The management protocol for differentiated thyroid cancer includes whole body iodine-131 imaging, to detect residual thyroid tissue and distant metastasis, after thyroidectomy. However, the diagnostic dose of radioiodine may fail to detect the non-functioning or poorly functioning metastasis. We present a case where hybrid single photon-emission computed tomographic and computed tomographic (SPECT-CT) fusion imaging, using a diagnostic dose of iodine-131, was able to detect both functioning as well as non-functioning pulmonary metastases, prior to high-dose radioiodine therapy.
Carcinoma; hybrid imaging; iodine-131; SPECT-CT; thyroid
Background & objectives:
Radioiodine (131I) or radioactive iodine in low doses is used worldwide as the first line of management in the treatment of hyperthyroidism. Information is available on the extent and severity of cell damage after a high dose radioiodine (131I) therapy for thyroid cancer, but information is scanty on its cellular effects, its extent and severity of cell damage after a low dose 131I therapy. The present investigation was aimed to study the cytotoxic effects of a low dose 131I therapy in varying doses as is normally being used in routine clinical practice in the treatment of various forms of hyperthyroidism.
Peripheral blood lymphocytes were analyzed in 32 hyperthyroid patients. All of them received
131I in the form of sodium iodide solution orally. Blood lymphocytes were studied for the presence of chromosomal aberrations (CA) and micro nucleus (MN) using micronucleus assay. Blood samples of these patients were drawn prior to the treatment, on 7
thdays after the treatment.
The results indicated a positive relationship between 131I dose, CA and MN frequency. A statistically significant increase in CA and MN frequency in day 7 post- therapy and a decrease in mean levels of CA and MN on day 30 post-therapy were observed when compared to pre-therapy.
Interpretation & conclusions:
This study showed that the cytogenetic damage induced by
131I in low doses i.e., less than 555MBq was minimal and reversible. Patients can be motivated to undertake this safe and easy procedure as a first line of therapy in the treatment of hyperthyroidism.
chromosomal aberrations; hyperthyroidism; low dose 131I therapy; micronucleus assay
We evaluated the relationship between thyroid remnant size following thyroidectomy for differentiated thyroid carcinoma and surgical volume and specialisation by assessing pre-ablation radioiodine-131 (131I) thyroid bed uptake (TBU) scanning as a surrogate for residual thyroid tissue.
We analysed data of 651 patients in our thyroid cancer database. Patients' data were included if the following criteria were met: (1) diagnosis of differentiated thyroid carcinoma, (2) total or near-total thyroidectomy, (3) pre-ablation 131I scan prior to radioiodine ablation (RAI), (4) no distant metastasis, and (5) >3,000 MBq ablative dose of 131I. 131I diagnostic whole-body scans and measurement of thyroglobulin levels were carried out 3-9 months after RAI. 305 patients were included in the final analysis.
Four endocrine, 19 otolaryngology and 25 general surgeons performed thyroidectomies with median pre-ablation 131I TBU values of 1.0, 1.8 and 2.9%, respectively (p = 0.0031). There was a statistically significant relationship between number of thyroidectomies performed and median pre-ablation 131I TBU values up to the optimal number of 11 operations beyond which there was no further significant difference between surgeons. There were differences in remnant size between endocrine and general surgeons (p = 0.001), otolaryngology and general surgeons (p = 0.023) but not between endocrine and otolaryngology surgeons (p = 0.167).
Using the pre-ablation 131I uptake scan as a surrogate for thyroid remnant quantification following thyroidectomy demonstrates the relationship between the surgical volume and size of thyroid remnant. The study also demonstrated beneficial effects of specialisation with specialist surgeons achieving the smallest thyroid remnant.
Thyroid cancer; Surgeon volume; Thyroid remnant;
Pre-ablation radioiodine scan; Surgical specialisation
The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi 131I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of 131I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind.
Acute myeloid leukaemia; Myeloid sarcoma of the uterine cervix; Radioiodine therapy
Objective: The aim of the present study was to evaluate the outcome of radioiodine treatment in thyrotoxicosis in childhood and adolescence.
Methods: This was a retrospective study of 27 patients (ages 7.2- 19.8 years) with a diagnosis of thyrotoxicosis who received iodine-131 (I-131) treatment from January 2007 to December 2011 in the Nuclear Medicine Division, Department of Radiology, Faculty of Medicine, Chiang Mai University. Gender, duration of antithyroid drug (ATD) treatment, 24-hour I-131 uptake, thyroid weight, total dose and number of treatments with I-131, and thyroid status at 6 months after treatment were recorded.
Results: The outcomes of 27 patients (85.2% female, 14.8% male) treated with radioactive iodine were analyzed to assess the effectiveness of therapy as related to dose and gland size. All children and adolescents received 150 µCi of I-131/g of thyroid tissue (n=27). Six 6 months after treatment, 44.5% of the patients were hyperthyroid, 14.8% were euthyroid, and 40.7% were hypothyroid. Of the 12 cases with hyperthyroidism, 2 cases needed a second dose of I-131 treatment, and they finally reached a hypothyroid state. The patients were classified into 2 groups according to treatment success (euthyroid and hypothyroid) and treatment failure (hyperthyroid). There were no significant differences in age, gender, duration of ATD treatment, 2- and 24-hour I-131 uptake, thyroid weight, and total I-131 dose between these two groups.
Conclusions: Radioiodine treatment is safe and effective for thyrotoxicosis in childhood and adolescence. It is suitable as a good second-line therapy for patients with severe complications, those who show poor compliance, and those who fail to respond to ATD treatment. .
Conflict of interest:None declared.
Radioiodine treatment; thyrotoxicosis; children; adolescence; outcome
It is possible to safely lower the basal metabolism of patients suffering from severe cardiac disease by administering multiple small doses of radioiodine in order to achieve symptomatic relief.
From the present study, multiple small doses of I131 appeared to be as effective as single or multiple large doses of this material and complications such as thyroiditis, temporary thyrotoxicosis and bone marrow depression were almost always avoided. No damage to the parathyroid glands or the recurrent laryngeal nerve was observed. No radiation sickness developed after therapy.
A scintigram of the thyroid gland was useful in determining the size, shape and function of the thyroid gland before and during radioiodine treatment and helped to determine the need for additional treatment. In order to prevent the distressing symptoms of the myxedema state, desiccated thyroid was administered when necessary.
In the series of 278 euthyroid patients with severe cardiac disease who were treated with radioactive iodine, results were excellent in 35 per cent of cases and good in 44 per cent. In 21 per cent there was no improvement.
Ablative approaches using radioiodine are increasingly proposed for the treatment of Graves′ disease (GD) but their ophthalmologic and biological autoimmune responses remain controversial and data concerning clinical and biochemical outcomes are limited. The aim of this study was to evaluate thyroid function, TSH-receptor antibodies (TRAb) and Graves′ ophthalmopathy (GO) occurrence after radioiodine thyroid ablation in GD. We reviewed 162 patients treated for GD by iodine-131 (131I) with doses ranging from 370 to 740 MBq, adjusted to thyroid uptake and sex, over a 6-year period in a tertiary referral center. Collected data were compared for outcomes, including effectiveness of radioiodine therapy (RIT) as primary endpoint, evolution of TRAb, and occurrence of GO as secondary endpoints. The success rate was 88.3% within the first 6 months after the treatment. The RIT failure was increased in the presence of goiter (adjusted odds ratio = 4.1, 95% confidence interval 1.4–12.0, P = 0.010). The TRAb values regressed with time (r = −0.147; P = 0.042) and patients with a favorable outcome had a lower TRAb value (6.5 ± 16.4 U/L) than those with treatment failure (23.7 ± 24.2 U/L, P < 0.001). At the final status, 48.1% of patients achieved normalization of serum TRAb. GO occurred for the first time in 5 patients (3.7%) who were successfully cured for hyperthyroidism but developed early and prolonged period of hypothyroidism in the context of antithyroid drugs (ATD) intolerance (P = 0.003) and high TRAb level (P = 0.012). On the basis the results of this study we conclude that ablative RIT is effective in eradicating Graves’ hyperthyroidism but may be accompanied by GO occurrence, particularly in patients with early hypothyroidism and high pretreatment TRAb and/or ATD intolerance. In these patients, we recommend an early introduction of LT4 to reduce the duration and the degree of the radioiodine-induced hypothyroidism.
Autoimmunity; Graves’ disease; ophthalmopathy; radioiodine therapy
Low iodine diet (LID) is recommended in patients with differentiated thyroid cancer before radioiodine administration. Patients with increased thyroglobulin (Tg) level, but negative 131I whole body scan present diagnostic and therapeutic dilemma. This study was designed to evaluate the benefit of a two-week LID in patients with elevated serum Tg levels and negative 131I whole body scans.
Patients and methods.
For the impact assessment of two-week LID on radioiodine tissue avidity, radioiodine scans before and after LID were compared. Sixteen patients with serum Tg > 2 μg/L, negative Tg-antibodies, and negative radioiodine scans underwent two-week LID before the 131I administration. Fourteen patients underwent diagnostic scanning and two patients received radioiodine therapy. Iodine concentration in the morning urine specimens were measured in each patient, a day before and 15th day after starting LID.
Following self-managed LID, patients were able to significantly reduce their iodine body content by 50% (range 28–65%, p<0,001). 13 patients (82%) accomplished mild iodine deficiency (50-99 μg/L) and one patient (6%) achieved targeted moderate iodine deficient state (<50 μg/L). All diagnostic post-LID scans were negative. Both post-therapy 131I scans showed radioiodine accumulation outside of normal 131I distribution (neck region and diffuse hepatic uptake). This study demonstrated that two-week LID is effective way to decrease total body iodine content, although without a visible effect on post-LID diagnostic 131I scans.
A more stringent dietary protocol and longer iodine restriction period are probably needed to achieve targeted moderate iodine deficiency in patients preparing for 131I administration. This might result in higher radioiodine avidity of thyroid remnant/metastases.
low iodine diet; urine iodine concentration; differentiated thyroid cancer; radioiodine
Malignant struma ovarii is a rare malignant germ cell tumor of the ovary. Due to the rarity of this disease, treatment has not been uniform throughout the published literature.
We present three cases of malignant struma ovarii. Following primary surgery, all were subsequently treated with thyroidectomy and 131I ablation therapy, two patients as first line management, one following the occurrence of metastatic disease.
Histological diagnosis of malignant struma ovarii is similar to that of well differentiated thyroid carcinoma (WDTC). In line with the latest advice on treatment of WDTC, we believe that the best option for patients with malignant struma ovarii is surgical removal of the ovarian lesion followed by total thyroidectomy which allows the exclusion of primary thyroid carcinoma, and in addition, allows radioiodine (131I) ablation therapy for (micro) metastasis. After thyroidectomy, thyroglobulin can be used as a tumor marker for follow-up. Moreover, nuclear medicine imaging using radioiodine (123I) can be performed to demonstrate metastatic carcinoma. A multidisciplinary approach is essential.
malignant struma ovarii; radioiodine therapy; thyroidectomy; germ cell tumors; multidisciplinary approach
Sorafenib can be considered as the effective option of treatment in patients with metastatic radioiodine refractory differentiated thyroid cancers. The cutaneous manifestations of Sorafenib include rash, desquamation, hand foot skin reactions, pruritus, alopecia and erythema. We report the first case of hypopigmentation related to sorafenib therapy.
We report the case of a middle aged gentleman with metastatic papillary carcinoma of thyroid diagnosed in 2005. He was managed with total thyroidectomy, radioactive iodine and TSH suppressive therapy. Despite receiving radioactive iodine 530 mci cumulative dose, patient had persistant disease with lung metastasis. Therefore a TKI, sorafenib, was started. He developed hypopigmentation of the skin more prominent on face six weeks after starting sorafenib treatment.He also developed diarrhea, desquamation of hands and feet, hair loss over scalp, eye brows and moustache. Sorafenib treatment was discontinued. His diarrhea stopped in one week and after four weeks his skin became normalized whereas he regained his hairs in six weeks.
To our knowledge, hypopigmentation in our patient appears to be the first reported of its kind in the literature to date. Sorafenib is used in Renal cell carcinoma, Hepatcellular carcinoma and radioactive iodine refractory thyroid carcinoma therefore it is very important to be aware of hypopigmentation as a potential side effect for both physicians and patients.
Thyroid Carcinoma; Sorafenib; Hypopigmentation
There is no ideal treatment for benign multinodular goitre. Besides surgery, which is recommended for large goitres or when malignancy cannot be excluded, the non-surgical treatment options are levothyroxine therapy and radioiodine (131I) therapy. Conventional 131I therapy [without recombinant human thyroid-stimulating hormone (rhTSH)] has been used for more than a decade in symptomatic non-toxic multinodular goitre, and although it does lead to significant thyroid volume reduction, relatively high activities of radioiodine are needed because of a frequent finding of a low thyroid radioiodine uptake. rhTSH, even when used in very small doses in combination with 131I therapy, enhances the thyroid volume reduction at lower 131I activities by doubling the thyroid radioiodine uptake. However, before rhTSH stimulation can be routinely used by clinicians to optimise the 131I therapy in multinodular goitre, aspects of this association, such as the cost-benefit and optimum rhTSH dose and safety, will have to be sufficiently clarified.
Background: Ablative radioiodine-131 (131I) therapy is used in the standart treatment procedure of thyroid carcinoma and procedures using 131I represent the majority of Nuclear Medicine therapeutic procedures. The principal route of 131I excretion after the administration of 131I is the urine. Amifostine is an organic thiophosphate ester prodrug and the kidney concentrations of the active metabolite WR-1065 are about 100 times higher than tumour concentrations. To our knowledge, there is no published data in literature presenting acute effect of radioiodine on renal tissue during high dose I-131 radioiodine treatment (RIT). Additionally, it is not known whether amifostine takes role in this process.
Materials and Methods: In this study, 50 healthy female Wistar albino rats, weighing 200–250 g and averaging 16 weeks old were utilised. The rats were randomly divided into ten groups. 1- Sham group (n=5), 2- Amifostine group (n=5): rats pretreated with 1 cc amifostine (200 mg/kg) by intraperitoneal injection, 3- Radioactive iodine first day group (RI-1) (n=5): rats treated with 1 cc oral 185 MBq radioactive iodine-131 and sacrification performed after 1st day, 4- Amifostine + Radioactive iodine first day group (A+RI-1) (n=5): rats pretreated with amifostine (200 mg/kg) by intraperitoneal injection and rats treated with 5mCi radioactive iodine-131 and sacrification performed after 1st day. 5- Radioactive iodine third day group (RI-3) (n=5), 6- Amifostine + Radioactive iodine third day group (A+RI-3) (n=5), 7- Radioactive iodine fifth day group (RI-5) (n=5), 8- Amifostine + Radioactive iodine fifth day group (A+RI-5) (n=5), 9- Radioactive iodine seventh day group (RI-7) (n=5) and 10- Amifostine + Radioactive iodine seventh day group (A+RI-7) (n=5). The renal cast formation and tubular damage are evaluated by a pathologist in a blinded manner.
Results: Ablative radioiodine-131 therapy induced renal tubular damage was significantly higher in the radioactive iodine fifth day group (RI-5) when compared with the Sham group (p=0.01) and Amifostine group (p=0.01).
Conclusions: A marked ablative radioiodine-131 induced renal toxicity was seen at fifth day of the therapy after a single RIT application and the main histopathological change was tubular damage. Amifostine have protective effects against ablative radioiodine-131 therapy and this effect is significant at fifth day of the therapy.
amifostine; radioiodine therapy; renal toxicity
The aim of this study was to review the outcome of ablative radioiodine treatment on ovarian function in young women treated for differentiated thyroid carcinoma. Of 1398 patients with differentiated thyroid cancer, 496 were women under the age of 40 at the time of diagnosis who had received radioiodine therapy. Of these, 322 received a single 3 GBq ablation dose of radioiodine while the remainder received subsequent treatment with 131I with a cumulative activity of 8.5–59 GBq for residual, recurrent, or metastatic disease. Transient amenorrhoea or menstrual irregularities lasting up to 10 months were experienced in 83 patients (17%). No cases of permanent ovarian failure were recorded. There were 427 children born to 276 women; only one patient wishing to achieve a successful pregnancy outcome has been unsuccessful. Four premature births and 14 miscarriages occurred but no congenital abnormalities were reported. The risk of permanent damage to the ovaries after ablative radioiodine treatment appears to be low and patients can be reassured they can have normal pregnancies after this treatment.
Radioiodine (131I) is a critical component in the treatment of differentiated thyroid cancer. We recently saw a patient with thyroid cancer who was hesitant to take 131I treatment because he had previously encountered an allergic reaction to administration of iodine-containing radiocontrast agent for computed tomography (CT) scanning. We were able to administer 131I treatment after discussion that his anaphylactic reaction was not due to iodine and that radioiodine (131I) treatment is unlikely to cause a reaction in the patient.
An allergy to iodine itself does not exist.When patients claim that they have an ‘iodine allergy’, ask them what substances they are allergic to and what kind of reaction occurred during use of such substances.Radioactive iodine is not a contraindication for patients who claim an ‘allergy to iodine’.
Fifty patients with uncomplicated Graves' disease were treated with radioactive iodine (I131). Twenty-six patients who were followed for one year or longer are the basis of this report. Twenty-five are now euthyroid; only one is not completely well.
The total dose of radioiodine administered varied from 0.5 to 10 millicuries. The average length of time necessary for return to a euthyroid state was from three to four months.
Hypometabolism developed in three patients, and in one the signs and symptoms of myxedema developed. No other complications ensued. One patient who apparently relapsed had complete return to normal after further iodine administration.
The determination of the uptake of radioactive iodine by the thyroid gland is a useful diagnostic procedure in differentiating conditions simulating hyperthyroidism.
Following treatment with radioactive iodine, the thyroid gland becomes smaller, the uptake of iodine by the gland is reduced, and the level of organic iodine in the plasma becomes normal.
In acute thyroiditis, in spite of a high basal metabolic rate, high content of organic iodine in the plasma and other evidences of “hyperthyroidism,” the uptake of I131 has been very low.
Metastatic thyroid cancers that are refractory to radioiodine (iodine-131) are associated with a poor prognosis. In mouse models of thyroid cancer, selective mitogen-activated protein kinase (MAPK) pathway antagonists increase the expression of the sodium–iodide symporter and uptake of iodine. Their effects in humans are not known.
We conducted a study to determine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. After stimulation with thyrotropin alfa, dosimetry with iodine-124 positron-emission tomography (PET) was performed before and 4 weeks after treatment with selumetinib (75 mg twice daily). If the second iodine-124 PET study indicated that a dose of iodine-131 of 2000 cGy or more could be delivered to the metastatic lesion or lesions, therapeutic radioiodine was administered while the patient was receiving selumetinib.
Of 24 patients screened for the study, 20 could be evaluated. The median age was 61 years (range, 44 to 77), and 11 patients were men. Nine patients had tumors with BRAF mutations, and 5 patients had tumors with mutations of NRAS. Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients with BRAF mutations and 5 of 5 patients with NRAS mutations). Eight of these 12 patients reached the dosimetry threshold for radioiodine therapy, including all 5 patients with NRAS mutations. Of the 8 patients treated with radioiodine, 5 had confirmed partial responses and 3 had stable disease; all patients had decreases in serum thyroglobulin levels (mean reduction, 89%). No toxic effects of grade 3 or higher attributable by the investigators to selumetinib were observed. One patient received a diagnosis of myelodysplastic syndrome more than 51 weeks after radioiodine treatment, with progression to acute leukemia.
Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. (Funded by the American Thyroid Association and others; ClinicalTrials.gov number, NCT00970359.)
With the recent increase in incidence of thyroid cancer, non-hospitalized low-dose (NH-LD) radioiodine treatment (RIT) has also increased rapidly. The radioactivity limit that is allowed to be administered without hospitalization depends on individual calculation, based partly on patients’ behavior. In this study, Korean patients’ behavior in relation to radiation safety in NHLD RIT was surveyed.
A total of 218 patients who underwent NH-LD RIT of 1.1 GBq 131I in a single center were surveyed. The patients underwent RIT with a standard protocol and the survey was performed by interview when they visited subsequently for a whole-body scan. The survey questionnaire included three parts of questions: general information, behavior relating to isolation during RIT, and awareness of radiation safety.
After administration of radioiodine, 40% of patients who returned home used mass transportation, and another 47% went home by taxi or in car driven by another person. Isolation at home was generally sufficient. However, 7% of patients did not stay in a separate room. Among the 218 patients, 34% did not go home and chose self-isolation away from home, mostly due to concerns about radiation safety of family members. However, the places were mostly public places, including hotels, resorts, and hospitals. About half of the patients replied that access to radiation safety information was not easy and their awareness of radiation safety was not satisfactory. As a result, 45% of patients wanted hospitalized RIT.
In many countries, including Korea, RIT is continuously increasing. Considering the radiation safety of patients’ family members or the public and the convenience of patients, the pretreatment education of patients should be enhanced. In addition, the hospitalization of patients having low-dose therapy is recommended to be seriously considered and expanded, with the expansion of dedicated treatment facilities.
Thyroid cancer; Radioiodine treatment; Behavior; Radiation safety; Hospitalization
Renal metastases from thyroid carcinoma are very rare, late recurrences of papillary thyroid carcinomas (PTC) are not reported in literature and there is no universal recommendation for optimum duration of follow-up of thyroid carcinoma. We present herein a case of late renal recurrence of follicular variant PTC (FV-PTC). This study is a case report of renal metastasis revealing a late recurrence of FV-PTC. An 81-year-old woman with previously treated FV-PTC 24 years ago by total thyroidectomy, lymph nodes dissection and radioiodine therapy presented with sudden gross-hematuria. Computerized tomography scan (CT-scan) revealed a 70-mm right renal mass and histological diagnosis after nephrectomy demonstrated recurrence of FV-PTC with a positive thyroglobulin immunostaining. Despite of 131I-radioiodine therapy postoperatively, the serum thyroglobulin (Tg) increased and positron emission tomography combined to CT-scan showed 4 years later, an abdominal lymph node and distant metastases. Now the patient is alive but her general condition is too poor for systemic adjuvant therapy. This case illustrates the need of prolonged follow-up after surgery of high-risk FV-PTC.
Late recurrence; renal metastasis; thyroid carcinoma
Radioactive iodine has been used for more than 50 years for the treatment of thyroid diseases. Differentiated thyroid cancers have the ability to trap iodine. Therefore, radioiodine can be used both diagnostically and therapeutically. In the follow-up of patients, it is critical to interpret radioiodine scans correctly.
Non-physiological Iodine-131 (I-131) extra-thyroidal uptake detected on post-therapy or diagnostic I-131 scanning are not always interpreted as functioning metastatic thyroid cancer.
This study provides detailed information and case samples of radiodine contamination artifacts and non-physiological, non-metastatic extra-thyroidal I-131 accumulation in whole-body I-131 imaging.
Thyroid Cancer; Radioiodine Scan; False Positive
Radioiodine is a routine therapy for differentiated thyroid cancers. Non-thyroid cancers may be treated with radio-iodine following transfection with the human sodium/iodide symporter (hNIS) gene. The glial fibrillary acidic protein (GFAP) promoter is an effective tumor-specific promoter for gene expression and thus may be useful in targeted gene therapy of malignant glioma. The present study used GFAP promoter-modulated expression of the hNIS gene in an experimental model of radioiodine-based treatment for malignant glioma. Cells were transfected using a recombination adeno-virus and evaluated in cells by studying the transfected transgene expression through western blot analysis, 125I uptake and efflux, clonogenicity following 131I treatment and radioiodine therapy using a U87 xenograft nude mouse model. Following transfection with the hNIS gene, the cells showed 95–70-fold higher 125I uptake compared with the control cells transfected with Ad-cytomegalovirus (CMV)-enhanced green fluorescent protein (EGFP). The western blotting revealed bands of ∼70, 49 and 43 kDa, consistent with the hNIS, GFAP and β-actin proteins. The clonogenic assay indicated that, following exposure to 500 μCi of 131I-iodide for 12 h, >90% of cells transfected with the hNIS gene were killed. Ad-GFAP-hNIS-transfected and 2 mCi 131I-injected U87 xenograft nude mice survived the longest of the three groups. The hNIS-expressing tumor tissue accumulated 99mTcO4 rapidly within 30 min of it being intraperitoneally injected. The experiments demonstrated that effective 131I therapy was achieved in the malignant glioma cell lines following the induction of tumor-specific iodide uptake activity by GFAP promoter-directed hNIS gene expression in vitro and in vivo. 131I therapy retarded Ad-GFAP-hNIS transfected-tumor growth following injection with 131I in U87 xenograft-bearing nude mice.
malignant glioma; sodium iodide symporter; glial fibrillary acidic protein promoter; radioiodine therapy
Hypercalcaemia is a recognised complication of hypothyroidism. We describe three patients who developed hypercalcaemia after thyroidectomy when thyroid supplements were discontinued. They were treated with thyroxine, dihydrotachysterol, and calcium after operation, and in all three cases serum calcium concentrations remained constant during combined treatment. Thyroxine treatment was discontinued several weeks before a radioiodine scan was performed; dihydrotachysterol and calcium were continued throughout. Serum calcium concentrations rose to hypercalcaemic levels in all cases. Elimination of dihydrotachysterol from plasma may be delayed in hypothyroidism, resulting in hypervitaminosis D. It is advisable to reduce the dose of dihydrotachysterol and to check serum calcium concentrations regularly in patients whose thyroid treatment is interrupted.
The overall survival rate of non-radioiodine avid differentiated (follicular, papillary, medullary) thyroid carcinoma is significantly lower than for patients with iodine-avid lesions. The purpose of this study was to evaluate toxicity and efficacy (response and survival) of peptide receptor radionuclide therapy (PRRT) in non-radioiodine-avid or radioiodine therapy refractory thyroid cancer patients. Sixteen non-radioiodine-avid and/or radioiodine therapy refractory thyroid cancer patients, including follicular thyroid carcinoma (n = 4), medullary thyroid carcinoma (n = 8), Hürthle cell thyroid carcinoma (n = 3), and mixed carcinoma (n = 1) were treated with PRRT by using 90Yttrium and/or 177Lutetium labeled somatostatin analogs. 68Ga somatostatin receptor PET/CT was used to determine the somatostatin receptor density in the residual tumor/metastatic lesions and to assess the treatment response. Hematological profiles and renal function were periodically examined after treatment. By using fractionated regimen, only mild, reversible hematological toxicity (grade 1) or nephrotoxicity (grade 1) were seen. Response assessment (using EORTC criteria) was performed in 11 patients treated with 2 or more (maximum 5) cycles of PRRT and showed disease stabilization in 4 (36.4%) patients. Two patients (18.2%) showed partial remission, in the remaining 5 patients (45.5%) disease remained progressive. Kaplan-Meier analysis resulted in a mean survival after the first PRRT of 4.2 years (95% CI, range 2.9-5.5) and median progression free survival of 25 months (inter-quartiles: 12-43). In non-radioiodine-avid/radioiodine therapy refractory thyroid cancer patients, PRRT is a promising therapeutic option with minimal toxicity, good response rate and excellent survival benefits.
Peptide radionuclide receptor therapy; non-radioiodine-avid; thyroid cancer; somatostatin receptors; survival analysis; 68Ga-DOTA-TOC; 68Ga-DOTA-TATE; positron emission tomography (PET)
Radioiodine (131I) therapy is widely accepted as an essential part of therapeutic regimens in many cases of differentiated thyroid cancer. Radiation-induced oxidative damage to macromolecules is a well known phenomenon. Frequently examined process to evaluate oxidative damage to macromolecules is lipid peroxidation (LPO), resulting from oxidative damage to membrane lipids. The aim of the study was to examine serum LPO level in hypothyroid (after total thyroidectomy) cancer patients subjected to ablative activities of 131I.
Materials and methods
The study was carried out in 21 patients (18 females and 3 males, average age 52.4 ± 16.5 years) after total thyroidectomy for papillary (17 patients) or follicular (4 patients) thyroid carcinoma. Hypothyroidism was confirmed by increased TSH blood concentration (BRAHMS, Germany), measured before 131I therapy. Activity of 2.8 - 6.9 GBq of 131I was administered to the patients orally as sodium iodide (OBRI, Poland). Concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), as an index of LPO (LPO-586 kit, Calbiochem, USA), were measured in blood serum just before 131I administration (day "0") and on the days 1-4 after 131I therapy. Sera from 23 euthyroid patients served as controls. Correlations between LPO and TSH or 131I activity were calculated.
Expectedly, serum LPO level, when measured before 131I therapy, was several times higher (p < 0.00001) in cancer patients than in healthy subjects, which is probably due to hypothyroidism caused by total thyroidectomy. However, we did not observe any differences between LPO levels after and before 131I therapy. LPO did not correlate with TSH concentration. In turn, negative correlation was found between 131I activity and LPO level on the day "2" after radioiodine treatment.
Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids, at least early, after therapy.
The pathogenesis of Graves' orbitopathy (GO) remains unknown. The hypothesis of a causal relationship between autoimmunity against the TSH receptor (TSHR) and GO is supported by clinical studies. Radioiodine treatment is associated with worsening or new onset of GO, possibly via antigen shedding or by inducing hypothyroidism. The coexistence of thyroid cancer with Graves' disease (GD) and GO is rare. Here we report 3 cases of reactivation of GO in patients who underwent treatment with recombinant human TSH (rhTSH) and radioiodine ablation. In each case, a thyroidectomy was performed to treat the GD, and an incidental thyroid cancer was discovered. In all 3 cases, reactivation of GO was observed 3–6 weeks after administration of rhTSH, despite maintaining euthyroidism, which was unaccompanied by a rise in serum TSHR antibodies after radioiodine and despite steroids in 1 of the 3 patients. These observations suggest that binding of either TSH or TSHR antibodies to the TSHR, independently of thyroid status, may be causally related to deterioration of GO. Clinicians should be aware of a possible association between rhTSH administration and reactivation of GO, which should be taken into account before prescribing rhTSH in patients with GO. Prophylactic steroids may need to be considered for patients at high risk of exacerbation of GO.
Graves' orbitopathy; Thyroid cancer; Graves' disease; Radioiodine; Recombinant human TSH
Radioactive iodine is commonly administered following thyroidectomy for differentiated thyroid carcinoma to ablate the thyroid remnant. The optimal administered activity of radioiodine is unknown.
Adult subjects (n = 160) diagnosed with papillary or follicular thyroid carcinoma were randomly allocated to receive either 1100 MBq (30 mCi) or 3700 MBq (100 mCi) activity of radioiodine (131I) following thyroidectomy. The study participants were prepared for ablation using thyroid hormone withdrawal. Ablation was considered successful when serum thyroglobulin concentration was less than 1 ng/mL and no uptake was present in 131I scan. Ablation was successful following one administration of radioiodine in 42 (52%; 95% CI, 41% to 63%) of the 81 evaluable study participants who received 1100 MBq, and in 43 (56%, 45% to 67%) of the 77 subjects who received 3700 MBq activity (P = .61). There was no difference between the groups in the numbers of repeat radioiodine treatments needed to complete ablation (P = .27). The higher activity was associated with more nausea and taste disturbances, and a longer stay in a radioprotected isolation unit. None of the participants died from thyroid cancer during a median follow up of 51 months; three subjects in the 3700 MBq group and none in the 1100 MBq group were diagnosed with distant metastases during follow-up. In a meta-analysis of four randomized studies that compared the 1100 and 3700 MBq activities, the 1100 MBq activity tended to be associated with a higher risk of unsuccessful ablation (relative risk 1.148, 95% CI 0.974 to 1.353, P = .10).
The results provide no conclusive evidence that 3700 MBq activity is more effective for ablation of the thyroid remnant than 1100 MBq activity. The 3700 MBq activity is associated with more adverse effects.