Effect of epinephrine on the peripheral metabolism of thyroxine.

10 normal young men received repository epinephrine repeatedly for 4 days during the course of a radiothyroxine (radio-T4) disappearance curve. During epinephrine administration, serum radio-T4 disappearance rate (k) slowed abruptly, fecal clearance decreased, urinary clearance was initially unchanged but later decreased slightly, volume of thyroxine distribution decreased, and external radioactivity over the liver remained unchanged. Beginning on day 2 of epinephrine and persisting at least 1 day after epinephrine was discontinued, serum thyroxine-binding globulin (TBG) maximal binding capacity increased, thyroxine-binding prealbumin (TBPA) maximal binding capacity decreased, and free T4 iodine decreased. Stable serum T4 iodine decreased during the experiment. Three indexes, namely the free T4 iodine, the reciprocal of TBG capacity, and the urinary radio-T4 "clearance" changed in parallel, suggesting that the increase in TBG capacity was responsible for a delayed decrease in radio-T4 metabolism. However, these changes were temporally dissociated from the decrease in k, which began and ended abruptly with initiation or discontinuing of epinephrine administration. This dissociation is unexplained, but may be caused by alterations in T4 binding in tissue sites.

A multicompartmental model for iodide, thyroxine, and triiodothyronine metabolism in normal and spontaneously hyperthyroid cats.

A comprehensive multicompartmental kinetic model was developed to account for the distribution and metabolism of simultaneously injected radioactive iodide (iodide*), T3 (T3*), and T4 (T4*) in six normal and seven spontaneously hyperthyroid cats. Data from plasma samples (analyzed by HPLC), urine, feces, and thyroid accumulation were incorporated into the model. The submodels for iodide*, T3*, and T4* all included both a fast and a slow exchange compartment connecting with the plasma compartment. The best-fit iodide* model also included a delay compartment, presumed to be pooling of gastrosalivary secretions. This delay was 62% longer in the hyperthyroid cats than in the euthyroid cats. Unexpectedly, all of the exchange parameters for both T4 and T3 were significantly slowed in hyperthyroidism, possibly because the hyperthyroid cats were older. None of the plasma equivalent volumes of the exchange compartments of iodide*, T3*, or T4* was significantly different in the hyperthyroid cats, although the plasma equivalent volume of the fast T4 exchange compartments were reduced. Secretion of recycled T4* from the thyroid into the plasma T4* compartment was essential to model fit, but its quantity could not be uniquely identified in the absence of multiple thyroid data points. Thyroid secretion of T3* was not detectable. Comparing the fast and slow compartments, there was a shift of T4* deiodination into the fast exchange compartment in hyperthyroidism. Total body mean residence times (MRTs) of iodide* and T3* were not affected by hyperthyroidism, but mean T4* MRT was decreased 23%. Total fractional T4 to T3 conversion was unchanged in hyperthyroidism, although the amount of T3 produced by this route was increased nearly 5-fold because of higher concentrations of donor stable T4. Analysis of the data indicates that the increased overall T4* turnover (decreased MRT) in hyperthyroidism is due to increased losses through pathways other than T3 formation. Conjugation, with subsequent deiodination, is proposed as one possibly important pathway. Results of this multicompartmental analysis are compared with those of noncompartmental analysis of the same data and with results of similar model analyses in other species.

Distribution of subcutaneous thyroxine, triiodothyronine, and albumin in man: comparison with intravenous administration using a kinetic model.

Distributional kinetics of radioiodinated T4 (T4), T3 (T3), and albumin (RISA), after simultaneous administration by the sc and iv routes of 125I- and 131I-labeled compounds, were measured in normal subjects. Data were analyzed by fitting them, using the SAAM technique, to models with three compartments for the iv administered compounds and a fourth compartment for the site of the sc injection. The radiopharmaceuticals administered sc transfered by first order kinetics from the injection site to plasma with half-lives of 20.4, 5.6, and 63.0 h for T4, T3, and RISA, respectively. Percentages of 3.3, 1.2, and 2.1 of the sc dose appeared directly in the vascular compartment. In some, but not all, studies with sc T4 and RISA, a portion of the disappearance from the sc site appeared to be due to in situ deiodination, rather than to transfer of the parent compound into the circulation. After T3 administration, both iv and sc, a product with kinetics similar to RISA appeared, accounting for 3% of the T3 decay for the averaged data and ranging from 0.9--19.4% in individual cases. Comparing T3 kinetic analysis by this technique (in which the iodoprotein byproduct is accounted for by modeling instead of chemical separation), the resulting parameters are similar to those reported by others after chemical separation of T3. Judging by compartment size and distributional kinetics, the model compartments derived for iv administration of these compounds appear to represent the vascular pool (central compartment), the hepatic and renal distribution sites (fast peripheral compartment), and other peripheral tissues (slow peripheral compartment). The latter, which presumably includes the site of sc injection, transfers into the central compartment at approximately the same rate as does the compartment representing the sc injection site itself.

A kinetic model of human thyroid hormones and their conversion products.

We have examined the in vivo distribution and metabolism of radiolabeled T4 and T3 in 14 normal subjects using a kinetic model. Tracer amounts of [131I]T4 and [125I]T3 were injected simultaneously, and plasma samples were obtained for up to 7 days thereafter. Separation of these samples by thin layer chromatography yielded kinetic curves for 131I- and 125I-labeled T4, T3, iodide, and iodoprotein, which were then used to develop a kinetic model. The model includes several features. 1) Submodels were developed for T4, T3, iodide, and iodoprotein which simultaneously fit the observed data. 2) Two other submodels were needed for data fit, the first representing rT3, the other representing other intermediates, including the various diiodothyronines. The latter submodel was patterned initially after 3,3'-diiodothyronine kinetics. It was required to account for the delay in appearance of labeled iodide produced from the degradation of T4, and rT3 and proved to be essential for the successful fit of the data. 3) The model accounts for the conversion of T4 to T3 and rT3. Even though rT3 is quantitatively significant as a degradation pathway for T4, its presence does not contribute significantly to total plasma radioactivity after T4 administration because of its rapid turnover in comparison with T4. 4) The small amount of iodoprotein formed is a major contributor to total plasma radioactivity within 3 days after T3 administration. 5) The model permits the elimination of two methodological errors: that due to the presence of labeled iodide, T3, or T4 contaminants in the administered labeled hormones, and that due to the small amount of cross-over between thin layer chromatography peaks. The model provides a concise description of our current understanding of thyroid hormone metabolism and suggests areas where further information is required.

Requirements for a treatment planning system for radioimmunotherapy.

Cancer-seeking antibodies carrying radionuclides can, in theory, be very powerful agents for the radiotherapy of cancer. However, as with all radiotherapy, the undesired dose to critical normal organs is the limiting factor that determines success or failure. The distribution of radiation dose in cancer and noncancer tissue is highly dependent on choices the therapist can make: choices of the antigens to be targeted, choices of the antibodies or antibody fragments to be used, choices of radionuclides, of amounts, of timing, and other electives. New technologies, especially of monoclonal antibody production, make the options myriad. Optimization of this therapy depends on a foreknowledge of the radiation dose distributions to be expected. The necessary data can be acquired by established tracer techniques, in individual patients, for particular treatment selections. These tracer techniques can now be implemented by advanced equipment for quantitative, tomographic radionuclide imaging and strengthened by dynamic modeling of the physiological parameters which govern radionuclide distribution, and hence radiation dose distribution.

Radiation dosimetry of radioiodinated thyroid hormones.

A physiologically based compartmental model for T4 and T3 metabolism in man was used to generate time-activity curves for residence of radioiodine in key organs. T4 and T3 labeled with 123I, 124I, 125I, and 131I were studied. Conditions modeled included radioactive iodine uptake (RAIU) values of 0%, 1%, 5%, 15% and 25%, and RAIU of 15% combined with various degrees of pharmacologic block of thyroidal RAIU. Using the MIRD "S" tables, rad doses were generated for each condition. While the shapes of the time-activity curves varied widely with alterations in physical and biological turnover and with changes in steady-state due to iodine administration, it was possible to calculate overall effective half-lives for each organ of interest from the integral of the time-activity curve projected by solution of the model. This overall effective half-life of the hormone for the body's exchangeable hormone compartments correlated well with calculated radiation dose to the thyroid in the unblocked state. With progressive degrees of iodine block, this correlation persisted, though with proportionately reduced thyroid radiation doses. Use and manipulation of a compartmental model, rather than the usual multiexponential model, for radiation dosimetry facilitates conceptualization and the projection of the effects of interventions such as iodide block.

Kinetics of the human thyroid trap: a compartmental model.

Thyroidal pertechnetate was measured continuously in normal subjects for 40 min after i.v. injection, using a multicrystal camera. Digital counts (1-min increments) were read directly from the magnetic tape and summed for the thyroid area and for adjacent neck background. The net thyroidal data were used as the basis for development of a compartmental model of the thyroidal trap, using the SAAM program. Input to the trap in the model is plasma pertechnetate radioactivity, measured frequently during the study and fitted to a multiexponential equation. Best fit of the thyroid data was achieved with a model in which the trap is described by two compartments, a fast ("follicular cell") compartment and a slower ("colloid") compartment. Iodide blockade, administered either during the study or 1 hr before its initiation, rapidly blocked the trap at the point of input from plasma into the follicular cells. Iodide did not affect the other parameters of the model.

Kinetics of the human thyroid trap: experience in normal subjects and in thyroid disease.

Kinetics of the thyroid pertechnetate trap were assessed in 85 studies of 39 normal subjects, in five untreated patients with Graves' disease (two of them both before and after treatment), in two hypothyroid patients, and in one patient each with Hashimoto's thyroiditis of recent onset, subacute thyroiditis, and massive anaplastic carcinoma. In normal subjects, the effects of sex, time of day, and the order of experimental sessions were studied. For the analysis, a three-compartment model was assumed for all studies. Data on thyroidal and neck-background pertechnetate were collected with a multi-crystal camera during 40 min after i.v. injection. Input to the two thyroidal compartments in the model--the follicular cell, V2, and the colloidal plasma-equivalent space, V3--is a multi-exponential function of plasma radioactivity, V1, which was measured frequently. None of the model parameters was systematically affected by the sex of the subject, and order of session did not consistently alter any parameter, except for V3, which was greater in session 2 than in session 1. That increase was not consistent among data subsets, however, and is believed to be spurious. Time of day affected only the exit rate constant from the colloid, lambda23, which is increased later in the day (P < 0.02). Distribution of the normal parameters was more nearly log-normal than normal. After 5% were excluded at the high end and 5% at the low end, the range for a parameter, p, was found empirically to be: antiln (mean ln p - 1.7 s.d. ln p), and antiln (mean ln p + 1.5 s.d. ln p). In Graves' disease, V2 is increased (P < 0.02), but the increases in V3 and in lambda21 (the clearance into the thyroid from serum) are much more dramatic (P < 10(-8)). After treatment, V3 and lambda21 fell toward normal. The hypothyroid patients showed no trap activity, and the trap was normal in the patient with early Hashimoto's thyroiditis. The patients with subacute thyroiditis and with anaplastic carcinoma had increases in V2, V3, and lambda21, but the pattern differed from that seen in Graves' disease.

Kinetics of the human thyroid trap: effects of iodide, thyrotropin, and propylthiouracil.

Effects on the thyroidal pertechnetate trap of iodide, thyrotropin (TSH), and propylthiouracil (PTU), compared with duplicated control studies, were assessed in normal subjects using i.v. [Tc99m] pertechnetate, a multicrystal scintillation camera, and a compartmental model. Sodium iodide (1 g), administered orally on two occasions, 2 wk apart, caused an early drop in plasma clearance into the follicular cell (p less than 0.05), with later return to normal clearance 1 wk after the second NaI dose. In this later study, exit from the colloid was elevated (p less than 0.01). Plasma equivalent volume of the "colloid" compartment was reduced in both postiodine studies (p less than 0.05). Thyrotropin, 10 units intramuscularly, was followed by no significant changes in trap parameters at 2 hr. At 24 hr, plasma clearance had doubled (p less than 0.05), and the plasma equivalent "colloid" volume had tripled (p less than 0.01). Propylthiouracil was given as a single 1 g dose 1 hr before a trapping study followed by 200 mg PTU every 8 hr for 1 wk. The first dose resulted in apparent reduction in all of the rate constants for transport across the basal and apical thyroid follicular cell membranes; these rates returned toward control levels after 1 wk. The plasma equivalent "follicular cell" volume was reduced to 66% of controls levels (p less than 0.025) after 1 wk PTU. These effects must be taken into account in the interpretation of studies of the trap based on PTU pretreatment to inhibit organification.

Stability of radiothyroxine plasma disappearance curve despite catharsis and unblocked thyroidal uptake of radioiodide.

Plasma radioactivity was measured over 21 days after an intravenous injection of 50 muCi of 125I-T4 in eight normal men. No thyroid-blocking medication was given. Four subjects (castor oil group) received 30 ml of castor oil on each of Days 13, 14, and 15, while the other four subjects (control group) were studied without medication. After A 5-day equilibration period, plasma 125I-T4 was measured on Days 5-13 in order to calculate the disappearance curve for each subject and to derive the mean for each experimental group. The curves were then extrapolated to Day 21. Measured radioactivity did not depart significantly from the extrapolated line, either during the castor oil period (Days 14, 15, and 16) or during the recovery period (Days 17, 19, and 21). The castor oil, therefore, had no observable effect on the clearance of plasma radioactivity. None of the subjects had a late increase in plasma radioactivity to suggest recirculation of radioiodide or buildup of iodoproteins. In normal subjects, radiothyroxine plasma levels up to 21 days are not significantly affected by short-term catharsis or by failure to block thyroidal radioiodide uptake.

Pertechnetate distribution in man after intravenous infusion: a compartmental model.

Using a primed infusion technique, distribution of pertechnetate was monitored in normal volunteer subjects over an 8-hr period. Two groups of subjects were studied, during hours 0-4 (n = 8) and hours 4-8 (n = 7), respectively, of the infusion. At 6.5 hr a large dose of NaI (1000 mg) was administered intravenously to the second group. Plasma, salivary, and urinary radioactivities were assayed, and external counts were made of radioactivities over the neck, thigh, and right upper abdomen. A kinetic model was developed for pertechnetate based upon the distribution data, the iodide perturbation, and known physiology for pertechnetate and iodide. The model has three major subsystems: (1) the thyroid trap; (2) a whole-body distribution, containing plasma and two extravascular compartments; and (3) the gastrointestinal tract, including the salivary, stomach (including upper small intestine), and two lower intestinal compartments. One of the latter, which turns over very slowly, is believed to represent bowel wall. The large NaI dose markedly reduced transport into compartments of the thyroid trap, the saliva, and the stomach and small intestine. This study shows that, in most respects, pertechnetate is distributed qualitatively but not quantitatively like iodide but that, unlike iodide, large bowel distribution plays an important role, especially in long-term studies.

A mathematical model for the distribution of fluorodeoxyglucose in humans.

UNLABELLED: The goals of this study were to define the total body distribution kinetics of 18F-fluorodeoxyglucose (FDG), to contribute to its radiation dosimetry and to define a suitable proxy for arterial cannulation in human FDG studies. METHODS: Time-activity FDG heart, lung, liver and blood data from paired fasting and glucose-loaded sessions in five adult human volunteers, together with published brain parameters, were incorporated into a multicompartmental model for whole-body FDG kinetics. Tau values were calculated from this model. We also compared the usefulness of activity in the left ventricle (LV), right ventricle (RV), left lung and right lung as proxy for arterial blood FDG sampling. RESULTS: No systematic difference was found in model parameters between the fasting and glucose-fed sessions, even for the parameter for transfer of FDG into the myocardium. Myocardial PET data fitted well to a model in which there is very rapid exchange indistinguishable from blood kinetics and transfer into an intracellular "sink." The lung data fitted to a simple sink representing the lung cells. The liver data required an additional intermediate exchange compartment between the plasma and a hepatic sink. In terms of total body distribution kinetics, unmeasured organs and tissues (probably the skeletal muscle and gut) become increasingly important with time and account for a mean of 76% of the decay-corrected FDG activity at infinity. Right lung activity, corrected to venous blood, represents the whole arterial blood curve better than the LV or RV. The tau values for radiation dosimetry of FDG in the heart, lungs, liver and bladder calculated from our model do not differ significantly from published results using other methods. Bladder tau decreased with voiding frequency and was markedly decreased with early voiding. CONCLUSION: Glucose loading state is not a good predictor of myocardial FDG uptake. The majority of FDG distribution at 90 min is in tissues other than the blood, brain, heart and liver. Bladder radiation will be much reduced if the patient voids early after FDG administration. Summed large volume right lung activity, normalized to venous blood activity, is a good proxy for arterial blood FDG sampling. The model presented may be expanded to include other FDG kinetics as studies become available.

Measurement method for radioactive thyroxine, triiodothyronine, iodide, and iodoprotein in samples with low activity.

A method is described that incorporates resin extraction and thin layer chromatography to isolate and separate radioiodinated thyroxine (T4), triiodothyronine (T3), iodoprotein, and iodide in samples of human plasma up to 3 ml. Tracer studies using this method showed that reverse T3 and 3',5' diiodothyronine (T2), as well as T4, were detected in the "T4 fraction," and that 3-3' T2 and 3' monoiodothyronine, as well as T3, were detected in the "T3 fraction." Monoiodotyrosine and diiodotyrosine (DIT) migrated more slowly than did T4 on the chromatogram, and a large amount of DIT was in the unextracted "iodoprotein fraction." Kinetic studies in 14 normal subjects given intravenous commercial [125I]T3 (T3*) and [131I]T4 (T4*), confirmed the quantitative importance of an iodoprotein in later samples after T3* administration, and its presence after T4*. T4* contamination of commercial T3* also became quantitatively important. On the other hand, despite confirmation of in vivo conversion of T4* to T3*, T3* contributed little quantitatively to the total concentration of radioactivity present even late after T4* injection, due to the more rapid turnover and greater distribution volume of T3*.

Multicompartmental analysis of the kinetics of radioiodinated monoclonal antibody in patients with cancer.

A conceptual biologic model was developed and used to analyze the behavior of 123I-Lym-1 monoclonal antibody against African human B cell lymphoma in patients with B cell lymphoma. Originally, the observed data could not be simulated with parameters for homologous immunoglobulins reported in the literature because of a major processor that was capable of distinguishing this murine immunoglobulin from the patient's own immunoglobulins. With a nonlinear parametric model, the data observed in patients could be fitted to the model. The nonlinear parameter determined the transfer of antibody from the intravascular to a processor compartment, primarily the liver. This transfer was a function of the number of free receptors in the processor. Model simulated curves for the time course of concentration of antibody in the blood for different amounts of injected antibody revealed that blood clearance of radiolabeled antibody was profoundly decreased by increased amount of injected antibody. This model provides an explanation for the observations that tumor imaging is improved with injection of larger amounts of antibody, and a basis for modifying the pharmacokinetic behavior of an antibody in order to optimize radioimmunodiagnosis and radioimmunotherapy.

The MIRD perspective 1999. Medical Internal Radiation Dose Committee.

The MIRD schema is a general approach for medical internal radiation dosimetry. Although the schema has traditionally been used for organ dosimetry, it is also applicable to dosimetry at the suborgan, voxel, multicellular and cellular levels. The MIRD pamphlets that follow in this issue and in coming issues, as well as the recent monograph on cellular dosimetry, demonstrate the flexibility of this approach. Furthermore, these pamphlets provide new tools for radionuclide dosimetry applications, including the dynamic bladder model, S values for small structures within the brain (i.e., suborgan dosimetry), voxel S values for constructing three-dimensional dose distributions and dose-volume histograms and techniques for acquiring quantitative distribution and pharmacokinetic data.

MIRD pamphlet No. 17: the dosimetry of nonuniform activity distributions--radionuclide S values at the voxel level. Medical Internal Radiation Dose Committee.

The availability of quantitative three-dimensional in vivo data on radionuclide distributions within the body makes it possible to calculate the corresponding nonuniform distribution of radiation absorbed dose in body organs and tissues. This pamphlet emphasizes the utility of the MIRD schema for such calculations through the use of radionuclide S values defined at the voxel level. The use of both dose point-kernels and Monte Carlo simulation methods is also discussed. PET and SPECT imaging can provide quantitative activity data in voxels of several millimeters on edge. For smaller voxel sizes, accurate data cannot be obtained using present imaging technology. For submillimeter dimensions, autoradiographic methods may be used when tissues are obtained through biopsy or autopsy. Sample S value tabulations for five radionuclides within cubical voxels of 3 mm and 6 mm on edge are given in the appendices to this pamphlet. These S values may be used to construct three-dimensional dose profiles for nonuniform distributions of radioactivity encountered in therapeutic and diagnostic nuclear medicine. Data are also tabulated for 131I in 0.1-mm voxels for use in autoradiography. Two examples illustrating the use of voxel S values are given, followed by a discussion of the use of three-dimensional dose distributions in understanding and predicting biologic response.

MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates.

This report describes recommended techniques for radiopharmaceutical biodistribution data acquisition and analysis in human subjects to estimate radiation absorbed dose using the Medical Internal Radiation Dose (MIRD) schema. The document has been prepared in a format to address two audiences: individuals with a primary interest in designing clinical trials who are not experts in dosimetry and individuals with extensive experience with dosimetry-based protocols and calculational methodology. For the first group, the general concepts involved in biodistribution data acquisition are presented, with guidance provided for the number of measurements (data points) required. For those with expertise in dosimetry, highlighted sections, examples and appendices have been included to provide calculational details, as well as references, for the techniques involved. This document is intended also to serve as a guide for the investigator in choosing the appropriate methodologies when acquiring and preparing product data for review by national regulatory agencies. The emphasis is on planar imaging techniques commonly available in most nuclear medicine departments and laboratories. The measurement of the biodistribution of radiopharmaceuticals is an important aspect in calculating absorbed dose from internally deposited radionuclides. Three phases are presented: data collection, data analysis and data processing. In the first phase, data collection, the identification of source regions, the determination of their appropriate temporal sampling and the acquisition of data are discussed. In the second phase, quantitative measurement techniques involving imaging by planar scintillation camera, SPECT and PET for the calculation of activity in source regions as a function of time are discussed. In addition, nonimaging measurement techniques, including external radiation monitoring, tissue-sample counting (blood and biopsy) and excreta counting are also considered. The third phase, data processing, involves curve-fitting techniques to integrate the source time-activity curves (determining the area under these curves). For some applications, compartmental modeling procedures may be used. Last, appendices are included that provide a table of symbols and definitions, a checklist for study protocol design, example formats for quantitative imaging protocols, temporal sampling error analysis techniques and selected calculational examples. The utilization of the presented approach should aid in the standardization of protocol design for collecting kinetic data and in the calculation of absorbed dose estimates.

Deiodination and deconjugation of the glucuronide conjugates of the thyroid hormones by rat liver and brain microsomes.

Radioiodinated thyroxine (T4) glucuronide (T4G) and triiodothyronine (T3) glucuronide (T3G), paired with T4 or T3, were incubated at 37 degrees C for 2 hours in the presence of dithiothreitol and microsomes that had been prepared from euthyroid rat liver or hypothyroid rat brain tissues, as sources of type I and type II iodothyronine 5'-deiodinases, respectively. Incubations with boiled microsomes served as controls. The incubated supernatant was analyzed by high-pressure liquid chromatography (HPLC) for content of T4, T4G, T3, T3G, and combined T2 and T2G. The deiodination of T4G resulted from incubation with both liver and brain microsomes, but was somewhat less active than the deiodination of simultaneously incubated T4. All batches of microsomes studied also caused deconjugation of both T4G and T3G. The data are compatible with the hypothesis that T4G can serve as an alternate pathway for conversion of T4 to T3 in these tissues.

Localization of human thyroxine absorption.

The distribution of intestinal absorption of 131I-labeled thyroxine (T4*) was studied in 4 normal subjects after oral and i.v. T4*, given in separate experimental sessions. In addition to collection of time-activity curves for plasma T4* from the two sessions, distribution and transport of T4* through the gut was quantified by external imaging. Time-activity curves were obtained for the stomach, duodenum, and upper jejunoileum. A multicompartmental model for systemic T4, with three distribution compartments and a single exit route, was employed. Additional, gastrointestinal, compartments were introduced. The stomach data were fitted to a model with three compartments, two for transport and a small sink of gastric activity that does not interact with the absorptive sites. Transfer from the duodenum to the upper jejunoileum and from the upper to the lower jejunoileum was modeled from fits to the peak T4* activities in the images of the duodenum and upper jejunoileum. The rate of transfer from the lower jejunoileum into more distal intestinal sites was fixed, but the impact on the results of using various values for this parameter was analyzed. The model calculations of absorption (mean +/- SD for 3 of the subjects) are duodenum, 15 +/- 5%, upper jejunoileum, 29 +/- 14%, and lower jejunoileum, 24 +/- 11%. The fourth subject, whose global absorption was abnormally low for uncertain reasons, had 17% absorption from the duodenum, 9% from the upper jejunoileum and none from the lower jejunoileum. Model projections mimicking clinical gut abnormalities known to affect T4 absorption were compatible with the results of published studies.

Colonic excretion of iodide in normal human subjects.

Patterns of fecal radioiodine excretion were studied in seven normal young men with intact, unblocked thyroid glands, who received repeated oral daily doses of [125I]iodide in an attempt to achieve isotopic equilibrium. Fecal radioactivity was assumed to have originated either in the circulating inorganic radioiodine (radioiodide) compartment or in the circulating hormonal protein-bound iodine (PBI) compartment. Activity in the PBI compartment was measured directly in serum samples from which radioiodide had been removed by dialysis or resin treatment. Activity in the radioiodide compartment was measured by the difference between total and hormonal radioiodine, and also as a projection from the rate of urinary excretion of radioiodine. These compartments were fitted to the observed sequential fecal radioiodine data in each subject to identify the origins of the fecal radioactivity, using the SAAM modeling program. The fraction of fecal radioactivity attributable to iodide was 0.55 +/- 0.35 (mean +/- SD) (geometric mean 0.44, range 0.25-0.96). In all cases, at least some contribution from the iodide compartment was required for model fit to the observed pattern of fecal radioiodine excretion. These data demonstrate that, despite long-existing opinion to the contrary, iodide is an important component of intestinal iodine excretion in humans. This finding explains the presence of colonic activity in postradioiodide images of athyreotic patients.