Replacement therapy for Addison's disease: recent developments.
BACKGROUND
The hormone deficiencies in Addison's disease (primary adrenal insufficiency) are conventionally treated with oral glucocorticoid and mineralocorticoid replacement but the available therapies do not restore the physiological hormone levels and biorhythm. Despite such treatment these patients self-report impaired health-related quality of life (HRQoL) and recent research has indicated increased mortality.


OBJECTIVE
We review the literature and recent developments in replacement therapy.


CONCLUSIONS
Patients with Addison's disease require mineralocorticoid replacement, i.e., fludrocortisone 0.05 - 0.20 mg once daily. Starting doses of glucocorticoids should be 15 - 20 mg for hydrocortisone or 20 - 30 mg for cortisone acetate, divided into two or three doses, and preferentially weight-adjusted. There are indications that the synthetic glucocorticoids have undesirable metabolic long-term effects, which make them less suitable as first-line treatment. Timed-release hydrocortisone tablets and continuous subcutaneous hydrocortisone infusion are promising new treatment modalities. Studies of replacement with the adrenal androgen dehydroepiandrosterone (DHEA) in adrenal failure have shown inconsistent benefit on HRQoL. DHEA, or possibly testosterone replacement is likely to be beneficial for selected groups of patients with Addison's disease but this remains to be shown. We here give our opinion of the best treatment and future direction of research in this area.
Løvås
Kristian
K
University of Bergen, Institute of Medicine, Section of Endocrinology, 5021 Bergen, Norway. Kristian.lovas@helse-bergen.no
Husebye
Eystein S
ES
D000224:Addison Disease / Q000097:blood / Q000188:drug therapy*; D000728:Androgens / Q000008:administration & dosage* / Q000627:therapeutic use; D004304:Dosage Forms; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000172:deficiency; D020249:Hormone Replacement Therapy; D006801:Humans; D008901:Mineralocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000172:deficiency; D011788:Quality of Life; D016896:Treatment Outcome
D000728:Androgens; D004304:Dosage Forms; D005938:Glucocorticoids; D008901:Mineralocorticoids