Water Intoxication In Patients With Neurogenic Diabetes Insipidus And Adrenal Failure: glucocorticoid and vasopressin secretions
by Kyuzi Kamoi, M.D., Nagaoka Red Cross Hospital, Niigata, Japan

In a past issue of Endless Water, a woman wrote that she has been suffering a number of problems after treatment for a pituitary tumor (1). After the surgery and radiation, she had pituitary diabetes insipidus and adrenal failure. Afterwards, her serum sodium levels had been going up and down. Probably, low level of serum sodium may be related to her intolerable symptoms due to increasing cranial pressure by cerebral edema, namely water intoxication.

We also have experienced such patients. One of them is a 25-year-old woman, who had panhypopituitarism including pituitary diabetes insipidus and adrenal failure due to ectopic germinoma at age 13. After radiation therapy, her pituitary gland was destroyed. Her plasma vasopressin levels were constantly low and did not respond to high plasma osmolality, suggesting her vasopressin secretion is completely deficient. She has received DDAVP and corticoid hormone with replacement of other hormones. Usually, she has been well and healthy. However, when she had cold, flu, or acute intestinal entrogastritis, she had always symptoms such as headache, fatigue, dizziness, loss of appetite or lethargy, indicating she had water intoxication. In fact, her levels of serum sodium and osmolality were low. Surprisingly, her vasopressin level was not low albeit its complete deficiency at the usual time. Iwasaki et al. reported the same case (2). The patient was a 69-year-old man who had a pituitary tumor and panhypopituitarism. Thus, the water intoxication, therefore, may be resulted from secretion of vasopressin induced by adrenal crisis due to the inflammatory or other stress.

Recent studies revealed a detailed mechanism of vasopressin secretion; vasopressin is primarily regulated by plasma osmolality, which is augmented by non-osmotic stimuli (3). Among the non-osmotic stimuli, the relationship between glucocorticoid and vasopressin secretion in human, however, has been remained unclear (3). For many decades, adrenal failure impairs water diuresis, which in turn causes dilutional hyponatremia in humans as well as in experimental animals. Although the direct effect of glucocorticoid deficiency on water permeability of the distal nephron could not be excluded, several lines of evidence strongly support a central role for vasopressin. We demonstrated that low serum sodium levels in patients with adrenal failure resemble those due to water intoxication by inappropriate secretion of vasopressin (4). Despite dilutional hyponatremia, vasopressin secretion is not suppressed and vasopressin in relation to plasma osmolality is constantly high (4). The loss of hypotonic suppression of the osmoregulated vasopressin normalizes after replacement of glucocorticoid. Vasopressin is mainly released from magnocellular neurons in the supraoptic nucleus and is also secreted from parvocellular neurons of the paraventricular nucleus. Corticotropin releasing hormone (CRH) causes release of adrenocorticotropin (ACTH), which in turn stimulates glucocorticoid secretion. The secretion of three hormones are regulated by the negative loop feedback system. Accordingly, glucocorticoid deficiency in adrenal failure stimulates production and release of CRH. CRH is produced and released from the parvocellular neurons of the paraventricular nucleus. Moreover, CRH stimulates vasopressin secretion. In addition, glucocorticoid possess an inhibitory effect on magnocellular neurons of the supraoptic nucleus and on the parvocellular neurons of the paraventricular nucleus. The hyponatremia in patients with adrenal failure, therefore, may be explained by the hypothesis that glucocorticoid deficiency may result in the stimulation of vasopressin production and secretion.

Based on this evidence, we should know that plasma vasopressin in some patients is secreted when adrenal crisis occurs by many kinds of stress, even though they have already proven neurogenic diabetic insipidus, which leads water intoxication. If such patients with neurogenic diabetes insipidus and adrenal failure feel intolerable symptoms as headache, fatigue, dizziness, loss of appetite or lethargy after receiving strong stress, they should take the medical examination to determine adrenal crisis immediately.

References:

1. White M. Stories/networking family to family. Endless Water. 1997;2:5.
2. Iwasaki Y, Kondo K, Hasegawa H, Oiso Y. Osmoregulation of plasma vasopressin in three cases with adrenal insufficiency of diverse etiologies. Horm Res 1997; 47: 38-44.
3. Robertson GL. Thirst and vasopressin function in normal and disordered states of water balance. J Lab Clin Med 1983; 101: 351-371.
4. Kamoi K, Tamura T, Tanaka K, Ishibashi M, Yamaji T. Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients with adrenal insufficiency. J Clin Endocrinol Metab 1993; 77: 1584-1588.