Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GH hypersecretion is a hallmark of acromegaly. It is unknown whether the secretory activity of somatotroph adenoma is autonomous or is still governed by central or peripheral mechanisms. In this study we investigated whether GH secretion in acromegaly 1) has a reproducible circadian pattern and 2) is inhibited by exogenous IGF-I. Eleven patients with newly diagnosed acromegaly were studied in 2 protocols. In protocol 1, peripheral blood was sampled every 10 min for 48 h in 6 patients for the determination of concordance between 24-h GH profiles. There was no significant day to day variability in mean 24-h output. There was, however, a significant time effect, and the 24-h GH secretion pattern was maintained between days. In protocol 2, 5 patients were sampled for GH every 10 min twice, once during infusion of normal saline and once during iv infusion of recombinant human IGF-I (10 microg/kg x h). The recombinant human IGF-I infusion increased plasma IGF-I to approximately 230% of the baseline concentration. This resulted in GH suppression (4220 +/- 1950 vs. 3223 +/- 1472 microg/liter.min; P = 0.001), but did not alter GH secretion pattern. There were highly significant cross-correlations for 10 of the 11 of the subjects in the two protocols when the lag was 0 min. By harmonic analysis, nocturnal augmentation of GH was maintained, and maximum daily GH occurred at approximately 2300 h. These data demonstrate that the pattern of GH secretion in acromegaly is not random, but is highly preserved with 24-h periodicity. In addition, negative feedback regulation by IGF-I is preserved, although the degree of negative feedback is grossly attenuated. Thus, secretory activity of somatotroph adenomas is not autonomous or haphazard, but is still subject to both feedback and feedforward regulatory mechanisms.
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PMID:Regulation of GH secretion in acromegaly: reproducibility of daily GH profiles and attenuated negative feedback by IGF-I. 1154 76

Acromegaly is caused by excessive secretion of growth hormone by a hypophyseal adenoma type of somatotropinoma. IGF-I is formed in the liver and mediates most biological actions of GH. Treatment of adenomas, which secrete GH, involves pharmacotherapy followed by surgery. Modern pharmacotherapy leaning is based on somatostatin analogues (factor restrictive secretion GH): octreotide, octreotide LAR and lanreotide. The aim of our study was estimation of efficiency of octreotide LAR in the patients with somatotropinoma prepared to neurosurgery intervention. We examined 16 patients (10 of women and 6 men) with the features of active acromegaly. In all cases the increased concentration of HGH and IGF-I were observed. The presence of pituitary adenoma in all patients was confirmed by MRI. The patients were treated with octreotide LAR monthly in dose 20 mg and 30 mg respectively. Before and after application of somatostatin analogues the concentration HGH, IGF-I, PRL in serum were marked. The concentration of GH before octreotide LAR therapy in all patients increased remarkable and ranged from 15.6 to 78.6 ng/ml, mean: 31.20 +/- 16.84 (norm: 0-10 ng/ml), also, in all cases the serum IGF-I level was increased and ranged from 451 to 1107.6 ng/ml, mean: 801.75 +/- 207.82 (norm: 100-400 ng/ml). The prolactin concentration ranged from 7.4 to 49.9 ng/ml, mean: 22.8 +/- 13.7 (norm: 2-20 ng/ml) and in 8 (50%) cases the increased of PRL concentration in serum was observed. After the administration of octreotide LAR the level of: GH [mean: 12.99 +/- 17.16 ng/ml (p < 0.001)], of IGF-I [mean 422.8 +/- 229 ng ml (p < 0.01)] statistical important decreased and prolactin in 8 with increased concentration [mean: 12.45 +/- 5.57 (p < 0.01)] were observed. Long acting somatostatin analogues--octreotide LAR is particular efficient in lowering of growth hormone and IGF-I in patients with somatotropinoma and shows efficiency in normalization of increased prolactin concentration. Because of extreme effectiveness of octreotide LAR, it should be used the routine treatment at the patients suffering from active acromegaly and preparing to neurosurgical treatment.
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PMID:[Estimation of efficacy of the octreotide LAR administration in the patients with somatotropinoma]. 1192 44

The activity of the GH/IGF-I axis as a function of parathyroid activity and calcium metabolism in humans has never been assessed. To address this issue, we studied 18 patients (5 men, 13 women; age range, 23-76 yr; mean, 61 yr) with primary hyperparathyroidism (PHP) due to solitary parathyroid adenoma. GH secretion was evaluated by serum IGF-I levels, spontaneous mean GH secretion over two morning hours, and GH response to arginine (ARG) alone or combined with GHRH. In five patients, serum GH concentrations were measured every 20 min for 24 h, and deconvolution analysis was performed. A group of 35 age- and sex-matched normal subjects served as controls. Mean serum IGF-I levels in PHP were lower than in normal controls, and in six PHP patients individual serum IGF-I levels were below the age-related normal range. The mean (+/-SE) peak GH response to ARG alone in PHP patients was significantly lower than in normal subjects (4.0 +/- 1.0 vs. 22.0 +/- 1.3 microg/liter; P < 0.001). Likewise, the mean (+/-SE) peak GH response to ARG plus GHRH was reduced in PHP patients (9.9 +/- 0.9 vs. 38.0 +/- 3.5 microg/liter; P < 0.001). The mean GH concentration over two morning hours in PHP was lower (0.20 +/- 0.05 vs. 1.34 +/- 0.31 microg/liter; P < 0.001). The mean GH concentration over 24 h in five PHP patients was lower than in six normal controls (0.3 +/- 0.1 vs. 0.7+/- 0.1 microg/liter; P < 0.05); the deconvolution analysis showed that 24-h GH production rate (3.0 +/- 1.7 vs. 28.2 +/- 4.7 microg/liter.d; P < 0.05) and mean secretory burst mass (1.2 +/- 0.7 vs. 10.5 +/- 2.6 microg/liter; P < 0.05), but not pulse frequency, were lower in PHP patients than in normal controls. GH half-life and approximate entropy values of 24-h GH profiles were similar in PHP patients and normal controls. No correlation was found between serum-ionized calcium or PTH levels and spontaneous or stimulated GH levels in PHP patients. In conclusion, this study demonstrates that PHP patients have a reduction in both spontaneous and stimulated GH secretion. Accordingly, PHP should be mentioned as a further example of a metabolic condition in which GH secretion in adults is reduced.
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PMID:GH secretion is impaired in patients with primary hyperparathyroidism. 1199 25

We describe a rare case of macroprolactinoma with subclinically synchronous growth hormone (GH) production. A 59-year-old man with a giant adenoma in his pituitary had elevated serum prolactin (PRL) and insulin-like growth factor (IGF)-I levels, despite normal levels of basal GH. Serum GH levels were paradoxically increased in response to an intravenous administration of thyrotropin-releasing hormone (TRH). Prolonged exposure to glucose as a result of oral glucose tolerance testing (oGTT) failed to decrease GH levels. Two-week treatment with cabergoline, a dopamine D2 receptor agonist, decreased serum PRL and GH levels, and size of the tumor. Immunohistochemistry and in situ hybridization revealed PRL-producing cells capable of synchronous GH production. Acidophilic stem cell adenoma may be responsible for these phenomena. The nature of high proliferation and invasive tumor growth should be kept in mind when managing patients with this cell type of adenoma. IGF-I levels should be followed in PRLoma, even when basal GH levels are within the normal range, because mixed PRL- and GH-producing tumors would lie underneath. Further endocrinological examinations such as TRH test and oGTT are recommended when elevated IGF-I levels are detected.
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PMID:A case of macroprolactinoma with subclinical growth hormone production. 1200 49

Several epidemiological studies have found that high levels of plasma insulin-like growth factor (IGF)-I and low levels of IGF-binding protein (IGFBP)-3 are related to an increased risk of colorectal cancer or late-stage adenomas. We examined the relation of body mass index, fasting and 2-h postload plasma glucose levels and plasma concentrations of IGF-I and IGFBP-3 to colorectal adenomas in middle-aged Japanese men. The study subjects comprised 157 cases of histologically diagnosed colorectal adenomas and 311 controls with normal colonoscopy or non-polyp benign lesions in a consecutive series of 803 men receiving a preretirement health examination at two hospitals of the Self Defense Forces (SDF). After adjustment for rank in the SDF, hospital, smoking and IGFBP-3, a statistically nonsignificant modest increase in the prevalence odds of colorectal adenomas was observed for the highest versus the lowest quartile level of IGF-I. The increase was slightly greater with further adjustment for 2-h glucose concentrations (adjusted odds ratio 1.8, 95% confidence interval 1.0-4.5, trend P=0.06). Men with high levels of IGFBP-3 showed only a minimal decrease in risk after adjustment for IGF-I. The association with IGF-I was less evident for advanced adenomas (>5 mm in size or tubulovillous/villous). Fasting and 2-h glucose and body mass index were more strongly positively associated with colorectal adenomas than IGF-I, especially with advanced adenomas, independently of IGF-I and IGFBP-3. The findings suggest that plasma IGF-I and IGFBP-3 may be involved in colorectal tumorigenesis regardless of the stage in growth of adenoma, but not as a mediator for the effects of being overweight or of hyperglycemia.
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PMID:Insulin-like growth factor (IGF)-I, IGF-binding protein-3 and colorectal adenomas in Japanese men. 1246 Apr 58

Acromegaly--do we already know everything about treatment of the somatotroph pituitary adenomas?--Acromegaly, an insidious neuroendocrine disorder, reduces life expectancy and leads to 3.5-fold increase in mortality. The main causes are cardiovascular, pulmonary and enhanced prevalence of deaths from malignancy. Successful therapy ought to normalize GH, IGF-I secretion, remove adenoma mass and its local pressure effects and preserve pituitary function to improve systemic morbidity and normalize mortality. The primary therapy for most patients with acromegaly caused by somatotroph pituitary adenoma is still transsphenoidal resection of the tumor. The results of the transsphenoidal surgery for pituitary adenoma for acromegaly depend on the volume of the tumor, its suprasellar and parasellar extension, especially to the cavernous sinus. The aim of this paper was to present the diagnostic criteria and principle therapy in these tumors. Our experience was based on the analysis of more than 150 patients operated on during the last five years and review of the literature.
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PMID:[Acromegaly--do we already know everything about treatment of the somatotroph pituitary adenomas?]. 1251 47

Stereotactic radiosurgery by gamma-knife (GK) is an attractive therapeutic option after failure of microsurgical removal in patients with pituitary adenoma. In these tumors or remnants of them, it aims to obtain the arrest of cell proliferation and hormone hypersecretion using a single precise high dose of ionizing radiation, sparing surrounding structures. The long-term efficacy and toxicity of GK in acromegaly are only partially known. Thirty acromegalic patients (14 women and 16 men) entered a prospective study of GK treatment. Most were surgical failures, whereas in 3 GK was the primary treatment. Imaging of the adenoma and target coordinates identification were obtained by high resolution magnetic resonance imaging. All patients were treated with multiple isocenters (mean, 8; range, 3-11). The 50% isodose was used in 27 patients (90%). The mean margin dose was 20 Gy (range, 15-35), and the dose to the visual pathways was always less than 8 Gy. After a median follow-up of 46 months (range, 9-96), IGF-I fell from 805 micro g/liter (median; interquartile range, 640-994) to 460 micro g/liter (interquartile range, 217-654; P = 0.0002), and normal age-matched IGF-I levels were reached in 7 patients (23%). Mean GH levels decreased from 10 micro g/liter (interquartile range, 6.4-15) to 2.9 micro g/liter (interquartile range, 2-5.3; P < 0.0001), reaching levels below 2.5 micro g/liter in 11 (37%). The rate of persistently pathological hormonal levels was still 70% at 5 yr by Kaplan-Meier analysis. The median volume was 1.43 ml (range, 0.20-3.7). Tumor shrinkage (at least 25% of basal volume) occurred after 24 months (range, 12-36) in 11 of 19 patients (58% of assessable patients). The rate of shrinkage was 79% at 4 yr. In no case was further growth observed. Only 1 patient complained of side-effects (severe headache and nausea immediately after the procedure, with full recovery in a few days with steroid therapy). Anterior pituitary failures were observed in 2 patients, who already had partial hypopituitarism, after 2 and 6 yr, respectively. No patient developed visual deficits. GK is a valid adjunctive tool in the management of acromegaly that controls GH/IGF-I hypersecretion and tumor growth, with shrinkage of adenoma and no recurrence of the disease in the considered observation period and with low acute and chronic toxicity.
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PMID:Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. 1284 50

We report the use of stereotactic radiosurgery delivered through an adapted linear accelerator [stereotactic multiple arc radiation therapy (SMART)] for pituitary adenomas not cured by conventional therapy. All 21 patients had undergone conventional radiotherapy (45-50 Gy); 18 had also undergone prior surgery. This cohort comprised 13 patients with somatotrope adenomas, four with corticotrope adenomas, one with a lactotrope adenoma, and three with nonfunctioning pituitary adenomas (median follow-up: 33 months, range: 3-72 months). SMART has proven effective, safe, and rapidly acting. We observed an accelerated reduction in GH and IGF-I levels in acromegaly, with normalization of GH and IGF-I levels in 58%. Mean GH fell from 21.1 mU/liter to 7.9 mU/liter (7 ng/ml to 2.6 ng/ml, P < 0.01, median 25 months) faster than our predicted fall to 50% at 2 yr with conventional radiotherapy. Mean IGF-I fell from 624 ng/ml to 384 ng/ml (P < 0.001). Tumor growth was controlled in two of three nonfunctioning pituitary adenomas, and three of four corticotrope adenomas. There were no adverse effects from SMART. Notably there have been no visual sequelae or further loss of anterior pituitary function in this heavily pretreated group. Our data indicate that SMART is an effective complementary therapy for pituitary adenomas that have displayed a suboptimal response to conventional therapy including external irradiation.
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PMID:Stereotactic radiosurgery XVI: a treatment for previously irradiated pituitary adenomas. 1460 70

Acromegaly is an endocrine disorder characterised by sustained hypersecretion of growth hormone (GH) with concomitant elevation of insulin-like growth factor (IGF)-I, and is associated with malignancy and premature mortality from cardiovascular and respiratory diseases. In particular, there may be an increased risk of colorectal neoplasia, but the exact extent of this is contentious. Colonoscopy-based studies of adenoma prevalence rates in acromegalic patients are misleading, but population-based studies on colorectal cancer risk are more consistent - a meta-analysis estimated a pooled risk ratio of 2.04 (95 % CI: 1.32, 3.14). Possible mechanisms underlying this increased risk include direct actions as a consequence of elevated levels of circulating GH and IGF-I and/or other perturbations within the IGF system. Other possible mechanisms include altered bile acid secretion, altered cellular immunity, hyperinsulinaemia, shared genetic susceptibility and increased bowel length. However, most explanations only offer indirect evidence, and the expectation of acromegaly as a natural model of colorectal carcinogenesis has not materialised. From a clinical perspective, it seems reasonable to consider a once-only colonoscopic screening at approximately age 55 years, but potential risks and benefits should be balanced.
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PMID:Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications. 1471 Mar 50

GH secretion is impaired in most patients with primary hyperparathyroidism (PHP), although the secretion of the other anterior pituitary hormones is unaffected. However, whether restoration of euparathyroidism is associated with reversal of GH deficiency in PHP patients is not known. To address this issue, we studied 30 consecutive patients with PHP due to a single parathyroid adenoma before and after parathyroidectomy. GH secretion was evaluated by peak serum GH after the maximal GHRH + arginine (Arg) stimulation test. A group of 35 age- and sex-matched normal subjects served as controls. Serum IGF-I concentration was below the normal age- corrected values in six of 30 patients before surgery and in four of 30 patients after parathyroidectomy (P = not significant). Mean serum peak GH values after the GHRH + Arg test were 17.5 +/- 2.8 micro g/liter before surgery and 23.8 +/- 2.5 micro g /liter after surgery (P = 0.0008). The GH response to the GHRH + Arg test was reduced in 20 (67%) and normal in 10 (33%) of 30 PHP patients at baseline; after surgery, 22 of 30 (73%) PHP patients had a normal GH response to the GHRH + Arg test, and only eight (27%) had an impaired GH secretion (P < 0.02). In conclusion, this study confirms that GH secretion is impaired in PHP patients and indicates that it is reversed in many patients after parathyroidectomy. Accordingly, GH deficiency in PHP patients must be considered a functional phenomenon for which GH therapy is not recommended.
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PMID:Improvement of growth hormone deficiency in patients with primary hyperparathyroidism after parathyroidectomy: results of a prospective study. 1500 12


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