What are the symptoms of adrenal insufficiency in a patient with a history of epilepsy and suspected pituitary disease?

Symptoms of Adrenal Insufficiency

Primary Clinical Manifestations

Adrenal insufficiency presents with a constellation of nonspecific symptoms that often delay diagnosis, requiring high clinical suspicion especially in patients with pituitary disease or epilepsy on medications that may affect cortisol metabolism.

Constitutional and Gastrointestinal Symptoms

• Profound fatigue and lack of energy occur in 50-95% of patients, representing the most common presenting symptom 1, 2
• Nausea and vomiting affect 20-62% of patients, frequently accompanied by anorexia 1, 3
• Unintentional weight loss and poor appetite occur in 43-73% of patients, often with morning nausea being particularly prominent 2, 4
• Abdominal pain with peritoneal irritation can mimic acute surgical conditions 3

Cardiovascular Manifestations

• Orthostatic (postural) hypotension is an early cardinal feature that occurs before supine hypotension develops 3
• Progressive hypotension can advance to shock and circulatory collapse in untreated cases 3, 5
• Salt craving is a specific clinical clue for primary adrenal insufficiency due to mineralocorticoid deficiency 4, 2

Neurological and Musculoskeletal Features

• Impaired cognitive function ranging from malaise and somnolence to confusion, loss of consciousness, and coma in severe cases 3, 5
• Muscle pain, cramps, and generalized weakness 3

Dermatological Signs (Primary Adrenal Insufficiency Only)

• Hyperpigmentation of skin and mucous membranes occurs in primary adrenal insufficiency due to elevated ACTH levels, but is absent in secondary adrenal insufficiency where ACTH is low 3, 2
• Increased pigmentation with uneven distribution suggests glucocorticoid under-replacement 4

Laboratory Abnormalities

Electrolyte Disturbances

• Hyponatremia is present in approximately 90% of newly diagnosed cases and can be indistinguishable from SIADH 4, 3
• Hyperkalemia occurs in only about 50% of cases, so its absence cannot rule out adrenal insufficiency 4, 3
• The combination of hyponatremia plus hyperkalemia suggests primary adrenal insufficiency, while hyponatremia without hyperkalemia suggests secondary adrenal insufficiency 4

Other Laboratory Findings

• Increased creatinine and BUN due to prerenal renal failure from volume depletion 3
• Hypoglycemia, particularly in children but less frequent in adults 3
• Mild to moderate hypercalcemia in 10-20% of patients 4, 3
• Metabolic acidosis due to impaired renal function and aldosterone deficiency 3

Special Considerations for Your Patient Context

Epilepsy and Medication Interactions

• Anticonvulsants are CYP3A4 inducers that increase cortisol clearance, potentially unmasking or worsening adrenal insufficiency 4
• Patients on antiepileptic medications may require higher glucocorticoid replacement doses if adrenal insufficiency is confirmed 4

Pituitary Disease Implications

• Pituitary lesions cause secondary adrenal insufficiency through ACTH deficiency, presenting with low-normal cortisol and low-normal ACTH 4
• Hypophysitis from pituitary disease commonly causes central adrenal insufficiency in >75% of cases, often accompanied by central hypothyroidism 6
• Headache (85%) and visual changes may accompany hypophysitis, though visual symptoms are uncommon 6

Critical Diagnostic Pitfalls

• Do not rely on electrolyte abnormalities alone—between 10-20% of patients have normal electrolytes at presentation 4
• Normal or even elevated plasma cortisol levels do not exclude relative adrenal insufficiency in physiologically stressed patients 3
• Treatment should never be delayed for diagnostic procedures when adrenal crisis is suspected—give hydrocortisone 100 mg IV immediately 3, 5
• When treating concurrent hypothyroidism and adrenal insufficiency, corticosteroids must be started several days before thyroid hormone to prevent precipitating adrenal crisis 4