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Biomedical subjects

K Kuma

Publications and source records attributed to K Kuma.

At least 235 records · Page 13Linked to original sources

Chronic thyroiditis as a risk factor of B-cell lymphoma in the thyroid gland.

In order to contribute to the etiological study of thyroid lymphomas, the development of lymphomas in pre-existing chronic thyroiditis was statistically investigated. A total of 5592 female patients (older than 25 years) with chronic thyroiditis diagnosed between 1965 and 1982 at Kuma Hospital in Hyogo Prefecture were followed up until December 31, 1984. From a total of 45623 person-years, 8 new cases of primary thyroid lymphoma were observed (O), all of which were judged to be B-cell type from their immunological or histopathological characteristics. Since the expected number of cases with malignant lymphomas (E1) and the expected number of cases with thyroid lymphomas (E2) were 2.45 and 0.10, respectively, the O/E1 and O/E2 ratios were 3.3 (P less than 0.01) and 80.0 (P less than 0.001), respectively. The average follow-up interval for the patients with thyroid lymphoma was 9.2 years. In the reference group, consisting of cases with Basedow's disease, an increased risk of thyroid lymphoma was not observed. The present results suggest that autoimmune reactions with a notable lymphocytic infiltrate may play an important role in the etiology of lymphomas in the thyroid gland.

Adult↗

Gastrin-releasing peptide immunoreactivity in medullary thyroid carcinoma.

Two cases of gastrin releasing peptide (GRP)-producing medullary thyroid carcinoma are presented. Immunohistochemical examination revealed the presence of GRP-like immunoreactivity (IR-GRP) in the primary tumor tissues. High concentration of IR-GRP was also demonstrated in extracts of the primary tumors by radioimmunologic means with use of a GRP-specific antiserum. Chromatographic analysis showed that the immunoreactivity was composed of at least two molecular forms: one behaved as synthetic porcine GRP on Sephadex G-50 gel filtration and the other as porcine GRP (14-27), a C-terminal active fragment of GRP. The IR-GRP was shown not to be attributed to bombesin-like immunoreactivity. Substance P-like immunoreactivity was not detected in the tumor tissues by either immunohistochemical or radioimmunologic means. This is, as far as the authors are aware, the first finding of IR-GRP as an ectopic product in medullary carcinoma.

Calcitonin↗

[A long-term follow-up study of patients with chronic lymphocytic thyroiditis--with special reference to histological findings].

It is generally believed that in the long-term observation of chronic thyroiditis, the goiter decreases in size with thyroid hormone therapy and the thyroid function drops gradually. On the other hand, the histological changes in so-called Hashimoto's thyroiditis have been recognized to show progressive loss of epithelium and increased fibrosis. In this study, goiter size, thyroid function, thyroid microsomal and thyroglobulin antibodies and histology in needle biopsy were investigated in 75 patients with chronic thyroiditis during an interval of more than ten years. Among 75 cases, 8 (11%) were hypothyroid at the first medical examination. Among 21 cases who received no treatment, 7 (33%) became hypothyroid during the period of more than ten years. Among 54 cases with thyroid hormone therapy, 16 (30%) showed a remarkable reduction in size of goiter, but among 21 cases without thyroid hormone therapy only 3 (14%) showed a remarkable reduction. This paper discusses changes in titers of thyroidal antibodies in 47 cases. Among these 47 cases, 21 increased titer of thyroglobulin antibody during the period of more than ten years. 10 (48%) out of these 21 cases showed a remarkable reduction in size of goiter. But among 11 cases with a decrease of titer of thyroglobulin antibody, only one (9%) showed a remarkable reduction in size of goiter. On the other hand, titer of thyroid microsomal antibody increased in 33 cases. 9 (27%) out of these 33 cases showed a remarkable reduction in size of goiter. Only one (13%) of 8 cases, which decreased titer of thyroid microsomal antibody, showed a remarkable reduction in size of goiter.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

Thyroid T4 5'-deiodinase activity in normal and abnormal human thyroid glands.

To investigate the activity of the thyroid gland to convert T4 to T3, we measured the activity of thyroid T4 5'-deiodinase in the following human thyroid glands: 9 normal glands, 5 Hashimoto's thyroiditis, 13 follicular adenomas, 11 methimazole (MMI)-treated Graves' disease (GD), 11 propranolol iodide-treated GD, and 8 propylthiouracil (PTU)-treated GD. The enzyme activity was determined by the ability of 100,000 X g pellet of the thyroid homogenate to convert T4 to T3 in vitro. Normal thyroids showed the enzyme activity of 1.59 +/- 0.18 (mean +/- SEM) pmol T3/mg protein/min. Euthyroid Hashimoto's thyroiditis displayed the enzyme activity of 1.01 +/- 0.15 pmol T3/mg protein/min, which was similar to the normal thyroid enzyme activity. The hypothyroid gland of Hashimoto's thyroiditis showed the enzyme activity of 1.8 pmol T3/mg protein/min. Follicular adenomas showed a wide range of enzyme activity with the mean level of 3.24 +/- 0.82 pmol T3/mg protein/min that did not differ significantly from that of the normal thyroids. Interestingly, one adenoma, despite TSH suppression that ordinarily decreases enzyme activity, showed the greatest activity of 11.0 pmol T3/mg protein/min. Graves' thyroids following treatment with MMI, PTU, and propranolol-iodide showed enzyme activities of 4.61 +/- 0.53, 3.95 +/- 0.43, and 3.51 +/- 0.46 pmol T3/mg protein/min, respectively; all these values were greater than that of the normal thyroids (P less than 0.01), but did not differ significantly when compared with each other. In summary, thyroid glands with Hashimoto's thyroiditis had activities of T4 to T3 conversion similar to the normal thyroid glands.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma.

Plasma calcitonin (CT) levels were measured serially in 54 patients surgically treated for medullary thyroid carcinoma. Patients with postoperative basal CT levels higher than 1 ng/ml measured within 1 month after surgery had a higher recurrence rate than those with lower CT levels (p less than 0.002). Patients with postoperative basal CT levels higher than 2 ng/ml had a lower survival rate than those with lower CT levels (p less than 0.01). However, preoperative basal CT levels had no significant correlation with life expectancy or recurrence during the present observation period. Serial measurements in 23 patients with elevated postoperative CT levels showed exponential increases in basal CT levels in 19 patients (p less than 0.05 in nine patients, 0.05 less than p less than 0.1 in four patients) and slight decreases in four (p less than 0.05 in one patient). Doubling time of CT levels calculated from the regression line in each patient showed the highest correlation with 3-year survival, recurrence within 5 years, and time interval between surgery and clinical recurrence of the tumor, allowing quantitative prediction of the prognosis.

Calcitonin↗

Bromocriptine therapy for hyperthyroidism due to increased thyrotropin secretion.

We describe a patient with TSH-induced hyperthyroidism successfully treated with bromocriptine. A 25-yr-old woman was found to have hyperthyroidism due to excessive TSH secretion; no pituitary tumor was found. Her serum T4 level ranged between 21.9 and 25.9 micrograms/dl and that of T3 between 283 and 314 ng/dl. Serum TSH was between 5 and 9 microU/ml with an exaggerated response to TRH. Basal metabolic rate was +26 to +38%. Serum PRL was also elevated (79 ng/ml). Administration of bromocriptine for 4 months decreased serum TSH and PRL levels to normal with a concomitant fall in levels of serum T3 and T4. Regression of the clinical manifestations of hyperthyroidism occurred during bromocriptine drug therapy. These results suggest that reduction in hypothalamic dopaminergic tone may have contributed to the inappropriately increased TSH secretion in the patient.

Adult↗

Resistance of peripheral tissues and pituitary to thyroid hormone.

We describe a 29-year-old male with thyroid hormone resistance. He was first seen because of a goiter, and was considered to have hyperthyroid Graves' disease. Despite subtotal thyroidectomy followed by radioiodine therapy, serum thyroxine levels were elevated with high serum TSH levels. Baseline thyroid function showed serum thyroxine of 16.6 micrograms/dl, free thyroxine of 4.60 ng/dl, triiodothyronine of 197 ng/dl, and TSH of 34 microU/ml. Triiodothyronine administration by gradually increased doses of 75, 150, 225, 300, and 375 micrograms/d over a 25-day period resulted in gradual reduction of serum TSH and T4 levels, but serum TSH still responded to TRH even during this period. The basal metabolic rate was--14% and showed a minimal rise even with large doses of triiodothyronine. The results led to the diagnosis of generalized thyroid hormone resistance including the pituitary gland. Increased pulse rate, finger tremor and emotional lability in the patient suggest that the severity of peripheral refractoriness to the hormone may vary from tissue to tissue. In addition, a reduced thyroidal responsiveness to TSH as a consequence of inappropriate radioiodine therapy was observed in this patient.

Adult↗

Relation of structural polarity to responses of cyclic 3', 5'-adenosine monophosphate accumulation and thyroid hormone release in cultured human thyroid follicles.

The relationship of structural polarity to functional activities was examined in cultured human thyroid follicles, which were isolated from the thyroid gland of patients with Graves' disease by collagenase treatment. Structural polarity was examined morphologically by electron microscopy, while the functional response to bovine TSH was examined by measuring intracellular cAMP accumulation and T3 release. In freshly isolated thyroid follicles, structural polarity was normal and TSH induced significant cAMP accumulation but no significant release of T3. After culture for 5 days the structural polarity of thyroid follicles became inverted in the absence of thyroid stimulators, but normal polarity was retained in the presence of TSH or dibutyryl cAMP [Bu)2 cAMP). The response to TSH of cAMP accumulation increased markedly after culture in either the presence or absence of TSH, suggesting that cAMP accumulation in response to TSH is not related to structural polarity. In contrast, thyroid follicles cultured without thyroid stimulators showed no significant T3 release in response to TSH, whereas those cultured with TSH or (Bu)2 cAMP showed significant T3 release in response to TSH. These data indicate that in cultured human thyroid follicles, the responses to TSH of cAMP accumulation and T3 release are not always correlated. Among many other explanations, the results were at least compatible with the idea that normal structural polarity is necessary for thyroid hormone release in response to TSH.

Bucladesine↗

Ratio of serum triiodothyronine to thyroxine and the prognosis of triiodothyronine-predominant Graves' disease.

Triiodothyronine (T3)-predominant Graves' disease is characterized by persistently high serum T3 level, normal serum thyroxine (T4) level, and high (greater than 20) serum T3/T4 ratio (nanograms/micrograms) during thionamide drug therapy. We studied the clinical course of 30 patients with T3-predominant Graves' disease. After receiving drug therapy for 1 to 4 years, 27 patients with T3-predominant Graves' disease had relapses, whereas only 9 control patients with Graves' disease whose serum T3/T4 ratio had become persistently normal (less than 20) had relapses. The T3-predominant patients had greater serum TSH receptor antibody activity, thyroid T4 5'-deiodinase activity, and decreased T3 content of thyroglobulin when compared with the control patients. Our findings show that patients with T3-predominant Graves' disease are unlikely to have a long-term remission with drug therapy. The cause of high serum T3/T4 ratio is due, in part, to the more active thyroid T4 5'-deiodinase that may be mediated by high levels of Graves' immunoglobulin.

Adolescent↗

[Chronology of medullary carcinoma of the thyroid].

In order to study the chronological progress of medullary carcinoma of the thyroid, clinical records and histological findings of 62 patients with the tumor were reviewed. Postoperative plasma calcitonin levels were examined in 54 patients. Among the patients with the disease of the hereditary type, those of 30 years of age younger with no lymph node involvement and a tumor weight less than 5 g were most likely to have normal plasma calcitonin levels postoperatively, provided total thyroidectomy were performed. The peak of age distribution of patients of the hereditary type without lymph node involvement was 15 years less than that of those with nodal involvement. In the sporadic type, there was no correlation between teh age and the nodal nodal involvement. Plasma calcitonin levels in the patients with residual tumor showed exponential increase according to the time course. The regression lines, log y = log a + bx (y: plasma calcitonin level, x: years after operation), were calculated in 23 patients followed 6 months or longer. The doubling time of the plasma calcitonin level (T2), given as 1/b log 2, correlated well with the tumor progression rate. T2 for patients of the hereditary type were 0.8 years or longer except for one. Four patients of the sporadic type with T2 of 0.1-0.3 year within 3 years after operation.

Adolescent↗

Plasma inactive renin in patients with hyperthyroidism.

Active and inactive PRA were measured after 1 h at rest in 16 normal controls and 20 patients with hyperthyroidism. In some of the patients these measurements were repeated after they had become euthyroid or received 90 mg propranolol for 1 week. Inactive PRA was determined as the difference between total PRA after trypsin activation and active PRA. Active PRA was significantly higher (P less than 0.01) in untreated patients than in normal subjects; however, the inactive PRA of patients was not different compared with that of normal subjects. Active PRA was normalized, and inactive PRA did not change after achievement of euthyroidism. The proportion of active of total PRA was significantly correlated with the levels of serum thyroid hormones (T3 and T4) in hyperthyroid patients (r = 0.46; P less than 0.05 and r = 0.55; P less than 0.01, respectively). The administration of propranolol reduced active PRA (P less than 0.05) and increased inactive PRA slightly but not significantly. These results indicate that in hyperthyroidism, the in vivo conversion of inactive renin to active renin is probably facilitated by increased sympathetic activity.

Adult↗

Induction of outer and inner ring monodeiodinases in human thyroid gland by thyrotropin.

The effects of TSH on iodothyronine 5- and 5'-deiodinations were investigated using cultured thyroid tissues from patients with Graves' disease. The addition of TSH to the culture medium stimulated all of the iodothyronine-deiodinating activities of thyroid tissues cultured for more than 4 days. Peak TSH-induced activities were found on the fifth day of culture, and increased activities were found up to 9 days. On the fifth day of culture, TSH enhanced both outer and inner ring monodeiodinations in a dose-responsive manner between 62.5 and 250 microU/ml. This stimulation by TSH was blocked by the addition of actinomycin D or propylthiouracil. Incubation of thyroid tissues with (Bu)2cAMP mimicked the action of TSH, and theophylline potentiated the action of TSH. These results suggest that TSH, in an action probably mediated by cAMP, induces synthesis of iodothyronine deiodinases in the thyroid gland.

Bucladesine↗

Iodine content of serum thyroglobulin in normal individuals and patients with thyroid tumors.

We indirectly estimated the iodine content of serum thyroglobulin (TG) in normal individuals and patients with benign and malignant thyroid tumors. Because insufficient TG is present in the serum to perform chemical determinations, equilibrium density centrifugation was used to determine its density, a measure of TG iodine content. In five patients undergoing thyroidectomy, serum TG was compared to TG extracted from the nodules and TG from the surrounding normal thyroid tissue. The iodine content of the tumor TG was much less than that of normal TG in four of the five patients. In patients with benign and malignant nodules, the iodine content of serum TG was lower than that of normal TG, and it was similar in patients with benign and malignant disease. In normal individuals, serum TG was also poor in iodine, similar to the serum TG from the patients, and in the same position as TG with virtually no iodine. These findings are in accord with our report that serum TG in rats is nearly completely devoid of iodine. TG could enter the circulation either by secretion of newly synthesized TG or release of stored TG from the thyroid. The findings show that serum TG in normal individuals does not result from the release of preexisting TG. More likely, it arises from the secretion of poorly iodinated, newly synthesized molecules. Since the elevated serum TG found in patients with nodules also is poor in iodine, it must come directly from the tumor rather than from destruction of surrounding normal thyroid tissue.

Adenocarcinoma↗

A study of thyroid function after subtotal thyroidectomy for Graves' disease: particularly on TRH tests, T3 suppression tests and antithyroid antibodies in euthyroid patients.

Of 305 patients who underwent subtotal thyroidectomy for Graves' disease between 1969 and 1975, recurrent hyperthyroidism was found in 31 (10.2%) and hypothyroidism in 18 (5.9%). The remaining 256 patients were clinically euthyroid, but an elevated serum TSH level was found in 104 (34.1%) and an elevated serum T3 level in 19 (6.28%). In 57 of 133 clinically and biochemically euthyroid patients, a TRH test, T3 suppression test and measurement of antithyroid antibodies were performed. Twenty-nine of the 57 patients (50.9%) showed an abnormal response to TRH. Eight of these (14.0%) showed an impaired or absent response. The T3 suppression test showed that 15 of the 57 patients (26.3%) were non-suppressible. Positive antithyroid antibodies, especially antimicrosomal antibodies, were more frequent in non-suppressible and TRH-non-responsive patients than in suppressible and TRH-responsive patients. It is suggested that after operation for Graves' disease: 1) only half of the clinically euthyroid patients were biochemically euthyroid, 2) of the clinically and biochemically euthyroid patients, there were many with abnormalities in TRH responsiveness and T3 suppressibility, and 3) thyroid functional status is unstable and long careful follow-up is important after operation for Graves' disease.

Adolescent↗