Evan T Blair1, John S Clemmer2, H Louis Harkey3, Robert L Hester2, W Andrew Pruett4. 1. University of Mississippi Medical Center, School of Medicine, Jackson, Mississippi, USA. 2. University of Mississippi Medical Center, Department of Physiology and Biophysics, Center for Computational Medicine, Jackson, Mississippi, USA. 3. University of Mississippi Medical Center, Department of Neurosurgery, Jackson, Mississippi, USA. 4. University of Mississippi Medical Center, Department of Physiology and Biophysics, Center for Computational Medicine, Jackson, Mississippi, USA. Electronic address: wpruett@umc.edu.
Abstract
BACKGROUND: Disturbances in water and electrolyte homeostasis are common after transsphenoidal surgery. These disorders are variable and unpredictable, increasing patient risk and complicating postsurgical treatment. Clinically, it is generally accepted that damage to the pituitary is the cause, but the mechanisms behind the response variability and underlying pathophysiology remain unknown. OBJECTIVE: To test the hypothesis that changing the degree of damage to the pituitary stalk produces a spectrum of water and electrolyte disturbance along which all presentations of postsurgical water and electrolyte disturbances can be identified. METHODS: We used HumMod, a large mathematical model of physiology, to simulate pituitary stalk damage at differing fractions: 20%, 40%, 60%, and 80%. The damaged neurons were modeled to undergo a 5-day countdown to degeneration and release stored antidiuretic hormone as they die, as is proposed to occur. RESULTS: Lower pituitary damage (20%) resulted in transient polyuria and intermediate damage (40%) was associated with delayed polyuria and diabetes insipidus. Higher levels of damage (60% and 80%) showed a triphasic pattern of diabetes insipidus. CONCLUSIONS: We postulate that our model provides a plausible mechanistic explanation for some varieties of postsurgical water and electrolyte disturbances, in which increasing damage to the pituitary potentiates the likelihood of a full triphasic response. However, our simulation shows that merely modifying the level of damage does not produce every presentation of water and electrolyte imbalance. This theory suggests that other mechanisms, which are still unclear and not a part of this model, may be responsible for postoperative hyponatremia and require further investigation.
BACKGROUND: Disturbances in water and electrolyte homeostasis are common after transsphenoidal surgery. These disorders are variable and unpredictable, increasing patient risk and complicating postsurgical treatment. Clinically, it is generally accepted that damage to the pituitary is the cause, but the mechanisms behind the response variability and underlying pathophysiology remain unknown. OBJECTIVE: To test the hypothesis that changing the degree of damage to the pituitary stalk produces a spectrum of water and electrolyte disturbance along which all presentations of postsurgical water and electrolyte disturbances can be identified. METHODS: We used HumMod, a large mathematical model of physiology, to simulate pituitary stalk damage at differing fractions: 20%, 40%, 60%, and 80%. The damaged neurons were modeled to undergo a 5-day countdown to degeneration and release stored antidiuretic hormone as they die, as is proposed to occur. RESULTS: Lower pituitary damage (20%) resulted in transient polyuria and intermediate damage (40%) was associated with delayed polyuria and diabetes insipidus. Higher levels of damage (60% and 80%) showed a triphasic pattern of diabetes insipidus. CONCLUSIONS: We postulate that our model provides a plausible mechanistic explanation for some varieties of postsurgical water and electrolyte disturbances, in which increasing damage to the pituitary potentiates the likelihood of a full triphasic response. However, our simulation shows that merely modifying the level of damage does not produce every presentation of water and electrolyte imbalance. This theory suggests that other mechanisms, which are still unclear and not a part of this model, may be responsible for postoperative hyponatremia and require further investigation.
Authors: Juan Manuel Canelo Moreno; Elena Dios Fuentes; Eva Venegas Moreno; Pablo Jesús Remón Ruíz; Cristina Muñoz Gómez; Ana Piñar Gutiérrez; Eugenio Cárdenas Valdepeñas; Ariel Kaen; Alfonso Soto Moreno Journal: Front Endocrinol (Lausanne) Date: 2022-08-23 Impact factor: 6.055