Comparison of the Vasopressin-2 Antagonist Tolvaptan and Fluid Restriction in the Treatment of Hyponatremia Following Pituitary Surgery

Patients of the Department of Neurosurgery, University of Erlangen-Nuremberg, undergoing surgery for sellar lesions were prospectively included. The study protocol was approved by the local Ethical Committee (Re.-No. 103_12 BC). Informed written consent was given by the participants or the next-of-kin in each case. Exclusion criteria comprised of those below 18 years of age, pregnancy and a drug intolerance.

Patients Baseline information included age, gender, BMI and the clinical presentation. The pre-operative work-up included an opthalmological examination, a 1.5 Tesla magnetic resonance imaging (MRI) with 2mm axial, coronal and sagittal sections revealing the tumor localization, extension, and its invasive behavior. Microsurgery was always performed by the same surgeon. The macroscopic delineation and invasiveness, the surgical manipulation of the pituitary stalk and extend of tumor resection, surgical complications, as well as an intraoperative cerebrospinal fluid (CSF) leak were documented. The tumor and the dura of the floor of the sella were examined histo-pathologically including the proliferation rate, regressive changes, atypical findings, and the existence of Crooke cells and periodic acid-Schiff (PAS) expression. Routine laboratory work-up included creatinine, urea, and alanine aminotransferase (ALT).

The pre- and postoperative endocrine testing of the pituitary function comprised the basal values of cortisol (CORT), growth hormone (GH), insulin-like growth factor (IGF) 1, thyroid stimulating hormone (TSH), free thyroxine (fT4), total triiodothyronine (tT3), luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (TES), estradiol (E2), and prolactin (PRL). Insufficiency of the corticotropic axis was determined by a short synacthen test (adreno-corticotropic hormone; ACTH)-test stimulating with 0.25 mg Syntropin (Synacthen, Novartis Pharma, Nuremberg, Germany) intra-venously and serum cortisol measurement at 0 and 30 minutes.

Surveillance Post-operatively, participants were transferred to the general floor. For a minimum of 10 days, fluid intake, body weight, and urine volume with specific gravidity are documented daily, along with blood pressure and heart rate three-times daily, blood samples for the assessment of electrolytes are taken on day 1, 2, 3, 5, 7, and 9. An endocrine dynamic testing was performed on day 7.

Analytical methods Venous blood samples were drawn in the morning between 7:00 and 9:00 am into pre-cooled tubes. Clotted samples were promptly centrifuged at 3,000 X g for 15 min at 4 degree Celsius, and then the plasma was frozen at -80 degree Celsius until analysis.