Oral Cholecystographic Agents Research Articles

Efficacy of iopanoic acid for treatment of spontaneous hyperthyroidism in cats

Iopanoic acid is an iodine containing oral cholecystographic agent that has been used to treat hyperthyroidism in humans and has recently been evaluated in an experimental model of feline hyperthyroidism. The aim of this study was to evaluate the efficacy of iopanoic acid in cats with spontaneous hyperthyroidism. Eleven cats were included in the study. Eight were treated initially with 50mg orally q 12h and three were treated with 100mg orally q 12h. Prior to treatment (baseline) and at 2, 4, and 12 weeks of treatment, owner questionnaires, physical exams, complete blood count, biochemistry analyses, and T(3) and T(4) concentrations were evaluated. The mean serum T(3) concentration decreased with treatment at all time periods compared to baseline. Mean T(4) concentrations were increased at weeks 4 and 12 compared to baseline. Five cats had a partial response during the initial 4 weeks of therapy, but the effects were transient and no significant improvements in clinical signs or physical exam findings were noted at any time period. Results suggest that iopanoic acid may be beneficial for acute management of thyrotoxicosis in some cats, but is not suitable for long-term management.

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.

Use of Oral Cholecystographic Agents in the Treatment of Amiodarone-Induced Hyperthyroidism

Use of Oral Cholecystographic Agents in the Treatment of Amiodarone-Induced Hyperthyroidism

Oral Cholecystographic Agents and the Thyroid

Oral cholecystographic agents (OCAs) are known to affect thyroid hormone metabolism by acting as potent inhibitors of type I and type II deiodinases, blocking the conversion of T(4) to T(3) and rT(3) to T(2). In addition, iodine released from the drug blocks thyroid gland secretion of thyroid hormone. These properties make OCAs a potentially useful drug therapy in patients with hyperthyroidism and other thyrotoxic disorders. Short-term treatment with OCAs rapidly reduces serum T(3) levels, with a lesser effect on T(4) levels. OCAs are not useful for long-term treatment, which is usually followed by exacerbation of hyperthyroidism with continued use. The lack of significant side effects makes these drugs an excellent short-term option in situations where a rapid clinical improvement is critical.

Oral Cholecystographic Agents and the Thyroid

Oral Cholecystographic Agents and the Thyroid

Stereochemical Control in Microbial Reduction. XXVIII. Asymmetric Reduction of α,β-Unsaturated Ketones with Bakers’ Yeast

Abstract Bakers’ yeast reduction of α,β-unsaturated ketones affords optically active saturated ketones contaminated by allylic and saturated alcohols as minor components. Stereoselectivity of the reduction of carbon–carbon double bond strongly depends on the structure of β-aryl substituent. The bakers’ yeast reduction of β-phenyl enones gives saturated ketones in moderate stereoselectivity. Stereoselectivity is not altered by substitution at the para-position, whereas introduction of a substituent at the ortho- or meta-position drastically improves the stereoselectivity. Deuterium-labeling experiments reveal that the enzymatic reduction of carbon–carbon double bond proceeds with formal trans-addition of hydrogens regardless the efficiency of stereoselectivity. The resulting optically active ketone was converted to the precursor of (S)-iopanoic acid, an inhibitor of thyroxine 5′-deiodinase that is a thyroid hormone-converting enzyme and an oral cholecystographic agent.

Acute l-thyroxine overdose; therapy with sodium ipodate: Evaluation of clinical and physiologic parameters

Two children with acute L-thyroxine overdose were treated with sodium ipodate, an oral cholecystographic agent. Initial thyroxine (T4) levels were elevated to 98.5 mcg/dL and 134.1 mcg/dL, with associated triiodothyroxine (T3) levels of 354 ng/dL and 402 ng/dL. T3 levels increased to a maximum of 662 ng/dL and 468 ng/dL. With administration of sodium ipodate, the T3 decreased with a simultaneous increase of rT3 level. Sodium ipodate effect lasted 72 hours. No toxic effect was noted. Interestingly, thyroid hormone levels correlated with systolic blood pressure but with no other physiologic parameter. Sodium ipodate appears to be a viable treatment modality for acute thyroid overdose in children.

Sodium ipodate in the preparation of Graves' hyperthyroid patients for thyroidectomy.

Sodium ipodate (SI) is an oral cholecystographic agent that also affects thyroid hormone metabolism. It inhibits the peripheral T4 to T3 conversion and the thyroidal hormone release. We investigated the safety and efficacy of SI (500 mg daily during 5 days) in the preparation for subtotal thyroidectomy of 7 Graves' hyperthyroid patients in whom treatment with thionamides was unsuccessful due to allergy or noncompliance. Plasma T3 levels (mean +/- SD) decreased from 4.90 +/- 1.80 nmol/l on day 0 to 1.70 +/- 0.30 nmol/l on day 4 of treatment. Thyroidectomy performed on day 5 of treatment was uneventful. In comparison with 14 Graves' hyperthyroid patients who underwent thyroidectomy during the same period after conventional preparation with thionamides and potassium iodide, the therapeutic outcome 1 year postoperatively was similar in both groups. However, in the mildly hypothyroid patients prepared with SI, the plasma thyroid-stimulating hormone level was transiently higher 3 and 6 months postoperatively. It is concluded (1) that SI is a safe and efficacious drug in the preparation of Graves' hyperthyroid patients for thyroidectomy; (2) the therapeutic outcome 12 months postoperatively is similar in SI and in conventionally prepared Graves' hyperthyroid patients, and (3) postoperative mild or subclinical hypothyroidism is more pronounced in SI than in conventionally prepared patients.

Oral cholecystosonography: a method for facilitating the diagnosis of cholesterol gallstones.

During the past two years, floating stones within the gallbladder have been demonstrated in five patients, by both oral cholecystography and sonography. We suggest coupling administration of an oral cholecystographic contrast agent with ultrasound examination in cases of equivocal sonographic findings. The combined study--oral cholecystosonography--can facilitate the demonstration of small cholesterol stones by inducing the phenomenon of layering.

Alterations in thyroid function after cholecystographic contrast agents.

The radiographic contrast agents commonly used for oral cholecystography have diverse effects on thyroid hormones in man. They may: (i) decrease serum triiodothyronine (T3) and increase reverse T3 in both hyperthyroid and euthyroid subjects, an effect attributable to inhibition of phenolic (outer) ring deiodination of iodothyronines; (ii) acutely increase serum thyroxine (T4) by displacing it from the liver, so inviting an erroneous diagnosis of hyperthyroidism; (iii) precipitate hyperthyroidism in apparently euthyroid subjects who have autonomous thyroid tissue. In comparison with the cholecystographic agents which are taken up by the liver, the renally-excreted contrast agents used for angiography or intravenous urography are much less potent in producing these effects. The paradox of T4 excess with normal T3 may arise after cholecystography, either by an acute T4 increase in a euthyroid subject, or by normalization of T3 in hyperthyroidism, thus creating a diagnostic dilemma. The recent trend towards use of oral cholecystographic agents in the urgent management of hyperthyroidism, because of their effect on serum T3, needs to be regarded with caution in view of the risk that hyperthyroidism may eventually be worsened if synthesis of T4 is not effectively blocked. For this reason, contrast media should probably be used in the treatment of hyperthyroidism only in conjunction with conventional antithyroid drugs. A history of exposure to contrast media should be sought in any acute or unexpected exacerbation of hyperthyroidism, or when T4 excess is found without an increase in T3.

Cardiac catheterization dye does not affect serum thyroid hormone concentrations or TSH secretion.

The iodinated contrast agents used in oral cholecystography impair peripheral iodothyronine-5'-deiodinase activity, resulting in a transient decrease in serum 3,5,3'-triiodothyronine (triiodothyronine, T3) and in increases in serum 3,3',5'-triiodothyronine (reverse T3, rT3) and thyroxine (T4) concentrations. A related iodinated contrast agent, diatrizoate, is employed in coronary angiography. The effect of diatrizoate (Renografin-76) on serum T4, T3, rT3, and thyroid stimulating hormone (thyrotropin, TSH) concentrations and the TSH and T3 responses to thyrotropin releasing hormone (TRH) were evaluated in seven euthyroid patients before and on the fifth day following coronary angiography. No significant changes were observed. Thus, diatrizoate, in contrast to the oral cholecystographic agents, appears to have little or no clinically important effect on thyroid hormone metabolism in man.

Development and preliminary pharmacologic evaluation of a zwitterionic oral cholecystographic agent.

A new zwitterionic iodinated molecule, 2-[3-(N-ethyl-2-hydroxyethyl) amino-acetamido-2, 4, 6-triiodobenzyl]-butyric acid (RCK-136) was synthesized, and its potential as an oral cholecystopaque was tested. In rats, 15 minutes following intravenous injection, RCK-136 reached maximum biliary concentration; 84% of the dose was excreted into bile. Biliary excretion of RCK-136 elicited a strong choleresis (44 ml of bile flow per mmol compound). Intravenous LD50 in rats averaged 390 mgI/kg. ED50 in rats, intradiencephalic, averaged 1.98 mgI/kg. The average densities of cholecystograms produced in three dogs with iosumetic acid and/or RCK-136 were comparable.

Effect of Iopanoic acid on the pituitary-thyroid axis: time sequence of changes in serum iodothyronines, thyrotropin, and prolactin concentrations and responses to thyroid hormones.

We have previously shown that some oral cholecystographic agents induce marked increase in basal and TRH-stimulated TSH concentrations in normal subjects. To define the relationship between circulating iodothyronines and pituitary secretion after oral cholecystography, temporal changes in the responses of serum TSH and PRL to a fixed dose of TRH (500 micrograms iv) and in serum T4, T3, and rT3 concentrations were assessed before, immediately after, and then at weekly intervals after the three daily doses of iopanoic acid (Ip). Both basal and TRH-stimulated TSH concentrations were significantly increased at the end of the period of Ip administration when the serum T3 concentration was decreased, were still above the pretreatment level 1 week after the course of Ip when the serum T3 had returned to pre-Ip levels, and returned toward normal 2 weeks after the course of Ip. The changes in serum T3 concentration were accompanied by reciprocal changes in rT3 concentration. PRL secretion was not significantly changed. To evaluate further the relationship between the enhanced TSH secretion and the changes in serum iodothyronine concentrations, subjects were given oral doses of T3 (5 micrograms every 4 h) or T4 (50 micrograms every 8 h) during the administration of Ip. In the subjects given Ip plus T3, serum T3 concentrations were maintained at pre-Ip levels, and both basal and TRH-stimulated TSH concentrations were not different from the control. Administration of T4 did not completely prevent the Ip-induced increment of TSH secretion. It is suggested that in subjects given Ip, 1) the serum T3 level is, at least partly, a determining factor for TSH secretion; and 2) the set-point of TSH secretion is appropriately tuned to either reduction or elevation of serum T3 concentration by a mechanism that is different from that in fasting subjects.

The effect of iopanoic acid on the regulation of thyrotropin secretion in euthyroid subjects.

Oral cholecystographic agents induce a decrease in serum T3 and an increase in serum T4 and rT3 concentrations in normal subjects. However, their effect on TSH secretion in man is unclear. In the present study, the serum TSH concentration was increased above baseline values 5 days after the administration of 3 g iopanoic acid (IA) in five of six euthyroid volunteers (an increase of borderline significance), and the TSH response to TRH was significantly augmented after IA administration. In four other euthyroid subjects who had received IA 3 days earlier, the administration of T3 (5 microgram, five times daily) for the next 2 days restored the serum T3 concentration toward baseline values and prevented the IA-induced increase in TRH-stimulated serum TSH concentrations. It is concluded from the present study that IA enhances pituitary thyrotroph sensitivity to TRH and that this effect may be related, at least in part, to the IA-induced decrease in circulating T3 as well as the previously demonstrated inhibitory effect of IA on the pituitary conversion of T4 to T3. This decrease in the serum T3 concentration after IA administration is due primarily to inhibition of peripheral 5-monodeiodination of T4 and, possibly, to a direct inhibitoy effect of excess iodide on the release of T3 from the thyroid.

EFFECTS OF THREE-DAY ORAL CHOLECYSTOGRAPHY ON SERUM IODOTHYRONINES AND TSH CONCENTRATIONS: COMPARISON OF THE EFFECTS AMONG SOME CHOLECYSTOGRAPHIC AGENTS AND THE EFFECTS OF IOPANOIC ACID ON THE PITUITARY-THYROID AXIS

The effects of repeated doses of oral cholecystographic agents on serum thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3) and thyrotrophin (TSH) concentrations were studied in 37 euthyroid male subjects. Iobenzamic acid, tyropanoic acid, iopanoic acid, and ipodate sodium, in a dosage of 3 g for 3 days, respectively, induced a significant decrease in serum T3 and an increase in rT3 within 24 h after the initial dose, followed by an increase in TSH and a slight increase in T4. The extent of the changes in rT3 varied between the agents, ipodate causing the greatest change, but without any relation to the changes in T3 or T4. Responses of serum T4, T3, rT3 and TSH concentrations to exogenous thyrotrophin-releasing hormone (TRH) and bovine TSH were also studied before and after 3-day doses of iopanoic acid. In 11 subjects given iopanoic acid, the response to TSH to TRH (500 micrograms, iv) was increased but the T3 response was unchanged. A dose of TSH (10 U.S.P. units, im) caused a significant increase in serum T3 and a decrease in TSH concentrations in 5 subjects both before and after cholecystography. It is thus suggested that in euthyroid subjects given multiple doses of oral cholecystographic agents, (1) the primary and consistent events are the reciprocal changes of serum T3 and RT3, although the extent of the changes is not coordinately reciprocal; (2) the responsiveness of the pituitary thyrotrophs and thyroid to TRH is preserved; and (3) the high basal and TRH-induced TSH in the serum may be ascribed to the decrease in the serum T3 concentration.

Determinants of the Rate of Intestinal Absorption of Oral Cholecystographic Contrast Agents in the Dog Jejunum

Successful opacification of the gallbladder during oral cholecystography depends on adequate absorption of the contrast agent from the intestine. The present studies were undertaken to define the specific characteristics of the intestinal mucosa and the properties of the various contrast agents which determine their rates of intestinal absorption. The polarity of the compounds was established by determining the ratios of their distribution between bulk solvents (benzene and water). In addition, the maximum aqueous solubility of each compound was determined. Using in vivo cannulated segments of dog jejunum, apparent passive permeability coefficients were measured. From these data, the apparent maximal rate of intestinal absorption was calculated. The six cholecystopaques studied differed markedly in polarity as judged by their varying ratios of distribution between benzene and water. The permeability coefficients varied inversely with the polarity of the compounds. However, the incremental changes in the coefficients were considerably less than the corresponding changes observed in the partition ratios. The rates of absorption of the more polar contrast agents (tyropanoate, iopronic acid, and iocetamic acid) were greater than the less polar compounds (iopanoic acid, sodium ipodate, and calcium ipodate) under the conditions in which the resistance of the unstirred water layer is not rate limiting and where bile acid micelles are not present.

A comparative trial of two oral cholecystographic contrast media—iocetamic acid (Cholebrin) and iopanoic acid (Telepaque)

A comparative trial was made between two oral cholecystographic agents, iocetamic acid (Cholebrin) and iopanoic acid (Telepaque), Fifty patients were given Cholebrin and another 50 were given Telepaque by random allocation. The cholecystographic qualities of the two contrast media showed no significant difference. It was noted that contrast medium within the bowel at the time of the investigation tended to be homogeneous rather than granular with Cholebrin, and the significance of this is discussed. Gastrointestinal side-effects were common with both contrast media, but there was a significantly lower incidence of diarrhoea with Cholebrin than with Telepaque. Various biochemical parameters of hepatic and renal function were measrued in 40 random patients and showed no clinically significant alteration following ingestion of the contrast media.

日本自動化健診学会委員会報告 胆のう造影剤および腸管内カズ吸着剤の血液生化学検査値に及ぼす影響

日本自動化健診学会委員会報告 胆のう造影剤および腸管内カズ吸着剤の血液生化学検査値に及ぼす影響

An evaluation of plain roentgenograms prior to oral cholecystography in children.

Plain roentgenograms were taken prior to oral cholecystography in 100 children. Three children had their gallstones obscured by the oral cholecystographic agent. Consideration should be given to obtaining plain roentgenograms in children with a strong clinical suspicion of gallbladder disease and a normal oral cholecystogram.

The Present Status of Imaging of the Gallbladder

Oral cholecystography is still the basic modality for the diagnosis of gallbladder disease. Now, for the first time since the introduction of this procedure in 1924, this status is being challenged by another diagnostic technique, ultrasonography of the gall bladder. Ultrasound studies have major advantages over conventional cholecystography. These are sufficiently important that it can be safely predicted that ultrasonography will eventually become the primary diagnostic tool for evaluating the gallbladder. Just as the use of colonoscopy has provoked a new analysis of the barium enema examination in the evaluation of the colon, the introduction of ultrasound examination of the gallbladder has revealed the fact that false-negative oral cholecystograms are not rare. Before ultrasonography this information was unobtainable, because of the surgeon's proper reluctance to perform a cholecystectomy in patients with normal oral cholecystograms. Indeed, the availability of an accurate alternate diagnostic procedure has stimulated a reevaluation of other difficulties associated with oral cholecystography. These include problems involved with non-visualization and impaired visualization of the gallbladder after a single dose of contrast material, misunderstandings concerning the uses of oral cholecystography compared to those for intravenous cholangiography and uncertainty regarding the value of cholecystokinin cholecystography in the diagnosis of acalculous cholecystitis. Knowledge of the pharmacokinetics of the oral cholecystographic contrast agents has been long overdue, considering the extensive use of these compounds in clinical practice for more than 50 years. However, information on this subject has finally reached a stage where the data can be applied to ensure that cholecystography is done with maximun efficiency and safety and with the least radiation exposure. The purpose of this report is to review the problems involved with imaging of the gallbladder by oral cholecystography and to discuss the indications, interpretation and accuracy of gallbladder imaging with ultrasonography. Data concerning the use of computerized tomography for evaluation of the gallbladder are still preliminary but are discussed.