Antidiuretic Hormone

Antidiuretic hormone (ADH) is synthesized in the hypothalamus and transported to the posterior pituitary gland. ADH’s major action is on the distal or collecting tubules of the kidney where it promotes reabsorption of solute free water. ADH secretion is stimulated by an increase in plasma osmolality via osmoreceptors and by a decrease in plasma volume via volume receptors.

The two major clinical syndromes of antidiuretic hormone secretion are neurogenic diabetes insipidus (DI), an ADH deficiency disorder, and the syndrome of inappropriate ADH secretion (SIADH), a disorder of excess ADH synthesis.

Test

DI

SIADH

Normal

Serum sodium

>145 meq/L

<130 meq/L

135-145 meql/L

Plasma osmolality

>295 mOsm

<275 mOsm

278-298 mOsm

Urine osmolality

<300 mOsm

>1200 mOsm

50–1200 mOsm

U/P osmol ratio

<1

>4

3-4

Urine output

>2.5 L/d

Decreased

~2.5 L/d

DI is the chronic excretion of very high volumes of hypo-osmotic urine due to ADH deficiency. Polyuria triggers the thirst mechanism resulting in increased polydipsia. If water intake is inadequate dehydration occurs. DI can be categorized as neurogenic and nephrogenic. In neurogenic DI, ADH secretion by the pituitary or hypothalamus is decreased. ADH deficiency can be partial or complete, depending on the degree of disturbance to the hypothalamus or pituitary. In nephrogenic DI, ADH production and secretion are adequate and appropriate, but the kidneys do not respond to the hormone because of damage to the renal tubules.

Plasma osmolality, urine osmolality and serum sodium are the principal laboratory tests used to diagnose ADH abnormalities. Polyuria increases plasma osmolality to >295 mmol/L and serum sodium to >145 meq/L. Urine osmolality is <300 mmol/L. In partial neurogenic DI, urine osmolality may range between 300 and 800 mmol/L.

Diabetes insipidus can be confirmed with an overnight water deprivation test. This test should be done if a baseline serum osmolality is <295 mosmol. Fluid intake is restricted for 12 to 18 hours and the body weight, urine osmolality, volume and plasma osmolality are measured every 1-2 hours. The test should be discontinued if body weight falls by more than 3%. The objective is to obtain consecutive urine osmolality's which do not differ by more than 30 mosmol. At this point, 1 ug of DDAVP is administered and a urine specimen is collected one hour later to determine osmolality. Results are interpreted as follows:

Urine Osmolality

Interpretation

50% increase

Neurogenic DI

10 - 50% increase

Partial Neurogenic DI

<10% increase

Nephrogenic DI

One can also measure antidiuretic hormone levels at maximum dehydration, which helps differentiate neurogenic from nephrogenic DI. In neurogenic DI, ADH levels decrease as plasma osmolality increases. Conversely, in nephrogenic DI ADH levels increase with increasing plasma osmolality.

SIADH is the clinical condition that results from inappropriate continued secretion of ADH in the presence of low serum osmolality. The low serum osmolality is due to the retention of water by the kidney in response to ADH. The low serum sodium concentration is due to the dilutional effect of water retention and to the loss of sodium in the urine. Initial symptoms include anorexia, nausea, vomiting, and headache. Cerebral symptoms begin to appear when serum sodium is less than 125 meq/L. Severe hyponatremia (sodium <110 meq/L) or rapidly developing hyponatremia can cause cerebral edema, which is expressed as irritability, confusion, disorientation, convulsions, hemiparesis, and coma.

The major causes of SIADH include neoplasia, pulmonary disorders, neurological disorders and certain drugs. Drugs most commonly associated with SIADH are clofibrate, chlorpropamide, vincristine, cyclophosphamide, phenothiazines, tricyclic antidepressants, thiazides, and carbamazepine.

Laboratory test results that favor a diagnosis of SIADH include; serum sodium <120 meq/L, serum osmolality <280 mOsm, decreased BUN, decreased serum uric acid, urine osmolality >100 mOsm, and urine sodium >20 meq/L. Other diagnostic criteria include the absence of dehydration, edema, adrenal insufficiency, hypothyroidism or renal failure.