2025 PACUPrep BCCCP Preparatory Course Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Syndrome of Inappropriate Antidiuretic Hormone (SIADH) in Critical Care: Diagnosis, Management, and Transitions
Diagnostic Criteria and Differential Evaluation of SIADH

Diagnostic Criteria and Differential Evaluation of SIADH

Lesson Objective

Apply diagnostic criteria to confirm SIADH and differentiate it from other causes of hyponatremia in critically ill patients.

I. Introduction to SIADH Diagnosis

Rationale: Early recognition and differentiation of cardiogenic shock (CS) from other shock states are paramount for initiating life-saving therapies. The initial assessment combines physical examination with key laboratory markers to confirm the presence of both cardiac dysfunction and end-organ hypoperfusion.

  • Key features: hypotonic hyponatremia + euvolemia + inappropriately concentrated urine + natriuresis.
  • Mandatory exclusion of adrenal insufficiency, hypothyroidism, renal failure, and diuretic effects.
Key Pearl

SIADH is always a diagnosis of exclusion—failure to rule out other causes is the most frequent error.

II. Assessing Serum Osmolality and Volume Status

A. Hypotonic Hyponatremia Criteria

  • Confirm serum osmolality <275 mOsm/kg via freezing-point osmometry.
  • Correct sodium for hyperglycemia: corrected Na = measured Na + 2.4 × [(glucose – 100) / 100].
  • Exclude pseudohyponatremia (hyperlipidemia, paraproteinemia) by comparing measured vs calculated osmolality.

B. Clinical Euvolemia Assessment

  • Physical exam: no orthostatic vital changes, no dry mucosa, no edema or JVP elevation.
  • ICU caveats: mechanical ventilation and vasopressors distort exam findings.
  • Lab surrogates (urine studies) offer more objective euvolemia data.
Key Pearl

In the ICU, rely on urine osmolality/sodium for volume assessment rather than physical signs alone.

III. Urine Studies Interpretation

A. Urine Osmolality >100 mOsm/kg

  • Indicates persistent ADH activity and impaired free water excretion.
  • Values ≤100 mOsm/kg point to primary polydipsia or low solute intake, excluding SIADH.

B. Urine Sodium >40 mEq/L

  • Reflects renal sodium handling in euvolemia; lower values suggest hypovolemia or edematous states.
  • Diuretics and natriuretic peptides can confound—obtain drug history and consider washout.
Key Pearl

A dilute urine (≤100 mOsm/kg) effectively rules out SIADH; a high urine sodium in context of euvolemia strongly supports it.

IV. Exclusion of Alternative Etiologies

Systematic workup prevents misdiagnosis and harmful treatments.

  • Adrenal Insufficiency: morning cortisol <5 µg/dL or abnormal cosyntropin test.
  • Hypothyroidism: elevated TSH and low free T4—only severe cases cause hyponatremia.
  • Renal Failure: GFR <30 mL/min with elevated BUN/Cr impairs water excretion.
  • Diuretics/Drugs: thiazides, SSRIs, carbamazepine; require ≥24–48 h washout before urine studies.
Key Pearl

Always reconcile medications; thiazide-induced hyponatremia mimics SIADH laboratory profile.

V. Integrated Diagnostic Algorithm

A stepwise flow enhances diagnostic accuracy and expedites management.

Figure 1: Integrated Diagnostic Algorithm for SIADH. This algorithm outlines the key steps in diagnosing SIADH, emphasizing the confirmation of hypotonic hyponatremia, assessment of euvolemia, interpretation of urine studies, and exclusion of other potential causes.

1. Confirm Hypotonic Hyponatremia
(Serum Osmolality <275 mOsm/kg)

2. Assess Volume Status
(Clinical Exam & Urine Surrogates)

3. Euvolemic?

No

Not SIADH
(Hypo/Hypervolemic)

Yes

4. Urine Osm >100 mOsm/kg AND Urine Na >40 mEq/L?

No

Re-evaluate
(e.g., Polydipsia, Low Solute)

Yes

5. Exclude:

  • Adrenal Insufficiency, Hypothyroidism
  • Renal Failure

6. Review & Pause Potential
SIADH-Inducing Drugs

SIADH Diagnosis Likely

7. Consider Copeptin (if available/unresolved)

8. Early Endocrine/Nephrology Consult

Key Pearl

Copeptin may help differentiate SIADH from hypovolemia but remains investigational in many settings.

VI. Pearls, Pitfalls, and Practical Tips

  • Timing: draw labs before IV fluids or diuretics to avoid confounding results.
  • Mixed etiologies: critically ill patients often have overlapping causes—reassess if sodium response is atypical.
  • Repeat testing: if clinical status or therapy changes, repeat serum and urine studies.
  • Multidisciplinary approach: involve nephrology/endocrinology early in challenging cases.
Key Pearl

In sepsis or multi-organ dysfunction, dynamic reassessment is essential—SIADH may coexist with other hyponatremia mechanisms.

References

  1. Verbalis JG et al. Diagnosis, evaluation, and treatment of hyponatremia: Expert recommendations. Am J Med. 2013;126:S1–42.
  2. Spasovski G et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014;170:G1–47.
  3. Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med. 1967;42:790–806.
  4. Hoorn EJ, Halperin ML, Zietse R. Diagnostic approach to hyponatraemia: traditional vs physiology-based. QJM. 2005;98:529–540.
  5. Janicic N, Verbalis JG. Evaluation and management of hypo-osmolality. Endocrinol Metab Clin North Am. 2003;32:459–481.
  6. Schrier RW. Body water homeostasis: disorders of urinary dilution/concentration. J Am Soc Nephrol. 2006;17:1820–1832.
  7. Fenske W et al. Copeptin in differential diagnosis of hyponatremia. J Clin Endocrinol Metab. 2009;94:123–129.
  8. Liamis G, Milionis H, Elisaf M. A review of drug-induced hyponatraemia. Am J Kidney Dis. 2008;52:144–153.
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