Switching from immediate-release to fractionated dual-release hydrocortisone may improve metabolic control and qol in selected primary adrenal insufficiency patients
Open accessAbstract
Objective: The use of once-daily dual-release HC (DR-HC) in primary adrenal insufficiency (PAI) is often associated with benefits in metabolic parameters when compared to immediate-release HC (IR-HC). In this study, we evaluated the effects on clinical, biochemical and metabolic parameters of switching from IR-HC to lower-dose DR-HC given both in once and fractionated daily doses. Methods: Twenty autoimmune-PAI subjects were included. Patients on 30 mg/day divided in three doses IR-HC regimen (group A) were switched to DR-HC 25 mg/day given in two daily doses (20 mg in the morning and 5 mg at 2.00 p.m.); patients on 25 mg/day divided in two doses IR-HC regimen (group B) were switched to DR-HC 20 mg once daily. Biochemical and metabolic parameters, BMI and quality of life (QoL) were evaluated at the baseline and six months after the switch. Results: Our small non-randomized study with short follow up showed significant benefits in both group A and group B without any apparent side-effects. After the switch to DR-HC, a significant decrease in adrenocorticotropic hormone (ACTH), HbA1c, total cholesterol, triglycerides, LDL, cholesterol, BMI as well as a significant improvement in QoL, were observed in both groups. At 6 months, ACTH levels were lower in group A while HbA1C and total cholesterol were lower in group B. Conclusion: The DR-HC is a valid and effective therapeutic strategy to improve the metabolic control and the QoL in PAI. The reduction of ACTH levels with DR-HC regimens reflects a better biochemical control of PAI, obtained by using a lower dose and more physiological HC formulation. Both once-daily and fractionated daily doses of DR-HC showed advantages compared with IR-HC formulation.
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Modified-release hydrocortisone is associated with a significant reduction in body mass index.
“Studies have reported a significant reduction in body mass index, improved lipid profile, better glycaemic control and improved quality of life in those who are in the MR-HC group (58, 59).”
From Hypoglycaemia in adrenal insufficiency (2023) · cites this paper as [59]
Modified-release hydrocortisone is associated with better glycaemic control.
“Studies have reported a significant reduction in body mass index, improved lipid profile, better glycaemic control and improved quality of life in those who are in the MR-HC group (58, 59).”
From Hypoglycaemia in adrenal insufficiency (2023) · cites this paper as [59]
Modified-release hydrocortisone is associated with improved quality of life.
“Studies have reported a significant reduction in body mass index, improved lipid profile, better glycaemic control and improved quality of life in those who are in the MR-HC group (58, 59).”
From Hypoglycaemia in adrenal insufficiency (2023) · cites this paper as [59]
Modified-release hydrocortisone is associated with an improved lipid profile.
“Studies have reported a significant reduction in body mass index, improved lipid profile, better glycaemic control and improved quality of life in those who are in the MR-HC group (58, 59).”
From Hypoglycaemia in adrenal insufficiency (2023) · cites this paper as [59]
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Cites
Bornstein, S. R., Allolio, B., Arlt, W., Barthel, A., Don-Wauchope, A., Hammer, G. D., Husebye, E. S., Merke, D. P., Murad, M. H., Stratakis, C. A., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1710 · Cited by 1,769 · see citing works
Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes
Spiegel, K., Knutson, K., Leproult, R., Tasali, E., & Cauter, E. V. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00660.2005 · Cited by 1,175 · see citing works
Erichsen, M. M., Løvås, K., Skinningsrud, B., Wolff, A. B., Undlien, D. E., Svartberg, J., Fougner, K. J., Berg, T. J., Bollerslev, J., Mella, B., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1368 · Cited by 422 · see citing works
Johannsson, G., Nilsson, A. G., Bergthorsdottir, R., Burman, P., Dahlqvist, P., Ekman, B., Engström, B. E., Olsson, T., Ragnarsson, O., Ryberg, M., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1926 · Cited by 329 · see citing works
Hahner, S., Loeffler, M., Fassnacht, M., Weismann, D., Koschker, A.-C., Quinkler, M., Decker, O., Arlt, W., & Allolio, B. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0685 · Cited by 282 · see citing works
Erichsen, M. M., Løvås, K., Fougner, K. J., Svartberg, J., Hauge, E. R., Bollerslev, J., Berg, J. P., Mella, B., & Husebye, E. S. (2009) · European Journal of Endocrinology · doi:10.1530/eje-08-0550 · Cited by 240 · see citing works
Isidori, A. M., Venneri, M. A., Graziadio, C., Simeoli, C., Fiore, D., Hasenmajer, V., Sbardella, E., Gianfrilli, D., Pozza, C., Pasqualetti, P., et al. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30398-4 · Cited by 211 · see citing works
Glucocorticoid replacement therapy: are patients over treated and does it matter?
Peacey, S. R., Guo, C., Robinson, A. M., Price, A., Giles, M. A., Eastell, R., & Weetman, A. P. (1997) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1997.780907.x · Cited by 205 · see citing works
Johannsson, G., Bergthorsdottir, R., Nilsson, A. G., Lennernas, H., Hedner, T., & Skrtic, S. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0170 · Cited by 173 · see citing works
Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy
Debono, M., Ross, R. J. M., & Newell-Price, J. D. C. (2009) · European Journal of Endocrinology · doi:10.1530/eje-08-0874 · Cited by 137 · see citing works
Quinkler, M. O., Nilsen, R. M., Zopf, K., Ventz, M., & Øksnes, M. (2015) · European Journal of Endocrinology · doi:10.1530/eje-14-1114 · Cited by 126 · see citing works
Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy
Johannsson, G., Falorni, A., Skrtic, S., Lennernäs, H., Quinkler, M., Monson, J. P., & Stewart, P. M. (2015) · Clinical Endocrinology · doi:10.1111/cen.12603 · Cited by 122 · see citing works
Giordano, R., Guaraldi, F., Marinazzo, E., Fumarola, F., Rampino, A., Berardelli, R., Karamouzis, I., Lucchiari, M., Manetta, T., Mengozzi, G., et al. (2015) · Endocrine · doi:10.1007/s12020-015-0681-z · Cited by 100 · see citing works
Øksnes, M., Bensing, S., Hulting, A.-L., Kämpe, O., Hackemann, A., Meyer, G., Badenhoop, K., Betterle, C., Parolo, A., Giordano, R., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1901 · Cited by 99 · see citing works
Giordano, R., Marzotti, S., Balbo, M., Romagnoli, S., Marinazzo, E., Berardelli, R., Migliaretti, G., Benso, A., Falorni, A., Ghigo, E., et al. (2009) · Journal of Endocrinological Investigation · doi:10.1007/bf03345773 · Cited by 84 · see citing works
Feek, C. M., Ratcliffe, J. G., Seth, J., Gray, C., Toft, A. D., & Irvine, W. J. (1981) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1981.tb00634.x · Cited by 76 · see citing works
Björnsdottir, S., Sundström, A., Ludvigsson, J. F., Blomqvist, P., Kämpe, O., & Bensing, S. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3561 · Cited by 70 · see citing works
Hair cortisol content in patients with adrenal insufficiency on hydrocortisone replacement therapy
Gow, R. V., Koren, G., Rieder, M. J., & Uum, S. H. M. V. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.04001.x · Cited by 60 · see citing works
Suliman, A. M., Freaney, R., Smith, T. P., McBrinn, Y., Murray, B., & McKenna, T. J. (2003) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2003.01860.x · Cited by 50 · see citing works
Co-morbidities, management and clinical outcome of auto-immune Addison’s disease
Leelarathna, L., Breen, L., Powrie, J., Thomas, S. M., Guzder, R., McGowan, B. M., & Carroll, P. (2010) · Endocrine · doi:10.1007/s12020-010-9359-8 · Cited by 49 · see citing works
Modified-Release Hydrocortisone: Is It Time to Change Clinical Practice?
Stewart, P. M. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00046 · Cited by 28 · see citing works
Laureti, S., Falorni, A., & Santeusanio, F. (2003) · Journal of Endocrinological Investigation · doi:10.1007/bf03345252 · Cited by 27 · see citing works
Rousseau, E., Joubert, M., Trzepla, G., Parienti, J. J., Freret, T., Vanthygem, M. C., Desailloud, R., Lefebvre, H., Coquerel, A., Reznik, Y., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0135975 · Cited by 20 · see citing works
Dual-release Hydrocortisone in Addison’s Disease – A Review of the Literature
Giordano, R., Guaraldi, F., Berardelli, R., Karamouzis, I., Angelo, V. D., Zichi, C., Grottoli, S., Ghigo, E., & Arvat, E. (2010) · touchREVIEWS in Endocrinology · doi:10.17925/ee.2014.10.01.75 · Cited by 4 · see citing works
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Martinez, G. J., Appleton, M., Kipp, Z. A., Loria, A. S., Min, B., & Hinds, T. D. (2023) · Physiological Reviews · doi:10.1152/physrev.00021.2023 · Cited by 108 · see citing works
Hypoglycaemia in adrenal insufficiency
Lee, S. C., Baranowski, E. S., Sakremath, R., Saraff, V., & Mohamed, Z. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1198519 · Cited by 32 · see citing works
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Cera, G., Locantore, P., Novizio, R., Maggio, E., Ramunno, V., Corsello, A., Policola, C., Concolino, P., Paragliola, R. M., & Pontecorvi, A. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11206156 · Cited by 21 · see citing works
Self-citationNovel agents to treat adrenal insufficiency: findings of preclinical and early clinical trials
Peel, A., Rushworth, R. L., & Torpy, D. J. (2024) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2024.2311207 · Cited by 8 · see citing works
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White, P. C. (2022) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000723 · Cited by 7 · see citing works
Cera, G., Corsello, A., Novizio, R., Donna, V. D., Locantore, P., & Paragliola, R. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111779 · Cited by 6 · see citing works
Self-citationChiloiro, S., Vicari, A., Mongelli, G., Costanza, F., Giampietro, A., Mattogno, P. P., Lauretti, L., Olivi, A., Marinis, L. D., Doglietto, F., et al. (2024) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-024-09898-6 · Cited by 5 · see citing works
Self-citationMeyer, G., Gruendl, M., Chifu, I. O., Hahner, S., Werner, J., Weiß, J., Kienitz, T., Quinkler, M. O., Badenhoop, K. W. J., Herrmann, E. M., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12196392 · Cited by 5 · see citing works
Frigerio, S., Carosi, G., Ferrante, E., Sala, E., Polledri, E., Fustinoni, S., Ambrosi, B., Chiodini, I., Mantovani, G., Morelli, V., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1093838 · Cited by 5 · see citing works
Mazzeo, P., Tizianel, I., Sabbadin, C., Voltan, G., Antonelli, G., Ceccato, F., & Barbot, M. (2025) · Endocrine · doi:10.1007/s12020-025-04328-2 · Cited by 2 · see citing works
Fletcher‐Sandersjöö, S., Westeinde, A. V., Spelman, T. D., Hirvikosi, T., Lajić, S., & Bensing, S. (2025) · Clinical Endocrinology · doi:10.1111/cen.70028 · Cited by 1 · see citing works
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Ben-Shlomo, A., Koh, M., Kremen, S. A., & Wertheimer, J. C. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnaf029 · Cited by 1 · see citing works
Silvestro, O., Costa, L., Ferraù, F., Merlo, E. M., Cannavò, S., Feldt-Rasmussen, U., & Martino, G. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1901783
- Authors
- Delle Cese, F., Corsello, A., Cintoni, M., Locantore, P., Pontecorvi, A., Corsello, S. M., & Paragliola, R. M.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- University of Rome Tor Vergata (IT)
- Corresponding author
- Corsello, Salvatore Maria
- ORCID
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2021-02-01
- Volume
- 11
- Pages
- 610904-610904
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC7883639
- OpenAlex
- W3128825137
- Cited by
- 13
- References
- 24
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 2
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- Addison's disease, cortisol, dose reduction, dose fractionation, once-daily dosing, ACTH, HbA1c, lipid profile, body mass index, quality of life, autoimmune adrenal insufficiency, metabolic control
- MeSH terms
- Adrenal Insufficiency, Adult, Aged, Anti-Inflammatory Agents, Delayed-Action Preparations, Drug Administration Schedule, Drug Compounding, Female, Humans, Hydrocortisone, Male, Middle Aged, Prospective Studies, Quality of Life
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