Patients with intracranial disorders are prone to develop hyponatremia with inability to prevent the loss of sodium in their urine. This was originally referred to as "cerebral salt wasting," but more recently is thought to be secondary to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Blood volume determinations were made in 12 unselected neurosurgical patients with intracranial disease who fulfilled the laboratory criteria for SIADH. Ten of the 12 patients had significant decreases in their red blood cell mass, plasma volume, and total blood volume. The finding of a decreased blood volume in patients who fulfill the laboratory criteria for SIADH is better explained by the original concepts of cerebral salt wasting than by SIADH. The primary defect may be the inability of the kidney to conserve sodium.

RIA for the measurement of oxytocin in human plasma is described. Extraction of oxytocin from larger peptides in plasma used acetone precipitation with a 75% +/- 2 SEM recovery of oxytocin. Nonspecific binding of the assay was less than 4%, and the minimum level of detection was 0.2 microunits/tube. No cross-reactivity was noted with neurophysins, arginine, or lysine vasopressin. The mean basal level (+/- SEM) of oxytocin in men was 1.80 +/- 0.07 microunits/ml and was not different in normal women (1.71 +/- 0.07 microunits/ml). Changes in posture had no effect on the levels of oxytocin. Samples obtained every 15 min over 4 h showed no pulsatile secretion of oxytocin. In women chronically receiving estrogen as an oral contraceptive, oxytocin was greater than normal, (4.59 +/- 0.51 microunits/ml; P less than 0.01). Estrogen-stimulated neurophysin was also elevated (8.45 +/- 1.99 ng/ml; P less than 0.005). Acute ingestion of estrogen caused an increase in the level of oxytocin in plasma by 12 h and a concomitant elevation of estrogen-stimulated neurophysin. When the neurophysin was isolated from plasma obtained from a subject after ingestion of estrogen, the neurophysin from plasma comigrated on a polyacrylamide gel with a human pituitary standard of estrogen-stimulated neurophysin. In the studies in which neurophysin was elevated, the correlation between the level of oxytocin and the level of estrogen-stimulated neurophysin in plasma was significant (P less than 0.01). The observation that estrogen administration stimulates the release of oxytocin and estrogen-stimulated neurophysin provides additional evidence that this neurophysin is the oxytocin-neurophysin of man.

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A positive correlation was observed between the midcycle elevation of estrogen (E) and the level of oxytocin-and estrogen-stimulated neurophysin (ESN), the protein carrier of oxytocin, in the plasma of five of six women. The time of the maximal level of E was associated with a level of oxytocin significantly greater than that in either the early follicular or late luteal phase (P < 0.025). Likewise, the level of ESN at midcycle was greater than the level of ESN in the early follicular or late luteal phase (P < 0.0.1). Other than states of lactation or pregnancy, this is the only described cyclic secretion of oxytocin in humans. Since oxytocin chronologically correlates with a rise in the level of E at midcycle, a role for oxytocin in ovulation may be considered. (J Clin Endocrinol Metab 53: 1229, 1981 O UR LABORATORY has recently described a sensitive and specific RIA for the measurement of oxytocin in human plasma (1, 2). There is strong evidence that oxytocin is associated with human neurophysin I or estrogen-stimulated neurophysin (ESN) and that AVP is associated with human neurophysin II or nicotine-stimulated neurophysin (NSN) (2, 3). The only known pharmacological stimulus for oxytocin secretion and its associated neurophysin in the human is the administration of estrogen (2, 4). Both oxytocin and ESN were elevated in the plasma of normal men and women after the ingestion of estrogen, either acutely or chronically (2, 5). Oxytocin increased as early as 12 h after the ingestion of a single dose of 100 jug estrogen orally, and the elevation was sustained until 36 h. This elevation in the level of oxytocin was not a natural spontaneous fluctuation of oxytocin because levels of oxytocin in plasma measured serially over 4 h showed no fluctuations in the level of oxytocin in either individuals who were ingesting estrogen or those not receiving the hormone.Several investigations support the concept that physiological elevations of estrogen are associated with the elevation of ESN in plasma. For example, an elevation of ESN in plasma has been noted throughout pregnancy from the end of the first trimester (6), presumably related to a coincident increase in the level of estrogen. Levels of ESN in the plasma of patients with cirrhosis with feminization were elevated and were believed to be the result of estrogen excess (7). Most convincingly, in the rhesus monkey, Robinson et al. (8) found a close correlation among the midcycle surge of LH, the midcycle elevation of estrogen, and a midcycle increase in ESN. Similarly, Legros et al. (9) were able to detect an elevation of neurophysin at the time of midcycle in women. In some of the women, the neurophysin remained elevated throughout the luteal phase. To assess oxytocin in plasma at midcycle, a sensitive and specific assay for oxytocin was required. The evidence presented in this report indicates that there is an increase in the level of oxytocin in plasma at midcycle which corresponds chronologically to the peak level of estrogen. Materials and Methods Selection of s...

A monkey model of subarachnoid hemorrhage (SAH) was used to study both the incidence of hyponatremia and natriuresis and the associated changes in antidiuretic hormone (ADH) secretion and salt and water balance. Following SAH, seven of nine monkeys became natriuretic and hyponatremic. The natriuretic period lasted an average of 4.4 +/- 0.4 days. The mean nadir of serum sodium content was 125.7 +/- 1.6 mEq/liter, and occurred on the average on the 5th day following SAH. The sodium balance after SAH was negative as compared to the preoperative positive sodium balance (p less than 0.001). The plasma vasopressin level was usually elevated for a day following surgery, but there was no significant difference in the levels during the preoperative period and during the period of natriuresis following SAH. The daily urine output and aldosterone levels were not significantly different, and the plasma volume was slightly, but not significantly, decreased after SAH. Four of the animals that had a hyponatremic and natriuretic response following SAH showed a normal regulation of vasopressin in response to both a water challenge and hypertonic saline challenge. The three monkeys that underwent sham procedures did not become hyponatremic and natriuretic postoperatively. The sham-operated monkeys did not show significant differences in their plasma vasopressin levels, urine volume, plasma volume, and aldosterone levels following surgery. These observations are more consistent with primary natriuresis as the cause of hyponatremia rather than the syndrome of inappropriate secretion of ADH. The cause of the renal loss of sodium is not known, but the possibility of a brain natriuretic factor or an alteration in the neural control of the kidney should be considered.