Sun21November1151AM 1

A 74-year-old woman presents to the Emergency department with a change in her mental state over the past few hours. She has a medical history of ischaemic heart disease, hypertension and hypothyroidism. Medication includes hydrochlorothiazide, aspirin, ramipril and levothyroxine.

On physical examination, she has decreased skin turgor, orthostatic hypotension and is disorientated in time and place. There are no focal neurological signs.

Initial biochemical tests are as follows:

Na 111 mmol/L 135-145

K 4.1 mmol/L 3.5-5.1

Cl 105mmol/L 99-101

Bic 29 mmo/L 22-29

Urea 16.4mmol/L 1.7-8.3

Creatinine 320µmol/L 44-80

Glucose 13.5mmol/L 3.5-5.5

Plasma osmolality 278mOsm/kg

Urinary osmolality 450mOsm/kg

TSH 6.2 miu/L 0.1-6.0

Free T4 10.1 pmol/L 10-25

Free T3 1.4nm/L 1.0-2.5

Which one of the following is the most likely cause of this patient's clinical state?

(Please select 1 option)

Hyperglycaemia

Drug idiosyncrasy Correct

Uraemia

Hypothyroidism

Cerebrovascular accident

Explanation

This patient has a significant hyponatraemia. It is sufficiently low to give rise to clinical manifestations.

The symptoms and signs of hyponatraemia are mainly neurological and are related both to the severity and in particular to the rapidity of onset of the change in the plasma sodium concentration.

Patients may also have symptoms related to concurrent volume depletion and to possible underlying neurologic disorders that predispose to the electrolyte abnormality.

125 - 130mmol/L - Nausea and malaise

115 - 125mmol/L - Headache, lethargy, seizures and coma

<120mmol/L - Up to 11% present with coma.

The thiazide diuretics act on the distal convoluted tubule; as a result, they do not interfere with medullary function or with ADH-induced water retention.

In vitro data indicate that thiazides increase water permeability and water reabsorption in the inner medullary-collecting duct, an effect that is independent of ADH. In addition to water retention, the combination of increased sodium and potassium excretion (due to the diuretic) and enhanced water reabsorption (due to ADH) can result in the excretion of urine with a sodium plus potassium concentration higher than that of the plasma. Loss of this fluid can directly promote the development of hyponatraemia independent of the degree of water intake.

Ramipril and other ACE inhibitors may rarely cause severe hyponatraemia. The mechanism for this is unclear.

The normal response to hyponatraemia is to suppress ADH secretion completely, resulting in the excretion of a maximally dilute urine with an osmolality below 100 mOsm/kg of water and a specific gravity of 1.003 or lower. Higher values indicate an inability to excrete free water normally that is generally due to the continued secretion of ADH.

Most hyponatraemic patients are unable to produce dilute urine, and their urine osmolality may be 300 mOsm/kg of water or even greater. In those patients with hyponatraemia and a low plasma osmolality, the urine osmolality can be used to distinguish between impaired water excretion and primary polydipsia, in which water excretion is normal but intake is so high that it exceeds excretory capacity. In patients with impaired water excretion due to hypovolaemia the urine osmolality often exceeds 450 mOsm/kg of water.

In the absence of adrenal insufficiency or hypothyroidism, the two major causes of hyponatraemia with hypo-osmolality and inappropriately concentrated urine are volume depletion and the syndrome of inappropriate ADH secretion (SIADH). These disorders can usually be distinguished by measuring the urine sodium concentration, which is typically below 25 mmol/L with volume depletion and above 40 mmol/L in patients with SIADH.

Whilst the degree of hyperglycaemia and uraemia and dehydration alone might not contribute to this patient's clinical state, they are contributing factors.

Answer Statistics

1

5%

2

78%

3

8%

4

6%

5

5%

Times answered: 266