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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-nine patients with acromegaly (8 untreated and 21 previously treated in various ways) and 16 normal men were given iv bolus doses of human pancreatic tumor GH-releasing factor (hpGRF-40). Twenty-five of the 29 patients responded to hpGRF-40 with elevations of plasma GH. The magnitude of the responses varied widely. Responses of untreated patients were generally similar to those of the normal subjects. Previously treated patients had a significantly lower response than normal individuals [change in GH, 7.5 +/- 1.8 vs. 42.0 +/- 11.0 ng/ml (mean +/- SEM); P less than 0.01], and 4 patients who had received radiation therapy failed to respond to hpGRF-40. There was no significant correlation between the magnitude of the response and patients' age, sex, baseline GH levels, GH responsiveness of TRH, or GH suppression after oral glucose administration. Patients studied both pre- and postoperatively were responsive to hpGRF-40 at all times tested, but the magnitude of the response decreased after successful surgical removal of the adenoma. Thus, most patients with treated or untreated acromegaly respond to hpGRF-40, but their responses do not clearly distinguish them from normal subjects. GH-releasing hormone testing is unlikely to replace other endocrine tests available for the diagnosis and evaluation of acromegaly.
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PMID:Effects of growth hormone-releasing factor on growth hormone secretion in acromegaly. 391 54

This study reports the clinical and biological follow-up 5-11 yr after transsphenoidal selective adenomectomy in 25 patients with acromegaly. Eight patients had microadenomas, and 17 had macroadenomas. Initial normalization of plasma GH levels (basal values, less than 5 ng/ml; glucose-suppressed concentrations, less than 2.5 ng/ml) was achieved in all 8 patients with microadenomas and in 13 patients with macroadenomas. Of these, 3 patients with normal GH levels and dynamics had relapse of GH hypersecretion after intervals between 1-6 yr after microadenoma removal. Recurrence of pituitary adenoma was documented by surgery in 1 patient and by computed tomographic scanning in 2 others. Normal basal and glucose-suppressed plasma GH concentrations were maintained 7.4 +/- 0.5 (+/- SEM) yr after adenomectomy in 7 patients with microadenomas and in all 10 patients with macroadenomas. Thus, 88% of the patients with microadenomas and 59% of the patients with macroadenomas were cured, and the overall cure rate was 68%. We conclude that recurrence of acromegaly after successful surgery may occur late after adenoma removal and that it cannot be predicted by normal postoperative GH levels and dynamics. However, in view of the overall cure rate, transsphenoidal adenomectomy remains a most valuable treatment for acromegaly.
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PMID:Acromegaly: biochemical assessment of cure after long term follow-up of transsphenoidal selective adenomectomy. 405 86

A rapid and relatively simple method for measurement of inorganic pyrophosphate (PPi) in biological samples has been described. The mean +/-SEM of plasma samples from 94 normal subjects was 1.8+/-0.06 muM, giving a normal range (99% confidence limits) of 0.16 - 3.40 mumol/liter. Analysis of 17 plasma samples in duplicate showed a standard deviation of 0.18, giving a 99% probability that a single determination of plasma PPi would be +/-0.68 muM of the true value. The mean PPi levels in plasma from subjects with osteoarthritis, pseudogout, acromegaly, and uremia were significantly greater than the normal mean (P < 0.01). Samples from rheumatoid arthritis showed PPi levels distributed about a mean identical to the normal mean. Plasma inorganic orthophosphate levels correlated positively with PPi levels in samples from normal subjects and in samples from patients with osteoarthritis, pseudogout, and uremia, but not with acromegaly. This correlation was statistically significant only in the normal samples and in those from patients with osteoarthritis.
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PMID:Measurement of inorganic pyrophosphate in biological fluids. Elevated levels in some patients with osteoarthritis, pseudogout, acromegaly, and uremia. 435 76

The first half of this manuscript is devoted to a review of the methods used and the results obtained in the published measurements of the normal responses to tests of the three main types of hypothalamic-pituitary-adrenocortical (HPA) activity in man. These are, I, basal, unstressed activity leading to appropriate levels of total daily production of cortisol in the characteristic circadian pattern; II, responses to feedback stimulation of HPA activity by metyrapone administration; and III, responses to tests of the effects of stress on the HPA system including the effects of hypoglycemia, induced fever, vasopressin administration, and ACTH injections and infusions. The advantages and shortcomings of each type of procedure are discussed. The second half of this paper describes the authors' attempts to establish the limits of normality of standard and modified methods of evaluating the HPA system. The defined limits of normality have been used to assess the HPA function in 158 patients with known or suspected disorders of the HPA system. In normal controls, halfhourly plasma cortisol determinations established the normality of circadian and postprandial fluctuations and of mean plasma cortisol concentration, 6.2 +/- 0.3 (SEM) micrograms/dl, which were closely approximated by determinations every 6 h. Metyrapone, given in a dose of 500 mg every 2 h for 24 h increased urinary 17-OHCS excretion to 10.5-32.6 mg/day or to 1.7-7.8 times basal excretion rate. Increasing rates of insulin infusion disclosed significant relationships between resulting plasma glucose and cortisol concentrations. The slopes of the delta cortisol/delta glucose responses were similar after insulin infusions (0.46 +/- 0.05) and after insulin injections, 0.15 U/kg (0.43 +/- 0.09), and were always greater than 0.20 micrograms/mg. This index provides a useful objective measure of the normality of responses to hypoglycemic stress, 0.20-0.87 micrograms/mg. Adrenocortical responses to iv infusions of ACTH (cosyntropin 0.25 mg) may be equivocal at 2 h but are clear cut at 4, 6 and 8 h. Of 158 patients in whom hypopituitarism was known or suspected because of the presence of a pituitary tumor, acromegaly, hyperprolactinemia, or clinical features, HPA function was found to be entirely normal in 88 patients and partially or severely abnormal in the remaining 70 patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Normal and abnormal function of the hypothalamic-pituitary-adrenocortical system in man. 608 18

In a significant proportion of patients with acromegaly, a non-specific increase in plasma growth hormone (GH) has been recognized following administration of thyrotropin-releasing hormone (TRH) or luteinizing hormone-releasing hormone (LH-RH), probably due to the lack of the specificity of the receptor in their tumor cells. In this study, the effects of corticotropin-releasing factor (CRF), a newly isolated hypothalamic hormone, in addition to TRH and LH-RH, on plasma levels of GH and the other anterior pituitary hormones were evaluated in 6 patients with acromegaly. Synthetic ovine CRF (1.0 microgram/kg), TRH (500 micrograms) or LH-RH (100 micrograms) was given as an iv bolus injection, in the morning after an overnight fast. Blood specimens were taken before and after injection at intervals up to 120 min, and plasma GH, adrenocorticotropin (ACTH), thyrotropin, prolactin, luteinizing hormone, follicle-stimulating hormone and cortisol were assayed by radioimmunoassays. A non-specific rise in plasma GH was demonstrated following injection of TRH and LH-RH, in 5 of 6 and 2 of 5 patients, respectively. In all subjects, rapid rises were observed in both plasma ACTH (34.3 +/- 6.2 pg/ml at 0 min to 79.5 +/- 9.5 pg/ml at 30 min, mean +/- SEM) and cortisol level (9.1 +/- 1.3 micrograms/dl at 0 min to 23.4 +/- 1.2 micrograms/dl at 90 min). However, plasma levels of GH and the other anterior pituitary hormones did not change significantly after CRF injection. These results indicate that CRF specifically stimulates ACTH secretion and any non-specific response of GH to CRF appears to be an infrequent phenomenon in this disorder.
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PMID:Effect of synthetic ovine corticotropin-releasing factor on growth hormone secretion in patients with acromegaly. 609 67

In 6 of 7 acromegalic patients a single subcutaneous injection of 50 micrograms of a new octapeptide somatostatin analogue (SMS 201-995) reduced serum growth hormone (GH) from 30 +/- 12 ng/ml to 1.4 +/- 0.4 (mean +/- SEM). Serum GH remained below basal concentration for 9 h. In the remaining patient who had very high basal preprandial serum GH, SMS 201-995 produced a reduction in serum GH of only 20%. Plasma glucose concentrations were increased to the upper limits of the normal range when a high-carbohydrate meal was consumed 2 h after injection. In non-diabetic patients plasma glucose did not exceed 129 mg/dl. The 40% decrease in plasma glucagon, which lasted for 7 h after SMS 201-995 injection, was not statistically significant. No side-effects and no rebound phenomenon were observed. These results suggest that SMS 201-995 may be the first somatostatin analogue suitable for the clinical management of acromegaly.
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PMID:Long-acting and selective suppression of growth hormone secretion by somatostatin analogue SMS 201-995 in acromegaly. 614 24

Human pancreatic growth hormone releasing factor 1-44 (hpGRF), 100 micrograms was administered as an i.v. bolus injection to eleven patients with acromegaly. The mean serum growth hormone (GH) levels rose (P less than 0.001) from 54 +/- 20 ng/ml to 215 +/- 126 ng/ml (+/- SEM) 20 min after the injection. Although the maximum response of GH levels was highly variable it correlated positively with the individual GH levels (P less than 0.01, Rs = +0.80). Thus the higher the GH levels, the greater the responsiveness to hpGRF. Administration of somatostatin (SRIF), 300 micrograms/h, lowered basal GH levels from 76 +/- 38 ng/ml to 13 +/- 5 ng/ml (P less than 0.01) after 1 h. hpGRF administration during concomitant SRIF infusion also led to highly variable growth hormone responses. The maximum GH responses again correlated positively with the GH level before hpGRF after 1 h of SRIF administration (P less than 0.05, Rs = +0.79). GH responses to hpGRF were completely blocked by SRIF in three out of four patients whose GH levels decreased to normal levels during SRIF infusion. Our data illustrate that the pituitary in acromegaly is normally responsive to both SRIF and hpGRF but at a higher setting of basal GH levels.
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PMID:Growth hormone responsiveness to human pancreatic growth hormone releasing factor in acromegaly: modulatory effects of basal hormone levels and of concomitant somatostatin administration. 615 Jul 72

Urinary excretion of free adrenaline, noradrenaline and dopamine was examined in 12 patients with active acromegaly before and during long-term therapy (6-22 months) with ergoline derivatives bromocriptine (20-30 mg daily) and lisuride (1-2 mg daily). A significant fall in noradrenaline values (4.5 +/- 0.95 (SEM) nmol/h on v.s. 15.3 +/- 3.8 nmol/h before the treatment, P less than 0.01) was found in the treated patients. Adrenaline excretion rose in most patients but the difference was not significant (1.43 +/- 0.33 nmol/h on v.s. 1.02 +/- 0.36 nmol/h before the treatment, P greater than 0.05). No significant change was seen in the dopamine excretion (71.3 +/- 9.58 nmol/h on v.s. 75.0 +/- 7.0 nmol/h before the treatment, P greater than 0.05). Our studies confirm the blood pressure lowering effect of bromocriptine and lisuride even when used on a long-term basis. This effect seems to be associated with reduced sympathetic activity.
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PMID:Urinary excretion of free catecholamines in long-term treatment with dopaminergic agonists. 615 6

Female pet dogs exhibiting either glucose intolerance alone or glucose intolerance and acromegaly were investigated. Some dogs developed the disorder(s) during dioestrus and some animals developed the disorder(s) after they were given medroxyprogesterone acetate (MPA). Elevated fasting plasma glucose levels (12.3 +/- 1.9 mM, mean +/- SEM) were accompanied by fasting hyperinsulinaemia (144 +/- 21 microU/ml, mean +/- SEM) and drastic elevation of plasma growth hormone (GH) levels (112.6 +/- 45 ng/ml, mean +/- SEM). An iv glucose tolerance test (IVGTT) performed on all dogs revealed non-suppressibility of GH levels and glucose intolerance. Plasma concentrations of glucose, insulin and GH during IVGTT in affected dogs differed significantly from the concentrations measured in normal dogs during the same test. MPA withdrawal and/or ovariohysterectomy (OVx-HYx) in affected animals was followed by reversal of GH levels to normal and improved glucose tolerance. Acromegaly associated soft tissue changes were also reversible after MPA withdrawal and/or OVx-HYx when GH levels had dropped. In 5 dogs which had developed diabetes during dioestrus and in which a spontaneous decrease in plasma progesterone occurred during the investigation a concomittant decrease in GH levels was observed. Plasma GH measured at different stages of pregnancy in 45 dogs was found to be elevated in one animal only. The results show that the development of spontaneous diabetes/acromegaly occurring in some female dogs is related to progestagen (progesterone/MPA) exposure and that reversal of the signs is achieved by progesterone/MPA withdrawal. The results suggest that diabetes/acromegaly in the dogs studied was caused by progesterone/MPA-evoked GH elevation. Finally, the findings also suggest that the GH axis normally not appreciably responsive to progestagen exposure in some dogs becomes and/or is paradoxically controlled by physiologic levels of endogenous progesterone or low doses of MPA.
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PMID:Progesterone-controlled growth hormone overproduction and naturally occurring canine diabetes and acromegaly. 622 90

A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95+/-9.4 ng/ml; mean+/-SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm(3)) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract. The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia and then revert to normal after removal of the GRF source. Thus, in patients with acromegaly a consideration of ectopic GRF secretion should be made, and therefore, careful pituitary histology is mandatory. Consideration for chest and abdominal computer tomographic scans before pituitary surgery, in spite of their low yield, may be justified.
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PMID:Somatotroph hyperplasia. Successful treatment of acromegaly by removal of a pancreatic islet tumor secreting a growth hormone-releasing factor. 629 May 40


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