What is hypocortisolism?

What is Hypocortisolism?

Hypocortisolism is adrenal insufficiency—a syndrome of inadequate cortisol production by the adrenal glands that can be primary (adrenal gland failure), secondary (pituitary dysfunction), or iatrogenic (glucocorticoid-induced). 1

Definition and Classification

Hypocortisolism represents a state of cortisol deficiency that manifests in three distinct forms 1, 2:

• Primary adrenal insufficiency (Addison's disease): Direct failure of the adrenal cortex to produce cortisol, aldosterone, and androgens, characterized by low cortisol with elevated ACTH 3, 1
• Secondary adrenal insufficiency: Pituitary or hypothalamic disorders causing inadequate ACTH production, characterized by low cortisol with low or inappropriately normal ACTH 4, 1
• Glucocorticoid-induced adrenal insufficiency: Suppression of the hypothalamic-pituitary-adrenal axis from exogenous steroid administration—the most common form 1

Clinical Presentation

The clinical features are often nonspecific and overlap with many other conditions 2, 5:

• Fatigue (50-95% of cases) 1
• Nausea and vomiting (20-62% of cases) 1
• Anorexia and weight loss (43-73% of cases) 1
• Hypotension and postural dizziness 3, 2
• Hyperpigmentation (only in primary adrenal insufficiency due to elevated ACTH) 3
• Hypoglycemia (particularly in children, but can occur in adults during stress) 6

Laboratory Findings

The biochemical diagnosis requires specific patterns 3, 1:

• Primary adrenal insufficiency: Morning cortisol <5 µg/dL (<138 nmol/L), ACTH elevated, low DHEAS, often with hyponatremia (90% of cases) and hyperkalaemia (50% of cases) 3, 1
• Secondary adrenal insufficiency: Morning cortisol 5-10 µg/dL (138-276 nmol/L), ACTH low or inappropriately normal, low or low-normal DHEAS 4, 1
• Confirmatory testing: ACTH stimulation test (250 µg cosyntropin) with peak cortisol <18 µg/dL (500 nmol/L) at 30 or 60 minutes confirms the diagnosis 3, 1, 5

Critical Illness Context

In critically ill patients, the diagnosis becomes more complex 3:

• Relative adrenal insufficiency (RAI): Inadequate cortisol response to stress despite potentially normal baseline levels 3
• Diagnostic criteria in critical illness: Random total cortisol <10 µg/dL (276 nmol/L) or delta cortisol <9 µg/dL (250 nmol/L) after ACTH stimulation 3
• Important caveat: Low albumin and cortisol-binding globulin in cirrhosis and critical illness can falsely suggest adrenal insufficiency when measuring total cortisol; free cortisol or salivary cortisol may be more accurate 3

Life-Threatening Complication: Adrenal Crisis

Adrenal crisis is a medical emergency characterized by hypotension/shock, hyponatremia, altered mental status, and death if untreated 1:

• Occurs when patients with adrenal insufficiency face acute illness, physical stress, or inadequate glucocorticoid therapy 1
• Emergency treatment: Never delay treatment for diagnostic testing—give IV hydrocortisone 100 mg immediately (or dexamethasone 4 mg if diagnosis uncertain and stimulation testing needed) 3
• Requires aggressive IV fluid resuscitation (at least 2 L normal saline) 3

Common Pitfalls

Several clinical scenarios complicate diagnosis 3, 5:

• Exogenous steroid use: Creates iatrogenic secondary adrenal insufficiency with low morning cortisol—cannot rely on simple cortisol measurement in these patients 3
• Nonspecific symptoms: Commonly reported features do not reliably distinguish biochemically confirmed adrenal insufficiency from other conditions in hospitalized patients 5
• TSH elevation: Patients with untreated primary adrenal insufficiency may have TSH levels of 4-10 IU/L due to lack of cortisol's inhibitory effect—this resolves with glucocorticoid replacement 3
• Starting thyroid hormone before steroids: In patients with both adrenal insufficiency and hypothyroidism, always start corticosteroids several days before thyroid hormone to prevent precipitating adrenal crisis 3, 4

Essential Patient Management

All patients diagnosed with hypocortisolism require 3, 1:

• Glucocorticoid replacement: Hydrocortisone 15-25 mg daily in divided doses (or prednisone 3-5 mg daily) 3, 1
• Mineralocorticoid replacement: Fludrocortisone 0.05-0.3 mg daily for primary adrenal insufficiency only 1
• Medical alert identification: Bracelet or card indicating adrenal insufficiency 3, 1
• Stress dosing education: Instructions to double or triple glucocorticoid doses during acute illness 3, 1
• Injectable glucocorticoids: Hydrocortisone 100 mg IM injection kit for emergencies 1
• Endocrine consultation: Strongly recommended for diagnosis confirmation and management 3, 4