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This article presents an overview of the use of radioactive iodine (131-I) in the treatment of patients with differentiated thyroid cancer. Topics reviewed include definitions; staging; the 2 principal methods for selection of 131-I dosage; the indications for ablation, adjuvant treatment, and treatment; the recommendations for the use of 131-I contained in the guidelines of the American Thyroid Association and the Society of Nuclear Medicine and Molecular Imaging; the dosage recommendations and selection of dosage approach for 131-I by these organizations; the use of recombinant human thyrotropin for radioiodine ablation, adjuvant therapy, or treatment; and the MedStar Washington Hospital Center approach.

The detection of recurrent disease in differentiated thyroid cancer (DTC) patients with elevated or rising serum thyroglobulin (Tg) levels and multiple negative conventional imaging studies can be challenging, especially when 18F-FDG PET/CT scan is also negative. We report a patient and review the literature on the diagnostic use of 99mTc-sestamibi scans to identify the source of elevated or rising Tg in patients with negative conventional imaging including negative 18F-FDG PET/CT scans. A 73-year-old woman was referred for widely-invasive metastatic follicular thyroid cancer with bone metastasis to her left mandible. She had a total thyroidectomy, left mandibular resection, and 131I therapy of 145 mCi (5.4 GBq) and her subsequent unstimulated serum Tg level was 29 ng/ml (TgAb negative). At six months’ follow-up, her stimulated Tg was 527 ng/ml (TSH 188 mIU/L, TgAb negative). All imaging studies performed within the prior 12 months were reported as negative for recurrence or metastasis; this included neck ultrasound, diagnostic radioiodine scan, chest CT and, 18F-FDG PET/CT. The patient was injected with 24.6 mCi (910 MBq) of 99mTc-sestamibi intravenously, and whole-body and SPECT/CT images were acquired. The 99mTc-sestamibi whole-body posterior image demonstrated abnormal focal uptake in the right posterior calvarium and corresponded to an occipital lytic bone lesion on the SPECT/CT. The patient underwent surgical resection of the skull metastasis, and pathology confirmed metastatic follicular thyroid cancer. Five months post-surgery, the suppressed Tg was markedly reduced and remained stable at ~3.2 ng/ml. With the knowledge of the DTC recurrence location, the two sets of 18F-FDG images were re-evaluated. The more thorough and targeted interpretation underscored the importance of structured image reporting. The current literature on the utility of 99mTc-sestamibi scans when radioiodine, 18F-FDG PET/CT, and other imaging studies are negative is sparse and inconsistent. 99mTc-sestamibi may have a role in thyroid cancer localization when physical exam, neck ultrasound, radioiodine scan, chest/abdomen CT, and 18F-FDG PET/CT does not identify the source of elevated Tg levels in DTC.

Unlike virtually all other cancer types, thyroid cancer is unique in that patient age is a key component in its staging. Pathologists and clinicians worldwide have accepted an age cutoff of 45 years for staging; in 2018, this advances to age 55 years in the eighth edition of the American Joint Commission on Cancer staging system.

Amifostine is a potent scavenger of reactive oxygen species that is used for the salivary gland protection during therapy with radioactive iodine for thyroid cancer. There are no data on the potential effect of amifostine on thyroid cancer cells.We investigated the effects of the active form of amifostine (WR-1065) on the response of thyroid cancer cells to treatment with DNA-damaging agents. WR-1065 was examined in human thyroid cancer cell lines (FTC133, TPC1, BCPAP and C643) and embryonic fibroblast cells NIH3T3. DNA damage was induced by exposure to H2O2(0.1 mM), by treatment with the radiomimetic neocarzinostatin (NCS 250 ng/mL) and by γ-radiation (6 Gy). DNA damage, cell viability and apoptosis were examined.We demonstrated the selective action of WR-1065 (0.1 mM), which prevented oxidative stress–induced DNA damage in fibroblasts, but did not protect thyroid cancer cells from DNA damage and apoptosis documented by caspase-3 and PARP cleavage after exposure to H2O2, NCS and γ-radiation. Prolonged exposure to WR-1065 (0.1 mM for 24 h) was toxic for thyroid cancer cells; this treatment decreased the number of viable cells by 8% in C643 cells, 47% in TPC cells, 92% in BCPAP cells and 82% in FTC 133 cells. The cytotoxic effects of WR-1065 were not associated with induction of apoptosis.Our data show that amifostine has no protective effect on thyroid cancer cells against DNA-damaging agents in vitroand suggest that amifostine will not attenuate the efficacy of radioiodine treatment in patients with thyroid cancer.

This article discusses the more controversial areas of the management of differentiated thyroid cancer, namely, the utility of pretherapy staging radioiodine scans; the prescribed activity for iodine-131 remnant ablation, adjuvant treatment, and distant metastases; preparation with thyroid hormone withdrawal versus recombinant human thyroid-stimulating hormone; and the classification of radioiodine refractory differentiated thyroid cancer. The author reviews various aspects of the controversies, such as the recommendations of the 2015 guidelines of the American Thyroid Association, arguments for and against the various controversies, and selected references.

Objective:The objective of the study was to evaluate the effects of dosimetrically guided I-131 prescribed activities on hematopoiesis reflected by changes in complete blood counts (CBCs).Design:This was a retrospective analysis.Setting:The study was conducted at an academic center.Patients:A total of 152 patients with differentiated thyroid cancer who had 185 dosimetrically guided I-131 treatments.Interventions:There were no interventions.Main Outcome Measures:Repeated-measure ANOVA was used for the analysis of the differences in the averages of CBCs that were documented at baseline and 1, 6, 12, 24–36, and 48–60 months after I-131 treatment.Results:All parameters decreased to their respective nadir at 1 month and then gradually returned toward baseline values. White blood cells (WBCs) and platelets (PLTs) were the most significantly affected cells. At 1 month, the decrease was 29.6% (P< .0001) for WBCs and 25% (P< .0001) for PLTs, whereas at 12 months, the decrease was 15.5% (P< .0001) and 13% (P< .0001), respectively. Lymphocytes appeared to be more susceptible to I-131 than neutrophils (ANCs). The decreases were small in absolute numbers for red blood cells, hematocrit and hemoglobin not surpassing 10%. Multivariate analysis demonstrated that the ratio of administered prescribed activity-to-maximum tolerated activity was associated with the decreases in WBCs (P= .0038), ANCs (P= .0063), and red blood cells (P= .029), with borderline significance for PLTs (P= .057) and hemoglobin (P= .057).Conclusions:Dosimetrically guided I-131 resulted in statistically significant decreases in CBC parameters, which were more prominent in WBCs and PLTs. Lymphocytes were more severely affected than ANCs, whereas all parameters reached a nadir at 1 month and then gradually returned toward baseline values over the 5-year follow-up of our study.

The protective effect of sialagogues following 131I therapy became controversial after a study proposed that sialagogues increase the reaccumulation of 131I in the parotid glands (PGs) to a level higher than when sialagogues are not administered (‘rebound effect’). The present study examined PG radiopharmacokinetics within 2–4 h after radioiodine administration to evaluate whether sialagogues cause a ‘rebound effect’.

BACKGROUND: The optimal management of high-risk patients with differentiated thyroid cancer (DTC) consists of thyroidectomy followed by radioiodine (131I) therapy. The prescribed activity of 131I can be determined using two approaches: 1) empiric prescribed activity of 131I (E-Rx); and 2) dosimetry-based prescribed activity of 131I (D-Rx). AIM: The aim of the study was to compare the relative treatment efficacy and side effects of D-Rx vs. E-Rx. METHODS: A retrospective analysis was performed of patients with distant metastases and/or locoregionally advanced radioiodine-avid DTC who were treated with either D-Rx or E-Rx. Response to treatment was based on RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria. RESULTS: The study group consisted of 87 patients followed for 51 ± 35 months, of whom 43 were treated with D-Rx and 44 with E-Rx. Multivariate analysis, controlling for age, gender, and status of metastases revealed that the D-Rx group tended to be 70% less likely to progress (odds ratio, 0.29; 95% confidence interval, 0.087–1.02; P = 0.052) and more likely to obtain complete response (CR) compared to the E-Rx group (odds ratio, 8.2; 95% confidence interval, 1.2–53.5; P = 0.029). There was an association in the D-Rx group between the observed CR and percentage of maximum tolerable activity given as a first treatment of 131I (P = 0.030). The advantage of D-Rx was specifically apparent in the locoregionally advanced group because CR was significantly higher in D-Rx vs. E-Rx in this group of patients (35.7 vs. 3.3%; P = 0.009). The rates of partial response, stable disease, and progression-free survival, as well as the frequency of side effects, were not significantly different between the two groups. CONCLUSION: Higher efficacy of D-Rx with a similar safety profile compared to E-Rx supports the rationale for employing individually prescribed activity in high-risk patients with DTC.

The objective of this study was to evaluate the detection of the foci of radioiodine (RAI) uptake in the thyroid bed and neck of patients with well-differentiated thyroid cancer using a pinhole collimator (PiHC) compared with either whole-body images (WBIs) or individual images obtained using a parallel-hole collimator (PaHC).

Thyroid disease in general, and hypothyroidism in particular, are very common in women. In the USA, the most common cause of primary thyroid deficiency is on an autoimmune basis due to lymphocytic (Hashimoto) thyroiditis. Because there are thyroid hormone receptors in virtually every tissue of the body, the manifestations of hypothyroidism are varied, but problems with abnormal menses, conception, fertility, and pregnancy can be especially troubling in young women. The single most important diagnostic test is measurement of serum thyrotropin (TSH). The overwhelming majority of patients with hypothyroidism are treated with a single daily dose of synthetic levothyroxine with the goal of therapy being restoration of a normal metabolic state with return of the TSH level down to the range of 0.5 to 1.5 mlU/L. “Subclinical” hypothyroidism refers to those patients with early or mild thyroid hypofunction manifested as slight elevations of thyrotropin (∼4–10 mlU/L) although serum thyroxine (T4) and triiodothyronine (T3) levels are within their reference ranges. The entity is somewhat controversial in regard to its consequences if left untreated, and whether or not we should be screening patients, at least susceptible populations, for the condition. Reports indicate an association between subclinical hypothyroidism and poor outcomes of pregnancy, as well as dyslipidemias, atherogenesis, and increased mortality in the long term. We believe these consequences are sufficiently compelling to warrant screening and treatment with levothyroxine when found to halt progression to overt hypothyroidism, and improve symptoms, pregnancy outcomes, lipid abnormalities, and cardiovascular function.

In the absence of definitive studies relating radioiodine dose to outcomes, selection of a dose of radioiodine to treat metastatic thyroid carcinoma is problematic, and several approaches have been used. These include empiric fixed doses and doses used on dosimetric approaches specific for each patient. This paper is a review of the rationale and technique for dosimetrically-determined doses of radioiodine for the treatment of metastatic thyroid carcinoma. This review (1) discusses the alternatives for selection of a dose, (2) discusses the two major approaches for determining radioiodine doses dosimetrically, (3) briefly reviews several modifications of these approaches, (4) reviews the literature regarding the results, (5) discusses the side effects of these different approaches, and (6) concludes with recommendations for patient management and future research. This review does not address use of dosimetrically-determined doses of radioiodine for the initial ablation of thyroid tissue postoperatively.

Abstract: Pneumonia is the feared consequence of persistent aspiration of saliva. Although some persons with impaired protection of the laryngeal airway are thought to be at risk, it is not known with certainty which factors are important. Some patients receive tracheostomies to enhance airway safety, often without clear evidence of aspiration of oropharyngeal secretions. A simple, readily available technique is described by which oral secretions are scintigraphically labeled with technetium-99m sulfur colloid via slow intraoral infusion. Subsequent sequential chest imaging with a gamma camera allows detection and tracking of the aspirated material. Three persons are described in whom this technique was used. Inone, the scintigraphic analysis was instrumental in implicating infected saliva as the likely source of recurrent pulmonary infections. Although the method is useful in detecting aspiration of saliva in high risk persons, more study is needed to equate the degree of aspiration visualized with the risk of pulmonary disease.