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)

The episodicity of 24 h GH release was studied in 18 patients with active acromegaly, 12 patients 7-10 days after pituitary surgery, 14 patients long after operation (3-17 years), and 21 healthy gender- and age-matched control subjects, using a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). Blood samples were taken at 10-min intervals for 24 h, and plasma GH concentrations were measured by immunofluorometric assay (detection limit 11.5 ng/l). For this study we selected operated patients who were biochemically in remission, defined by normal circulating IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) concentrations, normal glucose-suppressed plasma GH concentration (<0.38 microg/l), and the normalization of the paradoxical rise of GH to TRH or GnRH. In patients with active acromegaly ApEn was 1.23+/-0.04, with no overlap with the control subjects (P = 1.2 x 10[-16]), who had an ApEn of 0.40+/-0.04. ApEn in patients shortly after surgery was 0.71+/-0.09 (P < 0.001 vs controls), and long after surgery 0.56+/-0.05 (P < 0.011 vs controls). ApEn values in treated and untreated patients correlated significantly with the plasma concentration of IGF-I (r=0.531) and IGFBP-3 (r=0.598), and the log-transformed 24h GH secretion rate (r=0.749). Shortly after surgery only one-third of the patients had a normal ApEn value, whereas long after surgery about 70% of the patients had a normal ApEn value. Although ApEn eventually normalized in about 70% of the operated patients, the cause of the persistence of abnormal GH release in the remainder of the subjects is not known, and might reflect permanent hypothalamic-pituitary dysfunction or a very early recurrence of the somatotroph adenoma.
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PMID:Reduced disorderliness of growth hormone release in biochemically inactive acromegaly after pituitary surgery. 957 97

Acromegaly, an indolent disorder of growth hormone (GH) hypersecretion is most typically caused by a somatotroph cell adenoma and may be treated by several modalities. Transsphenoidal surgical resection of micro-adenomas by experienced neurosurgeons results in biochemical normalization (postglucose GH <2 ng/mL, assay-dependent, age- and sex-matched IGF-I levels) in 70% of patients. However, over 65% of GH-secreting adenomas are invasive or macroadenomas, and over 50% of these patients have persistent postoperative GH hypersecretion. Irradiation of adenomas results in attenuation of GH secretion to more than 5 ng/mL in 50% of subjects after 12 yr. However, the percent of parents who normalize IGF-I levels is less certain. Most of these patients develop associated pituitary failure and rarely develop other local adverse effects. About 60% of patients receiving somatostatin analogs achieve normalized IGF-I levels. Efficacy of medical management with somatostatin analogs may be improved by increasing injection frequency, changing delivery modes to depot preparations, and in the future, development of novel SRIF receptor subtype-specific analogs. An integrated approach to acromegaly management based upon relative risks and benefits of the currently available therapeutic modes is presented that allows for a national individualized strategy designed to achieve maximal biochemical control of GH hypersecretion and elevated IGF-I levels.
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PMID:Current treatment guidelines for acromegaly. 970 26

Eleven adult males, previously submitted to neurosurgery because of a pituitary lesion (three with craniopharyngioma, three with clinically non-functioning adenoma and five with macroprolactinoma) were treated with recombinant GH for 12 months after the diagnosis of GH deficiency was made. Circulating FSH, LH, prolactin, testosterone, 17 beta-estradiol (E2), dehyroepiandrosterone (DHEA-S), androstenedione. 17-OH-progesterone (17OHP), IFG-I, and steroid hormone-binding protein (SHBG) levels were assayed before and after CG test at study entry and 6 and 12 months after GH treatment. A significant increase in plasma IGF-I levels was obtained after 6 and 12 months of GH treatment. In addition, CG-stimulated, but not baseline, testosterone levels showed a significant increase after 6 and 12 months of GH treatment when compared with study entry (9.6 +/- 0.5 and 9.9 +/- 0.5 vs 7.9 +/- 0.5 ng/ml; P < 0.05). Baseline, but not CG-stimulated, serum 17OHP levels were significantly increased only after 12 months of GH treatment (1.7 +/- 0.1 vs 1.4 +/- 0.1 ng/ml; P < 0.05). No significant difference was found as far as both basal and CG-stimulated E2, androstenedione, DHEA-S and SHBG were concerned. With regards to the semen analysis, only seminal plasma volume was significantly increased after 12 months of GH treatment (2.9 +/- 0.3 vs 1.7 +/- 0.3 ml; P < 0.05). No significant change in sperm count, motility and abnormal forms was observed. These data show that GH treatment displays a clear-cut effect upon Leydig cell function and increases the production of seminal plasma volume in fertile adult males with isolated GH deficiency.
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PMID:The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency. 1021 17

A 43-year-old woman was admitted to our hospital for further treatment of acromegaly with high plasma GH and IGF-I levels after transsphenoidal adenomectomy and subsequent treatment with bromocriptine. Physical examination and magnetic resonance imaging (MRI) showed an active acromegalic appearance with residual pituitary macroadenoma. Laboratory findings revealed an increase in basal levels of plasma GH (21.3 microg/L) and plasma IGF-I (470 ng/ml). Plasma GH levels were suppressed from 21.3 microg/L to 9.9 microg/L following oral administration of 75 glucose and did not respond to either TRH or LHRH injection. When plasma GH levels were measured after repeated blood sampling every 20 min for 24 h and sleep stages were analyzed, there were three GH peaks during the night which corresponded to the slow-wave sleep. Mean plasma GH levels which corresponded to the slow-wave sleep stages were much greater than those of other sleep stages during the night. After the patient was treated with intermittent sc injections of octreotide (40 microg/every 2 h, 480 microg/day) in combination with oral administration of bromocriptine (15 mg/day, t.i.d.), episodic GH release was somewhat suppressed but plasma GH levels were slightly increased, corresponding to the slow-wave sleep stage during the night. Mean plasma GH levels were much higher during the sleeping period than the waking period for 24 h before and after the treatment. These findings suggest that GH secretion is correlated to the slow-wave sleep in this particular patient with pituitary GH producing adenoma.
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PMID:An acromegalic patient with pulsatile secretion of growth hormone (GH) coincident with the slow-wave sleep. 1039 50

To elucidate the contribution of growth factors to the development, growth and behavior of human pituitary adenomas, the authors used competitive reverse transcription-polymerase chain reactions to quantify expression of mRNAs for growth factors extracted from pituitary adenomas. As previously diagnosed by endocrinologic evaluation, the pituitary adenomas in this study consisted of six prolactin-producing, six growth hormone (GH)-producing, four follicle-stimulating hormone producing and six nonfunctioning adenomas. The mRNAs examined included those for platelet-derived growth factor (PDGF) B-chain, transforming growth factor (TGF)-beta1, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF)-I and -II; proliferating cell nuclear antigen (PCNA) as an indicator of cell proliferation; and pituitary-specific transcription factor-1 (Pit-1) which is a nuclear transcription factor expressed in the anterior pituitary. All factors except the last were expressed in all adenomas, and expression of PDGF B-chain, TGF-beta1, EGF, bFGF and IGF-II did not differ between the four adenoma varieties. Pit-1 was expressed only in GH- and prolactin-producing adenomas. PCNA expression also showed no differences. However, IGF-I mRNA in GH-producing adenomas was significantly lower than in prolactin-producing and nonfunctioning adenomas despite high serum IGF-I levels (1121+/-253 ng/ml). The analysis on IGF-I receptor mRNA was significantly lowered in GH-producing adenoma compared with the other types of adenoma. These findings suggest that the attenuation of negative feedback through the pituitary GH-IGF-I axis may be involved in development of GH-producing adenoma.
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PMID:Quantitative analysis of growth-related factors in human pituitary adenomas. Lowered insulin-like growth factor-I and its receptor mRNA in growth hormone-producing adenomas. 1049 42

Insulin-like growth factor (IGF)-I is an important mitogen required by some cell types to progress from the G1 phase to the S phase of the cell cycle. IGF binding proteins (IGFBPs) can have opposing actions, in part by binding IGF-I, but also by direct inhibitory effects on target cells. As mitogens and anti-apoptotic agents, IGFs may be important in carcinogenesis, possibly by increasing the risk of cellular transformation by enhancing cell turnover. Indeed, many types of neoplastic cells express or overexpress IGF-I receptors, which stimulate mitogenesis when activated by IGF-I in vitro. In vivo, tissue IGF bioactivity is determined not only by circulating IGF-I and IGFBP levels, but also by local production of IGFs, IGFBPs, and possibly IGFBP proteases that enhance IGF-I availability by cleaving IGFBPs. Because determinants of tissue IGF bioactivity appear to be regulated in parallel with circulating IGF-I level, it is reasonable to hypothesize that the substantial intraindividual variability in circulating levels of IGF-I and IGFBP-3 may be important in determining risk of some cancers. In recent epidemiologic studies, relatively high plasma IGF-I and low IGFBP-3 levels have been independently associated with greater risk of prostate cancer in men, breast cancer among premenopausal women, and colorectal adenoma and cancer in men and women and possibly lung cancer. These include prospective data from the Physicians' Health Study and the Nurses' Health Study. In general, two- to fourfold elevated risks have been observed for prostate cancer in men in the top quartile of IGF-I relative to those in the bottom quartile, and low levels of IGFBP-3 were associated with an approximate doubling of risk. For breast cancer, an association with IGF-I for postmenopausal women was not apparent, but strong associations were observed for premenopausal cases in the Nurses' Health Study. Further study is needed to confirm this subgroup finding in women. Recent data also indicate that high IGF-I and low IGFBP-3 increase risk of colorectal cancer and large or villous adenomas. Of note, for colorectal neoplasia, fourfold elevated risks were observed in men and women with low IGFBP-3, whereas high IGF-I was associated with a doubling of risk. These emerging epidemiologic data indicate that high levels of IGF-I and low levels of IGFBP-3 are associated with an increased risk of at least several types of carcinoma that are common in economically developed countries. Further study is required to determine the clinical relevance of these findings.
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PMID:Insulin-like growth factor-I and binding protein-3 and risk of cancer. 1059 42

Spontaneous and stimulated GH secretion is blunted in hypercortisolemic states due to increased hypothalamic somatostatinergic tone. However, no data are available on the characteristics of GH secretion in patients with incidentally discovered adrenal adenomas. They represent an interesting model for studying GH secretion, as a slight degree of cortisol excess may frequently be observed in such patients who do not present with any clear Cushingoid sign. In the present study, 10 patients (3 men and 7 women, aged 48-63 yr) with an adrenal mass discovered serendipitously underwent, on separate occasions, a GHRH injection alone or combined with an infusion of the functional somatostatin antagonist, arginine. Thirteen age-matched healthy volunteers served as controls. Briefly, arginine (30 g) was infused from -30 to 0 min, and GHRH (100 microg) was injected as a bolus at 0 min, with measurement of serum GH [immunoradiometric assay (IRMA)] every 15 min for 150 min. Plasma IGF-I (RIA after acid-ethanol extraction) was measured in a morning sample. The diagnosis of cortical adenoma was based on computed tomography features and pattern of uptake on adrenal scintigraphy. Patients with obesity and/or diabetes were excluded. The study design included also an endocrine work-up aimed to study the hypothalamic-pituitary-adrenal axis [urinary free cortisol (UFC) excretion, serum cortisol at 0800 h, plasma ACTH at 0800 h, morning cortisol after overnight 1 mg dexamethasone]. Five of 10 patients showed abnormalities of the hypothalamic-pituitary-adrenal axis, including borderline or increased UFC excretion in 4 of them accompanied by blunted ACTH in 2 cases and failure of cortisol to suppress after dexamethasone in 1; the fifth patient displayed low ACTH and resistance to dexamethasone suppression. However, all patients had a unilateral uptake of the tracer on the side of the mass with suppression of the contralateral normal adrenal gland. As a group, the patients displayed greater UFC excretion and lower ACTH concentrations than the controls. GH release after GHRH treatment was blunted in patients bearing adrenal incidentaloma compared with controls (GH peak, 5.7 +/- 5.2 vs. 18.0 +/- 7.0 microg/L; P < 0.0001), whereas GHRH plus arginine was able to elicit a comparable response in the 2 groups (GH peak, 33.5 +/- 20.3 vs. 33.7 +/- 17.5 microg/L; P = NS). The ratio between GH peaks after GHRH plus arginine and after GHRH plus saline was significantly greater in patients than in controls (751 +/- 531% vs. 81 +/- 45%; P = 0.0001). Similar data were obtained when comparing GH area under the curve after GHRH plus saline or GHRH plus arginine between the 2 groups. In summary, the present data suggest that in patients with incidental adrenal adenomas the GH response to GHRH is blunted due to increased somatostatinergic tone, as it can be restored to normal by pretreatment with the functional somatostatin antagonist arginine. The blunted GH release to GHRH may be an early and long lasting sign of autonomous cortisol secretion by the adrenal adenoma.
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PMID:Growth hormone (GH) responses to GH-releasing hormone alone or combined with arginine in patients with adrenal incidentaloma: evidence for enhanced somatostatinergic tone. 1072 81

Active acromegaly is almost always the result of a benign growth hormone (GH)-secreting adenoma of the pituitary gland. Because the same pituitary stem cell can produce both GH and prolactin (PRL), many acromegalic patients also have hyperprolactinemia. The advantages of surgical excision of pituitary adenomas associated with acromegaly include: (1) prompt decrease in GH; (2) reliable and immediate relief of the mass effect from the tumor (decompression of the optic nerves and chiasm), and (3) the opportunity to obtain tumor tissue for characterization and investigative study. Currently, more than 97% of operations for removal of pituitary tumors associated with acromegaly are done using the transsphenoidal approach rather than craniotomy. Technical advances to make the surgery safer continue to evolve, and include endoscopic approaches, computer-guided image-based intraoperative visualization, and intraoperative magnetic resonance imaging. Criteria for satisfactory remission of acromegaly after surgery are the same as those used for medical management. They include normal insulin-like growth factor (IGF)-I and suppression of GH to undetectable levels (<1.0 ng/ml) during an oral glucose tolerance test (OGTT). Data from a recent series of 86 patients operated upon for acromegaly at the University of Virginia and followed for more than 1 year have been reviewed. In patients receiving surgery as the initial procedure, 67% had a normal IGF-I, and 52% suppressed to <1.0 ng/ml in an OGTT. There was one true recurrence of disease diagnosed 81 months after surgery. Results are best in patients with noninvasive microadenomas. Gamma knife radiosurgery has been a valuable adjunct in those patients who fail to achieve postoperative remission. Pathological evaluation of the tumors revealed that 16% expressed GH only, 25% stained for GH and glycoprotein hormones (follicle stimulating hormone, thyroid hormone, thyroid stimulating hormone, alpha-subunit), 21% for GH and PRL, and 33% for GH, PRL and glycoprotein hormones. There was one acidophil stem cell tumor and 10% had the mammosomatotroph subtype. This contemporary series was free of mortality or serious complications. One patient had a transient cerebrospinal fluid leak and 3 developed transient SIADH with hyponatremia. Surgical treatment remains an important aspect of the combined management of patients with acromegaly.
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PMID:Pituitary surgery for the management of acromegaly. 1097 Nov 9

Excessive GHRH stimulation leads to somatotrope hyperplasia and, ultimately, pituitary adenoma formation in the metallothionein promoter-driven human GHRH (hGHRH) transgenic mouse. This pituitary phenotype is similar to that observed in humans with ectopic production of GHRH. In both mice and man, GHRH hyperstimulation also results in dramatic increases in circulating GH and IGF-I. To determine whether GH/IGF-I modulates the development and growth rate of GHRH-induced pituitary tumors, pituitary growth and histology were evaluated in mice generated from cross-breeding metallothionein promoter-driven hGHRH transgenic mice with GH receptor binding protein (GHR) gene disrupted mice (GHR(-/-)). Expression of the hGHRH transgene in 2-month-old GHR intact (GHR(+)) mice resulted in the doubling of pituitary weight that was largely attributed to an increase in the number of GH-immunopositive cells. Pituitary weight of GHR(+) hGHRH mice did not significantly change between 2 and 6 months of age, whereas at 12 months, weights increased up to 100-fold those of GHR(+) pituitaries, and 70% of the glands contained grossly visible adenomas. All adenomas stained positively for GH, whereas some showed scattered PRL staining. Pituitaries of GHR(-/-) mice were half the size of those of GHR(+) mice. Although reduced in size, the histological features of GHR(-/-) mouse pituitaries were suggestive of somatotrope hyperplasia. Despite evidence of somatotrope hyperplasia, pituitaries from GHR(-/-) mice as old as 28 months of age were similar in size to those of 2-month-old mice and did not show signs of adenoma formation. Expression of the hGHRH transgene in GHR(-/-) mice did not significantly increase pituitary size between 2 and 6 months of age. However, at 12 months the majority of GHR(-/-), hGHRH pituitaries developed adenomas with mean pituitary weight and histological features similar to those of GHR(+), hGHRH mice. These observations demonstrate that intact GH signaling is not required for GHRH tumor formation. Although the majority of GHR(+), hGHRH and GHR(-/-), hGHRH pituitaries developed tumors by 12 months of age, a small subset remained morphologically indistinct from those at 2 months of age. These observations taken together with the fact that overt tumor formation is preceded by a static pituitary growth phase between 2 and 6 months, indicates that protective mechanisms are in place to maintain pituitary mass despite hGHRH hyperstimulation.
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PMID:The effect of GHRH on somatotrope hyperplasia and tumor formation in the presence and absence of GH signaling. 1151 52

The results of transsphenoidal surgery as initial therapy for GH-secreting pituitary adenomas in 57 acromegalic patients were analyzed retrospectively. Patients with prior surgery or radiation therapy were excluded from the study. Three different criteria were used to define remission: glucose-suppressed (nadir) GH less than 1.0 microg/liter, a normal sex- and age-adjusted IGF-I level, and postoperative random GH levels of 2.5 microg/liter or less. Additionally, we analyzed the neuropathological data, including immunohistochemistry and ultrastructural categorization, and the surgical complications. The short-term remission rate (6-wk postoperative follow-up visit), as determined by a random GH measurement of 2.5 microg/liter or less, was 48.8%; the remission rate, as determined by nadir GH, was 51.4%. For 57 patients followed for 12 months or more after surgery (mean, 37.7 months), surgical remission was achieved in 70.2%, 66.7%, and 61.1%, respectively, for patients assessed by normal IGF-I, random GH, and nadir GH. One patient (1.1%) developed recurrence of active acromegaly 81 months after initially successful surgical therapy. Extrasellar growth of the tumor (P = 0.04) and dural invasion by the adenoma (P = 0.008) were significant univariate predictors of a poor outcome. Tumor size was significantly greater in patients with persistent or recurrent acromegaly (P = 0.02). Patients with tumors of the ultrastructural categories of mixed GH/PRL cell and mammosomatotroph adenomas had the lowest remission rates (50% and 42.9%, respectively). There were no perioperative deaths, and there was no serious morbidity. The permanent complication rate was 3.3% (1 permanent DI and 2 nasal septal perforations). Surgical management of acromegaly currently provides prompt, effective, and satisfactory initial treatment for the majority of patients. Using stringent criteria for remission, primary transsphenoidal surgery for GH-secreting pituitary adenomas is effective and often definitive therapy for acromegaly. These results provide a benchmark for the contemporary results of surgical management as assessed by modern outcome criteria.
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PMID:Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria. 1154 28


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