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 including fatigue (50-95% of cases), nausea and vomiting (20-62%), anorexia and weight loss (43-73%), with hyperpigmentation being a distinguishing feature in primary adrenal insufficiency. 1

Chronic Presentation Symptoms

Constitutional Symptoms

• Fatigue and malaise are the most common presenting symptoms, occurring in 50-95% of patients with adrenal insufficiency 1
• Weight loss and anorexia occur in 43-73% of cases, often accompanied by poor appetite 1
• Muscle pain or cramps are frequently reported 2

Gastrointestinal Symptoms

• Nausea occurs in 20-62% of patients, frequently accompanied by vomiting 3, 1
• Morning nausea and lack of appetite are particularly common in primary adrenal insufficiency, often representing glucocorticoid under-replacement 3
• Abdominal pain may occur, sometimes with peritoneal irritation 2

Cardiovascular Symptoms

• Orthostatic hypotension reflects insufficient mineralocorticoid therapy in primary adrenal insufficiency 2
• Postural hypotension and dizziness are common presenting features 4
• Salt craving is a specific clinical clue for primary adrenal insufficiency due to mineralocorticoid deficiency 3, 5

Dermatologic Features

• Hyperpigmentation is a distinguishing feature of primary adrenal insufficiency, caused by elevated ACTH levels 5
• Normal skin color is observed in secondary adrenal insufficiency due to low ACTH 2

Acute Adrenal Crisis Symptoms

Life-Threatening Presentation

• Severe weakness, confusion, and altered mental status including loss of consciousness and coma are not uncommon 2, 6
• Hypotension and shock with dehydration are hallmark features requiring immediate recognition 2
• Unexplained collapse should immediately raise suspicion for adrenal crisis 6, 7

Associated Features

• Severe vomiting and/or diarrhea are common precipitating events and presenting symptoms 2
• Abdominal pain may mimic an acute abdomen 2

Laboratory Manifestations

Electrolyte Abnormalities

• Hyponatremia is present in 90% of newly diagnosed cases and is the most common electrolyte abnormality 3, 6
• Hyperkalemia occurs in only ~50% of cases, so its absence does not rule out adrenal insufficiency 2, 3, 6
• Hypoglycemia may occur, particularly in children 2

Other Laboratory Findings

• Increased creatinine caused by prerenal renal failure 2
• Mild hypercalcemia sometimes occurs 2

Distinguishing Primary vs. Secondary Adrenal Insufficiency

Primary Adrenal Insufficiency Features

• Hyperpigmentation, salt craving, and both hyponatremia plus hyperkalemia suggest primary adrenal insufficiency 3, 5
• Low morning cortisol (<5 µg/dL) with high ACTH levels characterize primary disease 1

Secondary Adrenal Insufficiency Features

• Hyponatremia without hyperkalemia suggests secondary adrenal insufficiency 3
• Low or intermediate morning cortisol (5-10 µg/dL) with low or low-normal ACTH characterize secondary disease 1
• Absence of hyperpigmentation due to low ACTH levels 2

High-Risk Clinical Scenarios

Medication-Related Risk

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

Critical Illness Context

• Vasopressor-resistant hypotension in critically ill patients warrants consideration of adrenal insufficiency 3
• Unexplained collapse with gastrointestinal symptoms (vomiting or diarrhea) should immediately raise suspicion 3

Critical Pitfalls to Avoid

• Do not rely on electrolyte abnormalities alone to make or exclude the diagnosis—between 10-20% of patients have normal electrolytes at presentation 3
• Never delay treatment of suspected acute adrenal crisis for diagnostic procedures—mortality is high if untreated 2, 6, 7
• The absence of hyperkalemia cannot rule out adrenal insufficiency, as it is present in only about 50% of cases 2, 3

Treatment Implications for Autoimmune Context

For patients with a history of autoimmune disorders, up to 50% develop another autoimmune disorder during their lifetime, making vigilance for concomitant autoimmune diseases essential 5. Annual screening for associated autoimmune conditions including thyroid function, diabetes, pernicious anemia, and celiac disease is mandatory 3, 6.