Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Definitions:

• Inappropriate secretion of ADH (vasopressin) that leads to retention of water and hyponatraemia.

Pathophysiology:

• Excess ADH is secreted from the posterior pituitary or an ectopic source

-Elevated levels lead to water retention and excretion of concentrated urine. This has two major effects: hyponatremia and volume expansion

• Despite volume expansion, edema is not seen in syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

This is because natriuresis (excretion of excessive sodium in urine) occurs despite hyponatremia

• Reasons for natriuresis

- Volume expansion causes an increase in atrial natriuretic peptide (increases urine sodium excretion)

- Volume expansion leads to a decrease in proximal tubular sodium absorption

- The renin–angiotensin–aldosterone system is inhibited

Etiology:

Clinical Presentation:

• Acute hyponatremia—Signs and symptoms are secondary to brain swelling (osmotic water shifts, leading to increased ICF volume)

- Lethargy, somnolence, weakness

- Can lead to seizures, coma, or death if untreated

• Chronic hyponatremia

- May be asymptomatic

- Anorexia, nausea, and vomiting

- CNS symptoms are less common because chronic loss of sodium and potassium from brain cells decreases brain edema (secondary water shifts from ICF to ECF)

Diagnosis:

• SIADH is a diagnosis of exclusion (after other causes of hyponatremia have been ruled out).

• The following help in supporting the diagnosis:

- Hyponatremia and inappropriately concentrated urine; plasma osmolality, 270 mmol/kg

- Low serum uric acid level

- Low BUN and creatinine

- Normal thyroid and adrenal function, as well as renal, cardiac, and liver function

- Measurement of plasma and urine ADH level

- Absence of significant hypervolemia

- Absence of hypokalaemia (or hypotension)

Hyponatraemia is very common during illness in frail elderly patients and it may sometimes be clinically difﬁcult to distinguish SIADH from salt and water depletion

Managment:

• Correct the underlying cause, if known.

• For asymptomatic patients

- Water restriction is usually sufficient (500–1000 mL daily)

- Use normal saline in combination with a loop diuretic if faster results are desired

- Lithium carbonate or demeclocycline are other options (with side effects)—reversible form of nephrogenic diabetes insipidus

• For symptomatic patients

- Restrict water intake

- Give isotonic saline. Hypertonic saline may occasionally be indicated in severe cases (potentially dangerous and should only be used with extreme caution)

• Do not raise the serum sodium concentration too quickly. Rapid flux of water into the ECF can result in central pontine myelinolysis (demyelination syndrome may result). A general guideline is that the rate of sodium replacement should not exceed 0.5 mEq/L per hour

Complications:

• Cerebral edema may be observed when plasma osmolality decreases faster than 10 mOsm/kg/h. This can lead to cerebral herniation

• Noncardiogenic pulmonary edema may develop, especially in marathon runners

• CPM is the feared complication of excessive, overly rapid correction of hyponatremia.

Typical features are disorders of upper motor neurons, including spastic quadriparesis and pseudobulbar palsy, as well as mental disorders ranging from confusion to coma.

References:

Kumar, P. and Clark, M. (n.d.). Kumar & Clark's clinical medicine. 8th ed. Spain: Elsevier Ltd., pp.993-994.
Kim, J. and Mukovozov, I. (n.d.). Toronto Notes 2017. 33rd ed. Toronto, Ontario, Canada: Toronto Notes for Medical Students, Inc., p.E19.
Agabegi, S. and Agabegi, E. (n.d.). Step-up to medicine. 4th ed. Lippincott Williams & Wilkins, a Wolters Kluwer business, pp.179-1780.
Emedicine.medscape.com. (2018). Syndrome of Inappropriate Antidiuretic Hormone Secretion: Practice Essentials, Background, Pathophysiology. [online] Available at: https://emedicine.medscape.com/article/246650-overview#a7 [Accessed 23 Sep. 2018].

First author: Fajr Alqahtani

Format Editor: Noura Abdullah Alsubaie