Novel agents to treat adrenal insufficiency: findings of preclinical and early clinical trials

References

• Chabre O, Goichot B, Zenaty D, et al. Group 1. Epidemiology of primary and secondary adrenal insufficiency: prevalence and incidence, acute adrenal insufficiency, long-term morbidity and mortality. Ann Endocrinol. 2017 Dec;78(6):490–494.
   PubMed Web of Science ®Google Scholar
• Rushworth RL, Torpy DJ. The changing epidemiology of adrenal insufficiency: iatrogenic factors predominate. J Endocr Soc. 2023 Jan 6;7(3):bvad017. doi: 10.1210/jendso/bvad017. PubMed PMID: 36777466; PubMed Central PMCID: PMCPMC9909161.
   PubMed Web of Science ®Google Scholar
• Nowotny H, Ahmed SF, Bensing S, et al. Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis. Endocrine. 2021 Mar. 71(3):586–594. doi: 10.1007/s12020-021-02649-6. PubMed PMID: 33661460; PubMed Central; PMCID: PMCPMC7929907. eng
   PubMed Web of Science ®Google Scholar
• Chapman SC, Llahana S, Carroll P, et al. Glucocorticoid therapy for adrenal insufficiency: nonadherence, concerns and dissatisfaction with information. Clin Endocrinol (Oxf). 2016 May. 84(5):664–671. doi: 10.1111/cen.12991. PubMed PMID: 26641418; eng
   PubMed Web of Science ®Google Scholar
• Lousada LM, Mendonca BB, Bachega T. Adrenal crisis and mortality rate in adrenal insufficiency and congenital adrenal hyperplasia. Arch Endocrinol Metab. 2021 Nov 3;65(4):488–494. doi: 10.20945/2359-3997000000392. PubMed PMID: 34283908; eng
   PubMed Web of Science ®Google Scholar
• Rushworth RL, Torpy DJ. Modern hydrocortisone replacement regimens in adrenal insufficiency patients and the risk of adrenal crisis. Horm Metab Res. 2015 Aug;47(9):637–642. PubMed PMID: 25951324; eng
   PubMed Web of Science ®Google Scholar
• 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 Jun;47(6):427–432. PubMed PMID: 25738995; eng
   PubMed Web of Science ®Google Scholar
• Rahvar AH, Haas CS, Danneberg S, et al. Increased cardiovascular risk in patients with adrenal insufficiency: a short review. Biomed Res Int. 2017;2017:3691913. PubMed PMID: 29376070; PubMed Central PMCID: PMCPMC5742446. eng
   PubMed Web of Science ®Google Scholar
• Martin-Grace J, Dineen R, Sherlock M, et al. Adrenal insufficiency: physiology, clinical presentation and diagnostic challenges. Clin Chim Acta. 2020 Jun;505:78–91.
   PubMed Web of Science ®Google Scholar
• Kupczyk D, Bilski R, Kozakiewicz M, et al. 11β-HSD as a new target in pharmacotherapy of metabolic diseases. Int J Mol Sci. 2022 Aug 11;23(16):8984.
   PubMed Web of Science ®Google Scholar
• Chapman K, Holmes M, Seckl J. 11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. Physiol Rev. 2013 Jul;93(3):1139–1206. PubMed PMID: 23899562; PubMed Central; PMCID: PMCPMC3962546. eng
   PubMed Web of Science ®Google Scholar
• Ramamoorthy S, Cidlowski JA. Corticosteroids: mechanisms of action in health and disease. Rheum Dis Clin North Am. 2016 Feb:42(1);15–31, vii. doi: 10.1016/j.rdc.2015.08.002. PubMed PMID: 26611548; PubMed Central; PMCID: PMCPMC4662771. eng.
   PubMed Web of Science ®Google Scholar
• Timmermans S, Souffriau J, Libert C. A general introduction to glucocorticoid biology. Front Immunol. 2019:10:1545. doi: 10.3389/fimmu.2019.01545. PubMed PMID: 31333672; PubMed Central; PMCID: PMCPMC6621919. eng
   PubMed Web of Science ®Google Scholar
• Williams DM. Clinical pharmacology of corticosteroids. Respir Care. 2018 Jun;63(6):655–670. PubMed PMID: 29794202; eng
   PubMed Web of Science ®Google Scholar
• Purnell JQ, Brandon DD, Isabelle LM, et al. Association of 24-hour cortisol production rates, cortisol-binding globulin, and plasma-free cortisol levels with body composition, leptin levels, and aging in adult men and women. J Clin Endocrinol Metab. 2004 Jan. 89(1):281–287. doi: 10.1210/jc.2003-030440. PubMed PMID: 14715862; eng
   PubMed Web of Science ®Google Scholar
• Dineen R, Stewart PM, Sherlock M. Factors impacting on the action of glucocorticoids in patients receiving glucocorticoid therapy. Clin Endocrinol (Oxf). 2019 Jan;90(1):3–14. PubMed PMID: 30120786; eng
   PubMed Web of Science ®Google Scholar
• Esteban NV, Loughlin T, Yergey AL, et al. Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. J Clin Endocrinol Metab. 1991 Jan;72(1):39–45. doi: 10.1210/jcem-72-1-39. PubMed PMID: 1986026; eng
   PubMed Web of Science ®Google Scholar
• Werumeus Buning J, Touw DJ, Brummelman P, et al. Pharmacokinetics of oral hydrocortisone - results and implications from a randomized controlled trial. Metabolism. 2017 Jun;71:7–16.
   PubMed Web of Science ®Google Scholar
• Dorne JL, Walton K, Renwick AG. Human variability in CYP3A4 metabolism and CYP3A4-related uncertainty factors for risk assessment. Food Chem Toxicol. 2003 Feb;41(2):201–224. PubMed PMID: 12480298; eng
   PubMed Web of Science ®Google Scholar
• Spiga F, Walker JJ, Terry JR, et al. HPA axis-rhythms. Compr Physiol. 2014 Jul;4(3):1273–1298. doi: 10.1002/cphy.c140003. PubMed PMID: 24944037; eng
   PubMed Web of Science ®Google Scholar
• Ishida A, Mutoh T, Ueyama T, et al. Light activates the adrenal gland: timing of gene expression and glucocorticoid release. Cell Metab. 2005 Nov;2(5):297–307. doi: 10.1016/j.cmet.2005.09.009. PubMed PMID: 16271530; eng
   PubMed Web of Science ®Google Scholar
• Balsalobre A, Brown SA, Marcacci L, et al. Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science. 2000 Sep 29;289(5488):2344–2347.
   PubMed Web of Science ®Google Scholar
• Son GH, Cha HK, Chung S, et al. Multimodal regulation of circadian glucocorticoid rhythm by central and adrenal clocks. J Endocr Soc. 2018 May 1;2(5):444–459.
   PubMedGoogle Scholar
• Joseph JJ, Golden SH. Cortisol dysregulation: the bidirectional link between stress, depression, and type 2 diabetes mellitus. Ann N Y Acad Sci. 2017 Mar;1391(1):20–34. PubMed PMID: 27750377; PubMed Central; PMCID: PMCPMC5334212. eng
   PubMed Web of Science ®Google Scholar
• Werumeus Buning J, Brummelman P, Koerts J, et al. Hydrocortisone dose influences pain, depressive symptoms and perceived health in adrenal insufficiency: a randomized controlled trial. Neuroendocrinology. 2016;103(6):771–778.
   PubMed Web of Science ®Google Scholar
• Guarnotta V, Amodei R, Giordano C. Metabolic comorbidities of adrenal insufficiency: focus on steroid replacement therapy and chronopharmacology. Curr Opin Pharmacol. 2021 Oct;60:123–132. doi: 10.1016/j.coph.2021.07.003. PubMed PMID: 34416524; eng
   PubMed Web of Science ®Google Scholar
• Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016 Feb. 101(2):364–389. doi: 10.1210/jc.2015-1710. PubMed PMID: 26760044; PubMed Central; PMCID: PMCPMC4880116. eng
   PubMed Web of Science ®Google Scholar
• Ceccato F, Scaroni C. Central adrenal insufficiency: open issues regarding diagnosis and glucocorticoid treatment. Clin Chem Lab Med. 2019 Jul 26;57(8):1125–1135. doi: 10.1515/cclm-2018-0824. PubMed PMID: 30427776; eng
   PubMed Web of Science ®Google Scholar
• Huayllas MKP, Netzel BC, Singh RJ, et al. Serum cortisol levels via radioimmunoassay vs liquid chromatography mass spectrophotometry in healthy control subjects and patients with adrenal incidentalomas. Lab Med. 2018 Jul 5;49(3):259–267.
   PubMed Web of Science ®Google Scholar
• Zha L, Li J, Krishnan SM, et al. New diagnostic cutoffs for adrenal insufficiency after cosyntropin stimulation using Abbott architect cortisol immunoassay. Endocr Pract. 2022 Jul;28(7):684–689. doi: 10.1016/j.eprac.2022.04.003. PubMed PMID: 35487459; eng
   PubMed Web of Science ®Google Scholar
• Vogeser M, Kratzsch J, Ju Bae Y, et al. Multicenter performance evaluation of a second generation cortisol assay. Clin Chem Lab Med. 2017 May 1;55(6):826–835.
   PubMed Web of Science ®Google Scholar
• Siampanopoulou V, Tasouli E, Angelousi A. Diagnostic strategies in adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2023 Jun 1;30(3):141–153. doi: 10.1097/med.0000000000000806. PubMed PMID: 37036291; eng
   PubMedGoogle Scholar
• El-Farhan N, Rees DA, Evans C. Measuring cortisol in serum, urine and saliva - are our assays good enough? Ann Clin Biochem. 2017 May;54(3):308–322. PubMed PMID: 28068807; eng
   PubMed Web of Science ®Google Scholar
• Paragliola RM, Corsello A, Troiani E, et al. Cortisol circadian rhythm and jet-lag syndrome: evaluation of salivary cortisol rhythm in a group of eastward travelers. Endocrine. 2021 Aug. 73(2):424–430. doi: 10.1007/s12020-021-02621-4. PubMed PMID: 33543430; PubMed Central; PMCID: PMCPMC8263446. eng
   PubMed Web of Science ®Google Scholar
• Greff MJE, Levine JM, Abuzgaia AM, et al. Hair cortisol analysis: an update on methodological considerations and clinical applications. Clin Biochem. 2019 Jan;63:1–9.
   PubMed Web of Science ®Google Scholar
• Mason HL, Myers CS, Kendall EC. The chemistry of crystalline substances isolated from the suprarenal gland. J Biol Chem. 1936 July 01;114(3):613–631. doi: 10.1016/S0021-9258(18)74790-X.
   Google Scholar
• Kendall EC. Hormone of the adrenal cortex. Bull N Y Acad Med. 1953 Feb;29(2):91–100. PubMed PMID: 13009391. PubMed Central; PMCID: PMCPMC1877288. eng
   PubMedGoogle Scholar
• Hench PS, Kendall EC, Slocumb CH, et al. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone; compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis. Proc Staff Meetings Mayo Clin. 1949 Apr 13;24(8):181–197. PubMed PMID: 18118071; eng
   PubMed Web of Science ®Google Scholar
• Burns CM. The history of cortisone discovery and development. Rheum Dis Clin North Am. 2016 Feb;42(1);1–14. vii. doi: 10.1016/j.rdc.2015.08.001. PubMed PMID: 26611547; eng
   PubMed Web of Science ®Google Scholar
• Thorn GW, Koepf GF, Lewis RA, et al. CARBOHYDRATE METABOLISM IN ADDISON’S DISEASE. J Clin Invest. 1940 Nov; 19(6):813–832. doi: 10.1172/jci101185. PubMed PMID: 16694798; PubMed Central PMCID: PMCPMC435017. eng
   PubMedGoogle Scholar
• Benedek TG. History of the development of corticosteroid therapy. Clin Exp Rheumatol. 2011 Sep-Oct;29(5 Suppl 68):S-5–12. PubMed PMID: 22018177; eng
   Web of Science ®Google Scholar
• Czock D, Keller F, Rasche FM, et al. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61–98.
   PubMed Web of Science ®Google Scholar
• Heazelwood VJ, Galligan JP, Cannell GR, et al. Plasma cortisol delivery from oral cortisol and cortisone acetate: relative bioavailability. Br J Clin Pharmacol. 1984 Jan;17(1):55–59. doi: 10.1111/j.1365-2125.1984.tb04999.x. PubMed PMID: 6691888; PubMed Central; PMCID: PMCPMC1463287. eng
   PubMed Web of Science ®Google Scholar
• Mazziotti G, Formenti AM, Frara S, et al. MANAGEMENT OF ENDOCRINE DISEASE: risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects. Eur J Endocrinol. 2017 Nov. 177(5):R231–r248. doi: 10.1530/eje-17-0154. PubMed PMID: 28583942; eng
   PubMed Web of Science ®Google Scholar
• Hahner S. Acute adrenal crisis and mortality in adrenal insufficiency: still a concern in 2018. Ann Endocrinol. 2018 Jun;79(3):164–166. PubMed PMID: 29716733; eng
   PubMed Web of Science ®Google Scholar
• Ngaosuwan K, Johnston DG, Godsland IF, et al. Increased mortality risk in patients with primary and secondary adrenal insufficiency. J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2759–e2768.
   PubMed Web of Science ®Google Scholar
• Erichsen MM, Løvås K, Fougner KJ, et al. Normal overall mortality rate in Addison’s disease, but young patients are at risk of premature death. Eur J Endocrinol. 2009 Feb;160(2):233–237. doi: 10.1530/eje-08-0550. PubMed PMID: 19011006; eng
   PubMed Web of Science ®Google Scholar
• Rushworth RL, Torpy DJ, Falhammar H. Adrenal crises: perspectives and research directions. Endocrine. 2017 Feb;55(2):336–345. PubMed PMID: 27995500; eng
   PubMed Web of Science ®Google Scholar
• Bancos I, Hatipoglu BA, Yuen KCJ, et al. Evaluation of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome. J Clin Transl Endocrinol. 2021 Mar;24:100256.
   PubMedGoogle Scholar
• Barclay JL, Petersons CJ, Keshvari S, et al. Thrombospondin-1 is a glucocorticoid responsive protein in humans. Eur J Endocrinol. 2016 Feb;174(2):193–201. doi: 10.1530/eje-15-0964. PubMed PMID: 26578641; eng
   PubMed Web of Science ®Google Scholar
• Å B S, Wolff AB, Björnsdottir S, et al. Potential transcriptional biomarkers to guide glucocorticoid replacement in autoimmune Addison’s disease. J Endocr Soc. 2021 Mar 1;5(3):bvaa202.
   PubMed Web of Science ®Google Scholar
• Chantzichristos D, Svensson PA, Garner T, et al. Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial. eLife. 2021 Apr 6;10. PubMed PMID: 33821793; PubMed Central; PMCID: PMCPMC8024021. eng. doi: 10.7554/eLife.62236
   PubMed Web of Science ®Google Scholar
• Merza Z, Rostami-Hodjegan A, Memmott A, et al. Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia. Clin Endocrinol (Oxf). 2006 Jul;65(1):45–50. doi: 10.1111/j.1365-2265.2006.02544.x. PubMed PMID: 16817818; eng
   PubMed Web of Science ®Google Scholar
• Løvås K, Husebye ES. Continuous subcutaneous hydrocortisone infusion in Addison’s disease. Eur J Endocrinol. 2007 Jul;157(1):109–112. PubMed PMID: 17609409; eng
   PubMed Web of Science ®Google Scholar
• Björnsdottir S, Øksnes M, Isaksson M, et al. Circadian hormone profiles and insulin sensitivity in patients with Addison’s disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy. Clin Endocrinol (Oxf). 2015 Jul. 83(1):28–35. doi: 10.1111/cen.12670. PubMed PMID: 25400085; eng
   PubMed Web of Science ®Google Scholar
• Gagliardi L, Nenke MA, Thynne TR, et al. Continuous subcutaneous hydrocortisone infusion therapy in Addison’s disease: a randomized, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2014 Nov; 99(11):4149–4157. doi: 10.1210/jc.2014-2433. PubMed PMID: 25127090; eng
   PubMed Web of Science ®Google Scholar
• Oksnes M, Björnsdottir S, Isaksson M, 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 May; 99(5):1665–1674. doi: 10.1210/jc.2013-4253. PubMed PMID: 24517155; eng
   PubMed Web of Science ®Google Scholar
• Nella AA, Mallappa A, Perritt AF, et al. A phase 2 study of continuous subcutaneous hydrocortisone infusion in adults with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2016 Dec; 101(12):4690–4698. doi: 10.1210/jc.2016-1916. PubMed PMID: 27680873; PubMed Central PMCID: PMCPMC5155681. eng
   PubMed Web of Science ®Google Scholar
• Simunkova K, Løvås K, Methlie P, et al. Pulsatile subcutaneous hydrocortisone replacement in primary adrenal insufficiency. Horm Metab Res. 2023 Jul;55(7):471–478. doi: 10.1055/a-2092-5228. PubMed PMID: 37172949; eng
   PubMedGoogle Scholar
• Harbeck B, Kropp P, Mönig H. Effects of short-term nocturnal cortisol replacement on cognitive function and quality of life in patients with primary or secondary adrenal insufficiency: a pilot study. Appl Psychophysiol Biofeedback. 2009 Jun;34(2):113–119. PubMed PMID: 19387826; eng
   PubMed Web of Science ®Google Scholar
• Mortensen ML, Ornstrup MJ, Gravholt CH. Patients with hypocortisolism treated with Continuous Subcutaneous Hydrocortisone Infusion (CSHI): an option for poorly controlled patients. Int J Endocrinol. 2023:2023;5315059. doi: 10.1155/2023/5315059 PubMed PMID: 36994228; PubMed Central; PMCID: PMCPMC10042637. eng
   PubMed Web of Science ®Google Scholar
• Khanna A, Khurana R, Kyriacou A, et al. Management of adrenocortical insufficiency with continuous subcutaneous hydrocortisone infusion: long-term experience in three patients. Endocrinol Diabetes Metab Case Rep. 2015;2015:150005. PubMed PMID: 26124953; PubMed Central PMCID: PMCPMC4482159. eng
   PubMedGoogle Scholar
• Mallappa A, Nella AA, Sinaii N, et al. Long-term use of continuous subcutaneous hydrocortisone infusion therapy in patients with congenital adrenal hyperplasia. Clin Endocrinol (Oxf). 2018 Oct;89(4):399–407. doi: 10.1111/cen.13813. PubMed PMID: 30003563; PubMed Central PMCID: PMCPMC6166869. eng
   PubMed Web of Science ®Google Scholar
• Bryan SM, Honour JW, Hindmarsh PC. Management of altered hydrocortisone pharmacokinetics in a boy with congenital adrenal hyperplasia using a continuous subcutaneous hydrocortisone infusion. J Clin Endocrinol Metab. 2009 Sep;94(9):3477–3480. PubMed PMID: 19567522; eng
   PubMed Web of Science ®Google Scholar
• Cardini F, Torlone E, Bini V, et al. Continuous subcutaneous hydrocortisone infusion in a woman with secondary adrenal insufficiency. Endocrine. 2019 Feb;63(2):398–400. doi: 10.1007/s12020-018-1780-4. PubMed PMID: 30353412; eng
   PubMed Web of Science ®Google Scholar
• Sonnet E, Roudaut N, Kerlan V. Results of the prolonged use of subcutaneous continuous infusion of hydrocortisone in a man with congenital adrenal hyperplasia. ISRN Endocrinol. 2011;2011:219494. doi: 10.5402/2011/219494. PubMed PMID: 22363868; PubMed Central PMCID: PMCPMC3262628. eng.
   PubMedGoogle Scholar
• Broussard JR, Mitre N. Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma. J Pediatr Endocrinol Metab. 2015 Jul;28(7–8):947–949. PubMed PMID: 25781534; eng
   PubMed Web of Science ®Google Scholar
• Tuli G, Rabbone I, Einaudi S, et al. Continuous subcutaneous hydrocortisone infusion (CSHI) in a young adolescent with congenital adrenal hyperplasia (CAH). J Pediatr Endocrinol Metab. 2011;24(7–8):561–563.
   PubMed Web of Science ®Google Scholar
• Upton TJ, Zavala E, Methlie P, et al. High-resolution daily profiles of tissue adrenal steroids by portable automated collection. Sci Trans Med. 2023 Jun 21;15(701):eadg8464.
   PubMed Web of Science ®Google Scholar
• Newell-Price J, Whiteman M, Rostami-Hodjegan A, et al. Modified-release hydrocortisone for circadian therapy: a proof-of-principle study in dexamethasone-suppressed normal volunteers. Clin Endocrinol (Oxf). 2008 Jan;68(1):130–135. doi: 10.1111/j.1365-2265.2007.03011.x. PubMed PMID: 17803699; eng
   PubMed Web of Science ®Google Scholar
• Debono M, Ghobadi C, Rostami-Hodjegan A, et al. Modified-release hydrocortisone to provide circadian cortisol profiles. J Clin Endocrinol Metab. 2009 May;94(5):1548–1554. doi: 10.1210/jc.2008-2380. PubMed PMID: 19223520; PubMed Central PMCID: PMCPMC2684472. eng
   PubMed Web of Science ®Google Scholar
• Karunasena N, Margetson DN, Neal G, et al. Impact of food, alcohol and pH on modified-release hydrocortisone developed to treat congenital adrenal hyperplasia. Eur J Endocrinol. 2017 Apr;176(4):405–411. doi: 10.1530/eje-16-0948. PubMed PMID: 28100629; PubMed Central PMCID: PMCPMC5425936. eng
   PubMed Web of Science ®Google Scholar
• Whitaker M, Debono M, Huatan H, et al. An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure. Clin Endocrinol (Oxf). 2014 Apr;80(4):554–561. doi: 10.1111/cen.12316. PubMed PMID: 23980724; PubMed Central PMCID: PMCPMC3937303. eng
   PubMed Web of Science ®Google Scholar
• Clinicaltrials.gov. Chronocort versus plenadren replacement therapy in adults with adrenal insufficiency. [cited 2023 Dec 30]. Available from: https://ClinicalTrials.gov/show/NCT05222152
   Google Scholar
• Verma S, Vanryzin C, Sinaii N, et al. A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (Chronocort) vs. conventional hydrocortisone (Cortef) in the treatment of congenital adrenal hyperplasia. Clin Endocrinol (Oxf). 2010 Apr;72(4):441–447. doi: 10.1111/j.1365-2265.2009.03636.x. PubMed PMID: 19486026; PubMed Central PMCID: PMCPMC2866132. eng
   PubMed Web of Science ®Google Scholar
• Jones CM, Mallappa A, Reisch N, et al. Modified-release and conventional glucocorticoids and diurnal androgen excretion in congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2017 Jun 1;102(6):1797–1806.
   PubMed Web of Science ®Google Scholar
• Mallappa A, Sinaii N, Kumar P, et al. A phase 2 study of Chronocort, a modified-release formulation of hydrocortisone, in the treatment of adults with classic congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2015 Mar;100(3):1137–1145. doi: 10.1210/jc.2014-3809. PubMed PMID: 25494662; PubMed Central PMCID: PMCPMC5393506. eng
   PubMed Web of Science ®Google Scholar
• Merke DP, Mallappa A, Arlt W, et al. Modified-release hydrocortisone in congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2063–e2077.
   PubMed Web of Science ®Google Scholar
• Tschaidse L, Reisch N, Arlt W, et al. Modified-release hydrocortisone is associated with lower plasma renin activity in patients with salt-wasting congenital adrenal hyperplasia. Eur J Endocrinol. 2023 Jan 10;188(1):109–117.
   Web of Science ®Google Scholar
• Johannsson G, Bergthorsdottir R, Nilsson AG, et al. Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study. Eur J Endocrinol. 2009 Jul;161(1):119–130. doi: 10.1530/eje-09-0170. PubMed PMID: 19383806; eng
   PubMed Web of Science ®Google Scholar
• Johannsson G, Lennernäs H, Marelli C, et al. Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study. Eur J Endocrinol. 2016 Jul;175(1):85–93. doi: 10.1530/eje-15-1212. PubMed PMID: 27129362; PubMed Central PMCID: PMCPMC5065076. eng
   PubMed Web of Science ®Google Scholar
• Choudhury S, Tan T, Lazarus K, et al. The use of prednisolone versus dual-release hydrocortisone in the treatment of hypoadrenalism. Endocr Connect. 2021 Feb;10(2):R66–r76. doi: 10.1530/ec-20-0473. PubMed PMID: 33449916; PubMed Central PMCID: PMCPMC7983484. eng
   PubMed Web of Science ®Google Scholar
• Hydrocortisone Vs Prednisolone in AI (HYPER-AID). [cited 2023 Dec 30]. Available from: https://classic.clinicaltrials.gov/show/NCT03608943.
   Google Scholar
• Safety and efficacy of prednisolone in adrenal insufficiency disease (PRED-AID Study). [cited 2023 December 30]. Available from: https://classic.clinicaltrials.gov/show/NCT03936517.
   Google Scholar
• Johannsson G, Nilsson AG, Bergthorsdottir R, 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 Metab. 2012 Feb;97(2):473–481. doi: 10.1210/jc.2011-1926. PubMed PMID: 22112807; eng
   PubMed Web of Science ®Google Scholar
• Dineen RA, Martin-Grace J, Ahmed KMS, et al. Tissue glucocorticoid metabolism in adrenal insufficiency: a prospective study of dual-release hydrocortisone therapy. J Clin Endocrinol Metab. 2023 Jun 20;108(12):3178–3189.
   PubMed Web of Science ®Google Scholar
• Ceccato F, Selmin E, Sabbadin C, et al. Improved salivary cortisol rhythm with dual-release hydrocortisone. Endocr Connect. 2018 Sep 1;7(9):965–974.
   PubMed Web of Science ®Google Scholar
• Espiard S, McQueen J, Sherlock M, et al. Improved urinary cortisol metabolome in Addison disease: a prospective trial of dual-release hydrocortisone. J Clin Endocrinol Metab. 2021 Mar 8;106(3):814–825.
   PubMed Web of Science ®Google Scholar
• Giordano R, Guaraldi F, Marinazzo E, et al. Improvement of anthropometric and metabolic parameters, and quality of life following treatment with dual-release hydrocortisone in patients with Addison’s disease. Endocrine. 2016 Feb;51(2):360–368. doi: 10.1007/s12020-015-0681-z. PubMed PMID: 26184416; eng
   PubMed Web of Science ®Google Scholar
• Isidori AM, Venneri MA, Graziadio C, 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 Mar;6(3):173–185. doi: 10.1016/s2213-8587(17)30398-4. PubMed PMID: 29229498; eng
   PubMed Web of Science ®Google Scholar
• Nilsson AG, Bergthorsdottir R, Burman P, et al. Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study. Eur J Endocrinol. 2017 Jun;176(6):715–725. doi: 10.1530/eje-17-0067. PubMed PMID: 28292927; PubMed Central PMCID: PMCPMC5425941. eng
   PubMed Web of Science ®Google Scholar
• Guarnotta V, Di Stefano C, Giordano C. Long-term outcomes of conventional and novel steroid replacement therapy on bone health in primary adrenal insufficiency. Sci Rep. 2022 Aug 2;12(1):13280. doi: 10.1038/s41598-022-13506-5. PubMed PMID: 35918399; PubMed Central PMCID: PMCPMC9345970. eng
   PubMed Web of Science ®Google Scholar
• Delle Cese F, Corsello A, Cintoni M, et al. Switching from immediate-release to fractionated dual-release hydrocortisone may improve metabolic control and QoL in selected primary adrenal insufficiency patients. Front Endocrinol (Lausanne). 2020;11:610904. PubMed PMID: 33597926; PubMed Central PMCID: PMCPMC7883639. eng
   PubMed Web of Science ®Google Scholar
• Gasco V, Giannelli J, Campioni L, et al. Benefits of dual-release hydrocortisone treatment on central adiposity and health-related quality of life in secondary adrenal insufficiency. J Endocrinol Invest. 2023 Mar;46(3):587–597. doi: 10.1007/s40618-022-01940-1. PubMed PMID: 36251244; PubMed Central PMCID: PMCPMC9938071. eng
   PubMed Web of Science ®Google Scholar
• Guarnotta V, Mineo MI, Radellini S, et al. Dual-release hydrocortisone improves hepatic steatosis in patients with secondary adrenal insufficiency: a real-life study. Ther Adv Endocrinol Metab. 2019;10:2042018819871169. PubMed PMID: 31489172; PubMed Central PMCID: PMCPMC6713956. eng
   Web of Science ®Google Scholar
• Quinkler M, Miodini Nilsen R, Zopf K, et al. Modified-release hydrocortisone decreases BMI and HbA1c in patients with primary and secondary adrenal insufficiency. Eur J Endocrinol. 2015 May;172(5):619–626. doi: 10.1530/eje-14-1114. PubMed PMID: 25656494; eng
   PubMed Web of Science ®Google Scholar
• Guarnotta V, Ciresi A, Pillitteri G, et al. Improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency on dual-release hydrocortisone treatment: a 36-month retrospective analysis. Clin Endocrinol (Oxf). 2018 May;88(5):665–672. doi: 10.1111/cen.13554. PubMed PMID: 29368442; eng
   PubMed Web of Science ®Google Scholar
• Guarnotta V, Di Stefano C, Santoro A, et al. Dual-release hydrocortisone vs conventional glucocorticoids in adrenal insufficiency. Endocr Connect. 2019 Jul 1;8(7):853–862.
   PubMed Web of Science ®Google Scholar
• Dineen R, Martin-Grace J, Ahmed KMS, et al. Cardiometabolic and psychological effects of dual-release hydrocortisone: a cross-over study. Eur J Endocrinol. 2021 Feb;184(2):253–265. doi: 10.1530/eje-20-0642. PubMed PMID: 33513125; eng
   PubMed Web of Science ®Google Scholar
• Frigerio S, Carosi G, Ferrante E, et al. Effects of the therapy shift from cortisone acetate to modified-release hydrocortisone in a group of patients with adrenal insufficiency. Front Endocrinol (Lausanne). 2023;14:1093838. PubMed PMID: 36761196; PubMed Central PMCID: PMCPMC9902698. eng
   PubMed Web of Science ®Google Scholar
• Bannon CAM, Border D, Hanson P, et al. Early metabolic benefits of switching hydrocortisone to modified release hydrocortisone in adult adrenal insufficiency. Front Endocrinol (Lausanne). 2021;12:641247. PubMed PMID: 33776936; PubMed Central PMCID: PMCPMC7992002. eng
   PubMed Web of Science ®Google Scholar
• Esposito D, Bobbio E, Di Fraia R, et al. Patients with adrenal insufficiency have cardiovascular features associated with hypovolemia. Endocrine. 2020 Nov;70(2):412–420. doi: 10.1007/s12020-020-02458-3. PubMed PMID: 32813212; PubMed Central PMCID: PMCPMC7581570. eng
   PubMed Web of Science ®Google Scholar
• Quinkler M, Oelkers W, Remde H, et al. Mineralocorticoid substitution and monitoring in primary adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2015 Jan;29(1):17–24. doi: 10.1016/j.beem.2014.08.008. PubMed PMID: 25617169; eng
   PubMed Web of Science ®Google Scholar
• Ceccato F, Torchio M, Tizianel I, et al. Renin and electrolytes indicate the mineralocorticoid activity of fludrocortisone: a 6 year study in primary adrenal insufficiency. J Endocrinol Invest. 2023 Jan;46(1):111–122. doi: 10.1007/s40618-022-01889-1. PubMed PMID: 35947299; PubMed Central PMCID: PMCPMC9829625. eng
   PubMed Web of Science ®Google Scholar
• Frara S, Chiloiro S, Porcelli T, et al. Bone safety of dual-release hydrocortisone in patients with hypopituitarism. Endocrine. 2018 Jun;60(3):528–531. doi: 10.1007/s12020-017-1512-1. PubMed PMID: 29313195; eng
   PubMed Web of Science ®Google Scholar
• Hasenmajer V, Ferrari D, De Alcubierre D, et al. Effects of dual-release hydrocortisone on bone metabolism in primary and secondary adrenal insufficiency: a 6-year study. J Endocr Soc. 2023 Dec 1;8(1):bvad151.
   PubMed Web of Science ®Google Scholar
• Mongioì LM, Condorelli RA, La Vignera S, et al. Dual-release hydrocortisone treatment: glycometabolic profile and health-related quality of life. Endocr Connect. 2018 Jan;7(1):211–219. doi: 10.1530/ec-17-0368. PubMed PMID: 29233815; PubMed Central PMCID: PMCPMC5793805. eng
   PubMed Web of Science ®Google Scholar
• Boesen VB, Borresen SW, Christoffersen T, et al. The effect of dual-release versus conventional hydrocortisone on fatigue, measured by ecological momentary assessments. Endocrine. 2021 Feb;71(2):467–475. doi: 10.1007/s12020-020-02507-x. PubMed PMID: 33063273; eng
   PubMed Web of Science ®Google Scholar
• Rushworth RL, Torpy DJ, Falhammar H. Adrenal Crisis. N Engl J Med. 2019 Aug 29;381(9):852–861. doi: 10.1056/NEJMra1807486. PubMed PMID: 31461595; eng
   PubMed Web of Science ®Google Scholar
• Meijer OC, Koorneef LL, Kroon J. Glucocorticoid receptor modulators. Ann Endocrinol. 2018 Jun;79(3):107–111. PubMed PMID: 29731108; eng
   PubMed Web of Science ®Google Scholar
• Pofi R, Caratti G, Ray DW, et al. Treating the side effects of exogenous glucocorticoids; can we separate the good from the bad? Endocr Rev. 2023 May 30;44(6):975–1011.
   PubMed Web of Science ®Google Scholar
• Hua G, Zein N, Paulen L, et al. The glucocorticoid receptor agonistic modulators CpdX and CpdX-D3 do not generate the debilitating effects of synthetic glucocorticoids. Proc Natl Acad Sci U S A. 2019 Jul 9;116(28):14200–14209.
   PubMed Web of Science ®Google Scholar
• Buttgereit F, Strand V, Lee EB, et al. Fosdagrocorat (PF-04171327) versus prednisone or placebo in rheumatoid arthritis: a randomised, double-blind, multicentre, phase IIb study. RMD Open. 2019;5(1):e000889.
   PubMed Web of Science ®Google Scholar
• Mao L, Wei W, Chen J. Biased regulation of glucocorticoid receptors signaling. Biomed Pharmacothe. 2023 Sep;165:115145. doi: 10.1016/j.biopha.2023.115145. PubMed PMID: 37454592; eng
   PubMed Web of Science ®Google Scholar