At a Glance

The features of Hypothalamic (Central) Diabetes Insipidus (DI) include:

  • polyuria

  • inappropriately dilute urine

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  • hypernatremia and hyperosmolality if water-restricted

  • deficient plasma vasopressin

  • water-balance restored by exogenous vasopressin

Diabetes Insipidus (DI) is the inability to concentrate urine due to lack of action of vasopressin. Diabetes insipidus may be a consequence of vasopressin deficiency (Central DI) or inability of nephrons to respond to adequate concentrations of vasopressin (nephrogenic DI). In DI, dehydration and increased serum osmolality and sodium occur only if the individual has restricted access to water.

Central DI may be a consequence of:

  • head trauma

  • transphenoidal resection of anterior pituitary tumor

  • neoplasms (primary or metastatic)

  • granulomatous conditions including Langerhans cell histocytosis and neurosarcoid

  • infections (i.e., meningitis, encephalitis)

  • vascular insufficiency, infarction

DI will typically present with complaints of polyuria, nocturia, and thirst. The patient will not be dehydrated if he or she has free access to water. Serum electrolytes and renal and liver function may be within normal limits. Urine osmolality will typically be low (< 300 mosmols/kg H2O), and a 24-hour urine volume will be elevated at greater than 50 ml per kg of body weight. A 70 kg patient may have a daily urine volume exceeding 3500 mls. Serum osmolality and serum sodium may be normal, provided the patient does not become dehydrated. If water is restricted, these latter measurements will increase.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

A fluid deprivation test is the restriction of all oral intake in a carefully-controlled environment. The patient is typically weighed after the excretion of each liter of urine. Serum sodium, osmolality, and urine osmolality are determined regularly. During the course of the test, if DI is indeed present, the patient will continue to excrete copious volumes of urine and serum sodium and osmolality will increase, whereas urine osmolality with remain paradoxically low. At this stage, the BUN may be elevated, consistent with dehydration. The test is terminated once the patient has lost 3-5% of his or her body weight.(Table 1)

Table 1.
Initial Urine osmolality (mosmols/kg H2O) H2O Deprivation Test (typically 4-14 hours). Desmopressin Injection
>300 – solute diuresis (e.g., diabetes mellitus) In DI2 urine osmolality remains inappropriately low. A ratio of urine-to-plasma osmolality of <1.0 supports the diagnosis of DI. Serum osmolality will rise with water restriction. Central DI: Urine osmolality rises significantly, by 50%, often exceeding 700 mosmols/kg H2O
<300 – water diuresis (e.g., diabetes insipidus) In primary polydipsia, urine osmolality rises with water restrction. Nephrogenic DI: No response

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Nephrogenic DI may be caused by a variety of medications. However, this is not the case with central DI.

What Lab Results Are Absolutely Confirmatory?

At the end of the fluid deprivation, blood is drawn to determine plasma antidiuretic hormone (ADH or vasopressin). After this, the patient is administered 2 mcg of desmopressin (also called DDAVP, usually given at 0.03 mcg/kg), a synthetic analog of vasopressin. Urine osmolality is determined 2 hours later. In central DI, the plasma vasopressin is inappropriately low after fluid deprivation and urine osmolality increases significantly following DDAVP administration, usually by more than 50%. An MRI of the brain is indicated to look for evidence of hypothalamic disease.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

If a patient has partial or incomplete central DI or partial nephrogenic DI, fluid deprivation might result in a modest concentration of the urine, producing an effect similar to that encountered in primary polydipsia. Responses of urine osmolality to injected desmopressin may not be helpful because of overlap in the range of the responses. In this instance, there is utility in enhancing the serum osmolality by infusing hypertonic saline during the fluid restriction until the osmolality rises greater than 300 mosmol/kg H2O. The volume loss combined with hyperosmolality will further stimulate vasopressin secretion in a normal individual. Determination of plasma vasopressin as a function of serum osmolality can better distinguish partial DI states and primary polydipsia.