Hypertonic Saline Infusion Test Research Articles

Diagnostic value of a 3% hypertonic saline infusion test in differential diagnosis between adh deficiency and primary polydipsia

Diagnostic value of a 3% hypertonic saline infusion test in differential diagnosis between adh deficiency and primary polydipsia

The 3% hypertonic saline infusion test for the differential diagnosis of diabetes insipidus and primary polydipsia: assessment of diagnostic accuracy

AIM: assessment of the diagnostic accuracy of a 3% hypertonic saline infusion test in relation to a set of clinical and laboratory data (including a water deprivation test and MRI data) for differential diagnoses of diabetes insipidus (DI) and primary polydipsia (PP).METHODS: An interventional cross-sectional study was carried out at Endocrinology Research Centre From September 2021 to September 2023 ninety patients with polyuria-polydipsia syndrome were included. In order to assess the diagnostic characteristics, all the subjects underwent two tests with osmotic stimulation: a 3% hypertonic saline infusion test and a water deprivation test. Adverse events were assessed.RESULTS: Based on the results of clinical, anamnestic, laboratory and instrumental data, and the results of a water deprivation test, a final diagnosis of DI was made in 48 (53%) patients and PP in 42 (47%) patients. The agreement between the two samples is significant — Kappa = 0.823, 95% CI (0.707, 0.939). The operational parameters of the 3% hypertonic saline infusion test are: sensitivity 98% (95% CI: 89%; 100%); specificity 98% (95% CI: 87%; 100%), positive and negative predictive values 98% (95% CI: 89%–100%) and 98% (95% CI: 87%–100%). Respectively. Chills occurred significantly more often (31% vs. 12%), and dizziness and headache were more pronounced during the 3% hypertonic saline infusion test. The median duration of the water deprivation test in patients was 11 hours, and median duration of 3% hypertonic saline infusion test was 1.5 hour (P<0.001).CONCLUSION: The 3% hypertonic saline infusion test has a high overall diagnostic accuracy 98%; 95% CI 92% to 100%)) in relation to the classical set of clinical, laboratory and instrumental data of patients (including a water deprivation test), However, it is important the advantage of the latter is its short duration and, as a consequence, better tolerability and probably better compliance, while no significant differences in adverse events frequencies during the tests were identified.

Management of Nephrogenic Diabetes Insipidus: An Overview

Diabetes insipidus is a disorder in which the collecting tubules are impermeable to water provoking the excretion of large amounts of diluted urine. In central diabetes insipidus, the release of antidiuretic hormone is decreased, while in nephrogenic diabetes insipidus, the response of the kidneys to this hormone is defective. Common clinical manifestations include polyuria, nocturia, and polydipsia. Laboratory findings show electrolytic imbalance, particularly hypernatremia. Diagnosis can be determined by a hypertonic saline infusion and water deprivation test. In addition to a thorough medical history and physical examination, lab tests and imaging procedures are commonly required. Treatment strategies include diet restrictions, hydration, thiazide diuretics, indomethacin, chlorthalidone, amiloride, and desmopressin. The management of this disorder is facilitated by combining various therapies and considering contraindications to each treatment. However, further studies are necessary to develop safer and more effective medications to manage this complex condition.

Oxytocin levels in response to pituitary provocation tests in healthy volunteers.

Oxytocin, secreted into circulation through the posterior pituitary, regulates lactation, weight, and socio-behavioral functioning. Oxytocin deficiency has been suggested in patients with hypopituitarism; however, diagnostic testing for oxytocin deficiency has not been developed. The aim of this study was to investigate known pituitary provocation tests to stimulate plasma oxytocin. Sixty-five healthy volunteers underwent either the hypertonic saline or arginine infusion test, known to stimulate copeptin, or the oral macimorelin test, known to stimulate growth hormone. Plasma oxytocin was measured before and once plasma sodium level ≥ 150 mmol/L for the hypertonic saline, after 60 min for the arginine infusion, and after 45 min for the oral macimorelin test (expected peak of copeptin and growth hormone levels, respectively). Primary outcome was a change from basal to stimulated oxytocin levels using paired t-tests. As expected, copeptin increased in response to hypertonic saline and arginine infusion (P < 0.001), and growth hormone increased to oral macimorelin (P < 0.001). Oxytocin increased in response to hypertonic saline infusion from 0.4 (0.2) to 0.6 pg/mL (0.3) (P = 0.003) but with a high variance. There was no change to arginine infusion (P = 0.4), and a trend to lower stimulated levels to oral macimorelin (P = 0.05). Neither the arginine infusion nor the oral macimorelin test stimulates plasma oxytocin levels, whereas there was an increase with high variance upon hypertonic saline infusion. As a predictable rise in most participants is required for a reliable pituitary provocation test, none of the investigated pituitary provocation tests can be recommended diagnostically to identify patients with an oxytocin deficiency.

Oxytocin Levels in Response to Pituitary Provocation Tests in Healthy Volunteers

Background: Oxytocin, secreted into the circulation through the posterior pituitary, regulates lactation, weight, and socio-behavioral functioning. Oxytocin deficiency has been suggested in patients with hypopituitarism, however, diagnostic testing for oxytocin deficiency has not been developed. Known stimuli used in the diagnosis of pituitary deficiencies - the hypertonic saline and arginine infusion tests stimulating copeptin levels, and the oral macimorelin test stimulating growth hormone levels - have also been shown to stimulate oxytocin secretion in animal models. We hypothesized that these provocation tests would stimulate plasma oxytocin levels in humans. Methods: Basal plasma oxytocin levels were measured for all three tests. Stimulated plasma oxytocin was measured once plasma sodium >150 mmol/l for the hypertonic saline and after 45 minutes for the arginine infusion and the oral macimorelin test, expected peak of copeptin and growth hormone levels, respectively. Primary outcome was change between basal and stimulated oxytocin levels using a paired t-test. Results: Median (IQR) age of all participants was 24 years (22, 28), 51% were female. As expected, copeptin increased in response to hypertonic saline from 4.0 pmol/L [3.3, 6.7] to 34.2 pmol/L [23.2, 45.4] (p-value <0.001) and in response to arginine infusion from 4.6 pmol/L [3.2, 6.2] to 8.3 pmol/L [6.4, 10.8] (p-value <0.001). Growth hormone increased in response to oral macimorelin from 1.6 ng/mL [0.3, 17.2] to 106.0 ng/mL [73.3, 127.2] (p-value <0.001). Oxytocin levels increased in response to hypertonic saline infusion from 0.3 pg/mL [0.3, 0.5] to 0.6 pg/mL [0.4, 0.7] (p-value 0.007), while there was no change in response to arginine infusion (basal 0.4 pg/mL [0.4, 0.6], stimulated 0.4 pg/mL [0.3, 0.6], p-value 0.6), nor to oral macimorelin (basal 38.7 pg/mL [31.1, 66.9], stimulated 34.2 pg/mL [31.2, 48.2], p-value 0.3). Conclusion: We found that hypertonic saline infusion results in doubling of oxytocin levels. Further research will be important to determine whether this test could be used diagnostically to identify patients with oxytocin deficiency. In contrast to animal data, arginine and macimorelin did not stimulate oxytocin.

Course of serum potassium levels during the hypertonic saline infusion test for diagnosis of diabetes insipidus

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Copeptin-based diagnosis of diabetes insipidus.

Polyuria-polydipsia syndrome consists of the three main entities: central or nephrogenic diabetes insipidus and primary polydipsia. Reliable distinction between these diagnoses is essential as treatment differs substantially, with the wrong treatment potentially leading to serious complications. Past diagnostic measures using the classical water deprivation test had several pitfalls and clinicians were often left with uncertainity concerning the diagnosis. With the establishment of copeptin, a stable and reliable surrogate marker for arginine vasopressin, diagnosis of the polyuria-polydipsia syndrome has been newly evaluated. Whereas unstimulated basal copeptin measurement reliably diagnoses nephrogenic diabetes insipidus, two new tests using stimulated copeptin cutoff levels showed a high diagnostic accuracy in differentiating central diabetes insipidus from primary polydipsia. For the hypertonic saline infusion test, osmotic stimulation via the induction of hypernatraemia is used. This makes the test highly reliable and superior to the classical water deprivation test, but also requires close supervision and the availability of rapid sodium measurements to guarantee the safety of the test. Alternatively, arginine infusion can be used to stimulate copeptin release, opening the doors for an even shorter and safer diagnostic test. The test protocols of the two tests are provided and a new copeptin-based diagnostic algorithm is proposed to reliably differentiate between the different entities. Furthermore, the role of copeptin as a predictive marker for the development of diabetes insipidus following surgical procedures in the sellar region is described.

Diagnosis of central diabetes insipidus using a vasopressin radioimmunoassay during hypertonic saline infusion.

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia caused by impairment of arginine vasopressin (AVP) secretion. In this study, we evaluated plasma AVP concentrations during a hypertonic saline infusion test using a new AVP radioimmunoassay (RIA) which is now available in Japan. Thirteen control subjects, mostly with hypothalamo-pituitary disease but without CDI, and 13 patients with CDI were enrolled in the study. Whether or not subjects had CDI was determined based on the totality of clinical data, which included urine volumes and osmolality. Regression analysis of plasma AVP and serum Na concentrations revealed that the gradient was significantly lower in the CDI group than in the control group. The area under the receiver-operating-characteristic (ROC) curve was 0.99, and the <0.1 gradient cut-off values for the simple regression line to distinguish CDI from control had a 100% sensitivity and a 77% specificity. The ROC analysis with estimated plasma AVP concentrations at a serum Na concentration of 149 mEq/L showed that the area under the ROC curve was 1.0 and the <1.0 pg/mL cut-off values of plasma AVP had a 99% sensitivity and a 95% specificity. We conclude that measurement of AVP by RIA during a hypertonic saline infusion test can differentiate patients with CDI from those without CDI with a high degree of accuracy. Further investigation is required to confirm whether the cut-off values shown in this study are also applicable to a diagnosis of partial CDI or a differential diagnosis between CDI and primary polydipsia.

A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus

BackgroundThe indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin.MethodsFrom 2013 to 2017, we recruited 156 patients with hypotonic polyuria at 11 medical centers to undergo both water-deprivation and hypertonic saline infusion tests. In the latter test, plasma copeptin was measured when the plasma sodium level had increased to at least 150 mmol per liter after infusion of hypertonic saline. The primary outcome was the overall diagnostic accuracy of each test as compared with the final reference diagnosis, which was determined on the basis of medical history, test results, and treatment response, with copeptin levels masked.ResultsA total of 144 patients underwent both tests. The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). Overall, among the 141 patients included in the analysis, the indirect water-deprivation test determined the correct diagnosis in 108 patients (diagnostic accuracy, 76.6%; 95% confidence interval [CI], 68.9 to 83.2), and the hypertonic saline infusion test (with a copeptin cutoff level of >4.9 pmol per liter) determined the correct diagnosis in 136 patients (96.5%; 95% CI, 92.1 to 98.6; P<0.001). The indirect water-deprivation test correctly distinguished primary polydipsia from partial central diabetes insipidus in 77 of 105 patients (73.3%; 95% CI, 63.9 to 81.2), and the hypertonic saline infusion test distinguished between the two conditions in 99 of 104 patients (95.2%; 95% CI, 89.4 to 98.1; adjusted P<0.001). One serious adverse event (desmopressin-induced hyponatremia that resulted in hospitalization) occurred during the water-deprivation test.ConclusionsThe direct measurement of hypertonic saline–stimulated plasma copeptin had greater diagnostic accuracy than the water-deprivation test in patients with hypotonic polyuria. (Funded by the Swiss National Foundation and others; ClinicalTrials.gov number, NCT01940614.)

Increased arginine-vasopressin response to hypertonic stimulation and upright posture in idiopathic hyperprolactinemia

To evaluate the possible influence of idiopathic hyperprolactinemia on the arginine-vasopressin (AVP) response to osmotic and pressure-volumetric stimuli, 14 idiopathic hyperprolactinemic women and 13 normoprolactinemic women were studied during a hypertonic saline infusion test (0.51M NaCl infusion for 2h) and an orthostatic test (standing upright and maintaining an orthostatic position for 20min). In both experimental conditions, the AVP response was significantly higher in women with idiopathic hyperprolactinemia than in normal normoprolactinemic women. These results indicate that in women hyperprolactinemia influences the AVP response to hyperosmotic and hypovolemic stimuli.

Ｐａｔｔｅｒｎ ｒｅｖｅｒｓａｌ ＶＥＰにて視神経炎が示唆されたリンパ球性下垂体炎の１例

Lymphocytic hypophysitis (LYH) is a rare neuroendocrine disorder characterized by autoimmune inflammation of the pituitary gland. Visual disturbance is one of the most common and serious symptoms of LYH. Most of the visual symptoms in LYH are secondary to compression of the optic chiasm and some reports have described direct inflammatory involvement of the optic pathways. We describe a 30-year-old man with a 9-day history of bilateral blurred vision. Ophthalmic examination demonstrated severely impaired vision without temporal hemianopsia. Hypothyroidism, hypocortisolism, and hypogonadism were detected in laboratory tests. Central diabetes insipidus was diagnosed by a hypertonic saline infusion test. MRI revealed thickening of the pituitary stalk and enlargement of the hypophysis, which was enhanced with gadolinium. High intensity of the posterior lobe was not recognized on T1-weighted images. These findings established a clinical diagnosis of lymphocytic panhypophysitis. Methylprednisolone pulse therapy was introduced and his visual acuity gradually recovered. The anterior pituitary function improved, but desmopressin was still required. Pattern-reversal visual evoked potentials (VEP) have been widely used to detect optic nerve lesions caused by multiple sclerosis and brain tumors. However, there have been no previous reports of their usefulness for LYH. The P100 latency in our case was slightly prolonged and the amplitude was markedly reduced. These findings are similar to ischemic optic neuropathy and other conditions in which axonal damage is prominent. The prolonged latency and low amplitude on VEP examination in this case showed rapid improvement in parallel with the recovery of visual acuity. Taken together, our case implies the usefulness of pattern-reversal VEP for the diagnosis of optic neuritis in LYH, especially for the evaluation of its pathogenic mechanisms.

Fluid control in elderly patients with nocturia

To investigate the pathophysiology of nocturnal polyuria associated with aging. Fifty patients (mean age 67.7 years, range 50-87) with nocturia were recruited for this prospective study. Patients were classified into nocturnal polyuria (NP) and non-nocturnal polyuria (non-NP) groups based on records of their frequency-volume charts. A hypertonic saline infusion test was carried out to evaluate individual osmotic and volume control. In the NP group, there was a significantly increased nocturnal diuretic rate compared with the daytime diuretic rate. In the non-NP group, there was a significantly decreased nocturnal diuretic rate compared with the daytime rate. There was also a positive correlation between systolic blood pressure and nocturnal diuretic rate, and a negative correlation between systolic blood pressure and daytime diuretic rate in those with NP, but no correlation in those without NP. Thus, a close relationship between diuretic rates and systolic blood pressure was seen in NP patients. Moreover, a slight overall shift upward from the physiological range of plasma osmolality relative to arginine vasopressin after hypertonic saline loading was seen in those with NP compared with those without. An altered circadian rhythm was also seen in diurnal plasma arginine vasopressin levels in patients with and without NP. Patients with nocturnal polyuria are likely to have a more hypervolemic or vasoconstrictive condition. It is considered that non-osmotic control takes on a greater meaning in patients with nocturnal polyuria, though osmotic control contributes less to diuresis within the physiological plasma osmolality range with aging.

Diuretic pattern in adults with nocturnal polyuria: The possible contribution of blood pressure to the worsening of nocturnal polyuria

The present study was undertaken to investigate diuresis rate determinants of nocturnal polyuria (NP) in adults. A total of 33 patients aged 50-87 years (mean: 68.6), with nocturnal urine volumes exceeding 10 mL per kg body weight based on records of a frequency-volume chart, were enrolled to evaluate the relationships between diuresis rates and related variables. Multiple regression analyses were conducted to identify diuresis rate determinants, including brain natriuretic peptide. Furthermore, a hypertonic saline infusion test was conducted to examine the arginine vasopressin (AVP) response to plasma osmotic change. Nocturnal voids correlated negatively with the daytime diuresis rate (P = 0.019). Despite a similar total urine volume per kg body weight (TUV/kgBw), systolic and mean blood pressure (MBP) significantly correlated with the nocturnal diuresis rate positively and the daytime diuresis rate negatively. The MBP, which was selected as a representative variable for blood pressure, was found to be an independent determinant for the nocturnal. The MBP and TUV/kgBw were independent determinants for the daytime diuresis rate on multiple regression analyses. Neither age, AVP, nor brain natriuretic peptide were determinants for them. When divided into two groups using their median nocturnal diuresis rates (0.023 mL/kg/min), there was no difference in the prevalence of stroke and the taking of hypnotics between the groups. Overall, a hypervolemic condition or increased sympathetic nerve activity in NP was suggested using the hypertonic saline infusion test. These results indicate that blood pressure might play an important role as a determinant of increasing nocturnal diuresis in NP.

Posterior pituitary function in Sheehan’s syndrome

We studied posterior pituitary function in 27 patients with Sheehan's syndrome and 14 controls. All patients were investigated by water deprivation test and 26 of them by 5% hypertonic saline infusion test. None of the patients had symptoms of diabetes insipidus and all patients were on adequate glucocorticoid and thyroid hormone replacement therapy before testing. According to dehydration test, 8 (29.6%) patients had partial diabetes insipidus (PDI group) and 19 (70.3%) had normal response (non-DI group). During the 5% hypertonic saline infusion test, the maximal plasma osmolality was higher in PDI (305 +/- 4.3) and non-DI (308 +/- 1.7) groups when compared with controls (298 +/- 1.7 mOsm/kg; P < 0.005), but the maximal urine osmolality was lower in PDI group (565 +/- 37) than in non-DI (708 +/- 45) and control (683 +/- 17 mOsm/kg) groups (P < 0.05). The osmotic threshold for thirst perception was higher in PDI (296 +/- 4.3) and non-DI (298 +/- 1.4) groups when compared with control group (287 +/- 1.5 mOsm/kg) (P < 0.005). Basal plasma osmolalities were also higher in PDI (294 +/- 1.0) and non-DI (297 +/- 1.1) groups than in controls (288 +/- 1.2 mOsm/kg; P < 0.001). Our findings demonstrated that patients with Sheehan's syndrome have an impairment of neurohypophyseal function. The thirst center may be affected by ischemic damage and the osmotic threshold for the onset of thirst in patients with Sheehan's syndrome is increased.

A Clinical Investigation of Nocturnal Polyuria in Patients With Nocturia: A Diurnal Variation in Arginine Vasopressin Secretion and its Relevance to Mean Blood Pressure

Nocturia is a common lower urinary condition in the elderly population and nocturnal polyuria is recognized as a major factor responsible for nocturia. A functional change in osmotic or nonosmotic control regarding the water-salt balance with aging may contribute to nocturnal polyuria. This study evaluated plasma arginine vasopressin secretion function in symptomatic patients with nocturnal polyuria and the impact of mean blood pressure on nocturnal polyuria. A total of 29 patients who had nocturnal polyuria with 3 or more voids nightly and were screened with a 24-hour voiding diary were evaluated for their diurnal rhythm of arginine vasopressin secretion and osmotic response during a 5% hypertonic saline infusion test. Moreover, the relationships between the severity of nocturnal polyuria, ie the nocturnal polyuria index, or mean voided volume and mean blood pressure were assessed. Decreased nocturnal baseline arginine vasopressin according to plasma osmolality was found in 11 patients (38%) and the lack of a diurnal rhythm for arginine vasopressin secretion was observed in high proportion. A positive correlation between plasma arginine vasopressin and plasma osmolality was described with a linear regression line, expressed as arginine vasopressin = 0.27 (plasma osmolality - 285), resulting in a 2 to 3 mmol/l upward shift in the threshold of overall plasma arginine vasopressin secretion, although various osmotic sensitivities in arginine vasopressin secretion were observed in individuals. Mean voided volume increased during the night more than during the day (p <0.0001). A significant positive correlation of mean blood pressure with the mean daytime-to-nighttime single voided volume ratio and the nocturnal polyuria index was found (p = 0.0343 and 0.0109, respectively). An abnormal diurnal variation in arginine vasopressin secretion is highly prevalent in nocturnal polyuria. Moreover, it is relevant to mean blood pressure or sympathetic tone, such that the effects of nonosmotic control seem clinically implicated. Particular emphasis has been applied to the importance of considering comprehensive assessments not only of arginine vasopressin secretion function, but also of the possible underlying cardiovascular condition or hypertension in the treatment modality of nocturnal polyuria.

Spontaneous Resolution of Diabetes Insipidus After Pituitary Stalk Sectioning During Surgery for Large Craniopharyngioma-Endocrinological Evaluation and Clinical Implications for Surgical Strategy-

The mechanism of spontaneous resolution of diabetes insipidus (DI) was investigated after surgery for large craniopharyngioma. Twenty-two adult patients (mean age 48.9 years old), who underwent surgery via the anterior interhemispheric trans-lamina terminalis approach, were divided into three groups: Group I, the entire pituitary stalk was preserved (n = 2); Group II, the stalk was dissected distally from the tumor but ultimately sacrificed (n = 9); Group III, the stalk was not identified and was sacrificed (n = 11). All patients were discharged without neurological deficits 1 month after surgery. Four patients underwent gamma-knife treatment for residual tumor or recurrence. Postoperative endocrinological functions were normal in Group I, and no replacement therapy was required. Hormonal replacement for pan-hypopituitarism and DI was necessary in Groups II and III (mean follow-up period 5.9 years). DI resolved at 2.7 +/- 1.3 years after surgery in four patients in Group II, and a hypertonic saline infusion test revealed production of small amounts of intrinsic antidiuretic hormone (ADH). Urine osmolarity was high in the morning, and a significant increase in urinary osmolarity was noted after Pitressin injection. These results indicate induction of hypersensitivity of the distal renal tubules to small amounts of intrinsic ADH, resulting in decreased urinary output. Recovery from DI can be expected, despite permanent impairment of anterior pituitary function, if the pituitary stalk is dissected as distally as possible.

Pulsatile secretion pattern of vasopressin under basal conditions, after water deprivation, and during osmotic stimulation in dogs

Measurement of plasma osmolality (Posm) and plasma vasopressin (VP) concentration in response to hypertonicity is regarded as the gold standard for the assessment of VP release in polyuric conditions. Yet the interpretation of the VP curve as a function of Posm may be hampered by the occurrence of VP pulses. To determine whether VP is secreted in a pulsatile fashion in the dog and whether stimulation of VP release changes the secretion pattern of VP, we measured VP at 2-min intervals for 2 h under basal conditions, after 12 h of water deprivation, and during osmotic stimulation with hypertonic saline (20%) in eight healthy dogs. Vasopressin was secreted in a pulsatile fashion with a wide variation in number of VP pulses, VP pulse duration, and VP pulse amplitude and height. After water deprivation, total and basal VP secretion, the number of significant VP pulses, as well as the pulse characteristics did not differ from the basal situation. During osmotic stimulation, there was a large increase in both basal and pulsatile VP secretion, and the number of VP pulses and VP pulse height and amplitude were significantly increased. The VP pulse amplitude correlated significantly with the basal plasma VP concentration during osmotic stimulation. It is concluded that VP is secreted in a pulsatile manner in healthy dogs. The basal and pulsatile VP secretion increases during osmoreceptor-mediated stimulation. The VP pulses may occur to the magnitude that they may be interpreted as erratic bursts, when occurring in the hypertonic saline infusion test.

Pulsatile secretion pattern of vasopressin under basal conditions, after water deprivation, and during osmotic stimulation in dogs

Measurement of plasma osmolality (Posm) and plasma vasopressin (VP) concentration in response to hypertonicity is regarded as the gold standard for the assessment of VP release in polyuric conditions. Yet the interpretation of the VP curve as a function of Posm may be hampered by the occurrence of VP pulses. To determine whether VP is secreted in a pulsatile fashion in the dog and whether stimulation of VP release changes the secretion pattern of VP, we measured VP at 2-min intervals for 2 h under basal conditions, after 12 h of water deprivation, and during osmotic stimulation with hypertonic saline (20%) in eight healthy dogs. Vasopressin was secreted in a pulsatile fashion with a wide variation in number of VP pulses, VP pulse duration, and VP pulse amplitude and height. After water deprivation, total and basal VP secretion, the number of significant VP pulses, as well as the pulse characteristics did not differ from the basal situation. During osmotic stimulation, there was a large increase in both basal and pulsatile VP secretion, and the number of VP pulses and VP pulse height and amplitude were significantly increased. The VP pulse amplitude correlated significantly with the basal plasma VP concentration during osmotic stimulation. It is concluded that VP is secreted in a pulsatile manner in healthy dogs. The basal and pulsatile VP secretion increases during osmoreceptor-mediated stimulation. The VP pulses may occur to the magnitude that they may be interpreted as erratic bursts, when occurring in the hypertonic saline infusion test.

Osmoregulation of plasma vasopressin in diabetes mellitus with sustained hyperglycemia.

We studied osmoregulation of plasma vasopressin in 5 patients with newly diagnosed diabetes mellitus. All patients showed typical symptoms of uncontrolled diabetes mellitus such as marked hyperglycemia, polyuria, and polydipsia, but did not have advanced diabetic complications. Vasopressin release was studied using 5% hypertonic saline infusion test twice: before treatment when the patient was hyperglycemic, and after treatment 1 to 2 months later when the patient was euglycemic. Plasma vasopressin was measured by a sensitive and specific radioimmunoassay. The mean basal plasma vasopressin value in the patients was significantly higher in the hyperglycemic compared with the euglycemic state (3.75 +/- 0.70 vs 1.18 +/- 0.46 pmol/l, respectively; P < 0.05). The relationship of plasma vasopressin with serum sodium, but not plasma osmolality, during hyperglycemia showed an apparent hypersecretion of vasopressin. In both cases, the sensitivity of the vasopressin response to osmotic stimuli was significantly decreased. During euglycemia, the sensitivity of vasopressin secretion to either sodium or osmolality was almost normal, although a slight rise in the osmostat was observed compared with normal subjects. Together, we found that the positive correlation of vasopressin with sodium or osmolality is maintained but significantly altered in patients with untreated diabetes mellitus. Especially noteworthy is the lowered threshold and decreased sensitivity of osmotically-induced vasopressin secretion during hyperglycemia, which may be caused by multiple factors such as diabetes-associated hypovolemia, osmogenic effects of glucose and other osmoles, depletion of the pool of vasopressin available for release, and the metabolic derangement of osmoreceptor/magnocellular neurons.

Reproducibility of osmotic and nonosmotic tests of vasopressin secretion in men

We have studied the reproducibility of the thirst and arginine vasopressin (AVP) responses to osmotic and hypoglycemic stimulation in healthy volunteers undergoing repeat hypertonic (855 mmol/l) saline infusion and insulin tolerance tests (ITTs). Hypertonic saline infusion caused similar mean rises in plasma osmolality, AVP, and thirst on each occasion. Linear-regression analysis defined close relationships between the slopes (r = +0.72, P less than 0.05) and the abscissal intercepts (r = +0.89, P less than 0.001) of the regression lines relating plasma osmolality (Posmol) and plasma AVP (PAVP), and the group intraindividual component of the variance for the slopes and intercepts was 7 and 0.6%, respectively. There were close correlations between the slopes (r = +0.79, P less than 0.02) and the intercepts (r = +0.84, P less than 0.01) of the regression lines relating Posmol and thirst, and group intraindividual component of the variance was 14 and 0.7%, respectively. Hypertonic saline infusion was infused on four occasions in four subjects, and the results showed that the linear regression lines relating PAVP and Posmol and thirst and Posmol were reproducible within an individual. There were similar falls in blood glucose and elevations in PAVP in both ITTs. No relationship was defined between the fall in blood glucose and either the rise in PAVP or the area under the AVP curve (AUC). The intraindividual component of the variance for the rise in AVP and the AUC was 77 and 22.5%, respectively. The AVP and thirst responses to osmotic stimulation are highly reproducible, but there is considerable intraindividual variation in the AVP response to hypoglycemia.