hyperplasia: epidemiological studies in a nonbiased national cohort in Sweden. J Clin Endocrinol Metab. 2014 [cited 2023 Sep 27];99(4):1425–32. Available from: https://pubmed.ncbi.nlm.nih.gov/24476073/.

  164. Mallappa A, Debono M. Recent Advances in Hydrocortisone Replacement Treatment. Endocr Dev. 2016 [cited 2023 Sep 27];30:42–53. Available from: https://pubmed.ncbi.nlm.nih.gov/26683495/.

  165. Werumeus Buning J, Touw DJ, Brummelman P, Dullaart RPF, van den Berg G, van der Klauw MM, Kamp J, Wolffenbuttel BHR, van Beek AP. Pharmacokinetics of oral hydrocortisone - Results and implications from a randomized controlled trial. Metabolism. 2017 [cited 2023 Sep 27];71:7–16. Available from: https://pubmed.ncbi.nlm.nih.gov/28521880/.

  166. Sorgdrager FJH, Buning JW, Bos EH, Van Beek AP, Kema IP. Hydrocortisone Affects Fatigue and Physical Functioning Through Metabolism of Tryptophan: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2018 [cited 2023 Sep 27];103(9):3411–9. Available from: https://pubmed.ncbi.nlm.nih.gov/29982583/.

  167. Burger-Stritt S, Kardonski P, Pulzer A, Meyer G, Quinkler M, Hahner S. Management of adrenal emergencies in educated patients with adrenal insufficiency-A prospective study. Clin Endocrinol (Oxf). 2018 [cited 2023 Sep 27];89(1):22–9. Available from: https://pubmed.ncbi.nlm.nih.gov/29617051/.

  168. Gargya A, Chua E, Hetherington J, Sommer K, Cooper M. Acute adrenal insufficiency: an aide-memoire of the critical importance of its recognition and prevention. Intern Med J. 2016 [cited 2023 Sep 27];46(3):356–9. Available from: https://pubmed.ncbi.nlm.nih.gov/26968598/.

  169. Major A, Chacko K. Routine vaccinations as a precipitant of adrenal crisis in adrenal insufficiency. Intern Med J. 2018 [cited 2023 Sep 27];48(3):360–1. Available from: https://pubmed.ncbi.nlm.nih.gov/29512322/.

  170. Kampmeyer D, Lehnert H, Moenig H, Haas CS, Harbeck B. 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. 2016 [cited 2023 Sep 27];33:e13–5. Available from: https://pubmed.ncbi.nlm.nih.gov/27108240/.

  171. Kampmeyer D, Lehnert H, Moenig H, Haas CS, Harbeck B. Experience pays off! Endocrine centres are essential in the care of patients with adrenal insufficiency. Eur J Intern Med. 2016 [cited 2023 Sep 27];35:e27–8. Available from: https://pubmed.ncbi.nlm.nih.gov/27444736/.

  172. Shepherd LM, Tahrani AA, Inman C, Arlt W, Carrick-Sen DM. Exploration of knowledge and understanding in patients with primary adrenal insufficiency: a mixed methods study. BMC Endocr Disord. 2017 [cited 2023 Sep 27];17(1). Available from: https://pubmed.ncbi.nlm.nih.gov/28764794/.

  173. Nour MA, Gill H, Mondal P, Inman M, Urmson K. Perioperative care of congenital adrenal hyperplasia - a disparity of physician practices in Canada. Int J Pediatr Endocrinol. 2018 [cited 2023 Sep 27];2018(1). Available from: https://pubmed.ncbi.nlm.nih.gov/30214458/.

  174. Rushworth RL, Torpy DJ. Modern Hydrocortisone Replacement Regimens in Adrenal Insufficiency Patients and the Risk of Adrenal Crisis. Horm Metab Res. 2015 [cited 2023 Sep 27];47(9):637–42. Available from: https://pubmed.ncbi.nlm.nih.gov/25951324/.

  175. Louise Rushworth R, Slobodian P, Torpy DJ. Interruptions to supply of high-dose hydrocortisone tablets and the incidence of adrenal crises. Clin Endocrinol (Oxf). 2015 [cited 2023 Sep 27];83(6):999–1000. Available from: https://pubmed.ncbi.nlm.nih.gov/26018415/.

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  1. Division of Endocrinology, Department of Medicine and Research Center, Centre hospitalier de l’Université de Montréal (CHUM), 900 Saint-Denis Street, Montréal, QC H2X 0A9, Québec, Canada

    Luciana Martel-Duguech, Jonathan Poirier, Isabelle Bourdeau & André Lacroix

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LM and AL designed the plan, performed the review of literature and LM wrote the initial version of the manuscript. JP, IB and AL provided critical review and all authors approved the final version of the manuscript.

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Martel-Duguech, L., Poirier, J., Bourdeau, I. et al. Diagnosis and management of secondary adrenal crisis. Rev Endocr Metab Disord (2024). https://doi.org/10.1007/s11154-024-09877-x

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