What are the symptoms of adrenal insufficiency?

Symptoms of Adrenal Insufficiency

Adrenal insufficiency typically presents with nonspecific symptoms including profound fatigue (50-95%), nausea and vomiting (20-62%), anorexia, unintentional weight loss (43-73%), postural hypotension, muscle and abdominal pain, and hyponatremia. 1, 2

Primary vs. Secondary Adrenal Insufficiency Symptoms

Primary Adrenal Insufficiency

• Fatigue and weakness
• Anorexia and weight loss
• Nausea and vomiting
• Abdominal pain
• Postural hypotension
• Hyponatremia and hyperkalemia 3, 1
• Distinctive features:
  • Skin hyperpigmentation (due to elevated ACTH)
  • Salt craving 2

Secondary Adrenal Insufficiency

• Similar nonspecific symptoms (fatigue, weakness, nausea, weight loss)
• Generally normal electrolytes (sodium and potassium)
• No hyperpigmentation 3, 1

Laboratory Abnormalities

Primary adrenal insufficiency is characterized by:

• Low morning cortisol (<5 μg/dL)
• High ACTH levels
• Low DHEAS levels
• Decreased sodium, increased potassium 3, 1

Secondary adrenal insufficiency is characterized by:

• Low or intermediate morning cortisol (5-10 μg/dL)
• Low or low-normal ACTH levels
• Low DHEAS levels
• Generally normal electrolytes 3, 1

Adrenal Crisis Symptoms

Adrenal crisis is a life-threatening emergency that can occur in patients with adrenal insufficiency, particularly during times of stress or illness. Symptoms include:

• Hypotension and shock
• Severe hyponatremia
• Altered mental status
• Fever
• Decreased consciousness 1, 4

Clinical Presentation by Frequency

Symptom	Frequency
Fatigue	50-95%
Nausea and vomiting	20-62%
Anorexia and weight loss	43-73%
Hyperpigmentation	Common in primary AI
Postural hypotension	Common
Salt craving	Common in primary AI

High-Risk Groups

Be particularly vigilant for adrenal insufficiency in patients with:

• History of autoimmune disorders
• Recent glucocorticoid therapy or withdrawal
• Opioid use
• Azole antifungal therapy at high doses
• History of pituitary disorders or surgery 1, 4

Common Pitfalls in Diagnosis

• Delayed diagnosis due to nonspecific presentation
• Failure to recognize adrenal crisis as a medical emergency
• Overlooking adrenal insufficiency in patients with recent glucocorticoid withdrawal
• Not considering adrenal insufficiency in patients with unexplained hypotension, hyponatremia, or hyperkalemia 2, 4

Early detection based on clinical suspicion is crucial to prevent progression to adrenal crisis, which has high mortality if left untreated 4, 5.