Section of the neurohypophyseal stalk classically produces a triphasic response: diabetes insipidus (1st phase), hyponatremia or normonatremia (2nd phase), and diabetes insipidus (3rd phase). Transient hyponatremia without diabetes insipidus has been reported after transsphenoidal pituitary surgery. We report two additional cases of transient hyponatremia which occurred 6-8 days after pituitary surgery. We hypothesize that this outcome may be due to partial section or damage of the hypothalamiconeurohypophyseal tracts. The remaining intact vasopressin neurons function normally to protect against the diabetes insipidus of the first and third phase, but leak of vasopressin from the damaged tracts and posterior pituitary is sufficient to cause what can be described as an isolated second phase. To study this hypothesis in rats, partial damage to the hypothalamicneurohypophyseal tracts was produced by radio-frequency lesions. The lesions did not affect anterior pituitary function. A variety of responses in posterior pituitary function occurred, including classic triphasic response in 2 rats and transient hyponatremia in 20 of 35 lesioned animals. The mean sodium nadir was 128.7 ± 1.5 mEq/l in comparison to the sham-operated value of 140.0 ± 0.4 mEq/l. Of the 20 rats exhibiting transient hyponatremia, 12 went on to develop diabetes insipidus, and 8 recovered. In the recovered group, the transient hyponatremia occurred 1-3 days after lesioning and returned to normal by day 7 which corresponds to the timing of the second phase of the triphasic response in rats. Hyponatremia was accompanied by vasopressin levels inappropriate for the plasma sodium level, inappropriately concentrated urine, water retention, and natriuresis. Animals that recovered from hyponatremia had sufficient vasopressin function to maintain normal plasma sodium with normal levels of fluid intake and were able to tolerate 30 h of fluid deprivation with minimal dehydration and elevation of plasma sodium. However, in this group, the vasopressin release in response to hypertonic saline infusion was attenuated. At sacrifice immunohistochemistry of neurophysin was performed, and a portion of the hypothalamiconeurohypophyseal tract in the internal zone of the median eminence was found to be intact in all animals which recovered, i.e., there was partial section. Thus, in both the patients and in the animals, the transient hyponatremia had the characteristic etiology, timing, and duration of an isolated second phase of the triphasic response.

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