Water retention also occurs in the syndrome of inappropriate secretion of ADH (SIADH). In this condition, an endogenous source of ADH (either cerebral or tumour-derived) promotes water retention by the kidney in the absence of an appropriate physiological stimulus (Box 16.13). The clinical diagnosis requires the patient to be euvolaemic, with no evidence of cardiac, renal or hepatic disease potentially associated with hyponatraemia. Other non-osmotic stimuli that cause release of ADH (pain, stress, nausea) should also be excluded. Suppoive laboratory findings are shown in Box 16.13. In this situation, plasma concentrations of sodium, chloride, urea and uric acid are low with a correspondingly reduced osmolality. Urine osmolality, which should physiologically be maximally dilute (approximately 50 mmol/kg) in the face of low plasma osmolality, is higher than at least 100 mmol/kg and indeed is typically higher than the plasma osmolality. The urine sodium concentration is typically high (> 30 mmol/L), consistent with euvolaemia and lack of compensatory factors promoting sodium retention. Plasma and urine electrolytes and osmolality (Box 16.14) are usually the only tests required to classify the hyponatraemia. Doubt about clinical signs of ECF volume may be resolved with measurement of plasma renin activity. Measurement of ADH is not generally helpful in distinguishing between these categories of hyponatraemia. This is because ADH is activated both in hypovolaemic states and in most chronic hypervolaemic states, as the impaired circulation in those disorders activates ADH release through non-osmotic mechanisms. Indeed, these disorders may have higher circulating ADH levels than patients with SIADH. The only disorders listed in Box 16.12 in which ADH is suppressed are primary polydipsia and iatrogenic water intoxication, where the hypo-osmolar state inhibits ADH release from the pituitary. The treatment of hyponatraemia is critically dependent on its rate of development, severity and underlying cause. If hyponatraemia has developed rapidly (over hours to days), and there are signs of cerebral oedema such as obtundation or convulsions, sodium levels should be restored to normal rapidly by infusion of hypeonic (3%) sodium chloride. A common approach is to give an initial bolus of 100 mL, which may be repeated once or twice over the initial hours of observation, depending on the neurological response and rise in plasma sodium. On the other hand, rapid correction of hyponatraemia that has developed slowly (over weeks to months) can be hazardous, since brain cells adapt to slowly developing hypo-osmolality by reducing the intracellular osmolality, thus maintaining normal cell volume. DAVIDSON'S PRINCIPLES AND PRACTICE OF MEDICINE 22nd EDITION PAGE NO-438