UMLS:C0001430 - FACTA Search

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

We have previously shown that the somatostatin (SRIH) precursor (pro-SRIH) and SRIH are present in the normal human pituitary, whereas mature SRIH is never detected in GH-secreting adenomas associated with high plasma GH levels, and pro-SRIH is absent in 50% of them. Considering the fact that GHRH is present and released in vitro in higher amounts from GH adenomas than from normal human pituitaries, the possibility of a negative control exerted by GHRH on pituitary SRIH was investigated. When GH-secreting adenomas were incubated for 4 h in the presence of GHRH (10(-8) mol/L), the amount of pro-SRIH, quantified after Sephadex G-50 filtration of the acetic acid extracts, was significantly decreased. The percent inhibition was negatively correlated to the amount of endogenously released GHRH measured in the control incubation medium, suggesting a local negative feedback control exerted by pituitary GHRH on pituitary SRIH. This was further demonstrated when adenomas were incubated with a GHRH antibody. Indeed, the presence of the GHRH antibody resulted in a significant increase in the content of pro-SRIH in the adenoma. Similar results were obtained for in vitro SRIH release; exogenous GHRH induced an inhibition of SRIH release from GH-secreting adenomas, and the GHRH antibody had the opposite effect. Using a perifusion system, we showed the concomitance between the increase in GH release and the decrease in SRIH release after GHRH stimulation. Together, these results show in vitro a negative control exerted by GHRH (both exogenous and locally released) on adenomatous pituitary SRIH. This further amplifies the importance of autocrine or paracrine controls in these tumors.
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PMID:Growth hormone (GH)-releasing hormone tonically inhibits in vitro endogenous somatostatin in human GH-secreting tumors. 774 20

GH-secreting pituitary adenomas causing acromegaly can be classified into at least two types, i.e. the lactotroph-like adenoma and somatotroph-like adenoma. From a functional point of view, the lactotroph-like adenoma is characterized by positive GH responses to TRH and bromocriptine (Br) with a GH increase or decrease, respectively, whereas the somatotroph-like adenoma is characterized by a high GH response to GHRH and a low GH response to TRH and Br. In this study, we examined whether the loading of vasoactive intestinal peptide (VIP) and GnRH, another hypothalamic hormone capable of stimulating GH secretion in acromegaly, have a pathophysiological significance as TRH, GHRH, and Br tests. In 52 patients with active acromegaly, we performed iv bolus injections of TRH (500 micrograms), GHRH (100 micrograms), VIP (100 micrograms), and GnRH (100 micrograms), and a peroral administration of Br (2.5 mg), in order to compare the GH responses to these loads. There was a significant correlation that the higher was the GH response after TRH the greater was the GH decrease after Br. Although statistically insignificant, there was a trend (0.05 < p < 0.1) that the higher was the GH response after GHRH the smaller was the GH decrease after Br. In addition, as novel findings, we observed that the GH responses to GHRH, VIP, and GnRH were in significant positive correlations to each other, and that the higher were the GH responses after VIP and GnRH the smaller was the GH decrease after Br. In agreement with this, we also found that a simultaneous GH responsivity to VIP and/or GnRH in TRH-responsive acromegalics significantly enhanced the GH response to GHRH and lowered the Br responsiveness compared to the data of pure TRH-responders. From these results, we hypothesize that the positive GH responsiveness to VIP and GnRH, like that to GHRH, may be a feature of the somatotroph-like pituitary adenoma causing acromegaly. The present results appear to be of some help in understanding the basis of the great variabilities in the GH responses to various dynamic testings in acromegaly.
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PMID:Clinical significance of the growth hormone response to vasoactive intestinal peptide and gonadotropin-releasing hormone in acromegaly. 774 55

It has been suggested that pit-1 protein may play a role in the differentiation of the anterior pituitary cells. The present immunohistochemical studies were designed to elucidate the relationship between functional differentiation of pituitary adenoma and expression of pit-1 protein in human (h) GRF transgenic mice. Pituitaries from a 10 month old and a 6 month old transgenic mice were fixed in 4% paraformaldehyde and embedded in paraffin. The indirect immunoperoxidase method was performed using antibodies against hGRF, GH, PRL, ACTH, alpha subunit (SU), FSH beta SU, LH beta SU, TSH beta SU, and pit-1 protein. Immunohistochemical double staining was performed at light and electron microscopic levels. The pituitary glands of hGRF transgenic mice (both 10 month and 6 month old) demonstrated diffuse hyperplasia of GH positive cells with coexpression of hGRF within the same cells. There were also scattered cells which were positive for other hormones and hormone subunits in the hyperplastic pituitary. Three discrete nodules were found in the pituitary gland of a 10 month old hGRF transgenic mouse and were identified as adenomas. These adenomas were composed of enlarged round cells which were positive only for GH, hGRF, PRL and TSH beta SU. Pit-1 protein was intensely expressed in the nuclei of the adenoma cells. These results suggest the existence of an autocrine mechanism by hGRF in the formation of somato-lacto-thyrotroph adenoma via constitutive pit-1 expression.
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PMID:Immunohistochemical expression of PIT-1 protein in pituitary glands of human GRF transgenic mice: its relationship with hormonal expressions. 795 87

The simultaneous occurrence of a pituitary adenoma and an intracranial meningioma is a rare event. We report the coexistence of an eosinophilic pituitary adenoma and a endotheliomatous meningioma, in the sellar region, and evaluate their endocrine, neuro-radiological and immunohistochemical pattern. A 47-year-old woman affected by acromegaly was referred to us. Serum GH level was 82 ng/ml and remained unresponsive to both OGTT (75 g per os) and iv. GHRH 1-29 (100 micrograms); IGF-1 was 807 ng/ml. Eight hours after acute sc administration of octreotide (100 micrograms) GH returned to normal levels (2.3 ng/ml). CT scan showed a large intra- and suprasellar mass involving the right cavernous sinus, with a retrosellar extension along the tentorium. A slight and inhomogeneous enhancement, with a periferal rim of bright signal was apparent at MRI. Conversely, the retrosellar component showed a bright homogeneous enhancement. The patient, therefore, underwent neurosurgery. Histological examination revealed the coexistence of 2 types of tissue: areas of endotheliomatous meningioma were interspersed among sheets of acidophilic adenoma tissue. Immunohistochemical analysis was performed in order to determine the relationship between the two masses: a positive staining for GH was shown in the areas of adenoma, as against for GHRH, neither in the adenomatous tissue nor in the slices of meningioma. Although MRI showed a latero-sellar post-surgical residual of meningioma, serum GH value was < 1 ng/ml. In conclusion, the relationship between the GH-secreting adenoma and the meningioma is unclear; however the GH-hypersecretion is not induced by a hypothetic GHRH-activity from the meningioma.
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PMID:Coexistence of growth hormone-secreting pituitary adenoma and intracranial meningioma: a case report and review of the literature. 828 67

Pituitary tumorigenesis is characterized by initiation, implying spontaneous or acquired mutations and promotion, implying that tumour expansion is sustained by intrinsic or extrinsic promoting factors. Pituitary tumours have a doubling time of 100 to 700 days. Seventy per cent of cases occur in 30 to 50-year-old patients, but tumours with highest growth rate (prolactin and ACTH-secreting adenomas) are also encountered in patients < 20 years. Pituitary adenomas occur at a greater frequency in females but there is no vivo evidence for a direct role of sex hormones. Oestrogen can amplify tumour growth factors in pituitary cell lines. One-third of GH-secreting adenomas have elevated cAMP resting levels which appear to be caused by a somatic mutation in the Gs protein associated with the GHRH receptor. This maintains the adenylate cyclase system in a turned-on state. Patients with mutant Gs protein have higher GH levels, reduced GHRH response, elevated TRH response, good suppressibility by SRIH and smaller tumour size compared to other acromegalic patients. Hypothalamic releasing hormones may be able to sustain pituitary tumour development since some acromegalic patients with GHRH-secreting tumours may harbour a pituitary GH-secreting adenoma. A lack of inhibitory factors may also have a promoting role in tumour progression.
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PMID:Epidemiology and pathogenesis of pituitary adenomas. 839 32

The morphology of hyperplastic pituitaries in seven human growth hormone-releasing factor (hGRF) transgenic mice were compared to those of two normal control mice. Under continuous stimulation by hGRF, both the total volume of the pituitary and the size of individual cells increased, and a nodular lesion, designated a "hypertrophic nodule", was identified. Immunohistochemically, the hyperplastic pituitaries consisted of various numbers of cells immunoreactive for rGH, rPRL, hACTH, rLH beta, hFSH beta, and r alpha SU, whereas the "hypertrophic nodule" was composed of rGH, rPRL, and rTSH beta positive cells, similar to the adenoma. The presence of the "hypertrophic nodule", which was intermediate in appearance between the controls and the adenomas, suggests a close relation between continuous hGRF stimulation and the development of a hyperplasia-adenoma sequence in the pituitary.
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PMID:Immunohistochemical characterization of "hyperplasia-adenoma sequence" in the pituitaries of transgenic mice expressing a human growth hormone-releasing factor gene. 879 63

The aim of the present study was to characterize in a large series (N = 12) of cultured somatotrope adenomas the in vitro effects of the neuropeptide galanin on growth hormone (GH) secretion. This was contrasted with two peptides known to be GH secretagogues (GH-releasing hormone [GHRH] and thyrotropin-releasing hormone [TRH]) and a peptide with a known GH-inhibitory effect (the somatostatin analog octreotide). Groups of three wells were incubated for 4 hours with growth medium alone (control incubation), galanin, GHRH(1-29)NH2, TRH, or octreotide. Galanin and octreotide were applied at concentrations of 0.1, 1, and 10 mumol/L, and GHRH and TRH at concentrations of 0.01, 0.1, and 1 mumol/L. Galanin was able to inhibit GH release in nine of 12 cultured somatotrope adenoma cells. This inhibitory effect was clearly dose-dependent in five adenomas. Overall, the mean GH nadir after galanin was -36.1% in nine responder adenoma cultures versus control wells. Octreotide inhibited GH release in five of eight cultured somatotrope adenoma cells. The mean GH nadir after octreotide was -32.7% in five responder adenoma cultures compared with control wells. GHRH and TRH were able to stimulate GH release, respectively, in seven of 11 and in six of seven cultured somatotrope adenoma cells. The mean GH peaks after either GHRH or TRH in responder adenoma cultures were, respectively, +71.5% and +143.7% compared with levels in the control wells. In conclusion, the consistency and potency of the in vitro GH-inhibitory effect of galanin in a large series of somatotrope adenomas are at least similar to those of the most effective available GH-lowering agent, the somatostatin analog octreotide.
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PMID:Inhibitory effects of galanin on growth hormone (GH) release in cultured GH-secreting adenoma cells: comparative study with octreotide, GH-releasing hormone, and thyrotropin-releasing hormone. 910 48

The functional and morphological changes in the pituitary gland caused by a GHRH-producing pancreatic islet cell tumor that metastasized to the pituitary and caused somatotroph hyperplasia are described. A 52-yr-old woman presented with loss of visual acuity, diabetes insipidus, and acromegaly caused by a GHRH-producing endocrine carcinoma metastasized to the pituitary. The serum GHRH, GH, and insulin-like growth factor I levels of the patient were elevated. Immunohistochemical and in situ hybridization study revealed GHRH immunoreactivity and GHRH messenger RNA (mRNA) in the metastatic tumor cells. The anterior pituitary showed hyperplasia of somatotroph cells with intact acinar structure that did not contain an adenoma, determined by light microscopy using silver impregnation. Electron microscopy revealed hyperplastic characteristics of densely granulated somatotrophs. In situ hybridization documented strong signals for GH mRNA and pituitary-specific transcriptional factor Pit-1 mRNA in the hyperplastic somatotrophs. A weak signal for GHRH receptor mRNA was detected in these somatotrophs. However, using in situ RT-PCR, GHRH receptor mRNA was more conclusively observed in most of the somatotrophs. The excessive production of GHRH by metastatic tumor may have resulted in somatotroph hyperplasia by the synergistic effects of Pit-1 and GHRH receptor. It can be concluded that the pathogenesis of pituitary adenoma formation is primarily mediated by other factors than hypothalamic hormone.
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PMID:A growth hormone-releasing hormone-producing pancreatic islet cell tumor metastasized to the pituitary is associated with pituitary somatotroph hyperplasia and acromegaly. 925 62

We report a rare case of Cushing's syndrome due to bilateral adrenocortical adenomas in a 45-year-old female. She suffered from diabetes mellitus and hypertension for a decade, but her appearance was not Cushingoid. The plasma cortisol level in the morning was at the upper limit of the normal range, but did not show a diurnal rhythm or was suppressed by 1 mg of dexamethasone. The plasma level of ACTH was undetectable, and it failed to respond to human CRH (hCRH). Plasma cortisol responded well to synthetic ACTH. The urinary 17-OHCS level was high, and was not suppressed by 4 mg of dexamethasone. While these findings were consistent with a diagnosis of adrenocortical adenoma, computed tomography showed several nodules in both adrenal glands that suggested the presence of huge nodular adrenocortical hyperplasia or bilateral adrenocortical adenomas. Bilateral adrenalectomy demonstrated the presence of three adenomas, two in the right and one in the left adrenal. Analysis of the extract from each adenoma revealed that two of the three produced an excess amount of cortisol. Magnetic resonance imaging (MRI) of the brain suggested the presence of pituitary adenoma. Prior to adrenalectomy, TSH, GH or LH showed a low response to TRH, GHRH or LHRH, respectively. Since normal responses were restored after bilateral adrenalectomy, these abnormalities were attributed to hypercortisolemia.
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PMID:A rare case of Cushing's syndrome due to bilateral adrenocortical adenomas. 944 86

Gangliocytomas or gangliogliomas of the sellar region are very rare tumors. In a great proportion of those cases an adenoma of the anterior pituitary develops from the cell type that is hyperstimulated by the releasing hormone produced from the gangliocytoma. Five GHRH secreting gangliocytomas are reported. Four of these were localized adjacent to a GH secreting adenoma. In one case, no adenoma tissue was found beside the ganglicytoma. As only the adenomas can secrete GH, the adenomas and not the gangliocytomas are directly responsible for acromegaly so that such an adenoma has to be present in cases of acromegaly. A CRH secreting gangliocytoma was combined with an ACTH cell adenoma that had induced Cushing's disease. A ganglioglioma of the posterior pituitary had led to an inappropriate secretion of Vasopressin. The morphology of the different tumors is presented.
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PMID:[Combined neuronal and endocrine tumors of the sellar region]. 945 29

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