The nature of thyrotropin stimulation of thyroid function in Japanese quail: prolonged thyrotropin exposure is necessary to increase thyroidal 125I uptake

Single injections of thyrotropin (TSH) increase serum T4 and thyroidal 32P uptake but not thyroidal 125I uptake regardless of dosage, exposure time or age. Chronic TSH exposure, with 3 or more days of injection, does increase thyroidal 125I uptake. Studies using iodine (I) supplementation indicated that the increased thyroidal radioiodine uptakes seen with chronic TSH administration were not due to an I deficiency in the thyroid resulting from high hormone release. Labeled and unlabeled experiments comparing the effects of single vs. multiple injections of TSH were used to describe the effects of TSH on hormone release, hormone production and thyroidal I uptake.     

Thyroidal radioiodine uptake and thyrotropic potency of the pituitary in a freshwater catfish,Mystus vittatus (Bloch), in response to L-thyroxin,antithyroid drugs,and heavy doses of 131I

Summary Experiments were conducted to ascertain the thyroidal ¹³¹I uptake and thyrotropic potency of the pituitary gland in a freshwater catfish, in response to L-thyroxine, antithyroid drugs and heavy doses of radioiodine. L-thyroxine treatments slightly lowered thyroidal radioiodine uptake, and there was at least a trend of lowered TSH content in the pituitaries of these animals. Administration of antithyroid drugs (propylthiouracil, thiourea, KSCN) caused a significant decrease in radioiodine uptake and a highly significant increase in TSH content of the pituitary. Heavy doses of I¹³¹ almost completely blocked thyroidal iodine uptake but they were as effective as antithyroid drugs in elevating TSH content of the pituitary.I am greatly indebted to Dr. G. E. Pickford, Yale University, U.S.A. for her helpful suggestions; to Dr. A. G. Sathyanesan, Banaras Hindu University, India, for encouragements; to Professor S. P. Ray-Chaudhuri, Banaras Hindu University, India, for providing laboratory facilities. I am also grateful to Baxtor Laboratories Inc., Morton Grove, Illinois, U.S.A. for the gift of Crystalline L-thyroxine which was made available through the courtesy of Professor Paul Starr and Dr. Thomas Garrett.     

Methodical optimization of redioiodine uptake experiments in living rats

The paper deals with the estimation of thyroidal uptake of 131I in living rats. The animals are fixed in a specially marked glass tube. This tube is discontinuously moved over a scintillation counter within a lead collimator. Counts of 131I are estimated segmentically. The highest counts ratio with the geometrical factor of the appropriate segment is used to calculate the thyroidal radioiodine uptake. Similar results, obtained with an 131I-source placed in various segments of the top side of glass tube, indicate that the uptake values obtained in this manner exact. Thyroidal uptake values, which were received on living rats with this method (in vivo) and compared with values obtained with the prepared and plated thyroid of the same rats (in vitro) show a very high correlation (r = 0,99; p greater than 0,001). In repeated estimations of the thyroidal 131I-uptake on one animal a variation coefficient of 1.5% (n = 13) was obtained. The advantage of this in vivo method is the possibility to determine the thyroidal activity at various times after 131I-application (2 phase test) and by repeated 131I-applications under different conditions (diet, age, for instance).     

Effect of methyl thiouracil on radioiodine thyroidal retention in rats

Summary Some goitrogens like methyl thiouracil (MTU) because of their thynamide grouping act as antithyroid drugs inhibiting the organification of iodide, but do not alter the iodide transport. Their administration to an intact animal, therefore, might alter the thyroidal iodine kinetics. Here an attempt has been made to study the effect of MTU on thyroidal iodine kinetics in rats as well as to find out whether any difference in kinetics could be detected between different radioiodines, viz.,¹³¹I,¹²⁵I, and¹²³I. Cumulated thyroidal activity which is a time integral of the activity has been taken as the parameter to represent the sum effect of thyroidal iodine kinetics over a specific time period of interest.From the in vivo thyroidal activity measurements, carried out over extended periods of time, the cumulated activity was calculated for both MTU treated and normal rats that received¹³¹I,¹²⁵I, or¹²³I at different times before the MTU start. Within a day of the start of the MTU there is a rapid loss of thyroidal iodine. The severity of the loss depended upon the time that elapsed between the start of the MTU schedule and the particular radioiodine administered. The absence of isotopic effect on the uptake as well as on the rate of uptake for the three different radioiodine isotopes studied has been brought out.Alexander von Humboldt Fellow, on leave from Institute of Nuclear Medicine and Allied Sciences, Delhi -7, India     

Studies on the T3 suppression test by the 24-hour thyroidal 131I uptake in patients with Graves' disease: comparison of the effects of propylthiouracil and methylmercaptoimidazole

The T3 suppression test by the 24-hr thyroidal 131I uptake was reevaluated in patients with Graves' disease before and after withdrawal of antithyroid drug. Fifty patients had been treated with propylthiouracil (PTU) or methylmercaptoimidazole (MMI) for 12 to 70 months. They were prescribed a maintenance dose of antithyroid drug (PTU, 50 mg/day; MMI, 5 mg/day) at the time of investigation and regarded as euthyroid on the basis of serum T3, T4 and TSH levels. Each patient was given 75 micrograms T3 daily for 8 days in conjunction with PTU or MMI. The 24-hr thyroidal 131I uptake was then measured (post T3 uptake). In 30 patients whose post T3 uptake was below 35%, treatment was stopped and the T3 suppression test was repeated at one and 3 months later. During the two-year follow up, 24 remained well, while 6 relapsed within 4 to 12 months. In patients with sustained remission, the post T3 uptake was significantly lower in the MMI-treated group (13 cases, 7.7 +/- 1.0%) than in the PTU-treated group (11 cases, 18.6 +/- 1.9%). MMI withdrawal produced a marked rebound in the post T3 uptake, whereas none of the patients showed the rebound after PTU withdrawal. In patients who relapsed later, there was no difference in the post T3 uptake during treatment and the rebound occurred in the both groups following goitrogen withdrawal. Serum T3, T4 and TSH levels were within normal ranges at one and 3 months after cessation of antithyroid drug. From the results of the present study, it is concluded that criteria for T3 suppressibility by the 24-hr uptake should be determined by the antithyroid drug employed and by the time of investigation. There is a dissociation in the post T3 uptake values following withdrawal of the two different antithyroid drugs.     

A case of Graves' disease with false hyperthyrotropinemia who developed silent thyroiditis.

We encountered a patient who developed silent thyroiditis during the course of Graves' disease. The diagnosis of silent thyroiditis was made on the basis of a low thyroidal 131I uptake, no response to the thyrotropin releasing hormone (TRH) test, and subsequent hypothyroidism despite the presence of high titers of thyrotropin (TSH) receptor antibody (TRAb) and thyroid stimulating antibody (TSAb). The patient, in addition, had a discrepancy between serum TSH and thyroid hormone values. This was due to the presence of interfering substances that react to mouse IgG in the sera since serum TSH levels were decreased in a dose dependent manner by the addition of increasing amounts of mouse IgG to the sera. It should therefore be noted that silent thyroiditis can develop in patients with Graves' disease. Furthermore, clinicians should be aware that two-site immunoassay kits that use mouse monoclonal antibodies are subject to interference by some substances, possibly antibodies which react to mouse IgG.     

Effect of Ambient Salinity,Food-deprivation and Prolactin on the Thyroidal Response to TSH,and in vitro Hepatic T4 to T3 Conversion in Yearling Coho Salmon,Oncorhynchus kisutch

This study examines the effect of food deprivation, increased ambient salinity and prolactin administration on the thyroidal response to ovine TSH, and in vitro hepatic monodeiodination of T4 to T3 in coho salmon, Oncorhynchus kisutch. Fed fish and fish food-deprived for 18 days showed similar significant increases in plasma T4 9 and 24 h after a single injection of TSH. Plasma T3 levels were also elevated in both fed and food-deprived fish 9 h after the TSH injection but plasma T3 levels in the food-deprived fish were markedly lower than in the fed salmon. The increase in T4 and T3 evident in freshwater-acclimated fish after TSH administration was not found in salmon acclimated to 65% sea water. Prolactin, given alone (either as a single injection or a series of three daily injections) had no effect on plasma T4 or T3 levels. When given together with TSH prolactin prolonged the T4 and T3 elevating effect of TSH. Food-deprived salmon had lower in vitro hepatic T4 to T3 conversion rates than fed groups but T4 to T3 conversion did not appear to be affected by increased ambient salinity, or by prolactin and/or TSH administration.     

Diphasic effect of thyrotropin on the uptake and absorption of iodine-131 by thyroid cell culture]

The studies were performed on the primary culture of thyroid cells of newborn pigs. It was shown that thyroid-stimulating hormone (TSH) within the first 12th of its action inhibited uptake and organification of iodine-131. A negative influence of TSH on 131I uptake was retained both with its simultaneous introduction into the culture medium and with 30 min interval as well as when conducting experiments on the 1st, 3d, 5th and 7th days of cultivation. Previous 72h incubation with TSH sufficient for activation of all the links of iodine transport caused an increase in 131I uptake and organification.     

Inhibitory effect of large doses of propylthiouracil and methimazole on an increase of thyroid radioiodine release in response to thyrotropin.

Thyroidal radioiodine release increased shortly after a single injection of small doses of PTU, while moderate doses of MMI produced a similar increase of thyroidal radioiodine release with a latency of 7-9 hr. Large doses of PTU and MMI failed to augment thyroidal radioiodine release for at least 29 to 34 hr after the initial administration of goitrogens, although plasma TSH increased significantly because of goitrogen administration. An increase of thyroid hormone release in response to exogenous TSH was depressed by PTU and MMI in rats and mice treated with T4. Since this depression of TSH action only continued for a short period in spite of continuous administration of goitrogens, and since final thyroidal radioiodine release rate was similar to that produced by small doses of PTU, the effects mentioned were not simply due to general toxic action of goitrogens. It is suggested that large doses of PTU and MMI not only block thyroid hormone synthesis but also interfere with the action of TSH on thyroid hormone secretion.     

Pituitary hormones and growth retardation in rats raised at simulated high altitude (3800m).

Growth and the endocrine status of the pituitary and thyroid glands were studied in rats born and raised in a hypobaric chamber at a simulated high altitude of 3800 m (SHA); comparisons were drawn with similar rats at sea level. From birth until 40 days of age, SHA rats weighed significantly less than controls with the most striking growth impairment found in female SHA rats. Relative organ weights of anterior pituitary glands, ovaries and uteri from 40-day-old female SHA rats were significantly less than controls. Pituitary content of growth hormone (GH) was reduced in 40-day-old female SHA rats while the content of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were significantly increased over sea level controls. Plasma levels of GH, LH, FSH and thyrotropin (TSH) and pituitary TSH levels did not differ from control values. However, thyroidal uptake of 131I and plasma protein-bound 131I were significantly reduced in SHA rats as compared with controls. It is suggested that (1) the continuous exposure of developing female rats to hypoxia significantly impairs pituitary function and reproductive maturation, and (2) that despite other environmental factors acting on the developing organism at high altitude, growth retardation in rats born and raised at high altitudes is primarily a consequence of hypoxia.     

Cimetidine and hyperprolactinemia

Plasma TSH was determined in 12 normal subjects before and after administration of mg 400 of cimetidine i.v., an H2-receptor antagonist. TSH concentration remained unchanged. In 7 normal subjects, pretreated with bromocriptine; variation of plasma prolactin were studied before and after administration of mg 400 and 800 of cimetidine. Bromocriptine inhibited the increase of prolactin secretion, induced by cimetidine. It can be assumed that: a) cimetidine doesn't release hypothalamic TRH in portal vessels; b) that drug has no direct effect on pituitary cells; c) hypothalamic H2-receptor blockade by cimetidine decreases dopamine release from hypothalamus to pituitary gland.     

Diagnostic scintigraphy and effectiveness of 131I radioiodine therapy in differentiated thyroid carcinoma (DTC)

INTRODUCTION: Since the effect of pre-therapeutic scintigraphy on the outcome of DTC treatment is debated, we evaluated factors affecting the effectiveness of (131)I therapy with respect to the delay between diagnostic scintigraphy and the application of radioiodine. MATERIAL AND METHODS: In the studied group of 60 patients with DTC, mean age 54.6 +/- 13.0 years, four weeks prior to the planned diagnostics, L-thyroxine was withdrawn and the following tests performed: (131)I (4 MBq) uptake above the neck, thyroid volume by USG, TSH and hTg level. Wholebody scintigraphy (37 MBq) was performed. The time between this diagnostic scintigraphy and application of (131)I (3657 MBq) was calculated. Based on whole-body 131I scintigraphy (74 MBq) performed 1 year after radioiodine treatment, the patients were divided into: group I - 42 patients with no tracer accumulation, and group II--18 patients who continued to accumulate (131)I in the neck. RESULTS: The differences between the median values of (131)I uptake and of thyroid volumes, and between the TSH and hTg median values in the two groups of patients were found not to be statistically significant. The average times between diagnostic scintigraphy and (131)I treatment in group I and II (9.4 vs. 8.3 weeks, respectively) were not significantly different either. CONCLUSION: Despite the different effectiveness of supplementary (131)I treatment, patients in group I and group II showed no statistically significant differences in the studied parameters. It appears that the diagnostic (131)I activity of 37 MBq and the time between diagnostic scintigraphy and application of (131)I did not have any effect on the results of the treatment in our group of patients.     

The anti-oestrogen tamoxifen does not interfere with the dopaminergic control of prolactin and TSH release in normogonadotrophic oligozoospermic man

This study was designed to investigate the role of endogenous oestrogens in the dopaminergic regulation of prolactin and TSH release in 16 normogonadotrophic oligozoospermic men. Three months' administration of the oestrogen-receptor antagonist tamoxifen (10 mg twice daily), blocking oestrogen-receptors both in the CNS and peripherally, did not affect basal prolactin and TSH levels. Neither was the prolactin or TSH response to stimulation with the anti-dopaminergic agents metoclopramide (10 mg i.v.) (acting both in the CNS and peripherally) and domperidone (10 mg i.v.) (acting peripherally) affected by tamoxifen administration. The response of prolactin and TSH to metoclopramide proved to be no greater than to domperidone. It is concluded that: Endogenous oestrogens, in as far as receptor-mediated, do not affect basal or anti-dopaminergic stimulated release of both prolactin and TSH in normogonadotrophic oligozoospermic men. The anti-dopaminergic activity of metoclopramide in the release of prolactin and TSH is likely for the greater part peripheral.     

Seasonal characteristics of the effect of melatonin on thyroid function

Changes in pituitary-thyroid axis sensitivity to bioactive component of pineal gland, melatonin, have been detected. In winter (short days) melatonin (100 micrograms/100 g of rat body weight) decreased T3 T4, TSH content and 131I uptake by thyroid tissue. However, it was noted that in summer (long photoperiod) the same injection caused suppression of T3 plasma level and 131I uptake ability of the thyroid gland, with T4 and TSH blood levels remaining significantly increased.     

Pituitary cytology of radiothyroidectomised teleost Heteropneustes fossilis (Bloch.).

The pituitary of Heteropneustes fossilis is divisible into rostral (RPD) and proximal (PPD) pars distalis, and pars intermedia (PI). Neurohypophysis extensively ramifies in the PI. The RPD is formed of acidophilic prolactin cells and lead hematoxylin (H. Pb) positive ACTH cells. The latter is arranged around the neurohypophysial extensions. The PPD is comprised of thyrotrophs (TSH) and gonadotrophs which are stainable with PAS, AF, and aniline blue. Acidophilic somatotrophs (STH) and chromophobes are scattered throughout the PPD. In the pars intermedia PAS positive and H. Pb positive cells are present. The latter is believed to secrete MSH whereas the function of the former is yet to be confirmed. In the partly and completely thyroidectomised H. fossilis the TSH cells exhibited marked hypertrophy. They are located in the middle of the PPD flanked by the gonadotrophs on either side. Hypertrophy of the ACTH cells were also evident. But the other cell types did not show any marked changes as compared to the controls.     

The effect of dexamethasone on TSH and prolactin secretion after TRH stimulation

Serum thyrotropin (TSH) and prolactin levels were measured after intravenous administration of 400 μg of synthetic thyrotropin-releasing hormone (TRH) in 13 normal subjects and six hypothyroid patients before and after three days of administration of dexamethasone 2 mg per day. In the normal subjects dexamethasone suppressed baseline serum levels and secretion of TSH after TRH stimulation. On the other hand, it had no effect on the hypothyroid patients. In the control group dexamethasone also suppressed baseline serum levels but not secretion of prolactin after TRH stimulation. Dexamethasone had no effect on prolactin levels in the hypothyroid group. It is concluded that in normal patients short-term administration of dexamethasone has an inhibitory effect on TSH secretion at the pituitary level. As for prolactin, our results could indicate that TRH is a more potent stimulator of prolactin secretion than of TSH secretion, or that TSH and prolactin pituitary thresholds for TRH are different.     

The value of plasma TSH estimation and TRH stimulation test in the course of treatment of differentiated thyroid cancers.

Plasma TSH levels were measured on 114 occasions in 96 patients treated for differentiated thyroid cancer. Prior to thyroid surgery, plasma TSH levels were within the range of normal. Plasma TSH levels increased slightly following partial thyroid resection and definitely after total thyroid ablation. In patients where the removal of normal thyroid induced hormonogenesis in thyroid tumours, plasma TSH levels were dependent on the hormonal secretion of the tumour as shown by inverse relationship between TSH and both PBI and 131I uptake. The increase of radioiodide uptake following stimulation by exogenous bovine TSH was inversely related to the plasma thyrotropin levels. The suppressibility of enhanced thyrotropin levels was complete with individually adjusted doses of synthetic thyroid hormones. With the exception of patients on suppressive treatment, TRH administration induced increase in plasma TSH levels. The findings are discussed with regard to the role played by TSH in the induction of hormonogenesis in thyroid tumours. The practical values of TSH estimation and TRH stimulation seem to be low; the measurements of thyrotropin levels may be important for the estimation of the suppressive effect in the course of and following withdrawal of treatment with thyroid hormones.     

Biokinetics of iodine-131 in rat thyroid following lead and lithium supplementation

The impact of lead as an environmental pollutant on the I-131 uptake and retention in rat thyroid was assayed alone and in combination with lithium treatment. Lead treatment significantly stimulated the 2- and 24-h uptake of I-131 in the thyroid, and the 24-h uptake showed the maximum stimulation after 3 mo of lead treatment. On the contrary, lithium supplementation reduced the uptake significantly and the maximum decrease was noticed after 2 mo of lithium administration. Further, simultaneous lead and lithium treatment resulted in more pronounced increase in the uptake of I-131 by the thyroid, which was maximum after 3 mo of combined treatment. The thyroidal biological half-life of I-131 (T _biol) was found to be increased significantly following lead and lithium treatments when given separately. Interestingly, combined lead and lithium treatment given up to 2 mo further prolonged theT _biol of I-131, thus reflecting its increased retention.     

Activity of thyroid stimulating antibody and thyroid stimulation blocking antibody determined by radioiodine uptake into FRTL-5 cells

To investigate the pathophysiology of patients with autoimmune thyroid diseases, we measured serum thyroid stimulating antibody (TSAb) activity and thyroid stimulation blocking antibody (TSBAb) activity by determining the radioiodine (125I) uptake into FRTL-5 cells. FRTL-5 cells were pre-incubated for seven days with 5H medium and then incubated for 48 hours with patients' crude IgG prepared by polyethylene glycol precipitation. In order to measure TSBAb, 10 microU/ml TSH was also added. 125I was added one hour before the end of the 48 hour incubation period. After the incubation, the medium was aspirated, and the radioactivity in the cells was counted. In patients with untreated hyperthyroid Graves' disease, TSAb was detectable in 18 of 20 patients, the detectability being 90%, and activity showed a statistically significant positive correlation with TSAb activity determined by c-AMP accumulation. Out of 41 patients with hypothyroidism, TSBAb determined by 125I uptake was positive in six cases, the detectability being 14.6%. The inhibition of 125I uptake by one of these six IgGs was suggested to be at the TSH receptor level because it inhibited TSH induced c-AMP accumulation and showed positive thyrotropin binding inhibitor immunoglobulin (TBI I) activity, but did not inhibit the forskolin- and (Bu)2cAMP-induced 125I uptake. Inhibition of another IgG was suggested at the post-receptor level because it did not inhibit TSH induced cAMP accumulation and showed negative TBI I activity, but inhibited forskolin- and (Bu)2cAMP-induced 125I uptake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of lithium on thyroidal 131iodine uptake, its clearance, and circulating levels of triiodothyronine and thyroxine in lead-treated rats

The influence of lead acetate (50 mg per kg body weight) on the 131iodine (131I) biokinetics (uptake and retention) in rat thyroid and serum levels of triiodothyronine (T3) as well as thyroxine (T4) was evaluated as a function of time and in combination with lithium treatment. The 2-h and 24-h uptake of 131I in the thyroid was stimulated significantly by lead treatment. The 24-h uptake showed a maximum stimulation after 4 months of lead treatment. Lithium supplementation, however, showed the opposite effect by reducing the iodine uptake whereby the maximum decrease was noticed after 2 months of treatment. Further, simultaneous lead and lithium treatment resulted in an even more pronounced increase of 2-h 131I uptake with a maximum after 3 months. However, the 24-h uptake after 3 months and 4 months of treatment did not differ significantly from the lead treated reference groups. The thyroidal biological half-life of 131I (Tbiol) was found to have clearly increased following the lead/lithium treatment. Interestingly, the combined lead/lithium treatment applied for 4 months caused a further growth of Tbiol, thus reflecting an increased retention of 131I. A maximum increase of Tbiol was seen after 2 months of combined treatment. A progressive decline of the circulating T3 and T4 levels following lead or lithium treatment was noticed and was more pronounced after combined treatment.