What are the treatment differences between Addison's disease and Cushing's syndrome?

Treatment Differences Between Addison's Disease and Cushing's Syndrome

The fundamental treatment difference between Addison's disease and Cushing's syndrome is that Addison's disease requires lifelong hormone replacement therapy (glucocorticoids and mineralocorticoids), while Cushing's syndrome treatment focuses on reducing excess cortisol through surgery, medication, or radiation depending on the cause.

Addison's Disease (Primary Adrenal Insufficiency) Treatment

Glucocorticoid Replacement

• The preferred glucocorticoid treatment is hydrocortisone (HC) or cortisone acetate (CA), typically given in divided doses to mimic the natural circadian rhythm 1
• Standard starting doses are 15-25 mg/day of hydrocortisone or 20-30 mg/day of cortisone acetate, divided into 2-3 doses with the largest dose in the morning 1, 2
• Dosing schedule typically involves first dose upon awakening and last dose 4-6 hours before bedtime to avoid insomnia 1
• Monitoring is primarily clinical, as plasma ACTH and serum cortisol are not useful parameters for dose adjustment 1
• Signs of over-replacement include weight gain, insomnia, and peripheral edema, while under-replacement presents with lethargy, nausea, poor appetite, weight loss, and increased pigmentation 1

Mineralocorticoid Replacement

• Fludrocortisone (0.05-0.2 mg once daily) is required to replace aldosterone deficiency 2, 3
• Sodium chloride supplementation is often needed to compensate for increased renal sodium loss 1

Patient Education and Emergency Management

• Patients must be educated on increasing steroid doses during illness or injury and trained in intramuscular hydrocortisone administration during adrenal crisis 1
• All patients should wear a Medic Alert bracelet and carry a steroid card to inform medical personnel of their condition 1
• Immediate administration of hydrocortisone is critical in emergency situations to prevent mortality 1

Emerging Therapies

• Timed-release hydrocortisone tablets and continuous subcutaneous hydrocortisone infusion are promising new treatment modalities that better mimic physiological cortisol patterns 2, 4, 5
• Continuous subcutaneous hydrocortisone infusion can restore normal circadian variation of cortisol at a lower total daily dose (approximately 10 mg/m² body surface area/day) 5

Cushing's Syndrome Treatment

Treatment Based on Etiology

• Treatment approach depends on whether the cause is ACTH-dependent (pituitary or ectopic source) or ACTH-independent (adrenal) 1

ACTH-Dependent Cushing's Syndrome

• For pituitary tumors (Cushing's disease): surgical removal of the tumor is first-line treatment 1
• For ectopic ACTH-producing tumors: surgical removal of the tumor when possible 1
• If the primary tumor is unresectable, options include bilateral laparoscopic adrenalectomy or medical management 1
• Octreotide may be considered for ectopic Cushing's syndrome if the tumor is Octreoscan-positive, though it may be less effective in controlling ACTH secretion 1

ACTH-Independent Cushing's Syndrome

• For benign adrenal tumors: laparoscopic adrenalectomy with postoperative corticosteroid supplementation until HPA axis recovery 1
• For malignant adrenal tumors: open adrenalectomy with imaging to evaluate for metastases 1
• For bilateral multinodular hyperplasia: treatment depends on cortisol production symmetry - asymmetric production warrants unilateral adrenalectomy of the most active side, while symmetric production requires medical management 1

Medical Management

• Adrenostatic agents including ketoconazole (400-1200 mg/day) and mitotane are used to manage hypercortisolism 1
• Ketoconazole is most commonly used due to its availability and relatively tolerable toxicity profile 1
• Symptomatic management of complications like hypertension, hyperglycemia, hypokalemia, and muscle atrophy may be required 1

Key Differences in Monitoring and Follow-up

Addison's Disease

• Regular clinical assessment focusing on energy levels, mental concentration, pigmentation changes, and weight 1
• Annual monitoring should include serum sodium and potassium, thyroid function tests, plasma glucose, HbA1c, complete blood count, and vitamin B12 levels 6
• Dose adjustments based primarily on clinical symptoms rather than laboratory values 1

Cushing's Syndrome

• Monitoring depends on treatment approach but focuses on normalization of cortisol levels 1
• Post-surgical patients require monitoring for adrenal insufficiency and may need temporary glucocorticoid replacement 1
• Patients on medical therapy require monitoring of drug levels and side effects 1

Common Pitfalls and Caveats

• In Addison's disease, delaying hydrocortisone administration during emergencies can be fatal - treatment should never be delayed for diagnostic testing 6
• In Cushing's syndrome, malignancy should be suspected if the adrenal tumor is larger than 5 cm, has irregular margins, or shows local invasion 1
• Patients with treated Cushing's syndrome often require temporary glucocorticoid replacement after tumor removal until HPA axis recovery 1
• CYP3A4 is the key enzyme affecting hydrocortisone clearance, and concomitant medications can affect efficacy in Addison's disease patients 1