What are the treatment options for a man with symptoms of low cortisol levels, specifically adrenal insufficiency?

Symptoms of Low Cortisol in Men

Men with low cortisol (adrenal insufficiency) most commonly present with fatigue (50-95%), nausea and vomiting (20-62%), anorexia and weight loss (43-73%), along with nonspecific symptoms that often delay diagnosis. 1

Clinical Presentation

Primary Symptoms

• Fatigue and weakness are the most prevalent symptoms, occurring in 50-95% of patients with adrenal insufficiency 1
• Gastrointestinal symptoms including nausea (20-62%), vomiting, poor appetite, and weight loss (43-73%) are common presenting features 2, 1
• Morning nausea and lack of appetite are particularly characteristic of primary adrenal insufficiency and often indicate glucocorticoid under-replacement 2
• Salt craving is a specific clinical clue for primary adrenal insufficiency, reflecting mineralocorticoid deficiency 2

Additional Manifestations

• Hyperpigmentation with uneven distribution may be present in primary adrenal insufficiency due to elevated ACTH levels 2
• Hypotension and orthostatic symptoms including lightheadedness and dizziness occur due to mineralocorticoid deficiency in primary adrenal insufficiency 2, 3
• Unexplained collapse with hypotension should immediately raise suspicion for adrenal crisis 2, 3

Laboratory Abnormalities

• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases 2
• Hyperkalemia occurs in approximately 50% of primary adrenal insufficiency cases, but its absence does not rule out the diagnosis 2
• Hypoglycemia may occur, particularly in acute presentations 3

Distinguishing Primary vs. Secondary Adrenal Insufficiency

Primary Adrenal Insufficiency (Addison's Disease)

• Characterized by both glucocorticoid and mineralocorticoid deficiency 2, 3
• Hyponatremia plus hyperkalemia suggests primary adrenal insufficiency 2
• Salt craving and hyperpigmentation are specific to primary adrenal insufficiency 2
• Laboratory pattern: low cortisol with high ACTH 2, 1

Secondary Adrenal Insufficiency

• Involves glucocorticoid deficiency only, with intact mineralocorticoid function 2, 3
• Hyponatremia without hyperkalemia suggests secondary adrenal insufficiency 2
• Laboratory pattern: low cortisol with low or inappropriately normal ACTH 2, 1

Diagnostic Approach

Initial Testing

• Morning (8 AM) serum cortisol and plasma ACTH are the first-line diagnostic tests 2, 1
• Basic metabolic panel to assess sodium, potassium, and glucose 2
• Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 2
• Morning cortisol 5-10 μg/dL with low or low-normal ACTH suggests secondary adrenal insufficiency 1

Confirmatory Testing

• ACTH stimulation test (cosyntropin 250 mcg) is the gold standard when initial results are inconclusive 2, 4
• Measure cortisol at baseline and 30-60 minutes post-administration 2
• Peak cortisol <500-550 nmol/L (<18-20 μg/dL) is diagnostic of adrenal insufficiency 2, 1
• Peak cortisol >550 nmol/L rules out adrenal insufficiency 2

Important Diagnostic Pitfalls

• Never delay treatment of suspected adrenal crisis for diagnostic testing—draw blood for cortisol and ACTH, then treat immediately with IV hydrocortisone 100 mg 2, 3
• Exogenous steroids (prednisone, dexamethasone, inhaled fluticasone) suppress the HPA axis and confound test results 2
• Normal cortisol levels do not exclude early primary adrenal insufficiency—approximately 10% of patients with confirmed Addison's disease present with normal cortisol concentrations when ACTH is clearly elevated 5
• Absence of hyperkalemia cannot rule out adrenal insufficiency as it is present in only 50% of cases 2

Treatment Based on Severity

Adrenal Crisis (Severe Symptoms)

• Immediate IV hydrocortisone 100 mg bolus without delay for diagnostic testing 2, 3, 1
• IV 0.9% saline infusion at 1 L/hour (at least 2L total) 2, 3
• Continue hydrocortisone 100 mg IV every 6-8 hours until recovered 3

Moderate Symptoms

• Outpatient treatment at 2-3 times maintenance dose (hydrocortisone 30-50 mg total daily or prednisone 20 mg daily) 2, 3
• Taper to maintenance doses over 5-10 days as symptoms improve 3

Mild Symptoms/Maintenance Therapy

• Primary adrenal insufficiency: Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg at 7 AM, 5 mg at noon, 2.5-5 mg at 4 PM) PLUS fludrocortisone 0.05-0.1 mg daily 2, 3, 6, 1
• Secondary adrenal insufficiency: Hydrocortisone 10-20 mg morning and 5-10 mg afternoon WITHOUT fludrocortisone 3

Critical Patient Education

Emergency Preparedness

• All patients must wear a medical alert bracelet indicating adrenal insufficiency 2, 3
• Prescribe emergency injectable hydrocortisone 100 mg IM kit with self-injection training 2, 3, 1
• Educate on warning signs of adrenal crisis: severe weakness, confusion, abdominal pain, vomiting, hypotension 3

Stress Dosing

• Double the usual daily dose for minor illness (fever, cold) 3
• Triple the dose for moderate illness (gastroenteritis, flu) 3
• Immediate IV hydrocortisone 100 mg for severe illness, trauma, or inability to take oral medications 3, 1

Surgical Coverage

• Hydrocortisone 100 mg IV at induction, followed by continuous infusion of 200 mg/24 hours for major surgery 3
• Endocrine consultation before any surgery for stress-dose planning 2, 3

Common Pitfalls to Avoid

• Never initiate thyroid hormone replacement before adrenal replacement in patients with concurrent hypothyroidism and adrenal insufficiency, as this can precipitate adrenal crisis 2, 3
• Do not rely solely on electrolyte abnormalities for diagnosis—10-20% of patients have normal electrolytes at presentation 2
• Never use dexamethasone for long-term replacement in primary adrenal insufficiency as it lacks mineralocorticoid activity 3
• Patients on chronic steroids (prednisolone ≥5 mg for ≥4 weeks) require perioperative stress dosing even without diagnosed adrenal insufficiency 3