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Using a Physiological Model to Understand Water and Electrolyte Disturbances Following Transsphenoidal Pituitary Surgery

Disturbances in water and electrolyte homeostasis are common following transsphenoidal surgery. These disturbances are variable and unpredictable, increasing patient risk and complicating postsurgical treatment decisions. Clinically, it is generally accepted that damage to the pituitary stalk is the source of these disturbances, but the mechanisms behind the response variability and underlying pathophysiology remains unknown. The objective was to test the hypothesis that stepwise damage to the posterior pituitary produces a spectrum of water and electrolyte disturbance which can account for the full variety of disease presentation. We used HumMod, a large mathematical model of human 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 their stored ADH as they die, as is described in the literature. Pituitary damage changed the balance of water and electrolytes to various degrees. Lower damage (20%) resulted in transient polyuria, while intermediate damage (40%) was associated with a delayed polyuria and diabetes insipidus. Higher levels of damage (60 and 80%) resembled triphasic diabetes insipidus. We postulate that the results from this model can serve as a mechanistic basis for many varieties of postsurgical water and electrolyte disturbances, where increasing cellular damage to the pituitary potentiates the likelihood of a full triphasic response. However, our simulation suggests that water and electrolyte disturbances following pituitary surgery cannot be grouped into a spectrum of disease that depends only on the level of pituitary damage. Other mechanisms which are still unclear and not a part of this model are likely at play.