What is adrenal insufficiency (Addison's disease)?

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From the Guidelines

Adrenal insufficiency is a condition where the adrenal glands don't produce enough steroid hormones, particularly cortisol and sometimes aldosterone, and it is most commonly caused by prescribed glucocorticoid therapy, which can suppress the hypothalamo–pituitary–adrenal axis. It comes in two main forms: primary (Addison's disease), where the adrenal glands themselves are damaged, and secondary, where the pituitary gland fails to signal the adrenal glands properly. Symptoms include fatigue, weakness, weight loss, low blood pressure, salt cravings, and darkening of the skin in primary cases.

Key Points

  • Treatment centers on hormone replacement therapy, typically with oral hydrocortisone to replace cortisol, and sometimes fludrocortisone to replace aldosterone in primary insufficiency, as recommended by 1.
  • Patients need to carry emergency medication and wear medical alert identification, as stress situations require increased dosing to prevent life-threatening adrenal crisis, and they should be instructed on doubling doses for illness (stress dosing) 1.
  • During illness, injury, or surgery, doses may need to be doubled or tripled, and hydrocortisone 100 mg by intravenous (i.v.) injection should be given at induction of anaesthesia in adult patients with adrenal insufficiency from any cause, followed by a continuous infusion of hydrocortisone at 200 mg.24 h-1, until the patient can take double their usual oral glucocorticoid dose by mouth, as recommended by 1.
  • The condition occurs because cortisol regulates metabolism, blood pressure, and immune response, while aldosterone manages sodium and potassium balance, so their deficiency disrupts these essential bodily functions.

Management Considerations

  • All glucocorticoid-dependent patients are at risk of adrenal crisis as a consequence of surgical stress or illness, and it is essential to be able to recognise and diagnose this medical emergency, as stated by 1.
  • Patients with a long-standing diagnosis of adrenal insufficiency are often well informed about their disease, and anaesthetists should enquire closely about the patient’s history of glucocorticoid self-management, any previous episodes of adrenal crisis and how practised they are at medication adjustments for illness, injury or postoperative recovery, as recommended by 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. The answer to what adrenal insufficiency is, is not directly provided in the drug label. Adrenal insufficiency is mentioned as a condition being treated, but its definition is not given. 2

From the Research

Definition of Adrenal Insufficiency

Adrenal insufficiency (AI) is a condition characterized by an absolute or relative deficiency of adrenal cortisol production 3. It can be primary, secondary, or tertiary, depending on the cause of the deficiency. Primary AI is caused by direct adrenal failure, while secondary AI is caused by diseases affecting the pituitary, and tertiary AI is caused by diseases affecting the hypothalamus.

Types of Adrenal Insufficiency

  • Primary adrenal insufficiency (PAI): caused by direct adrenal failure 3
  • Secondary adrenal insufficiency (SAI): caused by diseases affecting the pituitary 3
  • Tertiary adrenal insufficiency (TAI): caused by diseases affecting the hypothalamus 3

Symptoms and Diagnosis

Symptoms of AI are non-specific and often overlooked or misdiagnosed, and are related to the lack of cortisol, adrenal androgen precursors, and aldosterone (especially in PAI) 3. Diagnosis is based on measurement of the adrenal corticosteroid hormones, their regulatory peptide hormones, and stimulation tests 3, 4.

Treatment and Management

The goal of therapy is to establish a hormone replacement regimen that closely mimics the physiological diurnal cortisol secretion pattern, tailored to the patient's daily needs 3. Treatment options include:

  • Glucocorticoid replacement therapy 5, 6
  • Mineralocorticoid replacement therapy 5
  • Adrenal androgen replacement therapy 5
  • Novel pharmaceutical preparations of hydrocortisone, such as dual-release hydrocortisone 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Adrenal insufficiency.

Nature reviews. Disease primers, 2021

Research

Adrenal insufficiency: diagnosis and management.

Current urology reports, 2006

Research

Replacement therapy for Addison's disease: recent developments.

Expert opinion on investigational drugs, 2008

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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