A 40-point SIADH work-up, emphasizing all major laboratory tests, urine studies, endocrine testing, medication review, and imaging used to establish SIADH and search for its cause.
A key point: SIADH is a diagnosis of exclusion. The basic pattern is hypotonic hyponatremia, inappropriately concentrated urine, usually urine sodium >30 mmol/L with normal salt intake, clinical euvolemia, and exclusion of adrenal insufficiency, hypothyroidism, significant renal dysfunction, and other causes.
SIADH WORK-UP — 40 POINTS
1. Serum sodium
Confirm the presence and severity of hyponatremia.
Typical SIADH: Na <135 mmol/L.
Full reference:
Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014;170(3):G1-G47. doi:10.1530/EJE-13-1020.
2. Measured serum osmolality
This is one of the most important first tests.
Typical SIADH produces hypotonic hyponatremia, generally plasma osmolality <275 mOsm/kg.
Full reference:
Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines. Journal of the American Society of Nephrology. 2017;28(5):1340-1349. doi:10.1681/ASN.2016101139.
3. Calculated serum osmolality
Useful when measured osmolality is unavailable or to compare with measured osmolality.
A common calculation incorporates sodium, glucose, and BUN.
Full reference:
Milionis HJ, Liamis GL, Elisaf MS. The hyponatremic patient: a systematic approach to laboratory diagnosis. CMAJ. 2002;166(8):1056-1062.
4. Serum glucose
Hyperglycemia can produce translocational hyponatremia, so glucose must be checked before labeling the hyponatremia SIADH.
Full reference:
Milionis HJ, Liamis GL, Elisaf MS. The hyponatremic patient: a systematic approach to laboratory diagnosis. CMAJ. 2002;166(8):1056-1062.
5. Serum potassium
Potassium abnormalities can provide important clues to alternative diagnoses.
Hypokalemia may accompany diuretic use, while hyperkalemia raises concern for adrenal insufficiency.
Full reference:
Pliquett RU, Obermüller N. Endocrine Testing for the Syndrome of Inappropriate Antidiuretic Hormone Secretion. In: Endotext. NCBI Bookshelf. Updated 2022.
6. Serum chloride
Include chloride in the basic electrolyte panel because it helps characterize volume and electrolyte abnormalities.
Full reference:
Pliquett RU, Obermüller N. Endocrine Testing for the Syndrome of Inappropriate Antidiuretic Hormone Secretion. In: Endotext. NCBI Bookshelf.
7. Serum bicarbonate
Useful in the broader electrolyte/acid-base assessment and can provide clues to vomiting, diuretic use, renal disease, or other competing diagnoses.
Full reference:
Miller NE, Rushlow D, Stacey SK. Diagnosis and Management of Sodium Disorders: Hyponatremia and Hypernatremia. American Family Physician. 2023;108(5):476-486.
8. BUN / serum urea
SIADH often has low or low-normal BUN/urea because of dilution and increased water retention.
Full reference:
Pliquett RU, Obermüller N. Endocrine Testing for the Syndrome of Inappropriate Antidiuretic Hormone Secretion. In: Endotext. NCBI Bookshelf.
9. Serum creatinine
Assess renal function because significant renal impairment can itself disturb water and sodium handling and complicate the diagnosis of SIADH.
Full reference:
Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014;170(3):G1-G47. doi:10.1530/EJE-13-1020.
10. eGFR
Calculate estimated GFR from creatinine to assess whether renal impairment could account for the abnormal sodium/water handling.
Full reference:
Miller NE, Rushlow D, Stacey SK. Diagnosis and Management of Sodium Disorders: Hyponatremia and Hypernatremia. American Family Physician. 2023;108(5):476-486.
11. Serum uric acid
SIADH frequently produces low serum uric acid.
This is supportive rather than diagnostic by itself.
Full reference:
Pliquett RU, Obermüller N. Endocrine Testing for the Syndrome of Inappropriate Antidiuretic Hormone Secretion. In: Endotext. NCBI Bookshelf.
12. Fractional excretion of uric acid (FE urate)
An elevated FE urate can support SIADH and may be particularly useful when diuretics make urine sodium difficult to interpret.
Endotext discusses FE urate >12% as a potentially useful finding.
Full reference:
Pliquett RU, Obermüller N. Endocrine Testing for the Syndrome of Inappropriate Antidiuretic Hormone Secretion. In: Endotext. NCBI Bookshelf.
13. Urine osmolality
Essential test.
In hypotonic hyponatremia, urine should normally become very dilute. In SIADH, urine remains inappropriately concentrated, typically >100 mOsm/kg.
Full reference:
Spasovski G, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014;170(3):G1-G47. doi:10.1530/EJE-13-1020.
14. Urine sodium
Usually >30 mmol/L in SIADH when dietary sodium intake is adequate and diuretics are absent.
Interpretation is more difficult with diuretics, low dietary sodium, or kidney disease.
Full reference:
Spasovski G, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014;170(3):G1-G47.
15. Urine potassium
Urine potassium can help characterize renal electrolyte losses and can be useful when calculating electrolyte-free water clearance.
Full reference:
Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines. JASN. 2017;28(5):1340-1349. doi:10.1681/ASN.2016101139.
16. Urine creatinine
Urine creatinine can be used with urine sodium and urine uric acid for fractional-excretion calculations.
Full reference:
Pliquett RU, Obermüller N. Endocrine Testing for SIADH. In: Endotext. NCBI Bookshelf.
17. Urine uric acid
Urinary uric acid can help characterize the renal handling of urate in suspected SIADH.
Full reference:
Pliquett RU, Obermüller N. Endocrine Testing for SIADH. In: Endotext. NCBI Bookshelf.
18. Urine specific gravity
A low specific gravity indicates dilute urine. In SIADH, urine is inappropriately concentrated relative to the hypotonic plasma.
Full reference:
Lewis JL III. Hyponatremia. Merck Manual Professional Edition.
19. TSH
Thyroid-stimulating hormone should be checked before diagnosing SIADH because hypothyroidism can contribute to hyponatremia.
Full reference:
Spasovski G, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014;170(3):G1-G47.
20. Free T4
TSH alone may not adequately characterize thyroid function, particularly with pituitary disease.
Free T4 should therefore be considered with TSH when evaluating unexplained euvolemic hyponatremia.
Full reference:
Verbalis JG, Greenberg A, Burst V, et al. Diagnosing and treating hyponatremia: expert panel recommendations. American Journal of Medicine. 2013;126(10 Suppl 1):S1-S42.
21. Morning serum cortisol
A morning cortisol is important because glucocorticoid deficiency can mimic SIADH.
Full reference:
Spasovski G, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014;170(3):G1-G47.
22. ACTH
ACTH helps distinguish primary adrenal insufficiency from central adrenal insufficiency when cortisol is abnormal or suspicion is significant.
Full reference:
Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism. 2016;101(2):364-389. doi:10.1210/jc.2015-1710.
23. ACTH/cosyntropin stimulation test
If adrenal insufficiency remains possible, a 250-µg ACTH stimulation test is the standard confirmatory test in adults when clinically appropriate.
Full reference:
Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. JCEM. 2016;101(2):364-389.
24. Plasma renin
Renin can help evaluate mineralocorticoid deficiency and other causes of renal sodium loss when adrenal disease is suspected.
Full reference:
Bornstein SR, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency. JCEM. 2016;101(2):364-389.
25. Serum aldosterone
Aldosterone can help evaluate mineralocorticoid function, particularly when hyponatremia is accompanied by hypotension, volume depletion, or hyperkalemia.
Full reference:
Pliquett RU, Obermüller N. Endocrine Testing for SIADH. In: Endotext. NCBI Bookshelf.
26. Serum magnesium
Magnesium abnormalities can coexist with diuretic use, gastrointestinal losses, renal disease, and other conditions that complicate the sodium abnormality.
Full reference:
Miller NE, Rushlow D, Stacey SK. Diagnosis and Management of Sodium Disorders. American Family Physician. 2023;108(5):476-486.
27. Serum phosphate
Useful when malnutrition, alcoholism, refeeding, renal disease, or broader electrolyte disturbances are part of the differential.
Full reference:
Miller NE, Rushlow D, Stacey SK. Diagnosis and Management of Sodium Disorders. American Family Physician. 2023;108(5):476-486.
28. Serum lipids
A lipid profile can help identify severe hyperlipidemia that may cause pseudohyponatremia, particularly depending on the laboratory measurement method.
Full reference:
Lewis JL III. Hyponatremia. Merck Manual Professional Edition.
29. Serum total protein / albumin
Marked hyperproteinemia can contribute to pseudohyponatremia with some laboratory methods. Albumin also assists with assessment of systemic illness and liver disease.
Full reference:
Milionis HJ, Liamis GL, Elisaf MS. The hyponatremic patient: a systematic approach to laboratory diagnosis. CMAJ. 2002;166(8):1056-1062.
30. Liver panel
AST, ALT, alkaline phosphatase, bilirubin, albumin and related tests help identify hepatic disease/cirrhosis, an important alternative cause of hyponatremia.
Full reference:
Miller NE, Rushlow D, Stacey SK. Diagnosis and Management of Sodium Disorders. American Family Physician. 2023;108(5):476-486.
31. BNP or NT-proBNP
When heart failure is possible, natriuretic peptides can support the evaluation, although they are not diagnostic of SIADH.
Full reference:
Miller NE, Rushlow D, Stacey SK. Diagnosis and Management of Sodium Disorders. American Family Physician. 2023;108(5):476-486.
32. Urinalysis
Urinalysis can reveal proteinuria, renal disease, infection, glucosuria, and other findings that may alter the differential diagnosis.
Full reference:
Miller NE, Rushlow D, Stacey SK. Diagnosis and Management of Sodium Disorders. American Family Physician. 2023;108(5):476-486.
33. Medication review
This is absolutely essential.
Review thiazides, SSRIs/SNRIs, carbamazepine/oxcarbazepine, antipsychotics, opioids, desmopressin, NSAIDs, chemotherapy drugs and other medications capable of promoting hyponatremia or ADH activity.
Full reference:
Spasovski G, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014;170(3):G1-G47.
34. Chest X-ray
A chest radiograph is commonly used when evaluating unexplained SIADH, looking for pulmonary disease, infiltrates, edema, or a lung mass.
Full reference:
Lewis JL III. Syndrome of Inappropriate ADH Secretion (SIADH). Merck Manual Professional Edition.
35. CT chest
If SIADH remains unexplained—especially in a smoker, patient with weight loss, pulmonary symptoms, or other cancer concerns—CT chest can evaluate for pulmonary malignancy, including small-cell lung cancer.
Full reference:
Verbalis JG, Greenberg A, Burst V, et al. Diagnosing and treating hyponatremia: expert panel recommendations. American Journal of Medicine. 2013;126(10 Suppl 1):S1-S42.
36. CT or MRI brain
Brain imaging is appropriate when there are neurologic symptoms, recent CNS disease/surgery/trauma, or no other explanation for SIADH.
It is not necessary for every patient with uncomplicated SIADH.
Full reference:
Lewis JL III. Syndrome of Inappropriate ADH Secretion (SIADH). Merck Manual Professional Edition.
37. MRI brain/pituitary when endocrine/CNS disease is suspected
MRI can be particularly useful when there is suspicion of pituitary disease, hypothalamic disease, CNS malignancy, inflammation, trauma, or unexplained secondary adrenal insufficiency.
Full reference:
Verbalis JG, Greenberg A, Burst V, et al. Diagnosing and treating hyponatremia: expert panel recommendations. American Journal of Medicine. 2013;126(10 Suppl 1):S1-S42.
38. Cancer-directed imaging
If there is no obvious cause of SIADH, investigate for malignancy according to age, symptoms, smoking history, examination, and other risk factors.
The lung is particularly important, because small-cell lung cancer is a classic cause of SIADH.
Full reference:
Lewis JL III. Syndrome of Inappropriate ADH Secretion (SIADH). Merck Manual Professional Edition.
39. Clinical volume-status examination
Assess for:
- Orthostatic hypotension
- Tachycardia
- Dry mucous membranes
- Skin turgor
- Edema
- Ascites
- JVD
- Weight change
- Fluid balance
SIADH is classically clinically euvolemic.
Full reference:
Spasovski G, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014;170(3):G1-G47.
40. Confirm the complete SIADH diagnostic pattern
Before labeling a patient SIADH, look for the combination of:
- Hypotonic hyponatremia
- Serum osmolality <275 mOsm/kg
- Urine osmolality >100 mOsm/kg
- Urine sodium generally >30 mmol/L with adequate dietary sodium
- Clinical euvolemia
- No recent diuretic explanation
- Adequate renal function
- No adrenal insufficiency
- No clinically important hypothyroidism
- No better alternative explanation.
Full reference:
Christensen B, et al. Approach to the Patient: Hyponatremia and the Syndrome of Inappropriate Antidiuresis (SIAD). Journal of Clinical Endocrinology & Metabolism. 2022;107(8):2362-2376.
Particularly important SIADH laboratory pattern
| Test | Typical SIADH pattern |
|---|---|
| Serum Na | ↓ |
| Serum osmolality | <275 mOsm/kg |
| Urine osmolality | >100 mOsm/kg |
| Urine Na | >30 mmol/L |
| BUN/urea | Low/low-normal |
| Creatinine | Usually normal |
| Uric acid | Often ↓ |
| FE urate | Often ↑, potentially >12% |
| TSH/free T4 | No significant hypothyroidism |
| Cortisol | Adequate |
| Potassium | Usually normal |
| Clinical volume | Euvolemic |
These findings need to be interpreted together rather than using one laboratory value as a stand-alone SIADH test.
One important correction to the terminology
Modern literature increasingly uses “syndrome of inappropriate antidiuresis (SIAD)” rather than SIADH, because elevated circulating ADH/vasopressin itself is not required to make the diagnosis. The European guideline specifically recommends against measuring vasopressin to confirm SIADH.
Core references:
- Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014;170(3):G1-G47. doi:10.1530/EJE-13-1020.
- Pliquett RU, Obermüller N. Endocrine Testing for the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH). Endotext, NCBI Bookshelf.
- Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines. Journal of the American Society of Nephrology. 2017;28(5):1340-1349.
- Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. JCEM. 2016;101(2):364-389.