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Endocrinology — Adrenal Pathology

Addison's Disease: Causes, Symptoms, and Treatments – Clinique Omicron

Addison's disease, also known as chronic primary adrenal insufficiency, is a rare condition in which the adrenal glands do not produce enough cortisol and, in most cases, aldosterone. Both of these hormones are essential for regulating blood pressure, energy metabolism, stress response, and fluid and electrolyte balance. In Canada, the prevalence is estimated to be around 100 to 140 cases per million population, across all origins. The most common cause in industrialized countries is autoimmune in nature: the immune system gradually attacks the adrenal cortex, leading to its partial or total destruction. Addison's disease progresses insidiously, which often delays diagnosis by several months, or even years. Without adequate hormone replacement therapy, it exposes the affected person to a potentially life-threatening adrenal crisis. However, early diagnosis and rigorous management allow individuals to lead a completely normal life.
Medical emergency: adrenal crisis (Addisonian crisis)

An adrenal crisis is a life-threatening emergency. It manifests as severe hypotension, intense vomiting, sharp abdominal pain, mental confusion, or loss of consciousness, often triggered by significant physiological stress (infection, surgery, trauma).

In case of suspected adrenal crisis, call 911 immediately:

Individuals with a known diagnosis should wear a medical alert card and have an injectable hydrocortisone kit at home, as recommended by their doctor.

Causes and mechanisms

Destruction of the adrenal cortex can result from several distinct pathological processes. In high-income countries, autoimmune causes account for approximately 70 to 90% of cases. In other settings, adrenal tuberculosis remains a major cause worldwide.

Cause Mechanism Relative frequency
Autoimmune Destruction of the adrenal cortex by anti-21-hydroxylase antibodies 70 to 90 1Q–3Q
Adrenal tuberculosis Bilateral granulomatous adrenal infection Varies by region
Fungal infections and HIV Infectious infiltration of the cortex Less frequent
Adrenal metastases Bilateral tumor invasion (lung, breast, kidney) Rare
Bilateral adrenal hemorrhage Ischemic necrosis (anticoagulants, meningococcal sepsis) Rare
Genetic disorders (e.g., adrenoleukodystrophy) Enzyme anomaly leading to toxic lipid accumulation Rare
ℹ️ Autoimmune Addison's disease is often associated with other autoimmune endocrine diseases, including Hashimoto's thyroiditis, type 1 diabetes, or celiac disease. This is then referred to as autoimmune polyendocrine syndrome (APS).

Symptoms

The clinical manifestations of Addison's disease are initially progressive and non-specific, which complicates rapid identification of the condition. The symptoms are mainly due to the deficiency in cortisol and aldosterone.

Symptom Underlying mechanism
Profound chronic fatigue Cortisol deficiency, the main regulator of energy metabolism
Low blood pressure and dizziness Aldosterone deficiency, reducing sodium and water retention
Cutaneous and mucosal hyperpigmentation Compensatory elevation of ACTH, stimulating melanocytes
Weight loss and anorexia Disruption of carbohydrate and lipid metabolism
Nausea, vomiting, abdominal pain Gastrointestinal effects of hormonal deficiency
Salt cravings Compensatory mechanism for hyponatremia
Depression, irritability, cognitive impairment Influence of Cortisol on Mood Regulation and Brain Function
Hypoglycemia (especially in children) Role of cortisol in hepatic gluconeogenesis
ℹ️ Hyperpigmentation affecting palmar creases, scars, gums, and sun-exposed areas is a highly suggestive clinical sign of primary Addison's disease. It is absent in secondary forms (pituitary insufficiency).

Diagnosis

The diagnosis is based on a combination of clinical and biological evaluations, and hormonal stimulation tests. It is made by a doctor, often confirmed by an endocrinologist.

  • Morning serum cortisol (low value suggestive if below 140 nmol/L)
  • Plasma ACTH measurement (elevated in primary insufficiency)
  • Synacthen (Cosyntropin) Stimulation Test: Diagnostic Reference for Confirming Adrenal Insufficiency
  • Anti-21-hydroxylase antibody assay (confirmation of autoimmune origin)
  • Blood ionogram: search for hyponatremia and hyperkalemia
  • Fasting blood glucose: screening for associated hypoglycemia
  • Adrenal imaging (CT scan) according to clinical indication
  • Thyroid screening and fasting blood glucose for screening of associated SPA

Treatments

Addison's disease does not resolve spontaneously. It requires lifelong hormone replacement therapy, tailored individually and adjusted according to physiological stress situations.

Treatment Role Usual procedure
Oral hydrocortisone Cortisol substitution 15 to 25 mg/day in 2 to 3 divided doses
Oral fludrocortisone Mineralocorticoid substitution (aldosterone) 0.05 to 0.2 mg/day in a single dose
Oral DHEA (selected cases) Improvement of well-being, libido, and mood 25 to 50 mg/day as evaluated
Triple dose rule (sick day rules) Adrenal Crisis Prevention During Stress Double or triple the hydrocortisone dose during fever, infection, surgery
Hydrocortisone injectable (emergency kit) Management of impending adrenal crisis 100 mg IM/SC in an emergency, while awaiting medical assistance
ℹ️ Anyone with Addison's disease must wear a medical alert bracelet or card indicating their diagnosis and emergency instructions. This simple measure can be life-saving in case of an inability to communicate.

Long-term monitoring

Regular medical follow-up is essential for adjusting dosages, screening for associated conditions, and educating the patient on the autonomous management of at-risk situations. Parameters periodically evaluated include orthostatic blood pressure, ionogram, blood glucose, bone density, and perceived quality of life.

Dose adjustments are required during pregnancy, surgeries, severe infections, or radiological examinations with preparation (e.g., colonoscopy). The treating physician and endocrinologist should be informed in advance.

Consult at Clinique Omicron

Clinique Omicron, at its service points in Quebec, offers medical consultations for the evaluation of symptoms suggestive of an endocrine disorder, including unexplained chronic fatigue, persistent hypotension, or abnormal skin pigmentation. Our physicians can perform the initial assessment, coordinate the necessary hormonal tests, and refer to an endocrinologist when diagnosis or management requires it. For individuals already diagnosed, a consultation at one of our service points also allows for structured follow-up, assessment of the adequacy of replacement therapy, and uninterrupted prescription renewals.

The content of this page is provided for informational purposes only and is not intended to replace the advice of a qualified healthcare professional. Consult a physician for any symptoms, questions or decisions you may have regarding your health.

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