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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