[Correlation between Expression of Signal Transducer and Activator of Transcription 3 and Pituitary Adenoma Subtypes].

OBJECTIVE: To investigate the correlation between signal transducer and activator of transcription 3 (STAT3) expression and pituitary adenoma subtypes. METHOD: The STAT3 expression profiles in different pituitary adenomas from 74 patients were determined using quantificational real-time polymerase chain reaction,Western blot,and immunohistochemistry. RESULTS: Expression of STAT3 was observed in all pituitary adenoma subtypes. The STAT3 expression level was highest in growth hormone adenoma when compared with other tumors including prolactin,follicle-stimulating hormone/luteinizing hormone-secreting adenoma,and adrenocorticotrophic hormone-secreting adenoma. The follicle-stimulating hormone/luteinizing hormone adenomas exhibited the lowest STAT3 expression levels. CONCLUSION: STAT3 is differentially expressed in pituitary adenoma subtypes, suggesting the cell-specific features of STAT3 regulation,although further investigations are still warranted to clarify the underlying mechanisms.

[Diagnosis and Treatment of Pituitary Carcinoma].

The early diagnosis and treatment of pituitary carcinoma is difficult. The diagnosis is often delayed, and the confirmation of a diagnosis requires the presence of distant subarachnoid,brain or systemic metastasis from the primary pituitary tumor in the sella and also needs the evidences of pathology and imaging of the primary pituitary carcinoma and metastases. Treatment of pituitary carcinoma includes surgery, radiation therapy ,hormone therapy, chemotherapy, and molecularly targeted therapy; however, these methods are mainly palliative and can not prolong the survival. The prognosis remains poor. Efforts should be made to develop more effective diagnosis and treatment options.

[Treatment of pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques].

OBJECTIVE: To study the effectiveness of treating giant pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques. METHODS: A total of 72 patients who underwent neuroendoscopic surgery and 55 patients who underwent microscopic surgery for giant pituitary adenomas were enrolled in this retrospective analysis. Both groups received expanded endoscopic endonasal transsphenoidal approach, intraoperative application of navigation, and Doppler.The clinical data of two groups were compared. RESULTS: The two groups were significantly different in total tumor removal rate, operation time, postoperative nasal patency, and postoperative recurrence rate (P=0.004, P=0.0003, P=0.000, and P=0.002, respectively), whereas the cerebrospinal fluid leakage, postoperative diabetes insipidus, and cranial nerve injury were not significantly different (P > 0.05). CONCLUSIONS: Expanded neuroendoscopic endonasal transsphenoidal approach assisted by multiple techniques is the preferred surgical method for giant invasive pituitary adenomas invading cavernous sinus.The lateral cavernous sinus approach and the further molecular biology research will bring more options for the treatment of invasive pituitary adenomas.

[Significance of pseudocapsule in the excision of pituitary adenomas in transsphenoidal surgery].

OBJECTIVE: To explore the significance of pseudocapsule in the excision of pituitary adenomas in transsphenoidal surgery. METHODS: For 22 patients with pituitary adenomas over a period of 2 years at Peking Union Medical College Hospital, resection of pseudocapsule was applied for complete tumor removal. Pituitary function test and radiological imaging were performed at pre-operation, 3 months post-operation and at subsequent 6-12 months intervals postoperatively. RESULTS: All pituitary adenomas were totally removed under microscope. The symptoms of headache, disorder of sight and visual field disappeared postoperatively in nonfunctional pituitary adenomas. The GH levels of 2/5 growth hormone secreting adenoma patients were 4.2 and 7.7 µg/L while it was under 1 µg/L for another 3. The postoperative level of prolactin was 4.3 µg/L in prolactin secreting adenoma. The level of adrenocorticotropic hormone decreased under 5 ng/L except one was 15.7 ng/L. Leakage of cerebrospinal fluid occurred intraoperatively in 3 patients and postoperatively in 1. No leakage was found after repair. Diabetes insipidus occurred in one patient and was controlled with Minirin. Pseudocapsule was confirmed by pathological examination. Special staining revealed reticulum fibers in pseudocapsule. CONCLUSION: Resection of pseudocapsule may achieve a higher remission rate without deteriorating pituitary function.

Advances in medical treatment of clinically nonfunctioning pituitary adenomas.

Clinically nonfunctioning pituitary adenomas are the most common types among pituitary adenomas. These tumors are usually diagnosed in their later stages due to the absence of clinical symptoms and detectable hormonal hypersecretion. Although these tumors are benign, they are hard to be completely removed during neurosurgery due to the massive invasion into the surrounding tissues at diagnosis. Furthermore, relapse is common. In recent years, medical treatment of pituitary adenomas has witnessed a rapid development. New medications have shown certain effectiveness in reducing the tumor size and improving the clinical symptoms.

[Aryl hydrocarbon receptor interacting protein gene and familial isolated pituitary adenomas].

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.

Screening for AIP gene mutations in a Han Chinese pituitary adenoma cohort followed by LOH analysis.

OBJECTIVE: The aryl hydrocarbon receptor interacting protein gene (AIP) is associated with pituitary adenoma (PA). AIP has not been sequenced in East Asian PA populations, so we performed this study in a Han Chinese cohort. DESIGN: Our study included six familial PA pedigrees comprising 16 patients and 27 unaffected relatives, as well as 216 sporadic PA (SPA) patients and 100 unrelated healthy controls. METHODS: AIP sequencing was carried out on genomic DNA isolated from blood samples. Multiplex ligation-dependent probe amplification and microsatellite marker analyses on DNA from the paired tumor tissues were performed for loss of heterozygosity analysis. RESULTS: We identified three common and four rare single nucleotide polymorphisms (SNPs), one intron insertion, one novel synonymous variant, four novel missense variants, and a reported nonsense mutation in three familial isolated PA (FIPA) cases from the same family. Large genetic deletions were not observed in the germline but were seen in the sporadic tumor DNA from three missense variant carriers. The prevalence of AIP pathogenic variants in PA patients here was low (3.88%), but was higher in somatotropinoma patients (9.30%), especially in young adults (≤30 years) and pediatric (≥18 years) paients (17.24% and 25.00% respectively). All AIP variant patients suffered from macroadenomas. However, the AIP mutation rate in FIPA families was low in this cohort (16.67%, 1/6 families). CONCLUSION: AIP gene mutation may not be frequent in FIPA or SPA from the Han Chinese population. AIP sequencing and long-term follow-up investigations should be performed for young patients with large PAs and their families with PA predisposition.