Atlas of pathophysiology, 2 Edition

Part II - Disorders

Endocrine Disorders

Diabetes insipidus

A disorder of water metabolism, diabetes insipidus results from a deficiency of circulating vasopressin (also called antidiuretic hormone, or ADH) or from renal resistance to this hormone. The three forms of diabetes insipidus are neurogenic, nephrogenic, and psychogenic. Neurogenic diabetes insipidus is caused by a deficiency of ADH; nephrogenic diabetes insipidus, by the resistance of renal tubules to ADH. Diabetes insipidus is characterized by excessive fluid intake and hypotonic polyuria. A decrease in ADH levels leads to altered intracellular and extracellular fluid control, causing renal excretion of a large amount of urine.

Age Alert

Diabetes insipidus may begin at any age and is slightly more common in men than in women.

In uncomplicated diabetes insipidus, the prognosis is good with adequate water replacement, and patients usually lead normal lives.

Causes

·   Neurogenic: stroke, hypothalamic or pituitary tumor, cranial trauma or surgery

·   Nephrogenic: X-linked recessive trait, end-stage renal failure

·   Psychogenic: primary polydipsia or sarcoidosis

·   Transient diabetes insipidus: certain drugs, such as lithium, phenytoin, or alcohol

Pathophysiology

Diabetes insipidus is related to an insufficiency of ADH, leading to polydipsia and polyuria.

Neurogenic, or central, diabetes insipidus is an inadequate ADH response to changes in plasma osmolarity. A lesion of the hypothalamus, infundibular stem, or posterior pituitary partially or completely blocks ADH synthesis, transport, or release.

Neurogenic diabetes insipidus has an acute onset. A three-phase syndrome can occur, which involves:

·   progressive loss of nerve tissue and increased diuresis

·   normal diuresis

·   polyuria and polydipsia, reflecting permanent loss of the ability to secrete adequate ADH.

Nephrogenic diabetes insipidus is caused by an inadequate renal response to ADH. The collecting duct's permeability to water doesn't increase in response to ADH. Nephrogenic diabetes insipidus is generally related to disorders and drugs that damage the renal tubules or inhibit the generation of cyclic adenosine monophosphate in the tubules. In addition, hypokalemia or hypercalcemia impairs the renal response to ADH. A rare genetic form of nephrogenic diabetes insipidus is an X-linked recessive trait.

Psychogenic diabetes insipidus is caused by an extremely large fluid intake. This primary polydipsia may be idiopathic or reflect psychosis or sarcoidosis. The polydipsia and resultant polyuria wash out ADH more quickly than it can be replaced. Chronic polyuria may overwhelm the renal medullary concentration gradient, rendering the kidneys partially or totally unable to concentrate urine.

Regardless of the cause, insufficient ADH causes the immediate excretion of large volumes of dilute urine and consequent plasma hyperosmolality. In conscious individuals, the thirst mechanism is stimulated, usually for cold liquids. If diabetes insipidus ensues, severe dehydration, shock, and renal failure can result.

Signs and symptoms

·   Polydipsia and polyuria up to 20 L/day (cardinal symptoms)

·   Nocturia

·   Sleep disturbance and fatigue

·   Headache and visual disturbance

·   Abdominal fullness, anorexia, and weight loss

·   Fever

·   Changes in level of consciousness

·   Hypotension

·   Tachycardia

Diagnostic test results

·   Urinalysis shows almost colorless urine of low osmolality and low specific gravity.

·   Water deprivation test identifies vasopressin deficiency, resulting in renal inability to concentrate urine.

Treatment

·   Vasopressin to control fluid balance and prevent dehydration until the cause of diabetes insipidus can be identified and eliminated

·   Hydrochlorothiazide with potassium supplement

·   Desmopressin acetate

·   Chlorpropamide

·   Fluid intake to match output

P.279

MECHANISM OF ADH DEFICIENCY

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Clinical Tip

Laboratory values for patients with diabetes insipidus

Value

Normal

Diabetes insipidus (DI)

Serum ADH

<2.5 pg/ml

Decreased in central DI, may be normal with nephrogenic or psychogenic DI

Serum osmolality

285 to 300 mOsm/kg

>300 mOsm/kg

Serum sodium

136 to 145 mEq/L

>145 mEq/L

Urine osmolality

300 to 900 mOsm/kg

<300 mOsm/kg

Urine specific gravity

1.005 to 1.030

<1.005

Urine output

1 to 1.5 L/24 hr

30 - 40 L/24 hours

Fluid intake

1 to 1.5 L/24 hr

>50 L/24 hours

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