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

Seven patients with hyperthyroidism due to a TSH-secreting pituitary macroadenoma have been observed of a total of 800 patients with pituitary tumors over a period of 15 yr. Serum TSH levels varied between 1.1-36.3 mU/L. The serum alpha-subunit level was low in 1 case, while in 4 other cases the concentration was elevated and varied between 3.7-7.8 micrograms/L. Serum TSH beta levels were normal in the 4 cases in which it was determined. Serum GH or PRL levels were elevated in 5 cases. In 1 patient the cosecretion of TSH, GH, and PRL was confirmed by immunocytochemical examination. Serum TSH and alpha-subunit responses to TRH, GnRH, CRF, GRF, dexamethasone, methimazole, T3, and bromocriptine administration were variable when studied. Serum TSH and alpha-subunit circadian rhythms were absent in 1 case and inverted in another. A serum alpha-subunit pulsatility without TSH pulses was observed in 1 patient. Five patients underwent transsphenoidal adenomectomy. Three of 4 patients operated on in our center were cured, but a recurrence of the adenoma was found in 1 of them after 5 yr. The fifth patient was not cured. Treatment with octreotide in 3 patients resulted in normalization of serum TSH, GH, and thyroid hormones levels. Cosecretion of PRL in 1 case and alpha-subunit in 2 cases was also inhibited. Partial tachyphylaxis occurred in 1 patient. In summary, heterogeneity in clinical presentation, hormonal expression, and therapeutic response appears to characterize these TSH-secreting adenomas.
 ...
PMID:Thyrotropin-secreting pituitary adenomas: report of seven cases. 170 11

Eight patients with active acromegaly due to GH-producing pituitary adenoma were studied. GH secretory dynamics in vitro was evaluated by adding GRF, CRF, or a somatostatin analog, SMS 201-995 to the perifusate of dispersed cells from tumors. A comparison was made between the data obtained in preoperative tests for GH secretion and those obtained in experiments in vitro. Before operation, the GRF test (100 micrograms, iv) resulted in no GH response in three of six patients examined. The CRF test (100 micrograms, iv) resulted in a paradoxical GH increase in two of the same six patients. In vitro studies performed on adenoma cells revealed that exposure to GRF (100 ng/ml) elicited an increase in GH in seven of eight patients examined. Exposure to CRF (100 ng/ml) caused an enhanced GH secretion in four of the same eight patients. There were cases in which GH response to these hypothalamic hormones was observed in vitro but not in vivo, whereas there was only one case in which CRF caused an increase in GH in vivo but not in vitro. Thus, GH secretory dynamics was not always the same in vivo and in vitro. The discrepancy could be ascribed to the different secretory status of hypothalamic hormone (e.g., GRF or somatostatin) in vivo in each acromegalic patient.
 ...
PMID:Comparative in vivo and in vitro studies on abnormal GH secretion in patients with acromegaly. 249 48

The effects of ovine corticotropin releasing factor (o-CRF) on plasma aldosterone, 18-OH-corticosterone (18-OHB), plasma adrenocorticotropin (ACTH) and cortisol were determined in eight patients with primary aldosteronism, six with aldosterone-producing adenoma (APA) and two with idiopathic hyperaldosteronism (IHA). The results were compared with those in six normal subjects and eleven patients with essential hypertension (EHT, 5 with low renin and 6 with normal renin). In patients with APA, the peak plasma aldosterone and 18-OHB responses to 100 micrograms iv of o-CRF (226% and 113% increase from baseline, respectively) were greater than those in EHT and normal subjects. The net integrated aldosterone and 18-OHB responses (840 +/- 156, and 419 +/- 121 ng/dl.hr, respectively) were also significantly greater (p less than 0.01) in APA than those in normals and EHT. In two patients with IHA, both the peak and net integrated aldosterone response were smaller than those in APA, in spite of nearly identical plasma ACTH and cortisol responses. These results suggest that augmented responses of mineralocorticoids to o-CRF may be characteristic of aldosteronism due to APA, mediated by CRF-induced ACTH, and possibly other proopiomelanocortin (POMC)-derived peptides.
 ...
PMID:Effects of corticotropin-releasing factor (CRF) on aldosterone and 18-hydroxycorticosterone in essential hypertension and primary aldosteronism. 283 82

In an attempt to characterize GH and PRL secretion in acromegaly, the effects of various stimuli on GH and PRL release by cultured pituitary adenoma cells derived from acromegalic patients were studied. In addition, the PRL responses of somatotroph adenoma cells were compared to those of prolactinoma cells. GH-releasing hormone-(1-44) (GHRH) consistently stimulated GH secretion in all 14 somatotroph adenomas studied in a dose-dependent manner. The sensitivity as well as the magnitude of the GH responses to GHRH were highly variable in individual tissues. Somatotroph adenomas that did not respond to dopamine were more sensitive and had greater GH responses to GHRH. In 8 of 9 somatotroph adenomas that concomitantly secreted PRL, the addition of GHRH likewise increased PRL release. Omission of extracellular Ca2+ blocked the stimulatory effect of GHRH on GH and PRL secretion. When cells were coincubated with 0.1 nM somatostatin, GH and PRL secretion induced by 10 nM GHRH were completely blocked in most adenomas. Similarly, coincubation of dopamine resulted in inhibition of GHRH-induced hormone secretion in some adenomas. Addition of TRH to the incubation medium, on the other hand, significantly stimulated GH secretion in 8 of 14 adenomas, while TRH stimulated PRL release in all of the adenomas. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) produced an increase in GH and PRL secretion in other adenomas. In prolactinoma cells, somatostatin and dopamine unequivocally suppressed PRL secretion; however, other stimuli including GHRH, VIP, and CRF were ineffective. TRH induced a significant increase in PRL secretion in only one prolactinoma. These results suggest that responsiveness to GHRH and somatostatin is preserved in somatotroph adenomas; the responsiveness to GHRH is inversely correlated to that to dopamine; and PRL cells associated with somatotroph adenomas possess characteristics similar to those of GH cells. Further, the GH stimulatory actions of TRH and VIP are different.
 ...
PMID:Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture. 285 94

Synthetic ovine corticotropin-releasing factor (o-CRF) stimulated adrenocorticotropin (ACTH) release at the concentration of 10(-10) M or more in monolayer culture of rat anterior pituitary cells. Dexamethasone, 10(-7) M, inhibited this effect. In 5 healthy human subjects, o-CRF, 1 microgram/kg iv bolus, increased plasma ACTH levels from less than 10 pg/ml to 40.4 +/- 11.0 (mean +/- SD) after 30-60 min, and plasma cortisol from 12.8 +/- 2.8 micrograms/dl to 23.6 +/- 3.1 after 45-60 min. Of 7 patients with Cushing's disease (CD), five showed an exaggerated response of plasma ACTH and cortisol, one an exaggerated response of plasma ACTH but low response of plasma cortisol and the other no response of both hormones. The significant positive correlation between the inhibition of plasma cortisol by dexamethasone and the response of plasma ACTH and cortisol to o-CRF in CD was seen. No response of plasma ACTH and cortisol to o-CRF was seen in each one patient with Cushing's syndrome due to an adrenocortical adenoma, ectopic ACTH syndrome (but low response at retesting), isolated ACTH deficiency and Sheehan's syndrome. In one patient with Addison's disease an exaggerated response of plasma ACTH but no response of plasma cortisol was seen. In 4 of 5 healthy subjects and 5 of 7 patients with CD, plasma ACTH and cortisol levels showed a second peak at 120--210 min after o-CRF administration. To clarify the prolonged effect of o-CRF in human in vivo, the disappearance rates of injected o-CRF were evaluated by radioimmunoassay in 3 patients with cured Cushing's syndrome. A biexponential decay curve showed t1/2 values of 9.3 +/- 0.4 min and 79.6 +/- 0.7 min (mean +/- SE). From the chromatographic profile, a portion of injected o-CRF was thought to be bound to macromolecule (s). o-CRF, as a specific secretagogue of ACTH, is thought to be useful tool in evaluating patients with hypothalamo-pituitary-adrenal disorders.
 ...
PMID:[Studies for clinical application of ovine corticotropin-releasing factor]. 298 91

The 41-amino acid CRF fulfils all the criteria for a corticotrophin releasing factor, although considerable evidence suggests that other factors, particularly VP, also play a physiologically significant role in controlling ACTH release. Although human CRF has now been identified as a 41-residue peptide, most studies to date have used oCRF-41 in their exploration of the physiology and pathology of the hypothalamic--pituitary--adrenal axis. Low doses of oCRF-41 appear to be safe, and for specific tests of the readily-releasable pool of ACTH and related peptides 100 micrograms is a practical dose for most purposes. Although serious side-effects have only been noted at doses above 100 micrograms, it is reasonable to monitor all patients administered CRF-41 with great care, and in particular to be alert to hypotension, especially in patients with corticosteroid deficiency. There is little doubt that, in combination with the standard insulin-tolerance test, the CRF test is a useful means of diagnosing hypothalamic or portal dysfunction in patients with secondary adrenal failure. However, in the diagnosis and differential diagnosis of Cushing's syndrome, the role of the CRF test remains unclear. In normal subjects, a high basal cortisol level usually inhibits the response to CRF, such that a greatly enhanced response is suggestive of pituitary-dependent Cushing's syndrome. In patients with diagnosed ACTH-dependent Cushing's syndrome, an absent response to CRF predisposes towards an ectopic source of ACTH. However, there are exceptions in all directions, and it is uncertain whether the CRF test will prove of greater value than the traditional procedures, such as the dexamethasone suppression test. The differential diagnosis of depression and Cushing's disease may be its greatest value. In terms of treatment, there are as yet few data on the usefulness of CRF in expediting recovery of the pituitary-adrenal axis following long-term suppression, such as in patients with Cushing's syndrome treated by removal of a unilateral adenoma or trans-sphenoidal microadenomectomy. It is possible that such treatment may eventually be a useful application of CRF, although data are not yet available.
 ...
PMID:The CRFs and their control: chemistry, physiology and clinical implications. 300 78

Three cases of ACTH dependent Cushing's syndrome are reported with emphasis on diagnostic value of selective venous sampling. Case 1. A 44-year-old female was admitted to our hospital with clinical diagnosis of Cushing's disease. Endocrinological examination revealed typical data of Cushing's disease. High resolution CT scan showed an empty sella turcica, and a chest film showed multi-cystic lesion in the left lower lung field. In the first trial of selective venous sampling, central to peripheral ACTH ratio (C/P ratio) was high at the superior vena cava. So, an ectopic ACTH producing lung tumor was strongly suspected. Further examinations for lung tumor were performed, and finally showed lung cryptococcosis. Therefore, selective venous sampling was performed again, and pituitary ACTH dependency was diagnosed. An eccentric pituitary microadenoma was successfully removed by transsphenoidal surgery. Case 2. A 54-year-old female was admitted to our hospital with clinical diagnosis of Cushing's disease. In the endocrinological examinations plasma ACTH was not respond to provocation of LVP or CRF. In selective venous sampling, C/P ratios of ACTH were not greater than 2.0 at any sampling site. Further examinations showed lung tumor in the lower lobe of left lung. This tumor was surgically proved to be an ectopic ACTH producing lung carcinoid. Case 3. A 24-year-old female was admitted to our hospital for the purpose of further examination of Cushing's disease. Three years previously exploratory transsphenoidal surgery demonstrated an empty sella without adenoma. She received postoperative radiation therapy with a dose of 5000 rad. Endocrinological examination showed typical data due to Cushing's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[ACTH dependent Cushing's syndrome with an empty sella turcica: report of three cases with emphasis on diagnostic value of selective venous sampling]. 300 18

ACTH-secreting pituitary adenoma cells were cultured from specimens obtained by transphenoidal hypophysectomy in five patients with Cushing's disease. The majority of adenoma cells (90%) stained specifically with antiserum against human ACTH. The electrophysiological properties and response to hormones of these cells were studied with intracellular recording techniques under current clamp and voltage clamp conditions. Most (80%) of the cells fired action potentials that were Ca2+-dependent inasmuch as they were blocked by Co2+ (5 mM) and by removal of Ca2+ from the medium, but were unaffected by tetrodotoxin (0.3 mM) and by Na+ removal. The cells responded to factors known to stimulate ACTH release, including high K+, CRF, and angiotensin II (AII). High K+ (50 mM) induced a membrane depolarization in association with an increase in conductance. CRF (100 nM) produced a depolarization, a decrease in conductance, an increase in spike firing, and an increase in spike duration. Although AII was inactive in ordinary recordings, in cells loaded with lithium (Li+) to promote the phospholipid-dependent second messenger system, the peptide produced an increase in spike firing and spike duration with no change in membrane potential. The combination of CRF and AII (CRF + AII; 100 nM each) in Li+-loaded cells caused a greater excitatory effect than either peptide alone. Under voltage clamp, the response either to CRF or to CRF + AII could be attributed, at least in part, to the inhibition of a slow, voltage-dependent K+ current that is persistently active at resting potential. These results indicate that modulation of action potential firing may be an early step in the regulation of ACTH release from pituitary cells by known secretagogues. Since action potentials in these cells are associated with Ca2+ entry, the resulting changes in intracellular Ca2+ levels could mediate the effects of the hormones on secretion.
 ...
PMID:Electrical properties of cultured human adrenocorticotropin-secreting adenoma cells: effects of high K+, corticotropin-releasing factor, and angiotensin II. 303 72

We have studied the diurnal rhythm of pars distalis and pars intermedia-type immunoreactive (IR)-POMC peptides and cortisol in 3 normal dogs and 1 dog with Cushing's syndrome and have documented the responses to a variety of agents in 42 dogs with Cushing's disease, 2 of which were known or presumed to have pars intermedia tumors and another of which had both pars distalis and pars intermedia adenomas, and in 20 dogs with adrenocortical adenomas causing Cushing's syndrome. The normal dogs did not have a diurnal plasma POMC peptide rhythm; the dog with Cushing's disease appeared to have a similar number of secretory episodes of increased amplitude. Plasma POMC peptides and cortisol in animals with Cushing's disease did not suppress normally with low dose dexamethasone. Five animals with Cushing's disease did suppress with high dose dexamethasone, the dog with dual adenomas suppressed only partially, and 1 dog with a pars intermedia adenoma did not suppress at all. The response to insulin-induced hypoglycemia was similar in normal dogs and 4 dogs with Cushing's disease, but 3 animals with adrenal tumors did not respond. The response to metyrapone was normal in 6 dogs with Cushing's disease and, surprisingly, in 1 with adrenal tumor. Arginine vasopressin stimulated POMC peptide secretion in normal and 6 Cushing's dogs, as well as alpha MSH, a pars intermedia-type POMC peptide, in a dog presumed to have a pars intermedia tumor. Ovine CRF stimulated pars distalis-type POMC peptide secretion in normal dogs and 17 dogs with Cushing's disease, but not in 15 dogs with adrenal tumor; IR-alpha MSH was unaffected. TRH appeared to stimulate IR-ACTH in normal animals, but not in those with Cushing's disease. Dopamine had no apparent effect in 2 normal and 1 Cushing's dogs. Initial plasma disappearance t1/2 values of IR-ACTH and lipotropin were 22-27 min. In summary, responses in normal and Cushing's dogs were generally what would be predicted from previous human and animal studies, but some of those in animals with pars intermedia tumors and even in normal dogs were different from what had been anticipated. Canine Cushing's syndrome provides an interesting model for an uncommon human disorder.
 ...
PMID:Plasma immunoreactive proopiomelanocortin peptides and cortisol in normal dogs and dogs with Cushing's syndrome: diurnal rhythm and responses to various stimuli. 312 32

The study shows the results of transsphenoidal microsurgery in 23 patients with Cushing's disease (CD). Out of the 21 patients with tumour confined to the sella, 18 who had selective adenomectomy, and 1 who underwent total hypophysectomy had correction of hypercortisolism. None of the patients with extrasellar extension of the tumour was cured. In 2 cases no adenoma was found intra-operatively. Post-operative hypoadrenalism was documented in all the patients who remitted clinically. By 3-26 months after surgery, adequate cortisol secretion was found in 12 patients, nine of whom regained diurnal variation of cortisol secretion and ten cortisol responsiveness to hypoglycaemia; a normal or near normal response of cortisol to CRF was documented in 11 out of 17 patients tested. Thyroid and gonadal function was restored in all but two patients in clinical remission, whereas GH responsiveness to hypoglycaemia appeared impaired in 11. Two patients had recurrence of the disease 2 and 3 years, respectively, after successful adenomectomy. In our experience transsphenoidal selective adenomectomy is an effective treatment for most patients with CD; additional therapeutic approaches should be considered for patients bearing pituitary tumours with extrasellar extension, whose surgical outcome is often disappointing.
 ...
PMID:Transsphenoidal microsurgery for Cushing's disease. 376 49


1 2 Next >>