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. 2021 Aug 3;185(3):355-364.
doi: 10.1530/EJE-21-0346.

Oxytocin levels in response to pituitary provocation tests in healthy volunteers

Clara O Sailer  1   2 , Bettina Winzeler  1   2 , Sandrine A Urwyler  1   2 , Ingeborg Schnyder  1 , Julie Refardt  1   2 , Anne Eckert  3   4 , Nimmy Varghese  3   4 , Martin Fassnacht  5   6 , Irina Chifu  5 , Elizabeth A Lawson  7 , Joseph G Verbalis  8 , Wiebke Fenske  9 , Mirjam Christ-Crain  1   2
Affiliations

Oxytocin levels in response to pituitary provocation tests in healthy volunteers

Clara O Sailer et al. Eur J Endocrinol. .

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.

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Figures

Figure 1:
Figure 1:
Percent change in plasma copeptin (a) and oxytocin levels (b) upon hypertonic saline infusion test. The middle line represents the median, the outer lines of the box the interquartile range (IQR). The lines between basal and stimulated hormonal levels indicate each individual participant. A percent change of 0% refers to the same basal and stimulated level, values >0% refer to an increase and values >0% refer to a decrease in stimulated hormone levels in reference to the basal level.
Figure 2:
Figure 2:
Percent change of plasma copeptin (A) and oxytocin (B) levels upon arginine infusion test. The middle line represents the median, the outer lines of the box the interquartile range (IQR). The lines between basal and stimulated hormonal levels indicate each individual participant. A percent change of 0% refers to the same basal and stimulated level, values >0% refer to an increase and values >0% refer to a decrease in stimulated hormone levels in reference to the basal level.
Figure 3:
Figure 3:
Percent change of growth hormone (A), copeptin (B) and oxytocin (C) levels upon oral macimorelin test. The middle line represents the median, the outer lines of the box the interquartile range (IQR). The lines between basal and stimulated hormonal levels indicate each individual participant. A percent change of 0% refers to the same basal and stimulated level, values >0% refer to an increase and values >0% refer to a decrease in stimulated hormone levels in reference to the basal level.
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