What are the symptoms and treatment options for a patient with a history of autoimmune disorders, suspected of having adrenal insufficiency?

Symptoms of Adrenal Insufficiency

Adrenal insufficiency presents with nonspecific symptoms that are easily missed, but recognizing the pattern of fatigue, gastrointestinal complaints, hypotension, and electrolyte abnormalities—particularly in patients with autoimmune disorders—is critical to preventing life-threatening adrenal crisis.

Cardinal Clinical Features

Most Common Presenting Symptoms

• Fatigue and weakness occur in 50-95% of patients and represent the most frequent complaint, often profound and out of proportion to other findings 1, 2
• Gastrointestinal symptoms including nausea (20-62%), vomiting, anorexia, and weight loss (43-73%) are hallmark features that should immediately raise suspicion 1, 2, 3
• Orthostatic hypotension and unexplained hypotension reflect inadequate cortisol and, in primary adrenal insufficiency, mineralocorticoid deficiency 4, 2
• Salt craving is a specific clinical clue for primary adrenal insufficiency due to mineralocorticoid deficiency 4, 2

Additional Symptoms

• Hyperpigmentation occurs specifically in primary adrenal insufficiency due to elevated ACTH levels, appearing as darkening of skin creases, scars, and mucous membranes 4, 2
• Muscle and joint pain or cramps are frequently reported and often accompanied by abdominal pain 4, 2
• Morning nausea and lack of appetite are particularly common and may indicate glucocorticoid under-replacement in diagnosed patients 4
• Dizziness, severe or continuing headaches warrant immediate evaluation 5

Laboratory Abnormalities

Electrolyte Disturbances

• Hyponatremia is present in 90% of newly diagnosed cases and represents the most common electrolyte abnormality 4, 6, 1
• Hyperkalemia occurs in only ~50% of cases, so its absence cannot rule out adrenal insufficiency—this is a critical pitfall to avoid 4, 6, 1
• Hypoglycemia may occur, particularly in children, but can present in adults as well 4, 1

Other Laboratory Findings

• Increased creatinine from prerenal renal failure is common 4
• Mild hypercalcemia sometimes occurs, though the mechanism is unclear 4
• Acidosis may be present in severe cases 7

Life-Threatening Presentation: Adrenal Crisis

Recognition of Adrenal Crisis

• Severe weakness, confusion, altered mental status, including loss of consciousness and coma, are not uncommon in acute adrenal crisis 4
• Hypotension and shock with dehydration are hallmark features requiring immediate intervention 4, 1
• Severe vomiting and/or diarrhea are common precipitating events and presenting symptoms 4
• Unexplained collapse should immediately trigger consideration of adrenal crisis 4, 6

Critical Action Required

• Never delay treatment of suspected acute adrenal crisis for diagnostic procedures—mortality is high if untreated 4, 6, 7
• Immediate administration of IV hydrocortisone 100 mg bolus plus 0.9% saline infusion at 1 L/hour is required if adrenal crisis is suspected 4, 6, 7
• Draw blood for cortisol and ACTH before treatment if possible, but do not delay therapy 4, 6

Distinguishing Primary vs. Secondary Adrenal Insufficiency

Primary Adrenal Insufficiency Features

• Hyperpigmentation is present due to elevated ACTH (absent in secondary adrenal insufficiency) 4, 2
• Both hyponatremia and hyperkalemia suggest primary adrenal insufficiency, though hyperkalemia is absent in half of cases 4
• Salt craving indicates mineralocorticoid deficiency specific to primary disease 4, 2

Secondary Adrenal Insufficiency Features

• Normal skin color due to low ACTH levels 4
• Hyponatremia without hyperkalemia suggests secondary adrenal insufficiency 4
• May have additional pituitary hormone deficiencies 4

Special Considerations for Autoimmune Disorders

High-Risk Populations

• Patients with autoimmune disorders are at increased risk for autoimmune adrenalitis, which accounts for ~85% of primary adrenal insufficiency cases in Western populations 4, 6, 2
• Up to 50% of patients with autoimmune adrenalitis develop another autoimmune disorder during their lifetime, requiring vigilance for concomitant conditions 2
• Annual screening for associated autoimmune conditions including thyroid function, diabetes, pernicious anemia (vitamin B12), and celiac disease is recommended 4, 6

Glucocorticoid-Induced Adrenal Insufficiency

• Any patient taking ≥20 mg/day prednisone or equivalent for ≥3 weeks who develops unexplained hypotension should be presumed to have adrenal insufficiency until proven otherwise 4, 6
• Glucocorticoid-induced adrenal insufficiency is common and should be suspected in patients who have recently tapered or discontinued supraphysiological doses of glucocorticoids 1

Diagnostic Approach When Symptoms Present

Initial Testing

• Paired measurement of early morning (8 AM) serum cortisol and plasma ACTH is the first-line diagnostic test 4, 6, 1
• Basic metabolic panel to assess sodium, potassium, CO2, and glucose 4
• Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 4, 6

Confirmatory Testing

• Cosyntropin stimulation test is the gold standard for confirming adrenal insufficiency when initial results are indeterminate 4, 6, 1
• Administer 0.25 mg cosyntropin IV or IM, measure cortisol at 30 and 60 minutes 4, 6
• Peak cortisol <500 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency 4, 6, 1

Etiologic Workup for Primary Adrenal Insufficiency

• Measure 21-hydroxylase (anti-adrenal) autoantibodies as the first step in determining underlying cause 4, 6
• If autoantibodies are negative, obtain CT imaging of the adrenals to evaluate for hemorrhage, tumors, tuberculosis, or other structural causes 4, 6

Treatment Based on Symptom Severity

Severe Symptoms or Adrenal Crisis

• Immediate IV hydrocortisone 100 mg bolus, followed by 100 mg every 6-8 hours 4, 6, 7
• 0.9% saline infusion at 1 L/hour (at least 2L total) 4, 6, 7
• Identify and treat underlying precipitants 7

Moderate Symptoms

• Outpatient treatment at 2-3 times maintenance dose with hydrocortisone 30-50 mg total daily or prednisone 20 mg daily 4, 7
• Taper to maintenance doses over 5-10 days 7

Mild Symptoms or Maintenance Therapy

• Primary adrenal insufficiency: Hydrocortisone 15-25 mg daily in divided doses PLUS fludrocortisone 50-200 μg daily 4, 6, 7, 1
• Secondary adrenal insufficiency: Hydrocortisone 15-25 mg daily in divided doses alone (no mineralocorticoid needed) 4, 7, 1

Critical Patient Education Requirements

Emergency Preparedness

• All patients must wear a medical alert bracelet or necklace indicating adrenal insufficiency 4, 6, 7
• Prescribe emergency injectable hydrocortisone 100 mg IM kit with self-injection training 4, 6, 7
• Educate on stress dosing: double dose for minor illness, triple dose for moderate illness, use IV hydrocortisone for severe illness 4, 7

Warning Signs of Adrenal Crisis

• Severe weakness, confusion, abdominal pain, vomiting, hypotension 7
• Instruct patients to seek immediate medical attention if these symptoms develop 7