Clara O Sailer1,2, Bettina Winzeler1,2, Sandrine A Urwyler1,2, Ingeborg Schnyder1, Julie Refardt1,2, Anne Eckert3,4, Nimmy Varghese3,4, Martin Fassnacht5,6, Irina Chifu5, Elizabeth A Lawson7, Joseph G Verbalis8, Wiebke Fenske9, Mirjam Christ-Crain1,2. 1. Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland. 2. Department of Clinical Research, University of Basel, Basel, Switzerland. 3. Psychiatric University Hospital (UPK), University of Basel, Basel, Switzerland. 4. Transfaculty Research Platform Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland. 5. Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany. 6. Central Laboratory, University Hospital Würzburg, Würzburg, Germany. 7. Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. 8. Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA. 9. Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Medical Center Bonn, Bonn, Germany.
Abstract
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: 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. 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 0.4 (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). CONCLUSION: 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.
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: 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. 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 0.4 (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). CONCLUSION: 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.
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