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Improvement of anthropometric and metabolic parameters, and quality of life following treatment with dual-release hydrocortisone in patients with Addison’s disease

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Abstract

In patients with Addison’s disease (AD), a dual-release preparation of hydrocortisone (Plenadren, PLEN) has been demonstrated to maintain cortisol levels in a more physiological range than conventional glucocorticoid therapy, and to exert positive effects. This study aimed to assess variations of anthropometric, metabolic, and hormonal parameters in patients with AD after switching from conventional hydrocortisone (HC) treatment to PLEN. In nineteen AD patients (15 F and 4 M, age 27–65 years) treated with HC 20 mg/day thrice daily, body weight, BMI, waist circumference, fasting glucose, HbA1c, serum lipids, plasma renin activity, electrolytes, and blood pressure were evaluated at baseline, and 1, 3, 6, and 12 months after switching from HC to PLEN. At baseline, and after 1 and 12 months of PLEN, blood ACTH and cortisol (at 0800 h at fasting, and 30, 60, 90, 120, and 240 min after drug ingestion), and health-related quality of life (HRQoL), using 30-AddiQoL questionnaire, were evaluated. During PLEN, waist and serum lipid progressively decreased. After 12 months of PLEN, a significant difference was observed in waist circumference (P = 0.007), HbA1c (P = 0.002), total and LDL-cholesterol levels (P < 0.05). ACTH levels at 240 min and the area under the curve (AUC) were lower (P < 0.05) during PLEN than HC, while cortisol peaks and AUC were similar. 30-AddiQoL total score also improved (P = 0.04) during PLEN. In AD patients, PLEN reduces central adiposity, and improves glucose and metabolism parameters and HRQoL.

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References

  1. W. Arlt, B. Allolio, Adrenal insufficiency. Lancet 361, 1881–1893 (2003)

    Article  CAS  PubMed  Google Scholar 

  2. G.M. Besser, W.J. Jeffcoate, Endocrine and metabolic diseases. Adrenal diseases. Br. Med. J. 1, 448–451 (1976)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. W. Oelkers, S. Diederich, W. Bahr, Therapeutic strategies in adrenal insufficiency. Ann. Endocrinol. 62, 212–216 (2001)

    CAS  Google Scholar 

  4. A. Falorni, V. Minarelli, S. Morelli, Therapy of adrenal insufficiency: an update. Endocrine 43, 514–528 (2013)

    Article  CAS  PubMed  Google Scholar 

  5. E.S. Husebye, B. Allolio, W. Arlt, K. Badenhoop, S. Bensing, C. Betterle, A. Falorni, E.H. Gan, A.L. Hulting, A. Kasperlik-Zaluska, O. Kämpe, K. Løvås, G. Meyer, S.H. Pearce, Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J. Intern. Med. 275, 104–115 (2014)

    Article  CAS  PubMed  Google Scholar 

  6. H. Derendorf, H. Möllmann, J. Barth, C. Möllmann, S. Tunn, M. Krieg, Pharmacokinetics and oral bioavailability of hydrocortisone. J. Clin. Pharmacol. 31, 473–476 (1991)

    Article  CAS  PubMed  Google Scholar 

  7. R. Bergthorsdottir, M. Leonsson-Zachrisson, A. Odén, G. Johannsson, Premature mortality in patients with Addison’s disease: a population-based study. J. Clin. Endocrinol. Metab. 91, 4849–4853 (2006)

    Article  CAS  PubMed  Google Scholar 

  8. S. Bensing, L. Brandt, F. Tabaroj, O. Sjöberg, B. Nilsson, A. Ekbom, P. Blomqvist, O. Kämpe, Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency. Clin. Endocrinol. 69, 697–704 (2008)

    Article  Google Scholar 

  9. M.M. Erichsen, K. Løvås, K.J. Fougner, J. Svartberg, E.R. Hauge, J. Bollerslev, J.P. Berg, B. Mella, E.S. Husebye, Normal overall mortality rate in Addison’s disease, but young patients are at risk of premature death. Eur. J. Endocrinol. 160, 233–237 (2009)

    Article  CAS  PubMed  Google Scholar 

  10. I.L. Ross, R. Bergthorsdottir, N.S. Levitt, D.A. Schatz, G. Johannsson, A.D. Marais, Increased cardiovascular risk in south african patients with Addison’s disease. Horm. Metab. Res. 45, 905–910 (2013)

    Article  CAS  PubMed  Google Scholar 

  11. I.L. Ross, R. Bergthorsdottir, N. Levitt, J.A. Dave, D. Schatz, A.D. Marais, G. Johannsson, A.D. Marais, Cardiovascular risk factors in patients with Addison’s disease: a comparative study of South African and Swedish patients. PLoS One 9(3), e90768 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  12. R. Giordano, S. Marzotti, M. Balbo, S. Romagnoli, E. Marinazzo, R. Berardelli, G. Migliaretti, A. Benso, A. Falorni, E. Ghigo, E. Arvat, Metabolic and cardiovascular profile in patients with Addison’s disease under conventional glucocorticoid replacement. J. Endocrinol. Invest. 32, 917–923 (2009)

    Article  CAS  PubMed  Google Scholar 

  13. L. Leelarathna, L. Breen, J.K. Powrie, S.M. Thomas, R. Guzder, B. McGowan, P.V. Carroll, Co-morbidities, management and clinical outcome of auto-immune Addison’s disease. Endocrine 38, 113–117 (2010)

    Article  CAS  PubMed  Google Scholar 

  14. H. Filipsson, J.P. Monson, M. Koltowska-Häggström, A. Mattsson, G. Johannsson, The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients. J. Clin. Endocrinol. Metab. 91, 3954–3961 (2006)

    Article  CAS  PubMed  Google Scholar 

  15. M.F. Dallman, S.F. Akana, S. Bhatnagar, M.E. Bell, A.M. Strack, Bottomed out: metabolic significance of the circadian trough in glucocorticoid concentrations. Int. J. Obes. Relat. Metab. Disord. 24(Suppl 2), S40–S46 (2000)

    Article  CAS  PubMed  Google Scholar 

  16. S. Hahner, M. Loeffler, B. Bleicken, C. Drechsler, D. Milovanovic, M. Fassnacht, M. Ventz, M. Quinkler, B. Allolio, Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur. J. Endocrinol. 162, 597–602 (2010)

    Article  CAS  PubMed  Google Scholar 

  17. S. Hahner, C. Spinnler, M. Fassnacht, S. Burger-Stritt, K. Lang, D. Milovanovic, F. Beuschlein, H.S. Willenberg, M. Quinkler, B. Allolio, High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency—a prospective study. J. Clin. Endocrinol. Metab. 100, 407–416 (2015)

    Article  CAS  PubMed  Google Scholar 

  18. K. Lovas, J.H. Loge, E.S. Husebye, Subjective health status in Norwegian patients with Addison’s disease. Clin. Endocrinol. 56, 581–588 (2002)

    Article  Google Scholar 

  19. S. Hahner, M. Loeffler, M. Fassnacht, D. Weismann, A.C. Koschker, M. Quinkler, O. Decker, W. Arlt, B. Allolio, Impaired subjective health status in 256 patients with adrenal insufficiency on standard therapy based on cross-sectional analysis. J. Clin. Endocrinol. Metab. 92, 3912–3922 (2007)

    Article  CAS  PubMed  Google Scholar 

  20. B. Bleicken, S. Hahner, M. Loeffler, M. Ventz, B. Allolio, M. Quinkler, Impaired subjective health status in chronic adrenal insufficiency: impact of different glucocorticoid replacement regimens. Eur. J. Endocrinol. 159, 811–817 (2008)

    Article  CAS  PubMed  Google Scholar 

  21. G. Johannsson, R. Bergthorsdottir, A.G. Nilsson, H. Lennernas, T. Hedner, S. Skrtic, Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study. Eur. J. Endocrinol. 161, 119–130 (2009)

    Article  CAS  PubMed  Google Scholar 

  22. G. Johannsson, A.G. Nilsson, R. Bergthorsdottir, P. Burman, P. Dahlqvist, B. Ekman, B.E. Engström, T. Olsson, O. Ragnarsson, M. Ryberg, J. Wahlberg, B.M. Biller, J.P. Monson, P.M. Stewart, H. Lennernäs, S. Skrtic, 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. 97, 473–481 (2012)

    Article  CAS  PubMed  Google Scholar 

  23. A. Falorni, A. Nikoshkov, S. Laureti, E. Grenbäck, A.L. Hulting, G. Casacci, F. Santeusanio, P. Brunetti, H. Luthman, A. Lernmark, High diagnostic accuracy for idiopathic Addison’s disease with a sensitive radiobinding assay for autoantibodies against recombinant human 21-hydroxylase. J. Clin. Endocrinol. Metab. 80, 2752–2754 (1995)

    CAS  PubMed  Google Scholar 

  24. K. Løvås, S. Curran, M. Oksnes, E.S. Husebye, F.A. Huppert, V.K. Chatterjee, Development of a disease-specific quality of life questionnaire in Addison’s disease. J. Clin. Endocrinol. Metab. 95, 545–551 (2010)

    Article  PubMed  Google Scholar 

  25. M. Øksnes, S. Bensing, A.L. Hulting, O. Kämpe, A. Hackemann, G. Meyer, K. Badenhoop, C. Betterle, A. Parolo, R. Giordano, A. Falorni, L. Papierska, W. Jeske, A.A. Kasperlik-Zaluska, V.K. Chatterjee, E.S. Husebye, K. Løvåsm, Quality of life in European patients with Addison’s disease: validity of the disease-specific questionnaire AddiQoL. J. Clin. Endocrinol. Metab. 97, 568–576 (2012)

    Article  PubMed  Google Scholar 

  26. A.S. Mason, Epidemiological and clinical picture of Addison’s disease. Lancet 2, 744–747 (1968)

    Article  CAS  PubMed  Google Scholar 

  27. L. Plat, R. Leproult, M. L’Hermite-Baleriaux, F. Fery, J. Mockel, K.S. Polonsky, C.E. Van, Metabolic effects of short-term elevations of plasma cortisol are more pronounced in the evening than in the morning. J. Clin. Endocrinol. Metab. 84, 3082–3092 (1999)

    CAS  PubMed  Google Scholar 

  28. U. Elbelt, S. Hahner, B. Allolio, Altered insulin requirement in patients with type 1 diabetes and primary adrenal insufficiency receiving standard glucocorticoid replacement therapy. Eur. J. Endocrinol. 160, 919–924 (2009)

    Article  CAS  PubMed  Google Scholar 

  29. G. Arnaldi, V.M. Scandali, L. Trementino, M. Cardinaletti, G. Appolloni, M. Boscaro, Pathophysiology of dyslipidemia in Cushing’s syndrome. Neuroendocrinology 92(Suppl 1), 86–90 (2010)

    Article  CAS  PubMed  Google Scholar 

  30. B. Ekman, J. Blomgren, P.O. Andersson, M. Carlsson, H.J. Arnqvist, Variable sensitivity to the glucocorticoid activity of cortisol in patients with primary adrenal insufficiency: assessment with ACTH profiles. Horm. Metab. Res. 42, 961–966 (2010)

    Article  CAS  PubMed  Google Scholar 

  31. B. Ekman, M. Bachrach-Lindström, T. Lindström, J. Wahlberg, J. Blomgren, H.J. Arnqvist, 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. 77, 18–25 (2012)

    Article  CAS  Google Scholar 

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Acknowledgments

The study was supported by a University of Turin Grant (ex 60 %, year 2013).

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Authors and Affiliations

  1. Department of Clinical and Biological Sciences, University of Turin, 10126, Turin, Italy

    Roberta Giordano & Alessia Rampino

  2. Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy

    Roberta Giordano, Federica Guaraldi, Elisa Marinazzo, Federica Fumarola, Ioannis Karamouzis & Ezio Ghigo

  3. Clinical Biochemistry Laboratory, “Città della Salute e della Scienza di Torino” University Hospital, 10126, Turin, Italy

    Manuela Lucchiari, Tilde Manetta & Giulio Mengozzi

  4. Division of Oncological Endocrinology, Department of Medical Sciences, University of Turin, 10126, Turin, Italy

    Rita Berardelli & Emanuela Arvat

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  1. Roberta Giordano
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Correspondence to Roberta Giordano.

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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 51, 360–368 (2016). https://doi.org/10.1007/s12020-015-0681-z

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