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The use of oral radiographic contrast agents in the management of hyperthyroidism.

Oral iodinated radiographic contrast agents such as ipodate and iopanoic acid form an important part of the armamentarium used to treat hyperthyroidism. They rapidly and dramatically reduce serum triiodothyronine (T3) levels by inhibiting conversion of thyroxine (T4) to T3 in the periphery and by blocking secretion from the thyroid. Potential risks from the large iodine load resulting from their use limit their widespread applicability. In addition, they are ineffective when used alone on a long-term basis. However, these agents may be especially useful in treating thyrotoxic patients preoperatively, in neonatal Graves' disease, in massive levothyroxine ingestion, and when other conventional antithyroid drugs are unsuccessful or contraindicated.

Administration, Oral↗

Coexistence of struma ovarii and Graves' disease.

A 30-year-old woman with hyperthyroidism due to coexisting Graves' disease and struma ovarii is described. Physical examination revealed a diffusely enlarged thyroid and an abdominal mass. CT scan of the abdomen showed a 25-cm predominantly cystic right ovarian mass. 123I uptake and scan showed 75% thyroid uptake at 4 h and a focus of intense uptake in the left upper quadrant of the abdomen. Preoperative treatment for the hyperthyroidism included propylthiouracil, propranolol, and ipodate. Surgery was performed and pathologic examination of the ovarian mass revealed struma ovarii.

Adult↗

Methylothermus thermalis gen. nov., sp. nov., a novel moderately thermophilic obligate methanotroph from a hot spring in Japan.

A novel moderately thermophilic methanotroph, strain MYHT(T), was isolated from a hot spring in Japan. The isolate grew on methane or methanol at 37-67 degrees C, and optimally at 57-59 degrees C. It was found to be a Gram-negative aerobe, with colourless colonies of non-motile coccoid cells, possessing type I intracytoplasmic membranes and regularly arranged surface layers of linear (p2) symmetry. Strain MYHT(T) expressed only the particulate methane monooxygenase and employed the ribulose monophosphate pathway for formaldehyde assimilation. It is a neutrophilic and halotolerant organism capable of growth at pH 6.5-7.5 (optimum pH 6.8) and in up to 3% NaCl (optimum 0.5-1% NaCl). Phylogenetic analysis based on 16S rRNA gene sequence analysis indicated that strain MYHT(T) is most closely related to the thermophilic undescribed methanotroph 'Methylothermus' HB (91% identity) and the novel halophilic methanotroph Methylohalobius crimeensis 10Ki(T) (90% identity). Comparative sequence analysis of particulate methane monooxygenase (pmoA) genes also confirmed the clustering of strain MYHT(T) with 'Methylothermus' HB and Methylohalobius crimeensis 10Ki(T) (98 and 92% derived amino acid sequence identity, respectively). The DNA G+C content was 62.5 mol%. The major cellular fatty acids were C(16:0) (37.2%) and C(18:1)omega9c (35.2%) and the major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. The major ubiquinone was Q-8. On the basis of comparative phenotypic and genotypic characteristics, a new genus and species, Methylothermus thermalis gen. nov., sp. nov., is proposed, with MYHT(T) as the type strain (=VKM B-2345(T)=IPOD FERM P-19714(T)).

Bacterial Typing Techniques↗

Hepatic kinetics and magnetic resonance imaging of gadolinium ethoxybenzyl diethylenetriaminepentacetic acid (Gd-EOB-DTPA) in dogs.

This complex study was designed to measure the transport and excretion characteristics of gadolinium ethoxybenzyl diethylenetriaminepentacetic acid (Gd-EOB-DTPA) in dog's livers following bolus and infusion. Simultaneous T1 magnetic resonance imaging was performed to measure maximum signal enhancement. Anaesthetized dogs had cannulation of the common bile duct and urinary bladder for collections and cannulation of the femoral artery and vein for monitoring, blood sampling and infusion. Gd-EOB-DTPA was administered by bolus (range 12.5-200 mumol/kg) and infusion (range 0.4-6.4 mumol/min per kg). An hepatic transport maximum 0.09-0.15 mumol/min/kg was achieved with a blood concentration of 0.03-0.06 mumol/mL. Marked hepatic affinity for Gd-EOB-DTPA was demonstrated with measurements of liver concentration. Maximum T1 signal enhancement was achieved with blood Gd-EOB-DTPA concentration of 0.02-0.03 mumol/mL and a liver concentration of 1-2 mumol/g. The transport maximum for Gd-EOB-DTPA in the dog was similar to that for ipodate and iodipamide and effective imaging was achieved with sub-maximal doses. The maximum signal enhancement at blood concentrations less than required for maximum transport suggest a wide latitude for effective clinical imaging.

Animals↗

Single-visit oral cholecystography for inpatients.

A new one-day medication schedule for single-visit oral cholecystography is described, using both Telepaque (iopanoic acid) tablets and Oragrafin Sodium (sodium ipodate) capsules. A definitive report is rendered at the first sitting; no repeat studies are performed. Preliminary results in 45 patients demonstrate the accuracy of this technique. One-day medication makes single-visit oral cholecystography suitable for hospitalized patients.

Cholecystography↗

Binding and degradation of 3,5,3'-triiodothyronine and thyroxine by rat intestinal bacteria.

Intestinal bacteria hydrolyze conjugates of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) secreted in bile, but it is not clear whether they have any other role in metabolism, storage, transport, or action of thyroid hormone in the intestines. We have examined aspects of T3 and T4 binding and degradation processes in fresh feces and cecum contents, obtained from normal control rats and from rats partially decontaminated by treatment with oral antibiotics for 2-3 wk. Samples were homogenized in phosphate buffer, fractionated, and subjected to various test conditions and incubated at 37 degrees C with 125I-labeled T3 (T3*) or T4 (T4*) for 2 or 24 h. Supernatants of high-speed centrifuged incubates were chromatographed to test for degradation products, and percentage binding was measured in the pellets. Substantial binding of T3* and T4* was found in all control rat feces and cecum content samples by 2 h, but binding was absent or significantly reduced in partially decontaminated rat samples. Bacterial binding of T3* and T4* were further shown to be competitive with graded doses of bovine serum albumin. Considerable degradation of T3* and T4* to labeled iodide (I*) only was also observed in feces and cecum content samples and was much greater in control rat than in corresponding partially decontaminated rat samples. Light had no effects in our system and heat reduced I* production. Propylthiouracil and sodium ipodate had little effect or equivocal effects, but dithiothreitol substantially inhibited I* production.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Deiodination of reverse 3, 3', 5'-triiodothyronine by hepatic nuclear protein preparations.

A reassessment of the binding characteristics of [125I]rT3 to putative receptors in nuclear protein extracts of rat and pig liver revealed that significant deiodination of radioligand occurred during incubation. When previously reported separation procedures are used, released radioiodine is included in the protein-bound [125I]rT3 fraction during separation of protein bound from free hormone by Sephadex G-25 chromatography. This misclassification produces artefacts in binding curves and Scatchard plots used to calculate binding affinity and capacity. Previously reported affinities and capacities derived by this methodology are therefore erroneous. Deiodination of rT3 in the nuclear protein extracts appears to be mediated by outer ring deiodinase. Whereas dithiothreitol markedly enhanced radioiodine generation, the enzyme inhibitors ipodate and salicylate reduced iodine production. These effects produced dramatic changes in apparent binding curves for the radioreceptor assay. When [125I]T3 was incubated with nuclear protein extract, no significant deiodination was detected. Whereas it is likely that the deiodinase is a microsomal contaminant of the nuclear preparation, as suggested by the presence of glucose-6-phosphatase in the nuclear protein preparation, the possibility of an intrinsic nuclear-linked deiodinase cannot be overlooked.

Animals↗

Characterization of thyrotropin-induced increase in iodothyronine monodeiodinating activity in mice.

To further characterize the effect of TSH administration on thyroid iodothyronine monodeiodinating activity, we have evaluated the in vitro conversion of T4 to T3 (outer ring deiodination) and T3 to 3,3'-diiodothyronine (T2; inner ring deiodination) by mouse thyroid, liver, and kidney homogenates, comparing tissues from TSH-treated mice (0.1-200 mU bovine TSH, ip, for 1-3 days) with tissues from saline-treated controls. The in vitro conversion activity was studied in the presence of 1-20 mM dithiothreitol; most of the studies were carried out at 4 mM. Studies were carried out at optimal pH 6.5 for outer ring and 7.8 for inner ring deiodination. The iodothyronine monodeiodinase in mouse thyroid is similar to the ones in liver and kidney. It is heat labile (inactivated at 56 C for 5 min), inhibited by propylthiouracil (0.2 mM) and ipodate (0.2 mM), and unaffected by methimazole (up to 20 mM), ascorbate (up to 0.1 M) or KI (up to 20 mM). The mean +/- SE baseline rates of T4 to T3 and T3 to T2 conversion were 100 +/- 6.3 and 56.5 +/- 2.9 pmol/mg thyroid protein X 30 min at 37 C, respectively. A significant increase in each conversion activity was found after TSH treatment (0.2 U, ip, daily for 3 days); T4 to T3 conversion rose to 282 +/- 15.4, and T3 to T2 increased to 153 +/- 7.4 pmol/mg thyroid protein (P less than 0.001). A 12.8% increase in thyroid weight was found in the TSH-treated group (P less than 0.03 compared with saline control group). Similar but less marked increased in monodeiodinating activities were seen in the liver. A minimal but significant increase in inner ring monodeiodination with no significant increase in T4 to T3 converting activity was found in kidney, which, in the mouse, has markedly less outer ring deiodinase than liver or thyroid. The iodothyronine monodeiodinating activities did not increase until 12 h in thyroid and 48 h in liver after the first dose of TSH. Significant increases in T4 to T3 and T3 to T2 conversion were seen with doses of TSH as low as 0.1 mU (ip, daily for 3 days), and there was a linear dose-response thereafter. The decay of the increased iodothyronine monodeiodinating activities after a single dose of TSH (0.2 U) appeared to be linear, with a decay t 1/2 of 1.3 days for T4 to T3 conversion and about 1.0 day for T3 to T2 conversion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Skin is an active site for the inner ring monodeiodination of thyroxine to 3,3',5'-triiodothyronine.

T4 (0.26 microM) was incubated in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA with homogenates (3-5 mg protein) of various rat tissues and up to 400 mM dithiothreitol (DTT) for 1 h at 37 C; the rT3 generated was measured by RIA of ethanol extracts of the incubation mixture. Among the various tissues of the male rat, homogenates of skin and cerebral cortex were very active in the conversion of T4 to rT3; other tissues demonstrated little or no T4 5-monodeiodinating activity (MA). The tissue content of rT3 was also greatest in these two tissues. The MA in skin increased linearly with incubation period (up to 4 h) and with increasing concentration of protein (up to 5 mg), substrate (up to 10 microM) and DTT (up to 400 mM); its optimal pH was 7.4, and optimal temperature was 37 C. Its Km and maximum velocity approximated 0.29 microM and 9.6 pmol/h X mg protein, respectively, in the presence of 400 mM DTT. There was no appreciable difference in T4 to rT3 MA of skin from different parts of the body. The MA was most abundant in microsomes and least in cytosol. The MA was unaffected by propylthiouracil (up to 25 microM), methimazole (up to 100 microM), sodium salicylate (up to 80 microM), or 8-anilino-1-naphthalene sulfonic acid (up to 75 microM). Ipodate (up to 80 microM) weakly inhibited the MA. T3 and 3,5-diiodothyronine inhibited dermal T4 to rT3 MA in a dose-dependent manner; T3 was 3-12 times more potent than 3,5-diiodothyronine on a molar basis in different experiments. Treatment of euthyroid rats with 3,5-dimethyl-3'isopropylthyronine (45 micrograms/day, ip) for 3 or 5 days significantly increased dermal T4 to rT3 MA. Similar treatment of rats with T4 (100 micrograms/day, ip) or T3 (20 or 80 micrograms/day, ip) did not change with MA appreciably. Hypothyroidism markedly inhibited the MA, and fasting inhibited it modestly. Pregnancy was associated with marked reduction in the MA of skin in the mother [0.30 +/- 0.11 (+/- SE) vs. 7.2 +/- 2.2 ng/h X mg protein; P less than 0.02] and fetus (0.67 +/- 0.075; P less than 0.025).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A radioimmunoassay for measurement of thyroxine sulfate.

A highly sensitive, specific, and reproducible RIA has been developed to measure T4 sulfate (T4S) in ethanol extracts of serum. rT3 sulfate (rT3S) cross-reacted 7.1%, and T3S cross-reacted 0.59% in the RIA; T4, T3, rT3, and 3,3'-diiodothyronine cross-reacted 0.004% or less. The recovery of nonradioactive T4S added to serum averaged 95%. The detection threshold of the RIA was 18 pmol/L. The coefficient of variation averaged 6.9% within an assay and 12% between assays. T4S was bound by T4-binding globulin and albumin in serum. The free fraction of T4S in four normal sera averaged 0.06% compared to a value of 0.03% for T4 (P < 0.001). The serum concentration of T4S was (mean +/- SE) 19 +/- 1.2 pmol/L in normal subjects, 33 +/- 10 in hyperthyroid patients with Graves' disease, 42 +/- 15 in hypothyroid patients, 34 +/- 6.9 in patients with systemic nonthyroidal illnesses, 21 +/- 4.3 in pregnant women at 15-40 weeks gestation, and 245 +/- 26 in cord blood sera of newborns; the value in the newborn was significantly different from normal (P < 0.001). The mean concentration of T4S in amniotic fluid samples at 15-38 weeks gestation was 106 +/- 22 pmol/L (cf. normal adults; P < 0.001). Administration of sodium ipodate (Oragrafin; 3 g, orally) to hyperthyroid patients was associated with a transient increase in serum T4S. The T4S content of the thyroid gland was less than 1/4000th that of T4. We conclude that 1) T4S is a normal component of human serum, and its levels are markedly increased in newborn serum and amniotic fluid; and 2) the sulfation pathway plays an important role in the metabolism of T4 in man.

Blood Proteins↗

Use of oral cholecystographic agents in the treatment of amiodarone-induced hyperthyroidism.

We describe here five cardiac patients with type II amiodarone-induced hyperthyroidism who were treated prospectively with a combination of an oral cholecystographic agent (sodium ipodate, Oragrafin, or sodium iopanoate, Telepaque) and a thionamide (propylthiouracil or methimazole); amiodarone was discontinued in all patients. All patients improved substantially clinically within a few days of treatment and became euthyroid or hypothyroid in 15-31 wk when treatment was discontinued. Four of the five became hypothyroid and required long-term treatment with L-T(4); the remaining patient was euthyroid, but died from cardiomyopathy and congestive heart failure at 29 wk, when he had been off oral cholecystographic agent and thionamide for 6 wk. We did not find any clinical or biochemical adverse effects of the treatment. Our study suggests that a combination of oral cholecystographic agent and thionamide is a safe and effective treatment of type II amiodarone-induced hyperthyroidism. Data also suggest that hypothyroidism is a common end result of type II amiodarone-induced hyperthyroidism.

Administration, Oral↗

Integrating and promoting medical podcasts into the library collection.

Podcasts offer a way for medical professionals to listen to current information in medicine from an iPod, MP3 player, handheld device, or computer. As podcasts become more popular, libraries may be interested in integrating programs into the library collection. South Pointe Medical Library evaluated medical podcasts relevant to the scope of the library collection and explored methods for finding and organizing such programs in ways that are efficient for both the librarian and the patron. doi:10.1300/J115v26n01_03.

Access to Information↗

[Monodeiodination of thyroxine to 3,3', 5-triiodothyronine and 3,3', 5'-triiodothyronine in human kidney homogenate (author's transl)].

The renal cortex, later proved by histology to be free of carcinoma, was obtained from the kidneys of 9 patients undergoing nephrectomy for hypernephroma or ureteral carcinoma. The cortex was homogenized in a cold 50mM Tris-HCl buffer, pH 7.5, and centrifuged at 800 X g. Supernatants (1.8 mg protein, referred to as "homogenate") were enriched with 2 micrograms of T4 and were incubated for varying periods at different temperatures. The T3 and rT3 formed were extracted into ethanol and measured by RIA. Reaction mixtures contained 5mM dithiothreitol, without which formation of T3 and rT3 from T4 was negligible. The production of T3 and rT3 from T4 was abolished by prior heating of the homogenate to 56 degrees C for 30 min. In fresh homogenates, the production of T3 and rT3 increased with an increased concentration of homogenate (0.2-1.8 mg protein), increased incubation temperature up to 37 degrees C, increased incubation time up to 60 min, and increased T4 concentration up to 8 micrograms/tub. T3 production from T4 was near maximal at pH 6.5 and rT3 production at pH 10. At the standard pH of 7.5, rates of net T3 and rT3 production were 58 and 45%, respectively, of those at the optimum pH. Degradation of rT3 was rapid, while degradation of T3 was negligible. Both T3 and rT3 production from T4 were inhibited in a dose dependent manner by ipodate, propylthiouracil and salicylate. The apparent Km values for monodeiodination of T4 to T3 was 10 microM. Among the usual subcellular fractions of the kidney homogenate, microsomes were most potent in deiodinating T4 to T3 and to rT3. These results indicate that the human renal cortex contains the enzymes generating T3 and rT3 from T4.

Humans↗

Uptake of iopanoic acid and its glucuronide conjugate by rat hepatocytes in primary culture.

Uptake of iopanoic acid (IOP) and iopanoate glucuronide (IOP-G) was studied in 3-day primary cultures of rat hepatocytes isolated by the collagenase perfusion method. 125I activity of cells after incubation with 125I-IOP (10-100 microM) and 125I-IOP-G (10-100 microM) was used as a measure of uptake. At each concentration, uptake was linear for the first 45 sec. In the absence of albumin, the initial uptake velocity was directly proportional to the concentration or IOP or IOP-G and was nonsaturable up to 100 microM. The calculated uptake rate constants for IOP and for IOP-G were 0.059 and 0.048 nmole/(mg protein X min X microM), respectively. IOP uptake was not inhibited by sodium taurocholate nor by the contrast agents iodipamide, ipodate, and iopronic acid. The data indicate that the enhancement of IOP excretion by bile salts noted in vivo does not occur at the uptake step and that the hepatic uptake of both IOP and IOP-G in the absence of albumin is limited by diffusion.

Adsorption↗

Iopanoic acid as an adjunct to carbimazole in the management of hyperthyroidism.

BACKGROUND: The thiourea drugs take a few weeks to control the symptoms of hyperthyroidism whilst iodine containing radiographic contrast agents (iopanoic acid and sodium ipodate) have a more rapid effect. There is no report on the use of iopanoic acid administered in conjunction with carbimazole, so we evaluated the efficacy of this combination in the early medical management of patients with hyperthyroidism. METHODS: Thirty hyperthyroid patients diagnosed by clinical and biochemical criteria were randomized into two treatment groups. Group A (n = 16) received iopanoic acid (500 mg orally twice a day for the first 3 weeks) and carbimazole (30 mg orally in three divided doses) while group B (n = 14) received carbimazole alone. Clinical examination and estimation of serum total T3, total T4 and TSH were done by radioimmunoassay at the start of therapy, weekly for 4 weeks and then at 6, 8 and 12 weeks. RESULTS: In the initial 3 weeks, iopanoic acid induced a significantly greater fall in mean serum total T3 levels (Z = 2.298, p < 0.02) and a slower fall in mean serum total T4 (Z = 2.396, p < 0.05) in group A patients compared to those in group B. This was accompanied by earlier clinical improvement in group A patients. The mean serum total T3 and T4 values rose to higher levels in group A at 4 weeks, one week after discontinuation of iopanoic acid. At the end of 12 weeks, however, there was no significant difference in the mean serum total T3 and T4 levels between the two groups (p > 0.05). Biochemical euthyroidism (i.e. total T3 < 3 nmol/L and total T4 < 170 nmol/L) was achieved later in group A patients than in group B (10.4 +/- 5.0 weeks v. 3.6 +/- 1.2 weeks, p < 0.0001). CONCLUSIONS: Iopanoic acid given together with carbimazole induces rapid clinical improvement in hyperthyroid patients than carbimazole alone. However, the delayed achievement of euthyroidism may preclude its routine use in the management of patients with hyperthyroidism except in those with thyrotoxic emergencies.

Adult↗

Podcasts--an emerging form of digital publishing.

Podcasting has recently emerged as an important information technology tool for health professionals and consumers around the world. Prestigious journals, international conferences, universities and government agencies among other entities are starting to publish digital informotion via audio and video podcasts. Podcosting is distinguished from other forms of digital audio-video content because it can be subscribed to (using Real Simple Syndication or RSS) and easily accessed from a personal computer. Further, it can be downloaded to a mobile device, such as an iPod where the user is able to listen to or watch it anywhere, anytime. Podcosting is used in new and evolving ways to publish information for healthcare education, patient care, professional continuing education, and in support of healthcare research. In addition to a description of what podcasting is, how podcasts are created, and how they are used, this paper addresses four critical issues that are emerging concerning podcasts. These issues are intellectual property and copyright, podcast preservation, podcast location, and podcast standards. As podcasting matures and new uses are discovered, we will see podcasting incorporated into our education, research and patient care publication paradigm.

Computers, Handheld↗

UCLA conference. Autoimmune thyroid diseases--Graves' and Hashimoto's.

Thyroid-related autoimmune diseases (Graves' thyroid disease, Graves' ophthalmopathy, and Hashimoto's thyroiditis) may occur alone or in any association. The diagnosis of Hashimoto's thyroiditis requires multiple criteria; pathologic changes in the thyroid are not due to antibodies but may result from cytotoxic lymphocytes or a deficiency of suppressive T cells. In Graves' and Hashimoto's diseases the increased prevalence of HLA-B8 may not be significant, but that of HLA-AW30 in Hashimoto's disease is. In 48 first-degree relatives of patients with Graves' disease, thyroid abnormalities were frequent but not correlated with HLA type. Elevated serum thyroglobulin levels in all patients with hyperthyroidism fell to normal after surgical resection or radioiodine therapy. Patients whose illness recurred after antithyroid drug treatment was stopped had higher pretreatment thyroglobulin levels and no fall during treatment; those whose illness remitted had lower initial levels and a significant fall during treatment. Sodium ipodate lowered serum triiodothyronine and thyroxine levels in hyperthyroid patients and may be useful in the treatment of hyperthyroidism.

Animals↗

Amiodarone inhibits T4 and T3 secretion but does not affect T4 deiodination to T3 in perfused dog thyroid lobes.

Amiodarone interferes with thyroid hormone homeostasis in several ways. In the present study we assessed if amiodarone has direct effects on thyroid secretion of T4 and T3 and on intrathyroid T4 deiodination to T3 as studied in perfused dog thyroid lobes. 10(-4) mol/l amiodarone inhibited the TSH stimulated T4 secretion to 73.0 +/- 8.3 per cent of control (mean +/- SE, n = 4, p less than 0.05) and T3 secretion to 68.3 +/- 6.2 per cent of control (p less than 0.05). Amiodarone did not alter intrathyroidal T4 deiodination to T3 since the T4/T3 ratio in thyroid effluent was not affected. The mechanism behind the amiodarone effect on the thyroid is unknown but probably different from that responsible for the effect of certain other iodine containing aromatic compounds (e.g. ipodate).

Amiodarone↗