What is the appropriate workup for a patient presenting with salt cravings?

Workup for Salt Cravings

The workup for salt cravings must begin with immediate exclusion of primary adrenal insufficiency through simultaneous morning cortisol and ACTH measurement, as this is life-threatening, followed by comprehensive electrolyte assessment to differentiate between salt-wasting tubulopathies (Bartter and Gitelman syndromes), cerebral salt wasting, and other endocrine disorders. 1, 2

Initial Life-Threatening Condition: Primary Adrenal Insufficiency

Primary adrenal insufficiency must be ruled out first because it is immediately life-threatening and presents with salt craving alongside fatigue, weight loss, hyperpigmentation, nausea, and orthostatic hypotension. 1

First-line testing:

• Simultaneous morning cortisol and ACTH levels (before 8 AM, before any steroid administration) 1
• Basal cortisol <250 nmol/L (<9 mcg/dL) with elevated ACTH is diagnostic 1
• Basal cortisol <400 nmol/L (<14.5 mcg/dL) with elevated ACTH raises strong suspicion and warrants empiric treatment if clinically unstable 1
• If initial results are indeterminate, proceed with cosyntropin stimulation testing 1

Treatment if confirmed: Hydrocortisone 15-25 mg daily in divided doses plus fludrocortisone 50-200 µg daily 1

Core Diagnostic Laboratory Panel

Once adrenal insufficiency is excluded, obtain the following simultaneously to establish the diagnostic pattern:

Serum studies:

• Sodium, potassium, chloride, bicarbonate, creatinine, glucose 2, 3
• Magnesium and calcium 2, 3
• Plasma aldosterone and renin activity with calculation of aldosterone-to-renin ratio 2

Urine studies (spot or 24-hour collection):

• Urine sodium, chloride, and osmolality 2
• Urinary calcium-to-creatinine ratio 2, 3

Differential Diagnosis Based on Electrolyte Patterns

Bartter Syndrome

Diagnostic features: 1, 2

• Hypokalemia with metabolic alkalosis
• Inappropriately elevated urinary chloride (>20 mEq/L)
• Elevated plasma renin activity
• Normal to low blood pressure
• Polyuria, rapid weight loss, dehydration

Confirmatory testing: Genetic testing for SLC12A1, KCNJ1, CLCNKB, BSND, CASR genes 1, 2

Treatment: Pharmacologic doses of sodium chloride supplementation (5-10 mmol/kg/day) combined with potassium chloride, plus NSAIDs (indomethacin or ibuprofen) with gastric acid inhibitors 2

Gitelman Syndrome

Diagnostic triad (pathognomonic): 1, 2, 3

• Hypokalemia with metabolic alkalosis
• Hypomagnesemia
• Hypocalciuria (urinary calcium-to-creatinine ratio <0.2) - this distinguishes it from Bartter syndrome 3

Clinical presentation: Muscle weakness, fatigue, salt cravings, often family history 2, 3

Confirmatory testing: Genetic testing for SLC12A3 mutations 1, 2, 3

Treatment: 1, 2, 3

• Magnesium supplementation is the cornerstone - use organic magnesium salts (citrate, lactate) for better bioavailability, target serum magnesium 1.8-2.2 mg/dL
• Potassium chloride (NOT potassium citrate), target serum potassium 3.0 mmol/L
• Follow-up every 6-12 months in specialized centers with tubular disorder expertise

Cerebral Salt Wasting

Diagnostic features: 1, 2

• Hyponatremia with evidence of extracellular volume depletion
• Inappropriately high renal sodium loss (>20 mmol/L)
• High urine osmolality relative to serum osmolality
• Context: Recent intracranial pathology (subarachnoid hemorrhage, traumatic brain injury, neurosurgery)

Critical distinction: This requires sodium and volume replacement, NOT fluid restriction (opposite of SIADH treatment) 2

Primary Hyperaldosteronism (Aldosterone-Secreting Tumors)

Diagnostic features: 1, 2

• Hypertension, weakness, hypokalemia
• Plasma aldosterone-to-renin ratio >30

Confirmatory testing: Saline suppression test or salt loading test 1, 2

Medication-Induced (Corticosteroid Withdrawal)

Consider in patients with: 1

• Chronic corticosteroid use (≥20 mg/day prednisone equivalent for ≥3 weeks)
• Salt craving, hypotension, gastrointestinal symptoms after dose reduction or discontinuation
• Morning cortisol <250 nmol/L with low/normal ACTH confirms secondary adrenal insufficiency

Common Pitfalls to Avoid

Do not confuse Gitelman with Bartter syndrome: The presence of hypocalciuria (urinary calcium-to-creatinine ratio <0.2) is pathognomonic for Gitelman syndrome. 3

Do not use potassium citrate in Gitelman syndrome: Only potassium chloride should be used, as citrate can worsen metabolic alkalosis. 2, 3

Do not fluid-restrict cerebral salt wasting: This is the opposite of SIADH management and will worsen outcomes. 2

Do not delay treatment in suspected adrenal crisis: If basal cortisol <400 nmol/L with elevated ACTH and patient is clinically unstable, initiate empiric treatment immediately. 1

Recognize psychiatric causes: While rare, pathological salt ingestion (salinophagia) occurs predominantly in women with psychiatric disorders, particularly eating disorders and depression, and can cause life-threatening hypernatremia. 4, 5, 6 However, this represents excessive salt intake causing hypernatremia, not true salt craving from physiologic deficiency.