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)

The human septal cartilage is of ectodermal origin and contributes to midfacial growth and development. Acromegaly is an endocrine disease due to growth hormone (Gh) excess originating from a somatotrophic adenoma of the pituitary gland. Excessive Gh levels lead to high insulin-like growth factor I (IGF I) concentrations, which are known to stimulate cartilage growth in vivo and in vitro. One of the salient clinical pictures is coarsening of the midface and enlargement of the septal cartilage. Septal cartilage was obtained from 8 acromegalic patients during transnasal hypophysectomy and from 10 healthy adults during septoplasty to analyse the following aspects of cartilage biochemistry, metabolism and growth. 1. Intracellular glycogen, the major source of energy of chondrocytes, was determined enzymatically and found to be drastically reduced in acromegaly. 2. Several intracellular enzymes, related to biomatrix degradation, showed a strict local pattern of distribution. Cathepsin B activity, a neutral proteinase degrading both the helical and nonhelical region of the collagen molecule was significantly increased in acromegaly, whereas alkaline phosphatase activity, an enzyme related to mineralization of the cartilage at the chondroosseous junction was depressed in acromegaly. 3. The cell density in some areas of the septal cartilage was increased in acromegaly, whereas the clonal proliferation rate of its chondrocytes in response to serum and growth factors was decreased. Chondrocytes both of healthy adults and acromegalic patients could be effectively stimulated by insulin-like growth factor I and II and to a lesser extent by epidermal growth factor.
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PMID:Human nasal septal cartilage: analysis of intracellular enzyme activities, glycogen content, cell density and clonal proliferation of septal chondrocytes of healthy adults and acromegalic patients. 252 4

GH secretion and mRNA levels were measured in cultured human GH adenoma cells incubated in serum-free medium for up to 48 h. A human recombinant insulin-like growth factor I (IGF-I) analog, Thr-59-IGF-I (6.5 nM), inhibited basal GH secretion by up to 60% in tumor cell cultures. The 30-50% stimulation of GH secretion by GH-releasing hormone (GHRH) was prevented by simultaneous exposure of the cells to IGF-I (6.5 nM). Gel electrophoresis of total RNA derived from GH cell adenoma tissue, followed by transfer and hybridization with 32P-labeled human GH cDNA, revealed a distinct mRNA species of about 1.0 kilobases. Using cytoplasmic dot blot hybridization, IGF-I inhibited the levels of human GH mRNA sequences in these cells and also prevented the GHRH-induced stimulation of GH mRNA. A monoclonal antibody to the type I IGF-I receptor (alpha IR3) prevented the inhibitory effects of IGF-I on basal and GHRH-stimulated GH secretion. This antibody also prevented the IGF-I-induced suppression of GH mRNA sequences. PRL secretion in these cells was not altered by IGF-I. Furthermore, relative levels of beta-actin mRNA were unaltered by IGF-I. Thus, IGF-I suppresses basal and GHRH-stimulated GH secretion and GH mRNA levels in pituitary adenoma cells, indicating that IGF-I acts selectively on the somatotroph to directly regulate GH gene expression.
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PMID:Insulin-like growth factor I regulates growth hormone secretion and messenger ribonucleic acid levels in human pituitary tumor cells. 301 22

Studies have demonstrated the presence of epidermal growth factor receptors in human parathyroid tumors. However, there is little information on the effect of other peptide growth factors on parathyroid cell growth. We therefore studied the interaction of insulin-like growth factor I (IGF-I) with human parathyroid tumor cells. Parathyroid tissues were obtained from 24 patients with primary or secondary hyperparathyroidism. There were 15 solitary adenomas, 5 carcinomas, and 4 hyperplastic tissues. First, the binding of [125I]IGF-I to the crude membrane fractions was studied by competitive inhibition with unlabeled IGF-I. Second, isolated parathyroid cells were cultured with IGF-I and examined for DNA synthesis. The IGF-binding protein (IGFBP) content of tissue homogenates was determined by ligand blot analysis. The binding of [125I]IGF-I to parathyroid membranes was dependent on time, temperature, and pH of the medium. Maximum binding was obtained after incubation for 18 hours at 4 degrees C. Specific binding to parathyroid cancer membranes (mean +/- SE, 10.75 +/- 10.55%/mg protein) was significantly (p < 0.05) greater than that in adenoma tissues (3.71 +/- 2.11%/mg). The value in hyperplastic tissues (4.78 +/- 2.97%/mg) was not different from that in adenomas. Affinity cross-linking and autoradiography demonstrated the type I IGF receptors. Cultured parathyroid cells responded to IGF-I with increased DNA synthesis. The parathyroid tumor tissues expressed IGFBPs. These results suggest that IGF-I and IGFBPs are involved in the growth regulation of parathyroid tumor cells.
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PMID:Insulin-like growth factor I receptors and insulin-like growth factor-binding proteins in human parathyroid tumors. 753 95

We studied the tumor-seeking agent technetium-99m-labeled pentavalent dimercaptosuccinic acid ([99mTc](V)DMSA) to visualize 21 growth hormone (GH)-, nine prolactin (PRL)-, two mixed GH/PRL-, six adrenocorticotrophin (ACTH)-secreting and 15 clinically non-functioning pituitary adenomas, three craniopharyngiomas and one dysgerminoma of the sella. All non-adenomas and 31 out of 53 adenomas were studied before treatment: 22 after surgery and/or radiotherapy. Eight cases of acromegaly were studied before and after chronic treatment with octreotide, whereas three cases of acromegaly, one of prolactinoma and two of non-functioning adenoma were imaged before and after adenomectomy. As a control group, 27 patients without any clinical evidence of pituitary adenoma were studied: 10 of them were operated on previously and treated with iodine-131 for metastatic thyroid carcinoma, 10 had brain tumors and the remaining seven patients had functional pituitary hypersecretion (four Klinefelter's syndrome, two primary hypothyroidism and one Addison's disease). The scintigraphy was repeated after testosterone in Klinefelter's syndrome, L-thyroxine in primary hypothyroidism and cortisone administration in Addison's disease. Seventeen GH-secreting (81%), seven PRL-secreting (78%), three ACTH-secreting (50%), 15 non-functioning (100%) and one (50%) mixed adenoma significantly concentrated [99mTc](V)DMSA, showing elevated tumor-to-background (T/B) ratios. The T/B ratios were similar in untreated and surgically treated adenomas (11.2 +/- 5.6 vs 11.8 +/- 6.2). Radiotherapy significantly lowered the [99mTc](V)DMSA uptake to 5.1 +/- 2.8 (p < 0.1 vs untreated patients). Non-adenomatous lesions of the sella turcica did not concentrate [99mTc](V)DMSA in the pituitary as well as brain tumors and 8 out of 10 metastatic thyroid cancers. The treatment with octreotide normalized GH and insulin-like growth factor I levels and reduced [99mTc](V)DMSA from 15.7 +/- 4.8 to 13.5 +/- 3.9 (p < 0.05). Conversely, adequate substitutive therapy completely inhibited the uptake of the radiotracer in Klinefelter's syndrome, in primary hypothyroidism and in Addison's disease. The [99mTc](V)DMSA scintigraphy showed an overall sensitivity of 81% (43/53) in detecting pituitary adenomas, which was increased to 95% for lesions greater than 10 mm in size. High-quality images with minimal total body radiation were obtained, enabling a good in vivo characterization of viable adenomatous tissue as well as an accurate monitoring of the effects of different therapeutic regimens.
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PMID:Technetium-99m pentavalent dimercaptosuccinic acid imaging in patients with pituitary adenomas. 762 36

In this study, we compared the clinical and endocrinological characteristics, neuroimaging findings, surgical outcome, and conventional histological findings (including immunohistochemistry) with the electron microscopic appearance of 31 growth hormone (GH)-producing adenomas. By electron microscopy, these 31 tumors were divided into 23 densely granulated somatotroph adenomas (DG adenomas) and 8 sparsely granulated somatotroph adenomas (SG adenomas). SG adenomas more frequently affected younger women, but no significant correlation was found between the adenoma type and the characteristic signs and symptoms of acromegaly, the incidence of diabetes mellitus or hypertension, or the basal serum GH and insulin-like growth factor I levels. A distinct response of GH to thyrotropin-releasing hormone, bromocriptine, or GH-releasing hormone was significantly more common in patients with DG adenomas than in those with SG adenomas, whereas the incidence of a response to gonadotropin-releasing hormone or oral glucose was not significantly different between the two groups. An analysis of neuroimaging findings and surgical results indicated that SG adenomas were more likely to be macroadenomas with suprasellar extension or invasive tumors and had a lower surgical cure rate. However, postoperative radiotherapy seemed to be similarly effective in both types of adenoma to prevent a tumor recurrence and to reduce postoperative GH basal level in serum. Light microscopy showed that DG adenomas were mainly acidophilic and were immunopositive not only for GH but also for prolactin (43%), the beta subunit of thyroid-stimulating hormone (26%), and the alpha subunit of glycoprotein hormone (87%), whereas SG adenomas were almost all chromophobic and only revealed immunopositivity for GH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology. 768 91

The growth-promoting activities of tumor-conditioned media (TU-CM) obtained from 23 cultured human nonfunctioning pituitary adenomas were studied in vitro. TU-CM obtained from adenoma cell cultures increased both cell counts (range: 108-179%; control = growth in serum-free medium = 100%) and 3H-thymidine incorporation (112-139%) of rat pituitary cell cultures, indicating that TU-CM contains growth-stimulating substances. TU-CM was also able to stimulate the growth of normal fibroblasts (3H-thymidine incorporation: 164-178%; cell counts: 145-157%) and endothelial cells (3H-thymidine incorporation: 131-149%; cell counts: 181-217%), suggesting the presence of - possibly angiogenic-growth factors that act on these cell types. However, the growth of hormone-producing cells was also stimulated, since TU-CM increased 3H-thymidine incorporation into rat pituitary cells in the presence of D-Val-MEM, a medium specifically inhibiting growth of fibroblasts. Addition of neutralizing antibodies against transforming growth factor alpha (TGF-alpha), epidermal growth factor (EGF), insulin-like growth factor I (IGF-I) and basic fibroblast growth factor (bFGF), either alone or in different combinations, reduced the growth-promoting activity of TU-CM on rat pituitary cells (range: 96-71%; control = growth effect of TU-CM without antibodies = 100%), strongly indicating the presence of these growth factors in TU-CM. All 4 antibodies together completely inhibited the growth-stimulatory activity of TU-CM, strongly suggesting that these growth factors play the major role among growth-stimulating substances in TU-CM. This is the first study giving evidence that TGF-alpha, EGF, IGF-I and bFGF are secreted by nonfunctioning adenoma cells indicating that the growth factors could be involved in growth regulation of pituitary adenomas by paracrine or autocrine mechanisms.
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PMID:Secretion of polypeptide growth factors by human nonfunctioning pituitary adenoma cells in culture. 841 19

Octreotide (OCT) administration provides a biochemical cure in most acromegalic patients. This drug, however, causes several side effects and is very expensive. Acute testing has been reported to predict chronic responsiveness to OCT administration. The aim of this retrospective study was to evaluate which test, if any, among acute testing, short-term (1 month) administration, and 111In-pentetreotide (111In-DTPA-Phe-D-OCT) scintigraphy, is best in predicting response to long-term OCT treatment. Sixty-eight patients with active acromegaly were studied. An acute test (100 micrograms sc OCT) was performed as usual: a GH decrease greater than or equal to 50% of baseline was considered a positive response. GH and insulin-like growth factor I (IGF-I) were then assayed after 1 month (300 micrograms daily) and 3 months (150-600 micrograms daily) of OCT administration. GH was considered normalized when decreased less than or equal to 5 micrograms/L. Twenty-six of 68 patients were subjected to 111In-pentetreotide scintigraphy. Linear correlation analysis of the results was performed. Sensitivity, specificity, and positive and negative predictive values of the three tests were also calculated. Thirty-eight of 68 patients (56%) responded to the acute test. Among these 38 patients, 20 experienced normalization of GH and IGF-I levels during long-term therapy, as did 8 patients who did not respond to the acute test. No significant correlation was found between GH percent decrease during acute testing and long-term therapy (r = 0.11). Seven patients who responded to the acute test and 2 who did not respond had adenoma shrinkage during therapy. Conversely, GH and IGF-I decrease after short-term treatment significantly correlated with long-term treatment (r = 0.76 and 0.64, P < 0.01). Of the 26 patients subjected to 111In-pentetreotide scintigraphy, 13 had significant tracer uptake: normalization of GH and IGF-I was obtained in 8 patients. A significant correlation was found between tracer uptake and GH/IGF-I inhibition after 3 months of therapy (r = 0.6; P < 0.05). In the whole population, the positive predictive value of acute testing, short-term OCT administration, and 111In-penetreotide scintigraphy was 53%, 70%, and 73%, respectively, when the GH normalization (< 5 micrograms/L) after 3 months of therapy was considered. Moreover, 111-In-pentetreotide scintigraphy had the highest specificity (100% in patients with baseline GH values below 50 micrograms/L) compared with that of acute testing and short-term OCT administration. The acute test cannot be considered as a valuable index to identify patients' responsiveness to long-term OCT therapy, but it can be useful to test tolerability. By contrast, 1 month of OCT administration or the in vivo imaging of somatostatin receptors by 111-In-pentetreotide might better indicate the patients who might effectively benefit from this treatment.
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PMID:Prediction of efficacy of octreotide therapy in patients with acromegaly. 896 77

Medical treatment of acromegaly with dopamine agonists possesses 2 main advantages: the oral administration and the low costs. In this study, we reported on the results of chronic treatments with quinagolide (CV 205-502), cabergoline (CAB) and long-acting depot preparation of bromocriptine (BRC-LAR) in 34 acromegalics. Patients were divided into three groups on the basis of different treatment: CV 205-502 given to 16 patients at the dose of 0.3-0.6 mg/day for 6 months; CAB given to 11 patients at the dose of 1.0-2.0 mg weekly for 6 months; and BRC-LAR injected into 7 patients at the dose of 100 mg/month for 6-12 months. Basal and oral glucose tolerance test-stimulated serum GH levels, basal and TRH-stimulated PRL levels, plasma insulin-like growth factor I (IGF-I) levels, computed tomography scan, and/or magnetic resonance imaging were assessed before and quarterly during treatments. The chronic administration of CV 205-502, CAB, and BRC-LAR caused a significant decrease of circulating GH, IGF-I, and PRL levels (P < 0.005). Normalization of circulating GH and IGF-I levels was obtained in 7 of 16 (43.8%) patients treated with CV 205-502. Serum GH response to oral glucose tolerance test (oGTT) significantly improved (P < 0.005), and PRL levels were significantly suppressed during treatments. No correlation was found between basal and TRH-stimulated PRL levels and GH suppression during different therapies. Immunohistochemical staining revealed 19 GH-positive and 10 GH + PRL-positive adenomas. A significant association was found between GH/PRL staining and responsiveness to chronic treatments (chi 2 = 7.985, P < 0.005). Three patients had significant adenoma shrinkage. Slight nausea and hypotension which spontaneously disappeared within therapy progression, were referred by 5/16 patients during CV 205-502 and 2/7 during BRC-LAR. The results of this study indicate that CAB and BRC-LAR cannot be considered as useful medical approaches for acromegalics, whereas CV 205-502 normalized circulating GH and IGF-I levels in 47.8% of patients.
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PMID:Effect of different dopaminergic agents in the treatment of acromegaly. 902 47

Although it has been demonstrated that acromegalic patients have an increased risk of neoplasms, especially colon neoplasms, gastric cancer with acromegaly is very rare--only five cases have been reported to date in Japan. We report here a rare case of gastric cancer with acromegaly in a 58-year-old woman, whose acromegalic change began at age 44. This patient showed typical clinical features of acromegaly, with increased concentrations of blood growth hormone (GH) and insulin-like growth factor I (IGF-I); she had four types of neoplasms; gastric cancer, colon tubular adenoma with moderate atypia, pancreatic mucinous cystadenoma, and subcutaneous lipoma. The gastric cancer was macroscopically 0-IIc type, 3.0 x 2.5 cm in size, and histologically diagnosed as a poorly differentiated adenocarcinoma with limited invasion of the mucosal layer. The previously documented stimulatory effects of GH and/or IGF-I on tumorigenesis and cell proliferation may have been responsible for the development of the multiple neoplasms in our patient.
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PMID:A rare case of gastric cancer in an acromegalic patient. 925 Sep 2

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

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