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Therapeutic management of adrenal insufficiency

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Replacement therapy in adrenal insufficiency comprises treatment with glucocorticoids, mineralocorticoids and adrenal androgen precursors. Initiation of hormone replacement therapy in newly diagnosed adrenal insufficiency leads to rapid and impressive improvements. However, despite the use of established replacement concepts, well-being is often not fully restored in patients with adrenal insufficiency, and life expectancy may even be reduced. This has led to a reconsideration of current replacement strategies. Several studies demonstrate that addition of dehydroepiandrosterone (DHEA) to the treatment regimen may lead to further improvement of general well-being and also sexual function. However, long-term trials with DHEA are still lacking, and DHEA alone is not able to restore subjective health status to normal. Further innovations comprise the development of delayed-release glucocorticoid preparations that better allow mimicking of circadian cortisol secretion and may have the potential to significantly improve the treatment of patients with adrenal insufficiency. However, future studies have to prove the clinical importance of physiological cortisol day profiles. To date, no relevant risk factors for susceptibility to adrenal crisis are known, and patient education is key for a successful prevention strategy. In our experience the well-educated patient often guides the physician not familiar with this disease.

Section snippets

Glucocorticoid replacement

In the 1930s lipid extracts from adrenal glands were introduced for the treatment of adrenal insufficiency, and the mortality rapidly dropped from 100% to a seemingly normal life expectancy. The synthesis of 11-deoxycortisone (11-DOC) in 1937 and cortisone in 1949 represented major improvements in therapy. However, since the introduction of fludrocortisone for mineralocorticoid replacement in the 1950s, the treatment regimens remained almost unchanged (Table 1).

Adrenocorticotropic hormone

Prevention and management of adrenal crisis

During stressful events adrenal glucocorticoid production rate can rapidly rise to up to six times normal levels. Acute adrenal insufficiency is a rare but life-threatening condition that develops as a result of inadequate adrenal steroid production not matching increased demands during stress (e.g. during infection). Early diagnosis is the key for effective and life-saving treatment of affected patients. In our series of 444 patients with chronic primary or secondary adrenal insufficiency, 42%

Summary

Initiation of hormone replacement therapy in newly diagnosed adrenal insufficiency leads to impressive and rapid improvements. However, current long-term standard mineralocorticoid and glucocorticoid treatment regimens fail to fully restore well-being and life expectancy to normal in many patients. Several studies suggest that the addition of DHEA may further improve well-being, particularly in women. However, large long-term trials with DHEA are still lacking, and DHEA is therefore not yet

References (64)

  • A. Krazeisen et al.

    Determination of cDNA, gene structure and chromosomal localization of the novel human 17beta-hydroxysteroid dehydrogenase type 7(1)

    FEBS Letters

    (1999)
  • F. Callies et al.

    Influence of oral dehydroepiandrosterone (DHEA) on urinary steroid metabolites in males and females

    Steroids

    (2000)
  • M.D. Majewska et al.

    The neurosteroid dehydroepiandrosterone sulfate is an allosteric antagonist of the GABAA receptor

    Brain Research

    (1990)
  • D. Liu et al.

    Dehydroepiandrosterone activates endothelial cell nitric-oxide synthase by a specific plasma membrane receptor coupled to Galpha(i2,3)

    The Journal of Biological Chemistry

    (2002)
  • S.S. Kim et al.

    Dehydroepiandrosterone replacement in addison's disease

    European Journal of Obstetrics, Gynecology, and Reproductive Biology

    (2001)
  • C. Henzen et al.

    Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment

    Lancet

    (2000)
  • K. Lovas et al.

    Subjective health status in Norwegian patients with Addison's disease

    Clinical Endocrinology

    (2002)
  • S. Hahner et al.

    Impaired subjective health status in 256 patients with adrenal insufficiency on standard therapy based on cross-sectional analysis

    The Journal of Clinical Endocrinology and Metabolism

    (2007)
  • R. Bergthorsdottir et al.

    Premature mortality in patients with Addison's disease: a population-based study

    The Journal of Clinical Endocrinology and Metabolism

    (2006)
  • J.R. Kerrigan et al.

    Estimation of daily cortisol production and clearance rates in normal pubertal males by deconvolution analysis

    The Journal of Clinical Endocrinology and Metabolism

    (1993)
  • G.P. Kraan et al.

    The daily cortisol production reinvestigated in healthy men. The serum and urinary cortisol production rates are not significantly different

    The Journal of Clinical Endocrinology and Metabolism

    (1998)
  • L. Barbetta et al.

    Comparison of different regimens of glucocorticoid replacement therapy in patients with hypoadrenalism

    Journal of Endocrinological Investigation

    (2005)
  • N. Alonso et al.

    Evaluation of two replacement regimens in primary adrenal insufficiency patients. effect on clinical symptoms, health-related quality of life and biochemical parameters

    Journal of Endocrinological Investigation

    (2004)
  • S. Laureti et al.

    Improvement of treatment of primary adrenal insufficiency by administration of cortisone acetate in three daily doses

    Journal of Endocrinological Investigation

    (2003)
  • S.R. Peacey et al.

    Glucocorticoid replacement therapy: are patients over treated and does it matter?

    Clinical Endocrinology

    (1997)
  • T.A. Howlett

    An assessment of optimal hydrocortisone replacement therapy

    Clinical Endocrinology

    (1997)
  • P.M. Mah et al.

    Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency

    Clinical Endocrinology

    (2004)
  • W. Arlt et al.

    Quality of glucocorticoid replacement in adrenal insufficiency: clinical assessment vs. timed serum cortisol measurements

    Clinical Endocrinology

    (2006)
  • K. Lovas et al.

    Continuous subcutaneous hydrocortisone infusion in Addison's disease

    European Journal of Endocrinology

    (2007)
  • J. Newell-Price et al.

    Modified-release hydrocortisone for circadian therapy: a proof-of-principle study in dexamethasone-suppressed normal volunteers

    Clinical Endocrinology

    (2008)
  • G. Johannsson et al.

    Long-acting hydrocortisone for glucocorticoid replacement therapy

    Hormone Research

    (2007)
  • W. Oelkers et al.

    Diagnosis and therapy surveillance in Addison's disease: rapid adrenocorticotropin (ACTH) test and measurement of plasma ACTH, renin activity, and aldosterone

    The Journal of Clinical Endocrinology and Metabolism

    (1992)
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