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Biomedical subjects

M Azukizawa

Publications and source records attributed to M Azukizawa.

At least 19 recordsLinked to original sources

[Hyperthyroidism due to a TSH-secreting pituitary tumor].

A 28-year-old female with a 12-year history of goiter is presented. She had both clinical and laboratory evidence of hyperthyroidism, and her serum TSH was persistently and markedly elevated after treatment with antithyroid drugs. A TRH stimulation test resulted in no further rise in serum TSH after cessation of medication. Menses were regular and serum prolactin levels were normal. Serum LH and FSH responses to LHRH stimulation test were normal. No other evidence of pituitary or peripheral endocrine deficiencies existed. She underwent a subtotal thyroidectomy followed by 131I therapy three years later. A pituitary adenoma with sphenoidal and suprasellar extension was completely removed by transphenoidal approach. On light microscopy, it was mostly composed of chromophobic cells with occasional calcification showing sinusoidal pattern. On electron microscopy, most of the cells contained fine granules, which suggested thyrotroph. The immunoperoxidase technique revealed TSH beta in the cytoplasm of some adenoma cells. Three days postoperatively the patient's serum TSH levels returned to normal. TRH stimulation test produced a normal response in serum TSH. The patient was diagnosed hypothyroid by laboratory findings and is currently on thyroid replacement therapy. The patient became pregnant and delivered twice prior to the operation for pituitary adenoma. The previously reported TSH secreting adenomas associated with hyperthyroidism were reviewed.

Adenoma↗

Effects of exposure of pregnant rats to TRH on development of the pituitary-thyroid axis in their progeny.

TRH (10 and 1000 micrograms/kg body weight (BW] was injected ip into pregnant rats daily from day 0 to 20 of pregnancy, and the pituitary-thyroid axis of their pups (Mat-TRH rats) was examined on days 0, 4, 10, 21 and 90 after birth. The pituitary TSH content of male Mat-TRH rats was significantly lower on day 4, and higher on day 10 than that of control rats. The serum TSH was significantly higher on day 10 (except female 10 micrograms/kg group). An exaggerated TSH response to exogenous TRH (10 micrograms/kg BW; ip) was observed on day 10 (males, 1000 micrograms/kg group). The serum T4 level of female Mat-TRH rats was low on day 4 (1000 micrograms/kg group), and higher on day 10. On days 21 and 90, the levels of pituitary TSH, serum TSH and T4 in Mat-TRH rats were similar to those in controls, but the TSH response to TRH was still exaggerated (1000 micrograms/kg group). No significant difference between control and TRH-treated mothers was seen on days 10 and 90 postpartum except for a decreased pituitary TSH content on day 10 in the 1000 micrograms/kg group. It is concluded that repeated administration of TRH to pregnant rats shows an effect on the pituitary-thyroid axis function of their progeny in later life.

Animals↗

Thyroidal responses to human chorionic gonadotropin in the chick and rat.

The thyrotropic activity of human chorionic gonadotropin (hCG) has been examined in the chick and the rat. Uptake of 32PO4 by chick thyroid increased significantly with injection of bovine thyrotropin (bTSH) with a maximum response at 2.4 mU per chick. On the other hand, no significant stimulation of 32PO4 uptake was detected with injection of graded doses of highly purified hCG up to 0.25 mg per chick. 1 mg of partially purified hCG, equivalent in biological potency to the maximum dose of highly purified hCG used in the chick, did induce a significant increase in 32PO4 uptake. In rats, highly purified hCG stimulated a very significant release (p less than 0.001) of 125I from the thyroid and partially purified hCG had a thyrotropic activity equivalent to 0.42 microU bTSH/U hCG, identical to the value we reported in mice, 0.42 microU bTSH/U hCG. The duration of hCG action on thyroidal release of 125I in the rat was longer than that for bTSH, as it is in the mouse. hCG also induced a significant rise in the serum level of triiodothyronine in rats. We conclude that pure hCG is a weak thyrotropic substance in the rat but not in the chick. These results and other evidence suggest an inhibitory role for the densely glycosylated 30 amino acid residue C-terminal extension on the beta-subunit of hCG which limits, by steric hindrance, the interaction of the TSH-like hCG 'core' with thyrotropin receptors.

Animals↗

Effects of neonatal exposure to TRH on development of the pituitary-thyroid axis in rats.

TRH (10 and 1000 micrograms/kg body weight) was administered ip daily to neonatal rats from day 0 to 9 after birth (Neo-TRH rats) and their pituitary-thyroid axis was examined on days 4, 10, 21 and 90. The pituitary TSH content in Neo-TRH rats was significantly smaller than in controls on days 4 and 10. The serum TSH levels in Neo-TRH rats were significantly lower than those in controls on days 4 (male group only), 10 and 21 (only 10 micrograms/kg group). The serum T4 levels in Neo-TRH rats were lower than in controls on day 10. The reduced pituitary TSH content and serum TSH and T4 were restored to control levels on day 90. However, the response of serum TSH to exogenous TRH (10 micrograms/kg/ip) was blunted in Neo-TRH rats on days 10, 21 and 90. It is concluded that repetitive administration of TRH during the neonatal period suppresses the pituitary-thyroid axis in neonatal life, even after the basal hormone level has been restored to normal.

Animals↗

A case of pituitary adenoma with possible simultaneous secretion of thyrotropin and follicle-stimulating hormone.

A TSH- and FSH-screening pituitary adenoma was demonstrated in a 23-yr-old man who presented with bitemporal hemianopsia, but without clinical or laboratory evidences of hyper- or hypothyroidism or hypogonadism. Basal TSH (29-45 microunits/ml) and FSH (44-63 mIU/ml) were moderately elevated. GH and ACTH secretion were impaired, and basal PRL and testosterone were normal. TRH and LRH elicited a significant increase in TSH and FSH, respectively. The plasma glycoprotein alpha-subunit concentration was normal, and its response to simultaneous administration of TRH and LRH was low. Plasma TSH was not suppressed completely by exogenous T3. After operation and radiotherapy, elevated TSH and FSH as well as failure of T3 to suppress TSH were corrected. No significant changes in thyroid hormone concentration in the blood were detected in spite of the reduction of TSH. TSH and FSH concentrations in the tumor extract were lower than those in normal pituitaries. Histologically, the tumor was very vascular and consisted mostly of a single type of cell. The tumor cells were positively stained for FSH beta-subunit by immunohistochemical study, but for none of other pituitary hormones or subunits examined. Electron microscopic examination revealed relatively abundant single type secretory granules of high electron density. It is possible that the tumor simultaneously secreted TSH and FSH, the former possibly being immunologically active, but biologically inactive.

Adenoma↗

Hyperalimentation in treatment of anorexia nervosa.

Ten patients with anorexia nervosa were treated with intravenous hyperalimentation (IVH) and/or psychotherapy. The five patients were treated with both IVH and psychotherapy. The five patients were treated with both IVH and psychotherapy. Their body weight rose from 66 +/- 3% (mean +/- SE) to 78 +/- 6% of their ideal weight during hospitalization, and then to 91 +/- 5% during ambulatory observation for a period of 6 to 36 months. Another group of 5 patients were treated only with psychotherapy. Their body weight increased 69 +/- 3% to 73 +/- 1% of their ideal weight during hospitalization, and then to 78 +/- 1% during during the observation period at the out-patient department during a period of 6 to 48 months. The former group gained more weight than the latter group during hospitalization (P less than 0.025) and during ambulatory observation (P less than 0.025), respectively. These results suggest that IVH is one effective remedy for anorexia nervosa and that good results can be expected from IVH and psychotherapy used in combination.

Adolescent↗

Fluctuation of the plasma TRH level in normal subjects in a 4-hour observation period.

Radioimmunoassayable TRH and TSH were measured in plasma samples taken at 5 min intervals for 4 hr (2100-0200 hr) from 4 normal male subjects. Three subjects showed a TSH surge at 2135 hr, 2455 hr and 0150 hr, respectively. The mean plasma TRH level of the 4 subjects was 10.3-11.7 pg/ml. Plasma TRH showed random fluctuation, which did not coincide with the nocturnal increase in plasma TSH.

Adult↗

Kinetic aspects of the antigen-antibody reaction in various radioimmunoassays: effect of delayed addition of labeled or unlabeled antigens on sensitivity of assay.

The kinetics of the antigen-antibody reaction were examined systematically in four kinds of double-antibody radioimmunoassay (RIA). In all the RIAs, the dose-response curves obtained on delayed addition by 24 to 48 h of labeled antigens (curves B), were shifted downwards and to the left of those obtained on simultaneous addition of the reagents (curves A), resulting in improved sensitivity of the assay. On the contrary, the dose-response curves obtained on delayed addition of unlabeled antigens (curves C), were shifted upwards and to the right of curves A, resulting in reduced sensitivity. In human thyrotropin (hTSH) RIA, curves B and C approached curves A very little, even after 168 h of incubation. A similar phenomenon was observed with anti-hTSH antisera from five different sources at two incubation temperatures, and the dilution curves of 125I-labeled hTSH and unlabeled hTSH appeared to be parallel. Therefore, the phenomenon observed with hTSH RIA could not be attributed to the assay conditions or to peculiar properties of the reagents used. In insulin RIA, the reversibilities of the shifts of curves B and C were slight but comparable to those observed in hTSH RIA. In 1-3,5,3'-triiodothyronine RIA, curves B and C gradually approached curves A on prolonged incubation and curves B became nearly identical with curves A after 98 h of incubation. On the other hand, in alpha-fetoprotein (AFP) RIA, curves B and C did not approach curves A, even on prolonged incubation for up to 288 h. The "equilibrium affinity constants" of the antibodies were of the same order of magnitude, thus it is unlikely that differences in the constants can account for the differences in the reversibility of these RIAs. In APF RIA, a significant amount of the antigen-antibody complex was precipitated without second antibody after centrifugation at 3000 X g. These findings suggest that the extent of dissociation of the immune complexes depends on their size, which in turn is related to the molecular weight of the antigen.

Antigen-Antibody Reactions↗

Radioimmunoassay for human pancreatic amylase: comparison of human serum amylase by measurement of enzymatic activity and by radioimmunoassay.

A radioimmunoassay (RIA) for human pancreatic amylase has been developed for the determination of human serum amylase content. The assay was shown to be sensitive (7 ng/ml), reproducible and specific, but human pancreatic amylase and salivary amylase could not be distinguished by the antiserum used. In normal subjects, the mean concentration of amylase determined by the RIA was found to be 122.1 ng/ml (range: 55--250 ng/ml). A good correlation was observed between the concentration of amylase and its enzymatic activity in normal subjects. In some instances with high amylase activity, however, the rise in enzymatic activity was not accompanied by increasing amount of amylase content.

Amylases↗

Longitudinal study or serum thyroid hormones, chorionic gonadotrophin and thyrotrophin during and after normal pregnancy.

Measurements of serum levels of thyroxine (T4), free T4, 3,5,3'-triiodothyronine (T3), free T3, 3,3',5'-triiodothyronine (reverse T3, rT3), thyroxine-binding globulin capacity (TBGcap), chorionic gonadotrophin (hCG) and thyrotrophin (TSH) were carried out prospectively in eight women with uncomplicated pregnancies, in order to examine interrelationships between the thyroid gland and thyroid stimulating hormones during pregnancy. During pregnancy the levels of T4, free T4, T3, rT3 and TBGcap were significantly elevated, and TSH was decreased. It was noted that the elevation of T4 was maintained from the 8th to the 27th week of gestation while the level of TBGcap progressively increased. The levels of free T4 and rT3 in the first and third trimesters were significantly higher than those of age-matched, non-pregnant women. The levels of hCG showed a biphasic variation, with a peak in the 8th to 15th weeks, followed by a decline in the second trimester and a small, secondary elevation in the 32nd to 39th weeks. This later elevation was positively correlated with changes in free T4 and free T3 levels. The increase of serum T4 accompanied by an increase of free T4 in the first trimester appeared due to augmented secretion of T4, rather than being secondary to the elevated levels of TBGcap.

Adolescent↗

Relationship of iodide-induced increase in TSH response to TRH to changes in serum thyroid hormones.

Large doses of iodide (500 mg three times a day) administered to normal men for 10--12 days caused a rise in basal serum TSH and a concomitant rise in the peak TSH response to TRH. The basal and peak levels of TSH were highly correlated (p less than 0.001). However, the iodide-induced rise in the peak TSH after TRH was poorly correlated with concomitant changes in serum thyroid hormones. Serum T3 wa not lower after iodide and, while serum T4 was somewhat lower, the fall in serum T4 was unexpectedly inversely rather than directly correlated with the rise in the peak TSH response to TRH. Thus, increased TSH secretion after iodide need not always be directly correlated with decreased concentrations of circulating thyroid hormones even when large doses of iodide are used. Clinically, a patient taking iodide may have an increased TSH response in a TRH stimulation test even though there is little or no change in the serum level of T3 or T4.

Adolescent↗