What is the cause of hyponatremia (low sodium level) and elevated BUN (Blood Urea Nitrogen)/creatinine ratio in this patient, and how to differentiate between Addison's disease and SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)?

Diagnostic Approach to Differentiate SIADH from Addison's Disease in Hyponatremia

Your patient's sodium of 128 mmol/L with elevated BUN/creatinine ratio requires immediate evaluation for adrenal insufficiency before assuming SIADH, as Addison's disease presents identically to SIADH but requires fundamentally different treatment with glucocorticoid replacement rather than fluid restriction. 1, 2

Critical First Steps: Rule Out Addison's Disease

The single most important test is a morning serum cortisol level (ideally 8 AM) with simultaneous ACTH measurement. 2, 3 This must be done before any treatment because:

• Addison's disease can present with hyponatremia (sodium 120-128 mmol/L), high urine osmolality, and elevated urine sodium—features indistinguishable from SIADH 2, 4
• Your patient's elevated BUN/creatinine ratio (23, reference 6-22) is a red flag suggesting volume depletion, which is more consistent with Addison's disease than SIADH 5, 2
• Patients with Addison's disease do NOT respond to fluid restriction but achieve rapid normalization of sodium with glucocorticoid replacement 2, 6

Specific Laboratory Tests to Order Now:

1. Morning (8 AM) serum cortisol - expect <100-140 nmol/L in Addison's disease 2
2. Plasma ACTH - markedly elevated (>100 pg/mL) in primary adrenal insufficiency 3
3. Serum uric acid - typically LOW (<4 mg/dL) in both SIADH and Addison's disease, so this won't differentiate 1, 7, 8
4. Spot urine sodium and osmolality - both will show urine sodium >20-40 mEq/L and urine osmolality >300-500 mOsm/kg in either condition 7, 9, 2
5. 21-hydroxylase antibodies - positive in autoimmune Addison's disease 3

Key Distinguishing Features

Addison's Disease (Primary Adrenal Insufficiency):

• Elevated BUN/creatinine ratio (your patient has 23, which is HIGH) 5, 2
• Low serum cortisol (<140 nmol/L or <5 mcg/dL) 2, 6
• Markedly elevated ACTH (>100 pg/mL) 3
• Hypotension and orthostatic changes (check blood pressure lying and standing) 2, 6
• Hyperkalemia may be present (your patient's potassium is 3.9, which is normal, but doesn't rule out Addison's) 3, 6
• Skin hyperpigmentation (from elevated ACTH) 3
• Does NOT respond to fluid restriction 2
• Responds dramatically to hydrocortisone replacement 2, 6

SIADH:

• Normal to slightly LOW BUN/creatinine ratio (not elevated like your patient) 5
• Normal cortisol and ACTH levels 9, 2
• Euvolemic on exam (no orthostatic hypotension, normal blood pressure) 7, 9
• Normal potassium (your patient has this) 9
• Low serum uric acid, creatinine, and urea 5, 4
• Responds to fluid restriction 9, 4

Critical Diagnostic Algorithm

Step 1: Check morning cortisol and ACTH immediately 2, 3

• If cortisol <5 mcg/dL (140 nmol/L) → proceed to Step 2
• If cortisol >15 mcg/dL → Addison's unlikely, consider SIADH

Step 2: If cortisol is low or borderline, perform cosyntropin (ACTH) stimulation test 2

• Give 250 mcg cosyntropin IV
• Measure cortisol at 0,30, and 60 minutes
• Inadequate response (<18-20 mcg/dL peak) confirms adrenal insufficiency 2

Step 3: Measure ACTH to differentiate primary vs. secondary adrenal insufficiency 2, 3

• ACTH >100 pg/mL = Primary adrenal insufficiency (Addison's disease) 3
• ACTH low or inappropriately normal = Secondary adrenal insufficiency (pituitary/hypothalamic) 2

Step 4: Check 21-hydroxylase antibodies if primary adrenal insufficiency confirmed 3

Volume Status Assessment

Your patient's elevated BUN/creatinine ratio strongly suggests volume depletion, which is MORE consistent with Addison's disease than SIADH. 5, 2 However, physical examination alone is unreliable (sensitivity 41%, specificity 80%) 1, 7. Look for:

• Orthostatic vital signs (drop in BP >20 mmHg or pulse increase >20 bpm when standing) 2, 6
• Dry mucous membranes, decreased skin turgor 1, 7
• Absence of edema, ascites, or jugular venous distension (rules out hypervolemic hyponatremia) 1, 7

Common Pitfalls to Avoid

1. Never start fluid restriction before ruling out Addison's disease - this can be life-threatening in adrenal crisis 2, 6
2. Don't rely on serum potassium alone - not all Addison's patients have hyperkalemia initially 3, 6
3. Don't assume SIADH just because urine sodium is elevated - Addison's disease also causes renal salt wasting 2, 8, 6
4. The elevated BUN/creatinine ratio in your patient is a major clue - this is NOT typical of SIADH 5, 2

Immediate Management Pending Results

Do NOT order sodium chloride tablets yet. 1 Instead:

1. Hold any fluid restriction until Addison's disease is ruled out 2
2. If patient is symptomatic or cortisol comes back very low (<5 mcg/dL), start empiric hydrocortisone 100 mg IV immediately - don't wait for ACTH stimulation test results in acute illness 2, 3
3. Provide isotonic saline (0.9% NaCl) for volume repletion if Addison's suspected 1, 2
4. Correct sodium slowly - maximum 6-8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 9

Treatment Based on Final Diagnosis

If Addison's Disease Confirmed:

• Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg AM, 5 mg noon, 5 mg evening) 2, 3
• Fludrocortisone 0.05-0.2 mg daily for mineralocorticoid replacement 3
• Sodium normalizes within days with glucocorticoid replacement alone 2, 6
• Patient requires lifelong hormone replacement and stress-dose steroids during illness 3

If SIADH Confirmed:

• Fluid restriction to 1 L/day 1, 9
• Oral sodium chloride 100 mEq three times daily if no response to fluid restriction 1, 9
• Treat underlying cause (medications, malignancy, pulmonary disease) 9

The bottom line: Your patient's elevated BUN/creatinine ratio makes Addison's disease more likely than SIADH, and this distinction is life-saving because the treatments are opposite. 5, 2, 4