Syndrome of Inappropriate ADH Secretion (SIADH)
This is a condition characterised by continued excessive ADH secretion from the posterior pituitaray gland or another source in spite of plasma hypotonicity and a normal or expanded plasma volume. This results in dilutional hyponatraemia, in which the sodium remains normal but total body fluid increases.
- Disordered hypothalamic-pituitary secretion of ADH.
- Ectopic production of ADH, e.g. from a small-cell lung cancer.
- Cancer: many tumours cause SIADH, but the most common is small-cell lung cancer.
- Brain: meningitis, cerebral abscess, head injury, subarachnoid haemorrhage, Guillain-Barré syndrome, tumour.
- Lung: pneumonia, tuberculosis, lung abscess.
- Metabolic: porphyria, alcohol withdrawal.
- Drugs: opiates, chlorpropamidem carbamezapine, ciprofloxacin, cyclophosphamide, vincristine.
- Other: hypothyroidism, sarcoidosis.
- In health, ADH acts on the distal convoluted tubule and the collecting duct of the nephron to cause retention of water (but not solute), which causes dilution of the blood and a decrease in the concentration of solutes such as sodium.
- When the plasma becomes too diluted, the osmolality is low and this is detected by osmoreceptors in the hypothalamus which respond by inhibiting ADH secretion, and preventing a further increase in fluid volume and reduction in osmolality.
- In SIADH, however, the release of ADH is no longer inhibited when plasma osmolality falls, and this means that when an individual ingests water, their plasma osmolality continues to fall in an unopposed fashion. It is thus described as a ‘hypoosmolar state’.
- As the main plasma solute is sodium, SIADH is often detected by a reduced serum sodium concentration. This is not because sodium has been lost in the urine etc., but because the normal quantity of sodium is now diluted.
- SIADH is primarily a condition that results in the abnormal handling of water load, and not a problem of excessive solute loss. For this reason, it is usually treated with fluid restriction (especially water restriction) +/- diuretics which can decrease reabsorption of water.
- Care must be taken so as not to correct water balances in SAIDH patients too rapidly.
- Myalgia/generalised muscle weakness
- Hyporeflexia, ataxia, tremor
- Cheyne-Stokes respiration (an abnormal pattern of periodically progressively deeper and faster breathing followed by a gradual decrease to apnoea in cycles of 30-120 seconds)
- Mild dilutional hyponatraemia (serum sodium 115-125 mmol/L).
- Fits and coma if severe hyponatraemia (<115mmol/L).
It is important to distinguish SIADH from other causes of dilutional hyponatraemia.
- Euvolaemic hyponatraemia – low blood sodium with no evidence of extracellular fluid overload
- Low serum sodium
- High urine sodium
- Low plasma osmolality with ‘inappropriate’ urine osmolality >100mOsmol/kg (and typically > plasma osmolality)
- Continued urinary sodium excretion >30mmol/L
- Absence of hypokalaemia, hypotension and hypovolaemia
- Normal renal, adrenal and thyroid function.
SIADH or Salt and Water Deprivation?
Hyponatraemia is common during illness and in frail elderly patients. It is sometimes difficult to distinguish SIADH from salt and water deprivation. To try to do so, however, you can give a trial of 1-2L 0.9% saline; sodium depletion will respond to this, whereas SIADH will not.
- Do not require treatment, other than of underlying cause.
- Water restriction: 500-1000mL in 24h.
- Demeclocycline 600-1200mg daily, inhibits the action of ADH on the kidney (i.e. causes nephrogenic DI) and may be useful if water restriction is poorly tolerated or ineffective.
- Tolvaptan, a V2 antagonism, is used to treat hyponatraemia secondary to SIADH, but it is expensive so is used sparingly. Patients who receive an initial dose of this are often managed with life-long fluid restriction afterwards.
- Hypertonic saline, with furosemide to prevent circulatory overload, is necessary in severe cases.