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

Growth hormone (GH) disorders are characterized with clinical presentation of GH excess or deficiency. The pathogenesis and pathophysiology of GH disorders have been extensively studied with the sake of recent development of sensitive immunoassays and molecular cell biology. Highly sensitive immunoassays for GH have revealed the normal and abnormal GH secretory dynamics even under the detectable levels by conventional radioimmunoassay. Glucose loading clearly suppressed GH levels less than 1ng/ml in normal subjects. Clinical utility of insulin like growth factor-I (IGF-I) for diagnosing GH disorders was also evaluated. We have established the age- and sex-matched reference values of IGF-I and IGF binding protein-3 (IGFBP-3) in Japanese. Both IGF-I and IGFBP-3 had the similar diagnostic values for GH deficiency. Genetic alterations in GH secreting pituitary adenomas have been extensively studied. Gs alpha mutation has been found in about 30-40% of acromegaly. The prevalence of this mutation was previously considered low but recent studies showed even higher incidence in Japan. Other oncogenic mutations were considered rare in acromegaly. It is noteworthy that GH secreting adenoma tissues had high content of activated cyclic AMP responsive element-binding proteins (CREB). We have identified new mutation in GH-1 gene in patients with familial isolated GH deficiency type II, which resulted in the skipping of exon 3.
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PMID:[Recent progress in the diagnosis of growth hormone (GH) disorders]. 931 Dec 56

To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human pituitary GH-secreting adenoma was investigated in monolayer cell culture. It was found that Ca2+ channel blockers nicardipin and nifedipin inhibited basal and growth hormone releasing hormone (GRH)-stimulated GH secretion in 87.5% and 100.0% of the GH adenomas, respectively, demonstrating that in most human pituitary GH adenomas, the basal and GRH regulated GH secretion is Ca2+ dependent. The GRH and sometostatin (SRIF) agonist octreotide regulated the processes of GH secretion via Ca2+ had defects in different steps including receptor, postreceptor Ca2+ channel and Ca(2+)-GH secreting coupling in 6(66.6%) and 5(55.5%) cases of 9 GH adenomas respectively. Among them, the defects in GRH receptor and SRIF regulated Ca2+ channel are the main causes of the dysfunction of GH adenomas. These defects may be related to GH hypersecretion in GH adenomas. Our data provides advance evidences for intrinsic defects of GH adenomas.
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PMID:The role of calcium ion in the pathogenesis of human pituitary GH-secreting adenomas. 938 85

Background: There is much evidence that growth hormone plays an important role in the development and function of the reproductive system of both males and females. Growth hormone exerts its effects on the ovarian follicular cycle directly or by local production of insulin-like growth factor 1 (IGF-1). It is known that growth hormone deficiency during childhood may delay pubertal development, but there is limited data about primary amenorrhea in GH-deficient girls with sufficient stimulated gonadotropin levels.Methods: Case series.Results: In the evaluation of primary amenorrhea and delayed puberty, 3 cases of adolescent females aged 17-19 years were identified as isolated GH-deficiency. Among the 3 patients, 2 had history of intracranial surgery due to hydrocephalus (shunt operation) or prolactin-secreting pituitary macro-adenoma (transphenoidal surgery, one year before). 17-year-old patient with shunted hydrocephalus and 19-year-old patient with primary amenorrhea showed short statue (< 5%) and delayed bone maturation. The patient undertaken transphenoidal surgery for prolactinoma showed normal height and bone maturation. There was no familial history of delayed puberty. On physical examination, 3 patients showed variable degree of breast development from Tanner stage II to IV without sex-steroid replacement. In sella MRI, small pituitary gland were identified in 2 patients with short statue and delayed bone maturation. All of the 3 patients underwent combined pituitary function test. After insulin-induced hypoglycemia, peak growth hormone levels of the 3 patients were 0.08, 1.4 and 1.4 ng/ml and were compatible with growth hormone deficiency. Peak LH after intravenous gonadrelin (FACTREL) were 19.0 to 56.1 mIU/ml and LH % responses were 217 to 1100% and were hence defined as not being gonadotropin deficiency. Other anterior pituitary functions were normal in all of the 3 patients.Conclusions: We found isolated growth hormone deficiency as the only identifiable cause for primary amenorrhea in three patients with sufficient gonadotropins secretion. These findings suggest a complementary role of GH to gonadotropins in the occurrence of menarche.
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PMID:Growth hormone deficiency as the only identifiable cause for primary amenorrhea 1086 82

There is increasing evidence suggesting that the neurotransmitter gamma-aminobutyric acid (GABA) is a local factor involved in the regulation of endocrine organs. Examples of such functions are documented in the pancreas, but recent results suggest that GABA may act in a similar way in the pituitary, in which GABA receptors are expressed and pituitary growth hormone (GH) cells provide a source of GABA. We hypothesised that GABA secreted in somatotropes may act as an autoregulatory signaling molecule. To test this hypothesis we first examined the nature of GABA receptors expressed by GH cells. RT-PCR analysis demonstrated that GABA-B receptor subunits R1 and R2 are present in the whole rat pituitary. Laser microdissection of immunostained GH cells, followed by RT-PCR as well as immunoelectron microscopy, showed that GABA-B receptors are expressed on somatotropes. To investigate GABA-B receptor function in somatotropes, we used rat GH3 adenoma cells, which, like pituitary GH cells, express GABA-B R1 and R2 (as assessed by RT-PCR and immunoelectron microscopy) and produce GABA (checked by high performance liquid chromatography). After inhibition of endogenous GABA synthesis, GH production was stimulated by baclofen, a chromatography). After inhibition of endogenous GABA synthesis, GH production was stimulated by baclofen, a GABA-B receptor agonist. By contrast, blocking GABA-B receptors by an antagonist, phaclofen, decreased GH levels. We conclude that in GH-producing cells, GABA acts as an autocrine factor via GABA-B receptors to control GH levels.
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PMID:An autocrine role for pituitary GABA: activation of GABA-B receptors and regulation of growth hormone levels. 1221 49

Growth hormone (GH)-producing pituitary adenomas can be ultrastructurally divided into two major types: densely granulated and sparsely granulated. The latter type of adenoma characteristically exhibits globular accumulations of cytokeratin filaments known as fibrous bodies, which are immunohistochemically identifiable as juxtanuclear dot-like immunoreactivity. We hypothesize that the formation of fibrous body might be related to dysfunction of adhesion molecules, because of the functional relationship between intermediate filaments and the cadherin-catenin complex and frequent observation of loss of cohesiveness of the adenoma cells. Our recent immunohistochemical study showed that expression of E-cadherin and its undercoat proteins, alpha-, beta- and gamma-catenin, in GH cell adenomas with prominent fibrous bodies was significantly reduced compared with GH cell adenomas without fibrous bodies and the normal adenohypophysial cells. Although no mutation of exon 3 of the beta-catenin gene was found in any GH cell adenomas with fibrous bodies, methylation-specific polymerase chain reaction analysis revealed that the E-cadherin promoter region was methylated in 37.5% of these adenomas, two of which displayed total methylation, but not in GH cell adenomas without fibrous bodies. We conclude that the decreased expression of the E-cadherin-catenin complex and methylation of the E-cadherin gene promoter region are events associated with the formation of fibrous bodies in GH cell adenomas. It remains to be clarified to explain the mechanism by which down-regulation of adhesion molecules is involved in the abnormal assembly of intermediate filaments.
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PMID:Down-regulation of E-cadherin and catenins in human pituitary growth hormone-producing adenomas. 1528 43

Acromegaly is associated with considerable morbidity and excess mortality; however, after effective treatment, both morbidity and mortality risks improve. Growth hormone excess in acromegaly can be controlled in many patients by pharmacotherapy alone, and with a combination of transsphenoidal surgery and pharmacotherapy in almost all patients. Since the clinical introduction of pegvisomant, a growth hormone-receptor antagonist, the role of radiotherapy is restricted. This review focuses on the treatment options for acromegaly (e.g., surgery, radiotherapy and pharmacotherapy with the depot preparations of the somatostatin analogues octreotide long-acting release formulation, lanreotide slow-release formulation and lanreotide Autogel, the growth hormone antagonist pegvisomant and the dopamine agonist cabergoline). Pharmacological characteristics of these drugs and the clinical and adverse effects are discussed individually and in relation to the other treatment modalities. The evidence for biochemical goals aimed at during medical treatment and the costs of pharmacotherapy are discussed. A new treatment algorithm is proposed, in which the choice between primary medical treatment and primary surgery is individualised, dependent on adenoma size and extension, patient factors (age, preference for therapy, contraindication for surgery), surgical experience of the centre and octreotide sensitivity of the adenoma. The high cost of lifelong medical treatment, especially of pegvisomant, must be weighed against the cost of a single surgical procedure.
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PMID:Current pharmacotherapy for acromegaly: a review. 1625 71

The molecular pathogenesis of lung cancer, especially multiple and synchronous bronchioloalveolar carcinomas (BACs), is still unknown. Here, we report two cases of multiple BACs associated with acromegaly, and discuss about the possible relationship between these two pathological condition. The first patient was a 52-year-old female with a history of Hardy's surgery for pituitary growth hormone cell adenoma 2 years earlier. The second patient was a 57-year-old female with acromegaly and obstructive sleep apnea syndrome. Both patients were non-smokers and showed a high serum level of insulin-like growth factor I (IGF-I) at the time of admission, even though the level of growth hormone had decreased. High-resolution computed tomography (HRCT) revealed multiple small nodules with pure ground-glass opacity (GGO) in both lungs of the first patient and a small nodule with pure GGO in the right lung of the second one. Partial resection for these tumors were performed under video-assisted thoracoscopic surgery. Resected lung specimens of the first case revealed one papillary adenocarcinoma, seven BACs, and 11 atypical adenomatous hyperplasias (AAHs). The second case showed two foci of BACs. Immunohistochemically, all BACs were strongly positive for IGF-IR which is a specific receptor for IGF-I, and all AAHs were also weakly positive for IGF-IR. Since IGF-I is known as a potent growth factor for normal as well as cancerous cells, it might play an important role for tumorigenesis and/or tumor progression of BACs through its interaction with and/or upregulation of IGF-IR. In addition, much attention should be paid to detect lung lesions in acromegaly with high serum level of IGF-I.
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PMID:Multiple bronchioloalveolar carcinomas in acromegaly: a potential role of insulin-like growth factor I in carcinogenesis. 1694 17

A pituitary acidophil adenoma in a domestic shorthaired cat with diabetes mellitus and elevated serum somatomedin C level is described. Growth hormone production by the neoplasm was confirmed by an appropriate reaction using an immunoperoxidase technic.
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PMID:Growth Hormone-producing Pituitary Adenoma, Elevated Serum Somatomedin C Concentration and Diabetes Mellitus in a Cat. 1742 32

Recent molecular pathological investigations have elucidated the cytodifferentiation of pituitary cells and identified several transcriptional factors that regulate this cytodifferentiation of pituitary cells. The patterns of cytodifferentiation are closely related to the pathogenesis of pituitary adenomas. Meanwhile, the role of hypothalamic hormones in the development of pituitary adenomas has recently attracted the attention of investigators. The expression of growth hormone-releasing hormone and corticotrophin releasing hormone in corticotroph adenomas have been demonstrated in somatotroph adenomas and corticotropin adenomas, respectively. This finding indicates that the endogenous expression of hypothalamic hormones and their receptors in human pituitary adenoma cells has ample significance in the autocrine or paracrine regulation of pituitary hormone production and tumor extension induced by hypothalamic hormones produced by adenoma cells. The recent progress in surgical techniques for treatment of pituitary adenomas has provided several alternatives: transsphenoidal surgery vs. transcranial surgery, sublabial approach vs. endonasal approach, and microsurgery vs. endoscopic surgery. There have also been developments in the medical treatment of pituitary adenomas. The frequently used dopamine agonist, cabergoline, is very effective for treating prolactin-producing adenoma. Long-acting octreotide and pegvisomant are now available for the treatment of growth hormone producing adenoma. Cabergoline is also used for growth hormone producing adenoma. Temozolomide has recently been used for atypical adenomas or pituitary carcinomas. Adult growth hormone deficiency sometimes occurs in postoperative patients with pituitary adenomas. Growth hormone replacement is recommended to maintain the quality of life of these patients.
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PMID:[Recent trends in the pathophysiology and treatment of pituitary adenomas]. 1969 85

Growth hormone (GH)-producing pituitary adenomas have been classified into densely and sparsely granulated adenomas. The latter are chromophobic with weak GH-positivity and characteristically possess fibrous body (FB), aggregation of cytokeratin filaments. We report eight cases of unusual chromophobic adenomas. GH-immunoreactivity was detected in most adenoma cells in five cases and scattered in three cases. However, it appeared much weaker than that seen in ordinary GH-producing adenomas because of spotty immunoreactivity. Although intracytoplasmic organelles were well-developed, secretory granules were small and sparse. FB was not identified in any cases. Thyroid-stimulating hormone was positive in four cases. Pit-1 protein was positive in all eight cases. A weak labeling with GH probe was detected in two of two cases examined by in situ hybridization. Acromegalic features were evident in four cases, while mild or absent in four cases. GH levels were below 5 microg/l in four cases and 5-10 microg/l in the remaining cases. Macroadenomas and invasive adenomas were seen in seven and six cases, respectively.Pituitary adenomas that show a faint GH-immunoreactivity but lack FB do not fit the established classification. These adenomas may be a distinct pituitary adenoma type of Pit-1 lineage with endocrinologically low activity.
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PMID:Pituitary adenomas that show a faint GH-immunoreactivity but lack fibrous body: Pit-1 adenoma with endocrinologically low activity. 2011 11


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