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Kalman Kovacs - One of the best experts on this subject based on the ideXlab platform.
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a clone of elusive parents Gonadotroph Adenoma female type
Ultrastructural Pathology, 2012Co-Authors: A Baborie, Kalman Kovacs, Christina Daousi, Mohsen Javadpour, Kumar Das, H White, I A Macfarlane, Eva HorvathAbstract:A 69-year-old woman presented with visual disturbance. Perimetry testing revealed a bitemporal hemianopia. Brain MRI demonstrated a 2.2-cm gadolinium-enhancing pituitary mass. Previously she had been treated for hypothyroidism, hypertension, and dyslipidemia. She had hyperprolactinemia. Endoscopic transsphenoidal debulking improved her visual field defects. Histology showed a chromophobic Adenoma. Electron microscopy showed elongated, polar cells with long, slender processes. The small uniform secretory granules were peripherally disposed, collecting heavily within cell processes. Based on electron microscopical characteristics the tumor is consistent with an ACTH-negative female Gonadotroph Adenoma. The parent cell of this rare variant of a pituitary Adenoma is yet unknown.
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lineage specific restraint of pituitary Gonadotroph cell Adenoma growth
PLOS ONE, 2011Co-Authors: Vera Chesnokova, Svetlana Zonis, Kolja Wawrowsky, Anat Benshlomo, Cuiqi Zhou, Yoel Toledano, Yunguang Tong, Kalman KovacsAbstract:Although pituitary Adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting Adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary Adenoma growth. Thirty six Gonadotroph-derived non-functioning pituitary Adenomas all exhibited DNA damage, but undetectable p21 expression. However, these Adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of Gonadotroph and in 26% of somatotroph lineage Adenomas (p = 0.006). Murine LβT2 and αT3 Gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted Gonadotroph cell Adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine Gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced Gonadotroph proliferation. FOXL2, a tissue-specific Gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign Adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary Gonadotroph Adenoma cell growth.
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unusual double pituitary Adenoma a case report
Pathology International, 2011Co-Authors: Fabio Rotondo, Bernd W Scheithauer, Eva Horvath, Nasima Khatun, Thomas R Marotta, Michael D Cusimano, Kalman KovacsAbstract:We report the case of a 60-year-old woman with Cushing disease. Magnetic resonance imaging (MRI) revealed a large sellar and suprasellar mass involving the right cavernous sinus, consistent with pituitary macroAdenoma. It was resected by transsphenoidal surgery. Light microscopy revealed two separate pituitary Adenomas with different histologic and immunohistochemical features. One was amphophilic and strongly Periodic Acid-Schiff (PAS) positive, the other chromophobic and PAS negative. The former tumor was immunopositive for adrenocorticotropic hormone (ACTH); approximately 30% tumor cells were immunopositive for MGMT (O6-Methylguanine-DNA Methyl-Transferase). The second tumor was a PAS negative, luteinizing hormone (LH) and alpha subunit immunopositive Gonadotroph Adenoma. In this tumor, about 90% of the cells were immunopositive for MGMT. The Ki-67 nuclear indices of the two tumors were 6% and 2%. Our case represents a rare combination of two morphologically different pituitary Adenomas, one producing ACTH and the other LH and alpha subunit. The two tumors differed not only in Ki-67 labeling indices but in MGMT immunoexpression as well.
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effect of gamma knife radiosurgery on a pituitary Gonadotroph Adenoma a histologic immunohistochemical and electron microscopic study
Pituitary, 2003Co-Authors: Shozo Yamada, Eva Horvath, Toshiaki Sano, Sergio Vidal, Kalman KovacsAbstract:The morphologic findings in a pituitary macroAdenoma removed from a 65-year old man by the transsphenoidal approach 9 months after gamma knife surgery are reported. The tumor was immunoreactive for FSH beta and showed ultrastractural features consistent with an oncocytic Gonadotroph Adenoma. Accumulation of connective tissue separating small groups of Adenoma cells was evident. Several dilated vessels and numerous vascular endothelial growth factor immunopositive Adenoma cell were noted. By electron microscopy the endothelial linings frequently showed discontinuities with platelet accumulation attached to the gaps. Several vessels were severely injured showing necrosis of endothelial cells. It can be concluded that gamma knife surgery caused severe alterations in pituitary Adenoma microcirculation indicating that vascular injury plays a crucial role in tumor shrinkage.
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double Adenoma of the pituitary a somatotroph Adenoma colliding with a Gonadotroph Adenoma
Journal of Endocrinological Investigation, 2000Co-Authors: Luis V Syro, Eva Horvath, Kalman KovacsAbstract:Pituitary collision tumors are rare. They may create difficult diagnostic problems and their histogenesis is not clear. We report here an unusual case of a somatotroph Adenoma colliding with a Gonadotroph Adenoma.The 64-year-old man had clinical acromegaly. His blood growth hormone level was elevated and magnetic resonance imaging demonstrated a pituitary tumor. The surgically removed sellar mass was investigated by histology, immunocytochemistry and electron microscopy. Morphologic study revealed a collision tumor; one was a somatotroph Adenoma, the other a Gonadotroph Adenoma. Authors call attention to the difficulties in clinical, imaging and pathological diagnosis. Detailed morphologic studies are needed to establish the presence of two distinct tumors composed of two different cell types.
Peter J Snyder - One of the best experts on this subject based on the ideXlab platform.
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exacerbation of ovarian hyperstimulation by leuprolide reveals a Gonadotroph Adenoma
Fertility and Sterility, 2002Co-Authors: Arthur J Castelbaum, Homayoun Bigdeli, Kalmon D Post, Martin F Freedman, Peter J SnyderAbstract:Abstract Objective To report a case of a Gonadotroph Adenoma diagnosed after a dramatic increase in estradiol level and ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist. Design Case report. Setting Outpatient practice and university hospital. Patient(s) A 35-year-old woman who presented with infertility, amenorrhea, and an elevated basal estradiol concentration. Intervention(s) Ultrasonography, laparoscopy, endocrinologic assays, magnetic resonance imaging, transsphenoidal surgery, and immunocytochemical staining. Main outcome measure(s) Ultrasonography and laparoscopy demonstrated bilaterally enlarged ovaries containing multiple preovulatory follicles, similar in appearance in those women undergoing controlled ovarian hyperstimulation with exogenous FSH. The serum estradiol level was moderately elevated, the FSH level was within the normal range, and LH was suppressed. Administration of leuprolide acetate resulted in very elevated estradiol concentrations and even larger ovarian cysts. Magnetic resonance imaging demonstrated a sellar mass. Examination of the tissue excised by transsphenoidal excision of the mass showed a pituitary Adenoma that stained strongly for FSH. Result(s) Regular menses resumed soon after excision of the Gonadotroph Adenoma, followed by a spontaneous pregnancy. Conclusion(s) Gonadotroph Adenoma should be suspected in a reproductive age woman with oligomenorrhea or amenorrhea, infertility, multiple preovulatory follicles, and a persistently elevated serum estradiol concentration. Exacerbation of the ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist in this setting also strongly suggests a Gonadotroph Adenoma but can be avoided by recognizing the presenting features of this condition.
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Gonadotroph Adenoma in a premenopausal woman secreting follicle stimulating hormone and causing ovarian hyperstimulation
The Journal of Clinical Endocrinology and Metabolism, 1995Co-Authors: Ady Djerassi, Christos Coutifaris, V A West, Sylvia L Asa, Shiv Kapoor, Spyros N Pavlou, Peter J SnyderAbstract:The clinical manifestations of Gonadotroph Adenomas are almost always neurological, consequences of their large size, and are rarely endocrinological. We report an exception, a 39-yr-old woman whose Gonadotroph Adenoma caused supranormal serum concentrations of FSH, which resulted in the development of multiple ovarian cysts, persistent elevation of her serum estradiol concentration, and endometrial hyperplasia. She initially presented because of amenorrhea at age 30 yr and was treated for an intrasellar mass by transsphenoidal surgery at age 31 yr and again at age 36 yr. Before and after the second operation she had persistently supranormal plasma estradiol concentrations (> 1840 pmol/L) and endometrial hyperplasia. When she was evaluated at age 39 yr, transvaginal ultrasound showed multiple ovarian cysts and endometrial thickening. Her plasma estradiol level was markedly supranormal (2160 pmol/L), FSH was mildly supranormal (17.8 IU/L), and alpha-subunit was markedly supranormal (23.3 micrograms/L). Cha...
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new technique for quantitation of pituitary Adenoma size use in evaluating treatment of Gonadotroph Adenomas with a gonadotropin releasing hormone antagonist
The Journal of Clinical Endocrinology and Metabolism, 1993Co-Authors: G A Mcgrath, Spyros N Pavlou, R J Goncalves, Jayaram K Udupa, Robert I Grossman, Mark E Molitch, J Rivier, W W Vale, Peter J SnyderAbstract:Because administration for 1 week of the GnRH antagonist Nal-Glu GnRH had been shown to decrease FSH secretion from supranormal to normal in men with Gonadotroph Adenomas, we investigated the effect of prolonged administration of Nal-Glu on the size of Gonadotroph Adenomas. To quantitate the effect of Nal-Glu GnRH on Gonadotroph Adenoma size, we first developed a technique for calculating Adenoma volume. The technique involved collecting magnetic resonance (MR) imaging data from each Adenoma at 1-mm slice intervals in the coronal, axial, and sagittal views and using the Softvu computer program to calculate Adenoma volume from the MR data. The precision of this technique, as judged by the coefficients of variation of the calculations of the same view of the same study three times, was 1.7%, 1.0%, and 1.0% for each of three studies. When Nal-Glu GnRH (5 mg, sc, every 12 h) was self-administered for 3-12 months to five men with Gonadotroph Adenomas and supra-normal serum FSH concentrations, the serum FSH con...
James H Liu - One of the best experts on this subject based on the ideXlab platform.
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ovarian hyperstimulation syndrome caused by pituitary Gonadotroph Adenoma secreting follicle stimulating hormone
Obstetrics & Gynecology, 2007Co-Authors: Mohammadreza Ghayuri, James H LiuAbstract:BACKGROUND: We report a highly exceptional case in which a Gonadotroph Adenoma was diagnosed in a patient with normal follicle-stimulating hormone (FSH) levels. CASE: A 30-year-old woman with a Gonadotroph Adenoma presented with hyperstimulation syndrome and normal FSH levels. After treatment of her Adenoma she had regular menstrual cycles and subsequently conceived. CONCLUSION: Ovarian hyperstimulation caused by a Gonadotroph Adenoma in a premenopausal woman with normal FSH levels is extremely rare. However, we propose that Gonadotroph Adenomas be considered in the differential diagnosis of patients who have this constellation of abnormalities.
Eva Horvath - One of the best experts on this subject based on the ideXlab platform.
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a clone of elusive parents Gonadotroph Adenoma female type
Ultrastructural Pathology, 2012Co-Authors: A Baborie, Kalman Kovacs, Christina Daousi, Mohsen Javadpour, Kumar Das, H White, I A Macfarlane, Eva HorvathAbstract:A 69-year-old woman presented with visual disturbance. Perimetry testing revealed a bitemporal hemianopia. Brain MRI demonstrated a 2.2-cm gadolinium-enhancing pituitary mass. Previously she had been treated for hypothyroidism, hypertension, and dyslipidemia. She had hyperprolactinemia. Endoscopic transsphenoidal debulking improved her visual field defects. Histology showed a chromophobic Adenoma. Electron microscopy showed elongated, polar cells with long, slender processes. The small uniform secretory granules were peripherally disposed, collecting heavily within cell processes. Based on electron microscopical characteristics the tumor is consistent with an ACTH-negative female Gonadotroph Adenoma. The parent cell of this rare variant of a pituitary Adenoma is yet unknown.
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unusual double pituitary Adenoma a case report
Pathology International, 2011Co-Authors: Fabio Rotondo, Bernd W Scheithauer, Eva Horvath, Nasima Khatun, Thomas R Marotta, Michael D Cusimano, Kalman KovacsAbstract:We report the case of a 60-year-old woman with Cushing disease. Magnetic resonance imaging (MRI) revealed a large sellar and suprasellar mass involving the right cavernous sinus, consistent with pituitary macroAdenoma. It was resected by transsphenoidal surgery. Light microscopy revealed two separate pituitary Adenomas with different histologic and immunohistochemical features. One was amphophilic and strongly Periodic Acid-Schiff (PAS) positive, the other chromophobic and PAS negative. The former tumor was immunopositive for adrenocorticotropic hormone (ACTH); approximately 30% tumor cells were immunopositive for MGMT (O6-Methylguanine-DNA Methyl-Transferase). The second tumor was a PAS negative, luteinizing hormone (LH) and alpha subunit immunopositive Gonadotroph Adenoma. In this tumor, about 90% of the cells were immunopositive for MGMT. The Ki-67 nuclear indices of the two tumors were 6% and 2%. Our case represents a rare combination of two morphologically different pituitary Adenomas, one producing ACTH and the other LH and alpha subunit. The two tumors differed not only in Ki-67 labeling indices but in MGMT immunoexpression as well.
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effect of gamma knife radiosurgery on a pituitary Gonadotroph Adenoma a histologic immunohistochemical and electron microscopic study
Pituitary, 2003Co-Authors: Shozo Yamada, Eva Horvath, Toshiaki Sano, Sergio Vidal, Kalman KovacsAbstract:The morphologic findings in a pituitary macroAdenoma removed from a 65-year old man by the transsphenoidal approach 9 months after gamma knife surgery are reported. The tumor was immunoreactive for FSH beta and showed ultrastractural features consistent with an oncocytic Gonadotroph Adenoma. Accumulation of connective tissue separating small groups of Adenoma cells was evident. Several dilated vessels and numerous vascular endothelial growth factor immunopositive Adenoma cell were noted. By electron microscopy the endothelial linings frequently showed discontinuities with platelet accumulation attached to the gaps. Several vessels were severely injured showing necrosis of endothelial cells. It can be concluded that gamma knife surgery caused severe alterations in pituitary Adenoma microcirculation indicating that vascular injury plays a crucial role in tumor shrinkage.
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double Adenoma of the pituitary a somatotroph Adenoma colliding with a Gonadotroph Adenoma
Journal of Endocrinological Investigation, 2000Co-Authors: Luis V Syro, Eva Horvath, Kalman KovacsAbstract:Pituitary collision tumors are rare. They may create difficult diagnostic problems and their histogenesis is not clear. We report here an unusual case of a somatotroph Adenoma colliding with a Gonadotroph Adenoma.The 64-year-old man had clinical acromegaly. His blood growth hormone level was elevated and magnetic resonance imaging demonstrated a pituitary tumor. The surgically removed sellar mass was investigated by histology, immunocytochemistry and electron microscopy. Morphologic study revealed a collision tumor; one was a somatotroph Adenoma, the other a Gonadotroph Adenoma. Authors call attention to the difficulties in clinical, imaging and pathological diagnosis. Detailed morphologic studies are needed to establish the presence of two distinct tumors composed of two different cell types.
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Gonadotroph Adenoma of the pituitary gland a clinicopathologic analysis of 100 cases
Mayo Clinic Proceedings, 1996Co-Authors: William F Young, Bernd W Scheithauer, Eva Horvath, Kalman Kovacs, Dudley H Davis, Raymond V RandallAbstract:Objective To determine the clinical and pathologic features in a large cohort of randomly selected patients with Gonadotroph pituitary Adenomas. Design We retrospectively reviewed clinical, surgical, and pathologic findings in 100 patients (79 men and 21 women, 30 to 82 years old) with this tumor. Results Diagnosis of a pituitary tumor was prompted by visual loss (43%), symptoms of hypopituitarism (22%) headache (8 %), or a combination of these findings (10%); 17% of the patients were asymptomatic. Visual field defects were present in 68% of the study group, and complete or partial anterior pituitary failure was present in 77%. Serum prolactin concentrations were increased (maximum, 110 ng/mL) in 33% of patients. Hypersecretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) was documented in 11 and 5 patients, respectively. The serum level of α-subunit was increased in 1 of 29 patients in whom it was measured. All patients had pituitary macroAdenomas, only 21% of which were grossly invasive. The surgical approach was transsphenoidal in all but two patients, who underwent transfrontal craniotomy; gross total tumor resection was achieved in 90%. By definition, all tumors had at least 10% immunoreactivity for LH, FSH, or both. All tumors were chromophobic. Ultrastructurally, the tumors were characterized as Gonadotroph Adenomas of "male" (45%) or "female" (9%) type as well as null-cell Adenomas of the oncocytic (35%) or nononcocytic (11%) type. After a median follow-up of 4.3 years, 69% of the patients who had had visual field defects noted normalization or improvement. Persistent or clinically recurrent pituitary tumor tissue was present in 42%. A second pituitary surgical procedure was required in eight patients. Conclusion Most patients with clinically evident Gonadotroph pituitary tumors have loss of vision and hypopituitarism. Hypersecretion of FSH or LH is unusual, and no distinct hormone-dependent clinical phenotype is present. Transsphenoidal surgical treatment generally yields normalization or improvement of visual field defects.
Shozo Yamada - One of the best experts on this subject based on the ideXlab platform.
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a case of functioning Gonadotroph Adenoma in a reproductive aged woman
Endocrine Journal, 2019Co-Authors: Mana Hirano, Shozo Yamada, Osamu Wadahiraike, Yuichiro Miyamamoto, Tomoyuki Fujii, Yutaka OsugaAbstract:A 34-year-old woman presented our hospital with complaint of irregular menstruation and abnormal uterine bleeding lasting for a month. After her second parturition at the age of 27, her menstrual cycle had been regular, but it suddenly became irregular at the age of 30. Transvaginal ultrasound revealed the presence of ovarian mass, and the patient underwent diagnostic laparoscopic surgery. Bilateral ovaries temporally shrink after puncture but the size soon resumed. Gonadotropins were almost normal, but estradiol and PRL levels turned out to be elevated, and cabergoline treatment was initiated. After referral to our hospital, we found that the ovaries showed multifollicular appearance. Brain magnetic resonance imaging showed an 18-mm macroAdenoma in the suprasellar area. To suppress the secretion of endogenous gonadotropins and estrogen, low-dose estrogen-progestin was prescribed. Surprisingly, the treatment temporarily reduced the size of the ovaries. The patient was referred to a neurosurgeon, and a functioning Gonadotroph Adenoma was suspected. After the resection of the pituitary tumor, her menstrual cycle became regular, and the size of bilateral ovaries became normal. We also noticed that her ovarian reserve judged by anti-Mullerian hormone had been almost diminished after the surgical treatment, probably reflecting the exhaustion of follicular pool. Women with multifollicular ovaries and elevated estradiol levels may have functioning Gonadotroph Adenomas, although the level of FSH is relatively normal, and ovarian reserve can be followed by measuring anti-Mullerian hormone.
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male Gonadotroph Adenoma report of three cases and a review of the literature
Internal Medicine, 2013Co-Authors: Hisato Tatsuoka, Shozo Yamada, Shojiro Inano, Yoshiyuki Hamamoto, Yuki Takahashi, Jun Takahashi, Toshiaki Sano, Hiroyuki KoshiyamaAbstract:We herein report three cases of Gonadotroph Adenoma in men (36-72 years of age) presenting with visual impairment and suprasellar masses measuring approximately 20 to 30 mm in diameter. Endocrinological examinations were normal, except for slightly increased follicle stimulating hormone (FSH) levels in two cases. Based on the tentative diagnosis of non-functioning pituitary Adenoma, transsphenoidal surgery was performed, which revealed that the tumors consisted of FSH- and LH-positive cells. As Gonadotroph Adenoma is very common among patients with clinically silent pituitary Adenoma, it should be diagnosed using pathological examinations.
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effect of gamma knife radiosurgery on a pituitary Gonadotroph Adenoma a histologic immunohistochemical and electron microscopic study
Pituitary, 2003Co-Authors: Shozo Yamada, Eva Horvath, Toshiaki Sano, Sergio Vidal, Kalman KovacsAbstract:The morphologic findings in a pituitary macroAdenoma removed from a 65-year old man by the transsphenoidal approach 9 months after gamma knife surgery are reported. The tumor was immunoreactive for FSH beta and showed ultrastractural features consistent with an oncocytic Gonadotroph Adenoma. Accumulation of connective tissue separating small groups of Adenoma cells was evident. Several dilated vessels and numerous vascular endothelial growth factor immunopositive Adenoma cell were noted. By electron microscopy the endothelial linings frequently showed discontinuities with platelet accumulation attached to the gaps. Several vessels were severely injured showing necrosis of endothelial cells. It can be concluded that gamma knife surgery caused severe alterations in pituitary Adenoma microcirculation indicating that vascular injury plays a crucial role in tumor shrinkage.
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Gonadotroph Adenoma of the pituitary mimicking a prolactinoma
Neurosurgery, 1991Co-Authors: Shozo Yamada, Eva Horvath, Kalman Kovacs, Tadashi Aiba, Taeko Shimizu, Yoshimasa Shishiba, Mitsuru HaraAbstract:In a 41-year-old woman with mild hyperprolactinemia and amenorrhea, preoperative hormonal and neuroradiological findings suggested the diagnosis of a macroprolactinoma. She underwent transsphenoidal surgery since the tumor size had not changed in spite of bromocriptine administration for 5 months. Consequently, this case was diagnosed as a female-type Gonadotroph Adenoma on the basis of its characteristic ultrastructural features including a honeycomb Golgi complex, even though endocrinological and immunohistochemical findings were not those of a typical Gonadotroph Adenoma.