Selective excision of adenomas originating in or extending into the pituitary stalk with preservation of pituitary function R. Bryan Mason, M.D., Lynnette K. Nieman, M.D., John L. Doppman, M.D., and Edward H. Oldfield, M.D. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke; Developmental Endocrinology Branch, National Institute of Child Health and Human Development; and Diagnostic Radiology Department, The Clinical Center, National Institutes of Health, Bethesda, Maryland; and Department of Neurosurgery, National Naval Medical Center, Bethesda, Maryland When the surgeon identifies an adenoma within the gland and selectively excises it, endocrine-active pituitary tumors are usually cured and pituitary function is preserved. Occasionally ectopic adenomas arise primarily in the pituitary stalk or arise superiorly in the midportion of the anterior lobe and extend upward within the stalk. To determine if these tumors can be selectively excised with preservation of pituitary function, the authors examined the outcome of selective adenomectomy in 10 patients with Cushing's disease with an ectopic adenoma originating in, and confined to, the stalk (four microadenomas) or an adenoma extending superiorly through the diaphragma sella and into the stalk (five microadenomas and one macroadenoma) from an operative series of 516 patients with Cushing's disease. To reach the adenoma transsphenoidally in these patients, the diaphragma sella was incised anteroposteriorly in the midline to the anterior edge of the stalk, the suprasellar cistern was entered, and the adenoma was selectively excised using care to limit injury to the infundibulum. After selective adenomectomy, Cushing's disease remitted in all patients. All patients were hypocortisolemic immediately after surgery and required hydrocortisone for up to 21 months. Apart from the adrenal axis, pituitary function was normal in five patients in the immediate postoperative period, including two patients with tumors confined to the stalk and three patients with preoperative hypothyroidism (one patient) and/or hypogonadism (three patients). Three others with transient postoperative hypothyroidism (one patient) or diabetes insipidus (two patients) had normal pituitary function within 7 months of surgery. One patient with hypothyroidism and one with hypogonadism before surgery had panhypopituitarism postoperatively. A patient with a microadenoma located high in the stalk next to the optic chiasm had bitemporal hemianopsia postoperatively. These results demonstrate the feasibility of achieving curative transsphenoidal resection and preservation of pituitary function in cases of pituitary adenomas that are confined to the pituitary stalk or tumors that extend superiorly within the stalk from an intrasellar origin. Key Words * pituitary adenoma * Cushing's disease * pituitary stalk Unauthenticated | Downloaded 10/02/21 04:19 PM UTC Most pituitary adenomas arise in the anterior lobe of the pituitary gland and can be excised selectively via transsphenoidal adenomectomy with elimination of tumor and preservation of pituitary function. However, some adenomas arise within, and remain localized to, the pituitary stalk. Other pituitary adenomas arise in the superior portion of the anterior lobe and extend superiorly into the stalk. In the past, suprasellar ectopic pituitary adenomas that involve the stalk have been removed by transcranial surgery.[3,6,12,16,19,21,24,26] Using these operations, tumor removal was often incomplete and most patients lost pituitary function.[6,16,24,26] We report 10 cases of patients with adrenocorticotropic hormone (ACTH)­secreting pituitary adenomas that originated in the infundibulum or extended into the infundibulum through the opening of the diaphragma sella. All patients underwent transsphenoidal selective adenomectomy and showed laboratory and clinical remission of their hypercortisolism. Seven patients with normal pituitary function before surgery retained normal function after surgery, one patient with abnormal pituitary function before surgery regained normal function, and two patients with impaired pituitary function preoperatively lost additional pituitary function as a result of the surgery. CLINICAL MATERIALS AND METHODS Patient Population Ten patients with adenomas that arose in the pituitary stalk above the diaphragma sella or extended superiorly into the stalk and above the diaphragma sella from the anterior lobe were identified from among 516 consecutively admitted patients who underwent transsphenoidal exploration for Cushing's disease at the National Institutes of Health between 1982 and 1995. Six patients (two women and four men, 26­60 years old) had adenomas that extended superiorly from the anterior pituitary into the stalk. One of these tumors was a macroadenoma (>= 10-mm maximum diameter). Four patients (two male and two female patients, 14­34 years old) had microadenomas that originated within, and remained confined to, the pituitary stalk. All 10 patients underwent a standard magnetic resonance (MR) imaging protocol[11] performed using a 1.5-tesla imaging system (Signa; General Electric, Minneapolis, MI). Studies included T1-weighted coronal and sagittal images of the pituitary fossa in 3-mm sections. Gadolinium-diethylenetriamine pentaacetic acid (DTPA) (0.1 mmol/kg body weight [Magnevist; Berlex Lab, Wayne, NJ]) was administered intravenously over 2 minutes. The T1-weighted coronal images were then repeated. All surgical procedures were performed by the same surgeon (E.H.O.). Laboratory Evaluation Preoperative determination of hypercortisolism and diagnosis of Cushing's disease were established using current conventional endocrinological and radiological evaluation. The biochemical response to surgery was measured according to a standardized protocol. Each patient received 0.5 mg of dexamethasone intravenously every 6 hours for 36 hours beginning immediately after surgery. On the 3rd postoperative day (>= 24 hours after the last 0.5-mg dose of dexamethasone), morning serum cortisol levels were drawn between 7 a.m. and 8 a.m., and urine was collected for a 24-hour urinary free cortisol (UFC) test. These determinates were repeated for several consecutive days. A response to surgery demonstrating remission of hypercortisolism was classified as hypocortisolism (morning cortisol level < 7 µg/dl; UFC < 20 µg/day) or eucortisolism (UFC 20•90 µg/day). Pituitary hypothyroidism was defined as subnormal levels of free tyroxin (< 0.9 mg/dl) with low or subnormal thyroid-stimulating hormone values. Hypogonadism was defined as the absence of menses in Unauthenticated | Downloaded 10/02/21 04:19 PM UTC a woman of reproductive age, inappropriately low follicle-stimulating hormone (< 25 ng/ml) in an amenorrheic woman older than 50 years of age or subnormal plasma testosterone (< 200 ng/ml) in a man. Partial hypopituitarism was defined as a deficiency in one or more, but not all, pituitary hormones. Panhypopituitarism was defined as a deficiency in all anterior pituitary hormones. Hypopituitarism was considered a result of surgery if hormonal replacement that was not needed preoperatively became necessary postoperatively. The immediate postoperative period was designated as the time from surgery to 3 months afterward, when the late postoperative period began.[27] Surgical Technique In all patients a transsphenoidal approach was used to resect the adenoma selectively (Fig. 1). Adenomas in the stalk always reached the pituitary capsule or the pia-arachnoid and, thus, lacked the type of capsule seen in adenomas of the pituitary gland. In contrast to intrasellar adenomas, which generally are quite easy to separate from surrounding normal tissue, the margin of adenomas within the stalk was more adherent to the stalk than is characteristic of the interface of the pseudocapsule of an adenoma and the anterior lobe. To develop a clear delineation of the pseudocapsule surrounding the adenoma and to separate the edge of the tumor from the stalk, an incision along the interface between the pseudocapsule and the stalk was made and developed with a No. 11 or No. 15 scalpel on a long bayonet handle. Blunt dissection using fine bipolar tips, microdiscs, and small ring curettes was performed to define the margin of the adenoma from the pituitary gland and to remove the remaining tumor. Unauthenticated | Downloaded 10/02/21 04:19 PM UTC Fig. 1. Drawings depicting the routine wide exposure of the anterior surface of the sella and bone removal to expose the medial portion of the cavernous sinus bilaterally. In patients in whom MR imaging indicated stalk involvement, the posterior portion of the planum sphenoidale (the posterior 4­6 mm) was removed by first drilling with a rough diamond burr until the plate of bone was paper thin, and then using a 2-mm-thin-footplate cervical Kerrison rongeur. Removal of the planum sphenoidale aided access to the suprasellar cistern, the pituitary stalk, and the superior surface of the gland. The dura mater covering the anterior pituitary surface was opened widely. Bilateral parasagittal incisions were made 8 to 10 mm apart in the dura overlying the planum sphenoidale. A transverse incision just above the anterior portion of the circular sinus was then used to connect the parasagittal incisions. The resulting dural flap was opened posteriorly while, initially, preserving the intact arachnoid. After entering the suprasellar cistern, the superior hypophyseal artery was identified and care was taken not to injure