Skip to main content

Advertisement

SpringerLink
Log in

Therapy of adrenal insufficiency: an update

  • Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Adrenal insufficiency may be caused by the destruction or altered function of the adrenal gland with a primary deficit in cortisol secretion (primary adrenal insufficiency) or by hypothalamic-pituitary pathologies determining a deficit of ACTH (secondary adrenal insufficiency). The clinical picture is determined by the glucocorticoid deficit, which may in some conditions be accompanied by a deficit of mineralcorticoids and adrenal androgens. The substitutive treatment is aimed at reducing the signs and symptoms of the disease as well as at preventing the development of an addisonian crisis, a clinical emergency characterized by hypovolemic shock. The oral substitutive treatment should attempt at mimicking the normal circadian profile of cortisol secretion, by using the lower possible doses able to guarantee an adequate quality of life to patients. The currently available hydrocortisone or cortisone acetate preparations do not allow an accurate reproduction of the physiological secretion pattern of cortisol. A novel dual-release formulation of hydrocortisone, recently approved by EMEA, represents an advancement in the optimization of the clinical management of patients with adrenal insufficiency. Future clinical trials of immunomodulation or immunoprevention will test the possibility to delay (or prevent) the autoimmune destruction of the adrenal gland in autoimmune Addison’s disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. W. Oelkers, Adrenal insufficiency. N. Engl. J. Med. 335, 1206–1212 (1996)

    Article  PubMed  CAS  Google Scholar 

  2. S. Ten, M. New, N. Maclaren, Clinical review 130: Addison’s disease 2001. J. Clin. Endocrinol. Metab. 86, 2909–2922 (2001)

    Article  PubMed  CAS  Google Scholar 

  3. T. Addison, On the constitutional and local effects of disease of the supra-renal capsules. 1855. Reproduced in Dr. Addison’s works. New Sydenham Soc. 36, 211–239 (1868)

  4. P. Aubourg, The expanding world of primary adrenal insufficiencies. Eur. J. Endocrinol. 137, 10–12 (1997)

    Article  PubMed  CAS  Google Scholar 

  5. S. Laureti, F. Santeusanio, A. Falorni, Recent advances in the diagnosis and therapy of primary adrenal insufficiency. Curr. Med. Chem. 2, 251–258 (2002)

    CAS  Google Scholar 

  6. A.S. Mason, T.W. Meade, J.A.H. Lee, J.N. Morris, Epidemiological and clinical picture of Addison’s disease. Lancet II, 744–747 (1968)

    Article  Google Scholar 

  7. J. Nerup, Addison’s disease—clinical studies. A report of 108 cases. Acta Endocrinol. (Copenh.) 76, 127–141 (1974)

    CAS  Google Scholar 

  8. S. Laureti, L. Vecchi, F. Santeusanio, A. Falorni, Is the prevalence of Addison’s disease underestimated? J. Clin. Endocrinol. Metab. 84, 1762 (1999)

    Article  PubMed  CAS  Google Scholar 

  9. M.F. Kong, W. Jeffcoate, Eighty-six cases of Addison’s disease. Clin. Endocrinol. (Oxf.) 41, 757–761 (1994)

    Article  CAS  Google Scholar 

  10. A.C. Willis, F.P. Vince, The prevalence of Addison’s disease in Coventry, UK. Postgrad. Med. J. 73, 286–288 (1997)

    Article  PubMed  CAS  Google Scholar 

  11. K. Løvas, E.S. Husebye, High prevalence and increasing incidence of Addison’s disease in western Norway. Clin. Endocrinol. (Oxf.) 56, 787–791 (2002)

    Article  Google Scholar 

  12. C. Betterle, C. Dal Pra, F. Mantero, R. Zanchetta, Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr. Rev. 23, 327–364 (2002)

    Article  PubMed  CAS  Google Scholar 

  13. A. Falorni, A. Brozzetti, F. Calcinaro, S. Marzotti, F. Santeusanio, Recent advances in adrenal autoimmunity. Expert Rev. Clin. Endocrinol. Metab. 4, 333–348 (2009)

    Article  CAS  Google Scholar 

  14. O. Winqvist, F.A. Karlsson, O. Kämpe, 21-Hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet 339, 1559–1562 (1992)

    Article  PubMed  CAS  Google Scholar 

  15. A. Baumann-Antczak, N. Wedlock, J. Bednarek, Y. Kiso, H. Krishnan, S. Fowler, B. Rees Smith, J. Furmaniak, Autoimmune Addison’s disease and 21-hydroxylase. Lancet 340, 429–430 (1992)

    Article  PubMed  CAS  Google Scholar 

  16. J. Bednarek, J. Furmaniak, N. Wedlock, Y. Kiso, A. Baumann-Antczak, S. Fowler, H. Krishnan, J.A. Craft, B. Rees Smith, Steroid 21-hydroxylase is a major autoantigen involved in adult onset autoimmune Addison’s disease. FEBS Lett. 309, 51–55 (1992)

    Article  PubMed  CAS  Google Scholar 

  17. A. Falorni, A. Nikoshkov, S. Laureti et al., 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, 2752–2755 (1995)

    Article  PubMed  CAS  Google Scholar 

  18. J. Colls, C. Betterle, M. Volpato, L. Prentice, B.R. Smith, J. Furmaniak, Immunoprecipitation assay for autoantibodies to steroid 21-hydroxylase in autoimmune adrenal diseases. Clin. Chem. 41, 375–380 (1995)

    PubMed  CAS  Google Scholar 

  19. H. Tanaka, M.S. Perez, M. Powell et al., Steroid 21-hydroxylase autoantibodies: measurements with a new immunoprecipitation assay. J. Clin. Endocrinol. Metab. 82, 1440–1446 (1997)

    Article  PubMed  CAS  Google Scholar 

  20. R. Nigam, E. Bhatia, D. Mei, L. Yu, A. Brozzetti, G.S. Eisenbarth, A. Falorni, Low prevalence of 21-hydroxylase antibodies in idiopathic Addison’s disease from India. Clin. Endocrinol. 59, 593–598 (2003)

    Article  CAS  Google Scholar 

  21. F. Kelestimur, The endocrinology of adrenal tuberculosis: the effects of tuberculosis on the hypothalamo-pituitary-adrenal axis and adrenocortical function. J. Endocrinol. Invest. 27, 380–386 (2004)

    PubMed  CAS  Google Scholar 

  22. P. Aubourg, On the front of X-linked adrenoleukodystrophy. Neurochem. Res. 24, 515–520 (1999)

    Article  PubMed  CAS  Google Scholar 

  23. E.R. McCabe, DAX1: increasing complexity in the roles of this novel nuclear receptor. Mol. Cell. Endocrinol. 265–266, 179–182 (2007)

    Article  PubMed  CAS  Google Scholar 

  24. J.C. Achermann, M. Ito, M. Ito, P.C. Hindmarsch, J.L. Jameson, A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat. Genet. 22, 125–126 (1999)

    Article  PubMed  CAS  Google Scholar 

  25. A.J. Clark, L. McLoughlin, A. Grossman, Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Lancet 341, 461–462 (1993)

    Article  PubMed  CAS  Google Scholar 

  26. A. Weber, T.F. Wienker, M. Jung, D. Easton, H.J. Dean, C. Heinrichs, A. Reis, A.J. Clark, Linkage of the gene for the triple A syndrome to chromosome 12q13 near the type II keratin gene cluster. Hum. Mol. Genet. 5, 2061–2066 (1996)

    Article  PubMed  CAS  Google Scholar 

  27. K. North, M.S. Korson, N. Krawiecki, J.M. Shoffner, I.A. Holm, Oxidative phosphorylation defect associated with primary adrenal insufficiency. J. Pediatrics 128, 688–692 (1996)

    Article  CAS  Google Scholar 

  28. H.C. Andersson, J. Frentz, J.E. Martínez, C.M. Tuck-Muller, J. Bellizaire, Adrenal insufficiency in Smith-Lemli-Opitz syndrome. Am. J. Med. Genet. 82, 382–384 (1999)

    Article  PubMed  CAS  Google Scholar 

  29. R. Perry, O. Kecha, J. Paquette, C. Huot, G. Van Vliet, C. Deal, Primary adrenal insufficiency in children: twenty years experience at the Sainte-Justine Hospital, Montreal. J. Clin. Endocrinol. Metab. 92, 4602–4608 (2005)

    Google Scholar 

  30. C. Betterle, C. Scalici, F. Presotto et al., The natural history of adrenal function in autoimmune patients with adrenal autoantibodies. J. Endocrinol. 117, 467–475 (1988)

    Article  PubMed  CAS  Google Scholar 

  31. A. De Bellis, A. Bizzarro, R. Rossi, V.A. Paglionico, T. Criscuolo, G. Lombardi, A. Bellastella, Remission of subclinical adrenocortical failure in subjects with adrenal autoantibodies. J. Clin. Endocrinol. Metab. 76, 1002–1007 (1993)

    Article  PubMed  Google Scholar 

  32. C. Betterle, M. Volpato, B. Rees-Smith et al., I. Adrenal cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of low progression to clinical Addison’s disease. J. Clin. Endocrinol. Metab. 82, 932–938 (1997)

    Article  PubMed  CAS  Google Scholar 

  33. C. Betterle, M. Volpato, B. Rees Smith, J. Furmaniak, S. Chen, R. Zanchetta, N.A. Greggio, B. Pedini, M. Boscaro, F. Presotto II, Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases: markers of high progression to clinical Addison’s disease. J. Clin. Endocrinol. Metab. 82, 939–942 (1997)

    Article  PubMed  CAS  Google Scholar 

  34. S. Laureti, A. De Bellis, V.I. Muccitelli et al., Levels of adrenocortical autoantibodies correlate with the degree of adrenal dysfunction in subjects with preclinical Addison’s disease. J. Clin. Endocrinol. Metab. 83, 3507–3511 (1998)

    Article  PubMed  CAS  Google Scholar 

  35. G. Coco, C. Dal Pra, F. Presotto et al., Estimated risk for developing autoimmune Addison’s disease in patients with adrenal cortex autoantibodies. J. Clin. Endocrinol. Metab. 91, 1637–1645 (2006)

    Article  PubMed  CAS  Google Scholar 

  36. B. Jacobs, C. Papewalis, M. Ehlers, M. Schott, Endocrine organs under the control of the immune system: potential implications for cellular therapies. Horm. Metab. Res. 42, 912–917 (2010)

    Article  PubMed  CAS  Google Scholar 

  37. K.I. Papadopoulos, B. Hallengren, Polyglandular autoimmune syndrome type II in patients with idiopathic Addison’s disease. Acta Endocrinol. (Copenh.) 122, 472–478 (1990)

    CAS  Google Scholar 

  38. A.A. Kasperlik-Zaluska, B. Migdalska, B. Czarnocka, J. Drac-Kaniewska, E. Niegowska, W. Czech, Association of Addison’s disease with autoimmune disorders—a long-term observation of 180 patients. Postgrad. Med. J. 67, 984–987 (1991)

    Article  PubMed  CAS  Google Scholar 

  39. P.M. Zelissen, E.J. Bast, R.J. Croughs, Associated autoimmunity in Addison’s disease. J. Autoimmunity 8, 121–130 (1995)

    Article  CAS  Google Scholar 

  40. A. La Marca, A. Brozzetti, G. Sighinolfi, S. Marzotti, A. Volpe, A. Falorni, Primary ovarian insufficiency: autoimmune causes. Curr. Opin. Obstet. Gynecol. 22, 277–282 (2010)

    PubMed  Google Scholar 

  41. G.S. Eisenbarth, P.A. Gottlieb, Autoimmune polyendocrine syndromes. N. Engl. J. Med. 350, 2068–2079 (2004)

    Article  PubMed  CAS  Google Scholar 

  42. P. Peterson, J. Pitkänen, N. Sillanpää, K. Krohn, Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a model disease to study molecular aspects of endocrine autoimmunity. Clin. Exp. Immunol. 135, 348–357 (2004)

    Article  PubMed  CAS  Google Scholar 

  43. A. Meager, K. Visvalingam, P. Peterson, K. Möll, A. Murumägi, K. Krohn, P. Eskelin, J. Perheentupa, E. Husebye, Y. Kadota, N. Willcox, Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med. 3, e289 (2006)

    Article  PubMed  CAS  Google Scholar 

  44. A. Meloni, M. Furcas, F. Cetani, C. Marcocci, A. Falorni, R. Perniola, M. Pura, A.S. Bøe Wolff, E. Husebye, D. Lilic, K.R. Ryan, A.R. Gennery, A.J. Cant, M. Abinun, G.P. Spickett, P.D. Arkwright, D. Denning, C. Costigan, M. Dominguez, V. McConnell, N. Willcox, A. Meager, Autoantibodies against type I Interferons as an additional diagnostic criteria for Autoimmune Polyendocrine Syndrome type 1. J. Clin. Endocrinol. Metab. 93, 4389–4397 (2008)

    Article  PubMed  CAS  Google Scholar 

  45. A. Falorni, A. Brozzetti, D. La Torre, C. Tortoioli, G. Gambelunghe, The association of genetic polymorphisms and autoimmune Addison’s disease. Expert Rev. Clin. Immunol. 4, 441–456 (2008)

    Article  PubMed  CAS  Google Scholar 

  46. P.W. Speiser, R. Azziz, L.S. Baskin, L. Ghizzoni, T.W. Hensle, D.P. Merke, H.F. Meyer-Bahlburg, W.L. Miller, V.M. Montori, S.E. Oberfield, M. Ritzen, P.C. White, Endocrine Society. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 95, 4133–4160 (2010)

    Article  PubMed  CAS  Google Scholar 

  47. A. Nordenström, S. Ahmed, J. Jones, M. Coleman, D.A. Price, P.E. Clayton, C.M. Hall, Female preponderance in congenital adrenal hyperplasia due to CYP21 deficiency in England: implications for neonatal screening. Horm. Res. 63, 22–28 (2005)

    Article  PubMed  CAS  Google Scholar 

  48. S. Pang, M.K. Shook, Current status of neonatal screening for congenital adrenal hyperplasia. Curr. Opin. Pediatr. 9, 419–423 (1997)

    Article  PubMed  CAS  Google Scholar 

  49. B.L. Therrell, Newborn screening for congenital adrenal hyperplasia. Endocrinol. Metab. Clin. North Am. 30, 15–30 (2001)

    Article  PubMed  CAS  Google Scholar 

  50. H.J. van der Kamp, J.M. Wit, Neonatal screening for congenital adrenal hyperplasia. Eur. J. Endocrinol. 151(Suppl 3), U71–U75 (2004)

    Article  PubMed  Google Scholar 

  51. G. Reimondo, S. Bovio, B. Allasino, M. Terzolo, A. Angeli, Secondary hypoadrenalism. Pituitary 11, 147–154 (2008)

    Article  PubMed  CAS  Google Scholar 

  52. P. Caturegli, C. Newschaffer, A. Olivi, M.G. Pomper, P.C. Burger, N.R. Rose, Auutoimmune hypophysitis. Endocr. Rev. 26, 599–614 (2005)

    Article  PubMed  CAS  Google Scholar 

  53. M.S. Cooper, P.M. Stewart, Corticosteroid insufficiency in acutely ill patients. N. Engl. J. Med. 348, 727–734 (2003)

    Article  PubMed  CAS  Google Scholar 

  54. E. Arvat, L. Di Vito, F. Lanfranco, M. Maccario, C. Baffoni, R. Rossetto, G. Aimaretti, F. Camanni, E. Ghigo, Stimulatory effect of adrenocorticotropin on cortisol, aldosterone, and dehydroepiandrosterone secretion in normal humans: dose-response study. J. Clin. Endocrinol. Metab. 85, 3141–3146 (2000)

    Article  PubMed  CAS  Google Scholar 

  55. S. Laureti, E. Arvat, P. Candeloro, L. Di Vito, E. Ghigo, F. Santeusanio, A. Falorni, Low dose (1 microg) ACTH test in the evaluation of adrenal dysfunction in pre-clinical Addison’s disease. Clin. Endocrinol. (Oxf.) 53, 107–115 (2000)

    Article  CAS  Google Scholar 

  56. S. Laureti, P. Candeloro, M.C. Aglietti, R. Giordano, E. Arvat, E. Ghigo, F. Santeusanio, A. Falorni, Dehydroepiandrosterone, 17alpha-hydroxyprogesterone and aldosterone responses to the low-dose (1 micro g) ACTH test in subjects with preclinical adrenal autoimmunity. Clin. Endocrinol. (Oxf.) 57, 677–683 (2002)

    Article  CAS  Google Scholar 

  57. A. Falorni, S. Laureti, A. De Bellis et al., Italian Addison Network Study: update of diagnostic criteria for the etiological classification of primary adrenal insufficiency. J. Clin. Endocrinol. Metab. 89, 1598–1604 (2004)

    Article  PubMed  CAS  Google Scholar 

  58. S. Laureti, P. Aubourg, F. Calcinaro, F. Rocchiccioli, G. Casucci, G. Angeletti, P. Brunetti, Å. Lernmark, F. Santeusanio, A. Falorni, Etiological diagnosis of primary adrenal insufficiency using an original flow-chart of immune and biochemical markers. J. Clin. Endocrinol. Metab. 83, 3163–3168 (1998)

    Article  PubMed  CAS  Google Scholar 

  59. E.S. Husebye, J. Perheentupa, R. Rautemaa, O. Kämpe, Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I. J. Intern. Med. 265, 514–529 (2009)

    Article  PubMed  CAS  Google Scholar 

  60. A. Falorni, S. Laureti, P. Candeloro et al., Steroid-cell autoantibodies are preferentially expressed in women with premature ovarian failure who have adrenal autoimmunity. Fertil. Steril. 78, 270–279 (2002)

    Article  PubMed  Google Scholar 

  61. G. Reato, L. Morlin, S. Chen, J. Furmaniak, B.R. Smith, S. Masiero, M.P. Albergoni, S. Cervato, R. Zanchetta, C. Betterle, Premature ovarian failure in patients with autoimmune Addison’s disease: clinical, genetic, and immunological evaluation. J. Clin. Endocrinol. Metab. 96, E1255–E1261 (2011)

    Article  PubMed  CAS  Google Scholar 

  62. A. Falorni, S. Chen, R. Zanchetta, L. Yu, C. Tiberti, M.L. Bacosi, J. Furmaniak, V. Bini, F. Dotta, G.S. Eisenbarth, B.R. Smith, C. Betterle, Measuring adrenal autoantibody response: interlaboratory concordance in the first international serum exchange for the determination of 21-hydroxylase autoantibodies. Clin. Immunol. 140, 291–299 (2011)

    Article  PubMed  CAS  Google Scholar 

  63. K. Lovas, E.S. Husebye, Replacement therapy in Addison’s disease. Expert Opin. Pharmacother. 4, 2145–2149 (2003)

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  65. N.V. Esteban, T. Loughlin, A.L. Yergay, J.K. Zawadki, J.D. Booth, J.C. Winterer et al., Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. J. Clin. Endocrinol. Metab. 72, 39–45 (1991)

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  67. R.M. Reynolds, P.M. Stewart, J.R. Seckl, P.L. Padfield, Assessing the HPA axis in patients with pituitary disease: a UK survey. Clin. Endocrinol. (Oxf) 64, 82–85 (2006)

    Article  Google Scholar 

  68. C.M. Feek, J.G. Ratcliffe, J. Seth, C.E. Gray, A.D. Toft, W.J. Irvine, Patterns of plasma cortisol and ACTH concentrations in patients with Addison’s disease treated with conventional corticosteroid replacement. Clin. Endocrinol. (Oxf.) 14, 451–458 (1981)

    Article  CAS  Google Scholar 

  69. R.S. Scott, R.A. Donald, E.A. Espiner, Plasma ACTH and cortisol profiles in Addisonian patients receiving conventional substitution therapy. Clin. Endocrinol. (Oxf.) 9, 571–576 (1978)

    Article  CAS  Google Scholar 

  70. W. Jeffcoate, Assessment of corticosteroid replacement therapy in adults with adrenal insufficiency. Ann. Clin. Biochem. 36(2), 151–157 (1999)

    PubMed  CAS  Google Scholar 

  71. S. Laureti, A. Falorni, F. Santeusanio, Improvement of treatment of primary adrenal insufficiency by administration of cortisone acetate in three daily doses. J. Endocrinol. Invest. 26, 1071–1075 (2003)

    PubMed  CAS  Google Scholar 

  72. W. Arlt, C. Rosenthal, S. Hahner, B. Allolio: Quality of glucocorticoid replacement in adrenal insufficiency: clinical assessment vs. timed serum cortisol measurements. Clin. Endocrinol. (Oxf.) 64, 384–389 (2006)

    Google Scholar 

  73. P.M. Mah, R.C. Jenkins, A. Rostami-Hodjegan, J. Newell-Price, A. Doane et al., Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clin. Endocrinol. (Oxf.) 61, 367–375 (2004)

    Article  CAS  Google Scholar 

  74. A.W. Meikle, J.D. Stringham, M.G. Woodward, D.T. Bishop, Heritability of variation of plasma cortisol levels. Metabolism 37, 514–517 (1988)

    Article  PubMed  CAS  Google Scholar 

  75. A.L. Barbato, R.L. Landau, Serum cortisol appearance-disappearance in adrenal insufficiency after oral cortisone acetate. Acta Endocrinol. (Copenh.) 84, 600–604 (1977)

    CAS  Google Scholar 

  76. R.W. Groves, G.C. Toms, B.J. Hougthon, J.P. Monson, Corticosteroid replacement therapy: twice or thrice daily? J.R.Soc.Med. 81, 514–516 (1988)

    PubMed  CAS  Google Scholar 

  77. L. Barbetta, C. Dall’Asta, T. Re, R. Libè, E. Costa, B. Ambrosi, Comparison of different regimens of glucocorticoid replacement therapy in patients with hypoadrenalism. J. Endocrinol. Invest. 28, 632–637 (2005)

    PubMed  CAS  Google Scholar 

  78. T.A. Howlett, An assessment of optimal hydrocortisone replacement therapy. Clin. Endocrinol. (Oxf.) 46, 263–268 (1997)

    Article  CAS  Google Scholar 

  79. A.H. Thomson, M.C. Devers, A.M. Wallace, D. Grant, K. Campbell et al., Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to patients with adrenal insufficiency. Clin. Endocrinol. (Oxf.) 66, 789–796 (2007)

    Article  CAS  Google Scholar 

  80. E. Charmandari, A. Johnston, C.G. Brook, P.C. Hindmarsh, Bioavailability of oral hydrocortisone in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J. Endocrinol. 169, 65–70 (2001)

    Article  PubMed  CAS  Google Scholar 

  81. B. Sauve, G. Koren, G. Walsh, S. Tokmakejian, S.H. Van Uum, Measurement of cortisol in human hair as a biomarker of systemic exposure. Clin. Invest. Med. 30, E183–E191 (2007)

    PubMed  CAS  Google Scholar 

  82. L.F. Hofman, Human saliva as a diagnostic specimen. J. Nutr. 131, 1621S–1625S (2001)

    PubMed  CAS  Google Scholar 

  83. A. Moreira, F. Arsati, de Oliveira Lima Arsati, Y.B., da Silva, D.A. de Araujo, V.C. Salivary cortisol in top-level professional soccer players. Eur. J. Appl. Physiol. 106, 25–30 (2009)

    Article  PubMed  CAS  Google Scholar 

  84. D. Riad-Fahmy, G.F. Read, R.F. Walker, Salivary steroid assays for assessing variation in endocrine activity. J. Steroid Biochem. 19, 265–272 (1983)

    Article  PubMed  CAS  Google Scholar 

  85. M. Groschl, Current status of salivary hormone analysis. Clin. Chem. 54, 1759–1769 (2008)

    Article  PubMed  CAS  Google Scholar 

  86. I. Perogamvros, B.G. Keevil, D.W. Ray, P.J. Trainer, Salivary cortisone is a potential biomarker for serum free cortisol. J. Clin. Endocrinol. Metab. 95, 4951–4958 (2010)

    Article  PubMed  CAS  Google Scholar 

  87. L.D. Dorn, J.F. Lucke, T.L. Loucks, S.L. Berga, Salivary cortisol reflects serum cortisol: analysis of circadian profiles. Ann. Clin. Biochem. 44, 281–284 (2007)

    Article  PubMed  CAS  Google Scholar 

  88. J.G. Lewis, Steroid analysis in saliva: an overview. Clin. Biochem. Rev. 27, 139–146 (2006)

    PubMed  Google Scholar 

  89. P. Wood, Salivary steroid assays – research or routine? Ann. Clin. Biochem. 46, 183–196 (2009)

    Article  PubMed  CAS  Google Scholar 

  90. J.W. Findling, H. Raff, Cushing’s Syndrome: important issues in diagnosis and management. J. Clin. Endocrinol. Metab. 91, 3746–3753 (2006)

    Article  PubMed  CAS  Google Scholar 

  91. H. Raff, Utility of salivary cortisol measurements in Cushing’s syndrome and adrenal insufficiency. J. Clin. Endocrinol. Metab. 94, 3647–3655 (2009)

    Article  PubMed  CAS  Google Scholar 

  92. H. Raff, Salivary cortisol and the diagnosis of Cushing’s syndrome: a coming age. Endocrine 41, 353–354 (2012)

    Article  PubMed  CAS  Google Scholar 

  93. E.M. Scott, H.H. McGarrigle, G.C. Lachelin, The increase in plasma and saliva cortisol levels in pregnancy is not due to the increase in corticosteroid-binding globulin levels. J. Clin. Endocrinol. Metab. 71, 639–644 (1990)

    Article  PubMed  CAS  Google Scholar 

  94. A.M. Maguire, G.R. Ambler, B. Moore, M. McLean, M.G. Falleti, C.T. Cowell, Prolonged hypocortisolemia in hydrocortisone replacement regimens in adrenocorticotrophic hormone deficiency. Pediatrics 120, e164–e171 (2007)

    Article  PubMed  Google Scholar 

  95. V. Wong, T. Yan, A. Donald, M. McLean, Saliva and bloodspot cortisol: novel sampling methods to assess hydrocortisone replacement therapy in hypoadrenal patients. Clin. Endocrinol. (Oxf.) 61, 131–137 (2004)

    Article  CAS  Google Scholar 

  96. K. Lovås, T.E. Thorsten, E.S. Husebye, Saliva cortisol measurement: simple and reliable assessment of the glucocorticoid replacement therapy in Addison’s disease. J. Endocrinol. Invest. 29, 727–731 (2006)

    PubMed  Google Scholar 

  97. K. Lovås, E.S. Husebye, Continuous subcutaneous hydrocortisone infusion in Addison’s disease. Eur. J. Endocrinol. 157, 109–112 (2007)

    Article  PubMed  CAS  Google Scholar 

  98. P. Restituto, J.C. Galofre, M.J. Gil, C. Mugueta, S. Santos et al., Advantage of salivary cortisol measurements in the diagnosis of glucocorticoid related disorders. Clin. Biochem. 41, 688–692 (2008)

    Article  PubMed  CAS  Google Scholar 

  99. E. Badrick, C. Kirschbaum, M. Kumari, A. Steptoe, K. O’Donnell, M. Marmot, The relationship between smokling status and cortisol secretion. J. Clin. Endocrinol. Metab. 92, 819–824 (2007)

    Article  PubMed  CAS  Google Scholar 

  100. A.M. Hansen, A.H. Garde, R. Persson, Sources of biological and methodological variation in salivary cortisol and their impact on measurement among healthy adults: a review. Scand. J. Clin. Lab. Invest. 68, 448–458 (2008)

    Article  PubMed  CAS  Google Scholar 

  101. J. Vialard-Miguel, N. Belaidi, L. Lembeye, J.B. Corcuff, Lemon juice alters cortisol assays in saliva. Clin. Endocrinol. (Oxf.) 63, 478–479 (2005)

    Article  Google Scholar 

  102. M. Groschl, R. Wagner, M. Rauh, H.G. Dorr, Stability of salivary steroids: the influences of storage, food and dental care. Steroids 66, 737–741 (2001)

    Article  PubMed  CAS  Google Scholar 

  103. M.C. Garcia, A. de Souza, G.P. Bella, D.M. Grassi-Kassisse, A.P. Tacla, R.C. Sapadari-Bratfisch, Salivary cortisol levels in Brazilian citizens of distintc socioeconomic and cultural levels. Ann.N.Y.Acad.Sci. 1148, 504–508 (2008)

    Article  PubMed  CAS  Google Scholar 

  104. G.L. Brown, E.L. McGarvey, E.A. Schirtcliff, A. Keller, D.A. Granger, K. Flavin, Salivary cortisol, dehydroepiandrosterone, and testosterone interrelationships in healthy young males: a pilot study with implications for studies of aggressive behavior. Psychistry Res. 159, 67–76 (2008)

    Article  CAS  Google Scholar 

  105. S. Hahner, M. Loeefler, 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  PubMed  CAS  Google Scholar 

  106. K. White, W. Arlt, Adrenal crisis in treated Addison’s disease: a predictable but under-managed event. Eur. J. Endocrinol. 162, 115–120 (2010)

    Article  PubMed  CAS  Google Scholar 

  107. A.J. Chakera, B. Vaidya, Addison’s disease in adults: diagnosis and management. Am. J. Medicine 123, 409–413 (2010)

    Article  Google Scholar 

  108. W. Oelkers, Mineralocorticoid substitution in pregnant Addisonian women. J. Endocrinol. Invest. 27, 406 (2004)

    PubMed  CAS  Google Scholar 

  109. P. Methlie, E.E. Husebye, S. Hustad, E.A. Lien, K. Løvås, Grapefruit juice and licorice increase cortisol availability in patients with Addison’s disease. Eur. J. Endocrinol. 165, 761–769 (2011)

    Article  PubMed  CAS  Google Scholar 

  110. H. Cooper, B. Bhattacharya, V. Verma, A.J. McCulloch, W.S. Smellie, A.H. Heald, Liquorice and soy sauce, a life-saving concoction in a patient with Addison’s disease. Ann. Clin. Biochem. 44, 397–399 (2007)

    Article  PubMed  CAS  Google Scholar 

  111. B. Ambrosi, L. Barbetta, L. Morricone, Diagnosis and management of Addison’s disease during pregnancy. J. Endocrinol. Invest. 26, 698–702 (2003)

    PubMed  CAS  Google Scholar 

  112. E. Barrett-Connor, K.T. Khaw, S.S.C. Yen, A prospective study of dehydroepiandrosterone sulfate, mortality and cardiovascular disease. N. Engl. J. Med. 315, 1519–1524 (1986)

    Article  PubMed  CAS  Google Scholar 

  113. P. Ebeling, V.A. Kiovisto, Physiological importance of dehydroepiandrosterone. Lancet 343, 1479–1481 (1994)

    Article  PubMed  CAS  Google Scholar 

  114. P. Sambrook, J. Birmingham, D. Champion, P. Kelly, S. Kempler, J. Freund, J. Eisman, Postmenopausal bone loss in rheumatoid arthritis: effect of estrogens and androgens. J. Rheumatol. 19, 357–361 (1992)

    PubMed  CAS  Google Scholar 

  115. R. Libè, L. Barbetta, C. Dall’Asta, F. Salvaggio, C. Gala, P. Beck-Peccoz, B. Ambrosi, Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism. J. Endocrinol. Invest. 27, 736–741 (2004)

    PubMed  Google Scholar 

  116. W. Arlt, F. Callies, J.C. van Vlijmen, I. Koehler, M. Reincke, M. Bidlingmaier, D. Huebler, M. Oettel, M. Ernst, H.M. Schulte, B. Allolio, Dehydroepiandrosterone replacement in women with adrenal insufficiency. N. Engl. J. Med. 341, 1013–1020 (1999)

    Article  PubMed  CAS  Google Scholar 

  117. P.J. Hunt, E.M. Gurnell, F.A. Huppert, C. Richards, A.T. Prevost, J.A. Wass, J. Herbert, V.K. Chatterjee, Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial. J. Clin. Endocrinol. Metab. 85, 4650–4656 (2000)

    Article  PubMed  CAS  Google Scholar 

  118. E.M. Gurnell, P.J. Hunt, S.E. Curran, C.L. Conway, E.M. Pullenayegum, F.A. Huppert, J.E. Compston, J. Herbert, V.K.K. Chatterjee, Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial. J. Clin. Endocrinol. Metab. 93, 400–409 (2008)

    Article  PubMed  CAS  Google Scholar 

  119. 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  PubMed  CAS  Google Scholar 

  120. 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. (Oxf.) 69, 697–704 (2008)

    Article  Google Scholar 

  121. 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  PubMed  CAS  Google Scholar 

  122. T. Rosén, B.A. Bengtsson, Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 336, 285–288 (1990)

    Article  PubMed  Google Scholar 

  123. J.W. Tomlinson, N. Holden, R.K. Hills, K. Wheatley, R.N. Clayton, A.S. Bates, M.C. Sheppard, P.M. Stewart, Association between premature mortality and hypopituitarism. West Midlands Propsective Hypopituitary Study Group. Lancet 357, 425–431 (2001)

    Article  PubMed  CAS  Google Scholar 

  124. J.L. Mills, L.B. Schonberger, D.K. Wysowski, P. Brown, S.J. Durako, C. Cox, F. Kong, J.E. Fradkin, Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients. J. Pediatr. 144, 430–436 (2004)

    Article  PubMed  CAS  Google Scholar 

  125. W.H. Ettinger, H.F. Klinefelter, P.O. Kwiterovitch, Effect of short-term, low-dose corticosteroids on plasma lipoprotein lipids. Atherosclerosis 63, 167–172 (1987)

    Article  PubMed  CAS  Google Scholar 

  126. H.K. Choi, J.D. Seeger, Glucocorticoid use and serum lipid levels in US adults: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 53, 528–535 (2005)

    Article  PubMed  CAS  Google Scholar 

  127. A.K. McDonough, J.R. Curtis, K.G. Saag, The epidemiology of glucocorticoid-associated adverse events. Curr. Opin. Rheumatol. 20, 131–137 (2008)

    Article  PubMed  Google Scholar 

  128. I. Karp, M. Abrahamowicz, P.R. Fortin, L. Pilote, C. Neville, C. Pineau et al., Recent corticosteroid use and recent disease activity: independent determinants of coronary heart disease risk factors in systemic lupus erythematosus? Arthritis Rheum. 59, 169–175 (2008)

    Article  PubMed  CAS  Google Scholar 

  129. D.H. van Raalte, D.M. Ouwens, M. Diamant, Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options? Eur. J. Clin. Invest. 39, 81–93 (2009)

    Article  PubMed  CAS  Google Scholar 

  130. K. Walker-Bone, Recognizing and treating secondary osteoporosis. Nat. Rev. Rheumatol. 8, 480–492 (2012)

    Article  PubMed  CAS  Google Scholar 

  131. G.P. Rossi, T.M. Seccia, C. Maniero, A.C. Pessina, Drug-related hypertension and resistance to antihypertensive treatment: a call for action. J. Hypertens. 29, 2295–2309 (2011)

    Article  PubMed  CAS  Google Scholar 

  132. J.L. Beaudry, M.C. Riddell, Effects of glucocorticoids and exercise on pancreatic β cell function and diabetes development. Diabetes Metab. Res. Rev. doi:10.1002/dmrr.2310 (2012)

  133. M.N. Nanjee, N.E. Miller, Plasma lipoproteins and adrenocortical hormones in men—positive association of low density lipoprotein cholesterol with plasma cortisol concentration. Clin. Chim. Acta 180, 113–120 (1989)

    Article  PubMed  CAS  Google Scholar 

  134. K.A. al-Shoumer, K.H. Cox, C.L. Hughes, W. Richmond, D.G. Johnston, Fasting and postprandial lipid abnormalities in hypopituitary women receiving conventional replacement therapy. J.Clin.Endocrinol.Metab. 82, 2653–2659 (1997)

    Article  PubMed  CAS  Google Scholar 

  135. V. Markussis, S.A. Beshyah, C. Fisher, P. Sharp, A.N. Nicolaides, D.G. Johnston, Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. Lancet 340, 1188–1192 (1992)

    Article  PubMed  CAS  Google Scholar 

  136. 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)

    PubMed  CAS  Google Scholar 

  137. R. Giordano, S. Marzotti, R. Berardelli, I. Karamouzis, A. Brozzetti, V. D’Angelo, G. Mengozzi, G. Mandrile, D. Giachino, G. Migliaretti, V. Bini, A. Falorni, E. Ghigo, E. Arvat, BCLI polymorphism of the glucocorticoid receptor gene is associated with increased obesity, impaired glucose metabolism and dyslipidemia in patients with Addison’s disease. Clin. Endocrinol. (Oxf.). doi:10.1111/j.1365-2265.2012.04439.x (2012)

  138. J.P. Devogelaer, J. Crabbé, C. Nagant de Deuxchaisnes, Bone mineral density in Addison’s disease: evidence for an effect of adrenal androgens on bone mass. Br. Med. J. (Clin. Res. Ed.) 294, 798–800 (1987)

  139. P.M. Zelissen, R.J. Croughs, P.P. van Rijk, J.A. Raymakers, Effect of glucocorticoid replacement therapy on bone mineral density in patients with Addison disease. Ann. Intern. Med. 120, 207–210 (1994)

    Article  PubMed  CAS  Google Scholar 

  140. C.M. Florkowski, S.J. Holmes, J.R. Elliot, R.A. Donald, E.A. Espiner, Bone mineral density is reduced in female but not male subjects with Addison’s disease. N. Z. Med. J. 107, 52–53 (1994)

    PubMed  CAS  Google Scholar 

  141. M.A. Valero, M. Leon, M.P. Ruiz Valdepeñas, L. Larrodera, M.B. Lopez, K. Papapietro, A. Jara, F. Hawkins, Bone density and turnover in Addison’s disease: effect of glucocorticoid treatment. Bone Miner. 26, 9–17 (1994)

    Article  PubMed  CAS  Google Scholar 

  142. S.R. Peacey, C.Y. Guo, A.M. Robinson, A. Price, M.A. Giles, R. Eastell, A.P. Weetman, Glucocorticoid replacement therapy: are patients over treated and does it matter? Clin. Endocrinol. (Oxf.) 46, 255–261 (1997)

    Article  CAS  Google Scholar 

  143. G.D. Braatvedt, M. Joyce, M. Evans, J. Clearwater, I.R. Reid, Bone mineral density in patients with treated Addison’s disease. Osteoporos. Int. 10, 435–440 (1999)

    Article  PubMed  CAS  Google Scholar 

  144. E. Jódar, M.P. Valdepeñas, G. Martinez, A. Jara, F. Hawkins, Long-term follow-up of bone mineral density in Addison’s disease. Clin. Endocrinol. (Oxf.) 58, 617–620 (2003)

    Article  Google Scholar 

  145. N. Chikada, T. Imaki, M. Hotta, K. Sato, K. Takano, An assessment of bone mineral density in patients with Addison’s disease and isolated ACTH deficiency treated with glucocorticoid. Endocr. J. 51, 355–360 (2004)

    Article  PubMed  CAS  Google Scholar 

  146. G. Bassotti, D. Di Sarra, D. Pietrobono, R. Schiaffini, T. Battocletti, T. D’Amico, P. Gargiulo, Polyglandular autoimmune endocrine insufficiency complicated by severe osteoporosis. Minerva Endocrinol. 31, 289–296 (2006)

    PubMed  CAS  Google Scholar 

  147. 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  PubMed  CAS  Google Scholar 

  148. K. Løvås, C.G. Gjesdal, M. Christensen, A.B. Wolff, B. Almås, J. Svartberg, K.J. Fougner, U. Syversen, J. Bollerslev, J.A. Falch, P.J. Hunt, V.K. Chatterjee, E.S. Husebye, Glucocorticoid replacement therapy and pharmacogenetics in Addison’s disease: effects on bone. Eur. J. Endocrinol. 160, 993–1002 (2009)

    Article  PubMed  CAS  Google Scholar 

  149. S. Björnsdottir, M. Sääf, S. Bensing, O. Kämpe, K. Michaëlsson, J.F. Ludvigsson, Risk of hip fracture in Addison’s disease: a population-based cohort study. J. Intern. Med. 270, 187–195 (2011)

    Article  PubMed  Google Scholar 

  150. K.R. Koetz, M. Ventz, S. Diederich, M. Quinkler, Bone mineral density is not significantly reduced in adult patients on low-dose glucocorticoid replacement therapy. J. Clin. Endocrinol. Metab. 97, 85–92 (2012)

    Article  PubMed  CAS  Google Scholar 

  151. G. Mazziotti, T. Porcelli, A. Bianchi, V. Cimino, I. Patelli, C. Mejia, A. Fusco, A. Giampietro, L. De Marinis, A. Giustina, Glucocorticoid replacement therapy and vertebral fractures in hypopituitary adult males with GH deficiency. Eur. J. Endocrinol. 163, 15–20 (2010)

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  153. S. Hahner, M. Loeffler, M. Fassnacht, D. Weismann, A.C. Koschker, M. Quinkler et al., 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  PubMed  CAS  Google Scholar 

  154. 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  PubMed  CAS  Google Scholar 

  155. 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  CAS  Google Scholar 

  156. 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. Løvås, 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  CAS  Google Scholar 

  157. 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  PubMed  CAS  Google Scholar 

  158. M. Debono, C. Ghobadi, A. Rostami-Hodjegan, H. Huatan, M.J. Campbell, J. Newell-Price, K. Darzy, D.P. Merke, W. Arlt, R.J. Ross, Modified-release hydrocortisone to provide circadian cortisol profiles. J. Clin. Endocrinol. Metab. 94, 1548–1554 (2009)

    Article  PubMed  CAS  Google Scholar 

  159. S. Verma, C. Vanryzin, N. Sinaii, M.S. Kim, L.K. Nieman, S. Ravindran, K.A. Calis, W. Arlt, R.J. Ross, D.P. Merke, A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (Chronocort) vs. conventional hydrocortysone (Cortef) in the treatment of congenital adrenal hyperplasia. Clin. Endocrinol. (Oxf.) 72, 441–447 (2010)

    Google Scholar 

  160. E.M. McConnell, P.M. Bell, C. Ennis, D.R. Hadden, D.R. McCance, B. Sheridan, A.B. Atkinson, Effects of low-dose oral hydrocortisone replacement versus short-term reproduction of physiological serum cortisol concentrations on insulin action in adult-onset hypopituitarism. Clin. Endocrinol. (Oxf.) 56, 195–201 (2002)

    Article  CAS  Google Scholar 

  161. D. Garcia-Borreguero, T.A. Wehr, O. Larrosa, J.J. Granizo, D. Hardwick, G.P. Chrousos, T.C. Friedman, Glucocorticoid replacement is permissive for rapid eye movement sleep and sleep consolidation in patients with adrenal insufficiency. J. Clin. Endocrinol. Metab. 85, 4201–4206 (2000)

    Article  PubMed  CAS  Google Scholar 

  162. 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  PubMed  CAS  Google Scholar 

  163. G. Johansson, A.G. Nilsson, R. Bergthorsdottir, P. Burman, P. Dahlqvist, B. Ekman, B.E. Engstrom, T. Olsson, O. Ragnarsson, M. Ryberg, J. Wahlberg, B.M.K. Biller, J.P. Monson, P.M. Stewart, H. Lennernas, 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  Google Scholar 

  164. A.J. Coles, S. Thompson, A.L. Cox, S. Curran, E.M. Gurnell, V.K. Chatterjee, Dehydroepiandrosterone replacement in patients with Addison’s disease has a bimodal effect on regulatory (CD4 + CD25hi and CD4 + FoxP3 +) T cells. Eur. J. Immunol. 35, 3694–3703 (2005)

    Article  PubMed  CAS  Google Scholar 

  165. S.H. Pearce, A.L. Mitchell, S. Bennett, P. King, S. Chandran, S. Nag, S. Chen, B.R. Smith, J.D. Isaacs, B. Vaidya, Adrenal steroidogenesis after b lymphocyte depletion therapy in new-onset Addison’s disease. J. Clin. Endocrinol. Metab. (2012). [Epub ahead of print]

  166. A. De Bellis, A. Falorni, S. Laureti et al., Time course of 21-hydroxylase antibodies and long-term remission of subclinical autoimmune adrenalitis after corticosteroid therapy: case report. J. Clin. Endocrinol. Metab. 86, 675–678 (2001)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Via E. Dal Pozzo, Perugia, 06126, Italy

    Alberto Falorni, Viviana Minarelli & Silvia Morelli

Authors
  1. Alberto Falorni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Viviana Minarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvia Morelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alberto Falorni.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Falorni, A., Minarelli, V. & Morelli, S. Therapy of adrenal insufficiency: an update. Endocrine 43, 514–528 (2013). https://doi.org/10.1007/s12020-012-9835-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-012-9835-4

Keywords

Search

Navigation