Quantification of salmon alpha- and thyrotropin (TSH) beta-subunit messenger RNA by an RNase protection assay: regulation by thyroid hormones

Brightness discrimination of black-white stimuli (1-37 Cd/m; CIE-31 chromatic coordinate X = 0.340, Y = 0.304) were studied using choice conditioning paradigm in two monkey (Macaque Rhesus). Confusion matrices were composed of probabilities of instrument responses to conditioned and differential stimuli in ten series in which one of the ten intensities was employed as a conditioned one. Confusion matrices were transformed into the correlation matrices between the vectors corresponding to the stimuli. Factor analysis of correlation matrices revealed two-dimensional circular structure of monkey's brightness perceptual space. This space was principally similar with that in humans, fishes, and rabbits. Two eigenvectors which constituted two-dimensional Euclidean space of brightness can be interpreted as bright and dark neuronal channels.     

Activities of thyroid hormones and related compounds in an in vitro thymocyte assay

Prior studies have demonstrated that the thyroid hormones L-triiodothyronine and L-thyroxine stimulate the rapid uptake of 1-amino-cyclopentane-1-carboxylic acid into isolated rat thymocytes. In the present study the effects of several groups of thyroid hormones and structurally related compounds were investigated to determine the structure-function relations required for stimulation of this membrane process. Particular attention was given to (a) analogues with modifications at the oxygen bridge, the phenolic hydroxyl group, and the group at the 3' position of the outer ring, and (b) the steric orientation of the thyroid hormones. The following were found to be important for maximal activity: (a) the L-isomer configuration, (b) the presence of a 4'-hydroxyl group, (c) the presence of one substituent in both the inner and outer rings (3 and 3' positions), (d) the distal orientation of the 3' substituent in the outer ring of L-triiodothyronine, and (e) the lipophilic character of the 3' substituent. Of lesser importance was the presence of halogen atoms, or an oxygen atom in the ether position. Since these structure-function relations seen in thymocytes parallel in many respects those relations seen in whole-animal studies, it is believed that thymocytes will be a useful tool for further studies of thyroid hormones and their analogues.     

Changes in thyroid hormones by treatment with aspirin and prednisolone in subacute thyroiditis with hyperthyroidism

Thyroid functions were studied in 11 patients with subacute thyroiditis accompanied by signs and symptoms of hyperthyroidism, and were compared with 13 patients with untreated thyrotoxicosis in which serum T4 was elevated to the identical level. Serum T3 was also elevated in subacute thyroiditis but to a significantly lower extent than in thyrotoxicosis. Therefore the ratio of T4/T3 was significantly higher in subacute thyroiditis than in thyrotoxicosis. Although duration of thyroid swelling was shorter in the group treated by prednisolone than by aspirin, the accelerated ESR, thyroid tenderness and fever subsided almost similarly in the two groups. Serum T4 and T3 levels declined more rapidly in treatment with prednisolone compared with aspirin. In patients treated by aspirin initial increase in T3 level occurred transiently with simultaneous decrease in the T4/T3 ratio. These changes suggest the increase in peripheral conversion of T4 to T3. Even in severe cases of subacute thyroiditis associated with hyperthyroidism, aspirin treatment is an effective therapy and there is no recurrence following withdrawal of the medication.     

Clinical significance of thyrotropin measurement by immunoradiometric assay and thyrotropin-releasing hormone test

The levels of serum TSH were measured by a sensitive immunoradiometric assay (IRMA) method and the responses of TSH to TRH stimulation were observed in three groups of hyperthyroidism, primary hypothyroidism and secondary hypothyroidism. The levels of serum TSH were found to be undetected in 98% (1/51) of the patients with hyperthyroidism, very high in 100% (35/35) of the patients with primary hypothyroidism and normal in 91% (30/33) of the patients with secondary hypothyroidism. TRH test showed no responses of TSH in all patients with hyperthyroidism, high responses in all patients with primary hypothyroidism and blunt responses in 69% (11/16) of patients with secondary hypothyroidism. The results indicate that the measurement of serum TSH by IRMA is a sensitive index in the diagnosis of hyperthyroidism and primary hypothyroidism, but can not be differentiated the secondary hypothyroidism from normal conditions. TRH test may be helpful in the differential diagnosis between secondary hypothyroidism and normal conditions.     

Effect of 1 alpha-hydroxyvitamin D3 on serum levels of thyroid hormones in hyperthyroid patients with untreated Graves' disease

We performed a randomized, open prospective study to determine the effect of 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3] on hyperthyroidism in patients with untreated Graves' disease. At the time of entry into the study, 30 patients were randomly assigned to receive a daily dose of 30 mg methimazole (MMI) (group A, n = 15) or the same dose of MMI supplemented with 1.5 micrograms 1 alpha (OH)D3 (group B, n = 15). These treatment regimens were continued for 24 weeks, and physicians were allowed to adjust MMI dosage during follow-up visits. Blood samples were collected, and serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), T3, T4, thyrotropin (TSH), alkaline phosphatase (ALP), and TSH-receptor antibody (TRAb) were determined. During the follow-up periods, all patients became euthyroid. The dose of MMI was not significantly different between these two groups. In contrast, decreases in mean serum FT3 and FT4 levels, as well as in mean serum T3 and T4 levels, were greater in group B. Correspondingly, the reciprocal increase in the mean TSH level was more prominent in group B. Mean TRAb levels did not differ between the two groups. Mean serum ALP levels in group B were significantly lower than in group A at 24 weeks. Thus, we suggest that concomitant administration of 1 alpha (OH)D3 is useful for treating hyperthyroidism in patients with Graves' disease.     

Low response of the thyroid gland to endogenous thyrotropin increased by thyrotropin-releasing hormone in patients with euthyroid Graves'' disease

A 48-year-old man was admitted because of persistent dry cough for six months. He had been a smoker for 25 years, averaging a pack a day, and demonstrated clubbing of the fingers. Basilar fine crackles were observed in both lung fields. Chest X-ray films on admission showed diffuse reticulonodular shadows. Chest computed tomograms showed low-attenuation areas mainly in the center of the upper lung field, and ground-glass opacity, air bronchiolograms, and perivascular interstitial thickening of the peripheral vessels mostly in the lower field. A Gascintigram disclosed mild accumulation in both lungs. A transbronchial lung biopsy specimen did not reveal special features. However, a biopsy specimen obtained by thoracoscopy showed evidence of respiratory bronchiolitis, with a mononuclear inflammatory process involving respiratory bronchioles and adjacent air space, associated with mild fibrous thickening of the peribronchiolar interstitium and surrounding alveoli septa. These findings suggested that the patient had respiratory bronchiolitis-associated interstitial lung disease, the second case to be reported in Japan.     

Hypothyroid patients showing shortened responsiveness to oral iodized oil have paradoxically low serum thyroglobulin and low thyroid reserve. Thyroglobulin/thyrotropin ratio as a measure of thyroid damage

In Central Africa, all of northern Zaire is very severely deficient in iodine. A peculiar feature of this endemia is that iodine deficiency and the ensuing thyroid gland stimulation not only leads to goitre formation but also to progressive thyroid involution and to myxoedematous cretinism. An iodine supplementation trial based on oral administration of small doses of iodine was made in 81 schoolchildren. All of them received a small dose of iodine (0.1 ml containing 48 mg) per os and the thyroid status was followed during 4 months. Blood and urine samples were collected at the start of the study, then 2 weeks, 2 months and 4 months after iodine administration. Before iodine supplementation the mean urinary iodine level was 0.18 +/- 0.02 micromol/l, and 10% of the subjects had a urinary iodine level below 0.08 micromol/l. Fifty-two percent of the subjects had a serum thyrotropin (TSH) level above 10 mU/l. All the subjects responded to the administration of iodine. and all of them recovered a euthyroid status. Most of them were still euthyroid at the end of the study. However. within 4 or even 2 months, some subjects (15 % of the total) reverted to hypothyroidism. At the entry of the study these subjects were all hypothyroid and had elevated TSH and paradoxically low serum thyroglobulin (TG) values. In myxoedematous cretins living in the same area, even lower serum TG levels were found. Together with the absence of goitre, a paradoxically low serum TG Suggests a low thyroid reserve, and in the present case a reduced amount of functional thyroid tissue. We show that the serum TG/TSH ratio may be used as a predictive index of thyroid reserve and of positive response to iodine administration. These data further suggest that thyroid damage is not confined to myxoedematous cretins. but is widely distributed in the phenotypically normal population. Widely distributed thyroid damage may render iodine prophylaxis based on oral administration unpredictable.     

Changes in pituitary and ovarian hormones following injection of ultra low dose LH-RH in normal and amenorrhoeic women

The results of the ultra low doses of synthetic LH-RH, 1.56, 3.125 and 6.25 mug, are presented in 8 normal women during the first week of the menstrual cycle and 14 patients with secondary amenorrhoea. Seven of these patients had "stress" amenorrhoea, and 7 had preceeding oligomenorrhoea. There was no significant difference between the mean basal gonadotrophin levels in the normal volunteers and those patients with secondary amenorrhoea. There was no significant difference in basal gonadotrophin levels or the response to LH-RH, between the two groups of amenorrhoea, stress and previous oligomenorrhoea. Basal FSH and oestradiol levels do not appear to influence the response to LH-RH. However, those patients with secondary amenorrhoea and a low basal LH (5 patients) had a significantly higher response to LH-RH at 1.56 and 3.125 mug than the amenorrhoeic patients with normal basal LH levels. Two patients with stress amenorrhoea and weight loss had an exaggerated response to LH-RH. The significance of this is discussed.     

Relationship of thyroid states and serum thrombomodulin (TM) levels in patients with Graves' disease: TM, a possible new marker of the peripheral activity of thyroid hormones

Thrombomodulin (TM) is a thrombin receptor glycoprotein that functions as an anticoagulant on the surface of endothelial cells. Serum TM is regarded as a new marker of generalized endothelial cell damage. Serum TM concentrations were measured in 75 patients with Graves' disease and 75 age- and sex-matched healthy subjects. Serum TM levels in patients in the hyperthyroid state were significantly increased, while those in patients in the hypothyroid state due to treatment were significantly decreased compared with levels in control subjects. All patients with untreated Graves' disease had markedly elevated TM levels. Serum TM levels correlated closely with thyroid hormone concentration (TM vs. free T4, r = 0.858; P = 0.001). Serial measurement of individual patients revealed that serum TM levels paralleled thyroid hormone concentration, reaching normal control values upon attainment of euthyroidism. On the other hand, there was no significant correlation between serum TM concentration and titer of antithyroglobulin antibodies, titer of antimicrosomal antibodies, serum thyroglobulin level, or goiter size, and serum TM was not directly influenced by TSH receptor antibodies or resting pulse rates. The close correlation between serum TM and thyroid hormone concentration suggests that thyroid hormones might influence the synthesis or metabolism of TM on the surface of endothelial cells in patients with Graves' disease.     

Thyroglobulin assay in the follow-up of patients with differentiated thyroid carcinomas: comparison of its value in patients with or without normal residual tissue

The usefulness of serum thyroglobulin (Tg) assay in the follow-up of differentiated thyroid carcinomas has been evaluated in 109 subjects divided into two groups. Group 1 included 64 patients who had undergone total thyroid ablation. In 40 of the 41 patients in complete remission serum Tg was undetectable during replacement therapy (TSH below 5 microunits/ml). In 18 out of the 40 patients serum TG was detectable following endogenous TSH stimulation. As 83% of these patients had ectopic uptake prior to the last radioiodine treatment, this release of Tg under TSH stimulation suggests the persistence of occult neoplastic tissue. Of the other 23 patients, 20 had bone or lung metastases and 3 patients had lymph node recurrences: in all these patients, serum Tg was detectable during replacement therapy and increased after TSH stimulation. Group 2 included 45 patients in whom normal residual thyroid tissue was present at the time of the investigation. Of these, 35 patients were in apparent remission and 19 of them had detectable Tg level within the normal range. The other 10 patients had detectable metastases and in 4 of these the Tg level was also within the normal range. Thus, no conclusion can be drawn from a normal Tg level in the presence of residual thyroid tissue. Bovine TSH stimulation did not improve significantly the diagnostic value of Tg assay in this group of patients.     

Effects of oral administration of anti-inflammatory doses of prednisone on thyroid hormone response to thyrotropin-releasing hormone and thyrotropin in clinically normal dogs

Prednisone was given orally to 12 dogs daily for 35 days at an anti-inflammatory dosage (1.1 mg/kg of body weight in divided dose, q 12 h) to study its effect on thyroxine (T4) and triiodothyronine (T3) metabolism. Six of these dogs were surgically thyroidectomized (THX-Pred) and maintained in euthyroid status by daily SC injections of T4 to study peripheral metabolism while receiving prednisone; 6 dogs with intact thyroid gland (Pred) were given prednisone; and 6 additional dogs were given gelatin capsule vehicle as a control group (Ctrl). Baseline T4 concentration after 4 weeks of treatment was not significantly different in dogs of the THX-Pred or Pred group (mean +/- SEM, 2.58 +/- 0.28 or 3.38 +/- 0.58 micrograms/dl, respectively) vs dogs of the Ctrl group (2.12 +/- 0.30 micrograms/dl). A supranormal response of T4 to thyrotropin was observed in dogs of the Pred group, but the T4 response to thyrotropin-releasing hormone was normal. Baseline T3 concentration in dogs of both steroid-treated groups was significantly (P < 0.05) lower after 2 and 4 weeks of prednisone administration vs pretreatment values, but normalized 2 weeks after prednisone was stopped. Free T3 (FT3) and T4 (FT4) fractions and absolute FT3 and FT4 concentrations were not altered by prednisone administration. Reverse T3 (rT3) concentration in vehicle-treated Ctrl dogs (26.6 +/- 3.5 ng/dl) was not different from rT3 concentration in dogs of the THX-Pred (25.7 +/- 4.3 ng/dl) and Pred (28.9 +/- 3.8 ng/dl) groups after 4 weeks of medication.(ABSTRACT TRUNCATED AT 250 WORDS)     

High prolactin levels may be missed by immunoradiometric assay in patients with macroprolactinomas

Coronary artery spasm induced by a guide wire is a very rare complication of percutaneous transluminal coronary angioplasty (PTCA). The authors describe a patient who developed coronary vasoconstriction distal to the dilated lesion during PTCA, which was refractory to intracoronary nitroglycerin and intravenous calcium antagonist injection and balloon angioplasty but responded promptly and completely to withdrawal of the guide wire from the coronary artery, suggesting that the spasm had been induced by the guide wire.     

Serum lipid levels and steroidal hormones in women runners with irregular menses

One cannot fail to be aware of the 'human rights' that are vividly thrust into our living rooms by the world's media; but, what are human rights and are they of relevance to British nursing practice? In a democratic state such as the UK, human rights infringements or violations are not typified as occurring in a health care system outwardly appearing to safeguard the interests of the patient/person. This paper examines some of the issues and concludes that the notion of human rights remains inconspicuous and peripheral to the 'real world' of clinical nursing practice. It challenges British nurses to reflect on their practice and outwardly demonstrate that nursing's contemporary language of human rights does not remain simply rhetorical in nature.     

Interaction between triiodothyronine and ovarian steroid hormones on the regulation of the release of thyrotropin and thyrotropin-releasing hormone in vitro

Laparoscopic access to the retroperitoneum without abdominal insufflation has recently been made possible by devices designed to create a dilated laparoscopic cavity maintained by a fixed retraction system. This technique was applied in 10 patients undergoing laparoscopic ligation of the internal spermatic vein via extraperitoneal and intraperitoneal approaches. Gasless laparoscopic varicocelectomy was completed in 7 of 8 men by the extraperitoneal route and in neither of the 2 men approached intraperitoneally. The mean operative time was 170+/-55 min and postoperative pain exceeded the norm for standard insufflative laparoscopic varicocelectomy. Whereas certain theoretical advantages are offered by the gasless extraperitoneal approach to varicocele ligation, exposure through the gasless technique is currently suboptimal. Further development of "retraction" technology is required, prior to its routine application for varicocele ligation.     

Plasma concentration of thyroid hormones in lambs fed poultry offal meal in replacement of soybean meal at two energy levels

Sixty growing Najedi ram lambs (23.5 kg BW: 3 months old) were divided randomly to 6 equal groups. Each group was fed on different (isonitrogenous) diet, being either high energy (2.79 Mcal ME/kg DM) or low energy (2.15 Mcal Me/kg DM), supplemented with either 0.5 or 10% poultry offal meal (POM) in replacement of an equal amount of soybean meal (SBM). Feeding was ad libitum for 15 weeks experimental period. Thyroid hormones levels in plasma were determined during the last 7 weeks of the experiment and were related to feed intake and body weight during the same period. Lambs fed high-energy diets showed higher (P < 0.01) levels of both thyroxine (T4) and triiodothyronine (T3) compared to those fed low-energy diets leading to lower T4 to T3 ratios. There was more conversion of T4 to T3 for more utilization of food by the lambs fed the 10% POM diet of the high-energy content.     

Epitopes for thyroid stimulating and blocking autoantibodies on the extracellular domain of the human thyrotropin receptor

The majority (97%) of functional epitopes for stimulating thyrotropin receptor (TSHR) antibodies (stimulating TSHRAbs) in a large cohort (n = 59) of Japanese Graves' patients exists on the N-terminal region of the extracellular domain of TSHR, between residues 25 and 165 numbering from the methionine start site. This was determined by measuring the loss of stimulating activity in the Cos-7 cells transfected with TSHR/lutropin-choriogonadotropin receptor (LH-CGR) chimeras wherein TSHR residues 89-165 (Mc2) or 8-165 (Mc1 + 2) are replaced by comparable LH-CGR residues. There is no comparable loss when stimulating TSHRAb activity is measured in an Mc4 chimera, wherein TSHR residues 261 to 370 are replaced. In contrast, immunoglobulin (IgG) preparations from 35 patients with Hashimoto's disease or idiopathic myxedema, who have blocking TSHRAbs causing hypothyroidism, loose blocking TSHRAb activity in the Mc4 chimera, but not the Mc2 or Mc1 + 2 chimeras. Thus, in a large population of Japanese patients with autoimmune thyroid disease caused by TSHR autoantibodies, the major functional epitope for stimulating TSHRAbs is on the N-terminal portion of the TSHR extracellular domain, whereas that for blocking TSHRAbs is on the C-terminal portion of the extracellular domain. To further evaluate the nature of the critical functional epitope between residues 90 to 165, we divided this region approximately in half, creating chimeras Mc2a and Mc2b with, respectively, residues 90-124 or 125-165 replaced by comparable LH-CGR residues. IgGs from all patients tested lost significant stimulating activity using the Mc2a and Mc2b chimeras; however, when present, residual stimulating TSHRAb activity was evident on one or the other half of the region or on both halves, indicating that both segments are required for expression of the stimulating TSHRAb epitope within residues 90-165. Finally, we have identified a complex epitope involving both the N- and C-terminal portion of the extracellular domain that appears to account for the small fraction of stimulating TSHRAbs whose activity is not solely dependent on residues 25 to 165. Thus, using chimeras Mc1 + 2 + 4, with TSHR residues 8-165 and 261-370 substituted, or chimera Mc1 + 2 + 3 + 4, with residues 8-370 substituted, as well as Mc2, Mc1 + 2, and Mc4, we show that the Graves' IgGs which maintain stimulating TSHRAb activity when residues 8-165 of the TSHR are replaced by LH-CGR residues have an epitope involving residues 90-165 and the immunogenic 15mer peptide (YYVFFEEQEDEIIGF), residues, 352-366. Because that peptide can decrease the stimulating TSHRAb activity of these Graves IgGs in assays with the Mc2 chimera alone, we speculate that this complex epitope may be important in an epitope spreading process involved in the formation of stimulating TSHRAbs.     

A role for thyroid hormones in the regulation of diet-induced thermogenesis in birds

The possible involvement of thyroid hormones in avian diet-induced thermogenesis (DIT) was investigated in two lines of cockerels divergently selected for high (R-) or low (R+) food efficiency. For a given body weight, R+ cockerels exhibited a higher food intake than R- cockerels (+49 to +76%) and increased DIT (+25%). Plasma thyroxine (T4) level did not differ between lines whatever the feeding status of the birds. Plasma 3,5,3'-triiodothyronine (T3) level was lower in fasted R+ than in fasted R- cockerels while the opposite was observed after a meal. Iopanic acid injections reduced both plasma T3 concentrations and heat production to the same levels in both lines. Hepatic 5'-deiodinase activity measured with an exogenous sulfhydryl group (dithiothreitol) did not differ between lines, but when the sulfhydryl group was omitted, the activity was higher in R+ than in R- birds (90 v. 42 pmol T3/min per liver). T3-binding capacity of isolated hepatic nuclei was higher (+76%) in R+ than in R- birds. Long-term or acute pair-feeding of R+ cockerels to the level of R- controls did not alter these results. The present results suggest that T3, mainly originating from peripheral conversion of T4 to T3, is involved in DIT in the R+ line. Availability of endogenous sulfhydryl groups appears to play an important part in the modulation of hepatic deiodinase activity. The higher concentration of nuclear T3 receptors may further increase the effects of the hormone, suggesting a major role of thyroid hormones associated with catecholamines in the stimulation of avian DIT. The underlying thermogenic mechanisms remain to be elucidated.