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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gonadotroph adenomas may exhibit qualitative and quantitative defects in gonadotropin biosynthesis and secretion. Hypersecretion of immunoreactive FSH dimers by these adenomas occurs frequently; however, it has not been known whether this FSH is biologically active. Using the granulosa cell aromatase bioassay and a highly specific immunoradiometric assay for FSH, we studied the serum bioactivity and bio- to immunoactivity (B/I) ratios of 14 men with FSH-secreting adenomas and compared these values to those of 11 age-matched normal men. In addition, three adenoma patients received TRH (400 micrograms, iv). The mean basal serum FSH level (international units per L), as measured by both bio- and immunoassays, and the FSH B/I ratios were significantly higher (P less than 0.02, by Kolmogorov-Smirnov test) in the adenoma patients than in normal men (mean +/- SEM; adenoma patients: bioactivity, 68.8 +/- 10.4; immunoreactivity, 34.8 +/- 13.7; B/I ratio, 3.4 +/- 0.6; normal men: bioactivity, 5.8 +/- 1.2; immunoreactivity, 6.4 +/- 0.8; B/I ratio, 0.90 +/- 0.1). Both bio- and immunoactive FSH rose after TRH injection, resulting in maintenance of the B/I (mean +/- SEM; pre-TRH: bio-FSH, 63.7 +/- 22.4; immuno-FSH, 28.0 +/- 14.1; B/I ratio, 2.8 +/- 1.2; post-TRH: bio-FSH, 125.6 +/- 42.7; immuno-FSH, 45.8 +/- 21.8; B/I ratio, 3.5 +/- 1.6). When gonadotroph adenoma cells from three separate patients were cultured and their conditioned media (n = 3) studied, relatively large amounts of both bio- and immuno-FSH were detected. Furthermore, the major isoelectric profile of bio-FSH (pH 4.9-3.0) in the conditioned medium from two such adenomas was shown by chromatofocusing to be comparable to that of purified human pituitary FSH (pH 5.2-3.6). We conclude that gonadotroph adenomas in men secrete FSH that is biologically active, both basally and in response to TRH.
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PMID:Gonadotroph adenomas in men produce biologically active follicle-stimulating hormone. 211 91

Gonadotropic cells are scattered in the anterior and tuberal lobes and make up 10 to 20% of the anterior pituitary cells. Having a morphofunctional plasticity, they secrete FSH and LH, most often simultaneously. These hormones are stored together in the granulations. In addition, under the action of regulating factors, especially GnRH, the cells can secrete one hormone or the other, or even the alpha subunit. Gonadotropic adenomas range third in frequency among operated pituitary adenomas (12% in our series). The diagnosis is based on the presence of at least 5% of immunoreactive cells with specific antibodies to gonadotropic hormones. These adenomas are distributed into 3 major types: FSH-LH adenoma, the most frequent one, FSH adenoma and alpha-subunit adenoma. The LH adenoma and the beta FSH and beta LH adenomas are very rare. Tumoral gonadotropic cells lose their morphofunctional differentiation. They also lose, to an extent varying according to the cases, their control mechanisms as well as their capacity of synthesis and excretion of both subunits. The alpha subunit, the oldest one in ontogeny, remains the most often and longest-secreted substance. There is a continuum from the gonadotropic adenoma with high plasma gonadotropins levels to the non-functioning adenoma.
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PMID:[Normal and tumorous human gonadotropic cells]. 212 92

To determine whether pituitary macroadenomas associated with supranormal serum FSH concentrations represent gonadotroph cell adenomas or nonsecreting adenomas that selectively impair LH secretion by normal gonadotroph cells, we studied the secretory behavior in dispersed cell culture of three pituitary adenomas from patients who had supranormal serum FSH concentrations. Similar comparisons were made for 11 other adenomas, which were associated with the in vivo hypersecretion of alpha-subunit (n = 4) or PRL/GH (n = 4) or with no obvious hypersecretion (n = 3). Adenomas associated with supranormal serum FSH in vivo released more FSH in culture (5.1-27.0 ng/well . 24 h) than they did other hormones (TSH, less than 0.33; GH, less than 0.10; PRL, less than 0.14 ng/well . 24 h) and more FSH than did PRL/GH-secreting (less than 0.1-0.9 ng/well . 24 h) and nonsecreting (less than or equal to 0.5 ng/well . 24 h) adenomas. Adenomas associated with supranormal serum alpha-subunit in vivo released not only more alpha-subunit in culture (7.2-22.0 ng/well . 24 h) than did other adenomas (0.1-2.4 ng/well . 24 h), but two of them also released as much FSH (12.7 and 17.0 ng/well . 24 h) as did adenomas associated with supranormal serum FSH. The close correlation between the hormonal secretory behavior in vivo and that in culture of the three pituitary macroadenomas associated with supranormal serum FSH concentrations suggests that these are indeed adenomas of gonadotroph cells that are hypersecreting FSH. The release of relatively large amounts of FSH by cultured cells of adenomas that appeared to be hypersecreting only alpha-subunit in vivo suggests that at least some alpha-subunit-secreting adenomas are also gonadotroph cell adenomas.
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PMID:Comparison of hormonal secretory behavior of gonadotroph cell adenomas in vivo and in culture. 241 10

Although the frequency of gonadotroph cell adenomas among all unselected pituitary adenomas is not yet known, it is probably much higher than previously suspected. The true incidence is probably somewhere between the 3-4% found in surgical and autopsy series, which is probably an underestimate because of its reliance on tissue content, and the 17% (24% when alpha-secreting adenomas are included) of 139 patients from this institution, which may be an overestimate of the incidence among all adenomas, because it is heavily weighted to very large adenomas in men only. Most patients who have been reported to have gonadotroph cell adenomas have similar clinical characteristics. Most are middle-aged men who have a history of normal pubertal development and a normal fertility history, and by examination are normally virilized and have testes of normal size. They are brought to medical attention because of visual impairment, which is the result of the enormous size of the adenoma. The most common hormonal characteristic of gonadotroph cell adenomas in vivo is hypersecretion of FSH, which is often accompanied by hypersecretion of FSH beta and alpha-subunit and less often by hypersecretion of LH beta or intact LH. Another common characteristic is secretion of FSH and/or LH in response to TRH. A few patients with gonadotroph cell adenomas hypersecrete intact LH and, therefore, have supranormal serum testosterone concentrations. A larger number have secondary hypogonadism because the adenomas are not secreting intact LH, but are compressing the normal gonadotroph cells and impairing LH secretion. These patients have concentrations of intact LH that are not elevated in spite of subnormal testosterone concentrations. Testosterone levels increase markedly in response to hCG. The hormonal characteristics of gonadotroph adenomas in dispersed cell culture are similar to their characteristics in vivo, including hypersecretion of FSH and LH subunits and responsiveness to TRH. Both the clinical and hormonal characteristics of gonadotroph cell adenomas usually make them readily distinguishable from pituitary enlargement due to long-standing primary hypogonadism. Pituitary adenomas that hypersecrete only alpha-subunit in vivo may also be adenomas of gonadotroph cells, because some of them secrete large amounts of FSH as well as alpha-subunit in culture. Most gonadotroph cell adenomas are now treated first by transsphenoidal surgery, to attempt to restore vision as quickly as possible, and then by supervoltage radiation to prevent regrowth of the remaining adenomatous tissue.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gonadotroph cell adenomas of the pituitary. 241 59

We studied gonadotropin hormone alpha-subunit and gonadotropin secretion in four patients with gonadotropin-producing pituitary adenomas. All four patients had elevated plasma alpha-subunit levels, ranging from 2.8-8.5 ng/ml (normal, less than 0.5 ng/ml). alpha-Subunit responses to LHRH were less than those in seven patients with primary gonadal failure. The relative proportions of the gonadotropin and alpha-subunit peaks in one patient were the same before and after LHRH administration, based on gel filtration studies of plasma. The alpha-subunit levels decreased little during testosterone treatment in the two adenoma patients so treated. Immunohistochemical study of the adenomas from two patients demonstrated definite staining with alpha-subunit and gonadotropin antisera. Elevated plasma levels of alpha-subunit and its relative unresponsiveness to LHRH stimulation or testosterone suppression suggest that the alpha-subunit originated in tumor tissue and that its measurement is useful for the diagnosis of a gonadotropin-producing tumor in patients with elevated plasma levels of LH and/or FSH.
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PMID:The significance of alpha-subunit as a tumor marker for gonadotropin-producing pituitary adenomas. 242 98

This immunohistochemical study disclosed that 9 of 15 GH secreting pituitary adenomas contained alpha subunit positive cells. These cases also contained PRL positive adenoma cells, but LH beta was negative. Of these 9 cases, 4 cases showed occasional FSH beta containing cells, 2 of these also contained a few TSH beta positive cells. By mirror section technique, variable numbers of adenoma cells were found to contain both GH and alpha subunit. Immunoelectron microscopically, both GH and alpha subunit were localized in secretory granules which suggested their co-release from the tumour cells. The presence of GH and alpha subunit in rough endoplasmic reticulum indicated their active production in the tumour. In the normal adult anterior pituitary gland, about 10% of GH cells contain FSH alpha, beta and LH beta subunits and had appearances suggesting the co-production of GH and FSH as well as LH. The colocalization of GH and FSH alpha is considered to be associated with the neoplastic transformation GH cells which possess the intrinsic potentiality of differentiation toward alpha subunit. However, the mechanism for the lack or deficiency of beta subunits in the neoplastic condition remains to be further investigated.
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PMID:Immunohistochemical colocalization of growth hormone (GH) and alpha subunit in human GH secreting pituitary adenomas. 244 84

Pituitary adenomas that secrete gonadotropins are generally believed to arise spontaneously rather than as a response to chronic primary gonadal failure. However, two women who were found to have gonadotroph adenomas several years after ovarian ablation have been reported. We describe a middle-aged man who developed bitemporal hemianopia and was found to have a large pituitary tumor 35 yr after castration. He had never received any replacement therapy. The tumor was considered to be a primary gonadotroph adenoma, rather than secondary gonadotroph hyperplasia, on the basis of its secretory capabilities, its reticulin patterns, and its specific immunostaining for human FSH beta, human LH beta, and alpha-subunit. Furthermore, the tumor did not decrease appreciably in size after 12 months of testosterone treatment, although plasma gonadotropin levels decreased. Unless the association of primary gonadal failure with a gonadotroph adenoma was coincidental, it suggests that some human gonadotroph adenomas may be secondary to failure of the gonads.
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PMID:Gonadotropin-producing pituitary adenoma in a man with long-standing primary hypogonadism. 244 14

The presence of mAB lu-5, a panepithelial, monoclonal antibody was studied in human adenohypophyses and pituitary adenomas by immunohistochemistry using the avidinbiotin-peroxidase complex technique. In nontumorous adenohypophyses, only corticotrophs showed strong immunoreactivity, whereas other adenohypophysial cell types exhibited little or no staining. Positive immunostaining was observed in corticotrophs spreading to the posterior lobe, in cells of squamous nests located in the pars tuberalis and several cells lining pars intermedia cavities. The Crooke's hyaline material in the cytoplasm of corticotrophs was immunopositive. In adenomatous corticotrophs and cytoplasmic fibrous bodies of sparsely granulated adenomatous somatotrophs, distinct mAB lu-5 immunoreactivity was evident. GH-, PRL-, TSH-, FSH-, LH-, alpha-subunit-producing adenomas, null cell adenomas and oncocytomas showed no convincing staining. Immunopositivity in corticotroph adenomas was diffusely distributed in the cytoplasm and was not located in secretory granules, indicating that mAB lu-5 did not stain ACTH. Immunoreactivity with mAB lu-5 was not specific for pituitary corticotrophs, since the antibody stained nontumorous epithelial cells and epithelial tumor cells in other organs as well. It can be concluded that mAB lu-5 is a valuable immunocytochemical marker in pituitary related studies, especially in those pituitary adenomas in which immunostaining for ACTH is weak or equivocal; in these cases, it can confirm the diagnosis of corticotroph adenoma. The antibody yields similar results as keratin antisera. In our experience, however, it gives a stronger, more distinct immunopositivity with less nonspecific background staining.
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PMID:Identification of corticotrophs in the human pituitary with mAB lu-5, a novel immunocytochemical marker. 244 79

The effect os SMS 201-995 (Sandostatin), a long-acting somatostatin analog, on different types of pituitary adenomas including alpha-subunit elevation is illustrated in this report. Treatment induced a fall in hCG levels in a woman with a pituitary adenoma producing only alpha-subunit. In 3 acromegalic patients, there was only a partial drop in GH and alpha-hCG. The same effect was observed in a woman with menopausal FSH and LH levels. SMS reduced plasma TSH and alpha-hCG in a case of thyrotropic adenoma. Two patients exhibiting FSH- and alpha-hCG-secreting adenomas did not respond to acute administration of SMS 201-995. More patients have to be treated before a definitive statement can be made on the usefulness of somatostatin analogs in the management of different types of pituitary adenomas.
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PMID:Plasma alpha-subunit levels during the treatment of pituitary adenomas with the somatostatin analog (SMS 201-995). 245 75

We have studied the effects of TRH and native gonadotrophin-releasing hormone (GnRH), and of a GnRH agonist (Buserelin; [D-Ser(But )6]GnRH(1-9) nonapeptide-ethylamide), on LH, FSH, alpha subunit and LH-beta subunit secretion from three human gonadotrophin-secreting pituitary adenomas in dispersed cell culture. During a 24 h study, treatment with 276 nmol TRH/l resulted in a significant (P less than 0.05) stimulated release of FSH and alpha subunit from all three adenomas, and LH from the two adenomas secreting detectable concentrations of this glycoprotein; treatment with 85 nmol GnRH/l significantly (P less than 0.05) stimulated the release of alpha subunit from all three, but FSH from only two and LH from only one adenoma. During a long-term 28-day study, basal FSH and alpha subunit concentrations were maintained, but secretion of LH, and LH-beta (detectable from one tumour only), declined with time from two of the three adenomas. Addition of Buserelin to the cultures resulted in the continuous (P less than 0.05) stimulation of alpha subunit secretion from all three adenomas, and of LH and FSH from two, whilst a transient stimulatory effect on LH and FSH secretion was seen from a third adenoma, with subsequent secretion rates declining towards control values. These data show that human gonadotrophin-secreting adenomas demonstrate variable stimulatory responses to hypothalamic TRH and GnRH, and that during chronic treatment with a GnRH agonist the anticipated desensitizing effect of the drug was not observed in two out of the three adenomas studied. The mechanisms for this is not clear, but such drugs are unlikely to be of therapeutic value in the management of gonadotrophin-secreting tumours. The data also suggest that GnRH and GnRH agonists have a differential effect on the in-vitro release of intact gonadotrophins and the common alpha subunit.
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PMID:Long-term effects of a gonadotrophin-releasing hormone agonist ([D-Ser(But)6]GnRH(1-9)nonapeptide-ethylamide) on gonadotrophin secretion from human pituitary gonadotroph cell adenomas in vitro. 246 May 76


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