Overview
Definition:
Adrenal insufficiency is a condition characterized by the insufficient production of steroid hormones by the adrenal glands, primarily cortisol and often aldosterone
In pediatrics, this can be congenital (primary adrenal insufficiency) or acquired, leading to inadequate response to physiological stress and potential adrenal crisis.
Epidemiology:
The incidence of primary adrenal insufficiency in children is estimated to be 1 in 10,000 to 1 in 20,000 live births
Congenital adrenal hyperplasia (CAH) accounts for the majority of primary adrenal insufficiency cases
Autoimmune adrenalitis is the most common cause of primary AI in older children and adults, but less frequent in neonates
Secondary and tertiary AI are caused by pituitary or hypothalamic dysfunction, respectively.
Clinical Significance:
Adrenal insufficiency is a life-threatening condition if not recognized and managed promptly
Children with AI require lifelong glucocorticoid replacement and careful management of intercurrent illnesses, as even minor stress can precipitate an adrenal crisis, leading to hypotension, hypoglycemia, and shock
Understanding stress dosing and sick-day rules is paramount for preventing these emergencies and ensuring optimal long-term outcomes.
Clinical Presentation
Symptoms:
Failure to thrive
Poor feeding and vomiting
Irritability and lethargy
Hypotonia
Hyperpigmentation (especially in primary AI)
Salt craving
Recurrent hypoglycemia
Fever
Dehydration
Abdominal pain.
Signs:
Hypotension, often refractory to fluid resuscitation
Tachycardia
Signs of dehydration
Hypoglycemia
Hyponatremia with hyperkalemia (in primary AI with mineralocorticoid deficiency)
Ambiguous genitalia (in certain CAH subtypes)
Poor weight gain.
Diagnostic Criteria:
Diagnosis is based on clinical suspicion and confirmed by hormonal assays
A low serum cortisol level (< 3 mcg/dL or < 85 nmol/L) is suggestive, but a provocative test is usually required
The ACTH stimulation test is the gold standard: assessing baseline cortisol and then measuring cortisol 30 and 60 minutes after an intramuscular or intravenous injection of synthetic ACTH (cosyntropin)
A peak cortisol < 18 mcg/dL (500 nmol/L) is diagnostic of adrenal insufficiency
For mineralocorticoid assessment, serum renin and aldosterone levels, along with electrolytes, are crucial, particularly in primary AI.
Diagnostic Approach
History Taking:
Detailed birth history (e.g., prolonged gestation, difficult delivery)
Family history of adrenal disorders or autoimmune diseases
History of neonatal crisis or prolonged illness
Medication history (e.g., prolonged corticosteroid use)
Presence of other endocrine or autoimmune disorders
Nutritional status and feeding patterns.
Physical Examination:
Thorough assessment of growth parameters (weight, height, head circumference)
Examination for signs of dehydration
Careful evaluation of vital signs (BP, HR, RR)
Assessment for hyperpigmentation, especially in creases and buccal mucosa
Examination for ambiguous genitalia in newborns
Palpation of abdomen for masses
Neurological assessment for hypoglycemia symptoms.
Investigations:
Initial investigations: Serum electrolytes (Na+, K+), glucose, cortisol, ACTH, renin, aldosterone
CBC, renal function tests
For suspected CAH: 17-hydroxyprogesterone
ACTH stimulation test: baseline cortisol, then cortisol at 30 and 60 minutes post-ACTH
Longer stimulation tests may be needed for partial insufficiency
Imaging: Adrenal ultrasound or CT scan may be considered for structural abnormalities or adrenal hemorrhage.
Differential Diagnosis:
Sepsis
Dehydration from gastroenteritis
Congenital metabolic disorders
Other causes of hypoglycemia (e.g., hyperinsulinism, ketotic hypoglycemia)
Electrolyte imbalances from renal causes
Other endocrine deficiencies
Factitious illness.
Management
Initial Management:
Immediate administration of intravenous fluids (0.9% normal saline) to correct dehydration and hyponatremia
Intravenous hydrocortisone (100 mcg/kg bolus, followed by continuous infusion or repeated boluses of 50-100 mcg/kg every 6-8 hours) is crucial to replace cortisol
Glucose supplementation may be needed to correct hypoglycemia
Electrolyte correction as per laboratory findings
Identify and treat any precipitating cause.
Medical Management:
Lifelong glucocorticoid replacement therapy: Hydrocortisone is preferred in children due to its short half-life, allowing for physiological dosing (usually 3-4 divided doses daily, with higher doses in the morning)
Typical maintenance dose is 4-7 mg/m²/day
Mineralocorticoid replacement (fludrocortisone) is required for primary AI with mineralocorticoid deficiency, dosed based on BP, renin, and electrolyte levels (typically 0.05-0.1 mg daily)
Androgen precursor replacement (e.g., DHEA) may be considered for girls with CAH and adrenal androgen excess.
Stress Dosing And Sick Day Rules:
Crucial for preventing adrenal crisis
**Sick Day Rules:** For mild illness (e.g., common cold, mild fever): Double the usual oral hydrocortisone dose for 24-48 hours
For moderate illness (e.g., vomiting, diarrhea, higher fever): Triple the usual oral hydrocortisone dose
If vomiting prevents oral intake, seek immediate medical attention for parenteral hydrocortisone
**Stress Dosing:** For significant stress (e.g., surgery, major trauma, severe illness): Intramuscular or intravenous hydrocortisone at a dose of 100 mcg/kg every 6-8 hours
Ensure patient and caregivers are educated on recognizing symptoms of impending crisis and administering emergency intramuscular hydrocortisone (e.g., Solu-Cortef®) via auto-injector if available.
Supportive Care:
Close monitoring of vital signs, fluid balance, glucose levels, and electrolytes
Regular follow-up with pediatric endocrinologist
Nutritional support to promote growth
Psychosocial support for the child and family
Education on disease management, medication adherence, and emergency preparedness.
Complications
Early Complications:
Adrenal crisis: life-threatening hypotensive shock, hypoglycemia, hyponatremia, hyperkalemia
Infections, often related to immunosuppression from glucocorticoids and underlying adrenal defect
Gastrointestinal symptoms like nausea, vomiting, and abdominal pain.
Late Complications:
Growth retardation due to inadequate or excessive glucocorticoid replacement
Osteoporosis
Cushingoid features from chronic over-replacement
Psychological and behavioral issues
Impaired immune response
Reproductive issues (especially in CAH).
Prevention Strategies:
Strict adherence to replacement therapy
Comprehensive education of patients and caregivers on sick-day rules and stress dosing
Prompt recognition and management of intercurrent illnesses
Regular medical follow-up to adjust medication doses as needed
Ensuring access to emergency parenteral hydrocortisone.
Prognosis
Factors Affecting Prognosis:
Early diagnosis and initiation of appropriate treatment
Adherence to medication and sick-day management
Severity of the underlying adrenal defect
Presence of co-existing autoimmune conditions
Prompt management of acute adrenal crises.
Outcomes:
With meticulous management and adherence to therapy, children with adrenal insufficiency can achieve normal growth and development, and lead relatively normal lives
The main challenge is preventing life-threatening adrenal crises through proactive stress dosing and sick-day management.
Follow Up:
Lifelong regular follow-up with a pediatric endocrinologist is essential
Monitoring of growth, pubertal development, bone mineral density, and endocrine function
Annual assessment of replacement therapy and adjustment of doses based on age, growth, and physiological stress
Education reinforcement for patients and families.
Key Points
Exam Focus:
Adrenal crisis is a medical emergency
Know the ACTH stimulation test interpretation
Hydrocortisone is the drug of choice for glucocorticoid replacement in children
Stress dosing increases are mandatory for illness/stress
Fludrocortisone is for mineralocorticoid replacement in primary AI.
Clinical Pearls:
Always suspect adrenal insufficiency in a child with unexplained shock, hypoglycemia, or hyponatremia with hyperkalemia
Educate families repeatedly on sick-day rules
written protocols are invaluable
Consider adrenal insufficiency in children on long-term steroids undergoing stress (e.g., surgery)
The "stress dose" of hydrocortisone is 100 mcg/kg IM/IV every 6-8 hours.
Common Mistakes:
Underestimating the severity of illness requiring increased cortisol
Delaying parenteral hydrocortisone in vomiting patients
Forgetting fludrocortisone in primary AI
Inadequate education of caregivers on recognizing and managing emergencies
Mistaking symptoms of adrenal crisis for sepsis without considering AI.