Akinari Hidaka

The Thyrotropin Receptor

This chapter has outlined the complex process required for thyroid growth and function. Both events are regulated by TSHR via a multiplicity of signals, with the aid of and requirement for a multiplicity of hormones that regulate the TSHR via receptor cross-talk: insulin, IGF-I, adrenergic receptors, and purinergic receptors. Cross-talk appears to regulate G-protein interactions or activities induced by TSH as well as TSHR gene expression. The TSHR structure and its mechanism of signal transduction is being rapidly unraveled in several laboratories, since the recent cloning of the receptor. In addition, the epitopes for autoantibodies against the receptor that can subvert the normal regulated synthesis and secretion of thyroid hormones, causing hyper- or hypofunction, have been defined. Studies of regulation of the TSHR minimal promotor have uncovered a better understanding of the mechanisms by which TSH regulates both growth and function of the thyroid cell. A key novel component of this phenomenon involves TSH AMP positive and negative regulation of the TSHR. Negative transcriptional regulation is a common feature of MHC class I genes in the thyroid. Subversion of negative regulation or too little negative regulation is suggested to result in autoimmune disease. Methimazole and iodide at autoregulatory levels may be important in reversing this process and returning thyroid function to normal. Their action appears to involve factors that react with the IREs on both the TSHR and the TG promoter. Too much negative regulation, as in the case of ras transformation, results in abnormal growth without function. TTF-1 is implicated as a critical autoregulatory component in both positive and negative regulation of the TSHR and appears to be the link between TSH, the TSHR, TSHR-mediated signals, TG and TPO biosynthesis, and thyroid hormone formation. Differentially regulated expression of the TSHR and TG by cAMP and insulin depend on differences in the specificity of the TTF-1 site, that is, the lack of Pax-8 interactions with the TSHR, and the IRE sites. Single-strand binding proteins will become important in determining how TSHR transcription is controlled mechanistically.

Serum CA 19-9 concentrations and computed tomography findings in patients with pancreatic carcinoma.

Carbohydrate antigen (CA) 19‐9 is a new tumor markerdefined by a monoclonal antibody. Serum CA 19‐9 concentrations and computed tomography (CT) findings were studied in 55 patients with histologically proven adenocarcinomaand in 22 patients with chronic pancreatitis. CA 19‐9 was useful in 83% of cases for the differential diagnosis between pancreatic carcinoma and chronic pancreatitisand serum CA 19‐9 levels in pancreatic carcinoma were highly related to the size of tumors. Serum CA 19‐9 levels greater than 37 U/ml were seen in patients with a tumor of less than 3 cm3 to 5 cmand greater than 5 cm in diameter 13% (1/8)90% (19/21)and 92% (24/26) of casesrespectively. Tumor locationhoweverwas unrelated to serum CA 19‐9 value. These results indicated that the measurement of serum CA 19‐9 concentrations would be useful in mostif not allcases for the differential diagnosis between pancreatic carcinoma and chronic pancreatitisand for the evaluation of tumor burden in patients with pancreatic carcinoma.

Recruitment of T lymphocytes and induction of tumor necrosis factor in thyroid cancer by a local immunotherapy

SummaryTo elucidate the mechanism of action for intratumoral injection of immunopotentiators, infiltrating mononuclear cells and tumor necrosis factor (TNF) were assayed by immunostaining tissue samples of differentiated thyroid cancer resected with or without presurgical local application of OK-432, a streptococcal preparation. Frozen sections of resected specimens were stained with monoclonal antibodies using either a conventional or a modified immunoperoxidase method. The tumors injected with OK-432 showed increased T lymphocyte infiltration and HLA-DR expression on cancer cells as compared to the non-injected controls. Among these T cells, the CD4+ subset was more numerous than the CD8+ population. In four out of the seven cases constituting the injected group, numerous TNF-positive cells were seen in clusters or lines as well as scattered, while none of the seven cases in the control group was associated with a considerable amount of these cells. In their morphology and distribution pattern, these TNF-positive cells appeared to be of macrophage lineage. Thus local injection of OK-432 in thyroid cancer was shown to recruit T lymphocytes of predominantly the CD4+ subset and to induce in situ production of TNF, a known potent tumoricidal cytokine. The present data warrant further studies in this direction besides wider clinical intratumoral application of the reagent.

Lymphoproliferative disorders of the thyroid gland : radiological appearances

Images of lymphoproliferative disorders of the thyroid by ultrasonography (US), computed tomography (CT), 99Tcm and 67Ga scintigraphy were analysed in eight patients (two men and six women, aged 42-83 years). Seven patients were diagnosed as having primary lymphoma and one plasmacytoma. Ultrasound revealed a solid mass with homogeneous and very low echogenicity clearly distinguishable from residual thyroid tissue in five patients, diffuse hypoechoic goitre in one and multiple irregular hypoechoic nodules in both lobes in the patient with plasmacytoma (Case 8). Computed tomography demonstrated a focal low-density area in six cases of lymphoma and decreased density throughout the gland in the other two patients. 99Tcm scintigraphy showed hemilobar enlargement with decreased and uneven trapping, cold area or complete lobar defect in six patients with lymphoma and no trapping in the case of plasmacytoma. 67Ga scintigraphy demonstrated high accumulation in lymphoma and faint accumulation in the case of plasmacytoma. Radiological manifestations with a focal lesion were considered typical and diagnostic of primary thyroid lymphoma, while in one case with diffuse infiltration through the whole gland, the differential diagnosis from Hashimotos thyroiditis could not be made. In the final case, cells infiltrated diffusely to form islands with patchy distribution among well preserved follicles, correlating with the multiple hypoechoic areas observed by US.

Endotoxemia in patients on hemodialysis

We examined endotoxins and limulus amebocyte lysate-reactive material (LAL-RM) in serum from 87 patients on hemodialysis, using the conventional chromogenic limulus test (CCLT) and a new specific endotoxin assay with factor G-free LAL (endotoxin-specific test: EST). All patients with regenerated cellulose dialyzers had increased CCLT values, whereas the EST values were not higher than in controls. This discrepancy can be explained by the LAL-RM which is cellulose-derived and cross-reacts with LAL via factor G. Using EST for measurements of endotoxin, 6 patients out of 87 had pathological endotoxemia and all of these patients were associated with either cirrhosis, infection, or malignancy. Some patients who had no complications showed fever before or during dialysis, but they did not have high endotoxin levels. EST is useful for the diagnosis of endotoxemia in patients on hemodialysis because of the presence of LAL-RM in serum. Endotoxemia is rare in patients on hemodialysis, if they are not associated with infection, cirrhosis, or other complications.

Acute Hepatic Failure following Transcatheter Arterial Embolization for the Treatment of Hepatocellular Carcinoma

We conducted a retrospective analysis to evaluate the risk factors associated with the occurrence of acute hepatic failure following transcatheter arterial embolization (TAE) for hepatocellular carcinoma. From 1984 to 1993 we performed a total of 623 embolization procedures in 369 patients with both hepatocellular carcinoma and chronic liver disease. Within 2 weeks after TAE, 13 patients (2.1%) experienced hepatic failure as characterized by a rapid increase in serum bilirubin levels and the development of hepatic encephalopathy of grade 2 or higher. These results indicated that the following are risk factors for acute hepatic failure after TAE: poor hepatic functional reserve; high-dose infusion of chemotherapeutic agents, and a history of multiple embolization procedures.

Abrupt onset of sensorineural hearing loss and tinnitus in a patient with capillary telangiectasia of the pons

Capillary telangiectasia is often found incidentally on magnetic resonance imaging and may be associated with minor neurologic symptoms, but there has been little evidence about whether such lesions are responsible for these symptoms. Here we report a case of capillary telangiectasia of the right mid pons, which was associated with the abrupt onset of tinnitus and sensorineural hearing loss. Examination of the auditory brain stem responses showed abnormalities of waves III and IV on the left and bilateral prolongation of the interwave intervals. Optokinetic nystagmus showed slight left-right asymmetry.

Increased uptake of iodine-131 in metastases of differentiated thyroid carcinoma associated with less severe hypothyroidism following total thyroidectomy.

Background. In an attempt to determine possible factors affecting the efficacy of iodine‐131 (I‐131) treatment for metastatic thyroid carcinoma, the authors focused their efforts on thyroid functions after total thyroidectomy.

Undifferentiated carcinoma of the thyroid gland : sonographic findings

We report high resolution sonographic (7.5 MHz) findings in four cases of undifferentiated carcinoma of the thyroid gland. Sonographic findings in these four cases included poorly marginated, hypoechoic masses associated with calcifications, and invasion of adjacent cervical structures. A knowledge of the sonographic features of undifferentiated carcinoma of the thyroid gland is of clinical importance, since the tumour has a grave prognosis, quite different from the relatively favourable prognosis of well differentiated thyroid carcinoma.

Thyrotoxic graves' disease with normal thyroidal technetium-99m pertechnetate uptake

We saw 24 thyrotoxic Graves’ patients with normal thyroidal uptake of technetium-99m pertechnetate (99mTc) out of 201 untreated thyrotoxic Graves’ patients seen over 4 years. The clinical and laboratory findings for these patients were studied and analysed.Thyroid uptake and scintigraphic examinations by means of99mTc, TBII and TSab activity measurement clearly distinguished these patients from other thyrotoxic disorders (destruction-induced thyrotoxicosis and autonomously functioning thyroid lesions). Different from other disorders, these patients had not lower but normal thyroid uptake and also showed diffuse and discrete trapping into the enlarged glands.These patients had significantly smaller goiters, a lower serum thyroid hormone level, and lower TBII and TSab activity, when compared with other high99mTc uptake groups with Graves’ disease, and their condition could be easily controlled with small amounts of antithyroid drugs.Our study indicates that thyrotoxic Graves’ disease with normal99mTc uptake exists and99mTc uptake study and TBII activity measurement is very useful for the diagnosis. The normal99mTc uptake thyrotoxic Graves’ patient might be early stage patients with general Graves’ disease and their early discrimination from general Graves’ patients is very advantageous for treatment and prognosis.