Overview

Definition:
-Adrenal crisis (Addisonian crisis) is a life-threatening condition characterized by an acute, severe deficiency of glucocorticoids and sometimes mineralocorticoids, leading to circulatory collapse, shock, and multi-organ dysfunction
-In pediatrics, it is often the initial presentation of primary adrenal insufficiency or occurs in children with known adrenal disorders during periods of stress.
Epidemiology:
-Primary adrenal insufficiency occurs in approximately 1-2 per 100,000 live births
-Congenital adrenal hyperplasia (CAH) is the most common cause of primary adrenal insufficiency in neonates and infants, particularly the salt-wasting forms
-Autoimmune adrenalitis is more common in older children
-The incidence of adrenal crisis is difficult to quantify but is a significant complication of untreated or inadequately treated adrenal insufficiency.
Clinical Significance:
-Prompt recognition and aggressive management of adrenal crisis are critical for survival in pediatric patients
-It is a medical emergency requiring immediate intervention with glucocorticoid replacement and supportive care
-Understanding the pediatric-specific nuances of presentation, diagnosis, and management, including age-appropriate dosing, is vital for residents preparing for DNB and NEET SS examinations, as this is a frequently tested topic with significant clinical implications.

Clinical Presentation

Symptoms:
-Sudden onset of severe weakness
-Profound lethargy and somnolence
-Vomiting and diarrhea
-Abdominal pain, often severe and diffuse
-Fever
-Hypotension and shock
-Hypoglycemia
-Irritability or confusion
-In infants, poor feeding, failure to thrive, and dehydration are common
-Cyanosis may be present in severe cases.
Signs:
-Profound hypotension, often unresponsive to fluid resuscitation alone
-Tachycardia
-Poor peripheral perfusion
-Cool, clammy skin
-Signs of dehydration
-Hyperpigmentation of skin and mucous membranes (more common in chronic insufficiency, less so in acute crisis unless it is the first presentation)
-Hypotonia
-Seizures (due to hypoglycemia or hyponatremia)
-Possible signs of underlying cause (e.g., congenital anomalies in CAH).
Diagnostic Criteria:
-Diagnosis is primarily clinical, supported by laboratory findings
-A high index of suspicion is essential
-Definitive diagnosis is made by demonstrating deficient cortisol production and a lack of response to ACTH stimulation, although this test is typically deferred until the patient is stable
-Electrolyte abnormalities (hyponatremia, hyperkalemia) are hallmark laboratory findings
-Hypoglycemia is also common.

Diagnostic Approach

History Taking:
-Inquire about history of adrenal insufficiency, congenital adrenal hyperplasia, autoimmune disorders, or endocrine conditions
-Ask about recent illness, surgery, trauma, or any stressor
-Family history of adrenal disorders
-Medication history, especially steroid use (to rule out secondary adrenal insufficiency).
Physical Examination:
-Assess vital signs carefully, noting hypotension, tachycardia, and signs of shock
-Evaluate hydration status
-Examine for hyperpigmentation
-Perform a thorough abdominal exam for tenderness
-Assess neurological status for lethargy, confusion, or seizures
-Look for any dysmorphic features suggestive of genetic syndromes.
Investigations:
-Immediate bedside glucose monitoring
-Serum electrolytes (sodium, potassium, chloride, bicarbonate)
-Serum cortisol (random, typically low)
-Serum ACTH (may be elevated in primary insufficiency, low/normal in secondary)
-Renin and aldosterone levels (to assess mineralocorticoid status, if indicated)
-Blood gas analysis (for acid-base status)
-Complete blood count (may show mild anemia or eosinophilia)
-Imaging: Adrenal ultrasound or CT scan if adrenal hemorrhage or mass is suspected
-Cosyntropin stimulation test (250 mcg IV) to assess ACTH reserve: measure baseline cortisol and cortisol 30-60 minutes after injection
-A peak cortisol < 18-20 mcg/dL (500-550 nmol/L) indicates adrenal insufficiency
-Interpretation: Low cortisol with high ACTH suggests primary adrenal failure
-low cortisol with low/normal ACTH suggests secondary adrenal failure.
Differential Diagnosis:
-Septic shock
-Hypovolemic shock
-Diabetic ketoacidosis
-Congenital adrenal hyperplasia (initial presentation)
-Inborn errors of metabolism
-Sepsis with adrenal involvement
-Hypoglycemia of other causes
-Gastroenteritis with severe dehydration.

Management

Initial Management:
-Immediate fluid resuscitation with isotonic saline (e.g., 0.9% NaCl) at 20 mL/kg bolus, repeated as needed
-Glucose administration (e.g., D10W) if hypoglycemia is present
-Initiate intravenous hydrocortisone therapy immediately, without waiting for diagnostic test results
-Address any precipitating factors.
Medical Management:
-Intravenous Hydrocortisone: For acute crisis, administer hydrocortisone 1-2 mg/kg IV/IM every 6-8 hours
-Once stable, can switch to oral hydrocortisone
-Pediatric Dosing of Hydrocortisone: Infants and children: 1-2 mg/kg IV/IM every 6-8 hours
-Maximum dose is typically 100 mg per dose
-Adolescents: 100 mg IV/IM as a bolus, followed by continuous infusion of 200 mg/24 hours, or 50-100 mg IV/IM every 6-8 hours
-Transition to oral therapy: Once hemodynamically stable and tolerating oral intake, switch to oral hydrocortisone
-Typical maintenance dose for children is 4-7 mg/kg/day divided into 2-3 doses, with the largest dose in the morning
-Stress dosing: During illness or stress, oral hydrocortisone doses need to be increased (e.g., 3-5 times maintenance dose, or 10-15 mg/kg/day, divided q4-6h)
-Mineralocorticoid Replacement: For primary adrenal insufficiency (e.g., Addison's disease, CAH), fludrocortisone is usually required
-Dose: 0.05-0.1 mg orally once daily
-Monitor electrolytes and blood pressure
-Adjust dose as needed
-Sodium bicarbonate may be used to treat severe metabolic acidosis if present.
Surgical Management:
-Generally not applicable, as adrenal crisis is a medical emergency
-Surgical intervention may be considered for complications like adrenal hemorrhage with retroperitoneal hematoma, though this is rare.
Supportive Care:
-Continuous monitoring of vital signs, fluid balance, and glucose levels
-Monitor electrolytes and acid-base status closely
-Mechanical ventilation may be required if respiratory compromise occurs
-Strict intake and output monitoring
-Provide adequate nutritional support once tolerated
-Education for parents/guardians on stress dosing, sick day rules, and emergency preparedness is paramount.

Complications

Early Complications:
-Circulatory collapse and shock
-Hypoglycemic seizures
-Hyponatremic or hyperkalemic cardiac arrhythmias
-Acute kidney injury
-Sepsis due to immunocompromise or poor perfusion
-Disseminated intravascular coagulation (DIC).
Late Complications:
-Recurrent adrenal crises if adherence to medication and stress dosing is poor
-Growth failure in children with inadequately treated adrenal insufficiency
-Osteoporosis
-Cardiovascular disease
-Psychiatric disturbances.
Prevention Strategies:
-Meticulous adherence to prescribed glucocorticoid and mineralocorticoid replacement therapy
-Comprehensive education of patients and caregivers on sick day rules, stress dosing protocols, and recognizing early signs of crisis
-Provision of emergency hydrocortisone injection kits (IM/IV) and instruction on their use
-Regular follow-up with pediatric endocrinologist
-Early recognition and management of precipitating factors like infections or stress.

Prognosis

Factors Affecting Prognosis:
-Timeliness of diagnosis and initiation of treatment
-Severity of the crisis
-Presence of precipitating factors and their management
-Underlying cause of adrenal insufficiency
-Patient's overall health status and presence of comorbidities
-Adherence to long-term therapy and patient/caregiver education.
Outcomes:
-With prompt and aggressive management, most children can recover from adrenal crisis
-However, it remains a life-threatening condition, and mortality can occur if treatment is delayed or inadequate
-Long-term outcomes depend on consistent management of adrenal insufficiency and prevention of future crises.
Follow Up:
-Regular endocrinology follow-up is essential for dose adjustments, monitoring growth and development, and reinforcing education
-Patients and families should have a clear emergency plan and access to medical advice at all times
-Monitoring for potential complications of long-term steroid therapy is also necessary.

Key Points

Exam Focus:
-Emergency treatment of pediatric adrenal crisis requires immediate IV hydrocortisone (1-2 mg/kg/dose q6-8h) and aggressive fluid resuscitation
-Differentiate primary vs
-secondary adrenal insufficiency based on ACTH levels
-Stress dosing is crucial for preventing crises during illness.
Clinical Pearls:
-Always consider adrenal crisis in any child presenting with shock, severe dehydration, vomiting, and abdominal pain, especially if there are electrolyte abnormalities
-Never withhold hydrocortisone while awaiting diagnostic tests in a suspected crisis
-Educate families on always carrying emergency hydrocortisone.
Common Mistakes:
-Delaying hydrocortisone administration
-Underestimating fluid and glucose requirements
-Inadequate stress dosing during illness
-Misinterpreting electrolyte patterns without considering the clinical context
-Forgetting mineralocorticoid replacement in primary adrenal insufficiency.