What are the differential diagnoses and treatment options for a patient experiencing salt cravings?

Differential Diagnoses for Salt Cravings

Salt cravings most commonly indicate primary adrenal insufficiency (Addison's disease), but must also prompt evaluation for salt-wasting tubulopathies (Bartter and Gitelman syndromes), cerebral salt wasting, and adrenal tumors causing mineralocorticoid deficiency. 1, 2, 3, 4

Primary Differential Diagnoses

Addison's Disease (Primary Adrenal Insufficiency)

• Most common serious cause presenting with salt craving, hyperpigmentation, fatigue, anorexia, orthostasis, nausea, muscle and joint pain 1
• Laboratory findings show decreased cortisol levels and increased adrenocorticotropic hormone (ACTH) levels 1
• Confirm diagnosis with cosyntropin stimulation test when clinically suspected 1
• Prevalence is approximately 1 in 20,000 persons in the United States and Western Europe 1
• Treatment requires replacement of both mineralocorticoids (fludrocortisone 0.1 mg daily) and glucocorticoids (hydrocortisone 10-30 mg daily in divided doses) 5, 1

Bartter Syndrome

• Characterized by renal salt wasting, polyuria, rapid weight loss, and signs of dehydration with salt craving as a typical feature beyond infancy 2
• Presents with hypokalemia, metabolic alkalosis, and elevated urinary chloride (>20 mEq/L) 2
• Most patients exhibit salt craving, although this is rarely a presenting symptom 2
• Genetic testing should include a minimal diagnostic panel for genes underlying Bartter syndrome and Gitelman syndrome 2
• Treatment includes pharmacologic doses of sodium chloride supplementation (5-10 mmol/kg/day) combined with potassium chloride (not potassium citrate) 2
• NSAIDs (indomethacin or ibuprofen) should be considered in symptomatic patients, especially in early childhood, with gastric acid inhibitors 2

Gitelman Syndrome

• Distinguished by the triad of hypokalemia, hypomagnesemia, and hypocalciuria (urinary calcium-to-creatinine ratio <0.2) with metabolic alkalosis 3
• Patients present with muscle weakness, fatigue, salt cravings, and often a family history of similar conditions 3
• Confirm through genetic testing for SLC12A3 mutations after demonstrating characteristic biochemical pattern 3
• Magnesium supplementation is the cornerstone of therapy, with organic magnesium salts (citrate, lactate) having better bioavailability than inorganic forms 3
• Potassium chloride (not potassium citrate) should be used with a target serum potassium of 3.0 mmol/L 3

Cerebral Salt Wasting (CSW)

• Characterized by hyponatremia, evidence of extracellular volume depletion, and inappropriately high renal sodium loss (typically >20 mmol/L) 4
• High urine osmolality relative to serum osmolality is characteristic 4
• Central venous pressure (CVP) typically <6 cm H₂O, distinguishing it from SIADH (CVP 6-10 cm H₂O) 4
• Critical distinction: CSW requires sodium and volume replacement, NOT fluid restriction as fluid restriction worsens outcomes 4
• More common in patients with poor clinical grade, ruptured anterior communicating artery aneurysms, and hydrocephalus 4

Aldosterone-Secreting Adrenal Tumors

• May present with hypertension, weakness, and hypokalemia 2
• Plasma aldosterone-to-renin ratio usually greater than 30 in primary hyperaldosteronism 2
• Confirmatory testing with saline suppression test or salt loading test may be indicated 2
• Excessive aldosterone production causes retention of sodium and excretion of potassium 2

Secondary Considerations

Diabetes Insipidus (Nephrogenic)

• Patients with nephrogenic diabetes insipidus may exhibit salt craving as part of their compensatory mechanism 6
• Characterized by polyuria, polydipsia, and inappropriately dilute urine (osmolality <200 mOsm/kg H₂O) with high-normal or elevated serum sodium 6
• Dietary modifications include low-salt diet (≤6 g/day) and protein restriction (<1 g/kg/day) 6
• Plasma copeptin levels >21.4 pmol/L indicate nephrogenic diabetes insipidus 6

Adrenal Insufficiency Secondary to Corticosteroid Withdrawal

• Patients on prolonged corticosteroid courses may develop secondary adrenal insufficiency upon tapering 2
• Signs include fatigue, decreased appetite, gastrointestinal distress, myalgia, joint pain, salt craving, dizziness, and postural hypotension 2

Behavioral/Psychiatric Causes

• Salinophagia in anorexia nervosa represents pathological salt ingestion, typically in purging subtype, motivated by desire to render food distasteful 7
• Salt addiction as a form of substance dependence has been proposed, with withdrawal symptoms including anorexia and nausea during salt abstinence 8

Diagnostic Algorithm

Initial Evaluation

1. Measure serum sodium, potassium, chloride, bicarbonate, creatinine, and glucose simultaneously 4, 9
2. Obtain serum cortisol and ACTH levels to evaluate for adrenal insufficiency 1
3. Check plasma aldosterone and renin activity with calculation of aldosterone-to-renin ratio 2
4. Measure urine sodium, chloride, and osmolality on spot or 24-hour collection 2

Confirmatory Testing Based on Initial Results

• If cortisol low with elevated ACTH: perform cosyntropin stimulation test for Addison's disease 1
• If hypokalemia with metabolic alkalosis and elevated urinary chloride: obtain genetic testing for Bartter/Gitelman syndrome 2, 3
• If hyponatremia with volume depletion and high urine sodium: consider cerebral salt wasting (check CVP if available) 4
• If aldosterone-to-renin ratio >30: perform saline suppression test and adrenal imaging 2
• If polyuria with dilute urine: measure plasma copeptin and consider water deprivation test 6

Critical Pitfalls to Avoid

• Never confuse cerebral salt wasting with SIADH - treatments are diametrically opposed (volume replacement vs. fluid restriction) 4
• Do not use potassium citrate in Bartter or Gitelman syndrome - it worsens metabolic alkalosis; always use potassium chloride 2, 3
• Avoid salt supplementation in Bartter syndrome patients with secondary nephrogenic diabetes insipidus as it worsens polyuria and risks hypernatremic dehydration 2
• Do not routinely use potassium-sparing diuretics in Bartter syndrome as they worsen salt wasting and risk critical hypovolemia 2
• Never restrict water access in diabetes insipidus patients - this is life-threatening and leads to severe hypernatremic dehydration 6
• Consider that up to 50% of patients with Addison's disease develop another autoimmune disorder during their lifetime, requiring vigilance 1