Increase In Antidiuretic Hormone Research Articles

SUN-699 Canagliflozin Induced Severe Hyponatremia- a Rare Life Threatening and Poorly Understood Complication- a Case Report

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors induce osmotic diuresis by inhibiting the proximal renal tubular reabsorption of the filtered glucose load. This can occasionally lead to severe dehydration, hypotension and in some cases, severe hyponatremia. The effects of SGLT2 inhibitors on sodium and water handling by the renal tubules is not well studied.Clinical Case: A 49-year-old male with history of type 2 diabetes mellitus on canagliflozin, an SGLT2 inhibitor, who was brought to the Emergency Room following a motor vehicle accident from acute onset of confusion and altered mental status. Initial trauma workup was negative. He was found to have severe hyponatremia to 118 mEq/ L (n 135–145 mEq/ L) and was also noted to be in euglycemic ketoacidosis with positive serum ketones (qualitative assessment) along with acute onset urinary retention. Urine toxicology was negative including negative blood alcohol level. Thyroid function was normal 1.080 mIU/ L (n 0.47- 6.90mIU/L). His total urine osmolar excretion was ~ 2400 mOsm in 12h (n 500–800 mOsm/kg of water/ 24 hours), confirming the diagnosis of his ongoing massive osmotic diuresis. On admission, his antidiuretic hormone (ADH) level was noted to be elevated to 9.1 pg/mL (n <4.3pg/ mL). This severe degree of hyponatremia was postulated to be secondary to canagliflozin causing massive osmotic diuresis resulting in severe intravascular volume depletion with reflex increase in antidiuretic hormone (ADH) compounded by increased free water intake by the patient.Conclusion: With more widespread use of this relatively new hypoglycemic medication with protective metabolic and cardiovascular benefits that include weight loss and reduction of BP in T2DM patients, it is equally important to understand the physiology of potentially life-threatening adverse effects associated with severe volume depletion by massive osmotic diuresis and electrolyte abnormalities that include hypernatremia (even hyponatremia), and the timely recognition of euglycemic ketoacidosis.

Urine specific gravity as a diagnostic tool for dehydration in children

Background Using clinical judgment to diagnose dehydration can be highly subjective. To diagnose dehydration, it would be ideal to have an accurate, inexpensive, objective and easy-to-perform diagnostic tool. In cases of dehydration, plasma osmolality rises, causing an increase in antidiuretic hormone (ADH) secretion. The increased ADH reduces urine production and increases urine osmolality. Previous studies have show that urine osmolality correlates well to urine specific gravity. We investigated if urine specific gravity can be a reliable and objective detennination of dehydration status.Objective To assess the accuracy of using urine specific gravity as a diagnostic tool to determine dehydration status of children with diarrhea.Methods We conducted the study in the pediatric ward of Sardjito Hospital from September 2009 to December 2009. Using a refractometer we measured urine specific gravity from patients with diarrhea. This measurement was then compared to a standard of acute body weight loss, with dehydration defined as weight loss of 5% or more. The cut-off value for defining dehydration using specific gravity measurements was detennined by a receiver-operator curve (ROC).Results Out of 61 pediatric patients who were recruited in this study, 18 (30%) had dehydration as defined by a body weight loss of 5% or more. Based on the ROC, we determined the cut off value for urine specific gravity to be 1.022. Using this value, urine specific gravity was 72% sensitive (95% CI 52 to 93), and 84% specific (95% CI 73 to 95) in determining dehydration status.Conclusion Urine specific gravity is less accurate than clinical judgment in determining dehydration status in children with diarrhea.

Antidiuretic hormone in elderly male patients with severe nocturia: a circadian study.

To investigate the circadian variation of plasma antidiuretic hormone (ADH) and urine output in patients with severe nocturia (> three times per night) and to assess the effect of oral desmopressin on nocturnal urine output in these patients. Twelve patients with severe nocturia and five age-matched controls without were assessed over 24 h (circadian sampling) during a 72-h hospital admission. Blood levels of ADH and changes of urine output were measured in the patients before and after the oral administration of desmopressin (0.2 mg, at 22.00 hours in the second day), and in the controls not treated with desmopressin. Compared with the normal control, the patients had no diurnal variation in urine output and greater nocturnal urine production, associated with a lack of nocturnal increase in ADH level. Compared with the baseline urine output, desmopressin significantly decreased night-time (23.00-08.00 hour) urine output in the patients (P < 0.05). Desmopressin significantly increased the osmolality of night-time urine (P < 0.05), and there was no systemic adverse reaction. Severe nocturia in a large proportion of elderly men with lower urinary tract symptoms is caused by nocturnal polyuria and natriuresis, because they have no nocturnal increase in ADH. These results suggest that desmopressin may be effective in decreasing nocturnal urine production in patients with severe nocturia who do not respond to conventional treatment.

Circadian antidiuretic hormone variation in elderly men complaining of persistent nocturia after urinary flow obstruction removal.

Persistence of nocturia after prostatic resection in healthy patients without symptoms referred to residual bladder instability and to pathological polyuria seems to be caused by an increased urine production at night. The more accreditate mechanism involved is the relevant decreased ADH secretion pattern which occurs at night. In our study, patients with nocturnal poliuria showed significantly low plasmatic vasopressin levels compared with a control group. The aim of this study was to evaluate whether the persistence of nocturia after prostatic resection in healthy patients, without symptoms referred due to residual bladder instability and important polyuria, could be due to a decrease or a lack of increase in antidiuretic hormone (ADH) nocturnal levels following increased urine production at night. Serum ADH, atrial natriuretic peptide (ANP) and osmolality were assessed at 4-h intervals in 12 patients complaining of residual nocturia (group A) and in a control group of 13 patients who had undergone a complete resolution of nocturia after prostate ablation (group B). In the 25 patients involved in the study (mean age 65.8 years), no significant differences were observed in the two groups concerning mean age (67.5 years for group A, 64 years for group B). Mean nocturnal urine volume (1080 +/- 490 ml) in group A patients was significantly higher than in group B (500 +/- 100 ml) (p < 0.001), while no significant differences were found in diurnal diuresis. Mean plasma vasopressin levels of the 12 patients showing an increased nocturnal micturition were found to be significantly lower at all 4-h intervals when compared with the control group (p < 0.05). Individual fluctuations in serum osmolality were slight and insignificant within the normal range in all patients. The diurnal variation of plasma atrial natriuretic peptide was within the reference limits for all subjects during the 24-h period. Our results lead us to believe that residual nocturia after prostatic resection seems to be caused by an increased urine production at night due to a decreased ADH secretion pattern.

Effects of adenosine infusion on renal function, plasma ANP and ADH concentrations and central hemodynamics in anesthetized pigs

1. 1. The effect of high-dose adenosine administration on atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) release is not completely understood, and data concerning the effect of adenosine on renal and systemic hemodynamics in the pig are lacking. Measurements of central hemodynamics, renal blood flow and urine production were made in anesthetized pigs during infusion of adenosine. The relationship between these parameters and the plasma concentrations of ANP, ADH and renal renin production was examined. 2. 2. Adenosine infusion at the rate of 140 mg/kg per minute resulted in a significant decrease in systolic, diastolic and mean arterial blood pressure as well as pulmonary arterial pressure. However, cardiac output and renal blood flow remained unchanged during adenosine infusion. Likewise, heart rate remained unchanged until the end of infusion when it increased significantly. Plasma ANP and ADH concentrations increased significantly within 30 min after adenosine infusion, reaching peak levels at 30 to 60 min. However, despite the significant decrease in arterial blood pressure, renal renin production did not change significantly. 3. 3. The adenosine-induced rise in ANP, which is normally released by atrial stretch, may represent a direct effect of adenosine on the cardiac myocytes. The increase in ADH may be a result of decreased arterial blood pressure triggering stimulatory signals from the aortic arch and carotid body receptors to hypothalamic-pituitary sites of ADH production/release. Urine flow decreased dramatically within 30 min of adenosine infusion. Thus adenosine infusion at the given rate led to marked reduction in systemic and pulmonary arterial pressures without significant change in cardiac output, heart rate and renal blood flow. This was associated with a marked increase in plasma ANP and ADH levels with no significant change in renal renin production despite a marked reduction in arterial blood pressure. 4. 4. Maintenance of renal blood flow despite marked reduction in perfusion pressure suggests that, at high doses, adenosine induces renal vasodilation in pigs as opposed to a combined afferent and efferent vasoconstriction known to occur under different experimental conditions.

Effect of Adrenocorticotropic Hormone on Plasma Glucocorticoids and Antidiuretic Hormone of Cattle Exposed to 20 and 33 C

Four open, dry Holstein cows in the University of Missouri Climatic Laboratory were used to study the effect of adrenocorticotropic hormone administration on glucocorticoids and antidiuretic hormone of plasma in two reversal trials at thermoneutral (20C, 50% relative humidity) and heat (33C, 50% relative humidity) conditions. Average glucocorticoids (saline versus adrenocorticotropic hormone) at thermoneutral were 8.3 and 41.2ng/ml while values for heat were 6.2 and 40.0ng/ml. The effect of heat on glucocorticoids of plasma was not significant. Injection of adrenocorticotropic hormone under thermoneutrality and heat caused a marked increase in antidiuretic hormone within 5min which lasted to 120min. At thermoneutral average untidiuretic hormone levels (saline versus adrenocorticotropic hormone) were .5 and 1.9 pg/ml while values for heat were 1.8 and 3.6 pg/ml. Antidiuretic hormone concentrations under heat were higher than thermoneutral in cows injected with saline and andrenocorticotropic hormone. The fast response of antidiuretic hormone of plasma to exogenous adrenocorticotropic hormone suggests that adrenocorticotropic hormone might act directly at higher levels of the central nervous system causing release of antidiuretic hormone.

Cerebral control of antidiuretic hormone release: effect of electrical stimulation of the medial aspect of the dog brain.

The medial aspect of the dog brain was electrically stimulated under chloralose anesthesia 4 hr after craniotomy. Stimulation of the anterior cingular region caused a significant increase of antidiuretic hormone (ADH) levels in the jugular vein blood, whereas stimulation of other nearby portions of the brain did not produce significant changes in ADH levels. Stimulation also produced autonomic and somatic responses such as inhibition of respiratory movement and changes in blood pressure. However, these changes were not always accompanied by changes in ADH titers in jugular vein blood. (Endocrinology 79: 871, 1966)

Role of hepatic blood flow in regulating plasma concentration of antidiuretic hormone after hemorrhage.

SummaryHemorrhage in splenectomized dogs under pentobarbital caused a decrease of hepatic blood flow (HBF) and an increase of antidiuretic hormone (ADH) concentration in the arterial plasma. The splanchnic extraction ratio for ADH remained at about 0.22 with all degrees of hemorrhage. Therefore as the HBF was reduced by hemorrhage, the splanchnic clearance of ADH decreased, and so did the percentage of total plasma ADH cleared by the splanchnic organs (mainly the liver) per unit time. After hemorrhage, the decrease in ADH clearance is not a major factor in causing the initial rapid rise in the circulating ADH concentration, but plays a part in maintaining this concentration at an elevated level.

The relation of emotional state to renal excretion of water and electrolytes in patients with congestive heart failure

Eight male patients with compensated congestive heart failure (and stabilized as to weight) were studied on a metabolic ward. Sodium and water intake was maintained constant. All urine was collected, the volume noted, and sodium and potassium excretion measured. These data were kept completely separate from a daily appraisal of the behavior, attitudes and emotional state of the subject. The contribution of the position of the body and muscular activity to the excretory pattern was also controlled and evaluated. Wide fluctuations in renal excretion of fluid and electrolytes were observed in all patients; these fluctuations could be correlated with attitudes and emotions. In situations which evoked feelings of discouragement or tension, renal excretion of water and sodium was decreased. The decrease in volume was often not proportionate to the marked retention of sodium, perhaps due to an increase in antidiuretic hormone in advanced congestive failure. In situations which evoked a reaction of excitement, anger or apprehension, renal excretion rates of sodium were increased as compared with excretion rates observed during neutral periods. A diuresis of sodium and water was also associated with periods of reassurance and active relaxation. Such alterations in excretory pattern related to the emotional state of the patient were sometimes greater than those attributable to body position or muscular activity. There was no significant variation in potassium excretion which could be correlated with a specific emotional state. The findings suggest that in the patient with decreased cardiac reserve prolonged states of tension or depression may be a precipitating factor for an episode of decompensation by the mechanism of fluid and sodium retention. A reassuring attitude on the part of the physician may be of substantial importance in the therapy of congestive heart failure.

Saluretic and toxic effects of amphenone in a patient with cirrhosis and ascites.

The precise pathogenesis of ascites in cirrhosis of the liver remains obscure. Portal hypertension, 1 , 2 decreased plasma osmotic pressure due to hypoalbuminemia, 3 , 4 increased lymphatic exudation from the liver, 5 , 6 increase of antidiuretic hormone, 7 and increase of sodium-retaining adrenocortical hormone 8 are among the factors considered in the pathogenesis of ascites. The marked decrease of sodium excretion and the presence of increased amounts of aldosterone in the urine of patients with cirrhosis and ascites 9 point to this sodiumretaining hormone as the possible culprit in the pathogenesis of ascites. The complexity of the pathogenesis of ascites is demonstrated schematically in Figure 1. Amphenone B (3,3-bis[ p -dimethylaminophenyl]butanone-2-dihydrochloride) (Fig. 2) was synthesized by Allen and Curwin, 11 in 1950, and has been shown to have principally an inhibiting effect on thyroid and adreno-cortical function. 12,13 Among its other effects are a progesterone- or estrogen-like effect on the female genitalia, with uterine enlargement 12 and a depressing effect on the central