What are the symptoms, laboratory findings, and treatment for aldosterone insufficiency?

Aldosterone Insufficiency: Clinical Manifestations and Laboratory Findings

Clinical Presentation

Aldosterone insufficiency presents with a constellation of symptoms dominated by volume depletion and electrolyte disturbances, most critically manifesting as hypotension (particularly orthostatic), dehydration, salt craving, and hyperkalemia. 1, 2

Cardinal Symptoms

• Hypotension and orthostatic hypotension are hallmark features, with orthostatic changes appearing before supine hypotension develops 2, 3
• Dehydration results from renal sodium wasting due to mineralocorticoid deficiency 1, 2
• Salt craving is a specific symptom reflecting the body's attempt to compensate for sodium loss 1
• Malaise and fatigue are prominent constitutional symptoms 1, 2
• Nausea, vomiting, and abdominal pain frequently occur, particularly during acute crisis 1
• Muscle pain, cramps, and weakness result from electrolyte disturbances 1, 2
• Weight loss and failure to thrive (especially in infants and children) are common presenting features 4, 5

Acute Crisis Manifestations

• Severe hypotension progressing to shock represents life-threatening decompensation 1, 2
• Impaired cognitive function, confusion, loss of consciousness, and coma can occur in severe cases 1, 2
• Abdominal pain with peritoneal irritation may mimic an acute surgical abdomen 1

Laboratory Findings

The classic laboratory triad consists of hyponatremia, hyperkalemia, and elevated creatinine from prerenal azotemia. 1, 2

Electrolyte Abnormalities

• Hyponatremia is present in approximately 90% of newly presenting cases 2, 3
• Hyperkalemia occurs in approximately 50% of patients with aldosterone insufficiency 2, 3
• Metabolic acidosis results from impaired renal function and aldosterone deficiency 2

Renal Function

• Increased creatinine and BUN due to prerenal renal failure from volume depletion 1, 2

Other Laboratory Findings

• Hypoglycemia is common in children but less frequent in adults 1, 2
• Mild hypercalcemia occurs in 10-20% of patients 2
• Low serum cortisol (<250 nmol/L or <10 mcg/dL) when primary adrenal insufficiency is present 2, 3
• Markedly elevated plasma ACTH is diagnostic of primary adrenal insufficiency 2, 3

Specific Diagnostic Testing

• Low or undetectable plasma aldosterone with elevated plasma renin activity confirms isolated aldosterone deficiency 4, 5, 6
• Plasma steroid profiles using liquid chromatography-mass spectrometry reveal reduced aldosterone synthase activity in aldosterone synthase deficiency 4
• 21-hydroxylase autoantibodies (21OH-Ab) are positive in approximately 85% of autoimmune Addison's disease cases 2, 3

Treatment Approach

Immediate treatment with hydrocortisone 100 mg IV bolus and aggressive fluid resuscitation with 0.9% saline (1 L over the first hour) must never be delayed for diagnostic procedures when adrenal crisis is suspected. 1, 2, 3, 7

Emergency Management

• Draw blood for cortisol, ACTH, electrolytes, creatinine, urea, and glucose before treatment, but do not delay therapy waiting for results 1, 2
• Administer hydrocortisone 100 mg IV bolus immediately to saturate 11β-hydroxysteroid dehydrogenase type 2, providing mineralocorticoid effect 1, 2, 3, 7
• Infuse 0.9% isotonic saline 1 L over the first hour, then continue at slower rate for 24-48 hours with total 3-4 L over 24 hours 1, 2, 3, 7
• Continue hydrocortisone 100-300 mg/day as continuous IV infusion or divided IV/IM boluses every 6 hours 1, 2, 3, 7

Maintenance Therapy

• Fludrocortisone (mineralocorticoid replacement) should be restarted when hydrocortisone dose falls below 50 mg/day 1
• Do not add separate mineralocorticoid during acute crisis, as high-dose hydrocortisone provides adequate mineralocorticoid activity 2
• Taper parenteral glucocorticoids over 1-3 days to oral therapy once precipitating illness permits 1, 7
• Transition to maintenance hydrocortisone 15-25 mg daily divided into 2-3 doses 2

Chronic Management of Isolated Aldosterone Deficiency

• Fludrocortisone treatment is the mainstay for isolated aldosterone synthase deficiency 4, 5
• Catch-up growth is achieved within median 2 months after treatment initiation in children 4
• Fludrocortisone can be discontinued in some patients (median age 6 years), though biochemical remission is not achieved and long-term surveillance is required 4

Common Precipitating Factors

• Gastrointestinal illness with vomiting/diarrhea is the most common trigger, as patients cannot absorb oral medications when needed most 1, 2, 7
• Infections of any type can precipitate crisis 1, 2, 7
• Surgical procedures without adequate steroid coverage 1, 2, 7
• Physical injuries, trauma, or myocardial infarction 1, 2, 7
• Severe allergic reactions or severe hypoglycemia in diabetic patients 1, 2
• Chronic under-replacement with fludrocortisone combined with low salt consumption contributes to recurrent crises 1, 2

Critical Clinical Pitfalls

• The absence of hyperkalemia does not exclude aldosterone insufficiency, as it is present in only 50% of cases 2
• Postural hypotension reflects insufficient mineralocorticoid therapy and/or low salt intake and should prompt dose adjustment 1
• Even mild upset stomach may precipitate crisis as oral medication absorption fails precisely when stress doses are needed 1, 2
• Never start thyroid hormone replacement before adequate glucocorticoid replacement in patients with multiple hormone deficiencies, as this can trigger crisis 2
• Monitor both sitting/standing and supine blood pressure for early detection of orthostatic hypotension, which represents an earlier warning sign than supine hypotension alone 2