From the Guidelines
Addison's disease should be treated with lifelong hormone replacement therapy, primarily with oral hydrocortisone (HC) or cortisone acetate (CA), with the preferred choice being either HC or CA, as no studies have shown one to be superior to the other 1. The treatment regimen typically involves administering HC or CA in two or three divided doses, with the first dose upon awakening and the last dose approximately 4–6 h before bedtime.
- The standard dose regimens for HC are 20 mg, 10 mg, and 2.5 mg, while for CA, they are 25 mg and 5 mg.
- Monitoring of glucocorticoid replacement predominantly relies on clinical assessment, including symptoms and signs of over-replacement, such as weight gain, insomnia, and peripheral oedema, and under-replacement, characterized by lethargy, nausea, poor appetite, weight loss, and increased pigmentation. Some key considerations in managing Addison's disease include:
- Concomitant administration of several drugs can affect HC efficacy, as shown in Table 4, highlighting the importance of careful medication management 1.
- Plasma ACTH and serum cortisol are not useful parameters for glucocorticoid dose adjustment, making clinical assessment crucial 1.
- In cases of suspected malabsorption, serum or salivary cortisol day curve monitoring may be useful to guide dosing, with morning, postdose peak level, and trough predose levels for subsequent dosages being the most useful in adjusting dose timings and quantities 1.
From the FDA Drug Label
INDICATIONS & USAGE Fludrocortisone acetate tablets, 0.1 mg are indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome. DOSAGE & ADMINISTRATION ... Addison's Disease In Addison’s disease, the combination of fludrocortisone acetate tablets with a glucocorticoid such as hydrocortisone or cortisone provides substitution therapy approximating normal adrenal activity with minimal risks of unwanted effects.
Addison's Disease Treatment: Fludrocortisone acetate tablets are indicated for partial replacement therapy in primary and secondary adrenocortical insufficiency in Addison’s disease. The usual dose is 0.1 mg daily, although dosage ranging from 0.1 mg three times a week to 0.2 mg daily has been employed, and should be administered in conjunction with a glucocorticoid such as hydrocortisone or cortisone 2 2.
From the Research
Definition and Causes of Addison's Disease
- Addison's disease, also known as primary adrenal insufficiency, is a rare disease caused by the deficiency of glucocorticoids and mineralocorticoids due to the destruction of the adrenal cortex 3, 4.
- The most common cause of Addison's disease is autoimmune adrenalitis, which results from the destruction of the adrenal cortex 4.
Symptoms and Diagnosis of Addison's Disease
- The clinical manifestations of Addison's disease include hyperpigmentation, fatigue, anorexia, orthostasis, nausea, muscle and joint pain, and salt craving 3, 4.
- The diagnosis of Addison's disease is confirmed by a cosyntropin stimulation test, which measures the levels of cortisol and adrenocorticotropic hormone (ACTH) 4.
- Measurement of basal plasma cortisol is an insensitive screening test, while synthetic adrenocorticotropin 1-24 can be used as a dynamic test 3.
Treatment and Management of Addison's Disease
- The treatment of Addison's disease involves replacement of the deficient hormones, including mineralocorticoids and glucocorticoids 5, 6, 4, 7.
- The recommended daily starting dose for hydrocortisone is 15-20 mg, divided into two or three doses, while the recommended dose for fludrocortisone is 0.05-0.20 mg once daily 5, 7.
- During times of stress, stress-dose glucocorticoids are required to prevent an inadequate physiologic response 4.
- New treatment modalities, such as modified-released hydrocortisone and continuous subcutaneous hydrocortisone infusion, have been developed to simulate the physiological serum cortisol rhythm more closely 5, 6.