Oxytocin Levels in Response to Pituitary Provocation Tests in Healthy Volunteers

Abstract 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.

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Oxytocin levels in response to pituitary provocation tests in healthy volunteers

Acta Endocrinologica ◽

10.1530/eje-21-0346 ◽

2021 ◽

Author(s):

Clara O Sailer ◽

Bettina Winzeler ◽

Sandrine A Urwyler ◽

Ingeborg Schnyder ◽

Julie Refardt ◽

...

Keyword(s):

Growth Hormone ◽

Healthy Volunteers ◽

Hypertonic Saline ◽

Diagnostic Testing ◽

Provocation Test ◽

Saline Infusion ◽

Plasma Sodium ◽

Arginine Infusion ◽

Provocation Tests ◽

Hypertonic Saline Infusion

Objective: 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. Design: 65 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 ≥150mmol/l for the hypertonic saline, after 60 minutes for the arginine infusion and after 45 minutes for the oral macimorelin test (expected peak of copeptin and growth hormone levels, respectively). Primary outcome was change from basal to stimulated oxytocin levels using paired t-tests. Results: 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 0.4pg/mL (0.2) to 0.6pg/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). Conclusion: Neither the arginine infusion nor the oral macimorelin test stimulate 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.

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Vasopressin responses to corticotropin releasing factor and hyperosmolality in conscious dogs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.251.6.r1235 ◽

1986 ◽

Vol 251 (6) ◽

pp. R1235-R1239

Author(s):

H. Raff ◽

M. M. Skelton ◽

D. C. Merrill ◽

A. W. Cowley

Keyword(s):

Hypertonic Saline ◽

Plasma Osmolality ◽

Corticotropin Releasing Factor ◽

Saline Infusion ◽

Conscious Dogs ◽

Plasma Sodium ◽

Plasma Vasopressin ◽

Cortisol Responses ◽

Osmotic Stimulus ◽

Hypertonic Saline Infusion

We recently reported that ovine corticotropin releasing factor (CRF) infusion in conscious dogs elevated plasma vasopressin. The present study examines the vasopressin, adrenocorticotropic hormone (ACTH), and cortisol responses to CRF infusion (20 ng X kg-1 X min-1), to hypertonic saline infusion (NaCl 0.054 meq X kg-1 X min-1), and to simultaneous coinfusion of CRF and NaCl (CRF + NaCl) without (no-dex) or with (dex-treated) dexamethasone pretreatment in six conscious dogs (6-8 experiments/dog). CRF had no significant effect on plasma sodium or osmolality, blood pressure, or heart rate. NaCl increased plasma sodium from 146 +/- 1 to 151 +/- 1 meq/l and plasma osmolality from 298 +/- 3 to 305 +/- 3 mosmol/kg. Vasopressin increased significantly during CRF (2.1 +/- 0.5 to 4.8 +/- 1.1 pg/ml) and NaCl (1.9 +/- 0.3 to 5.0 +/- 0.8 pg/ml). Coinfusion of CRF and NaCl resulted in a response larger than the sum of the two infusions alone (3.0 +/- 1.6 to 31.4 +/- 18.5 pg/ml). The ACTH response to CRF (45 +/- 8 to 288 +/- 88 pg/ml) was not augmented by coinfusion with NaCl. DEX attenuated the vasopressin and ACTH responses to each infusion. We conclude that CRF-induced increases in vasopressin are augmented by a simultaneous osmotic stimulus. In addition, the plasma vasopressin responses to CRF and/or hypertonic saline infusion are inhibited by glucocorticoid pretreatment.

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Sodium balance and the natriuresis of hypertonic saline infusion in dogs

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1976.230.5.1183 ◽

1976 ◽

Vol 230 (5) ◽

pp. 1183-1186 ◽

Cited By ~ 5

Author(s):

JA Diaz-Buxo ◽

JA Haas ◽

CE Ott ◽

JL Cuche ◽

GR Marchand ◽

...

Keyword(s):

Hypertonic Saline ◽

Salt Intake ◽

Isotonic Saline ◽

Saline Infusion ◽

Dietary Sodium ◽

Sodium Balance ◽

Plasma Sodium ◽

High Sodium ◽

Sodium Diet ◽

Hypertonic Saline Infusion

Recently, a paradoxical effect of dietary salt intake on the natriuresis following hypertonic saline infusion was observed in rats. In these experiments the effects of alterations in dietary sodium on the natriuretic response to a hypertonic saline load was studied in dogs. Dogs maintained on a high-sodium diet did not have a significantly different natriuresis than those on a low-sodium diet. When differences in sodium balance were amplified by the use of deoxycorticosterone, furosemide, and manipulation of dietary sodium, dogs in positive sodium balance showed a significantly enhanced initial excretion of sodium followed by a reversal of the pattern. Consequently, the cumulative sodium excretion was not different between low- and high-sodium groups. Since the cumulative natriuretic response to isotonic saline infusion was larger in dogs in positive sodium balance compared to those in negative sodium balance, the failure to detect a difference following hypertonic saline infusion was probably because of the increased plasma sodium concentration.

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Lidocaine coinfusion alleviates vascular pain induced by hypertonic saline infusion: a randomized, placebo-controlled trial

BMC Anesthesiology ◽

10.1186/s12871-021-01329-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhiping Song ◽

Shibiao Chen ◽

Yang Zhang ◽

Xiaoyun Shi ◽

Na Zhao ◽

...

Keyword(s):

Hypertonic Saline ◽

Saline Solution ◽

Time Slot ◽

Controlled Trial ◽

Saline Infusion ◽

Clinical Trial Registry ◽

Hypertonic Saline Solution ◽

Vas Scores ◽

Vascular Pain ◽

Hypertonic Saline Infusion

Abstract Background Hypertonic saline solution has been frequently utilized in clinical practice. However, due to the nonphysiological osmolality, hypertonic saline infusion usually induces local vascular pain. We conducted this study to evaluate the effect of lidocaine coinfusion for alleviating vascular pain induced by hypertonic saline. Methods One hundred and six patients undergoing hypertonic saline volume preloading prior to spinal anesthesia were randomly allocated to two groups of 53 each. Group L received a 1 mg/kg lidocaine bolus followed by infusion of 2 mg/kg/h through the same IV line during hypertonic saline infusion; Group C received a bolus and infusion of normal saline of equivalent volume. Visual analogue scale (VAS) scores of vascular pain were recorded every 4 min. Results The vascular pain severity in Group L was significantly lower than that in Group C for each time slot (P < 0.05). The overall incidence of vascular pain during hypertonic saline infusion in Group L was 48.0%, which was significantly lower than the incidence (79.6%) in Group C (P < 0.05). Conclusion Lidocaine coinfusion could effectively alleviate vascular pain induced by hypertonic saline infusion. Trial registration Chinese Clinical Trial Registry, number: ChiCTR1900023753. Registered on 10 June 2019.

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Reproducibility of osmotic and nonosmotic tests of vasopressin secretion in men

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.260.3.r533 ◽

1991 ◽

Vol 260 (3) ◽

pp. R533-R539 ◽

Cited By ~ 5

Author(s):

C. J. Thompson ◽

P. Selby ◽

P. H. Baylis

Keyword(s):

Blood Glucose ◽

Linear Regression ◽

Hypertonic Saline ◽

Linear Regression Analysis ◽

Plasma Osmolality ◽

Saline Infusion ◽

Intraindividual Variation ◽

Insulin Tolerance ◽

Vasopressin Secretion ◽

Hypertonic Saline Infusion

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.

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Hypertonic saline infusion for treating intracranial hypertension after severe traumatic brain injury

Critical Care ◽

10.1186/s13054-018-1963-7 ◽

2018 ◽

Vol 22 (1) ◽

Cited By ~ 8

Author(s):

Halinder S. Mangat

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Intracranial Hypertension ◽

Hypertonic Saline ◽

Severe Traumatic Brain Injury ◽

Saline Infusion ◽

Hypertonic Saline Infusion

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Tolvaptan Use to Treat SIADH in a Child

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-23.6.494 ◽

2018 ◽

Vol 23 (6) ◽

pp. 494-498

Author(s):

Adem Yasin Koksoy ◽

Meltem Kurtul ◽

Aslı Kantar Ozsahin ◽

Fatma Semsa Cayci ◽

Meltem Tayfun ◽

...

Keyword(s):

Hypertonic Saline ◽

Treatment Option ◽

Pediatric Patients ◽

Hormone Secretion ◽

Saline Infusion ◽

Fluid Restriction ◽

Effective Treatment Option ◽

Inappropriate Antidiuretic Hormone Secretion ◽

Electrolyte Abnormalities ◽

Hypertonic Saline Infusion

Hyponatremia is one of the most common electrolyte abnormalities encountered in the clinical setting in hospitalized patients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the leading cause of hyponatremia in most of these cases. While fluid restriction, hypertonic saline infusion, diuretics, and the treatment of underlying conditions constitute the first line of treatment of SIADH, in refractory cases, and especially for pediatric patients, there seems not to be any other choice for treatment. Tolvaptan, although its use in pediatric patients is still very limited, might be an attractive treatment option for correction of hyponatremia due to SIADH. Here we present a pediatric case of SIADH that was resistant to treatment with fluid restriction and hypertonic saline infusion and was treated successfully with tolvaptan. Tolvaptan could be a good, safe, and effective treatment option in pediatric SIADH cases that are resistant to treatment. However, the dosage should be titrated carefully.

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