eMedicine Specialties > Endocrinology > Pituitary Gland

Diabetes Insipidus

Author: Michael Cooperman, MD, Clinical Associate Professor of Endocrinology, Temple University; Chair, Department of Internal Medicine, Division of Endocrinology, Jeanes Hospital
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Updated: Feb 13, 2008

Introduction

Background

Central diabetes insipidus (DI) is characterized by decreased secretion of antidiuretic hormone (ADH), also known as arginine vasopressin (AVP), that results in polyuria and polydipsia by diminishing the patient's ability to concentrate urine. Diminished or absent ADH can be the result of a defect in one or more sites involving the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei, or the supraopticohypophyseal tract. In contrast, lesions of the posterior pituitary rarely cause permanent diabetes insipidus because ADH is produced in the hypothalamus and still can be secreted into the circulation.

Nephrogenic diabetes insipidus is characterized by a decrease in the ability to concentrate urine due to a resistance to ADH action in the kidney.¹ Nephrogenic diabetes insipidus can be observed in chronic renal insufficiency, lithium toxicity, hypercalcemia, hypokalemia, and tubulointerstitial disease. The rare hereditary form of nephrogenic diabetes insipidus is transmitted as an X-linked genetic defect of the V2 receptor gene. A rare autosomal variant is caused by mutation in the aqua porin gene AQP2, a water-channel exclusively expressed in the collecting ducts of the kidney.

Pathophysiology

ADH is the primary determinant of free water excretion in the body. Its main target is the kidney, where it acts by altering the water permeability of the cortical and medullary collecting tubules. Water is reabsorbed by osmotic equilibration with the hypertonic interstitium and returned to the systemic circulation. The actions of ADH are mediated through at least 2 receptors—V1 mediates vasoconstriction, enhancement of corticotrophin release, and renal prostaglandin synthesis; V2 mediates the antidiuretic response.

Frequency

United States

Diabetes insipidus is uncommon, with a prevalence of 1 case per 25,000 people.

Mortality/Morbidity

• Mortality is rare in adults as long as water is available.
• Severe dehydration, hypernatremia, fever, cardiovascular collapse, and death can ensue in children, elderly people, or in those with complicating illnesses.

Sex

• No significant sex differences in central or nephrogenic diabetes insipidus exist.
• Male and female prevalence are equal.

Clinical

History

The clinical presentation of diabetes insipidus (DI) depends on the cause, the severity, and the associated medical condition(s) of the patient.

• The most common form of diabetes insipidus is that which follows trauma or surgery to the region of the pituitary and hypothalamus. It may exhibit 1 of 3 patterns—transient, permanent, or triphasic. The triphasic pattern is observed more often clinically.  
  • First, a polyuric phase occurs and lasts 4-5 days. Inhibition of ADH causes the polyuric phase. An immediate increase in urine volume and a concomitant fall in urine osmolality occur.
  • Second, an antidiuretic phase of 5-6 days occurs, which results from release of stored hormone. The urine osmolality rises.
  • The third phase can be permanent diabetes insipidus, when stores of ADH are exhausted and the cells that produce more ADH are absent or unable to produce.
  • Polyuria, polydipsia, and nocturia (from 3-18 L) are the predominant symptoms.
  • In infants, crying, irritability, growth retardation, hyperthermia, and weight loss may be the most apparent signs.
  • In children, enuresis, anorexia, linear growth defects, and fatigability typically predominate.
• Patients with a nontraumatic onset typically have a much more indolent course. Pregnancy is associated with an increased risk of diabetes insipidus.
  • Polyuria, polydipsia, hydronephrosis, bladder enlargement, and signs of dehydration are common.
  • Symptoms and signs of simultaneous anterior pituitary dysfunction may be present but are rare.
  • The daily urine volume is highly variable (3-20 L/d), and patient tolerance of dehydration also varies among individuals.
  • Many patients have a predilection for drinking cold liquids, often water.
  • Neurologic symptoms vary with the patient's ability to access water; those with free access may have no symptoms at all.

Physical

The physical examination varies with the severity and chronicity of the diabetes insipidus.

• The examination findings may be entirely normal.
• Signs of dehydration and an enlarged bladder may be present; otherwise, no specific signs of diabetes insipidus exist.

Causes

Recent literature indicates 30% of cases to be idiopathic, 25% related to malignant or benign tumors of the brain or pituitary, 16% secondary to head trauma, and 20% following cranial surgery.

• Idiopathic diabetes insipidus is associated with destruction of cells in the hypothalamus, often as part of an autoimmune process. This is characterized by lymphocytic infiltration of the stalk and posterior pituitary. An MRI may show abnormalities of these structures. The presence of antibodies directed against vasopressin cells may help predict the development of central diabetes insipidus.
• Familial diabetes insipidus is rare. It is inherited as an autosomal dominant disorder, and mutations involving AVP- neurophysin gene have been identified. Mutations reported to date involve signal peptide region or, more commonly, neurophysin II. The mechanism by which the mutations impair AVP release is not understood but may involve the accumulation of the ADH precursor leading to the death of the ADH-producing cells.
• Diabetes insipidus after neurosurgery or trauma varies with the extent of damage. Approximately 10-20% of patients will experience diabetes insipidus following transsphenoidal removal of an adenoma. This percentage increases to 60-80% with large tumors. Not all cases of diabetes insipidus are permanent. The most common causes of postoperative polyuria are excretion of excess fluid given during surgery and an osmotic diuresis as a result of treatment for cerebral edema.²
• Primary intracranial tumors causing diabetes insipidus include craniopharyngioma or pineal tumors. Appearance of other hypothalamic manifestations may be delayed for as long as 10 years. Thus, periodic follow-up of patients diagnosed with idiopathic diabetes insipidus is necessary to detect slowly growing intracranial lesions.
• Other causes include cancer (eg, lung cancer, lymphoma, leukemia), hypoxic encephalopathy, infiltrative disorders (histiocytosis X, sarcoidosis), anorexia nervosa, and vascular lesions such as arteriovenous malformations or aneurysms.

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