Schwartz–Bartter syndrome

SIADH is a disorder in which excessive release of antidiuretic hormone causes the kidneys to retain free water, leading to dilutional hyponatraemia. It typically results in low serum sodium, low serum osmolality, and concentrated urine despite normal kidney and adrenal, and euvolaemia.

Six cardinal criteria form the enduring framework for SIADH diagnosis

• Hyponatraemia (Na⁺ <135 mEq/L)
• Low plasma osmolality (<275 mOsm/kg)
• Urine osmolality >100 mOsm/kg despite hyponatraemia
• Euvolaemic clinical state
• No adrenal, thyroid, pituitary, or renal insufficiency
• Reversal with fluid restriction

Pathophysiology: SIADH results from increased ADH secretion (central or ectopic) or enhanced renal response, independent of serum tonicity. Causes include:

• Malignancy – especially small cell lung carcinoma (ectopic ADH production)
• CNS disturbances – stroke, trauma, infection
• Pulmonary disease – pneumonia, tuberculosis
• Medications – SSRIs, carbamazepine, cyclophosphamide, vincristine
• Post-operative states and pain
• Hereditary SIADH – gain-of-function V2 receptor mutations

Clinical Features: Symptoms stem from cerebral oedema due to hyponatraemia with nausea, confusion, seizures, and coma. Treatment includes:

• Fluid restriction (first-line)
• Hypertonic saline for severe symptoms
• Loop diuretics + salt tabs (in chronic cases)
• Vasopressin receptor antagonists – e.g., tolvaptan, conivaptan

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History

1957 – First described by William B. Schwartz (1922-2009) and Frederic Bartter (1914-1983) in patients with bronchogenic carcinoma, marking the beginning of understanding paraneoplastic endocrine syndromes.

We have studied a syndrome of impaired water excretion that is characterized by hyponatremia, urinary sodium loss, and continued antidiuresis despite hypotonicity… The disorder is best explained by a sustained inappropriate secretion of ADH.

Schwartz and Bartter 1957

This case series demonstrated a unique combination of hyponatraemia, concentrated urine, and low serum osmolality in the absence of hypovolaemia or oedema, despite continuous antidiuresis. It laid the foundation for diagnostic criteria that remain largely unchanged.

1967 – Bartter and Schwartz then proposed a diagnostic criteria that remain largely unchanged today.

The diagnosis of this disorder should rest upon six major findings… hyponatremia, hypo-osmolality of the plasma, continued renal excretion of sodium, urine osmolality exceeding that of plasma, absence of clinical evidence of volume depletion, and normal function of adrenal and thyroid glands

Bartter and Schwartz, 1967

These six cardinal criteria form the enduring framework for SIADH diagnosis and remain widely used in clinical and academic settings.

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Comparative Context:

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Associated Persons

• Frederic Crosby Bartter (1914-1983)
• William Benjamin Schwartz (1922-2009)

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Alternative names

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References

Historical references

• Schwartz WB, Bennett W, Curelop S, Bartter FC. A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med. 1957 Oct;23(4):529-42.
• Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med. 1967 May;42(5):790-806.

Eponymous term review

• Botero-Velez M, Curtis JJ, Warnock DG. Brief report: Liddle’s syndrome revisited–a disorder of sodium reabsorption in the distal tubule. N Engl J Med. 1994 Jan 20;330(3):178-81.
• Hansson JH, Nelson-Williams C, Suzuki H, Schild L, Shimkets R, Lu Y, Canessa C, Iwasaki T, Rossier B, Lifton RP. Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet. 1995 Sep;11(1):76-82.
• Awadalla M, Patwardhan M, Alsamsam A, Imran N. Management of Liddle Syndrome in Pregnancy: A Case Report and Literature Review. Case Rep Obstet Gynecol. 2017;2017:6279460.
• Enslow BT, Stockand JD, Berman JM. Liddle’s syndrome mechanisms, diagnosis and management. Integr Blood Press Control. 2019 Sep 3;12:13-22.