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PubMed1992

Effects of hypothyroidism on rat circadian activity and temperature rhythms and their response to light.

Male rats made hypothyroid by administration of propylthiouracil plus sodium ipodate in drinking water were compared to controls in terms of period of circadian activity and temperature rhythms, amount of gross motor activity, and mean temperature. Animals were studied under entrainment, constant darkness (DD), and constant dim light (LL). There was no difference in the period of the circadian activity rhythm between groups in DD. However, hypothyroid rats showed significant blunting of the period-lengthening response to increasing ambient illumination. As expected, the period of the circadian temperature rhythm increased in controls with increasing ambient illumination. In contrast, the period of the circadian temperature rhythm in hypothyroid animals actually shortened under LL compared to DD. This blunting of the period-lengthening response to increasing ambient illumination of both activity and temperature rhythms in hypothyroid animals could not be explained by differences in activity level or mean temperature between the groups.

Animals↗

PubMed1982

Outer and inner ring monodeiodination of thyroxine by dog thyroid and liver: a comparative study using a particulate cell fraction.

In previous studies using perfused dog thyroids we have found evidence for a modulation of thyroid secretion by intrathyroidal thyroxine deiodinases. The purpose of the present study was to examine in detail the in vitro characteristics of thyroidal 5- and 5'-deiodinases of T4 and to make a comparison to T4 deiodinases from liver tissue. The sources of deiondinases were crude microsomal fractions prepared from thyroid and liver tissues obtained from the same dogs. Deiodinases from the two tissues behaved very similarly with respect to the time course of T3 and rT3 generation, dependency on the of added microsomes and substrate, and influence of temperature, pH, dithiothreitol, propylthiouracil, methimazol, ipodate, and added rT3. At pH 7.4, both T3 and rT3 were stable when added to the microsomal preparations. The apparent kinetic constants estimated from Lineweaver-Burk plots of T4 deiodination to T2 and rT3 by liver and thyroid microsomes, were similar for all reactions, (kinetic constant, 6.1-25.l1 microM). T3 generation was maximal at pH 6.2, and rT3 generation was maximal at pH 8.0. Even at pH 8.0, the generation of T3 was severalfold higher than that of rT3. In contrast to previous studies employing rat tissue, it was found that the addition of rT3 did not modify the deiodination of T4 to T3 unless the rT3 concentration exceeded that of T4. Thus, the canine thyroid contained T4 deiodinases very similar to those of a peripheral thyroid hormone target organ, the liver. These thyroidal deiodinases are probably responsible for the relatively high secretion of T3 and rT3 compared to that of T4 found in our previous studies. Further, the discrepancies between these and previous data obtained using rat tissues demonstrate that in such in vitro studies, great species variations are present in the stability of generated rT3 and the effect of rT3 on outer ring deiodination of T4 to T3.

Animals↗

PubMed1992

A radioimmunoassay of rat type I iodothyronine 5'-monodeiodinase.

A highly sensitive, specific, and reproducible RIA has been developed to measure rat type I iodothyronine 5'-monodeiodinase (5'-MD). A 16-amino acid peptide (LAP-744) corresponding to a portion of the carboxy-terminal region of the rat liver 5'-MD, as predicted from its cDNA, was synthesized, and rabbits were immunized with the peptide-BSA conjugate. In a final dilution of 1:15,000, our anti-5'-MD antibody bound about 30-35% of a tracer amount of [125I]LAP-744. The detection threshold of the RIA approximated 0.08 pmol LAP-744 or an equivalent amount of 0.08 pmol 5'-MD. Rat liver and kidney microsomes produced dose-response curves that were essentially parallel to that of LAP-744. No inhibition of binding of [125I]LAP-744 to antibody was produced by 0.3 mg or less rat microsomal proteins from testes, heart, brain, muscle, spleen, intestine, lung, placenta, or fetal liver. Recovery of nonradioactive LAP-744 added to spleen microsomes averaged 103%. The coefficient of variation averaged 4% within an assay and 11% between assays. In 16 normal rats studied, the mean (+/- SD) 5'-MD content was 2.4 +/- 0.22 pmol/mg protein in liver microsomes and 2.5 +/- 0.27 pmol/mg protein in kidney microsomes. Fasting of the rat for 2-4 days was associated with a significant reduction in both the activity and the content of the 5'-MD in liver and kidney. Hypothyroidism was also associated with a significant decrease in the activity and content of 5'-MD in both tissues. Significant opposite changes were observed in these parameters in hyperthyroidism. Treatment of the rat with sodium ipodate for 3 days was associated with a significant decrease in both the activity and the content of 5'-MD in liver and kidney. A similar treatment of the rat with propylthiouracil induced a clear reduction in the activity of 5'-MD in liver and kidney, but the content of the enzyme was significantly increased in both tissues. Rats treated with aurothioglucose for 3 days exhibited a significant decrease in 5'-MD activity in liver and kidney microsomes, whereas the tissue content of 5'-MD was not affected. A similar treatment of the rat with methimazole had no significant effect on either the activity or the content of 5'-MD.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1975

Gall-bladder emptying measured by a radioisotopic method.

A method of oral radioisotope cholecystography is described using 131I sodium ipodate. Gall-bladder emptying was measured by this method and radiographically: (a) in a model, (b) in 34 patients having oral cholecystography. There was a good correlation between the two methods of measuring volume changes, both in vitro and in vivo. The isotope cholecystogram has the advantage of a lower radiation hazard, and is the only satisfactory method of studying the onset, rate and duration of gall-bladder emptying. These may be easily measurable markers of disorders of the upper small bowel.

Cholecystography↗

PubMed1986

Thyroxine monodeiodination in normal human kidney tissue in vitro.

The present study deals with thyroxine monodeiodination in normal human kidney. To allow for comparison with previous reports, the present methods are similar to those used by others in rat tissue studies. The microsomal cell fraction of normal human kidney tissue was obtained by differential ultracentrifugation. The microsomes were incubated under various conditions and the deiodination products assayed with radioimmunoassay. A type I 5'-monodeiodinase was demonstrated, pH optimum around 6.5. Competitive inhibition was observed of T3 generation from T4 by rT3 with a Km of 3.0 microM and a Ki of 4 microM. Vmax was 26.1 pmol/min/mg protein. Likewise rT3 was generated from added T4, but it was rapidly degraded, while T3 was relatively stable as is the case in rat tissue preparations. Propylthiouracil inhibited 5'-deiodination in a dose dependent fashion with complete abolishment of deiodination at propylthiouracil concentration of 10(-4) M. Ipodate inhibited the reaction with complete inhibition at 10(-2) M. The data demonstrate that a human kidney particulate cell-fraction contained considerable amounts of T4 deiodinases, very similar to the type I deiodinase of various rat tissue, although the handling of rT3 and the inhibitory action of this iodothyronine on T4 to T3 conversion seem to be slightly different in the two species.

Humans↗

PubMed2003

Use of oral cholecystography agents in the treatment of hyperthyroidism of subacute thyroiditis.

AIM: In this study, we describe our experience in treating subacute thyroiditis patients with 2 OCAs (sodium ipodate and sodium iopanoate). METHODS: We studied 10 consecutive patients with subacute thyroiditis treated with 1 of the 2 oral cholecystography agents (OCAs). RESULTS: Hyperthyroidism was controlled and symptoms improved markedly in each case without any evidence of subsequent relapse of thyroiditis after withdrawal of OCAs. Three of the 10 patients had been treated previously with corticosteroids and had demonstrated relapse of thyroiditis and hyperthyroidism after tapering or withdrawal of steroids. We observed no side effects of treatment with OCAs. CONCLUSION: Our data suggest that OCAs are effective and safe agents for management of hyperthyroidism in patients with subacute thyroiditis, even when they have relapsed after treatment with corticosteroids.

Acute Disease↗

PubMed1980

Thyroid, renal, and hepatic function tests following cholecystography with high-dose contrast agents.

Serum biochemical tests were observed for about three weeks following oral cholecystography with fractionated high doses (6 g) of iopanoic acid (Telepaque) or sodium ipodate (Biloptin) in 24 and 29 patients, respectively. Both agents produced similar effects. No significant changes were seen in renal or hepatic function except for a mild increase in bilirubin on day 22. Serum urate decreased 10% on day 4, but the change was not significant. On days 4 and 11, there were significant increases in thyroid-stimulating hormone, thyroxine and free thyroxine index, and a moderate fall in triiodothyronine. Reverse triiodothyronine increased sharply on day 4. The pattern of changes observed suggests that these contrasts interfere with the extrathyroidal deiodination of iodothyronines. The temporary rise in thyroxine and free thyroxine index exceeded reference ranges in about half of all subjects, but they remained clinically euthyroid. Thyroid function tests should be interpreted with caution within three weeks of cholecystography.

Adult↗

PubMed1976

Five-hour reinforcement cholecystography.

Pathologic diagnoses were reviewed in 115 patients in whom gallbladder disease was diagnosed radiogically based on nonopacification with the calcium ipodate rapid reinforcement technique. In all instances, the gallbladder was diseased. Therefore, the rapid reinforcement technique is valid and considerably reduces the time necessary to complete reinforcement cholecystography. Because the time required in only 5 h, increased convenience and decreased cost may be realized without compromising diagnostic accurracy.

Cholecystography↗

PubMedDate not supplied

Iodothyronine and thyrotropin concentrations after iodoamide administration for angiographic studies.

In order to study the effect of iodoamide (a contrast medium widely used for urographic and arteriographic studies) on thyroid function, seventeen subjects were studied before and after arteriographic examinations employing this contrast compound. Serum concentrations of T4, T3, rT3 and TSH were not modified during the observation period by the administration of iodoamide. This finding is in contrast with the observation that iopanoic acid and ipodate, used for cholecystographic examinations, can reduce the serum concentrations of T4 and T3 with a concomitant increase in rT3. Therefore, iodoamide is not useful in the treatment of hyperthyroidism.

Adult↗

PubMed2005

General consumer communication tools for improved image management and communication in medicine.

We elected to explore new technologies emerging on the general consumer market that can improve and facilitate image and data communication in medical and clinical environment. These new technologies developed for communication and storage of data can improve the user convenience and facilitate the communication and transport of images and related data beyond the usual limits and restrictions of a traditional picture archiving and communication systems (PACS) network. We specifically tested and implemented three new technologies provided on Apple computer platforms. (1) We adopted the iPod, a MP3 portable player with a hard disk storage, to easily and quickly move large number of DICOM images. (2) We adopted iChat, a videoconference and instant-messaging software, to transmit DICOM images in real time to a distant computer for conferencing teleradiology. (3) Finally, we developed a direct secure interface to use the iDisk service, a file-sharing service based on the WebDAV technology, to send and share DICOM files between distant computers. These three technologies were integrated in a new open-source image navigation and display software called OsiriX allowing for manipulation and communication of multimodality and multidimensional DICOM image data sets. This software is freely available as an open-source project at http://homepage.mac.com/rossetantoine/OsiriX. Our experience showed that the implementation of these technologies allowed us to significantly enhance the existing PACS with valuable new features without any additional investment or the need for complex extensions of our infrastructure. The added features such as teleradiology, secure and convenient image and data communication, and the use of external data storage services open the gate to a much broader extension of our imaging infrastructure to the outside world.

Communication↗

PubMed1982

One enzyme for the 5'-deiodination of 3,3',5'-triiodothyronine and 3',5'-diiodothyronine in rat liver.

Many studies suggest that one enzyme is involved in the phenolic ring deiodination of iodothyronines in rat liver and kidney and another one in the tyrosyl ring deiodination. This study describes some characteristic of the phenolic ring (5'-) deiodination of rT3 and 3',5'-T2 by rat liver microsomes. At pH 7.2 the Km values of the 5'-deiodination of rT3 and 3',5'-T2 were 0.103 and 0.77 microM, respectively. 3',5'-T2 and rT3 inhibited the respective 5'-deiodination reactions competitively, the Ki values being 1.05 and 0.134 microM, respectively. Several radiographic contrast agents markedly inhibit the 5'-monodeiodination or rT3 and 3',5'-T2, the type of inhibition being competitive. Of these compounds iopanoic acid, ipodic acid and iophenoxic acid are the most potent inhibitors with Ki values of approximately 2 microM for both reactions. The non-iodine containing compound 8-anilino-1-naphthalene sulphonic acid (ANS) appeared to be a very strong competitive inhibitor of both 5'-deiodinations (Ki 4.3-4.7 microM), whereas salicylic acid, which as ANS inhibits the binding of iodothyronines to T4-binding globulin, inhibited these reactions to a much lesser extent (Ki 300-500 microM). On the other hand, diiodosalicylic acid was a very strong inhibitor. The beta-adrenergic blocker D,L-propranolol was a weak noncompetitive inhibitor of both 5'-deiodinations (Ki 0.4-0.7 mM). These reactions were also inhibited by various 2,6-diiodophenol derivatives, triiodophenol being the strongest and diiodotyrosine the weakest inhibitor tested. Comparing the Ki values of various inhibitors for the 5'-deiodination of rT3 and 3',5'-T2, a positive correlation between these values was found (r = 0.97). It was concluded that rT3 (to 3,3'-T2) and 3'-5'-T2 (to 3'-T1) monodeiodinating activities are very similar to each other and that there may just be one monodeiodinase catalyzing the 5'-deiodination of iodothyronines in rat liver.

Anilino Naphthalenesulfonates↗

PubMed1993

Desmethylimipramine, a potent inhibitor of synaptosomal norepinephrine uptake, has diverse effects on thyroid hormone processing in rat brain. I. Effects on in vivo uptake of 125I-labeled thyroid hormones in rat brain.

Several lines of evidence point to an interaction between amine uptake inhibitors (tricyclic antidepressants) and thyroid hormones. To examine this issue under conditions which would minimize secondary effects of drug treatment, desmethylimipramine (DMI), a highly specific norepinephrine uptake inhibitor, was given acutely as a single i.p. dose one hour before i.v. [125I]triiodothyronine (T3*) or [125I]thyroxine (T4*). Tissues were analysed after rat decapitation at 3, 5, 10, and 20 min intervals thereafter. DMI had a small but significant inhibitory effect on the brain uptake of both T3* (7.4%) and T4* (19%) over their respective 20-min time courses as indicated by two-way ANOVA. To examine the drug response further and to determine the effect of thyroid status on the response, hypothyroid (HYPO) and T4-induced hyperthyroid (HYPER) rats, were given i.v. T3* and, 5 min later, i.p. DMI or saline. They were killed 3 h later and tissue analysed. Because DMI effects on T4* uptake could not be evaluated over a 3 h period without blocking T4* to T3* conversion, sodium ipodate (60 mg/kg) was given in 2 doses before i.v. T4*. Under these conditions, DMI significantly reduced brain concentrations of the administered T3* and T4* in HYPO (15% and 19%) and in HYPER rats (13% and 25%). These results suggest that, as it does in the case of norepinephrine, DMI blocks the uptake site for T3 and T4 in rat brain. No information is available regarding the relationship, if any, between the thyroid hormone and norepinephrine uptake sites.

Animals↗

PubMed1984

3'-Monoiodothyronine degradation in rat liver homogenate: enzyme characteristics and documentation of deiodination by high-pressure liquid chromatography.

Characteristics of 3'-monoiodothyronine (3'-T1) degradation were examined in vitro in rat tissue homogenates. In rat liver homogenates, 3'-T1 degradation was optimal at pH 7.4, and was dependent upon time, temperature, and tissue concentration. The Michaeli's constant (Km) = 0.84 mumol/L. 3'-T1 degradation was enhanced by dithiothreitol and inhibited by propylthiouracil, sodium ipodate, ANS, and sodium azide but not by methimazole. Animals that fasted for three days had significant reductions in both hepatic T4 to T3 conversion (199 +/- 12 v 116 +/- 12 pg T3 generated/mg protein; P less than 0.001) and 3'-T1 degradation (588 +/- 31 v 148 +/- 53 pg 3'-T1 degraded/mg protein; P less than 0.001). To document that 3'-T1 degradation was occurring by deiodination, both liver and kidney homogenates were incubated with 125I-3'-T1 (approximately 3 microCi; 13.1 nmol/L). The reaction products were separated on a reverse-phase high pressure liquid chromatography (HPLC) column. In both tissues an iodide peak was generated, and no other radiolabeled peaks appeared except for 125I-3'-T1. These data suggest that 3'-T1 is metabolized by phenolic-ring monodeiodination and is enzymic in nature.

Animals↗

PubMed1986

The inner ring (5-) monodeiodination of thyroxine (T4) in cerebral cortex during fetal, neonatal, and adult life.

Inner ring (-5) monodeiodination of T4 was studied by incubating T4 (approximately 0.26 mumol/L) with rat cerebral cortical homogenate (approximately 4 mg protein) in the presence of dithiothreitol (up to 400 mmol/L) and quantifying the amount of the product, rT3, by a specific radioimmunoassay. The production of rT3 was dependent on duration of incubation (up to 2 hours), amount of tissue protein (up to 8 mg), temperature (optimal at 37 degrees C) and pH (optimal, 7.0) of the incubation mixture and the concentration of DTT (maximally stimulated at 400 mmol/L). The apparent Km and Vmax of the T4-inner ring monodeiodinating activity were 36 nmol/L and 1.75 pmol/mg protein/h, respectively. The activity was inhibited by T3 and 3,5-T2, but not by 3'5'-T2, PTU, methimazole, sodium salicylate, or 8-anilino-I-naphthalene sulfonic acid. Ipodate weakly inhibited T4-to-rT3 monodeiodination. Hyperthyroidism induced by T4 (100 micrograms/d IP X 3 days), T3 (80 micrograms/d IP X 3 days) or DIMIT (45 micrograms/d IP X 3 days) significantly stimulated T4-to-rT3 conversion; DIMIT was the most potent agent. Hypothyroidism inhibited T4-to-rT3 converting activity in cerebral cortex. Fasting for three days had no appreciable effect on T4-to-rT3 conversion in cerebral cortex. Cerebral cortical T4 5-deiodinase activity in the pregnant rat at term was about 50% of that in the adult nonpregnant rat, whereas that in the fetus was about three-fold higher than that in the nonpregnant adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1984

Deiodination of T4 to T3 and rT3 by microsomes from normal human thyroid tissue.

An enzyme system capable of monodeiodinating T4 to T3 and to rT3 in a microsomal fraction of normal human thyroid tissue is characterized. The pH optimum for 5'-monodeiodination of T4 to T3 was around 7.0 The Km (apparent) for the conversion of T4 to T3 was 5.7 mumoles/l. PTU, ipodate and rT3 inhibited T4 deiodination to T3. The rT3 inhibition was of the partial competitive type. rT3 accumulation could not be detected at pH 7.4 or lower. At higher pH values rT3 could be measured in the incubates; however, the concentration was much lower than that of T3. The pH optimum was 9.0. Added rT3 disappeared rapidly at pH 7.4. The results suggest a high affinity of the 5'-deiodinase in human thyroid tissue for rT3, as has previously been described in the rat, but in contrast to our previous findings in dog thyroid and liver. Using tissue from 3 highly differentiated thyroid medullary carcinomas, deiodination could not be demonstrated, while it was normal using paraneoplastic thyroid tissue from the same patients. This suggests that the deiodinases studied originated from the follicular and not the C-cells of the thyroid.

Humans↗

PubMed1989

The effect of interdialytic interval on protein metabolism: evidence suggesting dialysis-induced catabolism.

While examining protein metabolism in hemodialysis patients, we noted that lengthening the interdialytic intervals from two to three days reduced the dialysate nitrogen waste excretion (D-N2; mg/min) and lowered the patient's protein catabolic rate (PCR; g/kg/d). D-N2 was measured in the spent dialysate and PCR derived from urea kinetics while patients maintained a constant dietary intake. In the basal state (B), D-N2 decreased from 5.43 to 4.32 mg/min when the interdialytic interval was increased from two to three days (P less than 0.001). Similarly, PCR was reduced from 0.96 to 0.82 g/kg/d when the interdialytic period was extended. The same phenomenon was observed when subjects were taking either thyroid hormone (T3) or ipodate (lp) to increase or decrease body metabolism. In the T3 period, D-N2 was 6.12 and 5.06 mg/min and PCR was 1.08 and 0.92 g/kg/d, respectively, when the interdialytic intervals were two and three days (P less than 0.001). During the lp period, N-D2 was 4.78 and 4.03 mg/min and PCR was 0.88 and 0.76 g/kg/d, respectively, for the two- and three-day intervals (P less than 0.05). These data are consistent with dialysis-related protein catabolism. It appears that the longer interdialytic interval allowed the body to shift to a more anabolic state.

Adult↗

PubMed1992

Thyroid emergencies.

Thyroid storm is a rapid decompensation of severe hyperthyroidism which can best be described by the three criteria of hyperthermia, tachycardia and altered mental state with severe agitation. There has to be a precipitating factor such as infection, iodine contamination, surgery or even I-131 treatment. Severe hyperthyroidism not fulfilling the criteria of thyroid storm can also be an indication for emergency treatment, particularly in the elderly with heart disease. Suppressed serum TSH and elevated free T4 levels are essential to confirm the diagnosis. When rapidly available, radioiodine uptake of the thyroid can be useful. Therapy aims at rapidly reducing the active circulating hormone pool, hypermetabolic state, tachycardia, and finally hormone synthesis. Thyroid secretion can be blocked by ioipanoic acid or ipodate while hypermetabolic state can be reduced with beta-blockers or calcium channel-blockers. Treatment of hyperthyroidism in patients with iodine contamination is a real therapeutic challenge. Myxoedema coma, a complication of severe hypothyroidism, is defined by hypothermia (rectal temperature less than 36 degrees C), bradycardia, slow mentation, precipitating factor such as infection or drug overdose, and increased serum creatine phosphokinase levels. Diagnosis of severe hypothyroidism should be confirmed by serum measurements of TSH and free T4. Treatment consists of general supporting measures including rewarming, correction of serum electrolyte disturbances, and adequate alimentation. Thyroid hormone treatment should initially be aggressive using either 300-400 micrograms of T4 or 20-40 micrograms of T3 intravenously. Cortisone therapy may be added. Patients should be under close monitoring as arrhythmias and myocardial infarction are frequent complications of myxoedema coma and/or its treatment with thyroid hormones.

Acute Disease↗

PubMed2001

Management of a pregnant patient with Graves' disease complicated by thionamide-induced neutropenia in the first trimester.

A 31-year-old woman presented with neutropenia due to thionamide drug therapy for Graves' disease. She also reported 8 weeks of amenorrhoea and had a positive pregnancy test. Her drug therapy was discontinued and her neutropenia resolved uneventfully. The hyperthyroidism recurred a week later. After consideration of all treatment options, it was decided to observe until 14 weeks when an elective thyroidectomy was planned. Mother and fetus were monitored closely and both tolerated moderate hyperthyroidism well. At 14 weeks the patient underwent a total thyroidectomy after rendering her euthyroid with a short course of sodium ipodate. Labour was induced at 41 weeks. Delivery was complicated by fetal distress and precipitated a forceps delivery. A 3250 g male infant was born with poor Apgar score and required 2 h of ventilation. At 1 year, the child had reached all developmental milestones at appropriate times. Both mother and fetus may tolerate moderate thyrotoxicosis well in early pregnancy, an alternative that should be considered when thionamide drug therapy is contraindicated.

Adult↗