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

The authors reported a rare case of sellar germinoma which was misdiagnosed as nonfunctioning pituitary adenoma. A 32-year-old woman was admitted to our hospital because of amenorrhea and disturbance of left visual acuity. She had become amenorrhagic after her second delivery two years before. Neurological examination revealed she was normal except for diminished left visual acuity (Rt. = 1.2, Lt. = 0.5). The general condition was good. Urine volume and its specific gravity were within normal range. Endocrinological examination showed hyperprolactinemia (PRL 72 ng/ml) accompanied with impairment of GH, TSH, LH and FSH's reserve. Basal levels and reserve of the blood cortisol were normal. AFP and hCG were within normal range. CT scan revealed a homogenously enhanced intrasellar tumor which had a suprasellar portion (vertical length: 15 mm). T1 weighted MRI revealed low intensity tumor, and T2 weighted image revealed high intensity tumor. Sagittal MR image with gadolinium enhancement showed the pituitary gland anterior to the tumor. Transsphenoidal removal was performed. The histological diagnosis was pure germinoma. After the operation, the intracranial and spinal disseminations were disclosed. Complete neuraxis irradiation resulted in the complete remission of the tumor. Sellar germinoma without diabetes insipidus is considered to be very difficult to diagnose preoperatively. However, the authors proposed that anterior shift of the pituitary gland in sagittal MR image may be a clue to the diagnosis of sellar germinoma.
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PMID:[A case of sellar germinoma which was misdiagnosed as pituitary adenoma]. 176 58

Long-term results and statistical analysis of prognostic factors in a series of 214 patients with distant metastases from differentiated thyroid cancer (DTC) are reported here. These 214 were part of a total series of 1457 patients with DTC referred to our center from 1967 to 1987. All patients underwent surgery and 131-I therapy and were treated with TSH suppressive doses of thyroid hormones. After a mean follow-up of 7.3 years including clinical, scintigraphic, radiological and laboratory investigations, 24.4% of patients were alive without disease, 36.5% alive with disease, 1.8% dead without disease and 37.3% dead with disease. One of the main factors influencing the survival in our series was 131-I uptake (RIU) by metastatic tissue. No case of complete remission of disease was observed among patients with nonfunctioning metastases. Another important factor was the site of metastases, patients with bone metastases having the worst prognosis. The patient's age at diagnosis represented another important factor for survival; patients over 40 years, particularly those over 60 years had a bad prognosis. A clear interrelation was found among the factors advanced age, nonfunctioning metastases and bone metastases. Patients with these last clinical features were considered to be at high risk and generally had a fatal outcome. Another significant prognostic factor revealed by univariate analysis was the histologic type. Patients with follicular tumor showed a poorer prognosis in comparison to papillary tumor. When multivariate analysis was applied, the factors age at diagnosis, site of metastases and RIU proved to have a significant influence on survival, but not the histologic type. Lastly, the relative rate of males was higher in the group of patients with metastases in comparison to the whole series of DTC patients. Despite this, the factor sex did not influence survival.
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PMID:Distant metastases in differentiated thyroid cancer: long-term results of radioiodine treatment and statistical analysis of prognostic factors in 214 patients. 178 Oct 39

To study coexpression patterns in normal and adenomatous pituitaries, frozen (n = 4) and paraffin-embedded (n = 10), normal human glands and 34 pituitary adenomas were investigated, using immunoperoxidase and double-labeling immunofluorescence methods. Broad range monoclonal antibodies (mAB) against cytokeratins (CK) (lu-5, A45-B/B3, AE1/3, CAM 5.2) as well as anti-CK18 (DC10) and anti CK19 (A53-B/A2) were compared with mAB's against vimentin, epithelial membrane antigen (EMA), epithelial sialomucin (ESM 140 C1), GFAP (GF-2), neurofilament (2F11), Leu-7 (HNK-1) and polyclonal AB's against pituitary hormones (ACTH, FSH, LH, TSH, GH, PRL). CK and vimentin coexpressing endocrine cells, mainly of the ACTH type, were observed in the pars intermedia in 5 of 14 normal pituitaries. All hormone producing cells expressed CK. The mAB A53-B/A2 (CK19) stained selectively the folliculo-stellate cells in frozen and paraffin sections. EMA, sialomucin and Leu-7 antigen localized to different structures of normal pituitaries. 25 of 34 pituitary adenomas exhibited CK positive tumor cells. Coexpression of vimentin or neurofilament protein was rare (2 cases of each). 9 CK negative adenomas were also negative for other intermediate filament proteins. 6 hormone producing adenomas showed unusual positivity for CK19. Whereas EMA and sialomucin reactivity disappeared in adenoma tissues, an enhanced Leu-7 antigen expression in the GH and prolactin adenoma group was noted. The heterogeneity of antigen expression seen in normal and neoplastic pituitary cells calls for further functional studies and usage of a broad range of mAB's against intermediate filaments in immunohistochemical studies of the pituitary.
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PMID:Immunohistochemical studies on human pituitary gland and adenomas. 182 19

In order to assess the localization and physiologic redistribution of Golgi enzymes within mouse thyrotrophs, we studied the carbohydrate processing of TSH subunits in the presence of brefeldin A (BFA). Although this drug clearly causes endoglycosidase (endo) H-sensitive species to accumulate in most cell types, our purpose was to determine whether or not endoglycosidase H-resistant forms of free alpha-subunits and TSH subunits eventually accumulated in small but significant amounts within mouse thyrotrophic tumor cells or pituitary thyrotrophs incubated with BFA. This drug is known to block intracellular transport from the rough endoplasmic reticulum (RER) to the proximal Golgi. Stimulated thyrotrophs have been reported to have some Golgi enzymes active in their dilated RER. Accumulation of endo H-resistant forms in the presence of BFA might be explained by (1) drug-induced enhancement of Golgi to RER membrane recycling with further aberrant distribution of Golgi enzymes or (2) an uncharacteristic trapping of glycoproteins within Golgi elements that might be an unusual action of BFA peculiar to thyrotrophs. Free alpha-subunits and TSH were labeled in mouse thyrotrophic tumor tissue or pituitaries incubated in pulse-chase fashion with [35S]methionine in the absence or presence of BFA, carboxyl cyanide m-chlorophylhydrazone (CCCP), or swainsonine. The results in tumor and pituitary tissue were similar. In incubations without drugs, most TSH subunits (greater than 90%) became endo H-resistant after 5-h chase, and the majority (greater than 85%) were secreted. Doses of CCCP and BFA were selected that generally blocked the secretion of TSH subunits by greater than 85% (in some cases greater than 99%), presumably because of accumulation of secretory proteins in the RER. Yet, in the presence of CCCP, 35% and 42% of intracellular free alpha-subunits and TSH subunits, respectively, became endo H-resistant at 5 h chase. Compared to control incubations, intracellular subunits tended to remain endo H-sensitive in the presence of BFA, yet, compared to CCCP incubations, BFA slightly enhanced the attainment of endo H-resistance by free alpha-subunits and TSH subunits to 55% and 52%, respectively. Pretreatment of tumor tissue with BFA allowed more endo H-resistant species to appear, even during coincubation with CCCP. These data suggest that Golgi enzymes cycle back to the dilated RER of active thyrotrophs and that this phenomenon is enhanced by BFA.
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PMID:Processing to endoglycosidase H-resistant thyrotropin subunits occurs in the presence of brefeldin-A: evidence favoring the recycling of Golgi membranes to the rough endoplasmic reticulum in mouse thyrotrophs. 182 66

Tumor-promoting phorbol esters, e.g., 12-O-tetradecanoylphorbol 13-acetate (TPA), inhibit TSH-stimulated iodide organification in vitro implying a role for protein kinase C (PKC) in the regulation of differentiated thyroid function. To further explore the PKC dependence of this action of TPA, we studied the effects of PKC inhibition and downregulation on phorbol-mediated differentiated thyroid function in vitro. In addition, the effects of the nonphorbol PKC activator, phospholipase C (PLC) were studied. TPA (100 nM) inhibited TSH-stimulated iodide organification in cultured porcine thyroid cells by over 95% and caused PKC translocation in vitro. Exogenous PLC (1 U/mL) could mimic these effects of TPA. The PKC inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) inhibited TSH-stimulated iodide organification at concentrations exceeding 10 microM. However, partial recovery of phorbol- and PLC-inhibited iodide organification was seen in the presence of identical concentrations of H7. H7 had no effect on PKC translocation in porcine thyroid cell extracts. After 24 h of TPA treatment to induce PKC downregulation, no recovery of TSH-stimulated iodide organification was observed, suggesting that the effects of TPA were irreversible. These studies indicate that the effects of TPA and PLC on differentiated thyroid function are mediated, at least in part, by PKC. These findings provide further evidence for a role for PKC in the regulation of differentiated thyroid function.
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PMID:Phorbol ester and phospholipase C-mediated differentiated thyroid function in vitro: the effects of protein kinase C inhibition and downregulation. 182 67

A 24-year-old housewife presented with weight gain of about 30 kg, constipation and pitting edema of extremity nine years after having a thyroidectomy. Hormonal examination revealed low levels of serum T3 and T4 and high levels of serum TSH and PRL. She also had enlarged pituitary gland (pituitary hyperplasia) with suprasellar extension on CT and MRI image. Thyroid replacement therapy and follow-up by MRI were performed without resort to surgery, because she had no visual disturbance. Within about 1 month after thyroid replacement therapy, serum TSH and PRL were normalized. And also thyroid function was normalized by thyronine (T3). Following this results, pituitary hyperplasia regression was seen on MRI image. About 1 year after thyroid replacement therapy, pituitary hyperplasia regression was more seen on MRI image. Prolonged hypothyroidism can result in hypertrophy of the pituitary thyrotropin-secreting cells and prolactin secreting cells. So, it can increase pituitary weight (pituitary hyperplasia). Radiological examination, abnormal sellar x-ray films suggesting intrasellar tumor are common in patients with primary hypothyroidism. Suprasellar extension of pituitary mass (pituitary hyperplasia) due to hypothyroidism was reported by radiological examination (PEG, CT and MRI image), and regression of pituitary hyperplasia was revealed by radiological examination after thyroid replacement therapy. The first choice of this type of pituitary hyperplasia is thyroid replacement therapy unless the patient has a visual disturbance. However, if this replacement therapy is not effective for diminution of the tumor, surgical removal of the tumor should be considered.
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PMID:[A case of pseudo-TSH.PRL-producing pituitary adenoma with secondary hypothyroidism]. 187 88

Investigations using a radioimmunoassay in 92 patients with nodular goiter, thyroid adenoma and cancer have shown that changes in the levels of T4, T3 and TSH cannot be used in differential diagnosis of tumors. A high level of thyroglobulin (TG) in 70-75% of patients in the absence of antibodies to it and the presence of a "cold node" on a scan is suggestive of differentiated types of thyroid cancer. In these cases TG can serve as a tumor marker. A moderate level of Tg in 25-30% of cases against a background of a high level of antibodies to it does not permit its use as a tumor marker in such patients even in the postoperative period. High levels of TG and TSH despite the use of thyroid drugs in patients, operated on for differentiated types of thyroid cancer, may be suggestive of a possible manifestation of a recurrence or metastatic spreading.
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PMID:[Radioimmunologic analysis in the differential diagnosis of cancer of the thyroid gland]. 188 Dec 85

In the last ten years, 47 patients with distant metastases of differentiated thyroid carcinoma have been treated with 131I following total thyroidectomy. Post-therapy whole body 131I scans revealed detectable uptake in the metastatic lesions in 23 (62%) of 37 patients with lung metastases, 10 (67%) of 15 patients with bone metastases five (71%) of seven patients with mediastinal metastases, and neither of two patients with brain metastases. The concentration of 131I in the metastases was significantly correlated with serum T3 and T4 concentrations, and inversely correlated with serum TSH concentrations. Most of the patients with a strong positive scan were euthyroid, suggesting that thyroid hormones produced by the tumor compensated for hypothyroidism following total thyroidectomy. There was no significant relationship between serum thyroglobulin concentration during T4 replacement therapy and 131I uptake or the efficacy of therapy. Twenty patients with lung (54%), five with bone (33%), two with mediastinal (29%), and none with brain metastases showed tumor regression after treatment. Significantly increased 131I uptake in lung metastases, better therapeutic results and better prognosis were demonstrated in young patients. In conclusion, age, 131I whole body scanning and serum thyroid hormone concentrations are considered to be useful in predicting the efficacy of 131I treatment for distant metastases, especially in the lung.
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PMID:[Results of radioiodine therapy in 47 patients with distant metastases of differentiated thyroid carcinoma]. 189 47

3,4-Dihydro-6-[4-(3,4-dimethoxybenzoyl)-1 piperaznyl]-2(1H)-quinolinone (OPC 8212) is a new synthetic quinolinone with potent cardiac inotropic action in man. Long term oral administration of OPC induces goiter and thyroid tumor formation in rats, associated with decreases in serum T4 and increases in serum TSH concentrations. Studies were carried out to explore the mechanisms responsible for these drug induced abnormalities. OPC 8212, administered for 1 week at doses of 500 and 2000 mg/kg.day mixed with the diet, resulted in an increase in thyroid weight, a decrease in circulating T4 and free T4 concentrations and an increase in serum TSH concentrations. OPC decreased the 5'-deiodinase (5'-D) activity in liver homogenates and increased the 5'-D activity in pituitary homogenates, consistent with hypothyroidism. OPC 8212 did not affect thyroid iodine metabolism and hormone synthesis or the binding of T4 to serum binding proteins. The hepatic uptake of 125 I-T4 4 h after T4 administration was significantly increased in OPC 8212 treated rats. The biliary excretion of administered 125 I-T4 was increased in OPC 8212-treated rats and most of the increase was due to an increase in the excretion of T4-glucuronide. Hepatic T4-glucuronyltransferase activity measured in vitro in OPC 8212 treated rats was increased as compared to that of controls. It is concluded that the effect of OPC 8212 on lowering serum T4 with a compensatory rise in TSH leading to goiter formation is due to a drug-induced increase in hepatic T4 disposal. The induction of T4-glucuronyl-transferase appears to play an important role in the increased biliary excretion of T4 in OPC 8212-treated rats.
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PMID:Effect of the cardiac inotropic drug, OPC 8212, on pituitary-thyroid function in the rat. 190 94

Thyroid hormones (T3) and their receptors (TR) play a critical role in the function of the pituitary gland, particularly in thyrotropes, where they regulate expression of the alpha- and beta-subunits of TSH. Since the pituitary gland is composed of several cell types, we undertook a characterization of TR subtypes in a murine thyrotropic tumor (TtT-97), an excellent model in which to study thyroid hormone action in thyrotropes. We screened a thyrotrope cDNA library with rat TR alpha 1 and TR beta 1 cDNA probes and isolated cDNAs encoding the mouse TR alpha 1 and TR beta 1 isoforms as well as a partial clone corresponding to the non-T3 binding carboxy-terminal alpha 2 variant. The polymerase chain reaction was used to amplify additional cDNAs for the specific 5' domains of the mouse TR beta 1 and the pituitary-specific TR beta 2 amino-terminal variant. Using hybridization probes that discriminate between the alpha and beta isoforms and their variants, we demonstrated that thyrotropes contain TR alpha 1 and alpha 2 mRNAs as well as transcripts encoding Rev-erbA, which arise by transcription from the opposite strand of the TR alpha gene. In thyrotropes, the ratio of alpha 2 to TR alpha 1 mRNA levels more closely resembled the distribution in mouse brain than that in heart, where the mRNA levels of TR alpha 1 and alpha 2 are comparable. TR beta 1 and TR beta 2 mRNAs were detected in thyrotropes and were of similar size (approximately 6.4 kilobases). Despite the almost complete conservation between the rat and mouse TR beta 1 sequences at the protein level, the mouse and rat TR beta 2-specific N-terminal domains were less conserved, and the mouse protein was shorter by 39 amino acids at the N-terminus. Of the receptor species, only the mRNA encoding the TR beta 2 isoform, which was restricted to thyrotropes, was decreased by T3 treatment, although the mRNA for the alpha 2 variant was also reduced by T3 in thyrotropes and heart tissue. Levels of TR beta 1 mRNA were not changed in liver, but were increased in thyrotropic tumors and also somewhat in brain, an organ that is not responsive to T3 by classical criteria.
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PMID:Isolation and characterization of mouse complementary DNAs encoding alpha and beta thyroid hormone receptors from thyrotrope cells: the mouse pituitary-specific beta 2 isoform differs at the amino terminus from the corresponding species from rat pituitary tumor cells. 194 3


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