Role of hypothalamic neuropeptides in the development of hyponatremia in patients after transnasal adenomectomy

BACKGROUND: To date, the causes and predisposing factors for the development of water-electrolyte disturbances after transsphenoidal surgery for hypothalamic-pituitary masses are poorly understood. Neuropeptides such as apelin, copeptin, and brain natriuretic peptide, discovered in recent decades, have been shown in many studies to have a significant effect on the regulation of water-electrolyte metabolism and make them potential hormonal markers of severe postoperative electrolyte complications.

AIM: to study the features of secretion of hypothalamic neuropeptides during normal water and salt metabolism in the perioperative period and in the presence of water and electrolyte metabolism disorders.

MATERIALS AND METHODS: Patients above 18 years of age who were scheduled to undergo transnasal adenomectomy for underlying disease were included in the study. Patient recruitment was conducted from March 2021 to March 2022. All patients were monitored initially and further in the postoperative period of transnasal adenomectomy for the presence of water-electrolyte disturbances by blood sodium determination, as well as determination of apelin-12, copeptin, brain natriuretic peptide, and oxytocin levels in the first 12–24 hours, then on days 2–3, 4–5 and 6–7 postoperatively. Patients also filled in a diary of well-being and water balance.

RESULTS: It has been established that such a water-electrolyte complication as hyponatremia aggravates the postoperative period of transnasal adenomectomy in up to 15% of cases.Our study revealed no significant changes in the levels of apelin and brain natriuretic peptide or their correlation with the level of sodium in patients in both groups, as well as the relationship between neuropeptides. The most interesting effects on water-electrolyte metabolism are demonstrated by the neuropeptides oxytocin and copeptin, the secretion of which has the character of inadequately elevated levels with loss of inverse negative correlation with blood sodium concentration.

CONCLUSION: Our study revealed a high incidence of hyponatremia after transnasal adenomectomy — about 15% of cases, in the genesis of which hypothalamic neuropeptides copeptin and oxytocin seem to play a significant role. Oxytocin has the potential to be a hormonal marker of this severe complication.

1. Pigarova E.A., Dzeranova L.K., Zhukov AYu, Grigoriev AYu, Azizyan VN, Ivaschenko OV, Dedov II. [Electrolyte disorders after endoscopic transnasal neurosurgical interventions]. Endocrine Surgery. 2019;13(1):42-55. (In Russ.). doi: https://doi.org/10.14341/serg10205.

2. Wong P.C.Y., Guo J., Zhang A. The renal and cardiovascular effects of natriuretic peptides // Adv Physiol Educ. 2017. Vol. 41, № 2. P. 179–185. doi: https://doi.org/10.1152/advan.00177.2016.

3. Dabla P.K., Dabla V., Arora S. Copeptin: Role as a novel biomarker in clinical practice. Clin Chim Acta. 2011;412(1-2):22-8. doi: https://doi.org/10.1016/j.cca.2010.09.034.

4. Girault-Sotias P.-E. et al. Apelin and Vasopressin: The Yin and Yang of Water Balance // Front Endocrinol (Lausanne). 2021. Vol. 12. P. 735515. doi: https://doi.org/10.3389/fendo.2021.735515.

5. Badmaeva IN, Astafyeva LI, Kalinin PL, Kadashev BA, Kutin MA. Central diabetes insipidus after resection of sellar-suprasellar tumors: prevalence and predictors of manifestation. Burdenko’s Journal of Neurosurgery. 2021;85(6):111 118. (In Russ.). doi: https://doi.org/10.17116/neiro202185051111.

6. Adrogué H.J., Tucker B.M., Madias N.E. Diagnosis and Management of Hyponatremia: A Review // JAMA. 2022. Vol. 328, № 3. P. 280–291. doi: https://doi.org/10.1001/jama.2022.11176.

7. Patel K.S. et al. Prediction of post-operative delayed hyponatremia after endoscopic transsphenoidal surgery // Clin Neurol Neurosurg. 2019. Vol. 182. P. 87–91. doi: https://doi.org/10.1016/j.clineuro.2019.05.007.

8. Finnerty C.C. et al. The Surgically Induced Stress Response // JPEN J Parenter Enteral Nutr. 2013. Vol. 37, № 5 0. P. 21S-29S. doi: https://doi.org/10.1177/0148607113496117.

9. Chasseloup F., Tabarin A., Chanson P. Diabetes insipidus: Vasopressin deficiency… // Ann Endocrinol (Paris). 2024. Vol. 85, № 4. P. 294–299. doi: https://doi.org/10.1016/j.ando.2023.11.006.

10. Prete A., Corsello S.M., Salvatori R. Current best practice in the management of patients after pituitary surgery // Ther Adv Endocrinol Metab. 2017. Vol. 8, № 3. P. 33–48. doi: https://doi.org/10.1177/2042018816687240.

11. Constanthin P.E. et al. Increased oxytocin release precedes hyponatremia after pituitary surgery // Pituitary. 2021. Vol. 24, № 3. P. 420–428. doi: https://doi.org/10.1007/s11102-020-01121-4.

12. Jahangiri A. et al. Factors predicting postoperative hyponatremia and efficacy of hyponatremia management strategies after more than 1000 pituitary operations // J Neurosurg. 2013. Vol. 119, № 6. P. 1478–1483. doi: https://doi.org/10.3171/2013.7.JNS13273.

13. Brooks E.K., Inder W.J. Disorders of Salt and Water Balance After Pituitary Surgery // J Clin Endocrinol Metab. 2022. Vol. 108, № 1. P. 198–208. doi: https://doi.org/10.1210/clinem/dgac622.

14. Binu A. et al. Role of Copeptin in Predicting Postoperative Hyponatremia and Hypernatremia in Patients Undergoing Endoscopic Pituitary Adenoma Surgery // Neurosurgery. 2024. Vol. 95, № 3. P. 641–650. doi: https://doi.org/10.1227/neu.0000000000002927.

15. Flahault A. et al. Role of the Vasopressin/Apelin Balance and Potential Use of Metabolically Stable Apelin Analogs in Water Metabolism Disorders // Front Endocrinol (Lausanne). 2017. Vol. 8. P. 120. doi: https://doi.org/10.3389/fendo.2017.00120.

16. Roberts E.M. et al. Abnormal fluid homeostasis in apelin receptor knockout mice // J Endocrinol. 2009. Vol. 202, № 3. P. 453–462. doi: https://doi.org/10.1677/JOE-09-0134.

17. Hus-Citharel A. et al. Apelin Counteracts Vasopressin-Induced Water Reabsorption via Cross Talk Between Apelin and Vasopressin Receptor Signaling Pathways in the Rat Collecting Duct // Endocrinology. 2014. Vol. 155, № 11. P. 4483–4493. doi: https://doi.org/10.1210/en.2014-1257.

18. Azizi M. et al. Reciprocal regulation of plasma apelin and vasopressin by osmotic stimuli // J Am Soc Nephrol. 2008. Vol. 19, № 5. P. 1015–1024. doi: https://doi.org/10.1681/ASN.2007070816.

19. Gutkowska J. et al. Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart // Proc Natl Acad Sci U S A. 1997. Vol. 94, № 21. P. 11704–11709. doi: https://doi.org/10.1073/pnas.94.21.11704.