We reviewed our experience with 21 patients who had Cushing's disease due to ACTH-secreting macroadenomas to clarify the natural history of this disease. All patients had typical clinical and biochemical features of ACTH-dependent hypercortisolism. Their mean maximal tumor diameter was 1.6 +/- 0.1 cm, and the range was 1.0-2.7 cm. Six patients had cavernous sinus invasion, three had invasion of the floor of their sella, and nine had suprasellar extension. The observed remission rate was significantly lower in macroadenoma patients than in microadenoma patients (67% vs. 91%; chi(2) = 5.7; P < 0.02). Cavernous sinus invasion (odds ratio, 35; 95% confidence interval, 2.6-475; P < 0.008) and presence of a maximum tumor diameter 2.0 cm or more (odds ratio, 12.9; 95% confidence interval, 1.4-124; P < 0.02) emerged as the only predictors of residual disease after surgery. The observed recurrence rate was significantly higher in macroadenoma patients than in microadenoma patients (36% vs. 12%; chi(2) = 4.2; P < 0.05). Macroadenoma patients tended to suffer from recurrences earlier than did microadenoma patients (16 vs. 49 months). Stepwise multiple logistic regression did not identify any predictors of disease recurrence in macroadenoma patients. Eight macroadenoma patients underwent a total of nine repeat surgical procedures, but none of these resulted in clinical remissions. Only four of seven (57%) patients followed for a sufficient period of time achieved normal urinary free cortisol levels after conventional radiotherapy. Three (75%) of these four patients had re-recurrent hypercortisolism after brief periods of eucortisolism. Pharmacological agents and adrenalectomy were effective in the management of hypercortisolism in patients with residual and recurrent disease. Our results indicate that ACTH-secreting macroadenomas are more refractory to conventional treatments than are ACTH-secreting microadenomas.

Los adenomas hipofisarios representan un 15% de los tumores intracraneales benignos. Presentamos los resultados quirúrgicos obtenidos desde la introducción en nuestro centro del abordaje endoscópico endonasal transesfenoidal (EET) en 2005.Análisis retrospectivo de 121 pacientes con lesiones intraselares (58% mujeres; edad 55,7+/-16 años, rango 18-82) tratados mediante EET desde febrero del 2005 hasta enero del 2012, seguidos en promedio 4,58 años (rango 1,08-8,58).Incluimos 6 quistes de Rathke (3 intrasuprasellares, uno intrasellar y 2 suprasellares); 114 adenomas hipofisarios (16 microadenomas, 98 macroadenomas) y un caso con RMN normal. Los hallazgos basales incluían alteraciones hormonales en 59 pacientes (48,7%), seguidas de alteraciones del campo visual en 38 pacientes (31%); en 7 (5,8%) la presentación clínica fue una apoplejía hipofisaria. Logramos la resección completa en 77 casos (63,6%), subtotal en 29 (23,9%) y parcial en 15 (12,3%). En los pacientes con invasión de seno cavernoso de grado 3 y 4 la resección fue subtotal en 30% (12/39) y completa en 46% (18/39). Se obtuvo remisión hormonal en 16 pacientes con enfermedad de Cushing (84%), en 18 con prolactinoma (78,2%) y en 23 con acromegalia (89%). Hubo 12 casos (9%) de fístula de líquido cefalorraquídeo, 4 casos de diabetes insípida y 3 de SIADH/hiponatremia transitorias. Siete pacientes desarrollaron panhipopituitarismo. La tasa de mortalidad posquirúrgica fue de 2,4%. Ciento tres (85,3%) pacientes permanecieron ingresados menos de 48 horas tras la cirugía.Nuestros resultados son comparables con los de prestigiosos centros de referencia en patología hipofisaria; los resultados obtenidos mediante abordaje endoscópico en la neurocirugía hipofisaria son superiores a los de la microneurocirugía cuando existe invasión del seno cavenoso.Pituitary adenomas account for approximately 15% of intracranial benign tumors. The neurosurgical results achieved since the endoscopic endonasal transsphenoidal (EET) approach was introduced in our center in 2005 are reported here.A retrospective analysis of 121 patients with sellar lesions (58% females, age 55.7 ± 16 years, range 18-82) who underwent EET surgery from February 2005 to January 2012 and were followed up for a mean time of 4.58 years (range 1.08-8.58).Six Rathke cleft cysts (3 intra-suprasellar, 1 intrasellar, 2 suprasellar); 114 pituitary adenomas (16 microadenomas, 98 macroadenomas), and 1 case of normal MRI were included. Baseline findings included hormonal changes in 59 patients (48,7%) and visual field changes in 38 patients (31%); in 7 patients (5.8%), clinical presentation was pituitary apoplexy. Complete resection was achieved in 77 patients (63.6%), subtotal resection in 29 (23.9%), and partial resection in 15 (12.3%). In patients with Grade 3 and 4 cavernous sinus invasion, resection was subtotal in 30% (12/39) and complete in 46% (18/39). Hormonal remission was achieved in 16 patients with Cushing disease (84%), 18 patients with prolactinoma (78.2%), and 18 patients with acromegaly (85,7%). There were 12 cases (9%) of cerebrospinal fluid leak, 4 cases of diabetes insipidus, and 3 cases with transient SIADH/hyponatremia. Seven patients developed panhypopituitarism. Postoperative mortality rate was 2.4%. One hundred and three patients (85.3%) were discharged from the hospital less than 48 hours after surgery.Our results are similar to those reported by renowned pituitary units. Results achieved using an endoscopic approach in pituitary neurosurgery are better than those of microneurosurgery for cavernous sinus invasion.

Transsphenoidal adenomectomy is the preferred treatment for Cushing's disease. We analyzed a group of 124 patients with presumed Cushing's disease who were treated by transsphenoidal microsurgical adenomectomy between 1972 and 1995. Of these, 24 patients had macroadenomas, 92 had microadenomas, 4 had corticotroph hyperplasia, 2 had Nelson's syndrome, and 2 had bronchial carcinoid tumors. Mean follow-up was 60 months (range 3-164 months). Chart review and current clinical and biochemical data were analyzed to determine remission and recurrence rates and predictors of outcome. Remission was achieved in 15 of 22 (68%) patients with macroadenomas and in 72 of 79 (91%) patients with microadenomas. Recurrent disease occurred in 5 of 15 (33%) patients with macroadenomas, with a mean time to recurrence of 16.2 months. Conversely, 7 of 72 (9.7%) patients with microadenomas experienced a recurrence, albeit with a longer mean time to recurrence of 54 months. This difference in disease-free survival between...

Mutant, guanosine triphosphatase-deficient; alpha-subunits of the G protein, Gs, gsp ocogene have been discovered in 40% of GH-secreting pituitary adenomas. Therefore, we hypothesized that a novel G protein class, G alpha q, involved in pituitary signal transduction, might be involved in pituitary tumorigenesis. Recombinant mutations of G alpha q result in constitutive activation of phospholipase C and have transforming activity. Therefore, we screened tumor samples from 37 pituitary adenomas for the presence of activating mutations of the G alpha q gene. Importantly, our sample contains 8 FSH and LH adenomas. In the pituitary gland, FSH and LH are linked to the GnRH-G alpha q signaling cascade, making these tumors a logical choice for screening for G alpha q mutations. Complementary DNA (cDNA) was synthesized by RT-PCR with G alpha q specific primers to exclude pseudogene transcripts. Fragments of G alpha q cDNA-encompassing residues (Arg(183), Gln(209)) were screened by single-strand conformation polymorphism and then sequenced in both directions. No mutations were detected. We conclude that mutations in these regions of the G alpha q cDNA occur infrequently, if at all, in human pituitary adenomas. Alternative mechanisms underlying pituitary tumorigenesis should be explored.

Transcranial approaches to pituitary tumors were proposed by the pioneers of neurosurgery and are still adopted with different modifications in selected cases. The main goal of this surgery is to decompress the optic pathways. The kind of approach is mainly dictated by the dimension, location, and consistency of the tumor mass and by other coexistent vascular pathologies. The transcranial approaches most frequently adopted are grouped as fronto-pterional, transfrontal, and combined approaches. This article reviews the indications for each transcranial approach. Moreover, the transcranial approaches to pituitary tumors are described in detail, stressing technical aspects and the prevention of complications. Particular attention is given to the fronto-orbitozygomatic (FTOZ) approach with intradural and extradural decompression of the optic nerve. This approach is the one most frequently used in our recent experience. Results are encouraging in particular in terms of postoperative visual function. Complications related to these procedures and their perioperative management are also reported.

CUSHING'S DISEASE RESULTING from intrasellar corticotropin-releasing hormone (CRH)-secreting gangliocytomas is very rare, and only two such cases have been reported in the literature to date. The authors present a third case in which an adrenocorticotropic hormone-secreting pituitary adenoma was found in addition to a gangliocytoma in a 10-year-old girl with clinical and endocrinological symptoms of Cushing's disease. Computed tomographic and magnetic resonance imaging scans showed a suprasellar and parasellar tumor. A green-colored, heterogeneous tumor and a small adenoma were removed transsphenoidally. Histological examination revealed a large gangliocytoma immunoreactive for CRH and a small, mucoid cell pituitary adenoma immunoreactive for ACTH. This is the first case of such a tumor causing Cushing's disease in a child. It might exemplify induction of an ACTH-secreting pituitary adenoma by means of chronic overstimulation of CRH.

The results of transsphenoidal adenomectomy for growth hormone (GH)-secreting pituitary adenomas in acromegaly performed over a 17-year period were analyzed retrospectively to determine which preoperative factors significantly influenced the long-term surgical outcome. These variables were then used to develop a logistic regression model to determine the probability of surgical failure. The series consisted of 103 patients. Long-term follow-up study (mean duration 102 +/- 64 months) was performed to derive outcome analysis and determinants of failure. Surgical control was defined as a long-term postoperative serum basal GH level of less than 5 micrograms/liter, a long-term postoperative serum somatomedin C (SM-C) level of less than 2.2 U/ml, and a favorable clinical response. Eighteen (17.5%) patients did not meet these criteria. The overall control rate by the GH criteria was 81.3% and by the SM-C criteria 76.2%. By multivariate logistic regression analysis, tumor stage was the strongest predictor of outcome (p < 0.05). The preoperative GH level, tumor grade, and preoperative SM-C level were significant univariate predictors (p < 0.05). There were statistically significant differences in mean preoperative GH and SM-C levels (p < 0.05, t-test) and tumor stage (p < 0.05, chi-squared test) between patients whose acromegaly was controlled by surgery and those whose acromegaly was not. Furthermore, estimates were derived of the probability of surgical failure based on preoperative GH level, preoperative SM-C level, and tumor grade and stage. The authors believe these findings will enhance clinical decision-making for neurosurgeons considering transsphenoidal microsurgery in patients with acromegaly.

DESPITE RECENT ADVANCES in neurodiagnostic imaging, it may be difficult to differentiate tuberculum sellae meningiomas from pituitary macroadenomas preoperatively. Magnetic resonance (MR) imaging has supplanted computed tomography as the imaging modality of choice for sellar and parasellar lesions, but unenhanced MR imaging does not reliably distinguish between all tuberculum sellae meningiomas and pituitary macroadenomas. Accurate differentiation between these alternative diagnoses of a suprasellar mass is important because a tuberculum sellae meningioma always requires a craniotomy, whereas a transsphenoidal route is preferred for removing most pituitary macroadenomas. The gadolinium-enhanced MR images of seven patients with tuberculum sellae meningioma and seven with pituitary macroadenoma were reviewed retrospectively. Although no specific radiological feature was pathognomonic, a combination of several features allowed the correct diagnosis in all cases. Three characteristics of tuberculum sellae meningiomas distinguish them from pituitary macroadenomas: 1) bright homogeneous enhancement with gadolinium, as opposed to heterogeneous, relatively poor enhancement; 2) a suprasellar rather than a sellar epicenter of tumor; and 3) tapered extension of an intracranial dural base. Each of these findings can be subtle, but careful examination of gadolinium-enhanced, high-quality, thin section coronal and sagittal MR images of the parasellar region for this constellation of findings will allow the correct preoperative diagnosis in patients with either of these tumors.

Meeting Abstracts: Annual Meeting of the Southern Neurological Society, Washington, District of Columbia, April 3–5, 1992

Sellar magnetic resonance imaging studies obtained with half doses of gadopentetate dimeglumine (0.05 mmol/kg) were prospectively interpreted and retrospectively rated in 26 patients who subsequently underwent transsphenoidal sellar surgery for suspected pituitary adenoma. Studies included a sagittal scout view followed by a non-contrast-material-enhanced, an immediate postcontrast, and a delayed postcontrast T1-weighted image (obtained at 1.0 or 1.5 T). Ten of 11 confirmed microadenomas were identified prospectively; all were identifiable in retrospect. Macroadenomas (12 cases) were well demonstrated. The high signal intensity of the posterior pituitary and of intrasellar hemorrhage was obscured on postcontrast studies. Delayed images proved unnecessary. This prospective evaluation suggests that a half-dose study is comparable to retrospective studies in which full-dose techniques were used for detection of micro- and macroadenomas. Imaging times are reasonably short, and cost of contrast material is potentially reduced. Confirmation with larger studies is required, and careful endocrinologic and clinical follow-up of nonsurgical patients is necessary.

From 1977 to 1988, 56 patients with a preoperative diagnosis of Cushing's disease were treated by transsphenoidal microsurgical exploration of the pituitary gland. In 42 patients, a discrete tumor was found and a selective adenomectomy was performed. Total hypophysectomy was performed in nine patients. In an attempt to preserve pituitary function, a technique of subtotal hypophysectomy was utilized in the remaining five patients. Regular and adequate follow-up results were obtained in 53 patients. A sustained remission was obtained in 45 of these 53 patients for a remission rate of 84.9%. Eight patients were classified as therapeutic failures. The causes for failure included: 1) invasive tumor; 2) hyperplasia mistaken for an adenoma; 3) a presumed ectopic source of adrenocorticotropic hormone; 4) misdiagnosis; 5) atypical tumor; and 6) recurrence of disease after remission. In cases of therapeutic failure, the original diagnosis of Cushing's disease must be reevaluated and treatment continued until sustained remission is achieved. Necessary measures to help avoid surgical failures and an approach for further diagnostic and therapeutic maneuvers in these cases are discussed.