OBJECTIVE: Microscopic and endoscopic transsphenoidal approach (TSA) are major surgical techniques in the treatment of pituitary adenoma. Endoscopic endonasal transsphenoidal approach (EETSA) has been increasingly used for pituitary adenomas, however, its surgical outcome particularly in functioning pituitary adenoma has been debated. Here, we investigated the endocrine outcome of the patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH) secreting pituitary adenoma treated by EETSA. METHODS: We treated 80 patients with pituitary adenoma by EETSA since 2004, of which 12 patients were affected by functioning pituitary adenomas (9 GH, 3 ACTH, 0 PRL; 9 macro, 3 micro). Surgical outcome of those patients treated by EETSA was compared with that of the 11 functioning pituitary adenoma patients (8 GH, 3 ACTH; 8 macro, 3 micro) who underwent sublabial microscopic TSA between 1997 and 2003. RESULTS: Imaging remission based on postoperative MRI was achieved in 8 (73%) and hormonal remission in 5 (45%) of 11 patients treated by sublabial microscopic TSA. Imaging remission was observed in 10 (83%, p=0.640) and hormonal remission in 10 (83%, p=0.081) of 12 patients by EETSA. CSF leakage was noticed in 2 (17%) of EETSA group and in 2 (18%) of sublabial microscopic TSA group. Panhypopituitarism was observed in 1 (9%) of EETSA group and in 3 (27%) of sublabial microscopic TSA group. CONCLUSION: EETSA appears to be an effective and safe method for the treatment of functioning pituitary adenomas.
ACTH-Secreting Pituitary Adenoma ; Adrenocorticotropic Hormone ; Endoscopy ; Growth Hormone ; Growth Hormone-Secreting Pituitary Adenoma ; Humans ; Hypopituitarism ; Pituitary Neoplasms

OBJECTIVE: Silent corticotroph adenomas (SCA) are endocrine-inactive pituitary adenomas with positive immunohistochemistry staining for adrenocorticotropic hormone (ACTH). We investigated whether SCA-associated clinical profiles were more aggressive than hormonally negative adenomas (HNA).METHODS: Among 627 patients with pathologically proven endocrine-inactive pituitary adenomas between 2004 and 2013, positive immunohistochemistry revealed 55 SCAs and 411 HNAs. Surgical outcomes and radiological and endocrinological characteristics were compared.RESULTS: Strong female predominance was observed in the SCA group (p<0.001). Cavernous sinus invasion was identified in 22 (40%) SCA patients and 72 (17.6%) HNA patients (p<0.001). There were no differences in ACTH or cortisol levels between the two groups. The incidence of preoperative hypopituitarism and postoperative hormonal outcome did not differ between two groups. Total resection was achieved in 35 patients (63.7%) with SCA and 332 patients (80.8%) with HNA (p=0.007). When tumors were completely removed, recurrence rates were not statistically different between two groups (p=0.60). When complete resection was not achieved, tumors regrew from these remnants in seven patients (35.0%) with SCA and 12 patients (15.2%) with HNA (p=0.05).CONCLUSION: Total surgical resection for SCA is often challenging as these tumors frequently invade a cavernous sinus. Early remnant tumor intervention is justified, because untreated residual pituitary tumors regrow when patients were followed up for a long time. Prophylactic radiotherapy is not warranted for completely resected SCAs as tumor recurrence is uncommon.
ACTH-Secreting Pituitary Adenoma ; Adenoma ; Adrenocorticotropic Hormone ; Cavernous Sinus ; Corticotrophs ; Female ; Humans ; Hydrocortisone ; Hypopituitarism ; Immunohistochemistry ; Incidence ; Pituitary Neoplasms ; Radiotherapy ; Recurrence

OBJECTIVETo evaluate the distribution and expression of peroxisome proliferator activated receptor gamma (PPAR-gamma) in human pituitary adenomas.

METHODSThirty eight consecutive surgically resected pituitary adenomas and 5 normal pituitary tissues were enrolled in the study. Immunohistochemistry was used to confirm the distribution of PPAR-gamma. Expression of PPAR-gamma was evaluated by Western blot.

RESULTSPPAR-gamma immunoreactivity was located in the nucleoli of pituitary adenoma cells. PPAR-gamma was expressed in all human pituitary adenomas and normal pituitary tissues. Its expression in pituitary adenomas was significantly higher than in normal pituitary tissues (P < 0.01), and its expression in ACTH-secreting adenomas was significantly higher than in any other type of pituitary adenomas (P < 0.05).

CONCLUSIONSPPAR-gamma may play an important role in the generation, growth, and invasion of human pituitary adenomas. It may become a novel therapeutic target for these tumors.

ACTH-Secreting Pituitary Adenoma ; metabolism ; Adult ; Female ; Humans ; Male ; Middle Aged ; PPAR gamma ; biosynthesis ; metabolism ; Pituitary Gland ; metabolism ; Pituitary Neoplasms ; metabolism

The present case involves a 56-year-old woman with Cushing's disease due to pituitary macroadenoma. The patient had suffered from central obesity, general weakness for 1 year. Her serum cortisol levels were elevated throughout the observation period and the dexamethasone test failed to suppress the cortisol secretion. Plasma adrenocorticotropic hormone (ACTH) levels were significantly elevated (386 pg/mL). Sellar magnetic resonance imaging revealed a 3.1-cm pituitary tumor occupying the sellar region with extension to parasellar area. The pituitary mass was removed by transsphenoidal surgery incompletely and was pathologically identified as compatible to ACTH-producing pituitary adenoma by immunohistochemistry. Thereafter, cabergoline (1 mg/wk) was administered for the remnant adenoma, which gradually reduced ACTH levels in 7 days before starting radiation therapy. This case demonstrates the efficacy of cabergoline to treat Cushing's disease caused by pituitary macroadenoma.
ACTH-Secreting Pituitary Adenoma ; Adenoma ; Adrenocorticotropic Hormone ; Cushing Syndrome ; Dexamethasone ; Female ; Humans ; Hydrocortisone ; Immunohistochemistry ; Magnetic Resonance Imaging ; Middle Aged ; Obesity, Abdominal ; Pituitary Neoplasms ; Plasma

The goals of the pituitary tumor surgery are restoration of the normal pituitary function and relieving the mass effect on the adjacent normal brain structures. The main purpose of this study is to analyze our surgical results of growth hormone(GH) secreting pituitary adenomas which were treated extensive and aggressive surgical removal. The surgical results were reviewed in 36 patients treated between 1993 and 1997. The criteria of clinical remission are postoperative basal GH less than 5ng/ml and suppression of GH less than 2ng/ml in oral glucose tolerance test. As the results, 25 of 36 patients(69.4%) achieved surgical remission. Eleven patients who could not achieve remission by surgery were treated with medical treatment(octreotide, bromocriptine) and Gamma-knife surgery. In conclusion, the tumor morphology and extensiveness of tumor removal were well correlated with surgical outcome, and the aggressive resection of tumor seems to be the most important factor achieving remission in GH secreting pituitary adenomas.
Brain ; Bromocriptine ; Glucose Tolerance Test ; Growth Hormone* ; Growth Hormone-Secreting Pituitary Adenoma ; Humans ; Pituitary Neoplasms*

BACKGROUND: Oxytocin (OXT) has been reported to act as a growth regulator in various tumor cells. However, there is a paucity of data on the influence of OXT on cell proliferation of corticotroph adenomas. This study aimed to examine whether OXT affects cell growth in pituitary tumor cell lines (AtT20 and GH3 cells) with a focus on corticotroph adenoma cells. METHODS: Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were conducted with AtT20 cells to confirm the effects of OXT on hormonal activity; flow cytometry was used to assess changes in the cell cycle after OXT treatment. Moreover, the impact of OXT on proliferating cell nuclear antigen (PCNA), nuclear factor κB, and mitogen-activated protein kinase signaling pathway was analyzed by Western blot. RESULTS: OXT treatment of 50 nM changed the gene expression of OXT receptor and pro-opiomelanocortin within a short time. In addition, OXT significantly reduced adrenocorticotropic hormone secretion within 1 hour. S and G2/M populations of AtT20 cells treated with OXT for 24 hours were significantly decreased compared to the control. Furthermore, OXT treatment decreased the protein levels of PCNA and phosphorylated extracellular-signal-regulated kinase (P-ERK) in AtT20 cells. CONCLUSION: Although the cytotoxic effect of OXT in AtT20 cells was not definite, OXT may blunt cell proliferation of corticotroph adenomas by altering the cell cycle or reducing PCNA and P-ERK levels. Further research is required to investigate the role of OXT as a potential therapeutic target in corticotroph adenomas.
ACTH-Secreting Pituitary Adenoma ; Adrenocorticotropic Hormone ; Blotting, Western ; Cell Cycle ; Cell Line ; Cell Proliferation ; Corticotrophs ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Gene Expression ; Oxytocin ; Phosphotransferases ; Pituitary Neoplasms ; Polymerase Chain Reaction ; Pro-Opiomelanocortin ; Proliferating Cell Nuclear Antigen ; Protein Kinases ; Reverse Transcription

Familial isolated pituitary adenoma (FIPA) is an autosomal dominant disease, characterized by low penetrance, early-onset disease, more invasive tumor growth, as well as somatotroph and lactotroph adenomas in most cases. It has been indicated that the aryl hydrocarbon receptor interacting protein (AIP) gene is a tumor suppressor gene. Many heterozygous mutations have been discovered in AIP in about 20% of FIPA families. However, the exact molecular mechanism by which its disfunction promotes tumorigenesis of pituitary is unclear.
Growth Hormone-Secreting Pituitary Adenoma ; genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Pituitary Neoplasms ; genetics

Ectopic pituitary adenoma, occurring outside the sella turcica without any continuity with intrasellar pituitary gland is very rare. So far, less than 90 such cases have been reported in the literature. Regarding to ectopic locations, suprasellar region, sphenoid sinus and clivus have been reported in decending order of frequency. To our best knowledge, growth hormonesecreting ectopic pituitary adenoma in the clivus has never been reported. With the pertinent literature review, we present our unique case with its characteristic magnetic resonance imaging and immunohistochemical features.
Cranial Fossa, Posterior* ; Growth Hormone-Secreting Pituitary Adenoma* ; Magnetic Resonance Imaging ; Pituitary Gland ; Pituitary Neoplasms ; Sella Turcica ; Sphenoid Sinus

PURPOSE: To evaluate the diagnostic value of radiologic studies in the Cushing's disease MATERIALS AND METHODS: We analyzed retrospectively the CT(n=19, dynamic CT was not perfomed), MR (n=23, dynamic MR in 2 cases), and the results of inferior petrosal sinus sampling(IPSS)(n=13) in 25 patients(19 women, 6men, age range 16-58, mean 32.2) with pathologically-confirmed ACTH secreting pituitary adenoma. We analyzed the radiologic findings and determined how accurately each method could detect and lateralize the lesion within the pituitary gland. The results were compared with the surgical findings and with each other. RESULTS: Seven patients(28%) out of 25 had macroadenomas and the lesions were detected and correctly diagnosed by CT and MR in all. Eighteen patients(72%) had microadenoma. In patients with microadenoma the sensitivity was 38.5%(5/13) in CT, 64.7%(11/17) in MR, 90.9%(10/11) in IPSS. In two patients with dynamic MR, in whom the conventional Gd-enhanced MR showed false negative results, the lesions were detected as low signal intensity mass and correctly lateralized. Considering the results of both MR and IPSS, the sensitivity increased up to 94.1%(17/18). CONCLUSION: Considering the invasiveness of IPSS, Gd-enhanced MR, preferably dynamic, seems to be an imaging modality of choice in Cushing's disease. Combined use of IPSS in selected patients further increases the accuracy of diagnosis and lateralization.
ACTH-Secreting Pituitary Adenoma ; Diagnosis ; Female ; Humans ; Pituitary Gland ; Retrospective Studies

The authors have reported on 34 patients with pituitary adenoma who underwent surgical treatment. The preoperative and postoperative clinical manifestations, size, and extension of tumor, therapeutic modalities and changes of endocrinological symptoms and hormonal values. In a series of 34 adenomas, 7(25%) were non-secreting and 27(79%) produced a hypersecretion syndrome; human growth hormone(5), prolactin(17), mixed GH and PRL type(3), corticotropic adenoma(2). The principal symptoms were endocrinological symptoms(74%), visual disturbance(59%) and headache(50%) on a admission. Vision improved in 90% of the patients. Normal menstruation returned in 35.3% of the prolactinoma. Endocrine cure was possible in 24% of prolactin-secreting and 40% of GH-secreting and 33% of mixed GH, PRL adenomas and not improved in corticotropic adenomas. The mortality rate was 0.6%. Postoperative radiation therapy appeared to play a greater role.
Adenoma ; Craniotomy ; Female ; Humans ; Menstruation ; Mortality ; Pituitary Neoplasms* ; Prolactinoma