Doctors Revision

Endocrine & Metabolic System

Addison's Disease

A condition where the adrenal gland produces insufficient glucocorticoid hormones (and sometimes mineralocorticoids), often due to autoimmune destruction, infection (TB, HIV), or abrupt withdrawal of long-term steroid therapy.

Also known as: Adrenal Insufficiency, Hypoadrenalism

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Referral and warning signs

When to refer

Refer to hospital (H/RR)/Specialist (Endocrinologist) for: Suspected acute Addisonian crisis (URGENT). Diagnosis confirmation (hormone testing). Initiation and monitoring of chronic replacement therapy. Management of non-iatrogenic causes.

Red flags

  • Hypotension / Shock unresponsive to fluids
  • Altered mental status / Coma
  • Severe hypoglycemia
  • Significant hyperkalemia or hyponatremia
  • History suggesting abrupt steroid withdrawal presenting acutely ill

Signs and symptoms

  • Acute Crisis (Addisonian Crisis):
  • - Weakness, severe fatigue
  • - Shock, very low blood pressure (hypotension)
  • - Hypoglycaemic attacks
  • - Mental changes (irritability, restlessness, confusion, coma)
  • - Fever
  • - Nausea, vomiting, abdominal pain
  • - Hyponatremia (low sodium)
  • - Hyperkalemia (high potassium)
  • - Metabolic acidosis
  • Chronic Adrenal Insufficiency:
  • - Progressive weakness, fatigue
  • - Weight loss, anorexia
  • - Hyperpigmentation (darkening) of skin (esp. creases, scars, buccal mucosa) - *only if primary AI*
  • - Hypotension (often postural)
  • - Salt craving
  • - Gastrointestinal symptoms (nausea, vomiting, diarrhoea, constipation)
  • - Hair loss (axillary, pubic)
  • - Menstrual disturbances, infertility
  • - Symptoms worsen during stress (infection, surgery)

Risk factors

  • Abrupt cessation of long-term steroid treatment (most common iatrogenic cause)
  • Autoimmune adrenalitis
  • Tuberculosis affecting adrenals
  • HIV/AIDS (opportunistic infections, adrenalitis)
  • Adrenal haemorrhage (e.g., sepsis, anticoagulation)
  • Metastatic cancer to adrenals
  • Surgical adrenal removal
  • Certain medications affecting adrenal function

Diagnosis

Clinical assessment

Suspect acute crisis in patient with shock, hypoglycemia, electrolyte disturbance, +/- history of chronic symptoms or steroid use. Suspect chronic form with fatigue, weight loss, hyperpigmentation, hypotension. Careful drug history essential (steroid use). Differential diagnosis: HIV/AIDS wasting, TB, Cancer, Depression, Diabetes Mellitus, Hypothyroidism, Sepsis.

Investigations

  • Drug history (crucial for steroid withdrawal).
  • Blood tests (Acute): Glucose (low), Sodium (low), Potassium (high), Urea/Creatinine, Acid-base status (metabolic acidosis).
  • Hormone tests (Specialist level):
  • - Baseline Cortisol (typically low, esp. morning).
  • - ACTH Stimulation Test (Synacthen test): Definitive test for primary adrenal insufficiency (cortisol fails to rise adequately after ACTH injection).
  • - Plasma ACTH level: High in primary AI, Low/Normal in secondary AI (pituitary cause).
  • - Adrenal antibodies (if autoimmune cause suspected).
  • Imaging: Adrenal CT/MRI (look for atrophy, calcification - TB, haemorrhage, masses). Chest X-ray (rule out TB).

Diagnostic criteria

Clinical suspicion confirmed by biochemical evidence of adrenal insufficiency (low cortisol, inadequate response to ACTH stimulation).

Management

Non-pharmacological management

  • Acute Crisis: Aggressive IV fluid resuscitation (Normal Saline + Dextrose). Monitor vital signs, glucose, electrolytes closely. Identify and treat precipitating cause (e.g., infection).
  • Chronic: Patient education on condition, stress dosing, medical alert bracelet.

Pharmacological treatment

  • Acute Crisis (Addisonian Crisis):
  • - Hydrocortisone 100mg IV STAT, then 100mg IV Q6H until stable.
  • - Child 0-3 yrs: 25mg IV Q6H; 3-12 yrs: 50mg IV Q6H.
  • - Switch to oral replacement therapy once stable.
  • Chronic Replacement Therapy:
  • - Glucocorticoid: Hydrocortisone (preferred, mimics natural rhythm) OR Prednisolone 5-7.5mg daily (often single morning dose or split). Doses need to be increased during stress/illness ('stress dosing' - typically double or triple usual dose).
  • - Child: Prednisolone 1-5mg/day.
  • - Mineralocorticoid (if primary AI): Fludrocortisone (usually needed in primary AI, dose adjusted based on BP, electrolytes, renin).
  • Management of Iatrogenic (Steroid Withdrawal): Restart Prednisolone at previous dose (or slightly lower) and taper VERY SLOWLY (e.g., decrease by 2.5-5mg every 1-4 weeks, depending on dose/duration) under medical supervision.

Monitoring

Monitor clinical symptoms, weight, blood pressure (postural), electrolytes (Na, K). Monitor for signs of over/under-replacement. Patient needs regular follow-up.

Complications

  • Addisonian crisis (life-threatening)
  • Hypoglycemia
  • Hyperkalemia, hyponatremia
  • Hypotension, shock
  • Complications related to underlying cause (e.g., TB)

Prevention

  • Avoid abrupt cessation of long-term steroid therapy (gradual tapering essential).
  • Patient education on stress dosing for those on chronic replacement.
  • Medical alert identification.

Patient education

  • Nature of adrenal insufficiency.
  • Lifelong need for replacement therapy.
  • Importance of taking medication regularly.
  • Sick day rules / Stress dosing instructions (doubling/tripling dose during illness/surgery/stress).
  • Need for medical alert bracelet/card.
  • Symptoms of acute crisis and when to seek immediate help.
  • Avoidance of self-medication with steroids.

Uganda-specific notes

TB and HIV are important causes of primary adrenal insufficiency. Iatrogenic adrenal insufficiency due to inappropriate/abrupt withdrawal of steroid therapy (often prescribed for various ailments) is common. Access to hormone testing and specialist care is limited.

References

  • Uganda Clinical Guidelines (UCG) 2023

    Chapter 8, Section 8.1.1

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