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)

We experienced a 41-year-old acromegalic male (Case 1) in whom the basal plasma GH was extremely high (320-450 ng/mL) but plasma IGF-I was only slightly elevated (2.0-2.8 U/mL). His nutritional condition and associated diabetes mellitus did not appear to be responsible for the relatively low IGF-I level, and a GH-autoantibody in the plasma was absent. We thus performed gel filtration analyses of his plasma and somatotroph adenoma to determine elution patterns of immunoreactive (IR) and receptor active (RA) GH. For comparison, the same studies were carried out on plasmas and somatotroph adenomas obtained from three other acromegalics (Cases 2-4) whose basal plasma GH and IGF-I levels were 22-45 ng/mL and 3.5-6.0 U/mL, respectively. IR GH in Case 1's plasma distributed over an extremely wide range keeping similar titers rather than showing three discernible components (big-big, big, and little GH) as did plasmas and adenomas from Cases 2-4. And, most of the IR GH in Case 1's plasma was eluted in such fractions that contained low levels of RA GH, indicating a minor proportion of biologically active GH. However, interestingly, the chromatographic profile and total GH content of Case 1's adenoma were similar to those of Cases 2-4's adenomas. These results may, at least in part, explain the discrepancy between the plasma GH and IGF-I levels of Case 1. The unexpectedly different GH elution patterns between the plasma and adenoma from this patient, may suggest a contribution of certain plasma factor(s) to the unusual chromatographic profile of plasma GH.
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PMID:A marked molecular heterogeneity of growth hormone (GH) detected in the plasma but not pituitary of a patient with acromegaly: comparison with other acromegalics and an implication for discrepant plasma levels of GH and insulin-like growth factor. 150 22

Insulin-like growth factor (IGF)-II receptors were demonstrated in normal and neoplastic tissues of human thyroid. Specific binding of [125I]IGF-II to thyroid membranes was dependent on the time and temperature of incubation, and a steady state was achieved after 22 h of incubation at 4 degrees C. The binding of [125I]IGF-II was dose-dependently displaced by unlabelled IGF-II with 50% inhibition at an IGF-II concentration of 6 ng/ml. IGF-I had a relative potency of 1% compared to IGF-II, and insulin showed no inhibition at concentrations as high as 2000 ng/ml. Scatchard analysis of the binding data revealed a single class of IGF-II receptor with high affinity. Affinity crosslinking and autoradiography demonstrated the type II IGF receptors. Specific binding of [125I]IGF-II to thyroid papillary cancer tissues (mean [S.D.]13.2[1.3]% per 200 micrograms protein, n = 8) was significantly (P less than 0.01) higher than that to the surrounding normal tissues (4.8 [0.5]%). The binding in follicular cancer and follicular adenoma was also significantly higher than that in the corresponding normal tissues. The higher IGF-II binding to neoplastic tissues was due to an increase in the number of binding sites without any change of affinity. These results suggest that the increased IGF-II receptors may be involved in growth or functions of thyroid neoplasms.
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PMID:Insulin-like growth factor-II (IGF-II)/Mannose-6-phosphate receptors are increased in primary human thyroid neoplasms. 164 43

Some patients with active acromegaly have elevated plasma IGF-I concentrations with only minimal elevation of plasma GH. We compared adenomatous GH and SRIH expression in 3 such patients (patients No. 1, 2 and 3; basal plasma GH level less than 4 micrograms/l) and in 3 acromegalic patients with high basal plasma GH level (patients No. 4, 5 and 6; 51.7 +/- 16.1 micrograms/l, mean +/- SEM). By immunocytochemistry, all the tumours proved to be somatotropic adenomas. At the ultrastructural level, signs of low secretory activity were observed in adenomas from patients No. 2 and 3. Perifused adenoma cells of patients No. 1, 2 and 3 released very little GH compared with those of patients No. 4, 5 and 6 (1 +/- 0.37 vs 51.5 +/- 34.1 micrograms x (10(-6) cells) x min-1, p less than 0.001). Adenoma SRIH content was 65.7 and 30.6 pg/mg proteins in patients No. 1 and 2, whereas it was undetectable in the others (patients No. 4, 5 and 6). Northern blot analysis showed that the GH gene was poorly expressed in the adenomas from patients No. 1, 2 and 3 compared with the adenomas from patients No. 4, 5 and 6. SRIH mRNA was detected in all 6 adenomas. However, the signal was more intense in the adenomas from patients No. 1, 2 and 3 than in those from patients No. 4, 5 and 6.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone and somatostatin gene expression in pituitary adenomas with active acromegaly and minimal plasma growth hormone elevation. 169 8

Normal growth and secretion in the pituitary gland are dependent upon the co-ordinated action of a large number of extracellular growth factors, neuropeptides and peripheral hormones acting on their respective cellular receptors and via complex intracellular signalling pathways. The pituitary and hypothalamus are exposed to a large number of growth factors, several of which have well-documented effects on secretory function and may act as physiological modulators of pituitary hormone synthesis and release. IGF-I, for example, almost certainly acts as a feedback regulator of GH secretion. Despite well-documented mitogenic effects in other tissues, little is known about the role of these growth factors in normal pituitary cell turnover, compensatory hyperplasia or adenoma formation. There is now good evidence, however, that at least some of the hypothalamic releasing peptides are mitogenic for their respective pituitary cell subpopulations. The aetiology of pituitary tumours remains poorly understood but some appear to develop as a result of somatic mutation. Such mutations could enhance growth by causing altered expression of growth factors or their receptors, or constitutive activation of proteins involved in the intracellular mitogenic signal. Abnormalities have been documented at each of these levels in human pituitary tumours. The identification of an activating point mutation in the alpha subunit of Gs, the stimulatory regulatory peptide of adenylyl cyclase, in a proportion of somatotroph adenomas represents a major advance in our understanding of pituitary tumour pathogenesis. This and other findings may ultimately lead to new therapeutic approaches to the management of pituitary disease.
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PMID:Growth factors and the anterior pituitary. 175 13

We describe here 9 patients with somatotroph adenomas associated with mild features of acromegaly and basal plasma GH levels in the normal range. In 5 women and 4 men, 26 to 61 yrs old, the diagnosis of prolactinoma or non-secreting pituitary adenoma had been previously made on the basis of amenorrhea-galactorrhea or tumoral symptoms. However, they had discrete signs of coarsening of the facial features and moderate but evolutive changes of hand and foot sizes. Basal GH levels were in the normal range (0.4 to 4.5 micrograms/l, N less than 5 micrograms/l) but unaffected by oral glucose and insulin tolerance tests while IGF-I concentrations were elevated in all the cases (range 1.7 to 5.8 U/ml, N: 0.37-1.41 U/ml). Plasma PRL concentrations were elevated in 5 patients (range 16 to 80 micrograms/l, N less than 13 micrograms/l in men and N less than 19 micrograms/l in women). The 9 patients had a macroadenoma with an extrasellar extension in 8 of them and all were operated on by the transsphenoidal route. Immunocytochemical studies demonstrated IRGH-cells in all the adenomas and IRPRL-cells in 5 of them. Electron microscopic analysis of 3 tumors showed that the secretory granules were sparse and the Golgi apparatus poorly developed. Molecular biology of 7 tumors showed the presence of small amounts of GH mRNA. This result was in agreement with the morphological aspect, suggesting a low rate of GH synthesis. Thanks to these different approaches the diagnosis of silent somatotroph adenoma should sometimes be reconsidered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apparently silent somatotroph adenomas. 179 91

The presence of IGF-I receptors was demonstrated in normal and neoplastic tissues of human thyroid. Binding of (125I)IGF-I to thyroid membranes was dependent on time and temperature of incubation, and maximal binding was achieved at 4 degree C and 18 h of incubation. (125I)IGI-I binding was dose-dependently displaced by unlabelled IGF-I; half-maximal inhibition occurred at concentrations of 10-20 milligrams. IGF-II and insulin had relative potencies of 5 and 1% compared with IGF-I. Scatchard analysis of binding data revealed a single class of IGF-I receptors with high affinity (Ka: 1.2-8.6 x 10(9) 1/mol) in normal thyroid tissues. Affinity cross-linking and autoradiography demonstrated the type IIGF receptors. Specific binding of (125I)IGF-1 in thyroid cancer tissues (9.69 +/- 2.07% per 200 micrograms protein; mean +/- SEM, N = 8) was significantly (p less than 0.05) higher than that in the surrounding normal tissues (3.03 +/- 0.35%, N = 8). In contrast there was no difference in the binding between adenoma tissues (4.19 +/- 0.53%, N = 5) and the adjacent normal tissues (2.94 +/- 0.24%, N = 5). The higher IGF-I binding in cancer tissues was due to an increase in the binding capacity without any change in the affinity. The presence of IGF-I receptors suggests a possible role of IGF-I and its receptors in the growth of thyroid cancer cells.
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PMID:Expression of insulin-like growth factor receptors in primary human thyroid neoplasms. 254 61

The effects of a chronic treatment with octreotide were evaluated in 19 patients affected with functionless pituitary adenomas. Octreotide caused a significant decrease of GH and IGF-I levels in all the patients and no significant change in thyroid, adrenal and gonadal function. In contrast, during the therapy, the glucose response to an oral glucose tolerance test considerably increased and was delayed, while the insulin response decreased and was delayed. Serum alpha-subunit (alpha-SU) was above normal in 10 of 16 patients in which this evaluation was performed: octreotide caused a significant decrease (p < 0.01) of alpha-SU levels in 6 of these 10 patients. Octreotide did not induce any significant change in visual fields except in 1 patient, who had a great improvement of visual perimetry and a decrease of alpha-SU levels but unmodified CT scan features. In our series of patients, octreotide was ineffective in reducing tumor mass. The efficacy of octreotide might rely on the presence of somatostatin receptors on adenoma-cell membranes. Therefore patients with functionless adenomas to be treated with octreotide might be identified with pituitary scintiscan using the recently available labeled 111In-octreotide.
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PMID:Effects of a chronic treatment with octreotide in patients with functionless pituitary adenomas. 750 80

Nineteen acromegalic patients (12 females and 7 males, aged 24-71 yr) were studied for 1-6 yr after radiotherapy (RT), administered by X-rays (18 MeV) by linear accelerator, with parallel opposite beams (doses 45-50.4 Gy, 1.8 Gy daily). Basal GH levels gradually decreased from 6.3-76.2 micrograms/L (mean +/- SE, 27.8 +/- 4.9) to 0.3-43.4 micrograms/L (11.7 +/- 3.6 micrograms/L; p < 0.005) at the last assessment. The earliest significant decrease was observed after one yr (14.9 +/- 3.8 micrograms/L; p < 0.005). Significant changes were observed also in IGF-I values (basal values 1.93-6.85 mU/ml, 3.22 +/- 0.30; last assessment 0.55-4.57 mU/mL, 1.58 +/- 0.31; p < 0.01). The earliest significant decrease of IGF-I values was observed after 2 yr (1.61 +/- 0.16 mU/ml; p < 0.005). GH levels < 5 micrograms/L together with normal IGF-I values were observed in 9 patients, 2-4 yr after RT. No changes were observed in PRL values, either in patients with pretreatment normal or elevated PRL levels. The CT and/or MRI picture of macroadenoma disappeared after 6-12 months in 3/12 patients. Moreover, a reduction (20-55%) in the diameter of the adenoma was shown after 6-36 months in other 4 patients. After RT 5/16 (31%) patients required cortisol and 4/19 (21%) thyroid replacement therapy. In 2/3 men a gonadal impairment was shown, that did not occur in the three female patients with normal gonadal function before RT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal and radiological effects of megavoltage radiotherapy in patients with growth hormone-secreting pituitary adenoma. 825 43

GH and IGF-I levels are elevated in patients with acromegaly. At the time of diagnosis patients present with macroadenomas with a high surgical failure rate or microadenomas. Administration of octreotide (100 micrograms, three times daily) suppressed GH secretion during 8 h to < 5 micrograms/l in 47% and to < 2 micrograms/l in 26% of acromegalic patients after two weeks. IGF-I levels were normalized in up to 70% of patients. Increasing the dose of octreotide to 250 micrograms three times daily did not further improve results. Tumour shrinkage occurred in 37% after six months of treatment, while symptoms improved in 70%. Transient diarrhoea and nausea were noted in 88%, but after six months only 10% reported these symptoms. Gallbladder sludge and gallstones were noted in 19% of patients. IGF-I levels were normalized in 82% of patients with microadenoma and in 50% with macroadenoma. Well-defined pituitary adenomas are usually surgically removed. Invasive tumours are difficult to remove surgically but preoperative octreotide may shrink adenomas and improve response. Octreotide therapy, unlike surgery and irradiation, does not compromise pituitary function. This study suggests that octreotide therapy could be a viable primary management of small discreet adenomas. Where surgery and octreotide fail, other treatments of adenoma include bromocriptine and radiotherapy.
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PMID:Medical management of acromegaly--what and when? 837 5

The value of somatostatin receptor scintigraphy (SRS) to predict the effect of somatostatin analog therapy on pituitary adenomas is not clear, due to the use of different radiopharmaceuticals (123I-Tyr3-octreotide and 111In-pentetreotide) and the small number of patients in previous studies. We used 111In-pentetreotide scintigraphy in 49 patients in order to (i) correlate SRS results with basal tumor volume as well as volume- and hormone-response to 3 months of octreotide therapy (Oct-Tx). (ii) identify tumor remnants after incomplete surgery and (iii) evaluate any correlation with immuno histology. Twenty-five patients had a GH-secreting adenoma (GH-A, 15 prior to intended surgery, 10 with persistent/recurrent disease after previous therapy). Twenty-four patients had a clinically non-functioning adenoma (NF-A). For SRS, planar and single photon emission computer tomographic images (SPECT) were recorded 4 h and 24 h post injection. SRS grading was as follows: GO, no uptake: G1, uptake comparable to normal pituitary; G2, increased uptake: G3, very intense uptake. G2/3 was seen in 8/25 GH-A and in 12/24 NF-A. Pretreatment tumor volume (magnetic resonance imaging (MRI) tended to be related to 111In-pentetreotide uptake in GH-A with a tumor visible on MRI (G0/1 (n = 10) vs G2/3 (n = 8): 3.6 +/- 1.9 vs 10.5 +/- 6.5 cm3 (mean +/- S.E.), P = 0.051), but not in NF-A (G0/1 (n = 12) vs G2/3 (n = 12): 17.0 +/- 10.1 vs 14.3 +/- 3.6 cm3). SRS did not identify a tumor remnant in the 7 MRI-negative patients with persistent post-operative acromegaly. Basal GH (6-h profile) and IGF-1 in GH-A did not correlate with SRS results (G0/1 (n = 17) vs G2/3 (n = 8), GH: 32.3 +/- 18.2 vs 29.3 +/- 7.4 micrograms/l IGF-I: 851 +/- 80 vs 1038 +/- 153 micrograms/l). During Oct-Tx of GH-A neither tumor shrinkage nor GH suppression was related to SRS results. In 6 NF-A classified as gonadotropinomas (by their plasma glycoprotein hormone or alpha-subunit concentrations, basally and/or in response to TRH) 111In-pentetreotide uptake was not different from that of the non-gonadotropin/non-secreting adenomas. SRS results were not related to the immunohistological subtype in 22 GH-A (monohormonal mixed somatotrope/lactotrope, plurihormonal) or in 22 NF-A (null-cell adenomas, gonadotropinomas silent hormonal adenomas). We conclude that 111In-pentetreotide SRS reflects tumor volume poorly in GH-A and not at all in NF-A. It does not predict the effect of Oct-Tx on the volume of both GH-A and NF-A, nor on the GH concentration in GH-A. 111In-pentetreotide SRS is unable to identify post-operative tumor remnants not visible on MRI.
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PMID:Results of somatostatin receptor scintigraphy do not predict pituitary tumor volume- and hormone-response to ocreotide therapy and do not correlate with tumor histology. 915 Jun 92


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