What are the symptoms of primary adrenal disorders?

Symptoms of Primary Adrenal Disorders

Primary adrenal disorders present with a constellation of symptoms resulting from deficiency of glucocorticoids and mineralocorticoids, including fatigue (50-95%), nausea/vomiting (20-62%), anorexia, weight loss (43-73%), hypotension, and electrolyte abnormalities (hyponatremia and hyperkalemia). 1

Common Clinical Manifestations

General Symptoms

• Fatigue and weakness (present in 50-95% of cases)
• Anorexia and weight loss (43-73%)
• Nausea and vomiting (20-62%)
• Hyperpigmentation (50.4%) - particularly in skin creases, mucous membranes, and scars 2, 3
• Dizziness and postural hypotension
• Salt craving

Laboratory Abnormalities

• Hyponatremia (present in 90% of newly presenting cases) 2
• Hyperkalemia (in approximately 50% of patients) 2
• Hypoglycemia (33.7%) 3
• Elevated ACTH levels (96.4% in primary adrenal insufficiency) 3

Cardiovascular Manifestations

• Hypotension (31%) 3
• Postural hypotension (reflects insufficient mineralocorticoid therapy) 2
• Reduced cardiac output
• Decreased vascular tone

Gastrointestinal Symptoms

• Abdominal pain
• Diarrhea (may be episodic) 2
• Reduced appetite

Neuropsychiatric Symptoms

• Irritability
• Depression
• Apathy
• Confusion (in severe cases)

Specific Presentations Based on Etiology

Autoimmune Adrenal Insufficiency (Addison's Disease)

• May present with other autoimmune conditions:
  • Autoimmune thyroid disease
  • Autoimmune gastritis with vitamin B12 deficiency
  • Type 1 diabetes mellitus
  • Premature ovarian insufficiency
  • Vitiligo
  • Celiac disease 2

Congenital Adrenal Hyperplasia

• In young girls: virilization 4
• In children under 2 years: hypoglycemia, dehydration, and convulsions 4

Adrenal Crisis

Adrenal crisis is a life-threatening emergency that may occur in patients with undiagnosed or undertreated adrenal insufficiency:

• Severe hypotension or shock
• Acute abdominal pain
• Vomiting and diarrhea
• Altered mental status
• Fever
• Severe electrolyte abnormalities 5, 1

Diagnostic Considerations

Early detection based on clinical suspicion is crucial to prevent adrenal crisis. Key diagnostic findings include:

• Morning cortisol <5 μg/dL with elevated ACTH levels suggests primary adrenal insufficiency 1
• ACTH stimulation test showing peak cortisol <18 μg/dL and/or increment <9 μg/dL from baseline 5
• Electrolyte abnormalities (↓Na, ↑K) are characteristic of primary but not secondary adrenal insufficiency 5

Important Clinical Pitfalls

• Symptoms are often non-specific and may be mistaken for other conditions
• Hyponatremia may be only marginally reduced and hyperkalemia is present in only about half of cases 2
• In the presence of severe vomiting, hypokalaemia and alkalosis may occur instead of the typical hyperkalemia 2
• The duration of symptoms before diagnosis can be prolonged (average 5.6 months), leading to delayed treatment 3
• Adrenal crisis can be precipitated by intercurrent illness, trauma, surgery, or other stressors in undiagnosed cases 5

Early recognition of these symptoms is essential as untreated adrenal insufficiency can progress to life-threatening adrenal crisis with significant morbidity and mortality.