Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cases of TSH-secreting pituitary adenoma were reported. Endocrinological and immunohistochemical features of these cases were described and problems in diagnosis and treatment of the rare disease are discussed. [case 1] A 28 year-old woman suffered from hyperthyroidism with a relatively high value of serum TSH (T3; 350 ng/dl, T4; 10.0 micrograms/dl, TSH; 24.5 microU/ml). She was treated with antithyroid drug and then underwent subtotal thyroidectomy. Although the levels of serum T3 and T4 were lowered to within normal range, the level of serum TSH still remained high. One month later, she developed frontal headache, amenorrhea and bitemporal hemianopsia. A CT scan showed an enhanced mass in the sellar and suprasellar region. Preoperative endocrinological studies showed elevated values of TSH (47 microU/ml) and its alpha-subunit (9.0 ng/ml). The levels of both T3 (190 ng/dl) and T4 (10.0 micrograms/dl) were near the upper normal limit. Serum TSH was suppressed by administration of exogenous T3, but did not respond to exogenous TRH, l-Dopa nor bromocriptine. Under the diagnosis of TSH-secreting pituitary adenoma, the patient was operated on by craniotomy and received local radiation therapy (50 Gy). In 1990, 12 years after the treatment, she is well and endocrinologically normal. Immunohistochemical study revealed that most tumor cells were positive for TSH. [case 2] A 28 year-old woman visited our hospital for examination of hyperthyroidism. Serum level of TSH was detectable (4.5 microU/ml). A CT scan performed at that time disclosed no pituitary tumor. Thyroid function was normalized by antithyroid drug, but the level of TSH was still high and progressively increased.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Two cases of TSH-secreting pituitary adenoma; endocrinological, diagnostic and therapeutic approach to the disease]. 194

Differentiated rat thyroid cells, designated FRTL, are totally dependent on TSH for their growth. We continuously cultured FRTL cells in the absence of TSH and found that another type of cell appeared in the culture. The new cells were large, flattened and epithelial-like, and none of them exhibited thyroglobulin immunoreactivity. Since they grew independently of TSH, we further cloned these mutated cells by the limited dilution method in the absence of TSH. cAMP production in the cloned cells (FRTL-Tc) was stimulated dose-dependently by TSH. The TSH concentration that produced a maximal level of cAMP in FRTL-Tc cells was 1 order of magnitude higher than in FRTL cells. A [125I]TSH binding study confirmed that the FRTL-Tc cells had TSH receptors with the same binding capacity but a higher Kd than those of FRTL cells. A [125I]cyanopindolol binding study revealed that the FRTL-Tc cells had acquired beta 2-adrenergic receptors and that isoproterenol or epinephrine could stimulate cAMP production in the cells. TSH or beta-adrenergic agonists inhibited the growth of these cells, as did (Bu)2cAMP. When FRTL-Tc cells were transplanted into the sc tissue in Fisher rats, they grew as a tumor in all of the animals (n = 10). Metastasis of the tumors to the lung and liver occurred. These results indicate that FRTL-Tc cells are malignantly transformed cells with TSH receptors derived from thyroid epithelial cells and also suggest that the role of cAMP in the proliferation of the transformed cells might be different from that in normal cells.
 ...
PMID:Cloning of malignantly transformed rat thyroid (FRTL) cells with thyrotropin receptors and their growth inhibition by 3',5'-cyclic adenosine monophosphate. 196 81

High affinity somatostatin receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred human tumors. SS-R were found in most tumors originating from SS target tissues, i.e. GH- and TSH-producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors (including metastases) and brain tumors, including gliomas and neuroblastomas. SS-R were also expressed in several tumors originating from various other tissues, i.e. breast and small cell lung carcinomas, some colorectal cancers, and medullary thyroid carcinomas. In general, most of the SS-R+ tumors are well-differentiated and/or have neuroendocrine features. They often have low or absent epidermal growth factor receptor (EGF-R) expression. In some tumors (i.e. breast tumors) SS-R are not homogeneously distributed, making SS-R autoradiography a particularly useful tool for assessing SS-R status. SS-R are functional in pituitary and GEP tumors where they mediate hormone secretion inhibition. In these and in the other SS-R+ tumors, SS-R may also mediate antiproliferative effects of SS, as evidenced in animals where growth of SS-R+ tumor xenografts is inhibited by SS analogs. For diagnosis, SS-R+ tumors and metastases can be localized in vivo by scanning techniques after 123I-labelled SS analog injection.
 ...
PMID:Somatostatin receptors in malignant tissues. 198 Oct 10

Nodular goiter is a worldwide problem involving millions of persons. Endemic goiter, and associated cretinism, is totally preventable by ensuring an adequate dietary iodine intake and eliminating malnutrition and dietary goitrogens. Therapy, on the other hand, is difficult in that the goiters often do not regress and the cretinoid changes are irreversible. Nonendemic goiter due to autoimmune thyroid disease, genetic defects in thyroid hormone biosynthesis, and environmental goitrogens or neoplasia is not usually preventable. The usual therapy, involving TSH suppression by administration of L-thyroxine orally, will frequently bring about regression of early, diffuse goiters but is often ineffective in bringing about regression of large, multinodular goiters. In these patients, surgical removal of the goiter may be necessary for alleviation of obstructive symptoms. Further research is needed to elucidate the factors involved in the development of these multinodular goiters and to control the autocrine and paracrine factors involved in nodule growth.
 ...
PMID:The problem of the nodular goiter. 198 43

With the understanding that various drugs, industrial chemicals, and chemicals of environmental importance can increase thyroid hormone hepatic metabolism and excretion, it is important to consider whether compensation by the thyroid gland for this increased excretion can lead to stimulation of the hypothalamic-pituitary-thyroid axis and possibly secondary hyperplastic or neoplastic changes in the thyroid. The compounds discussed in this review all affect thyroid function by increasing biliary excretion of thyroid hormone metabolites. Numerous studies have been performed to elucidate the effect of these drugs on thyroid hormone equilibrium. Animals given PB compensate for the increased biliary excretion with an elevated TSH allowing maintenance of a euthyroid state. Human studies demonstrate increased thyroid hormone plasma clearance, but without an increased TSH. The effects of an experimental leukotriene antagonist are similar. In humans, diphenylhydantoin has been conclusively shown to cause a decrease in peripheral thyroid hormone levels, although without evident hypothyroidism or increase in TSH. Limited studies of rifampin and carbamazepine reveal similar results. Nicardipine in rats causes reproducible decreases in free T4 levels, although it does not clearly stimulate a rise in TSH levels. An experimental imidazole caused reversible lowering of peripheral thyroid hormone levels in rats; in this study TSH was not measured. Studies with aromatic hydrocarbons administered to rats reveal a general decrease in T4 levels, with a compensatory increase of TSH. The effects of chronic administration of a compound that can cause increased thyroid hormone metabolism with compensation via increased TSH production are of more than theoretical interest, as it has been well documented that constant stimulation of the thyroid gland in rats with supraphysiological levels of TSH causes goiter, thyroid hyperplasia, adenomas, and carcinomas. In humans with congenital metabolic thyroid deficiencies there is an increased incidence of thyroid neoplasia, suggesting an association with chronic increased TSH levels. In contrast, however, large epidemiological studies of areas of endemic goiter do not show an association of human thyroid cancer with iodine deficiency and presumed chronic thyroid gland stimulation. Histological evidence of thyroid follicular hyperplasia has been noted in rats after administration of phenobarbital, nicardipine, polycyclic hydrocarbons, and possibly an experimental imidazole. Increased thyroid gland size has been demonstrated in rats given phenobarbital, nicardipine, a leukotriene antagonist, and various polycyclic hydrocarbons. Thyroid carcinoma in rats has been associated with treatment with nicardipine and after exposure to several aromatic hydrocarbons.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The effect of hepatic enzyme-inducing drugs on thyroid hormones and the thyroid gland. 207 Jul 77

We report a patient with pregnancy-induced lymphocytic adenohypophysitis complicated by postpartum painless thyroiditis. A 27-year-old female noticed visual field defect in the 36th week of pregnancy. After delivery in the 39th week by cesarean section, she was admitted for close examination. Goiter was not palpable, and postpartum galactorrhea was not observed. Routine examination revealed no abnormal findings. On October 8, 1989, magnetic resonance imaging (MRI) revealed a tumor image (height 22.4mm) from the sella turcia to suprasellar cistern with a lower signal intensity than that of the white matter on T1 weighted images and a high signal intensity on T2 weighted images. Gd-DTPA contrast images showed a symmetrical and homogeneous tumor image at the same site. However, the posterior lobe of the pituitary gland appeared normal. These findings suggested lymphocytic adenohypophysitis. The LH was less than 0.3mIU/ml. The FSH (7.8mIU/ml), PRL (12ng/ml), GH (1.6ng/ml) and cortisol (10 micrograms/dl) levels were normal. T4 was 5.3 micrograms/dl, T3 67ng/dl, fT4 0.53ng/dl, which indicated mild hypothyroidism, but the TSH was normal. TRH test showed a slight increase in TSH and no response of PRL. Insulin tolerance test showed delayed response of GH and normal response of cortisol. LHRH test revealed no response of LH and delayed response of FSH. Anti-GH3 cell antibody and anti-thyroglobulin antibody were positive, but the anti-AtT20 cell antibody was negative. Since visual disturbance improved, and slight reduction in the mass (height 20.1mm) was confirmed by MRI after delivery on October 21, her course was observed without treatment. After 1 month, the LH became detectable, but the PRL and cortisol decreased to 2.5ng/ml and 6.0 micrograms/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[A case of pregnancy-induced lymphocytic adenohypophysitis complicated by postpartum painless thyroiditis]. 207 Aug 91

The beta-subunit gene of TSH is specifically expressed in thyrotrope cells of the anterior pituitary gland. To define the particular TSH beta-subunit gene sequences responsible for tissue-specific expression, TSH beta promoter fragments were assessed for promoter activity by gene transfer into TSH-expressing thyrotropic tumor cells (TtT-97). Previous studies have shown that the murine TSH beta gene promoter was more efficiently used in TtT-97 cells compared to other pituitary-derived cells or nonpituitary fibroblasts and that a 191-basepair DNA sequence of the 5' flanking region between -271 and -80 was sufficient for maximal promoter activity in thyrotropes. Further deletional analysis within this region has localized the area responsible for expression in thyrotropes to a 37-basepair region between -117 and -80 up-stream of the major transcriptional initiation site. DNase-I protection assays demonstrated that this functionally defined 5' flanking area, in addition to the adjacent sequences immediately up-stream and down-stream, interacts with protein factors present in nuclear extracts from TtT-97 tumor cells. When fused to a heterologous promoter, fragments derived from the region between -271 and -80 exhibited cell-specific activity, although this was not conferred solely by the TSH beta promoter fragment from -117 to -80. Heterologous promoter activity was further stimulated when fragments containing the areas from -271 or -201 to -77 were used, suggesting combinatorial cis interactions between these regions of the TSH beta promoter. DNase-I protection studies suggest that there are multiple protein-binding domains in the mouse TSH beta 5' flanking sequence. Only the more proximal domains, which encompass important promoter elements, appear to be required for efficient expression in thyrotropes, whereas other more up-stream sites of protein interaction may be involved in regulatory aspects of TSH beta gene expression.
 ...
PMID:Protein factors in thyrotropic tumor nuclear extracts bind to a region of the mouse thyrotropin beta-subunit promoter essential for expression in thyrotropes. 208 88

To study whether patients with idiopathic GH deficiency (IGHD) show a delayed GH response pattern to GHRH, 42 patients with IGHD, 14 patients with hypothalamic tumor (2ry GHD), and 23 normal short children (NSC) were examined as to their GH response patterns to GHRH together with their TSH and PRL response patterns to TRH. After TRH injection, the mean time of the TSH peak in IGHD (67.5 +/- 6.5 min, n = 36) and 2ry GHD patients (81.7 +/- 14.8 min, n = 9) was clearly delayed comparing to that of NSC (29.1 +/- 2.9 min, n = 16; both p less than 0.01). Similarly, the mean time of the PRL peak in IGHD (38.3 +/- 3.6 min, n = 36) and 2ry GHD patients (39.5 +/- 5.8, n = 11) was significantly delayed comparing to NSC (22.0 +/- 3.5 min, both p less than 0.01). In IGHD patients, the delayed response pattern of TSH and PRL was more remarkable in patients who had breech delivery than in those with normal delivery. In contrast, the mean time of the GH peak was similar in IGHD (62.1 +/- 4.0 min, n = 41), 2ry GHD (64.1 +/- 8.1 min, n = 11) and NSC (58.0 +/- 6.1 min, n = 23). However, the decline from peak GH (120 min GH/peak GH) was significantly smaller in IGHD (54.3 +/- 4.2%) and 2ry GHD (60.7 +/- 7.3%) than in NSC (39.0 +/- 8.1%) (both p less than 0.05). Further, in IGHD patients plasma GH response was greater in patients with normal delivery than in those with breech and asphyxia delivery. These results seem to indicate: 1) the stimulus-secretion mechanism is different between somatotrophs and thyrotrophs or lactotrophs in man, 2) IGHD patients have hypothalamic lesions as well as pituitary lesions, 3) such hypothalamo-pituitary lesions in IGHD patients are greater in patients with abnormal delivery than in those with normal delivery.
 ...
PMID:GHRH and TRH tests in patients with idiopathic and secondary GH deficiency--with special reference to GH response patterns to GHRH. 211 93

The case of a male child with Russel's syndrome due to a pilocytic astrocytoma located in the diencephalic region is presented. The diagnosis was made in the 16th month of age, but symptoms began in the 4th months of life, when he started losing weight. By the time he was admitted weight was 6150g and he was 74cm tall, with an emaciated aspect, no panniculus adiposus, irritated, and with symptoms of intracranial hypertension. There was convergent strabismus, vertical nystagmus of the left eye and bilateral papilledema. Tendinous reflexes were exacerbated and he had spastic tetraparesis. The endocrine evaluation showed a basal raise of GH (23ng/ml), TSH (6.2mUI/1) and prolactin (26ng/ml). The first two hormones did not respond to the acute test with TRH, while prolactin had a poor response. He was submitted to radiotherapy with linear acceleration (total dose of 4000 rads) and surgery, during which the tumor could not be completely removed due to its large size. After 9 months, the child is doing well, with a considerable weight gain (2500g).
 ...
PMID:[Russel's syndrome: diencephalic tumor in a child]. 211 20

We have studied the differential susceptibility to endoglycosidase F and H of oligosaccharides at the individual glycosylation sites of mouse TSH and free alpha-subunits. Mouse thyrotropic tumor tissue was incubated with D-[2-3H]mannose for 6 h. [3H]Man-labeled TSH and free alpha-subunits were obtained from homogenates using specific antisera and were digested with endoglycosidase F and H in their native states or after heat-denaturation and reduction in the presence of detergents. Tryptic fragments of the digestion products were then analyzed by reverse phase HPLC so that effects of endoglycosidase at the individual glycosylation sites could be determined. There was very little preferential cleavage by endoglycosidase H and F among the glycosylation sites of TSH subunits. Endoglycosidase F treatment of native free alpha-subunits showed slight preferential cleavage at Asn 82 of alpha-subunits after a 4 h incubation, whereas endoglycosidase H cleaved oligosaccharides equally well at Asn 56 and Asn 82. The Asn 82 oligosaccharide of native TSH heterodimers was also slightly preferentially cleaved by endoglycosidase F, but endoglycosidase H cleaved oligosaccharides equally well at all TSH glycosylation sites. Heat denaturation, reduction and the presence of detergent did not alter this slight preferential cleavage by endoglycosidase F at Asn 82 of alpha-subunits, suggesting that the primary structures of the TSH subunits in part influenced the efficiency of enzyme action at specific sites. Thus, the susceptibility to endoglycosidase F differs very slightly at the individual glycosylation sites of mouse TSH and free alpha-subunits, and these small differences could be due to properties of either the enzyme or substrates.
 ...
PMID:Susceptibility to endoglycosidase F and H at the individual glycosylation sites of mouse thyrotropin and free alpha-subunits. 211 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>