In Reply: Manifestations of Water and Sodium Disorders Following Surgery for Sellar Lesions

To the Editor: We feel compelled to discuss the letter by Lin and Wang,1 in the most recent issue of Neurosurgery, regarding water balance disorders after sellar surgery. The authors discuss their observation of an aquaresis in the later phases of hyponatremia after sellar surgery. Water balance disorders are common after sellar surgery, as the centers regulating tonicity and their effector organs all lie in close proximity to the sella.2 Interruption of arginine vasopressin (AVP) secretion leads to diabetes insipidus (DI), which is especially common in younger patients with suprasellar lesions, particularly craniopharyngioma, and high-grade intraoperative cerebrospinal fluid leaks, as summarized by the suprasellar, age, lesion, three score.3 Importantly, a patient need not be hypernatremic (a surrogate for hypertonicity) to be diagnosed with DI, so long as the patient can maintain water balance with the thirst response.3,4 Unique to sellar surgery, concomitant hypocortisolemia may mask the development of DI through downstream effects on the V2 receptor, and thus water balance should always be assessed after resuscitation of the glucocorticoid axis.5,6 The development of hyponatremia after sellar surgery is often more difficult to untangle, as several processes may contribute simultaneously. Hyponatremia after sellar surgery is often attributed to the syndrome of inappropriate antidiuresis (SIAD); however, this term should be reserved for cases with hypertonic urine, which is inappropriate relative to serum tonicity and most importantly the intravascular volume state.2 The most common culprit is an “isolated second phase” of the triphasic response. Here, infundibular injury is not sufficiently devastating to establish DI, as the population of undamaged neurons is sufficient to defend plasma tonicity. However, the neurons that have been injured undergo degeneration and release their stored AVP days after injury, producing a transient SIAD-like state (Figure 1). This mechanism explains the delayed occurrence of hyponatremia (cf. the immediate appearance of polyuria) after stalk damage. Concomitant hypocortisolemia7 is rarely a contributing factor to hyponatremia as these patients are often “covered” with prophylactic (supraphysiological doses of) glucocorticoids perioperatively.8 Lin and Wang invoke the contentious, uncommon, syndrome of cerebral salt wasting (we, and others, prefer the term cerebral-renal salt wasting, CRSW)2,9 as a further etiology of hyponatremia; however, this is more often seen after intracranial catastrophe, as the predominant putative mechanisms relate to dysfunctional sympathetic outflow and natriuretic peptide release, not pituitary dysfunction per se.2FIGURE 1.: Pathophysiology of the triphasic response. Interruption of axoplasmic flow in magnocellular neurons in the immediate postoperative period leads to DI. In the following days, AVP stored in terminal Herring bodies is released from degenerating neurons, causing a transient SIAD-like state. These AVP stores are soon exhausted and chronic DI ensues. In cases where the initial insult is less severe, the quantity of spared neurons is sufficient to defend tonicity, but unregulated release of stored AVP still occurs in damaged neurons, and a delayed, isolated period of hyponatremia ensues (isolated second phase). Reprinted by permission from the Copyright Clearance Center: Springer Nature, Neurosurgical Review, Hyponatraemia and hypernatraemia: disorders of water balance in neurosurgery, Castle-Kirszbaum M, Kyi M, Wright C, Goldscklager T, Danks RA, Parkin G, ©2021 Springer Nature Switzerland AG. AVP = arginine vasopressin; DI = diabetes insipidus; PVN = paraventricular nucleus; SIAD = syndrome of inappropriate antidiuresis; SON = supraoptic nucleus.The novel message of Lin and Wang's letter is their observation of “relative DI” in the later phases of postoperative hyponatremia. From this, they propose that postoperative hyponatremia may be divided into an early stage, resembling SIAD, and a late stage, resembling “transient DI.” We argue that, contextually, this late stage is merely the restorative phase of SIAD, where normal water balance has returned. Hyponatremia, by definition, is a state of water overload relative to the tonicity of the system. Thus, it follows that the physiological response to a hypotonic state is an aquaresis, facilitating restoration of normal tonicity. This aquaresis would ostensibly resemble DI, with large volumes of dilute urine; however, the cause is not pathological, but physiological. Moreover, description of this restorative phase is not novel, and forms part of our algorithmic approach to hyponatremia2 (Figure 2). A caveat occurs when this posthyponatremia aquaresis is persistent, in which case one must consider the differential of an evolving triphasic response. However, as the name implies, these patients have often displayed signs of polyuria and polydipsia prior to the development of hyponatremia.FIGURE 2.: Hyponatremia classified by urinary tonicity. Urinary tonicity is given by the urinary sodium ([Na+]u) and potassium ([K+]u) sum. When urinary tonicity is greater than plasma tonicity (approximated by plasma sodium ([Na+]p)) (ie, ([Na+]u + [K+]u) > [Na+]p) (purple boxes), the kidneys are causing free-water retention and AVP levels are elevated. In the setting of hyponatremia, these AVP levels may be appropriate to the effective volume state, or may be pathological (ie, SIAD). AVP levels should supress completely in the setting of hyponatremia, and thus a urinary tonicity that is slightly less than serum tonicity is still grossly abnormal, and suggests renal free-water retention. When urinary tonicity is far less than serum tonicity (ie, ([Na+]u + [K+]u) < [Na+]pw) (green boxes), aquaresis is occurring, and AVP levels are low. In the setting of hyponatremia, supressed AVP is physiological, and the cause of hyponatremia is nonrenal. The caveat is a renally driven process (eg, SIAD) that resolves prior to testing, and only the restorative phase is biochemically captured. Reprinted by permission from the Copyright Clearance Center: Springer Nature, Neurosurgical Review, Hyponatraemia and hypernatraemia: disorders of water balance in neurosurgery, Castle-Kirszbaum M, Kyi M, Wright C, Goldscklager T, Danks RA, Parkin G, ©2021 Springer Nature Switzerland AG.In conclusion, disorders of water balance after sellar surgery are complex. A transient restorative aquaresis after SIAD is common and physiological, and is reassuring that the patient is beginning to initiate independent water balance. Normal physiology should not be confused with new pathology to avoid unnecessary interventions. Funding This study did not receive any funding or financial support. Disclosures The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.