Brain metastasis from differentiated thyroid cancer in patients treated with radioiodine for bone and lung lesions

Brain metastasis of differentiated thyroid cancer (DTC) often is detected during treatment of other remote lesions. We examined the prevalence, risk factors and treatment outcome of this disease encountered during nuclear medicine practice. Of the 167 patients with metastasis to lung or bone treated 1-14 times with radioactive iodine (RAI), 9 (5.4%) also had lesions in the brain. Five were males and 4 females, aged 49-84, out of the original population of 49 males and 118 females aged 10-84 (mean 54.7) years. Three of them underwent removal of their brain tumors, 5 received conventional external beam irradiation, and 2 had stereotactic radiosurgery with supervoltage X-ray. None of the brain lesions showed significant uptake of RAI despite demonstrable accumulation in most extracerebral lesions. Seven patients died 4-23 (mean 9.4) months after the discovery of cerebral metastasis, brain damage being the primary or at least a contributing cause. The 8th and 9th patients remained relatively well for more than 42 and 3 months, respectively, without any evidence of intracranial recurrence. Our results confirmed that the brain is a major site of secondary metastasis from DTC. No statistically significant demographic risk factor was detected. Any suspicious neurological symptoms in the course of RAI treatment warrant cerebral computed tomography. As for therapy, from our initial experience, radiosurgery seemed promising as an effective and less invasive alternative to surgical removal.     

Diffuse radioiodine lung uptake in miliary thyroid carcinoma metastases

A diffuse pattern of homogeneous tracer uptake is seen by I-131 scintigraphy in a patient with widespread miliary lung metastases due to papillary thyroid carcinoma. This case report emphasizes the need to include metastatic thyroid carcinoma in the differential diagnosis of miliary lung nodules.     

Results of radioiodine therapy in patients with pulmonary metastases of differentiated thyroid cancer

Factors affecting the effect of 131I treatment and survival after pulmonary metastases in patients with differentiated thyroid cancer, were studied. Between 1984-1999, pulmonary metastases was observed in 51 out of 153 patients with differentiated thyroid cancer at our institution. Of these 41 patients had papillary and 10 follicular thyroid cancer. There were 37 females and 14 males with mean age (+/- S.D.) of 50.5 +/- 19.0 years. These 51 patients were subjected to 131I therapy. The effect of 131I treatment and the prognostic values of the following variables were examined: sex, age at the time of 131I treatment, histologic type of cancer, size of pulmonary metastases on CT, total-body scintigraphy with 201Tl and 131I, serum thyroglobulin levels and presence of metastases in distant sites other than lung. The effect of 131I treatment was evaluated by means of changes in the number and size of metastatic shadows on chest CT and by serum thyroglobulin levels. The minimum duration of follow-up was 12 months. Therapeutic 131I dose scans revealed detectable uptake in 25 of 51 patients. Therapeutic 131I dose uptake was achieved more frequently in patients under 40 years of age and in those with follicular cancers. Of the 51 patients, 13 were evaluated to be treated successfully. Those under 40 years of age, with 131I uptake in the lung and presence of other metastases showed a good response to treatment than others. Follicular cancer showed a more significant association with coarse type of lung metastases (> 5 mm in diameter on chest CT) and good 131I uptake than papillary cancer. Of all the variables studied, the best prognosis for survival was demonstrated by increased 131I uptake in pulmonary metastases. These results indicate that age, 131I uptake and presence of other metastases are important factors in predicting the effect of 131I treatment for pulmonary metastases of differentiated thyroid cancer.     

Follow-up of children and young adults with differentiated thyroid cancer treated with radioiodine

This is a retrospective study carried out in a group of 30 patients with differentiated thyroid cancer (age at diagnosis equal to or less than twenty years old). The aim of the study is to evaluate outcome after 131I therapy. Patients were classified into three groups on the basis of initial surgery, pathology and scintigraphic results: group I (thyroid extent), group II (locoregional extent), and group III (distant metastatic disease). Clinical parameters, 131I scans, serum thyroglobulin determinations and 131I therapeutic administered doses were evaluated in the follow-up. Some other complementary techniques such as chest X-ray and pulmonary function tests are also described. Scintigraphic absence of thyroid tissue has been observed in 83% of the cases; high thyroglobulin level is still detectable in 34% of the patients as a single evidence of disease, and 21% remain without any abnormal clinical, scintigraphic or analytical findings. Total doses administered have increased in groups I, II and III respectively, and have also been inversely proportional to the extension of lymph node surgery. At present, all the patients are alive and in good general condition. According to the results obtained, we conclude that children and young adults with DTC should undergo periodical 131I therapeutic doses in case of positive scans (once total thyroidectomy has been realized, with or without lymph node resection depending on the extension of disease). In our experience, the use of radioiodine is effective and safe in the follow-up of children and youngs with DTC.     

Symptomatic late-onset sialadenitis after radioiodine therapy in thyroid cancer

Objective

The aim of this study was to document the subjective and objective findings of symptomatic late-onset sialadenitis after radioiodine therapy in patients with differentiated thyroid cancer.

Methods

Subjective symptoms related to sialadenitis and Tc-99m pertechnetate salivary gland scintigram findings were assessed in 118 patients (26 males, 92 females) both before and during the late phase (mean 338 days) after the administration of radioiodine.

Results

Twelve of the 118 patients (10.2 %) complained of symptomatic sialadenitis in the late phase without symptoms during the early phase (within 7 days of radioiodine administration). Significant associations were found between subjective symptoms and visual scintigram findings during the late phase (p = 0.023). Furthermore, uptake and excretion by both parotid glands were significantly affected by radioiodine therapy.

Conclusions

Symptomatic late-onset sialadenitis occurred at an incidence of 10.2 %, and salivary gland function was affected in both parotids in most patients.     

131I治疗分化型甲状腺癌肺转移对肺功能的影响

目的探讨131I治疗分化型甲状腺癌肺转移对肺功能的影响.方法甲状腺癌肺转移患者58例,131I累积治疗剂量3.7～92.5 GBq,131I末次治疗后3个月行X线胸片、肺功能[肺活量(VC)、时间肺活量(FVC)、第1 s最大呼气量(FEV1)、最大通气量(MVV)]检测和99Tcm-DTPA气溶胶半清除时间测定.结果① 肺功能各指标在各累积剂量组之间差异无显著性(P>0.05);在性别组之间VC、FVC、FEV1差异无显著性(P>0.05),但MVV差异非常显著(P<0.01).②99Tcm-DTPA气溶胶半清除时间正常对照组(n=8)参考值为53.2±8.6.各组间比较差异均未见显著性(P>0.05).③1例43岁女性患者肺功能低下(其VC、FVC、FEV1和MVV分别为58.1%、58.1%、43.6%和37.2%),99Tcm-DTPA气溶胶半清除时间缩短(26.4 min),X线胸片示双肺纹多或粗,131I显像未见异常浓聚灶.该患者甲状腺乳头状癌肺转移12年,131I治疗8次,累积剂量51.8 GBq,不能排除肺纤维化.结论 131I治疗累积剂量对肺功能无显著影响.131I累积剂量>37 GBq者需警惕发生肺纤维化.结合X线胸片、肺功能和99Tcm-DTPA测定可综合评估甲状腺癌肺转移131I治疗后的肺损伤情况.     

Serial thyroid iodine content in hyperthyroid patients treated with radioiodine

X-ray fluorescent scanning was used to measure initial thyroidal iodine content in 64 patients diagnosed as being hyperthyroid and selected for I-131 therapy, and serially in 48 of these patients after therapy in an attempt to determine those patients that were at high risk of becoming hypothyroid. Iodine content fell rapidly after therapy, reaching a nadir at about three months. Based on the population studied, the chance of early hypothyroidism (within 12 months) is about 80% if the iodine content measured at three months is less than 2 mg. If the iodine content is greater than 2 mg, the chance is only about 14%. The serial measurement of thyroidal iodine content (with x-ray fluorescent scanning) may allow early identification of those patients at high risk of developing permanent hypothyroidism following a therapeutic dose of I-131.     

Visualization of nasolacrimal drainage system after radioiodine therapy in patients with thyroid cancer

The objective of this study was to report three cases with an accumulation of ¹³¹I in the nasolacrimal duct after radioiodine therapy for papillary thyroid cancer. A whole-body scan was taken 3 days after the administration of 3.7 GBq of ¹³¹I. Single-photon emission computed tomography (SPECT)/CT images were added when the location of a focal tracer uptake was undetermined on whole-body scans. In case 1, a 62-year-old woman complained of epiphora of the left eye after nine radioiodine therapies with a cumulative dose of 31.08 GBq. The left nasolacrimal duct was visualized at her tenth treatment with ¹³¹I. In case 2, a series of three radioiodine therapies had been given to a 73-year-old woman with a cumulative dose of 11.1 GBq. The accumulation of ¹³¹I was noted in the left nasolacrimal duct at her fourth treatment. She complained of epiphora of the left eye. In case 3, bilateral nasolacrimal ducts were visualized at the second radioiodine therapy in a 75-year-old woman. The patient had received 3.7 GBq of ¹³¹I at the first therapy. She did not complain of epiphora. It is possible that radiation from ¹³¹I that is secreted in tears and/or actively accumulated in the nasolacrimal duct may induce nasolacrimal duct obstruction. ¹³¹I in tears would be responsible for the visualization of nasolacrimal duct in the first two cases. ¹³¹I actively accumulated in the nasolacrimal duct might have been visualized in the third case. In summary, ¹³¹I is excreted in tears and is actively accumulated in the nasolacrimal duct. Obstruction of the lacrimal drainage system could occur after high-dose radioiodine therapy.     

Redifferentiation therapy with rosiglitazone in a case of differentiated thyroid cancer with pulmonary metastases and absence of radioiodine uptake

Treatment with radioiodine (RDI) has been shown to be an effective option in patients with differentiated thyroid cancer with recurrent or metastatic disease. However, in spite of having elevated levels of thyroglobulin in blood, in some of these patients, the whole body scan does not detect radioiodine uptake due to loss of differentiation of the neoplastic cells, thus leading to loss of efficacy of the treatment. That is why drugs with potential differentiating properties, like rosiglitazone or retinoids, are being studied. The aim of these drugs is to improve RDI uptake by the tumor cells. In this work, we have described the case of a patient in whom uptake of RDI by the pulmonary metastases, with subsequent decrease of their size, was achieved after treatment with rosiglitazone (8 mg/day for 2 months) as redifferentiation therapy.     

Scintigraphic evaluation of salivary gland dysfunction in patients with thyroid cancer after radioiodine treatment

PURPOSE: Sialadenitis is a well-recognized adverse effect of high-dose radioactive iodine treatment. This study was undertaken to determine whether Tc-99m pertechnetate salivary gland scintigraphy may be used for objective assessment of salivary gland function in patients with thyroid cancer treated with I-131. PATIENTS AND METHODS: The study group consisted of 71 patients (16 men, 55 women) with a mean age of 44 years (range, 16 to 73 years). Twenty-six (37%) patients were not given any radioiodine, and 18, 16, and 11 patients received doses of 100, 150, or 200 mCi (or higher), respectively. Parotid and submandibular glands were evaluated based on a four-grade scoring system. Correlation between the type of surgery, administered dose, time since therapy, subjective symptoms, and findings of salivary gland scintigraphy were evaluated. RESULTS: Subjective symptoms were questioned in 39 of the 45 patients who received radioactive iodine treatment. Fifty-four percent (21 of 39) of the patients reported xerostomia, of whom 86% (18 of 21) showed salivary gland dysfunction. Objective salivary gland dysfunction was observed in 69% (31 of 45) of patients. In 81% of the patients, the parotid glands were affected; in 13% of the patients, the submandibular glands were affected; and in 6%, both were affected ( < 0.000001). The frequency of salivary gland dysfunction showed a dose dependence to cumulative activity ( = 0.007). A greater complication rate was observed in patients with total thyroidectomy compared with subtotal surgery, although the correlation was not significant ( = 0.625). CONCLUSIONS: Parenchymal damage to the salivary glands induced by radioactive iodine treatment can be evaluated by salivary gland scintigraphy. The impairment is worse in the parotid glands and increases with the total dose.     

Guidelines for radioiodine therapy of differentiated thyroid cancer

Introduction  The purpose of the present guidelines on the radioiodine therapy (RAIT) of differentiated thyroid cancer (DTC) formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians and other members of the DTC-treating community on how to ablate thyroid remnant or treat inoperable advanced DTC or both employing large 131-iodine (¹³¹I) activities. Discussion  For this purpose, recommendations have been formulated based on recent literature and expert opinion regarding the rationale, indications and contraindications for these procedures, as well as the radioiodine activities and the administration and patient preparation techniques to be used. Recommendations also are provided on pre-RAIT history and examinations, patient counselling and precautions that should be associated with ¹³¹I iodine ablation and treatment. Furthermore, potential side effects of radioiodine therapy and alternate or additional treatments to this modality are reviewed. Appendices furnish information on dosimetry and post-therapy scintigraphy.     

Testicular function after radioiodine therapy for thyroid carcinoma

Radiotherapy can cause infertility in both men and women. However, few data are available concerning the effects of radioiodine therapy for thyroid carcinoma on testicular function. We investigated 25 men (age 23–73 years) with differentiated thyroid carcinoma in a longitudinal prospective trial. Follicle-stimulating hormone (FSH), inhibin B, luteinising hormone (LH) and testosterone were measured before (n=25) and 3 months (n=11), 6 months (n=18), 12 months (n=22), and 18 months (n=18) after radioiodine therapy [radioiodine dose (mean ± SEM): 9.8±0.89 GBq]. Before therapy, FSH was 5.4±0.77 IU/l; it increased significantly (P<0.001) to 21.3±2.4 IU/l after 6 months and fell to 7.4±1.3 IU/l after 18 months (normal range: 1.8– 9.2 IU/l). Inhibin B was significantly decreased (P<0.001) from 178±25.3 pg/ml before therapy to 22.2±5.5 pg/ml after 3 and 29.4±5.7 pg/ml after 6 months and rose to 154±23.3 pg/ml after 18 months (normal range 75– 350 pg/ml). LH and testosterone were within the normal range during the whole study (1.6–9.2 IU/l and 10.4–34.7 nmol/l, respectively). LH was significantly increased (P<0.001) from 2.8±0.33 IU/l before therapy to 5.9±0.69 IU/l 6 months after therapy and then fell slowly to 4.0±0.45 IU/l after 18 months. Total testosterone was significantly increased (P<0.01) from 12.8±0.99 nmol/l at baseline to 19.8±1.7 nmol/l after 12 months and 19.6±1.7 nmol/l after 18 months. The testosterone/LH ratio (normal range: 3.3–17.9 nmol/IU) fell from 5.8±0.66 nmol/IU to 3.0±0.36 nmol/IU after 3 months (P<0.01); it remained close to the latter value after 6 months (3.4±0.49 nmol/IU) and then rose to 5.5± 0.6 nmol/IU after 18 months. In conclusion, 3 and 6 months after radioiodine therapy all patients showed elevated FSH and decreased inhibin B levels, reflecting severely impaired spermatogenesis. At the same time a compensated insufficiency of the Leydig cell function was observed. Eighteen months after the last radioiodine therapy, mean values of gonadal function had completely recovered. Received 5 October and in revised form 27 December 1999     

Testicular function after radioiodine therapy for thyroid carcinoma

Radiotherapy can cause infertility in both men and women. However, few data are available concerning the effects of radioiodine therapy for thyroid carcinoma on testicular function. We investigated 25 men (age 23-73 years) with differentiated thyroid carcinoma in a longitudinal prospective trial. Follicle-stimulating hormone (FSH), inhibin B, luteinising hormone (LH) and testosterone were measured before (n = 25) and 3 months (n = 11), 6 months (n = 18), 12 months (n = 22), and 18 months (n = 18) after radioiodine therapy [radioiodine dose (mean +/- SEM): 9.8+/-0.89 GBq]. Before therapy, FSH was 5.4+/-0.77 IU/l; it increased significantly (P<0.001) to 21.3+/-2.4 IU/l after 6 months and fell to 7.4+/-1.3 IU/l after 18 months (normal range: 1.8-9.2 IU/l). Inhibin B was significantly decreased (P<0.001) from 178+/-25.3 pg/ml before therapy to 22.2+/-5.5 pg/ml after 3 and 29.4+/-5.7 pg/ml after 6 months and rose to 154+/-23.3 pg/ml after 18 months (normal range 75-350 pg/ml). LH and testosterone were within the normal range during the whole study (1.6-9.2 IU/l and 10.4-34.7 nmol/l, respectively). LH was significantly increased (P<0.001) from 2.8+/-0.33 IU/l before therapy to 5.9+/-0.69 IU/l 6 months after therapy and then fell slowly to 4.0+/-0.45 IU/l after 18 months. Total testosterone was significantly increased (P<0.01) from 12.8+/-0.99 nmol/l at baseline to 19.8+/-1.7 nmol/l after 12 months and 19.6+/-1.7 nmol/l after 18 months. The testosterone/LH ratio (normal range: 3.3-17.9 nmol/IU) fell from 5.8+/-0.66 nmol/IU to 3.0+/-0.36 nmol/IU after 3 months (P<0.01); it remained close to the latter value after 6 months (3.4+/-0.49 nmol/IU) and then rose to 5.5+/-0.6 nmol/IU after 18 months. In conclusion, 3 and 6 months after radioiodine therapy all patients showed elevated FSH and decreased inhibin B levels, reflecting severely impaired spermatogenesis. At the same time a compensated insufficiency of the Leydig cell function was observed. Eighteen months after the last radioiodine therapy, mean values of gonadal function had completely recovered.     

Enhanced radioiodine uptake in a patient with poorly differentiated papillary thyroid cancer after treatment with rosiglitazone

The effect of pretreatment with the peroxisome proliferator-activated receptor (PPAR) agonist, rosiglitazone, on radioiodine uptake and serum thyroglobulin levels in a patient with radioiodine-resistant papillary thyroid cancer is described. Treatment with rosiglitazone resulted in enhanced radioiodine uptake in areas of presumed metastatic disease in the neck that were previously only faintly seen, and serum thyroglobulin fell from a pretreatment level of 41 ng/mL to less than 2 ng/mL.     

Results of radioiodine therapy in 47 patients with distant metastases of differentiated thyroid carcinoma

In the last ten years, 47 patients with distant metastases of differentiated thyroid carcinoma have been treated with 131I following total thyroidectomy. Post-therapy whole body 131I scans revealed detectable uptake in the metastatic lesions in 23 (62%) of 37 patients with lung metastases, 10 (67%) of 15 patients with bone metastases five (71%) of seven patients with mediastinal metastases, and neither of two patients with brain metastases. The concentration of 131I in the metastases was significantly correlated with serum T3 and T4 concentrations, and inversely correlated with serum TSH concentrations. Most of the patients with a strong positive scan were euthyroid, suggesting that thyroid hormones produced by the tumor compensated for hypothyroidism following total thyroidectomy. There was no significant relationship between serum thyroglobulin concentration during T4 replacement therapy and 131I uptake or the efficacy of therapy. Twenty patients with lung (54%), five with bone (33%), two with mediastinal (29%), and none with brain metastases showed tumor regression after treatment. Significantly increased 131I uptake in lung metastases, better therapeutic results and better prognosis were demonstrated in young patients. In conclusion, age, 131I whole body scanning and serum thyroid hormone concentrations are considered to be useful in predicting the efficacy of 131I treatment for distant metastases, especially in the lung.     

A dose-effect correlation for radioiodine ablation in differentiated thyroid cancer

Purpose

The aim of this study was to determine the range of absorbed doses delivered to thyroid remnants, blood, and red marrow from fixed administrations of radioiodine and to ascertain whether the success of ablation is more dependent on these absorbed doses than on the administered activity.

Methods

Twenty-three patients received 3,000 MBq radioiodine following near-total thyroidectomy. The maximum absorbed dose to remnants was calculated from subsequent single photon emission tomography scans. Absorbed doses delivered to blood and red marrow were calculated from blood samples and from whole-body retention measurements. The protein bound iodine (PBI) was also calculated.

Results

Maximum absorbed doses to thyroid remnants ranged from 7 to 570 Gy. Eighteen of the 23 patients had a successful ablation. A significant difference was seen between the absorbed doses delivered to thyroid remnants, blood, and red marrow for those patients that had a successful ablation compared to those with a failed ablation (p?=?0.030, p?=?0.043 and p?=?0.048, respectively). The difference between the PBI values acquired at day 1 and day 6 were also indicative of response (p?=?0.074).

Conclusions

A successful ablation is strongly dependent on the absorbed dose to the thyroid remnant. Dosimetry-based personalized treatment can prevent both sub-optimal administrations, which entails further radioiodine therapy, and excessive administration of radioactivity, which increases the potential for radiation toxicity.     

Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer?

Salivary gland dysfunction is one of the common side effects of high-dose radioiodine therapy for thyroid cancer. The purpose of this study was to determine whether an early start of sucking lemon candy decreases salivary gland injury after radioiodine therapy. METHODS: The incidence of the side effects of radioiodine therapy on the salivary glands was prospectively and longitudinally investigated in 2 groups of patients with postsurgical differentiated thyroid cancer with varying regimens for sucking lemon candy. From August 1999 to October 2000, 116 consecutive patients were asked to suck 1 or 2 lemon candies every 2-3 h in the daytime of the first 5 d after radioiodine therapy (group A). Lemon candy sucking was started within 1 h after radioiodine ingestion. From November 2000 to June 2002, 139 consecutive patients (group B) were asked to suck lemon candies in a manner similar to that of group A. In the group B, lemon candies were withheld until 24 h after the ingestion of radioiodine. Patients with salivary gland disorders, diabetes, collagen tissue diseases, or a previous history of radioiodine therapy or external irradiation to the neck were excluded. Thus, 105 patients in group A and 125 patients in group B were available for analysis. There were no statistical differences in the mean age (55.2 y vs. 58.5 y), average levels of serum free thyroxine (l-3,5,3',5'-tetraiodothyronine) (0.40 ng/dL vs. 0.47 ng/dL), and the mean dose of (131)I administered (3.96 GBq vs. 3.87 GBq) between the 2 groups. The onset of salivary side effects was monitored during hospital admission and regular follow-up on the basis of interviews with patients, a visual analog scale, and salivary gland scintigraphy using (99m)Tc-pertechnetate. When a patient showed a persistent (>4 mo) dry mouth associated with a nonfunctioning pattern on salivary gland scintigraphy, a diagnosis of xerostomia was established. RESULTS: The incidences of sialoadenitis, hypogeusia or taste loss, and dry mouth with or without repeated sialadenitis in group A versus group B were 63.8% versus 36.8% (P < 0.001), 39.0% versus 25.6% (P < 0.01), and 23.8% versus 11.2% (P < 0.005), respectively. Permanent xerostomia occurred in 15 patients in group A (14.3%) and 7 patients in group B (5.6%) (P < 0.05). In both groups, bilateral involvement of the parotid gland was the most frequently seen and was followed by bilateral involvement of the submandibular gland. CONCLUSION: An early start of sucking lemon candy may induce a significant increase in salivary gland damage. Lemon candy should not be given until 24 h after radioiodine therapy.     

Outcome after radioiodine therapy in 107 patients with differentiated thyroid carcinoma and initial bone metastases: side-effects and influence of age

Initial bone metastases in patients with differentiated thyroid carcinoma are rare, especially in younger patients. Long duration of therapy and high activities of radioiodine are often necessary to induce remission of metastatic disease. The curative potential of radioiodine therapy, in particular in younger patients, has not yet been determined. In this retrospective study we evaluated the therapeutic outcome, total radioiodine activities and associated side-effects in 107 patients with initial bone metastases. Eight of the 107 patients were younger than 45 (37.5+/-7.3) years, and were classified as group 1 (stage II, "low risk", WHO classification). The remaining 99 patients were older than 45 (64.1+/-9.5) years, and formed group 2 (stage IV, "high risk", WHO classification). Total or partial remission was more frequently achieved in group 1 than in group 2 (62.5% vs 49.5%). Lower activities were needed in group 1 (18.89+/-15.08 GBq vs 41.97+/-31.25 GBq), and there were less marked alterations in the blood count in this group. In group 1, blood count alterations reached only grade I or II (WHO classification), whereas grade III and grade IV alterations as well as acute leukaemia were observed in group 2. In group 1, complete remission was achieved with radioiodine therapy (11.1 GBq) in three out of four patients with < or =3 bone metastases. Additional pulmonary metastases (present in 44 out of 107 patients) did not influence prognosis. We conclude that initial bone metastases in differentiated thyroid carcinoma can be treated with curative intent by means of radioiodine therapy, and that this approach has a particularly realistic chance of success in younger patients and those with a small number of metastases.