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

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

No abstract available.
ACTH-Secreting Pituitary Adenoma/complications/diagnostic imaging/surgery ; Adenoma/complications/diagnostic imaging/surgery ; Adolescent ; Biomarkers/urine ; Biopsy ; *Circadian Rhythm ; Creatinine/*urine ; Cushing Syndrome/*diagnosis/*urine ; Female ; Humans ; Hydrocortisone/*urine ; Magnetic Resonance Imaging ; Predictive Value of Tests ; Tomography, X-Ray Computed ; Treatment Outcome ; Urinalysis

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

BACKGROUNDAdrenocorticotrophin (ACTH)-secreting pituitary adenomas account for approximately 7% - 14% of all pituitary adenomas, but its pathogenesis is still enigmatic. This study aimed to explore mechanisms underlying the pathogenesis of ACTH-secreting pituitary adenomas.

METHODSWe used fiber-optic beadarray to examine gene expression in three ACTH-secreting adenomas compared with three normal pituitaries. Four differentially expressed genes from the three ACTH-secreting adenomas and three normal pituitaries were chosen randomly for validation by reverse transcriptase-real time quantitative polymerase chain reaction (RT-qPCR). We then analyzed the differentially expressed gene profile with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway.

RESULTSFiber-optic beadarray analysis showed that the expression of 28 genes and 8 expressed sequence tags (ESTs) were significantly increased and the expression of 412 genes and 31 ESTs were significantly decreased. Bioinformatic and pathway analysis showed that the genes HIGD1B, EPS8, HPGD, DAPK2, and IGFBP3 and the transforming growth factor (TGF)-β signaling pathway and extracellular matrix (ECM)-receptor interaction pathway may play important roles in tumorigenesis and progression of ACTH-secreting pituitary adenomas.

CONCLUSIONSOur data suggest that numerous aberrantly expressed genes and several pathways are involved in the pathogenesis of ACTH-secreting pituitary adenomas. Fiber-optic beadarray combined with pathway analysis of differential gene expression appears to be a valid method of investigating tumour pathogenesis.

ACTH-Secreting Pituitary Adenoma ; etiology ; genetics ; Adenoma ; etiology ; genetics ; Adult ; Disease Progression ; Expressed Sequence Tags ; Extracellular Matrix Proteins ; physiology ; Female ; Fiber Optic Technology ; Gene Expression Profiling ; Humans ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; methods ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; physiology ; Transforming Growth Factor alpha ; physiology

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

OBJECTIVETo discuss the effects of adrenalectomy (ADX) on the treatment of Cushing's disease(CD).

METHODSClinical data of 15 cases of CD between January 1980 and December 2005 were analyzed to evaluate operative indications, complications and the changes of hypercortisolism and hormone levels pre- and post- adrenalectomy.

RESULTSAll the patients involved underwent transsphenoidal pituitary surgery previously. Repeated transsphenoidal surgery was performed in 4 cases. Pituitary radiotherapy was done in 4 cases. The average time from original transsphenoidal operation to ADX was 25.7 months. Pre- and post- adrenalectomy serum cortisol median level were 1156.4 nmol/L and 99.4 nmol/L, the 24 h urinary-free cortisol median level were 315.0 and 5.4 microg, respectively. Hormone replacement therapy was needed in all cases. Average follow-up period was 47 months (9-120 months). Nelson syndrome (NS) appeared in 5 cases (33.3%), while 10 cases showed no NS.

CONCLUSIONSADX is an effective and symptomatic treatment to relieve hypercortisolism caused by CD but with the risk of NS. Longtime hormone replacement therapy and follow up are needed after ADX.

Adolescent ; Adrenalectomy ; adverse effects ; methods ; Adrenocorticotropic Hormone ; blood ; Adult ; Child ; Female ; Follow-Up Studies ; Humans ; Hydrocortisone ; blood ; Male ; Middle Aged ; Nelson Syndrome ; etiology ; prevention & control ; Pituitary ACTH Hypersecretion ; blood ; surgery ; Postoperative Complications ; prevention & control ; Retrospective Studies ; Treatment Outcome

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

A case of Nelson syndrome was presented. Male patient of 26 years old suffering from Cushing disease underwent an bilateral epinephrectomy, after that, Nelson syndrome developed and the patient was treated by Cobalt 60, the skin was discolored and head pain was relieved. Nelson syndrome is caused by total epinephrectomy E in Cushing disease’s patient, its clinical manifestation is typically a leader skin, head pain, high blood concentration of ACTH. The treatment of choice for this syndrome is an operation of pyfrophyse through sphenoidal bone or irradiation into hypophysal hole
Nelson Syndrome ; Cushing Syndrome ; Diseases

OBJECTIVETo discuss the etiology, diagnostic criteria and treatment of Nelson's syndrome.

METHODSTwenty-three patients with Nelson's syndrome who were treated in our department over the last 19 years were analyzed retrospectively. Removal of adenoma by the transsphenoidal approach was done in 21 patients and by transfrontal craniotomy in 2. The follow-up period ranged from six months to nine years.

RESULTSThe incidence of Nelson's syndrome was 7.7% in a series of 300 patients with Cushing's disease treated by microsurgery in the same period. Hyperpigmentation was relieved and adrenocorticotropic hormone (ACTH) levels decreased in all patients after tumor excision. Eight patients with visual disturbance improved after surgery. The curative and remission rates were 56.5% and 26.1%, respectively.

CONCLUSIONSTranssphenoidal microsurgical removal of pituitary ACTH adenoma is the first choice in the prevention and treatment of Nelson's syndrome. Regular follow-up examinations should be performed over a long time.

Adolescent ; Adult ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Microsurgery ; methods ; Middle Aged ; Nelson Syndrome ; epidemiology ; etiology ; surgery