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Management of Water and Sodium Disturbances after Transsphenoidal Resection of Pituitary Tumors
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.287679
Keywords: Diabetes insipidus, fluid, pituitary surgery, sodium, syndrome of inappropriate secretion of antidiuretic hormone
Fluid and electrolyte homeostasis are essential functions, regulated, in part, by the hypothalamic-pituitary-adrenal (HPA) axis. Patients with operative sellar pathologies, such as pituitary adenomas, are at risk for both preoperative and postoperative disturbances in the HPA axis. These problems are likely due to mass effect from the lesion, surgical manipulation of the pituitary gland, and/or local vascular alterations caused by the mass or by the surgical intervention itself.[1] The most common fluid and electrolyte disturbances following transsphenoidal resection of sellar masses involve the regulation of sodium. Sellar surgery places patients at risk of postoperative diabetes insipidus (DI) and the syndrome of inappropriate anti-diuretic hormone secretion (SIADH).[1],[2] The aim of this review is to discuss the important anatomical and physiological principles of water and sodium regulation in the HPA axis, the ways in which water and sodium physiology become dysregulated after transsphenoidal surgery, and an approach to monitoring for and minimizing complications related to sodium disturbances after sellar surgery.
The HPA axis components related to water regulation comprise the hypothalamus, the anterior and posterior pituitary, the adrenal gland, and their neuronal and secretory hormonal interconnections. Much of the water and sodium homeostasis in the HPA axis is governed by the tightly regulated synthesis and release of antidiuretic hormone (ADH).[2],[3],[4],[5],[6] The overall function of ADH is to raise the circulating blood volume and increase blood pressure, as will be described below.[6] Disruptions in ADH metabolism and secretion can lead to the commonly seen complications after sellar surgery. ADH is synthesized in the magnocellular neurons of the supraoptic and paraventricular nuclei in the hypothalamus.[7] The axons of the neurons in these nuclei project to the posterior pituitary gland via the hypothalamic-hypophyseal tract, making up a part of the pituitary stalk. ADH is transported along these axons from the hypothalamus and is stored in the posterior pituitary, awaiting its release.[2] Under ordinary conditions, the primary stimuli triggering ADH secretion into the circulation are: 1) a rise in plasma osmolality and 2) a decrease in blood pressure/circulating blood volume.[3],[5],[6],[7],[8],[9],[10] Under those conditions, ADH is secreted into the circulation and acts primarily on the kidneys by encouraging water reabsorption at the renal collecting duct. It also acts secondarily on the blood vessels themselves, stimulating vasoconstriction and a rise in blood pressure.[3],[5],[6],[7],[8],[9],[10] Taken in sum, elevated osmolality—indicating a hemo-concentrated state—and/or decreased circulating blood volume and low blood pressure are the primary triggers for ADH secretion. ADH, in turn, promotes water reabsorption and vasoconstriction, intended to lower plasma osmolality, and increase circulating blood volume and blood pressure.
Surgical manipulation of the pituitary gland during sellar surgery can lead to damage along the neuro-anatomical and hormonal secretory pathways above.[1],[2],[4],[8],[11],[12],[13],[14] Specifically, injury to the hypothalamus itself (rare during transsphenoidal surgery), the pituitary stalk, or the posterior pituitary gland can alter the metabolism and secretion of ADH. Diabetes inspidus (DI) Postoperative DI is the most common complication after pituitary surgery, occurring anywhere from 10 to 30% of patients.[15],[16],[17],[18],[19],[20] In most of these patients, DI is transient, with long-term persistent DI reported in fewer than 10% of patients.[1],[8],[12] More than half of patients see resolution within one week and approximately 80% within 3 months.[8],[12] Risk factors for persistent DI include younger age, male sex, preoperative DI, larger masses, and previous sellar surgeries.[2],[12],[17],[21] The hallmark of postoperative DI is insufficient secretion of ADH by the posterior pituitary gland due to surgical manipulation of the hypothalamus, pituitary stalk, or posterior pituitary gland. With insufficient ADH release, the body lacks the hormonal signal to appropriately retain water at the renal collecting ducts. This results in high output of dilute urine, or polyuria. Such diuresis results in high serum osmolality (>295 mOsm/kg) and hemoconcentration, therefore elevating serum sodium. The increase in serum osmolality leads to polydipsia.[1],[2] Clinically, patients who develop DI report copious, dilute urine output with insatiable thirst. Should their hypernatremia progress to dangerous levels, they may also develop weakness, nausea, muscle twitching, and progress to seizure and/or coma. Syndrome of inappropriate antidiuretic hormone release (SIADH) In contrast to DI, SIADH is a condition characterized by an abnormally high release of ADH. In the postoperative setting after pituitary surgery, SIADH is believed to develop because of degeneration of axons along the hypothalamic–hypophyseal tract. This degeneration leads to release of residual ADH stores within the axons.[2] With inappropriate ADH release, the urine becomes abnormally concentrated and water is retained within the circulation.[5] Elevated circulating water yields dilute serum and can produce a profound hyponatremia. Without close monitoring, patients who are no longer hospitalized and are consuming free water may further exacerbate their hyponatremia. Clinically, patients who develop SIADH notice oliguria or, in rare cases, anuria. Should their hyponatremia progress to dangerous levels, symptoms may also include nausea, vomiting, malaise, anorexia, muscle cramping, generalized weakness, lethargy, altered mental status, myoclonus, seizure, and coma.[1],[2],[4],[6],[8],[12] The triple phase response Not all patients will present with DI, SIADH, or both after pituitary surgery; however, a small subset of patients—approximately 3% in some estimates—will present with what is termed the “triple phase response.”[21] In the triple phase response, patients will exhibit an initial polyuric phase (consistent with DI), a subsequent antidiuretic phase, and an ultimate polyuric phase that is often chronic. The initial polyuric phase usually develops within the first 24-48 hours after surgery and is thought to be the result of iatrogenic damage to the HPA axis at the time of surgery. Frequently, this polyuric phase will progress to meeting criteria for DI and lasts approximately 1–4 days postoperatively.[21],[22],[23] Approximately 5-8 days after surgery, the initial damage to the HPA axis from the operation leads to degeneration of axons along the axis itself. This degeneration can lead to the release of stores of ADH that were residing in the axons, but could not be released because of the lack of a trigger from higher in the axis. The antidiuretic phase can last approximately 2-5 days as the now-released ADH acts on the kidneys and peripheral vasculature. This phase is marked by a temporary ability to concentrate the urine and, at times, profound hyponatremia and plasma hypoosmolality.[21],[22],[23] Finally, upon depletion of the ADH deposits, patients return to an ultimate polyuric phase, which is often chronic. The presentation mimics that of the initial polyuric phase, where patients will demonstrate a dilute polyuria, polydipsia, hypernatremia, and plasma hyperosmolality.[8],[21],[22],[23]
As discussed, water and salt metabolism can become dysregulated after transsphenoidal surgery for resection of pituitary tumors. Given the rapidity with which patients can develop severe and symptomatic postoperative DI and/or SIADH, it is essential to have a methodical approach for monitoring and treatment. Institutions around the world have different means of monitoring pituitary surgery patients postoperatively. Anecdotally, at some institutions, patients remain hospitalized through the initial DI and subsequent SIADH at-risk period—approximately 8-10 days—to monitor for and treat each condition if appropriate. In the United States, given the expense of inpatient care and perpetual need for additional hospital beds, this is not standard practice. Some institutions recommend discharging all patients on fluid restrictions with close follow-up, in an effort to combat the development of postoperative SIADH.[24] This has not been our practice, as much of our patient population lives in rural areas and has more-limited access to immediate care should they develop rebound hypernatremia from a fluid restriction. At the University of Utah, we developed a foundational protocol to standardize the postoperative management of all patients who have undergone transsphenoidal resection of pituitary tumors. [Figure 1] outlines the steps in our protocol described below.
Immediate postoperative period After transsphenoidal resection of a pituitary tumor, all patients are transferred to the neurosurgical critical care unit at our institution for further postoperative management. Vital signs and neurological examination, including visual assessment at the bedside, are performed. The senior author routinely places nasal tampon after tumor removal to specifically avoid the complication of early postoperative epistaxis. These are assessed frequently for evidence of haloing that may suggest cerebrospinal fluid leak. These tampons are then removed on postoperative day 1. Patients are also informed that they should immediately inform a nurse or physician if they develop salty taste in the back of their throat or concerning drainage through the packings and onto the mustache dressing. On arrival to their inpatient room, all patients have a large jug of free water at the bedside that they are encouraged to drink from to address thirst. This is present to allow them to compensate if they develop signs of DI. The jug does not contain a straw because straw use, nose blowing, sneezing, and use of an incentive spirometry all create high-pressure flow through the nasal sinus. Monitoring for DI and SIADH All patients' intake and output are strictly monitored during the duration of their stay. All urine output volumes are recorded both in the electronic medical record as well as on a urine-output log, posted on the outside of their door. If a patient has urine output that is greater than 250 ml per hour for two consecutive hours, the patient's nurse sends a urine specific gravity test for evaluation and notifies the physician on duty. If the urine output is greater than 400 ml per hour for two consecutive hours, the nurse also sends a serum sodium level for analysis and informs the physician on duty. Patients who are considered to be at high risk for developing DI will have a serum sodium study sent at 22:00 on the day of their operation, regardless of their urine output. High-risk patients include those with pituitary apoplexy or acromegaly and patients in whom intraoperative alcohol is used during the case. All patients, regardless of their urine output, have daily morning complete blood count and basic metabolic panel tests sent for monitoring. Regardless of whether a patient develops DI while an inpatient or requires treatment with desmopressin (discussed below), all postoperative patients receive a serum sodium check on postoperative day #7. Our average length of stay for pituitary surgery is 2.5 days, so most patients have been discharged before this time. This is an important point in that the small percentage of patients who have delayed SIADH cannot be predicted by their inpatient sodium levels in our experience. Because most patients have been discharged from the hospital before postoperative day #7, they are instructed to have this study drawn locally and have the results sent to our office as well as to the referring physician. The purpose of this is to monitor patients for further development of DI or, more likely, delayed SIADH. If there is evidence of further DI or SIADH on the postoperative day #7 serum sodium draw, patients are seen in clinic immediately for recommendations on further management. Treatment of DI As the above protocol is followed, serum sodium and urine specific gravity studies are sent at intervals dictated by the patient's own urine output as opposed to predetermined time points. Patients are encouraged to drink free water to satiety to compensate for the development of DI. Per protocol, if a patient develops hypernatremia to a sodium level >147 mEq/L with evidence of dilute urine on specific gravity studies, they are considered to be in uncompensated DI, and will be administered a one-time dose of desmopressin (1 μg). After administration of desmopressin, the patient will remain on the aforementioned monitoring protocol for determination of whether further treatments are needed. In general, we tend to undertreat DI in the early postoperative period if the patient is able to compensate with drinking ad lib. This avoids the complication of over treating the early DI, which then results in iatrogenic hyponatremia if the patient is discharged on desmopressin. In most patients, the DI will resolve in the first few days after surgery, so there is a risk of over treating the transient DI, resulting in potentially dangerous iatrogenic hyponatremia. Treatment of SIADH Patients who are found to be hyponatremic in the postoperative period after a pituitary operation may be developing SIADH. Should this occur, any desmopressin treatment for DI is immediately discontinued. If hyponatremia is significant (in our practice less than 130 mEq/L), the patient is put on a 1 L per day fluid restriction and daily sodium levels are checked. If hyponatremia does not resolve with these interventions, the patient is admitted to the hospital and is initially managed with a complete free water restriction and serial serum sodium studies every six hours. Additionally, first-line salt supplementation therapy includes administration of oral salt tablets (3 g) three times daily with meals. If patient is unable to take oral salt supplementation, intravenous 3% hypertonic saline boluses are used to increase serum sodium levels. These interventions are continued to support the patient through the period of postoperative SIADH. Assessing postoperative pituitary gland function On the first postoperative day, the endocrinology service is consulted on all postoperative pituitary patients. That night, all patients given nothing by mouth (NPO) except for free water intake at midnight. The following morning at 8:00 am, patients have pituitary function studies drawn. Specifically, the following serum laboratory studies are sent: adrenocorticotropic hormone, cortisol, prolactin, growth hormone, insulin-like growth factor-1, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and total T4. The endocrinology service offers recommendations for hormonal supplementation going forward based on the results of those pituitary studies. All patients on hormonal supplementation are expected to follow-up with the endocrinology service as an outpatient for long-term management of hypopituitarism.
Patients undergoing transsphenoidal resection of pituitary tumors are a special population at risk for a number of postoperative medical complications, including DI and SIADH. Disturbances in water and sodium homeostasis are believed to be attributable to direct damage to the HPA axis at the time of surgical intervention, and downstream consequences such as the triple phase response with SIADH are the sequelae of the initial surgical insult. Management of DI and SIADH in the postoperative pituitary patient should involve dedicated protocols to standardize monitoring and treatment of these conditions. At the University of Utah, this includes immediate postoperative monitoring and treatment of DI and surveillance after discharge with outpatient serum sodium checks. The endocrinology service is also involved for assistance with postoperative management of hypopituitarism.[25-28] An appropriate understanding of the relevant anatomy and physiology—coupled with standardized protocols for postoperative management—can aid with minimizing endocrinologic complications after pituitary surgery. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Figure 1]
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