Quantitative mapping of 4'-iododeoxyrubicin in metastatic squamous cellcarcinoma by secondary ion mass spectrometry (SIMS) microscopy.

Secondary ion mass spectrometry microscopy enables quantitative mapping of chemical elements in tissue sections. It was used for the detection of 127I contained in 4'-iododeoxyrubicin (IDX). Metastatic cutaneous squamous cell carcinoma from 7 patients participating in a phase I study (IDX dose, 80 mg/m2, 10-min i.v. infusion) were biopsied 10 min after drug administration and compared to 3 controls who did not receive any treatment (one squamous cell carcinoma and 2 gastric carcinomas). Biopsy specimens were fixed and embedded in methacrylate resin. Then, serial semithin sections (3 microns) were analyzed simultaneously with ionic and optimal microscopes in order to identify the histological structures given by the 31P distribution in which 127I in IDX was mapped. The iodine signal was undetected in controls and found mainly in the nuclei of tumor cells of the treated patients. Its concentration, measured in at least 30 nuclei of each specimen, was undetectable in 8% of the nuclei and 91% of them were within 1 and 16 ng/mg. The mean concentration of each specimen ranged from 5 to 23 ng/mg. This study demonstrates the capacity of ion microscopy to localize a cytotoxic drug (IDX) in a human biopsy specimen without the need for radioactive labeling and enables the evaluation of drug penetration in cancer cells which is critical for its activity.

Changes in 127I mice thyroid follicle studied by analytical ion microscopy: a key for the comprehension of amiodarone-induced thyroid diseases.

Analytical ion microscopy was used to evaluate the quantitative changes in thyroid 127I mapping induced by amiodarone in relation to the iodine intake. Mice were maintained on a normal diet (NID), on a low iodine diet (LID) or on a high iodine diet (HID) during 3 months. They received daily ip injections of amiodarone or NaI during the last 10 days. Microanalysis of iodine was performed on thyroid sections. In NID mice, the cellular 127I concentration (mean +/- SE: 0.90 +/- 0.06 micrograms/mg) was lower than that of follicular lumina (6.99 +/- 0.17). Amiodarone increased cellular concentration (2-fold) and decreased follicular concentration; NaI induced the same results. In LID mice, both concentrations, which were decreased 60- to 70-fold in comparison with NID, were restored by amiodarone, while NaI enhanced follicular concentration more than amiodarone. In HID mice, the follicular concentration (1.5-fold higher than normal) returned to a normal range with amiodarone, but cellular concentration (2.5-fold lower than normal) remained low, while NaI increased the cellular concentration 3-fold. These data show that iodine released by amiodarone has a bioavailability different from that of NaI. They indicate that thyroid response to amiodarone is related to dietary iodine intake, which, in turn, determines autoregulatory mechanisms. They also raise the question of the possible existence of an intrinsic property of amiodarone which would explain the specificity of its activity on thyroid iodine organification and the development of amiodarone-induced human thyroid diseases.

Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin.

Some years ago, we reported that colloid goiters could be produced experimentally in mice and rats by injection of TSH over a few days in the presence of ample iodine supply. This clearly showed that colloid accumulation and intense TSH stimulation are not mutually exclusive. In the present study, large colloid goiters, sharing many morphological and biochemical characteristics with human colloid goiters, were induced in rats and mice by treatment with 5,5-diphenyl-2-thiohydantoin (DPTH). This drug increases fecal loss of thyroid hormone and inhibits conversion of T4 to T3. Thus, DPTH raises TSH and induces macrofollicular colloid-rich goiters. In contrast to this, goiters induced by combined treatment with methimazole (MMI) or sodium perchlorate and DPTH are microfollicular, although serum TSH is increased to the same level as in rats treated with DPTH alone. The degree of iodine organification obviously determines if the follicle will sprout and form daughter follicles or if it will expand its hull. Thyroglobulin content of DPTH goiters is lower than that of normal glands but considerably higher than after MMI treatment, whereas total iodine content of DPTH goiters is only slightly lower than in normal glands, but also much higher than in MMI goiters. In DPTH goiters, a high proportion of total iodine is in the particulate fraction which probably contains the periodic acid Schiff-positive bodies floating in the colloid of DPTH treated glands. Acute DPTH administration does not inhibit iodide organification, but after treatment with DPTH for 1 day, chromatography suggests some inhibition of iodine organification and hormone synthesis by DPTH, but much less than by MMI. DPTH treatment causes considerable tissue damage and repair, such as follicular cell necrosis and invasion of the colloid by macrophages and granulation tissue. Therefore, DPTH goiters might well be a useful model not only for colloid goiter formation but also for inflammatory processes in the thyroid gland.

Plasma thyroglobulin measurements help determine the type of thyroid defect in congenital hypothyroidism.

Plasma thyroglobulin (Tg) measurements were conducted in infants with congenital hypothyroidism to determine their value in the classification of the thyroid defect. Twenty hypothyroid patients were examined before 50 days of age. Plasma T4, T3, TSH, and Tg were measured and a thyroid scan was performed on all the infants. On the basis of clinical evaluation and the thyroid scans, patients were divided into three groups: group I, ectopic or eutopic hypoplastic glands (n = 11); group II, goiters (n = 3); group III, athyreosis (n = 6). There were no differences among the mean (+/- SD) TSH values of the three groups (377 +/- 291, 402 +/- 202, and 757 +/- 421 microU/ml for group I, II and III respectively). The mean (+/- SD) plasma T4 and T3 levels were lower in group III patients than in the other groups [T4, 0.55 +/- 0.12 vs. 5.0 +/- 3.5 micrograms/100 ml (group I) and 2.7 +/- 1.9 micrograms/100 ml (group II); T3, 29.3 +/- 23 vs. 165 +/- 83 ng/100 ml (group I) and 220 +/- 150 ng/100 ml (group II). Plasma Tg was undetectable in all six infants with athyreosis, and varied from 15-600 ng/ml in group I patients (mean +/- SD, 125 +/- 171 ng/ml). Tg was undetectable in one infant with congenital goiter. We conclude that tg measurements are of value in the classification of infants with congenital hypothyroidism to help clarify the nature of the thyroid abnormality once hypothyroidism has already been diagnosed.

Evolution of thyroid 127I stores measured by X-ray fluorescence in subacute thyroiditis.

Evaluation of the thyroid iodine content by x-ray fluorescence was performed in 13 patients throughout the course of subacute thyroiditis. In the initial hyperthyroid phase of the disease, the iodine stores of the thyroid were not completely depleted. The iodine content (6.5 +/- 3 mg) was about 2.5 times lower than normal values when thyroiditis had developed in a normal thyroid (10 patients); in 3 patients with goiter, it was elevated (29.6 +/- 6.7 mg) but was still within the normal range of euthyroid goitrous patients. After clinical remission, the iodine content of the gland increased only in two patients (+105% and +43% over the initial value, respectively). For the other patients, the iodine content decreased (from -5% to -100% of the initial value). Restoration of iodine stores occurred subsequently and appeared to be a slow and progressive phenomenon; in six patient, the iodine content was still below normal values 12 months after clinical remission (6.6 +/- 1.6 mg). These data suggest that the course of subacute thyroiditis might be longer than would appear from the clinical data, the hormonal assays, or the radioactive thyroid uptake data.

Imaging and relative quantification of 127I in human thyroid follicles by analytical ion microscope: characterization of benign thyroid epithelial tumors.

Analytical ion microscopy (AIM) can be used for imaging and relative quantification of chemical elements in tissue sections. We used this technique to assess the changes in 127I mapping within thyroid follicular cells and follicular lumina in benign thyroid epithelial abnormalities from 17 patients and in macroscopically normal perinodular tissue surrounding solitary cold nodules from 8 patients. Among the 17 patients, 9 had simple goiters, 5 had toxic nodular goiters, and 3 had hypofunctioning (cold) nodules. The tissue samples were fixed chemically and embedded in methacrylate resin to ensure preservation of organified iodine, and thin sections were analyzed by AIM. 127I was found in the follicular lumina and follicular epithelial cells of most specimens. The local concentration of 127I, which is proportional to the ratio of the two secondary ion beam currents of iodine and carbon, was evaluated in 30 follicular lumina and 30 follicular epithelial cells of each specimen. In normal tissue, the relative 127I concentration within follicular cells (mean, 0.72; range 0.01-8.30) was much lower than that in follicular lumina (mean, 4.63; range, 0.18-36.74). In simple goiter tissue, follicular lumen (mean, 0.57; range, 0.00-5.76), and cell (mean, 0.17; range, 0.002-1.82) relative 127I concentrations were below normal, but both distributions remained different. On the contrary, in toxic nodular goiter tissue the follicular cell relative 127I concentration (mean, 0.96; range, 0.003-27.3) largely overlapped that of the follicular lumina (mean, 2.1; range, 0.001-36.5). The cold nodules had the lowest relative follicular lumina 127I concentration (mean, 0.008; range, undetectable-0.07), and the relative cellular 127I concentrations were undetectable in 67%. These results demonstrate the capacity of AIM to characterize the functional activity of thyroid tissue without prior administration of radio-iodine.

Effects of amiodarone therapy on thyroid iodine content as measured by x-ray fluorescence.

Thyroid iodine content (TIC) was measured by x-ray fluorescence in 68 patients who had received amiodarone treatment for varying intervals (1 g/week for 1-120 months). Thirty-six patients were euthyroid; the mean TIC of the patients (n = 15), who had been treated for less than 12 months was 30 +/- 19 (+/- SD) mg, twice the normal mean value (14.6 +/- 5.0 mg), and it was 39 +/- 17 mg in those (n = 16) who had been treated for 12-60 months and 29 +/- 6 mg in those (n = 5) who had been treated longer (greater than 60 months). Nineteen patients were hyperthyroid and had elevated TIC values. Of them, 6 patients had a goiter; their TIC (50 +/- 19 mg) was not significantly different from that of the hyperthyroid patients with no goiter (55 +/- 29 mg), but they became hyperthyroid more rapidly. Thirteen patients were hypothyroid; none had TIC values above the normal range, and it was below 2.5 mg in 5 patients. A sequential study was undertaken in 11 euthyroid patients who had no detectable antithyroid antibodies. TIC did not increase during treatment in 2 patients; both developed hypothyroidism, which was transient in 1 despite continuation of amiodarone treatment. The TIC initially increased during amiodarone treatment in the other 9 patients, leveling off at the end of the first year. The TIC rose well above the upper limit of the normal range in 4 patients, of whom 2 became hyperthyroid during the second year of treatment. TIC remained within the normal range in the other 5 patients, of whom 3 became hypothyroid after 12-24 months of treatment (1 subclinical, 2 overt). Although the TIC was significantly higher in the patients with hyperthyroidism than in the patients who remained euthyroid, the TIC test cannot be used to predict the occurrence of hyperthyroidism. The latter must be diagnosed on the basis of clinical symptoms and a frank elevation of serum thyroid hormone levels. Conversely, patients whose TIC values do not increase during treatment or remain within the normal range should be considered at risk for hypothyroidism.

Short and long term effects of radioiodine treatment on the iodine content of the thyroid gland.

Thyroid iodine content (TIC) was measured in nine patients with hyperthyroid Graves' disease for 5-26 months after treatment with 131I (100-125 muCi/g tissue). In all patients, TIC decreased; in eight patients it became undetectable within 5 +/- 3 (SD) months. This fall was parallel to those of serum T3 and T4 levels and was not prevented by the administration of large doses of stable iodine. In four patients, this decrease was irreversible and they became clinically hypothyroid. In the five other patients, it was partly reversible: the secondary increase of TIC was parallel to those of serum T3 and T4 and to a decrease in TSH levels. These data suggest that during the months after 131I treatment, determination of TIC may help to distinguish transient from irreversible hypothyroidism. The late effects of 131I were studied in 38 patients who had been treated for hyperthyroid Graves' disease from 1.5-22 yr previously. The 16 patients who, at the time of examination, were euthyroid with normal serum TSH levels (less than 8 microU/ml) had a TIC [3.2 +/- 3 (SD) mg] significantly lower than that of 10 euthyroid patients previously treated only with antithyroid drug therapy (16.7 +/- 8.2 mg). A significant negative correlation was found between log basal TSH and log TIC (r = 0.61, P less than 0.001) and a positive correlation between log T4 and log TIC (r = 0.56, P less than 0.002). The T3/T4 ratio in patients with undetectable TIC (19.9 +/- 7.9) was higher than that of the other patients (14.6 +/- 3.2) (P = 0.02, Wilcoxon test). This hormonal profile was not modified by iodide supplementation, which increased TIC only transiently. The turnover of thyroid iodine was accelerated, which appeared to be the consequence of a small thyroid functional mass and of hyperstimulation by TSH.

Evidence of iodine storage within thyroid stroma after iodine treatment: imaging by secondary ion mass spectometry (SIMS) microscopy in goitrous tissue.

We measured the 127I distribution within tyroid tissue to find out where intrathyroid iodine was deposited during iodine treatment in eight Tunisian female patients (aged 33-58 yr) with endemic euthyroid goiter. Before surgery, five patients were treated during 6 months either by Lugol's solution (group 1: three patients) or by Lugol's and L-thyroxine (group 2: two patients). All patients remained euthyroid during the course of the treatment, which supplied 3.8 mg/day iodine. Three other patients did not receive Lugol's solution (control group). Secondary ion mass spectrometry microscopy was used to map 127-I quantitatively on thyroid sections. Specimens obtained at thyroid surgery were divided macroscopically into nodular and extranodular tissue and chemically fixed to preserve organified iodine. The iodine profile of patients in group 1 did not differ from that in group 2: large amounts of iodine were localized in thyroid follicles and stroma of both nodular and extranodular tissues. In the control group, iodine within stroma was found only in the extranodular tissue. Despite the limited number of patients studied, these data suggest that stromal iodine might represent a storage compartment in times of large iodine supply.

Relationship between thyrotropin stimulation and radioiodine uptake in lung metastases of differentiated thyroid carcinoma.

To examine whether the injection of bovine TSH (bTSH) produces maximal radioactive iodine uptake (RAIU) in lung metastases in patients with differentiated thyroid cancer, 10 patients were studied 12 times. In 10 of these studies, an initial RAIU measurement was performed immediately after 3 injections of 10 IU bTSH given immediately after T3 withdrawal. Another RAIU measurement was performed 7-19 days after T3 withdrawal. Uptake increased in all patients even when it was clearly detectable immediately after bTSH stimulation. Thus, 3 days of bTSH stimulation in these patients did not lead to maximal 131I uptake, and it could only be reached after prolonged endogenous TSH stimulation. bTSH was not injected in the 2 other patients, in whom 6 RAIU measurements were carried out. Radioiodine uptake increased with time in both patients. It appears that both the level of endogenous TSH and the length of stimulation play a determining role in RAIU. This might explain why 3 days of bTSH stimulation are insufficient to elicit maximal 131I uptake.

Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma.

We assessed the results of treatment in 283 patients with lung or bone metastases from differentiated thyroid carcinoma who were followed for up to 40 yr (median, 44 months) after the discovery of the metastases. The survival rates from the time of discovery of the metastases were 53% at 5 yr, 38% at 10 yr, and 30% at 15 yr; 156 patients died. Multivariate analysis revealed that only 4 variables had an independent prognostic significance for survival. They were extensive metastases, older age at discovery of the metastases, absence of radioiodine uptake by the metastases, and moderately differentiated follicular cell type. The site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease. Remission was achieved in 79 patients after metastases were found. The only predictive factor for 5-yr disease-free survival after treatment of metastases was the initial extent of disease. Our results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.

Identification of the exon structure and four alternative transcripts of the thyroglobulin-encoding gene.

The human thyroglobulin (hTg)-encoding gene is a single-copy gene of more than 300 kb and composed of at least 42 exons. After studying the 5' portion of the Tg cDNA (from nucleotides (nt) 1 to 842), we have previously suggested the existence of alternative splicing of the hTg pre-mRNA in human thyroid tissue. Here, we describe four alternative splicings in the central region of the hTg pre-mRNA between nt 3597 and 4653. We have deduced from these results the exonic structure of this region (exons 16 to 22). Finally, the identification of alternative splicings has also allowed us to demonstrate the existence of a strong 5' splice site inside intron 16 of Tg.

Long-term effects in skin and thyroid after radiotherapy for skin angiomas: a French retrospective cohort study.

To evaluate the long-term effects of skin angioma irradiation, a recall programme was established which included the systematic recalculation of the radiation dose to the skin and the thyroid. 22% of the 6229 patients contacted had a dermatological examination which revealed cutaneous dystrophy in 81% of the 1137 exposed angiomas and in 39% of the 208 unexposed angiomas. The risk of dystrophy (telangiectasia, hypopigmentation, superficial and subcutaneous atrophy) was 12.1 higher (P less than 0.0001) among patients who had received a surface skin dose above 30 Gy than among those who had received a dose of 10 Gy or less. The relative risk for each dystrophy component increased significantly (P less than 0.001) with surface skin dose. Furthermore, 14 basal cell carcinomas (BCC) were observed in 12 patients from the exposed group for all quantities of radiation, with a mean latency period of 22 years. No BCC was observed for a surface skin dose below 10 Gy. Thyroid testing was done on a subgroup of 431 patients whose thyroid gland had been particularly exposed during angioma irradiation. After recalculation, the dose delivered to the gland was below 1 Gy in 98% of patients. Only 13 thyroid nodules were discovered (1 hot and 12 cold). 1 patient with a cold nodule had a malignant thyroid tumour 21 years after irradiation. He belonged to the group of 7 patients who had received a thyroid dose above 1 Gy. Although no morphological abnormality was found in 98% of the tested patients, most (92%) had a thyroid iodine content below 15 mg (the standard French value), while a raised serum thyroglobulin level (greater than 30 ng/ml) was observed in 17%. This might confer a higher risk of subsequently developing thyroid nodules.

A new solid-phase radioimmunoassay to measure IgG secreted by cultured human lymphocytes.

We describe a simple solid-phase radioimmunoassay (RIA) to detect IgG based on competitive binding between radiolabeled and unlabeled IgG for anti-IgG antibody physically adsorbed to the wells of polyvinyl microtiter plates. The assay is sensitive (1 ng), rapid, and is particularly suited for studies of in vitro IgG secretion by human peripheral blood lymphocytes, since such studies require large numbers of cultures. Conditions which permit measurement, by means of this assay, of helper and suppressor T cell effects on IgG production by human B cells in culture are described.

Thyroid iodine content and serum thyroid hormone levels in autoimmune thyroiditis: effect of iodide supplementation.

The relationship between thyroid iodine content (TIC) measured by x-ray fluorescence and serum TSH, T4, and T3 levels was investigated under iodide supplementation (0.5 mg/day for 1 to 9 mo). In five euthyroid control patients, whose TIC ranged from 2.5 to 14 mg, the TIC increased from 1.5 to 4 mg after 4 wk of treatment and had a tendency to plateau when the treatment was pursued. No significant changes in serum T4, T3, and TSH levels have been observed in these control subjects. Fourteen patients with autoimmune thyroiditis with low TIC (0-5 mg) were also studied. In six patients, the TIC increased significantly (3-10 mg over initial value after 3-7 mo of treatment). In parallel, there was a significant increase in serum T4 levels (35-150% over initial value) while T3 levels were modified in only two patients. In five patients serum TSH level decreased and was two- to seven-fold lower than before treatment whatever was its initial value; however, the spectrum of changes varied among patients from slight increase to a complete normalization of hormonosynthesis. In the eight other patients, iodide supplementation aggravated the thyroid disorders during the first months of treatment. The thyroid hormone blood levels dropped significantly in six patients (percent decrease below initial value: 20-100%) and was unchanged in the two others. An increase in the TSH blood level (X2-6) was observed in all patients except one. Concomitantly, the iodine stores were progressively depleted in three patients, unchanged in three and increased in two. When iodide treatment was pursued, an escape from this organification block was observed in two patients.

Significance of secondary ion mass spectrometry microscopy for technetium-99m mapping in leukocytes.

Secondary ion mass spectrometry (SIMS) microscopy is the only method potentially capable of mapping all the elements in the periodic table including stable and radioactive isotopes. We used this method to study 99mTc distribution by detecting and localizing of 99Tc, a daughter product which has the same mass and the same chemical properties. It was combined with albumin macroaggregates or with Hexamethylpropylene-amine oxime (HMPAO) in leukocytes. The efficiency of 99Tc ionization under Cs+ bombardment was higher than with an O2+ beam. By using high mass resolution we succeeded in detecting and localizing 99Tc in cell sections by eliminating polyatomic ions that arise from this biological matrix. The 99Tc specific signal was obtained with a mass resolution of 2000 for labeled albumin macroaggregates, and 5000 for HMPAO-labeled leukocytes. In the latter, the labeling varied from one cell to another and 99Tc was present in both the nucleus and the cytoplasm. The results indicate that SIMS microscopy can provide new insights into 99mTc dosimetry.

Radiolabeled somatostatin analog scintigraphy in differentiated thyroid carcinoma.

UNLABELLED: After intravenous administration of a radiolabeled somatostatin analog (octreotide), an image of the thyroid gland is frequently observed; few data are available, however, on somatostatin receptors in epithelial thyroid cells assessed in vitro and on images of differentiated thyroid carcinoma (DTC) with pentetreotide scintigraphy. METHODS: In four patients with metastatic thyroid carcinoma, whole-body scintigraphy was performed 4 to 48 hr after injection of 110 MBq of 111In-pentetreotide. The results were compared to data obtained with other imaging modalities, including scintigraphy performed after administration of a therapeutic dose of 131I. RESULTS: There were positive foci in distant metastases on 111In-pentetreotide scintigraphy. Pentetreotide scintigraphy was positive in two patients with an "insular" form of DTC, one of whom had a positive (faintly) 131I scan. Of the other two patients with papillary DTC without radioiodine uptake, only one exhibited a certain degree of pentetreotide scintigraphy positivity in distant metastases. CONCLUSION: These results show promise for exploration of insular thyroid carcinoma and suggest that these carcinomas may possess functional differentiation features, including somatostatin receptors.

SIMS microscopy imaging of the intratumor biodistribution of metaiodobenzylguanidine in the human SK-N-SH neuroblastoma cell line xenografted into nude mice.

Microdosimetric evaluations of targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (MIBG) require precise assessment of the intracellular and intratumor distribution of the drug. We report the use of secondary ion mass spectrometry (SIMS) microscopy, a technique capable of mapping any chemical element within a biological specimen, to determine 127I-MIBG biodistribution in human neuroblastoma SK-N-SH xenografted into nude mice. Highly specific images of 127I-MIBG biodistribution were mapped within the tumor after in vivo administration of the drug and sample processing with cryotechniques (high-speed freezing and cryo-embedding), which prevent MIBG diffusion from original sites of uptake. We showed that the biodistribution of the tracer was highly nonuniform within the tumor. At the cellular level, most of the drug accumulated in the cytosol and perinuclear areas. In contrast, chemical sample processing provided not only a considerable loss in sensitivity due to passive diffusion of the drug in the organic solvents, but also artefactual images mainly due to MIBG redistribution onto the cell nuclei. Based on our findings in this SK-N-SH experimental tumor model, we suggest that MIBG should be attached to long-range emitters, in the hope of irradiating the many tumorous areas that remain carrier-free.

Iodine concentration by the thymus in thyroid carcinoma.

A 14-yr-old boy underwent a total thyroidectomy with bilateral neck dissection for a papillary carcinoma with lymph node metastases. Total-body scanning with 3.7 GBq 131I revealed radioiodine accumulation in the anterior mediastinum. CT and MRI demonstrated a mediastinal mass which corresponded to the area of increased radioactivity. Five months later, another therapeutic dose of 131I was followed by a sternotomy and removal of the thymus because a hand-held radiodetecting surgical probe demonstrated that the thymus was the mediastinal structure which concentrated iodine. Thymus histology was negative for thyroid cancer metastases (as further confirmed by the negative immunostaining) and showed cystic Hassall's bodies. Secondary ion mass spectrometry microscopy demonstrated that iodine was located only in the Hassall's bodies, bound to proteins. This finding suggests that an acquired "thyroid follicle-like" structure, as that observed in cystic Hassall's bodies, could be responsible for the epithelial cell iodine uptake. In conclusion, we have provided evidence for the iodine-trapping property of the cystic Hassall's bodies of the thymus, which may be a possible cause of misleading mediastinal radioiodine uptake.

Thyroid iodine content measured by x-ray fluorescence in amiodarone-induced thyrotoxicosis: concise communication.

Iodine-induced thyrotoxicosis (liT) is characterized by (a) a low radioiodine uptake, increased by exogenous TSH, and (b) a spontaneous evolution towards cure within a few months. An hypothetical pathogenesis of liT is an initial inflation in the stores of thyroid hormones during iodine excess, followed by their sudden discharge into the circulation. Thyroid iodine content was measured by fluorescent scanning in 10 patients with amiodarone-induced thyrotoxicosis and in various control groups. Results were found to be high at the onset of the disease and to decrease during its course. The data agree with the hypothetical pathogenesis. Furthermore they may permit exclusion of a painless subacute thyroiditis, which is the main differential diagnosis of liT.