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1.  Selumetinib-Enhanced Radioiodine Uptake in Advanced Thyroid Cancer 
The New England journal of medicine  2013;368(7):623-632.
Background
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.
Methods
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.
Results
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.
Conclusions
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.)
doi:10.1056/NEJMoa1209288
PMCID: PMC3615415  PMID: 23406027
2.  Metastatic Follicular Thyroid Carcinoma Secreting Thyroid Hormone and Radioiodine Avid without Stimulation: A Case Report and Literature Review 
Case Reports in Endocrinology  2014;2014:584513.
Introduction. This is an extremely rare case of a patient with metastatic follicular thyroid cancer who continued to produce thyroid hormone and was iodine scan positive without stimulation after thyroidectomy and radioiodine (I-131) therapy. Patient Findings. A 76-year-old Caucasian male was diagnosed with metastatic follicular thyroid carcinoma on lung nodule biopsy. Total thyroidectomy was performed and he was ablated with 160 mCi of I-131 after recombinant human thyrotropin (rhTSH) stimulation. Whole body scan (WBS) after treatment showed uptake in bilateral lungs, right sacrum, and pelvis. The thyroglobulin decreased from 2,063 to 965 four months after treatment but rapidly increased to 2,506 eleven months after I-131. Thyroid stimulating hormone (TSH) remained suppressed and free T4 remained elevated after I-131 therapy without thyroid hormone supplementation. He was treated with an additional 209 mCi with WBS findings positive in lung and pelvis. Despite I-131, new metastatic lesions were noted in the left thyroid bed and large destructive lesion to the first cervical vertebrae four months after the second I-131 dose. Conclusions. This case is exceptional because of its rarity and also due to the dissociation between tumor differentiation and aggressiveness. The metastatic lesions continued to secrete thyroid hormone and remained radioiodine avid with rapid progression after I-131 therapy.
doi:10.1155/2014/584513
PMCID: PMC4220571  PMID: 25400957
3.  Radioiodine thyroid remnant ablation in patients with differentiated thyroid carcinoma (DTC): prospective comparison of long-term outcomes of treatment with 30, 60 and 100 mCi 
Thyroid Research  2010;3:9.
Background
The aim of this study is to compare the effectiveness of 131I therapy between three groups of DTC patients who received 30, 60 or 100 mCi for thyroid remnant ablation after total thyroidectomy and were postoperatively judged with low risk of cancer recurrence.
Methods
The project was designed as a two-stage, prospective randomized clinical trial. In 1998-2001 in a randomized prospective study the early comparison of treatment with 30 mCi vs 60 mCi suggested the lower 131I activity to be less effective, whereas in 2003-2005 the comparison between 60 vs 100 mCi showed no significant differences. The present study comprises the long-term assessment of the disease course in 3 study groups.
Results
A group of 309 DTC patients (285 women and 24 men) with no clinical, histopathological, sonographical or biochemical signs of persistent disease were included after total thyroidectomy and appropriate extent of neck lymph node dissection (265 with papillary and 44 with follicular thyroid cancer). For radioiodine thyroid remnant ablation, 30 mCi of 131I was applied in 86 patients, whereas 60 mCi in 128 and 100 mCi in 95 patients. The median follow-up was 10 years (2-12) for subjects treated with 30 mCi and 60 mCi and 6 years (2-6) for patients treated with 100 mCi of 131I. In the first evaluation, published previously, we observed that because of incomplete thyroid remnant ablation, the second 131I treatment was necessary in 10% patients, without difference between groups treated with 60 and 100 mCi and in 22% patients treated with 30 mCi. All patients entered full remission. To evaluate the long-term outcome of the adjuvant 131I treatment, the course of the follow-up and the most recent disease status were assessed by sonography, radiological examinations and serum Tg estimation (on LT4-suppressive treatment). Within the whole observation period local relapse was stated in 2 (2.4%), 4 (3%) and 3 (3%) patients treated with 131I activities of 30 mCi, 60 mCi and 100 mCi respectively and serum Tg concentration on LT4-suppressive treatment was low, without differences between groups.
Conclusions
No significant differences in the 5 years efficacy of thyroid remnant radioiodine ablation using 30, 60 and 100 mCi were observed in low-risk DTC patients operated by total thyroidectomy and neck lymph node dissection. However, patients treated initially with 30 mCi, required second course of radioiodine in 22%, while this was necessary only in 13,3% and 11,2% of patients treated with 60 mCi and 100 mCi respectively.
doi:10.1186/1756-6614-3-9
PMCID: PMC2989933  PMID: 21040579
4.  Hyperthyroidism (primary) 
Clinical Evidence  2008;2008:0611.
Introduction
Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy.
Key Points
Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. Thyrotoxicosis is the clinical effect of high levels of thyroid hormones, whether or not the thyroid gland is the primary source.The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma.About 20 times more women than men have hyperthyroidism.
There is consensus that antithyroid drugs (carbimazole, propylthiouracil, and thiamazole) are effective in treating hyperthyroidism, although we found no evidence comparing them with placebo or with each other. We found no evidence that antithyroid drugs plus thyroxine (block-replace regimens) improved relapse rates compared with titration regimens.Higher-dose antithyroid drugs work better when taken for longer (more than 18 months) than for a shorter time (6 months).The doses of antithyroid drugs reported in the studies we found are higher than are generally used in practice.
There is also consensus that radioactive iodine (radioiodine) is effective for hyperthyroidism. We don't know whether radioactive iodine increases risk of thyroid and extrathyroid cancer.Radioactive iodine can worsen ophthalmopathy in people with Graves' disease.Giving antithyroid drugs to people having radioiodine may increase the proportion of people with persistent or recurrent hyperthyroidism or who need further treatment.
There is consensus that thyroidectomy is effective for hyperthyroidism. Total thyroidectomy is more effective than subtotal thyroidectomy for hyperthyroidism.Replacement thyroxine will need to be given to people who become hypothyroid after thyroidectomy.
There may be some improvement in bone mineral density and thyroid-stimulating hormone levels after treatment with antithyroid treatment in women who have subclinical hyperthyroidism.
PMCID: PMC2907936  PMID: 19450325
5.  Hyperthyroidism (primary) 
Clinical Evidence  2010;2010:0611.
Introduction
Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy.
Key Points
Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone (TSH). Thyrotoxicosis is the clinical effect of high levels of thyroid hormones, whether or not the thyroid gland is the primary source.The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma.About 20 times more women than men have hyperthyroidism.
There is consensus that antithyroid drugs (carbimazole, propylthiouracil, and thiamazole) are effective in treating hyperthyroidism, although we found no evidence comparing them with placebo or with each other. We found no evidence that antithyroid drugs plus thyroxine (block-replace regimens) improved relapse rates compared with titration regimens.Higher-dose antithyroid drugs work better when taken for longer (greater than 18 months) than for a shorter time (6 months).The doses of antithyroid drugs reported in the studies we found are higher than are generally used in practice.
There is also consensus that radioactive iodine (radioiodine) is effective for hyperthyroidism. We don't know whether radioactive iodine increases risk of thyroid and extrathyroid cancer.Radioactive iodine can worsen ophthalmopathy in people with Graves' disease.Giving antithyroid drugs to people having radioiodine may increase the proportion of people with persistent or recurrent hyperthyroidism or who need further treatment.
There is consensus that thyroidectomy is effective for hyperthyroidism. Total thyroidectomy is more effective than subtotal thyroidectomy for hyperthyroidism.Replacement thyroxine will need to be given to people who become hypothyroid after thyroidectomy.
There may be some improvement in bone mineral density and TSH levels after treatment with antithyroid treatment in women who have subclinical hyperthyroidism.
PMCID: PMC3275323  PMID: 21418670
6.  Radioiodine-induced kidney damage and protective effect of amifostine: An experimental study 
Hippokratia  2012;16(1):40-45.
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.
PMCID: PMC3738391  PMID: 23930056
amifostine; radioiodine therapy; renal toxicity
7.  Radioactive Iodine for Thyrotoxicosis in Childhood and Adolescence: Treatment and Outcomes 
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.
doi:10.4274/Jcrpe.951
PMCID: PMC3701929  PMID: 23748061
Radioiodine treatment; thyrotoxicosis; children; adolescence; outcome
8.  Molecular imaging in thyroid cancer 
Cancer Imaging  2010;10(1):1-7.
Abstract
Molecular imaging plays an important role in the evaluation and management of thyroid cancer. The routine use of thyroid scanning in all thyroid nodules is no longer recommended by many authorities. In the initial work-up of a thyroid nodule, radioiodine imaging can be particularly helpful when the thyroid stimulating hormone level is low and an autonomously functioning nodule is suspected. Radioiodine imaging can also be helpful in the 10–15% of cases for which fine-needle aspiration biopsy is indeterminate. Therapy of confirmed thyroid cancer frequently involves administration of iodine-131 after surgery to ablate remnant tissue. In the follow-up of thyroid cancer patients, increased thyroglobulin levels will often prompt the empiric administration of 131I followed by whole body radioiodine imaging in the search for recurrent or metastatic disease. 131I imaging of the whole body and blood pharmacokinetics can be used to determine if higher doses of 131I can be given in thyroid cancer. The utility of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is steadily increasing. FDG is primarily taken up by dedifferentiated thyroid cancer cells, which are poorly iodine avid. Thus, it is particularly helpful in the patient with an increased thyroglobulin but negative radioiodine scan. FDG PET is also useful in the patient with a neck mass but unknown primary, in patients with aggressive (dedifferentiated) thyroid cancer, and in patients with differentiated cancer where histologic transformation to dedifferentiation is suspected. In rarer types of thyroid cancer, such as medullary thyroid cancer, FDG and other tracers such as 99mTc sestamibi, [11C]methionine, [111In]octreotide, and [68Ga]somatostatin receptor binding reagents have been utilized. 124I is not widely available, but has been used for PET imaging of thyroid cancer and will likely see broader applicability due to the advantages of PET methodology.
doi:10.1102/1470-7330.2010.0002
PMCID: PMC2842177  PMID: 20159663
Thyroid cancer; PET/CT; molecular imaging; papillary thyroid cancer; follicular thyroid cancer; FDG; nuclear medicine
9.  Laparoscopic partial nephrectomy of thyroid cancer metastasis: case report and review of the literature 
OncoTargets and therapy  2013;6:355-360.
Background
Follicular cell thyroid carcinoma is a quite aggressive form of thyroid cancer. About 10% of follicular thyroid carcinoma shows multiple metastases: lung and bone are the most common sites of metastasis. Renal involvement from thyroid primary cancer is very rare with incidence of 4.5%–5.9%.
Purpose
We report the first laparoscopic conservative treatment of renal metastasis from thyroid cancer. This is a new and useful approach in order to delay malignant disease progression and to reduce the surgical discomfort of the patient.
Patients and methods
We present the case of a 67-year-old woman, undergoing total thyroidectomy for follicular thyroid cancer with bone and lung metastasis. During adjuvant radiometabolic treatment, renal metastasis was diagnosed. Renal metastasis showed high metabolic activity, reducing the effectiveness of radioiodine therapy for secondary lesions. For this reason, we performed a laparoscopic simple enucleation of the single renal metastasis using extraperitoneal access and a clampless procedure.
Results
The excision of the renal lesion improved the effectiveness of adjuvant radioiodine therapy: two months after surgery, the patient underwent adjuvant radiometabolic treatment with iodine-131 (150 mCi) and the following whole body scan showed only a small uptaking area at the level of the vertebral metastasis. The lung micrometastases were not detectable. At 36 months follow-up, malignant disease was clinically stable and well controlled.
Conclusion
Minimally invasive renal surgery with preservation of renal function and rapid recovery contributed to the success of radioiodine therapy and delayed the progression of the disease.
doi:10.2147/OTT.S37402
PMCID: PMC3627344  PMID: 23596352
follicular thyroid carcinoma; renal metastasis; simple enucleation; laparoscopy; clampless; radiometabolic treatment
10.  Use of Pre-Ablation Radioiodine-131 Scan to Assess the Impact of Surgical Volume and Specialisation following Thyroidectomy for Differentiated Thyroid Carcinoma 
European Thyroid Journal  2013;2(4):275-281.
Background
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.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1159/000355911
PMCID: PMC3923598  PMID: 24783059
Thyroid cancer; Surgeon volume; Thyroid remnant; 
Pre-ablation radioiodine scan; Surgical specialisation

11.  Usefulness of low iodine diet in managing patients with differentiated thyroid cancer - initial results 
Radiology and Oncology  2011;45(3):189-195.
Background
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.
Results
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.
Conclusions
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.
doi:10.2478/v10019-011-0017-4
PMCID: PMC3423737  PMID: 22933955
low iodine diet; urine iodine concentration; differentiated thyroid cancer; radioiodine
12.  Long-term outcome of low-activity radioiodine administration preceded by adjuvant recombinant human TSH pretreatment in elderly subjects with multinodular goiter 
Thyroid Research  2009;2:6.
Background
Large multinodular goiter (MNG) in elderly people is a common finding which can require intervention. The long-term effect of radioiodine therapy on thyroid volume (TV) and function after recombinant human (rh) TSH pre-treatment was evaluated.
Methods
After baseline evaluation, 40 subjects over 60 years old with a large MNG were treated with 131I up to the activity of 600 MBq. Nineteen patients were pretreated with rhTSH (0.1 mg on 2 consecutive days; group 1) while 21 subjects underwent treatment without rhTSH pretreatment (group 2). TV was monitored every 6–12 months by ultrasonography. The median follow-up period was 36 months.
Results
At the baseline, the groups matched in terms of TV, 24-h radioiodine uptake (RAIU), urinary iodine and neck complaints. The number of subjects pretreated with anti-thyroid drugs was significantly (P = 0.01) greater in group 2 than in group 1; TSH was more suppressed (P = 0.003) and f-T3 was more elevated (P = 0.005) in group 2 than in group 1 patients. RhTSH increased 24-h RAIU in group 1 up to the baseline level observed in group 2. The 131I activity administered was similar in both groups. Adverse events were slight and similar in both groups. A permanent post-radioiodine toxic condition was reported only in 2 patients in group 2. After radioiodine therapy, hypothyroidism was observed in significantly more group 1 patients than group 2 patients (P = 0.002). While TV was reduced in both groups, the percentage TV reduction recorded at the last examination was significantly higher (P = 0.03) in group 1 than in group 2. MNG-related complaints were significantly reduced in both group 1 (P = 0.0001 vs baseline) and group 2 (P = 0.001) patients.
Conclusion
Low radioiodine activities after pretreatment with low-dosage rhTSH are able to reduce TV and improve MNG-related symptoms in elderly subjects.
doi:10.1186/1756-6614-2-6
PMCID: PMC2713215  PMID: 19566933
13.  Pituitary metastases from papillary carcinoma of thyroid: a case report and literature review 
Summary
Metastases to the pituitary gland are an uncommon complication of thyroid cancer. They resemble pituitary neoplasms posing a diagnostic challenge. We present a case of an aggressive non-radioiodine avid papillary thyroid cancer with recurrent pituitary metastases and a review of the literature. A 70-year-old woman with a history of papillary thyroid cancer and bony metastases presented with symptoms of hypoadrenalism and peripheral vision loss. Magnetic resonance imaging showed a large pituitary mass impinging on the optic chiasm. She underwent transsphenoidal resection followed by 131I ablation. Post-therapy scintigraphy showed no iodine uptake in the sellar region or bony metastases. Histology of the pituitary mass confirmed metastatic papillary thyroid cancer. Fifteen months later, she had a recurrence of pituitary metastases affecting her vision. This was resected and followed with external beam radiotherapy. Over 2 years, the pituitary metastases increased in size and required two further operations. Radioactive iodine was not considered due to poor response in the past. Progressively, she developed a left-sided III and IV cranial nerve palsy and permanent bitemporal hemianopia. There was a rapid decline in the patient's health with further imaging revealing new lung and bony metastases, and she eventually died 8 months later. To our knowledge, this is the first case of pituitary metastases from a radioiodine-resistant papillary thyroid cancer. Radioiodine-resistant metastatic thyroid cancer may exhibit rapid aggressive growth and remain poorly responsive to the currently available treatment.
Learning points
Differentiated thyroid cancer (DTC) has an excellent prognosis with <5% of the cases presenting with distant metastases, usually to lung and bone.Metastasis to the pituitary is a rare complication of DTC.The diagnosis of pituitary insufficiency secondary to pituitary metastases from DTC may be delayed due to the non-specific systemic symptoms of underlying malignancy and TSH suppression therapy for thyroid cancer.The imaging characteristics of metastases to the pituitary may be similar to non-functioning pituitary adenoma.Radioiodine refractory metastatic thyroid cancer has significantly lower survival rates compared with radioactive iodine-avid metastases due to limited therapeutic options.
doi:10.1530/EDM-13-0024
PMCID: PMC3922192  PMID: 24616765
14.  Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids - early effect 
Thyroid Research  2010;3:7.
Introduction
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.
Results
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.
Conclusions
Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids, at least early, after therapy.
doi:10.1186/1756-6614-3-7
PMCID: PMC2964524  PMID: 20925955
15.  Prognosis for fertility and ovarian function after treatment with radioiodine for thyroid cancer 
Postgraduate Medical Journal  2002;78(916):92-93.
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.
doi:10.1136/pmj.78.916.92
PMCID: PMC1742275  PMID: 11807191
16.  Radioiodine Thyroid Ablation in Graves’ Hyperthyroidism: Merits and Pitfalls 
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.
doi:10.4103/1450-1147.98731
PMCID: PMC3425234  PMID: 22942775
Autoimmunity; Graves’ disease; ophthalmopathy; radioiodine therapy
17.  Utility of Iodine-131 hybrid SPECT-CT fusion imaging before high-dose radioiodine therapy in papillary thyroid carcinoma 
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.
doi:10.4103/0972-3919.63599
PMCID: PMC2934597  PMID: 20844669
Carcinoma; hybrid imaging; iodine-131; SPECT-CT; thyroid
18.  Low vs. High Radioiodine Activity to Ablate the Thyroid after Thyroidectomy for Cancer: A Randomized Study 
PLoS ONE  2008;3(4):e1885.
Background
Radioactive iodine is commonly administered following thyroidectomy for differentiated thyroid carcinoma to ablate the thyroid remnant. The optimal administered activity of radioiodine is unknown.
Methodology/Principal Findings
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).
Conclusions/Significance
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.
Trial Registration
ClinicalTrials.gov NCT00115895
doi:10.1371/journal.pone.0001885
PMCID: PMC2270902  PMID: 18382668
19.  Outcome of 131I therapy in hyperthyroidism using a 550MBq fixed dose regimen 
The Ulster Medical Journal  2013;82(2):85-88.
Background
Radioiodine is the treatment of choice for relapsed hyperthyroidism although the optimum protocol is uncertain. Fixed dose radioiodine is increasingly popular but responses may vary.
Aim
To assess the outcome of 131I therapy in hyperthyroidism using a standard dose regimen in a regional referral centre and to explore factors influencing outcome.
Methods
We studied 449 patients (M:F 82:367; age range 13-89y, median 42y) with hyperthyroidism treated between 2003 and 2007 with a standard dose of 550MBq 131I. Patients were classified as either Graves’ disease, toxic multinodular goitre or indeterminate aetiology. Antithyroid drugs were routinely stopped at least 1 week before radioiodine.
Results
One year after radioiodine 334 (74%) were hypothyroid, 85 (19%) were euthyroid and 30 (7%) had required a further dose of 131I. Patients with Graves’ disease were more likely to become hypothyroid than those with toxic multinodular goitre (78% v 37%, p<0.001) and less likely to become euthyroid (11% v 55%, p<0.001). Free T4 >80pmol/L (normal range 9.0 – 19.0 pmol/L) at presentation was associated with an increased failure rate (17% compared with 5% and 3% for 40-79pmol/L and <40pmol/L respectively; p=0.01). Patients with either a small or no goitre were more likely to be successfully treated by a single dose (96%) than those with a medium/large goitre (85%, p<0.001). Anti-thyroid medication was taken by 345 (77%) (carbimazole n=319) patients up to 1 week prior to 131I and was associated with an increased failure rate (8% v 2%, p=0.027) compared to those who had not had antithyroid medication. Logistic regression showed free T4 at presentation to be the only independent risk factor for failure of the first dose of radioiodine (OR 2.5; 95% CI, 1.2–5.1, p=0.012).
Conclusion
A single standard dose of 550MBq 131I is highly effective in treating hyperthyroidism. The aetiology, severity of hyperthyroidism at diagnosis, goitre size and prior antithyroid medication all had a significant effect on outcome.
PMCID: PMC3756864  PMID: 24082285
Radioiodine; hyperthyroidism
20.  Transient cytotoxicity of 131I beta radiation in hyperthyroid patients treated with radioactive iodine 
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.
Methods:
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 thand 30 thdays after the treatment.
Results:
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.
PMCID: PMC3103173  PMID: 21537093
chromosomal aberrations; hyperthyroidism; low dose 131I therapy; micronucleus assay
21.  rhTSH-aided low-activity versus high-activity regimens of radioiodine in residual ablation for differentiated thyroid cancer: a meta-analysis 
Nuclear Medicine Communications  2013;34(12):1150-1156.
The effects of low-activity versus high-activity radioiodine regimens in thyroid remnant ablation for patients with differentiated thyroid carcinoma (DTC) under recombinant human thyrotropin (rhTSH) stimulation have been widely quoted but there has been no systematic review of the evidence. We undertook a systematic review of randomized controlled trials to assess the effects of low-activity radioiodine in thyroid remnant ablation in patients with DTC under rhTSH stimulation compared with high-activity radioiodine. Studies were obtained from computerized searches of MEDLINE, EMBASE, and the Cochrane Library (all until September 2012). Randomized controlled trials were included. Altogether, 637 patients with DTC who participated in three trials for residual ablation were included. Overall, studies had a low risk of bias. We found no statistically significant differences between low-activity (1.11/1.85 GBq) and high-activity (3.7 GBq) radioiodine treatment aided by rhTSH in terms of successful ablation rates on the basis of diagnostic scans [odds ratio (OR) 0.85, 95% confidence interval (CI) 0.49–1.47, P=0.56], thyroglobulin levels (OR 0.66, 95% CI 0.38–1.15, P=0.14), and health-related quality of life (mean difference 0.07, 95% CI −0.96 to 1.09, P=0.9). In addition, the subgroup analysis of 1.11 versus 3.7 GBq (OR 0.83, 95% CI 0.46–1.49, P=0.53) and 1.85 versus 3.7 GBq (OR 1, 95% CI 0.23–4.35, P=1) also showed no significant differences. The lower activity of 1.11 GBq showed significant benefit in terms of reduction in adverse events including neck pain, radiation gastritis, and salivary dysfunction during and after ablation (OR 0.63, 95% CI 0.42–0.93, P=0.02). Limited data from three randomized controlled trials suggested that an rhTSH-aided low radioiodine activity level of as low as 1.115 GBq may be sufficient for thyroid remnant ablation when compared with 3.7 GBq, with fewer common adverse effects in patients with metastasis-free DTC. Further evidence is needed to confirm the effects of low-activity radioiodine for thyroid remnant ablation. Radioiodine treatment of 1.11 GBq showed significant benefit in terms of reduction in adverse events including neck pain, radiation gastritis, and salivary dysfunction during and after ablation (OR 0.63, 95% CI 0.42–0.93, P=0.02). rhTSH-aided low radioiodine activity levels of 1.11 and 1.85 GBq are sufficient for thyroid remnant ablation as compared with 3.7 GBq, with fewer common adverse effects in patients with metastasis-free DTC. A well-designed study that compares low-activity with high-activity radioiodine ablation is needed to fully understand the long-term adverse effects and relapse or metastases.
doi:10.1097/MNM.0b013e328365ac05
PMCID: PMC3815118  PMID: 24025918
differentiated thyroid cancer; radioiodine; recombinant human thyrotropin
22.  One Month Is Sufficient for Urinary Iodine to Return to Its Baseline Value After the Use of Water-Soluble Iodinated Contrast Agents in Post-Thyroidectomy Patients Requiring Radioiodine Therapy 
Thyroid  2012;22(9):926-930.
Background
There is a concern regarding the use of iodinated contrast agents (ICA) for chest and neck computed tomography (CT) to localize metastatases in patients with differentiated thyroid cancer (DTC). This is because the iodine in ICA can compete with 131I and interfere with subsequent whole scans or radioactive iodine treatment. The required period for patients to eliminate the excess iodine is not clear. Therefore, knowing the period for iodine levels to return to baseline after the injection of ICA would permit a more reliable indication of CT for DTC patients. The most widely used marker to assess the plasmatic iodine pool is the urinary iodine (UI) concentration, which can be collected over a period of 24 hours (24U) or as a single-spot urinary sample (sU). As 24U collections are more difficult to perform, sU samples are preferable. It has not been established, however, if the measurement of iodine in sU is accurate for situations of excess iodine.
Methods
We evaluated 25 patients with DTC who received ICA to perform chest or neck CT. They collected 24U and sU urinary samples before the CT scan and 1 week and 1, 2, and 3 months after the test. UI was quantified by a semiautomated colorimetric method.
Results
Baseline median UI levels were 21.8 μg/dL for 24U and 26 μg/dL for sU. One week after ICA, UI median levels were very high for all patients, 800 μg/dL. One month after ICA, however, UI median levels returned to baseline in all patients, 19.0 μg/dL for 24U and 20 μg/dL for sU. Although the values of median UI obtained from sU and 24U samples were signicantly different, we observed a significant correlation between samples collected in 24U and sU in all evaluated periods.
Conclusion
One month is required for UI to return to its baseline value after the use of ICA and for patients (after total thyroidectomy and radioiodine therapy) to eliminate the excess of iodine. In addition, sU samples, although not statistically similar to 24U values, can be used as a good marker to evaluate patients suspected of contamination with iodine.
doi:10.1089/thy.2012.0099
PMCID: PMC3429278  PMID: 22827435
23.  Nabothian cyst associated with high false-positive incidence of iodine-131 uptake in whole-body scans after treatment for differentiated thyroid cancer 
Nuclear Medicine Communications  2013;34(12):1204-1207.
Objective
This study aimed to analyze the focal uptake of iodine-131 (131I) in the upper pelvis superior to the urinary bladder on whole-body images of patients who underwent this treatment after thyroidectomy for differentiated thyroid cancer.
Methods
Between June 2012 and March 2013, 205 patients (72 men and 133 women, with an average age of 47.9±11.7 years) who underwent 131I radioactive treatment after thyroid cancer surgery were analyzed retrospectively. Pathological findings confirmed papillary thyroid carcinoma. A whole-body scan was acquired 5 days after 100–120 mCi sodium iodide was administered orally to the patients. Single-photon emission computed tomography/computed tomography (SPECT/CT) scanning was carried out to locate the lesion; this showed abnormal intense activity in the upper pelvis superior to the urinary bladder, which was further evaluated by ultrasonography.
Results
Using 131I-SPECT scanning, five (3.76%) female patients were shown to have abnormal focal radioactivity in the lower abdomen. Subsequent SPECT/CT examination showed that the radioactivity was located in the cervix in four of the five patients and in the sigmoid colon in one patient. Transvaginal ultrasonography was performed in the former four patients, which revealed several echo-free regions in the cervix. These findings are consistent with the diagnosis of a nabothian cyst. Three of these patients were administered a second course of radioiodine therapy. Radioactive uptake was still visible at the same sites on whole-body imaging.
Conclusion
Nabothian cyst should be considered in cases in which abnormal uptake in the upper pelvis superior to the urinary bladder is detected on 131I whole-body scans after differentiated thyroid cancer resection.
doi:10.1097/MNM.0b013e328365911a
PMCID: PMC3815149  PMID: 24077637
131I whole-body imaging; false-positive finding; nabothian cyst; papillary thyroid cancer; radioiodine therapy
24.  Prognostic Value of Basal Serum Thyroglobulin Levels, but Not Basal Antithyroglobulin Antibody (TgAb) Levels, in Patients with Differentiated Thyroid Cancer 
Objective: The prognostic values of serum thyroglobulin (Tg) and antithyroglobulin antibody (TgAb) levels, measured immediately before I-131remnant ablation in patients with differentiated thyroid cancer (DTC), have been advocated by some researchers; however, it had controversial outcomes. This study was carried out to examine this dilemma and to check the clinical significance of basal serum Tg and TgAb levels and postablation iodine 131whole body scan(WBS) findings in DTC patients.
Methods: In this retrospective study, the records of 500 patients with differentiated thyroid cancer, who had undergone treatment between 2003 and 2010, were assessed. Of those, 149 patients with results of basal serum thyroglobulin concentration and whole body scan using radioactive iodine were included. Age, sex, tumour histology, basal thyroglobulin (Tg), anti-thyroglobulin (TgAb) and TSH concentration, radioactive iodine doses in each hospitalization, numbers of hospitalization, and results of whole body scans were recorded. The relationship among basal Tg, TgAb, TSH, and whole body scan with hospitalization number and total radioactive iodine doses were assessed.
Results: A total of 149 patients, including 123 (83%) females and 26 (17%) males, with a mean age of 40±15 years, took part in the study. The mean (SD) basal Tg, TgAb, and TSH were 91.7±169.2 ng/mL (0.1-1000 ng/mL), 250±893 U/mL (0-9000 U/m L), and 64.8±61.5 µU/mL (30-689 U/mLµ), respectively. A total of 52 (34.9%) cases had TgAb levels greater than 100 U/mL. The mean basal Tg in patients who were admitted three or more times was significantly greater than that of patients with one hospitalization (p=0.026). In addition, the mean of Tg in patients who received 7.4 GBq radioactive iodine or less was significantly lower than the others (p=0.003). The mean of TgAb and TSH were not different between these groups. In the results of the whole body scans, patients with metastasis had higher frequency of hospitalization (p=0.010) and received higher radioactive iodine levels (p<0.001).
Conclusions: The findings of this study showed that, in differentiated thyroid cancer, lower basal serum Tg levels and absence of metastasis in radioiodine scan after ablation treatment were correlated with fewer hospitalizations and lower doses of radioactive iodine. Basal TgAb and TSH had no relation. Therefore, it seems that basal Tg could help us in determining which patients need aggressive treatment.
doi:10.4274/mirt.39200
PMCID: PMC4067877  PMID: 24963446
thyroid cancer; thyroglobulin; anti-thyroglobulin
25.  Lung Dosimetry for Radioiodine Treatment Planning in the Case of Diffuse Lung Metastases 
The lungs are the most frequent sites of distant metastasis in differentiated thyroid carcinoma. Radioiodine treatment planning for these patients is usually performed following the Benua– Leeper method, which constrains the administered activity to 2.96 GBq (80 mCi) whole-body retention at 48 h after administration to prevent lung toxicity in the presence of iodine-avid lung metastases. This limit was derived from clinical experience, and a dosimetric analysis of lung and tumor absorbed dose would be useful to understand the implications of this limit on toxicity and tumor control. Because of highly nonuniform lung density and composition as well as the nonuniform activity distribution when the lungs contain tumor nodules, Monte Carlo dosimetry is required to estimate tumor and normal lung absorbed dose. Reassessment of this toxicity limit is also appropriate in light of the contemporary use of recombinant thyrotropin (thyroid-stimulating hormone) (rTSH) to prepare patients for radioiodine therapy. In this work we demonstrated the use of MCNP, a Monte Carlo electron and photon transport code, in a 3-dimensional (3D) imaging–based absorbed dose calculation for tumor and normal lungs.
Methods
A pediatric thyroid cancer patient with diffuse lung metastases was administered 37MBq of 131I after preparation with rTSH. SPECT/CT scans were performed over the chest at 27, 74, and 147 h after tracer administration. The time–activity curve for 131I in the lungs was derived from the whole-body planar imaging and compared with that obtained from the quantitative SPECT methods. Reconstructed and coregistered SPECT/CT images were converted into 3D density and activity probability maps suitable for MCNP4b input. Absorbed dose maps were calculated using electron and photon transport in MCNP4b. Administered activity was estimated on the basis of the maximum tolerated dose (MTD) of 27.25 Gy to the normal lungs. Computational efficiency of the MCNP4b code was studied with a simple segmentation approach. In addition, the Benua–Leeper method was used to estimate the recommended administered activity. The standard dosing plan was modified to account for the weight of this pediatric patient, where the 2.96-GBq (80 mCi) whole-body retention was scaled to 2.44 GBq (66 mCi) to give the same dose rate of 43.6 rad/h in the lungs at 48 h.
Results
Using the MCNP4b code, both the spatial dose distribution and a dose–volume histogram were obtained for the lungs. An administered activity of 1.72 GBq (46.4 mCi) delivered the putative MTD of 27.25 Gy to the lungs with a tumor absorbed dose of 63.7 Gy. Directly applying the Benua–Leeper method, an administered activity of 3.89 GBq (105.0 mCi) was obtained, resulting in tumor and lung absorbed doses of 144.2 and 61.6 Gy, respectively, when the MCNP-based dosimetry was applied. The voxel-by-voxel calculation time of 4,642.3 h for photon transport was reduced to 16.8 h when the activity maps were segmented into 20 regions.
Conclusion
MCNP4b–based, patient-specific 3D dosimetry is feasible and important in the dosimetry of thyroid cancer patients with avid lung metastases that exhibit prolonged retention in the lungs.
PMCID: PMC2967027  PMID: 17138741
MCNP4b; Monte Carlo; patient-specific dosimetry; thyroid carcinoma; 131I; lung metastases; SPECT/CT

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