What are the diagnostic steps and treatment for Addison's disease?

From the Guidelines

Diagnosing Addison's disease requires a stepwise approach beginning with clinical suspicion based on symptoms like fatigue, weight loss, salt craving, hyperpigmentation, and hypotension, followed by confirmatory testing with an ACTH stimulation test (Synacthen test) as recommended by the consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency 1. The diagnostic steps for Addison's disease include:

• Measuring morning cortisol and ACTH levels
• Confirmatory testing with an ACTH stimulation test (Synacthen test), where synthetic ACTH is administered and cortisol response is measured, with a normal response being a cortisol level above 550 nmol L1 after 30 and/or 60 min 1
• Measuring aldosterone levels, renin activity, and adrenal antibodies to determine the cause
• Imaging studies such as CT or MRI of the adrenal glands may be performed to identify structural abnormalities Treatment consists of lifelong hormone replacement therapy with glucocorticoids (typically hydrocortisone 15-25 mg daily divided into 2-3 doses) and mineralocorticoids (fludrocortisone 0.05-0.2 mg daily) as outlined in the consensus statement 1. Some key points to consider in the treatment of Addison's disease include:
• The preferred choice of glucocorticoid treatment is hydrocortisone (HC) or cortisone acetate (CA), with no studies showing one to be superior to the other 1
• Patients must carry emergency identification and be educated about stress dosing during illness or surgery, typically tripling their glucocorticoid dose during significant stress, with specific guidelines for different procedures outlined in Table 6 1
• Regular monitoring of electrolytes, blood pressure, and clinical symptoms is essential to adjust medication dosages, with plasma ACTH and serum cortisol not being useful parameters for glucocorticoid dose adjustment 1
• Patients should also be educated about the risk of adrenal crisis, which requires immediate treatment with injectable hydrocortisone (100 mg) and intravenous fluids, with a frequency of acute adrenal crises among patients with PAI being 6–8 per 100 patient-years 1

From the FDA Drug Label

DOSAGE & ADMINISTRATION Dosage depends on the severity of the disease and the response of the patient. Patients should be continually monitored for signs that indicate dosage adjustment is necessary, such as remission or exacerbations of the disease and stress (surgery, infection, trauma) 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.

The diagnostic steps for Addison's disease are not directly mentioned in the provided drug labels. However, the treatment for Addison's disease involves substitution therapy with a combination of:

• Fludrocortisone acetate tablets (0.1 mg daily, although dosage may range from 0.1 mg three times a week to 0.2 mg daily)
• A glucocorticoid such as hydrocortisone (10 mg to 30 mg daily in divided doses) or cortisone (10 mg to 37.5 mg daily in divided doses) 2. The treatment is indicated for primary and secondary adrenocortical insufficiency in Addison’s disease 2.

From the Research

Diagnostic Steps for Addison's Disease

• The diagnosis of Addison's disease can be made by measuring morning cortisol concentrations, with values of >350 nmol/l considered to safely rule out the disease 3
• Elevated corticotropin concentrations (>300 pg/ml) are indicative of primary adrenal insufficiency when cortisol levels are below 140 nmol/l (5 μg/dl) 3
• A cosyntropin stimulation test can be used to confirm the diagnosis of primary adrenal insufficiency 4
• Single measurements of plasma cortisol, adrenocorticotropic hormone (ACTH), aldosterone, and plasma renin activity (PRA) can be used as a definitive diagnostic test for primary adrenocortical insufficiency (PAI) 5
• The rapid ACTH injection test is an indirect screening test for adrenocortical insufficiency, and can be used in conjunction with single hormone measurements to diagnose PAI 5

Treatment of Addison's Disease

• Treatment of primary adrenal insufficiency requires replacement of mineralocorticoids and glucocorticoids 4
• During times of stress, such as illness or invasive surgical procedures, stress-dose glucocorticoids are required 4
• Management of primary adrenal insufficiency or autoimmune adrenalitis requires vigilance for concomitant autoimmune diseases, as up to 50% of patients develop another autoimmune disorder during their lifetime 4
• Hydrocortisone is a common treatment for Addison's disease, and can be adjusted based on patient symptoms and laboratory results 3, 6
• Mineralocorticoid replacement therapy, such as fludrocortisone, can be guided by measurements of plasma renin activity (PRA) to avoid under- and overtreatment 5

Special Considerations

• Oral contraceptive pills (OCPs) containing ethinyl oestradiol (EE) may increase total cortisol levels and suppress the hypothalamic-pituitary-adrenal (HPA) axis in patients with Addison's disease, leading to reversible suppression of the HPA axis and insulin resistance 7
• Patients with Addison's disease may require adjustments to their treatment regimen when taking OCPs containing EE, and alternative contraceptive agents may be considered 7