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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue specific G-protein mutations have been found in differentiated thyroid cancer with a higher prevalence in tumors from German than from American patients. Since activating mutations of Gs are principally comparable to chronic TSH stimulation of these tumor-thyrocytes such mutations may predict changes in tumor development and patient prognosis. The fundamental background and recent results of studies on mutational activation of G-proteins are presented.
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PMID:G-protein mutations in thyroid tumors. 146 9

The classic experimental model of thyroid neoplasia using radiation as a mutagen followed by long-term goitrogen treatment gives rise to multiple tumours in rats. Radiation alone, with suppression of TSH produces no tumours, TSH-induced growth alone causes a low level of tumorigenesis. Cell proliferation in this model is therefore critical. Epimutation as well as mutation is important. Rodent and human thyroid tumours show a clear stepwise progression, associated with both morphological and oncogene changes. In experimental animals the finding that monoclonal adenomas and carcinomas induced in the presence of long-term high TSH retain TSH dependency suggests that the step in the tumour progression requiring the development of TSH independent growth is bypassed, explaining the frequency of tumour development in this model. Normal thyroid follicular cell growth is limited, and a genotoxic effect before the growth plateau is more effective in carcinogenesis than a genotoxic effect after a period of growth. These observations will be interpreted in relation to the importance of thyroid tumours in regulatory toxicology and the pathobiology of thyroid tumours in man.
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PMID:Cell proliferation and thyroid neoplasia. 147 Nov 93

In a total of 1665 patients with malignant thyroid neoplasms 90 oxyphilic thyroid carcinomas (OTC) were found of whom 55 could be re-examined and newly classified. Morphological and clinical parameters influencing the clinical course were determined. During a mean follow-up period of 6.5 y metastases or local recurrent disease occurred in 12 patients (24%). Apart from 3 early manifestations of metastases, 9 patients developed recurrent disease within, on average, 4.7 y after thyroidectomy: local lymph node metastases and local recurrences occurred within an average of 5.4 y, distant metastases after only 2.7 y. Thyroglobulin proved to be reliable for follow-up with a sensitivity of 88% on levothyroxine and 75% on endogenous TSH-stimulation (specificity: 98%). The frequency of metastases and local recurrences correlated with age at the time of tumor diagnosis, the degree of invasiveness and the local tumor extension (pT4 vs. pT1-3), whereas other factors such as the absolute diameter of the tumor or patient's sex had no influence on the clinical course. The survival probability for 5 and 10 years was 95 and 75%, respectively. All OTC patients should be examined regularly at least once a year by cervical sonography and thyroglobulin measurement. Because 18% recurrences occurred within 4.7 y such examinations should be repeated beyond year 5 after thyroidectomy.
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PMID:[The clinical course of oxyphilic carcinoma of the thyroid]. 149 62

Our aim was to determine whether fucosylation of glycoproteins begins in the rough endoplasmic reticulum (RER) of active thyrotrophs. This would contrast with most cells studied, in which fucosylation generally is associated with the Golgi apparatus. Mouse thyrotropic tumor tissue was incubated with [35S]methionine for 2, 5, 7, 10, 30, and 90 minutes. TSH and free alpha-subunits were immunoprecipitated from cell lysates, and they displayed a time-dependent increase in affinity for lentil lectin (which binds oligosaccharides having core fucose), even at short times. Since no 20-30 minute lag in onset of TSH- and free alpha-subunit-lentil binding was appreciated, as might have been expected had fucosylation begun only in the Golgi, it appeared that fucosylation was beginning in the RER of thyrotrophs. Pituitary tissue from euthyroid and hypothyroid mice was incubated with [3H]fucose, then subjected to electron microscopic autoradiography. The pituitaries of hypothyroid mice had numerous "thyroidectomy cells," which had 40% of silver grains over dilated cisternae of RER. "Nonthyroidectomy" cells had few silver grains over RER; most were over secretory granules and Golgi areas. Thus, active mouse thyrotrophs appear to shift the subcellular site of fucosylation partially from Golgi to RER, and this phenomenon may represent one cellular mechanism whereby the endocrine regulation of the structure of TSH oligosaccharides is accomplished.
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PMID:Fucosylation of glycoproteins begins in the rough endoplasmic reticulum of mouse active thyrotrophs. 149 77

Some patients with thyrotropin (TSH)-producing pituitary tumors are more hyperthyroid than others despite similar TSH levels in serum, suggesting that qualitatively different TSH molecules with differing bioactivities may be secreted by different tumors. We used ricin and lentil lectin-affinity chromatography to test whether the TSH oligosaccharides varied among 12 patients with TSH-producing tumors. We found that each tumor secreted heterogeneous isoforms of TSH that differed in their extents of exposed galactose (Gal) residues, and their degrees of sialylation and core fucosylation. These biochemical parameters also varied markedly for TSH secreted by different tumors. Isoforms appeared to reflect poor sialyltransferase activity in two tumors and efficient sialyltransferase in the remainder. TSH secreted by tumors was more fucosylated than TSH secreted by control euthyroid persons. There was an inverse relationship between the sialylation and fucosylation of tumor TSH. No simple relationship between TSH oligosaccharide structures and bioactivity was evident, although mixtures of isoforms having the least and most sialylated TSH seemed to be the most bioactive clinically. In three patients from whom serum and medium TSH were both available, TSH in serum was more sialylated than TSH secreted by the tumor in vitro, perhaps reflecting slow clearance of sialylated isoforms from the circulation. Core fucosylation of serum TSH was less than that of medium TSH. These data prove that human tumors secrete TSH with heterogeneous oligosaccharide structures.
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PMID:Ricin and lentil lectin-affinity chromatography reveals oligosaccharide heterogeneity of thyrotropin secreted by 12 human pituitary tumors. 151 16

Results of 131I whole body scans and measurements of thyroglobulin (Tg) in the follow-up of 85 patients with differentiated thyroid cancer were analysed in a retrospective study. All patients were assumed to be tumor-free after therapy. During follow-up, cancer recurrence was observed in 11 patients. Out of 24 131I scans performed for suspected recurrence, cancer was localized in 5. Out of 71 routinely performed 131I scans and Tg measurements during hormone withdrawal, new pathologies were observed in each of two cases one year after the last therapy. 10 out of 11 tumor recurrences were observed in a high-risk group of 40 patients with follicular histology or stage III or IV (UICC 1987). One recurrence occurred in a low-risk group of 41 patients with papillary histology and UICC stage I or II. Later than one year after therapy no recurrence was observed in any patient who belonged to the low-risk group. These results indicate that 131I scans and Tg measurements under endogenous TSH stimulation are necessary in cases of suspected recurrences and probably on a routine basis one year after the last therapy in all patients. In the event of an inconspicuous further course this diagnostic procedure should be restricted to special high-risk groups. Using a cut-off level of 5 ng/ml as compared to 10 ng/ml, the number of false-negative Tg results under suppressive therapy decreased clearly whereas that of the "false-positive" results increased less pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Thyroglobulin, 131I-whole body scintigraphy and risk factors in the follow-up of differentiated thyroid cancer]. 156 Nov 18

Some pituitary hormones secrete hormones while others do not. Nonsecreting tumors can interfere with normal pituitary hormone secretion and produce tumor symptoms and signs like headaches and visual field defects. The most frequent hormone-secreting tumors are prolactinomas. Growth hormone or ACTH or gonadotropin or gonadotropin-alpha and beta chain-producing tumors are less frequent, TSH producing tumors are extremely rare. The most important elements of the diagnostic work-up are clinical signs and symptoms, assessment of pituitary function (measurement of TSH, free T4, LH, FSH, oestradiol/free testosteron, growth hormone, IGF-1, prolactin, ACTH, Cortisol, serum and urine osmolality), CT and/or MRI and, in patients with large tumors, a visual field exam. The treatment of choice of pituitary tumors is often surgery. Alternative therapies are radiation treatment (in nonoperable patients or when hormone levels are persistently elevated after pituitary surgery) and drug treatment (dopamine agonists in hyperprolactinemia, somatostatin analogues in acromegaly). Pituitary hormone deficiencies are treated depending on the specific deficiency with thyroxine, cortisone, oestrogen/gestagen/testosterone gonadotropines or ADH analogues.
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PMID:[Hypophyseal dysfunction and tumors]. 158 68

A 50 year old man with hyperthyroidism secondary to inappropriate secretion of TSH is described. On presentation T3 (42.1 nmol/L), T4 (265 nmol/L) and TSH (17.9 mU/L) were all markedly elevated. A diagnosis of a TSH-secreting pituitary tumor was suspected on the basis of a blunted TSH response to TRH and the absence of suppression of TSH by T3 or bromocriptine, but TSH/alpha subunit molar ratios were uncharacteristically less than 1. Nevertheless, the presence of a tumor was confirmed by computed tomography which demonstrated a 15 mm pituitary macroadenoma. The patient was treated with octreotide which resulted in normalisation of thyroid hormone levels. The duration of action of a single 100 micrograms injection of octreotide was at least 56 hours. The suppression of thyroid hormone levels was similar regardless of the treatment regimen with octreotide (100 micrograms tid, 250 micrograms bid, 100 micrograms bid and continuous subcutaneous infusion (CSI] and no escape was observed during a 16 month treatment period. TSH alpha subunit concentrations were also suppressed during long-term treatment with octreotide (3.3 micrograms/L falling to 1.1 micrograms/L), although no acute changes were noted after administration of single dose octreotide 100 micrograms. Three times the octreotide therapy was discontinued. The incremental rise in TSH and the maximum level of TSH achieved was less on each subsequent occasion, suggesting a suppressive effect of octreotide on the tumor itself. Despite suppression of TSH with octreotide over a 13 month period the pituitary tumor showed no shrinkage on repeat MRI scanning. In conclusion, this patient demonstrates that the differential diagnosis of inappropriate TSH secretion based only on biochemical test may be unreliable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:TSH producing pituitary tumor: biochemical diagnosis and long-term medical management with octreotide. 161 57

The SRIF analog octreotide (SMS 201-995) has been in clinical use for over 6 yr in the treatment of acromegaly and metastatic endocrine pancreatic and carcinoid tumors. The use of the analog in the treatment of acromegaly and TSH-secreting tumors is beyond the scope of this clinical review. Patient acceptance of the analog, given chronically by the sc route, has been excellent and side effects have been few with the exception of the development of gallstones. In endocrine pancreatic and carcinoid tumors the hypersecretion of hormones such as VIP, glucagon, and gastrin and the secretory products of carcinoid tumors (e.g. 5-hydroxytryptamine and tachykinins) and their clinical effects may be successfully blocked. This allows excellent palliation of such tumors and often enables the patients to return home and lead normal social lives. Initial hopes that long-term octreotide therapy would be an effective antitumor drug, reducing tumor growth, based on experimental animal models and human tumor cell lines, have not been born out in clinical practice. A reduction in gut tumor bulk due to octreotide, rarely or never occurs as a sustained phenomenon. Eventually a decrease in, and finally an absence of, clinical effectiveness occurs despite the reintroduction of other treatment modalities.
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PMID:Clinical review 23: The use of the long-acting somatostatin analog octreotide in the treatment of gut neuroendocrine tumors. 164 13

Although bromocriptine is the mainstay of treatment of macroprolactinomas, its therapeutic usefulness may be limited by poor tolerance, lack of consistent reduction in serum prolactin levels and tumour size, and the necessity for multiple dosing. Consequently new dopamine agonists have been developed, including the long acting non-ergot agonist CV205-502 which has been shown to date to be consistently effective in reducing serum PRL levels and causing tumour shrinkage. Twelve patients were treated for periods of up to 24 months with CV205-502 in doses ranging from 0.075 mg to 1.65 mg once daily. Clinical and psychiatric assessments, biochemical parameters, tumour size determination, and anterior pituitary function tests were performed regularly. Tumour shrinkage was noted in all patients, and varied from 11 per cent reduction to complete disappearance of tumour. Prolactin levels became normal in seven patients and were reduced by more than 90 per cent in the remaining five. Normal menstruation resumed in six of the eight women, one of whom conceived after one year of therapy; libido returned in all patients. Psychiatric complications occurred in three patients necessitating withdrawal of therapy in one. Significant weight loss was noted in 11 of 12 patients. Triglyceride concentrations fell from 1.5 +/- 0.1 to 1.0 +/- 0.1 mmol/l at 12 months (p = 0.006), and cholesterol fell from 6.3 +/- 0.4 to 5.3 +/- 0.3 mmol/l (p = 0.04). The mean TSH response 20 min following TRH injection fell from 14.3 +/- 2.9 to 8.7 +/- 1.3 mU/l at 2 months (p = 0.027). There was a significant increase in the peak growth hormone response to the insulin stress test from basal median (25th-75th centiles) values of 15 (4.4-25.5) mU/l to 24.5 (9-37) mU/l at 2 months (p less than 0.01) and 31 (19.3-63.5) at 12 months (p less than 0.005). CV205-502 is highly effective in the medical management of patients with macroprolactinomas, reducing prolactin levels and tumour size and restoring normal anterior pituitary function. It is, however, associated with the important side effects of weight loss and psychiatric complications which should be drawn to the attention of clinicians.
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PMID:Endocrine function, psychiatric and clinical consequences in patients with macroprolactinomas after long-term treatment with the new non-ergot dopamine agonist CV205-502. 168 93


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