Estimation of thyroxine and triiodothyronine distribution and of the conversion rate of thyroxine to triiodothyronine in man.

Studies on peripheral metabolism of simultaneously administered 125-I-labeled L-thyroxine ([125-I]T4) and 131-I labeled L-trilodothyronine ([131-I]T3) were performed in five normal subjects, in four patients with untreated hypothyroidism, and in 3 hypothyroid patients made euthyroid by the administration of T4. The fractional turnover rate (lambda 03) of thyroid hormones irreversibly leaving the site of degradation and the volumes of pool 1 (serum V1) of pool (interstitial fluid, V2), and of pool 3 (all tissues, V3)were obtained by using a three-compartment analysis. In addition to the turnover studies, the ratios for the in vivo T4 to T3 conversion were determined by paper chromatographic study in sera obtained 4, 7, and 10 daysafter the injection. The rate (K12) of the extrathyroidal conversion of T4 to T3 was also estimated by the compartment analysis. The T3 distribution volume (V3) of pool 3, in which T3 is utilized and degraded, was about 60% of totaldistribution volume (V=V1+V2+V3) in normal subjects, whereas only about 25% of the extrathyroidal T4 pool was in the intracellular compartment, indicating that T3 is predominantly an intracellular hormone..

The role of subunit sialic acid in the thyrotropic and gonadotropic activities of human chorionic gonadotropin.

The present studies were undertaken to delineate the role of sialic acid residues in the two subunits of hCG in relation to its hormonal activity. Sialic acid was removed by treatment of the individual subunits or intact hCG with insolubilized neuraminidase. Desialylated variants of hCG were obtained by combining an asialo subunit (as alpha or as beta) with its complementary intact or desialylated subunit. When tested in the hCG receptor assay using a rat testis fraction, none of the hCG variants exhibited any loss of activity compared with that of intact purified hCG. In in vitro bioassays that employed cAMP and testosterone generation in rat Leydig cells as indices of response, intact hCG and as alpha in combination with intact beta (as alpha-beta) were equipotent. In contrast, intact alpha-subunit combined with as beta (alpha-as beta) and desialylated intact hCG (asialo-hCG) showed activity that at the highest concentration of each tested (20 ng/ml) was no more than half of that evoked by intact hCG. In a TSH receptor assay in human thyroid membranes, loss of sialic acid from either one or both hCG subunits resulted in enhancement of binding affinity; the rank order of decreasing potency was asialo-hCG, alpha-as beta, as alpha-beta. However, despite their enhanced binding affinity, and like intact hCG itself, none of the variants elicited a cAMP response in either human thyroid membranes or cultured human thyroid cells. Rather, asialo-hCG and alpha-as beta, but not intact hCG and as alpha-beta, were effective antagonists of the stimulatory response induced by bovine TSH in thyroid cells. These findings indicate that desialylation of hCG enhances its binding affinity for hCG receptors in testis and, much more so, for TSH receptors in human thyroid. Desialylation also changes hCG from a full agonist to a partial agonist in testis and from a nonagonist to an antagonist in human thyroid. In all cases, sialic acid in the beta-subunit of hCG appears to have a predominant role in these effects.

Polyphloretin phosphate, an antagonist of thyrotropin action: evidence for an interaction with the hormone rather than the receptor.

Polyphloretin phosphate (PPP) is known to be an inhibitor of bovine TSH (bTSH)-induced stimulation of the thyroid in both in vivo and in vitro assays. The present studies were undertaken to delineate the mechanism of these effects. A high molecular weight PPP preparation strongly inhibited both the binding of 125I-labeled bTSH [( 125I]bTSH) to human thyroid membranes and the stimulation of adenylate cyclase evoked by bTSH therein. Inhibition of bTSH-induced adenylate cyclase activity by PPP was evident both in the absence and the presence of NaCl (150 mM) in the incubation medium. Incubation of membranes with PPP, followed by its removal, did not affect subsequent binding of [125I]bTSH, indicating that PPP did not bind firmly to or damage the TSH receptor. Gel chromatography on Sephadex G-100 revealed that [125I]bTSH incubated with PPP eluted earlier than [125I]bTSH alone, indicating that PPP had formed a higher molecular weight complex with [125I]bTSH. This effect could be prevented by the addition of an excess of unlabeled bTSH to the incubation mixture. Binding of [125I] bTSH in the higher molecular weight peak generated by incubation with PPP was less than half that in control specimens of [125I]bTSH. Studies with PPP were also conducted in a highly sensitive assay that employs cultured porcine thyroid cells and measures the cAMP response induced by bTSH. The inhibitory effect of PPP on bTSH-induced cAMP accumulation was also evident in this assay. However, the presence of divalent cations Ca++ and Mg++ in the assay medium greatly diminished the inhibitory effect of PPP. Similarly, addition of Ca++ and Mg++ to the incubation medium greatly reduced or abolished the inhibitory effect of PPP on [125I]bTSH binding. Both effects of these salts to lessen the inhibitory response to PPP were overcome by increasing the PPP concentration. Gel chromatographic studies revealed that Ca++ and Mg++ acted by inhibiting the formation of the high molecular weight complex of bTSH and PPP. From these findings, we conclude that PPP exerts its inhibitory effect on TSH-induced stimulatory responses in the thyroid, in vivo as well as in vitro, by forming a complex with the hormone. The complex either does not bind to TSH receptors or does so with much lower affinity.

Thyrotropin receptor antibodies in hypothyroid Graves' disease.

To clarify the relation of TSH receptor antibody (TRAb) to Graves' ophthalmopathy and thyroid function, the activities of TSH binding inhibitor immunoglobulins, thyroid-stimulating antibodies, and thyroid stimulation-blocking antibodies were measured in five patients with hypothyroid Graves' disease. The diagnosis was based on the presence of Graves' ophthalmopathy and either permanent or transient hypothyroidism without a history of treatment for hyperthyroid Graves' disease. TSH binding inhibitor immunoglobulins and thyroid-stimulating antibodies were detected in all five patients. Thyroid stimulation-blocking antibodies results indicated that a blocking type of TRAb was not a cause of hypothyroidism. Destructive changes in the thyroid were probably responsible for hypothyroidism, since 1) high antibody titers against thyroglobulin and thyroid microsomal antigen, 2) diffuse hypoechogenicity of the thyroid on ultrasonography, 3) absent or impaired responses of serum T3 after TRH or TSH stimulation, and 4) histological findings similar to those in Hashimoto's thyroiditis were observed. In all patients except one, thyroid function was changeable, with euthyroid and even subclinical hyperthyroid episodes occurring during the course of the illness. It is conceivable that such unstable thyroid function may be attributable to subtle changes in the balance between the effects of destructive changes in the thyroid and the stimulatory effects of TRAb. In conclusion, all patients had TRAb, suggesting a possible relationship between such antibodies and Graves' ophthalmopathy. Patients develop euthyroidism or subclinical hyperthyroidism during the course of the illness with high frequency.

Inhibition of thyrotropin-stimulated iodide uptake in FRTL-5 thyroid cells by crude immunoglobulin fractions from patients with goitrous and atrophic autoimmune thyroiditis.

We studied the effects of crude immunoglobulin (Ig) fractions of serum from patients with goitrous and atrophic autoimmune thyroiditis on TSH-, thyroid-stimulating immunoglobulin (TSI)-, forskolin-, and dibutyryl cAMP-stimulated 125I uptake by FRTL-5 thyroid cells. TSH-stimulated 125I uptake was inhibited by the Ig fractions from 15 patients with atrophic thyroiditis who had serum TSH binding inhibitor Igs (TBII), 10 (62.5%) of 16 TBII-negative patients with atrophic thyroiditis, 7 (43.8%) of 16 hypothyroid patients with goitrous thyroiditis who had no TBII activity, and only 2 (15.4%) of 13 euthyroid patients with goitrous thyroiditis who were negative for TBII. The mean inhibition of TSH-stimulated 125I uptake produced by the crude Igs from the former 3 groups of hypothyroid patients was statistically significant (P less than 0.001, P less than 0.001, and P less than 0.01, respectively) and correlated closely with the ability of the Ig fractions to inhibit TSI-stimulated 125I uptake (r = 0.882) and TSH-stimulated cAMP accumulation (r = 0.929). The inhibition of TSH- or TSI-stimulated 125I uptake by Ig samples containing TBII correlated significantly with the TBII activities. On the other hand, in the presence of Igs from TBII-negative hypothyroid patients, the inhibition of TSH-stimulated 125I uptake correlated significantly with that of forskolin-stimulated 125I uptake (r = 0.685). Although 6 (12.8%) of 47 Ig samples from hypothyroid patients inhibited dibutyryl cAMP-stimulated 125I uptake, the activities were marginal. These findings suggest that at least 2 types of antibodies are involved in the inhibition of TSH- or TSI-stimulated 125I uptake: 1 being a competitive inhibitor of TSH binding to its receptors, and another exerting influence on a step subsequent to TSH or TSI binding, presumably through adenylate cyclase inhibition.

A sensitive and practical assay for thyroid-stimulating antibodies using crude immunoglobulin fractions precipitated with polyethylene glycol.

A simple, sensitive, and practical assay for thyroid-stimulating autoantibodies (TSAb) was developed in which cryopreserved porcine thyroid cells were incubated with crude immunoglobulin fractions sedimented from serum with polyethylene glycol. In the assay, 1.4- to 2.0-fold and 6- to 12-fold increases in cAMP released into Hank's medium without NaCl were found at 1 and 10 microU/ml bovine TSH, respectively. TSAb were detected in 41 (97.6%) of 42 patients with untreated hyperthyroid Graves' disease, 29 (55.8%) of 52 patients with hyperthyroid Graves' disease who were euthyroid while taking antithyroid drugs, 22 (78.6%) of 28 patients with euthyroid Graves' disease, and none of the patients with simple goiter, adenomatous goiter, thyroid adenoma, or thyroid cancer tested. TSAb activities measured using porcine thyroid cells significantly correlated with those measured using human thyroid adenoma cells (r = 0.908; n = 46; P less than 0.001). Thyroid-stimulating activity was also detected in 11 (28.9%) of 38 patients with Hashimoto's thyroiditis. However, the activity was considered to be due to TSH in the patients' sera, because it was completely abolished by pretreatment with anti-TSH antibodies. Serum TSH concentrations lower than 50 microU/ml did not affect the assay result. In Graves' disease after cessation of antithyroid drugs, 85.7% (12 of 14) of TSAb-positive patients relapsed, while 77.8% (14 of 18) of TSAb-negative patients remained in remission. Thus, the assessment of TSAb was useful as an index to predict prognosis.

Inhibition of thyrotropin-induced growth of rat thyroid cells, FRTL-5, by immunoglobulin G from patients with primary myxedema.

We studied thyroid growth-blocking activity in immunoglobulin G (IgG) fractions of serum from 24 patients with primary myxedema, 24 patients with goitrous Hashimoto's thyroiditis, and 18 normal subjects by measuring the ability of their IgG to inhibit TSH-induced [3H]thymidine incorporation into DNA in a rat thyroid cell line, FRTL-5. Both groups of patients were receiving T4 when studied. [3H]Thymidine incorporation induced by 0.1 mU/ml bovine TSH was significantly inhibited by the addition of 2 mg/ml IgG from patients with primary myxedema (P less than 0.01), while it was not affected by IgG from the normal subjects or 23 of the 24 patients with goitrous Hashimoto's thyroiditis. IgG from patients with primary myxedema also inhibited the [3H]thymidine incorporation induced by Graves' IgG, but not that induced by forskolin, cholera toxin, (Bu)2cAMP or phorbol-12-myristate-13-acetate. The inhibition of TSH-induced [3H]thymidine incorporation by IgGs from patients with primary myxedema was significantly correlated with their inhibitory activities against both TSH-induced cAMP generation and TSH binding (P less than 0.001). These data indicate that these growth-blocking antibodies are directed against the TSH receptor and might be one of the causes of the thyroid atrophy in patients with primary myxedema.

Detection and properties of TSH-binding inhibitor immunoglobulins in patients with Graves' disease and Hashimoto's thyroiditis.

TSH-binding inhibitor immunoglobulins (TBII) have been detected in patients with Graves' disease and Hashimoto's thyroiditis by using the radioreceptor assay of TSH. In untreated Graves' patients, TBII levels correlated well with thyroidal 99mTc uptake at 30 min and the grade of epithelial hyperplasia of thyroid follicles. There were many Graves' patients whose sera contained high TBII levels but no detectable bioassayable thyroid-stimulating activity (LATS), and in these patients, close correlation was observed between serum levels of TBII and bioassayable LATS-protector activity. TBII were detectable in 2 (10%) of 20 patients with Hashimoto's thyroiditis, both of whom were clinically hypothyroid. The serum or IgG fraction from one of them, however, did not contain any significant LATS, LATS-protector, or human thyroid adenylate cyclase-stimulating activity and caused inhibition of adenylate cyclase stimulation by TSH. In that patient, TBII may be acting to block TSH binding to TSH receptors, thus causing TSH unresponsiveness and hypothyroidism.

A new in vitro assay for human thyroid stimulator using cultured thyroid cells: effect of sodium chloride on adenosine 3',5'-monophosphate increase.

A new sensitive in vitro assay for human thyroid stimulator (HTS) was developed using human thyroid adenoma cells in monolayer culture. After being cultured for 2 days, the cells were incubated in 0.3 ml Hank's solution without 0.8% NaCl (medium 1) and with thyroid stimulator (bovine TSH or 3 mg patient serum immunoglobulin G) at 37 C for 2 h. The cAMP generated in the cells and the medium during the incubation was measured by RIA. The assay was sensitive enough to elicit a 1.7- to 7.9-fold increase in cAMP at a TSH concentration of 10 microU/ml. HTS was detected in 33 (82.5%) of the 40 patients with untreated graves' disease using this assay system. In Hank's solution (medium 2), however, HTS was detected in only 5 (23.8%) of the 21 patients with untreated GRaves' disease. cAMP increment upon stimulation by either TSH or HTS in medium 1 was larger than that in medium 2, and the difference in the response to HTS using the two media was much greater than that in the response to TSH. Therefore, all HTS-immunoglobulin G studies showed higher activity using medium 1 than using medium 2 when expressed as bovine TSH equivalent. Analysis by the Lineweaver-Burk plot of dose-response curves of the effect of TSH and HTS stimulation on cAMP increment showed an increase in the Km upon the addition of NaCl to the medium. A similar inhibitory effect of NaCl (150 mM) was also observed in the assay system of human thyroid adenylate cyclase stimulator using crude plasma membrane fractions. In summary: 1) an assay for HTS measuring cAMP production in cultured thyroid adenoma cells was developed and the assay using low NaCL medium was found to be the most sensitive, and 2) the inhibitory effect of NaCl on the response to HTS was much greater than that on the response to TSH. These data suggest different behaviors of these two stimulators at their receptor sites.

Development of spontaneous hypothyroidism in patients with Graves' disease treated with antithyroidal drugs: clinical, immunological, and histological findings in 26 patients.

Graves' disease may result eventually in hypothyroidism in approximately 5-20% of patients. In a few such patients hypothyroidism was associated with TSH-blocking antibodies, but whether the frequency of TSH-blocking antibodies in such patients is as high as it is (21%) in patients with primary myxedema is not known. This study was undertaken to determine the presence of various immunoglobulins [TSH binding inhibitor immunoglobulins, thyroid-stimulating antibodies (TSAb), and TSH-blocking antibodies] in 26 patients with Graves' disease who developed hypothyroidism from 0.5-10 yr or more after discontinuation of antithyroid drug therapy. Eight of the 26 patients (31%) had TSH-blocking antibodies, 16 (61%) had TSAb, and 14 (54%) had thyroid hormone binding inhibitor immunoglobulins. Thyroid needle biopsies were performed in 9 patients. Three of 5 patients who had subclinical hypothyroidism had chronic lymphocytic thyroiditis, and all had positive TSAb titers. Three patients had the fibrous variant of chronic lymphocytic thyroiditis; their TSAb values were 902%, 431%, and 1290%. One patient had follicular hyperplasia. We conclude that TSH-blocking antibodies may account for hypothyroidism in approximately one third of patients with Graves' disease who were previously treated with antithyroid drugs, and that autoimmune thyroiditis is comparable for the hypothyroidism in the remaining two thirds of Graves' disease patients.

Role of thyrotropin receptor antibodies in the development of hyperthyroidism: follow-up studies on nine patients with Graves' disease.

TSH binding inhibitor immunoglobulin (TBII) and thyroid-stimulating antibody (TSAb) activities were measured serially for 4-32 months in nine patients before and during development of hyperthyroidism due to Graves' disease. Initially, all were euthyroid, seven had thyroid enlargement, one had proptosis, and seven had high serum titers of antithyroid microsomal antibodies. The occurrence of hyperthyroidism was preceded by detection of both TBII and TSAb in four patients and detection of TSAb alone in four patients. One patient had neither TBII nor TSAb when euthyroid. The mean initial TBII and TSAb activities were 10.2 +/- 15.2% (+/- SD) and 2677 +/- 4620%, respectively, when these patients were euthyroid. When they became hyperthyroid, both TBII and TSAb activities increased in all patients. At that time, TBII was detected in all but one (eight of nine subjects; 88.9%), with a mean activity of 58.8 +/- 23.4% (+/- SD), and TSAb was detected in all nine patients, with a mean value of 4508 +/- 4429%. These findings not only indicate the crucial role of TSH receptor antibodies in the development of hyperthyroidism due to Graves' disease, but also suggest that a certain period of subclinical Graves' disease exists before the onset of overt hyperthyroidism in most patients, in the sense that they have TSH receptor antibodies, especially TSAb, in their serum even though they are euthyroid.

The mechanism of spontaneous hypothyroidism in patients with Graves' disease after antithyroid drug treatment.

The natural course of Graves' disease results in hypothyroidism in up to 20% of patients previously treated with antithyroid drugs. The precise mechanisms are not known, although autoimmune destruction of thyroid tissue has been proposed. We studied sequentially obtained serum samples from three patients with hyperthyroid Graves' disease previously treated with an antithyroid drug who became hypothyroid to determine possible causes of their hypothyroidism. Antithyroglobulin and antithyroid microsomal autoantibodies, TSH binding inhibitory immunoglobulin (TBII), thyroid-stimulating antibody (TSAb), and thyroid stimulation-blocking activity were measured. Autoantibodies were markedly elevated throughout the clinical course in all three patients. Patient 1 had no TBII and blocking activity and extremely high TSAb when she was euthyroid as well as hypothyroid. Hypothyroidism was probably the result of autoimmune thyroid destruction. In patient 2, TSAb disappeared, and TBII and blocking activity increased markedly when she developed hypothyroidism, which thus appeared to result from blocking antibodies. Patient 3 had intermittent periods of hyper- and hypothyroidism before becoming and remaining euthyroid. While initially hypothyroid, TBII was weakly positive, and TSAb was strongly positive; subsequently, when hyperthyroidism recurred, TBII and TSAb were strongly positive. Hypothyroidism appeared to result from focal autoimmune thyroiditis. Patients with hyperthyroid Graves' disease may develop hypothyroidism later by different means. Autoimmune thyroiditis, diffuse or focal, with thyroid destruction is one mechanism. The appearance of antibodies that block TSH stimulation may be another.

Thyroid response, especially to thyrotropin-binding inhibitory immunoglobulins, in euthyroid relatives of patients with Graves' disease: a clinical follow-up.

Three hundred and fifty-three euthyroid relatives of Graves' disease patients were tested for TSH binding inhibitory immunoglobulins (TBII). Eighteen had elevated levels of TBII, and 232 who had negative TBII levels also agreed to be followed for a period of 6-30 months. TBII was chosen as the critical screening measurement for this study, rather than thyroid-stimulating antibodies (TSAb) and thyroid-stimulating blocking antibodies (TSBAb), because of the availability and ease of use of TBII RIA kits. Eleven of the 18 subjects with elevated TBII were T3 nonsuppressible (group I), and 10 of the 11 were TRH unresponsive. Nine of these 10 subjects showed TSH levels below 0.05 mU/L. The remaining 7 subjects were T3 suppressible and TRH responsive (group II). Alterations in thyroid status occurred in 8 of the 11 subjects in group I during follow-up. One developed hypothyroidism, and 7 became hyperthyroid. The hypothyroid subject had initial titers of TBII, TSAb, and TSBAb that were markedly elevated, and TSAb disappeared when she became hypothyroid. Six of the 7 subjects who developed hyperthyroidism had elevated TSAb and negative TSBAb titers while they were euthyroid. All 7 subjects in group II remained euthyroid during the follow-up period. Only 2 of the 232 relatives who initially had negative TBII titers became hyperthyroid during the follow-up period. The results indicate that euthyroid relatives with a family history of Graves' disease who have elevated TBII levels and suppressed basal serum TSH concentrations have a much higher potential to develop hyperthyroidism than those who have normal or negative TBII levels.

Diffuse bony uptake of thallium-201-chloride in the granulocyte colony-stimulating factor-producing lung carcinoma.

Diffuse uptake of 201TI in the axial bone is reported in a patient with large cell carcinoma of the lung who showed leukocytosis and an increased concentration of granulocyte colony-stimulating factor (G-CSF) in plasma. The abnormal bony uptake of 201TI disappeared in association with normalization of the elevated plasma G-CSF level after complete tumor resection. The production of G-CSF was confirmed by immunoperoxidase staining of the tumor tissue.

Follow-up study of postoperative patients with thyroid cancer by thallium-201 scintigraphy and serum thyroglobulin measurement.

The utility of 201TI scintigraphy and thyroglobulin measurement in the follow-up observation of postoperative patients with thyroid cancer was evaluated. Thallium-201 scintigraphy was performed in 149 postoperative patients with thyroid cancer. Serum thyroglobulin concentration was concomitantly evaluated in 86 patients. Among 55 patients with positive 201TI scans, 51 patients (92.7%) had recurrent diseases, while 80 of 94 patients (85.1%) with negative scans were free of disease. Twenty-five of 28 patients (89.3%) with elevated thyroglobulin levels were recurrent and 43 of 58 patients (74.1%) with normal thyroglobulin level had no recurrence nor metastasis. All 19 patients with positive 201TI scans and elevated thyroglobulin level had recurrent lesions. Seven of 10 patients with negative 201TI scans and elevated thyroglobulin level showed the presence of metastasis. By concomitant measurement of serum thyroglobulin, more than half of the recurrent patients with negative 201TI scintigraphy were detected. Both 201TI scintigraphy and serum thyroglobulin measurement should be undertaken in the follow-up evaluation of postoperative patients with thyroid cancer.

Tumoricidal cytokines enhance radioiodine uptake in cultured thyroid cancer cells.

UNLABELLED: We explored whether the stimulation of iodine uptake by interferons seen in rat thyroid cell line is reproducible in human thyroid cancer and thus applicable to enhance the efficacy of radioiodine therapy. METHODS: Surgical specimens from 12 papillary and 2 follicular adenocarcinomas were minced and seeded in culture trays. After 14-16 days in a medium supplemented with 5% calf serum, we measured cellular uptake of 125I during a 40-min incubation period. RESULTS: In 8 of 12 papillary and all 2 follicular carcinomas, interferon-gamma significantly stimulated iodine incorporation. The four nonresponder tumors had lower basal iodine uptake and relatively less differentiation of histologic features. The effect was dose dependent (0-100 U/ml), and the average maximum increase in responding cases was 35.1% over basal values. Tumor necrosis factor-alpha alone did not alter uptake, but at 300 U/ml it further enhanced the effect of interferon-gamma in the two follicular tumors. In addition to the pure cytokines, supernatant from lymphocyte culture conditioned with a bacterial immunostimulator also boosted radioiodine trapping in thyroid cancer cells. CONCLUSION: These in vitro results warrant animal experiments to test potential usefulness of tumoricidal cytokines in radioiodine therapy.

Evaluation of technetium-99m-MIBI scintigraphy in metastatic differentiated thyroid carcinoma.

UNLABELLED: Technetium-99m-methoxyisobutyl isonitrile (99mTc-MIBI) was evaluated for its ability to detect metastases from thyroid carcinoma. METHODS: Twenty-seven thyroidectomized patients with metastatic differentiated thyroid carcinoma, of whom 20, 9 and 12 had lung, lymph node and bone metastases, respectively, were examined with 99mTc-MIBI. The scan results were compared with those of 201TI and 131I whole-body scans. RESULTS: Increased accumulation of 99mTc-MIBI was observed in lung metastases of 15 patients (75.0%), 12 lymph node metastases (100.0%) and 29 of 31 bone metastases (93.5%). Increased accumulations of 201TI and 131I scans were seen in, respectively, 16 (80.0%) and 17 (85.0%) of the 20 patients with lung metastases, 12 (100.0%) and 5 (41.7%) of the 12 lymph node metastases and 28 (90.3%) and 27 (85.1%) bone metastases. Because of its better image quality, 99mTc-MIBI detected more lesions in the lung (n = 38) than 201TI did (n = 17). CONCLUSION: Technetium-99m-MIBI is clinically useful for detecting metastases from differentiated thyroid carcinoma and deserves clinical application in the postoperative follow-up of such patients.

Radioiodine uptake by squamous-cell carcinoma of the lung.

A patient with a history of total thyroidectomy for papillary carcinoma showed a solitary hot spot in the chest on post-therapy radioiodine imaging. Subsequent evaluation demonstrated that this lesion was a primary squamous-cell lung cancer. Our case illustrates a rare but important differential diagnosis from lung metastasis of thyroid cancer in 131I scintigraphy. Alternatively, this "aberrant uptake" might be a rather common phenomenon for lung neoplasms, although the underlying mechanism is not yet known. Future experimental studies might lead to a new application of radioiodine imaging in pulmonary oncology.

Scintigraphic findings of the thyroid in euthyroid ophthalmic Graves' disease.

UNLABELLED: The scintigraphic findings of the thyroid were analyzed in patients with euthyroid ophthalmic Graves' disease known to have some thyroid-related abnormalities. METHODS: Technetium-99m-pertechnetate images of the thyroid from 38 euthyroid ophthalmic Graves' disease patients with small, soft or nonpalpable goiter were analyzed. RESULTS: Scan images showed homogeneous (even) and nonhomogeneous (uneven) 99mTc uptake in 20 and 16 patients respectively. Poor images due to low uptake were observed in two patients. Six patients displayed alterations in scintigraphic appearance from even to uneven patterns after T3 suppression test. Statistical analysis revealed that the uneven pattern was more frequently observed in euthyroid ophthalmic Graves' disease patients than in 26 patients with hyperthyroid Graves' disease who were euthyroid during antithyroid drug therapy (p < 0.005). The scintigraphic heterogeneity was correlated with reduced uptake as well as a higher ratio of the uptake values after T3 treatment to the pretreatment values. Scintigraphically, hot or warm lesions were observed in most cases showing the uneven pattern (16/22; 73%). Rather low titers of antithyroglobulin, antimicrosomal antibodies and TSH-binding inhibitor immunoglobulins were detected in only 4 (10.5%), 7 (18.4%) and 12 (31.6%) patients respectively, while the prevalence of thyroid-stimulating antibodies (TSAb) was as high as 86.8% (33/38). The scintigraphic heterogeneity did not correlate with the detection of these antibodies but did correlated with the severity and duration of ophthalmopathy. CONCLUSIONS: The presence of functioning follicular cells with some autonomy that were heterogeneously distributed in the thyroid was observed in about half the euthyroid ophthalmic Graves' disease patients. Chronic stimulation by TSAb may be the underlying mechanism for these findings.

Myocardial oxidative metabolism in hyperthyroid patients assessed by PET with carbon-11-acetate.

UNLABELLED: Hyperthyroid patients often complain of cardiovascular symptoms because of increased metabolism. This study was designed to quantitatively evaluate myocardial oxidative metabolism in these patients. METHODS: Dynamic PET with 11C-acetate was performed in 19 patients who had not undergone treatment for hyperthyroidism. Eight were restudied 2 wk after oral administration of propranolol. The clearance rate constant of 11C-acetate (Kmono) was calculated with monoexponential fitting of tracer washout from the myocardium as a marker of myocardial oxidative metabolism. The results were compared with those in nine normal subjects both at rest and during dobutamine infusion. RESULTS: Kmono in our patients (0.109 +/- 0.028 min-1) was significantly increased compared to normal subjects (0.066 +/- 0.016 min-1) (p < 0.05). After propranolol treatment, Kmono decreased (0.082 +/- 0.014 min-1) but remained significantly higher in eight patients than normal subject levels (p < 0.05), while the rate pressure product decreased significantly (7500 +/- 1700) toward the normal range (7900 +/- 1500). CONCLUSION: These results suggest the possibility of excessive myocardial oxygen consumption in hyperthyroid patients. The clearance rate of 11C-acetate is a new and valuable index to assess myocardial oxidative metabolism not closely related to the pressure rate product or thyroid hormones in these patients.