A case of stunning of lung and bone metastases of papillary thyroid cancer after a therapeutic dose (3.7 GBq) of 131I and review of the literature: implications for sequential treatments.

Thyroid stunning is usually defined as the inhibition or suppression of iodide trapping by remnant thyroid tissue or by functioning metastases following a diagnostic dose of 131I. The risk of stunning increases progressively with larger doses. Because the threshold above which this effect occurs in thyroid remnants seems to be between 37 MBq and 111 MBq of 131I, therapeutic 131I doses of 3.7 GBq may cause stunning. We describe stunning of papillary thyroid cancer lung and bone metastases after a therapeutic dose of 131I (3.7 GBq). A T1 bone metastasis and bilateral lung metastases were diagnosed by post-therapeutic dose whole-body scan. Nuclear MRI detected another lesion at T4, whose 131I fixation was not obvious. An additional 0.7 GBq were given after recombinant TSH, 37 days after the therapeutic dose; 24 h later, uptake by the lung and T1 metastases had disappeared, but trapping was again seen 6 months later on the post-therapeutic scan. This re-appearance is evidence in favour of the transitory and reversible character of stunning, and confirms its correspondence to the decreased ability of viable thyroid cells to trap iodine and not to their destruction. A better understanding of stunning would make it possible, in the event of rapidly progressing disease and in conjunction with recombinant thyroid stimulating hormone (TSH), to give several therapeutic doses of 131I in close succession without each dose hampering the effectiveness of the subsequent one.

Upper retropharyngeal node involvement in differentiated thyroid carcinoma demonstrated by 131I scintigraphy.

We report four patients with papillary thyroid cancer who had upper retropharyngeal node involvement demonstrated by 131I scintigraphy. Three patients presented with a thyroid nodule and enlarged jugular nodes. Total thyroidectomy was performed with node dissection. Pathology demonstrated papillary carcinoma with several metastatic nodes. 131I scanning 4 weeks after surgery demonstrated increased uptake in an upper retropharyngeal node. In one patient, thyroidectomy had been performed 21 years previously. Increased thyroglobulin level led to 131I scanning, which showed focal retropharyngeal uptake. All four patients had asymmetrical uptake at mouth level with focal uptake close to the sagittal plane. A lateral projection showed focal uptake between the base of the skull and the mandibular angle, behind the region of the mouth and nose. CT in all cases and MRI in one case confirmed the presence of an enlarged node. The mass was removed surgically in two patients and pathology confirmed the papillary nature of the metastatic node. Two patients were treated by 131I. Focal uptake of 131I in the region of the mouth is ambiguous, since salivary uptake of 131I is a common finding on scintigraphy. In cases of asymmetrical uptake in the region of the mouth, a lateral projection of the head therefore allows the correct diagnosis.

Radioiodine therapy of the autonomous thyroid nodule in patients with or without visible extranodular activity.

UNLABELLED: Patients with an autonomously functioning thyroid nodule (ATN) may be present with various clinical, biochemical and scintigraphic features. To optimize 131I dose planning and treatment timing in these patients, relationships between dosimetric data and clinical follow-up events must be established. METHODS: We retrospectively reviewed the records of 88 patients who received 131I (intended dose of 80 Gy) for an ATN, of whom 39 had evidence of extranodular activity (ENA) and 76 presented with overt thyrotoxicosis. In all of the patients, dosage calculation was monitored to estimate precisely both beta and gamma absorbed doses received by the ATN and the nodule-free lobe. The mean duration of follow-up was 75 mo (max 180) and always included biochemical thyroid tests. Finally, we compared the dosimetric profiles of four dosage schemes which had been normalized by simulation to ensure that the same absorbed dose threshold value was always delivered to the ATN. RESULTS: About 75% of the patients were cured at 6 mo for a mean 305 MBq administered. The absorbed doses delivered to the nodule-free lobe ranged from 12% (no ENA) to 86% (ENA) of the values delivered to the ATN, mainly in the form of beta irradiation. Life-table estimates for hypothyroidism and death were 9.6% and 22% at 75 mo, respectively. Hypothyroidism mainly developed in patients with nonsuppressed TSH levels but regardless of ENA, which often accounted for multifocal disease. CONCLUSION: We suggest that fixed doses bordering on 370 MBq are advizable in younger individuals and in patients with mild thyrotoxocosis, while 555 MBq-740 MBq can be administered in other patients and that ENA indicates multifocal autonomy in patients with toxic ATN and is a further indication for radioiodine treatment which should be begun as soon as possible to avoid the development of cardiac complications.

[Distant metastasis of differentiated thyroid cancers. Diagnosis by 131 iodine (I 131) and treatment]. / Métastases à distance des cancers thyroïdiens différenciés. Diagnostic par l'iode 131 (I 131) et traitement.

Distant metastases in differentiated thyroid cancer involve mainly lung and bone. Lung metastases were found in 5% of papillary forms and 10% of follicular forms respectively. I 131 uptake was found in 55% of the cases irrespective of histology. Bone metastases were found in 20% of follicular and 3.5% of papillary forms, respectively. Ablation of post-operative thyroid remnants is obtained by administering 3.7 GBq 1 131; I 131 (.2 to .4 GBq) is then used to localize distant metastases and a further 3.7 to 7.4 GBq is administered for therapy. Results are good in lung metastases, with a survival of 72% at 5 years. Bone metastases cannot be cured with I 131 alone. Surgery is indicated as a first line therapy if possible. In order to reduce the vascularization of the metastase a pre-operative embolization should be attempted. After bone surgery a therapeutic dose of I 131 is given if a post-operative 1 131 uptake is found. Others treatments of bone metastases are palliative surgery, external radiotherapy, cementing of the metastases.

Influence of dose selection on absorbed dose profiles in radioiodine treatment of diffuse toxic goiters in patients receiving or not receiving carbimazole.

We retrospectively reviewed the records of 224 patients with diffuse goiters treated with radioiodine, half of which received carbimazole. In all the cases, we carefully monitored the calculation of dosage. A lower percentage of early hypothyroidism but a higher failure rate was observed in the carbimazole subgroup. Nevertheless, after one year, a constant (4.5%) incremental rate of hypothyroidism was found regardless of carbimazole administration. Since we were able to precisely estimate the absorbed doses in our series, we evaluated by simulation the dosimetric profiles of nine methods of dose selection (MDS). These MDS were calibrated in such a way that the same threshold value of absorbed dose would always be reached at the thyroid level. We showed that the more elaborate the MDS, the more accurate the irradiation at the thyroid level and the lower the radiation dose administered. In patients not receiving carbimazole, a rapid MDS using modified early uptake measurements to predict the 24-hr actual value was found to be advisable. With patients receiving carbimazole and if a goal is to delay the occurrence of hypothyroidism, we advise MDS based on either a 48-hr uptake or on the calculation of the individual half-life.

[Evaluation of conventional scintigraphy (iodine 131, iodine 123 and pertechnetate 99mTc04)]. / Evaluation de la scintigraphie conventionnelle (iode 131, iode 123 et pertechnetate 99mTc04).

Thyroid scintigraphy is required during the initial assessment of an isolated thyroid nodule. This is the only means of diagnosing a hot, cold or self-fixing nodule. The isotope used can be either radioactive iodine or pertechnetate Tc04. For a number of authors, the best images are obtained with iodine; Tc04 is less expensive and easily available. Only scintigraphy can highlight the true problems. Is a cold nodule benign or malignant? A fine-needle aspiration biopsy is performed, then controlling the size if surgery is unnecessary. Is it a hot toxic nodule, or is it likely to become toxic? The ultrasensitive TSH is monitored. The malignant hot nodule problem remains theoretical. Well-documented observations are still rare. The role of scintigraphy in the initial sequence of an isolated nodule investigation is discussed. The main limit of scintigraphy, which is its poor resolution, may offer the advantage of reducing ultrasound microsemiology abuse.

Localization of a salmon calcitonin-like molecule in one type of ultimobranchial cells in the freshwater turtle Pseudemys scripta.

Immunohistochemical methods using affinity adsorbed antibodies raised against the three families of calcitonins (CT) were applied to ultimobranchial (UB) cells in situ to investigate the nature of the Chelonian calcitonin molecule and its distribution in the ultimobranchial bodies of the freshwater turtle, Pseudemys scripta. In this species, the UB glands were present on both sides and consisted of scattered cell clumps between epithelial vesicular structures. The neighboring parathyroid tissue also contained two components, the majority being composed of similar vesicles, with occasional solid cell cords evenly distributed. Calcitonin immunoreactivity was found in the cell clumps of the UB gland and in the cell cords of the associated parathyroid, but not in the epithelial component lining the vesicles or in the amorphous material which sometimes filled the lumen. Turtle calcitonin was exclusively of the salmon type, as determined by the negative results obtained in situ after the use of antibodies raised against human and porcine molecules. The salmon-like calcitonin content of the ultimobranchial area was estimated as 15.2 ng; however, the molecule was undetectable in the circulation. In this work we localize the quantitate a salmon-like CT molecule in one type of ultimobranchial and parathyroid cell of a reptile for the first time.

[Value of the detection of antithyroid antibodies in thyroid pathology]. / Intérêt de la détection des anticorps antithyroïdiens en pathologie thyroïdienne.

Antithyroid microsomal hemagglutination antibody (MCHA) and antithyroglobulin hemagglutination antibody (TGHA) were measured in 629 patients with thyroid disease and 100 controls. Thyroid antibodies were present in 4% of control patients, only in women and at low titer. Thyroid antibodies prevalence was 97% in autoimmune thyroiditis (MCHA: 93%; TGHA: 53%), was 55% in Graves disease before treatment (MCHA: 46%; TGHA: 33%) and 90% in the first year following 131I therapy. Antibodies prevalence was 57% in myxoedema (MCHA: 52%; TGHA: 25%). In patients with iodine overload, antibodies prevalence was 29% in euthyroid patients, 25% in iodine-induced hyperthyroidism and 55% in iodine-induced hypothyroidism. Thyroid antibodies detection should be systematically performed in the routine evaluation of any thyroid disorder. Because of discrepancies between TGHA and MCHA positivity, their simultaneous detection should be performed.

Iodine-induced thyrotoxicosis: analysis of eighty-five consecutive cases.

Iodine-induced thyrotoxicosis was documented in eighty-five cases. Eighty per cent occur in apparently normal thyroid glands; 60% among them occur in males. Amiodarone accounted for 50% of iodine-induced thyrotoxicosis. Mean thyroid hormone levels at diagnosis were: FT1: 21.7 (normal mean: 7.5, arbitrary units); T3: 4.53 nmol 1(-1) (normal: 2.30 nmol 1(-1). Mean 131I- 24-h uptake was 3.5% (normal range in France 25-45%) and was activated by exogenous TSH (mean 27%). The spontaneous cure in nontreated cases was observed within an average 6 months. A phase of biological hypothyroidism (mean FT1: 3.7, T3: 1.23 nmol 1(-1), TSH: 9.6 microU ml-1 (normal TSH range: 1-7 microU ml-1] preceded the return to euthyroidism. Intrathyroid iodine content measured by X-ray fluorescence was high, then fell gradually. Thyroid tissue study showed a large quantity of intrathyroid iodine and the overiodination of thyroglobulin. Histological and electron microscopic studies are reported. Prednisone and in some cases propylthiouracile were found to be effective.

Would I-123 di-iodotyrosine provide a harmless deiodination test? Concise communication.

Defective iodotyrosine deiodinase activity may benefit from a specific treatment, thus requiring an unequivocal diagnosis. In reported cases this diagnosis has been obtained from an in vivo deiodination test making use of di-iodotyrosine (DIT) labeled either with I-131 or I-125. Dosimetric calculation indicates that such tests may result in unacceptable irradiation of the thyroid of a child wrongly suspected of having defective iodotyrosine deiodinase activity; therefore other methods are needed. The use of I-123 DIT is shown to be feasible, but even a 1:30 reduction in the thyroid dose still remains too high. Suppression of thyroid I- uptake by ClO4-, together with I-125 DIT, eliminates almost all thyroid irradiation and provides a sensitive, harmless, and rapid test.

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.

[Unusual concentrations of triiodothyronine in the serum due to anti-T3 autoantibodies]. / Concentrations insolites de la triiodothyronine du sérum dues à des autoanticorps anti-T3.

Abnormally high T3 serum concentrations incompatible with the patients' clinical thyroid status were observed in a case of Graves' disease and in a euthyroid patient with hyperlipaemia. T3 was in the form of immune complexes precipitable by polyethyleneglycol. Specific anti-T3 autoantibodies were detected in the serum gammaglobulin fraction. The T3 affinity constants of these autoantibodies were found to be as high as 1.10(10) and 7.2.10(10)l/mol respectively. The antibodies interfered with radioimmunological T3 determination, resulting in an apparent increase of T3. However, after extraction, true T3 serum levels remained higher than expected. These findings illustrate the importance of hormone concentrations, affinity constants of binding proteins and equilibrium between free and bound forms in the resulting hormonal effect.

[Iodine excess and iatrogenic thyroid pathology (author's transl)]. / Surcharge iodée et pathologie thyroïdienne iatrogène.

Iodine-induced thyroid disorder is frequent. Amiodarone is responsible for more than half cases of iodine-induced hypothyroidism and hyperthyroidism. Iodine-induced hypothyroidism is detected by the Perchlorate discharge test where its positivity suggests failure of the normal iodine organification. An inhibition of the thyroglobulin proteolysis is probably involved in the pathological process of iodine-induced hypothyroidism. Premature infants are unusually sensitive to iodine excess. Hypothyroidism has been induced in 50% of newborns of 34 weeks or less of gestation after the application, for a few days, of iodized antiseptics. Iodine-induced thyrotoxicosis account for 6% of patients with hyperthyroidism. It occurs most frequently in male with prior normal thyroid gland. The main diagnosis features are the activation of the 131I uptake by exogenous TSH and the spontaneous evolution towards cure. However, in some cases, the severity of the thyrotoxicosis or the slow spontaneous resolution require surgical or medical therapy. From different therapeutic trials it seems that only corticoids and Propylthiouracile are useful. PTU, believed as the drug of choice, has however an incomplete and inconstant effect. The histochemical aspects of the iodine-induced hypo and hyperthyroidism let suppose the possibility of some common mechanism.

[Iatrogenic thyroid pathology]. / La pathologie thyroïdienne latrogène.

A physiological dose of iodine is necessary for thyroid hormonogenesis, but in pharmacological dosage it is a danger. Massive intakes of iodine, always of medical origin (radiodiagnosis, therapeutic) trigger off a defence mechanism in the thyroid gland, called Wolff-Chaikoff effect. This useful mechanism may be defective and abnormalities of thyroid function may appear either in the form of hypothyroidsm with goitre or temporary hyperthyroidism. The increasing use of drugs containg iodine and certain specially noxious substances such as amiodarone in particular give this iatrogenic thyroid pathology a new dimension, for it is no longer seen only by the specialist but also by the general practitioner. It involves the doctor's reponsibility not only in diagnosis but also in treatment.