THE THIRST AXIS

Antidiuretic hormone (ADH, also called vasopressin) is synthesized in the hypothalamus and then migrates in neurosecretory granules along axonal pathways to the posterior pituitary gland. Secretion of ADH is determined principally by the plasma osmolality. The major hormonal action of ADH is on the collecting tubule of the kidney to cause water reabsorption. At high concentrations vasopressin also causes vasoconstriction. ADH secretion is suppressed at plasma osmolality below 280 mOsm/kg, thus allowing maximal water diuresis. Secretion increases to a maximum at a plasma osmolality of 295 mOsm/kg. Large falls in blood pressure or volume also stimulate vasopressin secretion.

Diabetes insipidus

Impaired vasopressin secretion (cranial diabetes insipidus (CDI)) or renal resistance to its action (nephrogenic diabetes insipidus (NDI)) leads to polyu-ria (dilute urine in excess of 3 L/24 h), nocturia and compensatory polydipsia. It must be distinguished from primary polydipsia, which is a psychiatric disturbance characterized by excessive intake of water, and other causes of polyuria and polydipsia, e.g. hyperglycaemia.

Aetiology

CDI is caused by disease of the hypothalamus: neurosurgery, trauma, primary or secondary tumours, infiltrative disease (sarcoidosis, histiocytosis) and idiopathic. Damage to the hypothalamo-neurohypophysial tract or the

posterior pituitary with an intact hypothalamus does not lead to ADH defi-ciency as the hormone can still ‘leak' from the damaged end of the intact neurone. Causes of NDI are listed in Table 14.12.

Clinical features

There is polyuria (as much as 15 L in 24 h) and polydipsia. Patients depend on a normal thirst mechanism and access to water to maintain normonatraemia.

Investigations

■ Urine volume must be measured to confirm polyuria.

■ Plasma biochemistry shows high or high-normal sodium concentration and osmolality. Blood glucose, serum potassium and calcium should be measured to exclude common causes of polyuria.

■ Urine osmolality is inappropriately low for the high plasma osmolality.

■ A water deprivation test is indicated for polyuric patients with normal blood glucose and serum electrolytes to determine if they have DI. Serum and urine osmolality, urine volume and body weight are measured hourly for up to 8 hours during fasting and without fluids. The test is abandoned if the bodyweight drops by > 3%, as this indicates significant dehydration. Serum osmolality remaining within the normal range (275-295 mOsm/ kg) and concentrated urine (>600 mOsmol/kg) is a normal response. Serum osmolality >300 mOsm/kg without adequate concentration of the urine (<600 mOsm/kg) indicates DI at which point desmopressin is given and urine osmolality is measured for a further 2-4 hours while allowing free fluids. NDI is diagnosed if urine osmolality stays the same and CDI diagnosed if urine osmolality increases by >50%.

■ MRI of the hypothalamus is performed in cases of CDI.

Management

Treatment of the underlying condition seldom improves established CDI. Desmopressin, administered orally, nasally or intramuscularly, is the

Table 14.12 Causes of nephrogenic diabetes insipidus

Hypokalaemia

Hypercalcaemia

Drugs: lithium chloride, dimeclocycline, glibenclamide

Renal tubular acidosis

Sickle cell disease

Prolonged polyuria of any cause

Familial (mutation in ADH receptor)

treatment of choice. In mild cases (3-4 L urine per day) thiazide diuretics, carbamezepine and chlorpropramide are used to sensitize the renal tubules to endogenous vasopressin. Treatment of the cause will usually improve NDI.

Syndrome of inappropriate ADH secretion (SIADH)

There is continued ADH secretion in spite of plasma hypotonicity and a normal or expanded plasma volume.

Aetiology

SIADH is caused by disordered hypothalamic-pituitary secretion or ectopic production of ADH, e.g. small-cell lung cancer (Table 14.13).

Clinical features

There is nausea, irritability and headache with mild dilutional hyponatraemia (serum sodium 115-125 mmol/L). Fits and coma may occur with severe hyponatraemia (<115 mmol/L).

Investigations

SIADH must be differentiated from other causes of dilutional hyponatraemia (p. 333). Criteria for diagnosis are:

■ Low serum sodium

■ Low plasma osmolality with ‘inappropriate’ urine osmolality >100 mOsmol/ kg (and typically higher than plasma osmolality)

■ Continued urinary sodium excretion (>30 mmol/L)

■ Absence of hypokalaemia, hypotension and hypovolaemia

■ Normal renal, adrenal and thyroid function.

Hyponatraemia is common during illness in frail elderly patients and it may sometimes be difficult to distinguish SIADH from salt and water depletion. Under these circumstances a trial of 1-2 L 0.9% saline is given. Sodium depletion will respond while SIADH will not.

Table 14.13 Causes of syndrome of inappropriate ADH

Cancer

Many tumours, of which the most common is small-cell cancer of the lung

Brain

Meningitis, cerebral abscess, head injury, tumour

Lung

Pneumonia, tuberculosis, lung abscess

Metabolic

Porphyria, alcohol withdrawal

Drugs

Opiates, chlorpropamide, carbamazepine, vincristine

Management

Mild asymptomatic cases need no treatment other than that of the underlying

cause. For symptomatic cases the options are:

■ Water restriction: 500-1000 mL in 24 hours.

■ Demeclocycline 600-1200 mg daily, inhibits the action of vasopressin on the kidney (i.e. causes nephrogenic DI) and may be useful if water restric-tion is poorly tolerated or ineffective.

■ The specific vasopressin antagonist, tolvaptan, is used for treatment of hyponatraemia secondary to SIADH. It is expensive and not yet widely used.

■ Hypertonic saline, with furosemide to prevent circulatory overload, is necessary in severe cases (Emergency Box 8.1, p. 336).

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

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