Therapy of adrenal insufficiency: an update

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.

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

“…Indeed, traditional synthetic glucocorticoids did not fully mimic physiological circadian cortisol rhythm, as serum cortisol levels were abundantly above the expected physiological levels right after tablet intake, with a rapid decrease in the following hours, often reaching undetectable levels [4,15].…”

Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy

“…Doubling or tripling of the daily dose, depending on the degree of stress, is recommended. 70 Subjective health status was significantly reduced compared with sex-and age-matched controls in a cross-sectional study of a large cohort of 427 patients with PAI (n = 232) or SAI (n = 195) in Germany, irrespective of whether individuals were treated with hydrocortisone, prednisolone or cortisone acetate. 71 A subsequent cross-sectional study of patients with PAI (n = 194) or SAI (n = 140) showed that those receiving daily doses of hydrocortisone of 30 mg or higher had significantly (P < 0Á05) impaired subjective health status according to two of eight dimensions of the Short-Form 36 health questionnaire ('general health perceptions' and 'role functioning physical') and in three of five Giessen Subjective Complaints List-24 scales ('gastric', 'heart' and 'global symptom' scores) compared with those receiving lower hydrocortisone doses.…”

“…The glucocorticoid doses should be increased in stressful situations, such as high body temperature, trauma, surgery and during any intercurrent illness. Doubling or tripling of the daily dose, depending on the degree of stress, is recommended …”

Delay in Diagnosis of Adrenal Insufficiency Is a Frequent Cause of Adrenal Crisis

“…It consists mainly in supplementing the deficient glucocorticoids and mineralocorticoids, which brings about a prompt and spectacular improvement [11, 12]. However, the lack of the proper diagnosis of adrenal insufficiency can have tragic sequel since this pathology leads to adrenal crisis and, if not treated with parenterally administered glucocorticoids, is lethal.…”