Diabetes Insipidus as a Complication after Pituitary Surgery

Jennifer A. Loh; Joseph G. Verbalis


Nat Clin Pract Endocrinol Metab. 2007;3(6):489-494. 

In This Article

Discussion of Diagnosis

Hypotonic polyuria is a very common complication of trans-sphenoidal surgery that occurs in 18-31% of patients postoperatively.[1,2] Factors found to increase the risk of postoperative diabetes insipidus include young age, male sex, large intrasellar mass, cerebrospinal fluid leak and resection of certain types of lesions, including craniopharyngiomas, Rathke-cleft cysts and adrenocorticotropic-hormone-secreting pituitary adenomas.[1,2] The course of postoperative diabetes insipidus can be transient, permanent, or triphasic, as described in classic studies of pituitary stalk transection.[3] In most cases, the disease is transient; only 2-10% of patients manifest prolonged polyuria.[1,2] This symptom is mostly a result of the fact that diabetes insipidus is permanent only if more than 80-90% of the arginine vasopressin (AVP)-secreting neurons in the supraoptic and paraventricular hypothalamic nuclei degenerate bilaterally.[4]

Transient diabetes insipidus almost always begins within 24-48 h of surgery, and usually abates within several days. Both transient diabetes insipidus and the first phase of the triphasic pattern are thought to be caused by temporary dysfunction of AVP-producing neurons, secondary to trauma to the connections between the magnocellular cell bodies and the nerve terminals in the posterior pituitary, or to axonal shock from perturbations in the vascular supply to the pituitary stalk and posterior pituitary (Figure 3). Transient diabetes insipidus usually resolves when AVP-secreting neurons recover their normal function.

Mechanisms that underlie the pathophysiology of the triphasic pattern of postoperative diabetes insipidus. (1) The first phase of diabetes insipidus is initiated by a partial or complete pituitary stalk section, which severs the connections between the cell bodies of AVP-secreting neurons in the hypothalamus and their nerve terminals in the posterior pituitary gland, which prevents AVP secretion. (2) This first phase is followed, after several days, by the second phase of inappropriate antidiuresis, which is caused by an uncontrolled release of AVP into the bloodstream from the degenerating nerve terminals in the posterior pituitary. (3) After all of the AVP stored in the posterior pituitary gland has been released, a third phase of diabetes insipidus develops if >80-90% of the AVP-secreting neuronal cell bodies in the hypothalamus have degenerated (the figure shows normal AVP-secreting neurons). Abbreviation: AVP, arginine vasopressin.

The triphasic pattern is relatively uncommon, and occurs in 3.4% of patients who undergo trans-sphenoidal surgery; only the first two phases occur in 1.1% of patients.[1] The first phase of diabetes insipidus typically lasts for 5-7 days, and is followed by a second, antidiuretic phase of the syndrome of inappropriate antidiuresis (SIADH), as in the case reported here. This second phase is caused by an uncontrolled release of AVP from either degenerating posterior pituitary tissue, or from the remaining magnocellular neurons whose axons have been severed (Figure 3).[3,4] In this phase, the urine becomes concentrated and urine output markedly decreases. Continued administration of excess water during this period can quickly lead to hyponatremia and hypo-osmolality, as occurred in this patient on postoperative day 6. The duration of the second phase is variable (2-14 days).[4] In the case reported here, the duration of antidiuresis was relatively short (<48 h), probably because the large intrasellar mass had already destroyed much of the posterior pituitary, which resulted in a reduced residual store of AVP.

Some patients with limited damage to the neurohypophysis manifest an 'isolated' second phase,[5] in which only SIADH occurs, without any previous or subsequent diabetes insipidus. An isolated second phase is reported to cause hyponatremia in 8-21% of patients after pituitary surgery.[1,6] After AVP stores are depleted, the third phase of chronic diabetes insipidus often, but not always,[1] ensues. In this phase, the number of neurons that remain capable of synthesizing AVP is insufficient, which results in permanent diabetes insipidus (Figure 3). Previous studies showed that the major determinant of whether diabetes insipidus following transection of the pituitary stalk is permanent is related to the level of the lesion: the closer the lesion is to the AVP-secreting neurons' cell bodies in the hypothalamus, the more likely it is that the cell bodies will degenerate.[7]

The diagnosis of diabetes insipidus should be considered when a patient excretes large volumes of dilute urine after neurosurgery, typically >2.5 ml/kg body weight per hour. When this symptom is noted, several other potential clinical scenarios should be considered as well. First, patients who undergo surgery in the suprasellar region often receive stress doses of glucocorticoids to prevent secondary adrenal insufficiency. If steroid-induced insulin resistance causes hyperglycemia, the resulting osmotic diuresis from glucosuria can be confused with diabetes insipidus. Urine and blood glucose should, therefore, be measured and any elevated glucose levels should be controlled to eliminate osmotic diuresis as a cause of the polyuria.

Second, excess fluid is sometimes administered intravenously during the perioperative period, which is normally excreted postoperatively. If the large postoperative diuresis is matched with continued intravenous fluid infusions, then a diagnosis of diabetes insipidus based on the resulting hypotonic polyuria is incorrect. If the serum sodium level is not elevated concomitantly with the presence of polyuria, the rate of parenteral administration of fluid should be slowed, and the serum sodium level and urine output should be carefully monitored. The diagnosis of diabetes insipidus can be confirmed by continued hypotonic polyuria in the presence of hypernatremia and/or hyperosmolality.[8]

The diagnosis of postoperative diabetes insipidus is based on both clinical and biochemical data. Patients characteristically complain of the abrupt onset of polyuria and polydipsia, usually in the first 24-48 h after neurosurgery,[4] and often describe a craving for ice-cold water, which quenches osmotically stimulated thirst well. Urine studies should reveal hypotonic urine, with specific gravity <1.005 or urine osmolality <200 mOsm/kg H2O. Urine output is typically voluminous (4-18 l daily). Serum hyperosmolality and hypernatremia also strongly support the diagnosis of diabetes insipidus. Most patients, however, have intact thirst mechanisms, so as long as they have free access to oral fluids, they do not present with either hyperosmolality or hypernatremia.[9] Consequently, it is often necessary to limit the patient's fluid intake until either hyperosmolality and/or hypernatremia develops, in order to confirm a diagnosis of diabetes insipidus.

MRI can also facilitate the diagnosis of diabetes insipidus. The presence of vasopressin and oxytocin is normally shown as a bright spot in the posterior pituitary on T1-weighted (contrast-enhanced) images. The lack of a posterior pituitary bright spot can help to confirm a diagnosis of postoperative diabetes insipidus.[10] The bright spot, however, might still be seen at the early phases of this disease,[11] so its presence does not exclude a diagnosis of diabetes insipidus. Given that this patient had clinical symptoms of diabetes insipidus, in her case the absence of a pituitary bright spot on the MRI scan (Figure 2B) supported the diagnosis.


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