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Pituitary adenomas of the multiple endocrine neoplasia type I syndrome.

In a series of 1,500 pituitary adenomas surgically resected at Mayo Clinic, 41 (2.7%) occurred in the setting of multiple endocrine neoplasia, type I (MEN-I). Of the 40 patients (18 males, 22 females), 21 (52%) presented with clinical evidence of a pituitary neoplasm, 13 with hyperparathyroidism, and two with functional islet cell tumor. Of the 41 tumors, 11 (27%) were microadenomas, and 30 (73%) were macroadenomas. Immunocytochemical studies demonstrated the following reactivities: GH (4), GH/PRL (6), GH/PRL/glycoprotein (7), GH/ACTH/glycoprotein (1), PRL (16), PRL/TSH (1), ACTH (3), and null cell adenoma (3). We conclude that, in comparison with pituitary adenomas occurring in the general population, those occurring in association with MEN-I are (1) more often endocrinologically functional, (2) more frequently GH- or PRL-producing, and (3) clinicopathologically similar in terms of the subjects age and sex as well as of tumor size and invasiveness.

Adenoma↗

Screening for MEN1 tumor suppressor gene mutations in sporadic pituitary tumors.

The molecular pathogenesis of the majority of sporadic pituitary tumors is largely unknown. Pituitary adenomas can develop sporadically or as a part of multiple endocrine neoplasia type 1 (MEN1). The MEN1 is thought to be a tumor suppressor gene based on loss of heterozygosity (LOH) for polymorphic markers on 11q13 in tumors of the pancreas, parathyroid, and pituitary. Most patients with familial and sporadic MEN1 carry germ-line mutations in the MEN1 gene. Two previous studies and recently a third one have analyzed mutations by sequencing the MEN1 gene in sporadic pituitary tumors but yielded conflicting results. This study was to investigate and clarify the potential role of MEN1 mutations, in sporadic pituitary adenomas. First, we examined 59 sporadic pituitary adenomas by analyzing LOH on 11q13 in the MEN1 minimal interval with microsatellite analysis. We found 3 tumors with LOH in 1 to 4 polymorphic markers in the MEN1 region. Sequencing analysis did not reveal any mutations in the coding region of the MEN1 gene. However, we found 3 polymorphisms, one of which was a novel CAC to CAT transition encoding His433His, in exon 9. The data show that while LOH occurs in some sporadic pituitary tumors, inactivating mutations of the tumor suppressor gene MEN1 are rare. These results also suggest there may be another additional tumor suppressor gene at this locus which is involved in the pathogenesis of sporadic pituitary neoplasms.

Adenoma↗

Contemporary therapy of prolactin-secreting adenomas.

Prolactin-secreting pituitary tumors are common benign pituitary neoplasm that cause amenorrhea, galactorrhea, and infertility. Inhibition of prolactin secretion by a dopamine agonist restores menses and reduces tumor size. This article outlines an approach to therapy and discusses the use of estrogen in women with prolactinomas.

Female↗

Cytological study on pituitary adenomas in senile untreated beagle bitches.

Pituitaries from 25 senile untreated Beagle bitches aged 7-11 years, have been examined using a specific staining technique. In 10 out of 25 animals (40%), pituitary adenomas were detected. In general, pituitary neoplasms were observed as small nodules (2-3.5 mm in diameter) during gross examination or a incidental findings during the microscopic examination. Histological examination showed that the adenomas observed during gross examination were made up either of ACTH cells or of a combination of ACTH and immature cells; the adenomas which were observed as incidental findings during microscopic examination were made up of ACTH, immature or intermediate zone cells. The possible histogenesis of pituitary adenomas, especially the immature cell adenoma, is discussed.

Adenoma↗

The Krüppel-like transcription factor 6 gene in sporadic pituitary tumours.

The oncogenes and/or tumour suppressor genes which may be involved in the transformation process for the vast majority of pituitary tumours remain unknown. There is substantial evidence for derangement of cell cycle control in such tumours, but cell cycle protein mutations identified in other human malignancies are restricted to only a very small subset of sporadic pituitary neoplasms. Krüppel-like factors are DNA-binding transcriptional regulators with diverse effects including the upregulation of the cell cycle protein p21(WAF1/CIP1). It has been reported that the Krüppel-like transcription factor 6 (KLF6) gene is mutated in a proportion (15-55%) of human prostate cancers, and more recent data are emerging regarding mutated KLF6 in nasopharyngeal carcinomas, astrocytoid gliomas and colorectal cancer. We therefore speculated that other tumours such as pituitary adenomas might also harbour such mutations that may be involved in the control of cell proliferation in the pituitary. The aim of the current study was thus to analyse the KLF6 gene for mutations in sporadic pituitary tumours. We analysed 60 pituitary adenomas (15 GH-, four ACTH-, two PRL-secreting and 39 non-functioning) with direct sequence analysis of exons 2 and 3 of the KLF6 gene, the region where most of the previously described mutations are located. Three non-functioning pituitary adenomas of the 60 pituitary tumours (5%) had two identical sequence changes in exon 2 (missense mutation Val165Met, 523G-->A and a silent substitution in Ser77Ser codon 261C-->T). Analysis of genomic DNA extracted from peripheral lymphocytes in one patient confirmed these changes to be present in the germline and they therefore probably represent polymorphisms, although we cannot exclude the possibility that these are predisposing germline mutations. We conclude that mutations of the KLF6 gene are unlikely to play an important role in sporadic pituitary tumorigenesis.

Adenoma↗

[Transnasal-sphenoided endosurgical and microsurgical technique of pituitary adenometomies].

OBJECTIVE: To evaluate the surgical technique of pituitary adenomas by naso-sphenoid way and the prevention of complication. METHOD: The pituitary adenomas in 19 cases were removed under endoscope and microscope by the transnasosphenoided way. Sphenoid-saddle base was restructed with lip-tendon-membrane and the nasal separate bone. RESULT: Seventeen cases had entire resection in the 19 patients. Two cases had subtotal resection. The symptoms were improved with no sever complications in 19 cases during the period of 3-36 months follow-up and no recovery in 17 cases. CONCLUSION: lt is a effective surgical technique that the pituitary neoplasms are removed by nasosphenoidal way under the endoscope and microscope with the alcohol for preventing the tumor recovery and with the lip-tendon-membrane and nasal separate bone for restructing the saddle base.

Adenoma↗

Results of neurosurgical treatment by a transsphenoidal approach in 10 patients with Nelson's syndrome.

Ten patients with Nelson's syndrome, nine women and one man, aged 22 to 61 years, were treated neurosurgically by a transsphenoidal approach. In four patients, microadenomas were found, ranging in diameter from 4 to 10 mm. Microscopically, mixed adenoma was diagnosed in six cases, basophilic adenoma in three patients, and chromophobe adenoma in one patient. The presence of argyrophilic nerve fibers in the adenoma tissue was noted in one case. The time of observation after transsphenoidal surgery ranged from 6 months to 10 years. Clinical remission was achieved in eight patients; in two of them, radiation therapy was used to complement surgical treatment. In two patients, recurrence of the pituitary neoplasm was observed; anaplasia was revealed at the second operation in one of them. Radiation therapy might be a useful adjunct to neurosurgery in Nelson's syndrome, especially in patients with anaplastic adenoma.

Adenoma↗

[Radiation therapy in two cats with pituitary tumors].

Two cats with large pituitary neoplasms (adenoma and adenocarcinoma) were treated with fractionated radiation therapy. Total doses of 40 Gy, respectively 36 Gy, were applied in 10 fractions of 4 Gy, and 3.6 Gy respectively. Side effects were minimal and transient. Anesthesia was well tolerated. Improvement of clinical signs could be observed during radiation therapy in both cats. One cat had a complete, the other a partial tumor response. One cat (suspicion of adenoma) was euthanized 1 3/4 years after therapy due to unrelated disease. No tumor was found on histopathology, however a small focal necrosis of brain tissue in the irradiated field was observed. The second animal with a pituitary adenocarcinoma was euthanized because of tumor recurrence 1 1/2 years after therapy. Radiation therapy was effective, despite the low total doses of radiation applied.

Adenocarcinoma↗

Vasospasm following transcranial removal of large pituitary adenomas. Report of three cases.

The authors report three cases of cerebral vascular spasm following transfrontal removal of large pituitary neoplasms. One patient awakened from surgery hemiparetic, but has since recovered. A second patient developed hemiparesis with confusion on the fifth postoperative day and eventually died. The third patient developed hemiplegia on the tenth postoperative day, but recovered completely. Vascular spasm was documented angiographically in all three cases. Possible mechanisms underlying this unusual complication are discussed.

Adenoma↗

Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) and guanylate kinase 1 (GUK1) are differentially expressed in GH-secreting adenomas.

Pituitary tumors, adenomas in their vast majority, represent around 10-15% of the intracranial neoplasms. Pituitary carcinomas are exceedingly rare. Clinically, these neoplasms cause hormonal dysfunctions, and mass effect symptoms as headache and visual disorders in the case of macroadenomas. Pituitary tumorigenesis is still poorly understood. In order to investigate the expression of cancer-related genes in pituitary tumors, we employed a human cancer cDNA macroarray membrane with 1176 well-characterized human genes related to cancer and tumor biology. We were able to identify several differentially expressed genes, among them hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) and guanylate kinase 1 (GUK1) which were over expressed in a pool of clinically nonfunctioning pituitary adenomas, compared with a spinal cord metastasis of a nonfunctioning pituitary carcinoma. HGS and GUK1 mRNA expression were chosen to be validated by quantitative RT-qPCR, however, only GUK1 had the differential expression confirmed between the adenomas and the metastasis of a pituitary carcinoma. We have also investigated HGS and GUK1 mRNA expressions in a series of 46 pituitary adenomas (18 nonfunctioning, 12 GH-secreting, nine PRL-secreting, and seven ACTH-secreting adenomas). HGS and GUK1 were significantly over expressed in GH-secreting adenomas, compared with ACTH-secreting adenomas and nonfunctioning tumors, and with PRL-secreting adenomas, respectively. We have shown that these genes, involved in tumorigenesis in other tissues, are as well over expressed in the pituitary tumors, however, their role in the oncogenesis of these tumors need to be further investigated.

ACTH-Secreting Pituitary Adenoma↗

Lymphocytic hypophysitis.

Lymphocytic hypophysitis (LH) is a rare but increasingly recognized inflammatory disorder of the pituitary, usually associated with pregnancy. Knowledge of this condition is largely anecdotal; the cause, incidence, and natural history are unknown. Cases are usually discovered at biopsy and surgical intervention for a presumptive pituitary neoplasm. Here we describe two cases of lymphocytic hypophysitis. In the first case the patient underwent surgery for presumptive adenoma, and pathology at resection established the diagnosis of lymphocytic hypophysitis. The second case was strongly suspicious for LH by history, endocrine profile, and imaging, and was managed nonoperatively. Though magnetic resonance imaging (MRI) features are not diagnostic, knowledge of imaging features together with clinical history may permit avoidance of surgery.

Adult↗

Treatment of acromegaly, Cushing disease and Nelson syndrome.

Since 1957 we have treated more than 429 patients who had pituitary neoplasms, most of which were hormone-secreting tumors. Long-term follow-up in the large group of patients treated for acromegaly shows a median survival of better than 16 years, with improvement over time. The short-term follow-up results in patients with Cushing* disease, Nelson syndrome and chromophobe adenoma are very encouraging. To compare these excellent results with those following surgical procedures, a large study of patients followed for a long period after the operations is needed.

Acromegaly↗

The sublabial transseptal transsphenoidal approach to sellar and parasellar lesions.

Multiple surgical approaches to the sella turcica have been described. The sublabial transseptal transsphenoidal approach provides a safe, cosmetically acceptable route to the sella with excellent exposure. Since 1976, we have employed this technique for the surgical treatment of pituitary neoplasms and parasellar tumors. The University of Washington experience with the sublabial transseptal transsphenoidal approach to the sella in a series of 253 patients is reported with respect to the otolaryngological aspects of the surgical technique, results, and complications of the procedure. In addition, a literature review of major studies that used this procedure is included, and the reported results and complications are compared to those of the present study.

Adolescent↗

[Malignant prolactinoma with intra- and extracranial metastasis: clinico-radiologic study].

Malignant prolactinomas are very rare pituitary neoplasms which can be identified not from the hystopathologic nor neuroimaging aspects but only retrospectively from the presence of distant metastases. A 32-year-old male patient was diagnosed of a pituitary prolactinoma because of bitemporal hemianopsia on the basis of cranial MRI aspect and raised blood prolactin level. Visual signs improved under bromocriptine treatment but after surgical and X-ray therapies patient developed paralysis of V and XII left cranial nerves and suffered from medulocerebelous angle, vertebrae, spinal epidural space, lung, liver, suprarenal and femoral metastases. Patient died 3 years after the diagnosis time. Prolactin levels raised 2000 ng/ml. This is the first case of malignant prolactinoma described in the spanish literature and the more large one in number of metastatic localizations between the malignant prolactinomas from the literature. These kind of neoplasms can be partially ameliorated under X-ray and bromocriptine treatment but there is not, by the moment, a curative chemotherapy.

Adult↗