What are the implications of having a low cortisol level, or adrenal insufficiency?

Low Cortisol Levels: Diagnosis and Management of Adrenal Insufficiency

A low cortisol level indicates adrenal insufficiency, a potentially life-threatening condition that requires prompt diagnosis, treatment with hormone replacement therapy, and patient education on stress dosing to prevent adrenal crisis. 1, 2

Types and Causes of Adrenal Insufficiency

• Primary adrenal insufficiency is characterized by low cortisol with high ACTH levels, often accompanied by mineralocorticoid deficiency (hyponatremia and hyperkalemia in about 50% of cases) 3, 2
• Secondary adrenal insufficiency presents with low cortisol and low ACTH levels, indicating a pituitary problem rather than direct adrenal failure 1, 2
• Tertiary adrenal insufficiency is most commonly caused by exogenous glucocorticoid use (iatrogenic) 2, 4

Clinical Presentation

• Patients typically present with non-specific symptoms including fatigue (50-95%), nausea and vomiting (20-62%), anorexia, and weight loss (43-73%) 2, 5
• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases and can mimic syndrome of inappropriate antidiuretic hormone secretion (SIADH) 3
• Hyperpigmentation may be present in primary adrenal insufficiency due to elevated ACTH levels 2, 4
• Symptoms may develop gradually and be easily overlooked or misdiagnosed due to their non-specific nature 5, 4

Diagnostic Approach

Initial Testing

• Morning (8 AM) measurements of serum cortisol and ACTH are essential for initial evaluation 3, 2
• Primary adrenal insufficiency: low cortisol (<5 μg/dL or <140 nmol/L) with high ACTH 2, 6
• Secondary adrenal insufficiency: low cortisol with low or low-normal ACTH 1, 2

Confirmatory Testing

• Cosyntropin (Synacthen) stimulation test: administer 0.25 mg cosyntropin IV/IM and measure cortisol at baseline and 30-60 minutes post-administration 3, 5
• A peak cortisol value below 500 nmol/L (18 μg/dL) confirms adrenal insufficiency 3, 2
• Important caveat: approximately 10% of primary adrenal insufficiency cases may present with normal cortisol concentrations but elevated ACTH, requiring clinical correlation 6

Additional Evaluation

• Assess electrolytes (hyponatremia, hyperkalemia) and glucose (hypoglycemia) 1, 3
• For secondary adrenal insufficiency, evaluate other pituitary hormones (TSH, FT4, LH, FSH, testosterone/estradiol) 1
• Consider MRI of the brain with pituitary/sellar cuts for suspected secondary adrenal insufficiency 1
• Test for 21-hydroxylase autoantibodies to identify autoimmune etiology in primary adrenal insufficiency 3

Treatment Algorithm

Immediate Management

• For severe symptoms or adrenal crisis: immediate IV hydrocortisone 100 mg and IV normal saline 1, 3
• Never delay treatment of suspected adrenal crisis for diagnostic testing 3

Maintenance Therapy

• Primary adrenal insufficiency: hydrocortisone 15-25 mg daily (typically 10-20 mg in morning, 5-10 mg in early afternoon) plus fludrocortisone 0.05-0.3 mg daily for mineralocorticoid replacement 1, 2
• Secondary adrenal insufficiency: hydrocortisone 15-25 mg daily or prednisone 3-5 mg daily (mineralocorticoid replacement not needed) 1, 2
• If multiple hormone deficiencies are present (e.g., hypothyroidism), always start corticosteroids several days before thyroid hormone to prevent precipitating adrenal crisis 1, 3

Long-term Management and Patient Education

• All patients need education on stress dosing (doubling or tripling doses during illness, surgery, or significant stress) 1, 2
• Provide medical alert bracelet for adrenal insufficiency 1
• Prescribe injectable glucocorticoids (e.g., hydrocortisone 100 mg IM) for emergency use 2
• Endocrine consultation prior to surgery or procedures for stress-dose planning 1, 3
• Regular monitoring for adequate replacement and development of other endocrine deficiencies 1

Special Considerations and Pitfalls

• Hyponatremia with hypo-osmolality requires ruling out adrenal insufficiency before diagnosing SIADH, as both conditions can present similarly 3
• Exogenous steroid use can confound interpretation of cortisol levels 3, 2
• The absence of hyperkalemia cannot rule out adrenal insufficiency, as it is present in only about 50% of cases 3
• Early detection based on clinical suspicion is crucial to prevent progression to adrenal crisis, which can be fatal if untreated 2, 5