What is Addison's disease, its etiologies, and treatment options?

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From the Guidelines

Addison's disease is a rare endocrine disorder that requires immediate attention and treatment to prevent life-threatening complications, and the primary treatment consists of hormone replacement therapy with glucocorticoids and mineralocorticoids. The primary etiologies of Addison's disease include autoimmune adrenalitis, tuberculosis, fungal infections, metastatic cancer, adrenal hemorrhage, and certain medications like ketoconazole or etomidate 1. Symptoms typically develop gradually and include fatigue, muscle weakness, weight loss, hyperpigmentation, salt craving, low blood pressure, and gastrointestinal disturbances.

Treatment and Management

The treatment of Addison's disease involves hormone replacement therapy with glucocorticoids, such as hydrocortisone, and mineralocorticoids, such as fludrocortisone 1. The preferred choice of glucocorticoid treatment is hydrocortisone or cortisone acetate, with no studies showing that one is superior to the other 1. Patients require lifelong treatment and must increase their glucocorticoid dose during times of illness, injury, or significant stress, typically doubling or tripling the dose for several days.

Dosage and Administration

The standard dose regimens for glucocorticoids are given in Table 3, with hydrocortisone available in 20,10, and 2.5 mg tablets, and cortisone acetate available in 25 and 5 mg tablets 1. The dosage is typically taken in two or three divided doses, with the first dose upon awakening and the last dose approximately 4-6 hours before bedtime.

Monitoring and Follow-up

Regular monitoring of electrolytes, blood pressure, and clinical symptoms is crucial to ensure adequate replacement therapy and prevent complications like adrenal crisis, which can be life-threatening if not promptly treated 1. Patient education is also essential, including the need to carry medical identification and emergency injectable hydrocortisone (100 mg) for adrenal crisis situations.

Special Considerations

During surgery, dental procedures, delivery, and invasive procedures, patients with primary adrenal insufficiency need to increase steroid doses according to the degree of stress induced, following the recommendations developed by the UK Addison’s disease self-help group and the physicians of the Addison’s disease clinical advisory panel (Table 6) 1. For example, during major surgery with long recovery time, patients should receive 100 mg hydrocortisone intramuscularly just before anesthesia, and continue 100 mg hydrocortisone intramuscularly every 6 hours until able to eat and drink, then double the oral dose for 48 hours, and then taper to the normal dose 1.

From the FDA Drug Label

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. Fludrocortisone acetate tablets, 0.1 mg are indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease

Addison's Disease is a condition characterized by primary or secondary adrenocortical insufficiency.

  • The etiology of Addison's disease is not explicitly stated in the provided drug labels, but it is mentioned that it involves adrenocortical insufficiency.
  • The treatment of Addison's disease involves substitution therapy with a combination of fludrocortisone acetate and a glucocorticoid such as hydrocortisone or cortisone, with the goal of approximating normal adrenal activity and minimizing unwanted effects 2.
  • The usual dose of fludrocortisone acetate for Addison's disease is 0.1 mg daily, although the dosage may range from 0.1 mg three times a week to 0.2 mg daily 2.

From the Research

Definition and Description of Addison's Disease

Addison's disease, also known as primary adrenal insufficiency, is a rare disorder characterized by the deficiency of glucocorticoid and mineralocorticoid hormones produced by the adrenal glands 3. The disease can present with a range of symptoms, including:

  • Orthostatic hypotension
  • Fever
  • Hypoglycemia
  • Malaise
  • Anorexia
  • Diarrhea
  • Weight loss
  • Joint and back pain
  • Darkening of the skin, especially in sun-exposed areas
  • Hyperpigmentation of the palmar creases, frictional surfaces, vermilion border, recent scars, genital skin, and oral mucosa

Etiologies of Addison's Disease

The exact cause of Addison's disease is not fully understood, but it is believed to result from the destruction of the adrenal cortex, which can be caused by various factors, including:

  • Autoimmune disorders
  • Infections, such as tuberculosis
  • Cancer
  • Genetic disorders
  • Trauma to the adrenal glands

Treatment of Addison's Disease

The treatment of Addison's disease involves replacing the deficient hormones with oral glucocorticoids and mineralocorticoids 4, 5. The typical treatment regimen includes:

  • Mineralocorticoid replacement with fludrocortisone, 0.05-0.20 mg once daily
  • Glucocorticoid replacement with hydrocortisone, 15-20 mg divided into two or three doses, or cortisone acetate, 20-30 mg divided into two or three doses
  • Timed-release hydrocortisone tablets and continuous subcutaneous hydrocortisone infusion are promising new treatment modalities
  • Replacement with the adrenal androgen dehydroepiandrosterone (DHEA) or testosterone may be beneficial for selected groups of patients, but this remains to be shown 4
  • The dose of fludrocortisone should be adjusted according to plasma-renin activity, with most patients requiring 0.2 mg to maintain adequate sodium and water balance 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Addison's disease.

Clinics in dermatology, 2006

Research

Replacement therapy for Addison's disease: recent developments.

Expert opinion on investigational drugs, 2008

Research

Current and emerging therapies for Addison's disease.

Current opinion in endocrinology, diabetes, and obesity, 2014

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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