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J R Soc Med. 2002 September; 95(9): 461–462.
PMCID: PMC1279997

Hyponatraemia without hypovolaemia

A J Clarke, MB BSc, V Toh, MRCP, S M Greenfield, MD FRCP, and J R Katz, MD MRCP

Hyponatraemia is commonly attributed to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), but other causes must first be excluded.


A man of 66 attended the emergency department because of confusion, unsteadiness, slurred speech, nausea and symptoms of prostatic obstruction. For the past month he had been troubled by fatigue and myalgia, and for ten days he had been experiencing nausea (treated by his general practitioner with prochlorperazine). Previously he had been well, and prochlorperazine was his only current medication. On examination he was not obviously dehydrated. Blood pressure was 120/80 mm Hg, with no postural drop. There were no focal neurological signs and no physical abnormalities were detected elsewhere, including the prostate. Initial investigation disclosed pronounced hyponatraemia (sodium 110 mmol/L), low serum osmolality (261 mosm/kg) and inappropriately high urine osmolality (462 mosm/kg). Other blood results, including prostate specific antigen, C-reactive protein, potassium and glucose, were normal. Free thyroxine was low at 6 pmol/L, but thyroid stimulating hormone was normal at 2.27IU/L. The working diagnoses at this point were SIADH and sick euthyroid syndrome.

The patient was admitted and the prochlorperazine was stopped. CT scans of the brain, thorax, pancreas, adrenals and the remainder of the abdomen were normal, as were findings on upper gastrointestinal tract endoscopy. He was fluid-restricted to 1 L per day and over nine days his sodium climbed to 137 mmol/L. The gait and speech disturbance rapidly resolved. When his fluid intake was lifted to 2 L/day, plasma sodium fell to 128 mmol/L and his symptoms began to relapse. A short tetracosactide (Synacthen) test gave the following results: at 0 min, cortisol < 30 nmol/L, corticotropin < 5 nmol/L; at 30 min and 60 min, cortisol 131 and 174 nmol/L, respectively. A long tetracosactide test gave a flat early cortisol response to 2 mg tetracosactide with a delayed peak after 24 h (Figure 1). An MRI scan of the brain and pituitary showed no abnormalities. Luteinizing hormone, follicle stimulating hormone, testosterone and prolactin levels were normal. A glucagon test suggested growth hormone deficiency. Secondary adrenal insufficiency was diagnosed and the patient's symptoms of fatigue, myalgia and nausea all responded to hydrocortisone replacement therapy. His prostatic symptoms also resolved. Plasma sodium became normal despite a fluid intake in excess of 3 L/day, and the thyroid dysfunction resolved without thyroxine treatment.

Figure 1
Long tetracosactide test. Mean normal cortisol response (Ref. 4) and patient's response to 2 mg tetracosactide. [open triangle] Normal; ○ patient


SIADH should not be diagnosed until hypoadrenalism has been excluded1. The long tetracosactide test in this patient showed a delayed peak at 24 h which was diagnostic of secondary adrenal insufficiency. Preservation of mineralo-corticoid function in this condition prevents the salt and water depletion seen in Addison's disease. In secondary adrenal insufficiency, hypocortisolism results in increased vasopressin secretion2 and an impairment of renal excretion of a water load independent of vasopressin effects3—hence the hyponatraemia. In the case presented here, cortisol deficiency also caused sick euthyroid syndrome.


1. Schwartz WB, Bennet 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;23: 529-42 [PubMed]
2. Raff H. Clucocorticoid inhibition of neurohypophysial vasopressin secretion. Am J Physiol 1987;252: R365-44 [PubMed]
3. Linas SL, Berl T, Robertson GL, Aisenbrey GA, Schrier RW, Anderson RJ. Role of vasopressin in the impaired water excretion of glucocorticoid deficiency. Kidney Int 1980;18: 58-67 [PubMed]
4. Ross, RJM. Protocols for common endocrine tests. In: Grossman A, ed. Clinical Endocrinology. Oxford: Blackwell Scientific Publications, 1992: 1015-32

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press