Hyponatremia presenting with hourly fluctuating urine osmolality

Summary The etiology of hyponatremia is assessed based on urine osmolality and sodium. We herein describe a 35-year-old Asian man with pulmonary tuberculosis and perforated duodenal ulcer who presented with hyponatremia with hourly fluctuating urine osmolality ranging from 100 to 600 mosmol/kg, which resembled urine osmolality observed in typical polydipsia and SIADH simultaneously. Further review revealed correlation of body temperature and urine osmolality. Since fever is a known non-osmotic stimulus of ADH secretion, we theorized that hyponatremia in this patient was due to transient ADH secretion due to fever. In our case, empiric exogenous glucocorticoid suppressed transient non-osmotic ADH secretion and urine osmolality showed highly variable concentrations. Transient ADH secretion-related hyponatremia may be underrecognized due to occasional empiric glucocorticoid administration in patients with critical illnesses. Repeatedly monitoring of urine chemistries and interpretation of urine chemistries with careful review of non-osmotic stimuli of ADH including fever is crucial in recognition of this etiology. Learning points: Hourly fluctuations in urine osmolality can be observed in patients with fever, which is a non-osmotic stimulant of ADH secretion. Repeated monitoring of urine chemistries aids in the diagnosis of the etiology underlying hyponatremia, including fever, in patients with transient ADH secretion. Glucocorticoid administration suppresses ADH secretion and improves hyponatremia even in the absence of adrenal insufficiency; the etiology of hyponatremia should be determined carefully in these patients.

Markers of systemic inflammation in response to osmotic stimulus in healthy volunteers

Osmotic stimulus or stress results in vasopressin release. Animal and human in vitro studies have shown that inflammatory parameters, such as interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α), increase in parallel in the central nervous system and bronchial, corneal or intestinal epithelial cell lines in response to osmotic stimulus. Whether osmotic stimulus directly causes a systemic inflammatory response in humans is unknown. We therefore investigated the influence of osmotic stimulus on circulatory markers of systemic inflammation in healthy volunteers. In this prospective cohort study, 44 healthy volunteers underwent a standardized test protocol with an osmotic stimulus leading into the hyperosmotic/hypernatremic range (serum sodium ≥150 mmol/L) by hypertonic saline infusion. Copeptin – a marker indicating vasopressin activity – serum sodium and osmolality, plasma IL-8 and TNF-α were measured at baseline and directly after osmotic stimulus. Median (range) serum sodium increased from 141 mmol/L (136, 147) to 151 mmol/L (145, 154) (P < 0.01), serum osmolality increased from 295 mmol/L (281, 306) to 315 mmol/L (304, 325) (P < 0.01). Median (range) copeptin increased from 4.3 pg/L (1.1, 21.4) to 28.8 pg/L (19.9, 43.4) (P < 0.01). Median (range) IL-8 levels showed a trend to decrease from 0.79 pg/mL (0.37, 1.6) to 0.7 pg/mL (0.4, 1.9) (P < 0.09) and TNF-α levels decreased from 0.53 pg/mL (0.11, 1.1) to 0.45 pg/mL (0.12, 0.97) (P < 0.036). Contrary to data obtained in vitro, circulating proinflammatory cytokines tend to or decrease in human plasma after osmotic stimulus. In this study, osmotic stimulus does not increase circulating markers of systemic inflammation.

Influenza A: another cause of SIADH?

The syndrome of inappropriate antidiuretic hormone (SIADH) secretion is a frequent cause of hyponatraemia. It is a dilutional hyponatraemia secondary to impaired urinary dilution in the absence of renal disease or any identifiable non-osmotic stimulus known to induce antidiuretic hormone secretion. SIADH can arise secondary to various respiratory tract infections; however, the association between SIADH and influenza A infection is described in only a few cases in the literature. The authors present a case report of influenza A that may have caused a profound SIADH-related hyponatraemia.

Intrahypothalamic Angiogenesis Induced by Osmotic Stimuli Correlates with Local Hypoxia: A Potential Role of Confined Vasoconstriction Induced by Dendritic Secretion of Vasopressin

We have previously shown that hyperosmotic stimulation of adult Wistar rats induces local angiogenesis within hypothalamic magnocellular nuclei, in relation to the secretion of vascular endothelial growth factor (VEGF) by the magnocellular neurons. The present study aimed at understanding how osmotic stimulus relates to increased VEGF secretion. We first demonstrate a correlation between increased VEGF secretion and local hypoxia. Osmotic stimulation is known to stimulate the metabolic activity of hypothalamic magnocellular neurons producing arginine vasopressin (AVP) and to increase the secretion of AVP, both by axon terminals into the circulation and by dendrites into the extracellular space. In AVP-deficient Brattleboro rats, the dramatic activation of magnocellular hypothalamic neurons failed to induce hypoxia, VEGF expression, or angiogenesis, suggesting a major role of hypothalamic AVP. A possible involvement of dendritic AVP release is supported by the findings that 1) hypoxia and angiogenesis were not observed in non osmotically stimulated Wistar rats in which circulating AVP was increased by the prolonged infusion of exogenous AVP, 2) contractile arterioles afferent to the magnocellular nuclei were strongly constricted by the perivascular application of AVP via V1a receptors (V1a-R) stimulation, and 3) after the intracerebral or ip administrations of selective V1a-R antagonists to osmotically stimulated rats, hypothalamic hypoxia and angiogenesis were or were not inhibited, respectively. Together, these data strongly suggest that the angiogenesis induced by osmotic stimulation relates to tissue hypoxia resulting from the constriction of local arterioles, via the stimulation of perivascular V1a-R by AVP locally released from dendrites.

Effects of prenatal ethanol exposure and sex on the arginine vasopressin response to hemorrhage in the rat

AVP synthesis, storage, and osmotically stimulated release are reduced in young adult rats exposed prenatally to ethanol (PE). Whether the reduced release of AVP to the osmotic stimulus is due to impairment of the vasopressin system or specifically to an osmoreceptor-mediated release is not known. The present experiments were done, therefore, to determine whether a hemorrhage-induced AVP response would also be diminished in PE-exposed rats. Pregnant rats were fed either a control liquid diet [no prenatal ethanol (NPE)] or a liquid diet with 35% of the calories from ethanol from days 7– 21 of pregnancy. Offspring were weaned at 3 wk of life. At 11 wk of age, femoral arterial catheters were surgically placed, and blood volumes were determined at 12 wk. Three days later, two hemorrhages of 10% of the blood volume were performed with samples taken before and 10 min after the hemorrhages. After a 20% blood loss, plasma AVP was 19% higher in NPE rats than in the PE rats despite no differences in mean arterial blood pressure (MABP). Also, hypothalamic AVP mRNA and pituitary AVP content were reduced in PE rats. Furthermore, confirming an earlier report of sex differences in AVP release, the hemorrhage-induced hormone response was twofold greater in female rats than male rats, regardless of previous ethanol exposure. These studies demonstrate that the AVP response to hemorrhage is reduced in PE rats independently of differences in MABP. The data are compatible with a theory of a reduced number of hemorrhage-responsive vasopressinergic neurons capable of stimulated AVP release in PE rats.