Bread Iodine Content and Thyroid Radioiodine Uptake: A Tale of Two Cities

The iodine content of bread consumed in the Bronx, New York, was found to be significantly lower than that of bread consumed in Columbia, Missouri. This difference in dietary intake of iodine could account for the lowered range of normal values for 24-hour ¹³¹I uptake tests in Columbia, and the persistence of the same normal range for this test over the past 28 years in the Bronx. A population with high iodine intake requires higher doses of radioactive iodine in the diagnosis and treatment of thyroid disease. Questions are raised regarding the relationship of high iodine intake to the risk of developing thyrotoxicosis.     

Comparison of Radioiodine Utilization in Adolescent and Young Adult and Older Thyroid Cancer Patients

ObjectiveDifferentiated thyroid cancer (DTC) is 1 of the most common cancers in adolescents and young adults (AYA, ages 15-39). Although most AYAs with DTC are considered low risk compared to older patients, there are no specific postoperative radioiodine (RAI) treatment recommendations despite the potential adverse effects specific to this age group, namely secondary malignancies and fertility difficulties. This study compares factors influencing RAI utilization in AYA and older patients.MethodsA total of 5,687 primary DTC patients were identified from the SEER (Surveillance, Epidemiology, and End Results) database between January 1, 2004 and January 31, 2009. The 2009 American Thyroid Association (ATA) guidelines were used to classify patients as low (LR) or intermediate/high risk (IHR) based on tumor characteristics. Multivariate logistic regression analysis was performed.ResultsOverall, 56.9% of AYA (n = 1,963) patients received postoperative RAI compared to 52.2% of older (n = 3,724) patients (odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.09-1.35, P = .001). For AYA patients, having a total thyroidectomy (TTx) (OR: 3.53, 95% CI: 2.7-4.61, P < .001) predicted RAI in a multivariate model whereas LR status (OR: 0.52, 95% CI: 0.43-0.63, P < .001) and northeast residence (OR: 0.39, 95% CI: 0.29-0.52, P < .001) decreased the probability. All 3 factors similarly affected older patients in addition to an increased likelihood after lymph node (LN) dissection. Additionally, after selecting for TTx (n = 1,077), no factor influenced the use of RAI for AYA patients, whereas LR (OR: 0.30, 95% CI: 0.21-0.43, P < .001) and northeast residence (OR: 0.39, 95% CI: 0.19-0.79, P = .008) were associated with decreased RAI use in older patients.ConclusionDespite their excellent prognosis, AYA thyroid cancer patients are more likely to receive postoperative RAI compared to older patients. Increased awareness of the unique survivorship implications for AYA patients will be an important aspect to address going forward. (Endocr Pract. 2014;20:405-411)     

Determinants of Long-Term Outcome after Radioiodine Therapy for Solitary Autonomous Thyroid Nodules

ObjectiveTo determine the incidence and clinical predictors of hypothyroidism in one institution after radioiodine treatment of solitary toxic nodules.MethodsWe retrospectively analyzed the outcome of radioiodine therapy in 105 patients with solitary autonomous thyroid nodules treated at our institution during a 10-year period (January 1996 to December 2005; mean duration of follow-up, 53 ± 34 months). Patients were monitored until the development of hypothyroidism, death, or the end of the study period. The cumulative incidence of hypothyroidism was determined by Kaplan-Meier life-table analysis, and predictors of hypothyroidism were determined by using a Cox regression model.ResultsThe cumulative incidence of hypothyroidism was 11% at 1 year, 33% at 5 years, and 49% at 10 years. The development of hypothyroidism was not associated with age, sex, radioiodine dose, radioiodine uptake, or degree of suppression of extranodal tissue on scintiscans. The predictors of occurrence of hypothyroidism were pretreatment with antithyroid medications (P = .004; relative risk = 1.94) and positive thyroid antibody status (P = .008; relative risk = 1.84). Antibody-positive patients showed an earlier progression toward hypothyroidism than did antibody-negative patients.ConclusionHypothyroidism is a common outcome of radioiodine treatment for autonomous thyroid nodules. In this study, coexistent thyroid autoimmunity and pretreatment with antithyroid medications were significant risk factors for the development of hypothyroidism. (Endocr Pract. 2008;14:543-549)     

Induction of Thyroid Gene Expression and Radioiodine Uptake in Melanoma Cells: Novel Therapeutic Implications

Both the MAP kinase and PI3K/Akt pathways play an important role in the pathogenesis of melanoma. We conducted the present study to test the hypothesis that targeting the two pathways to potently induce cell inhibition accompanied with thyroid iodide-handling gene expression for adjunct radioiodine ablation could be a novel effective therapeutic strategy for melanoma. We used specific shRNA approaches and inhibitors to individually or dually suppress the MAP kinase and PI3K/Akt pathways and examined the effects on a variety of molecular and cellular responses of melanoma cells that harbored activating genetic alterations in the two pathways. Suppression of the MAP kinase and PI3K/Akt pathways showed potent anti-melanoma cell effects, including the inhibition of cell proliferation, transformation and invasion, induction of G₀/G₁ cell cycle arrest and, when the two pathways were dually suppressed, cell apoptosis. Remarkably, suppression of the two pathways, particularly simultaneous suppression of them, also induced expression of genes that are normally expressed in the thyroid gland, such as the genes for sodium/iodide symporter and thyroid-stimulating hormone receptor. Melanoma cells were consequently conferred the ability to take up radioiodide. We conclude that dually targeting the MAP kinase and PI3K/Akt pathways for potent cell inhibition coupled with induction of thyroid gene expression for adjunct radioiodine ablation therapy may prove to be a novel and effective therapeutic strategy for melanoma.     

Predictors of Hypothyroidism Following Empirical Dose Radioiodine in Toxic Thyroid Nodules: Real-Life Experience

ObjectiveWe aimed to determine the factors predicting hypothyroidism after radioactive iodine (RAI) treatment in patients with toxic adenoma and toxic multinodular goiter.MethodsWe retrospectively collected the data of 237 patients with toxic multinodular goiter or toxic adenoma who had consecutively received RAI treatment between 2014 and 2020 at 2 medical centers. Patients who received the second RAI treatment and whose medical records could not be accessed were excluded from the study. Finally, 133 patients were included in the study. RAI was administered at an empirical dose of 15 or 20 mCi.ResultsThe median age of the 133 participants was 69 years (interquartile range, 62-75 years), and 64.7% of the participants were women. A total of 42.1% of the patients had toxic adenoma, whereas 57.9% of patients had toxic multinodular goiter. The median follow-up was 24 months (interquartile range, 11-38 months). During the follow-up, 61.7% of patients became euthyroid, 30.8% developed hypothyroidism, and 7.5% remained hyperthyroid. The median month of hypothyroidism onset was 4 months (interquartile range, 2-9 months). Regression analysis revealed 2 factors that could predict hypothyroidism: thyroid-stimulating hormone (odds ratio, 2.548; 95% CI, 1.042-6.231; P = .04) and thyroid volume (odds ratio, 0.930; 95% CI, 0.885-0.978; P = .005).ConclusionOverall, 30.8% of the cases developed hypothyroidism after the RAI treatment. Approximately 78% of hypothyroidism developed within the first 10 months. The risk of hypothyroidism was higher in patients with higher thyroid-stimulating hormone and smaller thyroid volume.     

Basis for Physician Recommendations for Adjuvant Radioiodine Therapy in Early-Stage Thyroid Carcinoma: Principal Findings of the Canadian-American Thyroid Cancer Survey

ObjectiveTo explore physician recommendations regarding radioiodine remnant ablation (RRA) as adjuvant treatment in early-stage well-differentiated thyroid carcinoma (WDTC), their rationale for administration of RRA, and their willingness to involve patients’ opinions in decision making about the use of RRA.MethodsWe surveyed a representative sample of specialty physicians in Canada and the United States and asked survey participants whether they would recommend adjuvant RRA after thyroidectomy for a 1.6-cm papillary thyroid carcinoma (Likert scale of agreement responses from 1 to 7; strong agreement ≥ 6). Factor analysis was performed to explore the rationale for recommendations. We asked whether physicians accepted the role of patients’ preferences in decision making about administration of RRA, and backward conditional logistic regression analysis was used to identify predictors of strong acceptance.ResultsThe effective response rate for the survey was 56.3% (486 of 864), with 62.8% (295 of 470 respondents) strongly recommending RRA. Strong RRA recommendations were founded in opinions that RRA (1) decreases WDTC-related mortality and recurrence and (2) facilitates WDTC follow-up at low risk of adverse effects. Approximately a third of the survey respondents (152 of 474) strongly agreed with incorporation of patients’ preferences in decision making regarding the use of RRA. Physicians without firm convictions about the efficacy of RRA in decreasing disease-related outcomes and those practicing in the United States were most likely to indicate strong support for incorporating patients’ preferences in decision making about RRA.ConclusionThe recommendations of physicians regarding use of adjuvant RRA are founded in beliefs in intervention efficacy and follow-up practices. Physicians in medical practice in the United States and those without strong convictions about RRA efficacy are most likely to incorporate patients’ views in individualizing decisions about RRA therapy. (Endocr Pract. 2008;14:175-184)     

Parathyroid Hormone Level Changes Following Radioiodine Therapy for Thyroid Cancer: A Prospective Observational Study

ObjectiveOur objective was to analyze the effect of radioiodine (RAI) therapy on parathyroid hormone (PTH) secretion.MethodsA total of 137 patients were included and divided into 2 groups based on pretherapy PTH levels. The residual thyroid tissue volume was classified into 4 grades (0-3), and a value of 0 indicated that there was no apparent residual tissue. We analyzed the PTH level changes among different time points in each group and the factors that could predict the PTH level changes.ResultsIn 113 patients with normal parathyroid gland function, the PTH level at baseline, 1 day, 7 days, 1 month, 3 months, and 6 months after RAI therapy did not show any significant difference; in 24 patients with decreased parathyroid gland function, the level of PTH immediately decreased after the implementation of RAI therapy but gradually returned to a pre-RAI therapy level within 6 months. On the seventh day after therapy, the mean value of PTH in patients with a residual thyroid tissue volume of extent of 0/1 was 8.0 ± 2.3 pg/mL, which was significantly higher than that in patients with a residual thyroid tissue volume of extent of 2/3 (P = .011). Similar phenomena were observed 1 month, 3 months, and 6 months after therapy.ConclusionRAI therapy had a significant transient adverse effect on parathyroid gland function in patients with decreased PTH secretion pretherapy, and the extent was associated with the amount of residual thyroid tissue.     

Radioiodine fallout and breast-feeding

The rationale for suspension of breast-feeding after exposure to radioiodine in fallout is presented.     

Unfavorable Responses to Radioiodine Therapy in N1b Papillary Thyroid Cancer: A Propensity Score Matching Study

Objective: Regional nodal metastases carry prognostic significance in papillary thyroid cancer (PTC). However, whether different locational nodal metastases correlate with different therapeutic responses remains controversial. We innovatively applied the response to therapy restratification system to evaluate the dynamic disease status after surgery and radioactive iodine (RAI) therapy in PTC patients with different locational nodal metastases.Methods: A total of 585 nondistant-metastatic PTC patients who underwent total thyroidectomy and RAI therapy were retrospectively enrolled. Patients with nodal metastases were categorized into N1a and N1b groups. Propensity score matching was used to balance the bias between the 2 groups. Therapeutic responses were dynamically evaluated, and responses to RAI therapy were classified into excellent (ER), indeterminate (IDR), biochemical incomplete (BIR) and structural incomplete response (SIR).Results: N1b group patients showed a significantly higher pre-ablation stimulated thyroglobulin (Ps-Tg) level than N1a group patients (7.4 ng/mL versus 3.2ng/mL, P<.001). After RAI therapy, N1b group patients took a longer time to achieve ER (9.86 months versus 3.29 months, P<.001) and exhibited a higher proportion of non-ER (IDR, BIR, and SIR) (39.15% versus 17.46%, P<.001) compared to N1a group patients. In logistic regression, N1b and Ps-Tg ≥10 ng/mL were confirmed to be independent factors predicting non-ER (odds ratio: 2.591, and 9.196, respectively). In Cox regression, patients with N1b disease and Ps-Tg ≥10 ng/mL showed significantly lower hazards for achieving ER (hazard ratio: 0.564, and 0.223, respectively).Conclusion: N1b PTC patients showed inferior responses to surgery and RAI therapy compared to N1a patients. N1b was confirmed to be an independent factor predicting unfavorable responses to RAI therapy.Abbreviations: AJCC = American Joint Committee on Cancer; ATA = American Thyroid Association; BIR = biochemical incomplete response; BRAF^V600E = proto-oncogene B-Raf V600E mutation; CI = confidence interval; CT = computed tomography; DNA = deoxyribonucleic acid; DTC = differentiated thyroid cancer; ER = excellent response; ETE = extrathyroidal extension; HR = hazard ratio; IDR = indeterminate response; LNM = lymph node metastasis; N1a = central cervical LNM; N1b = lateral cervical LNM; OR = odds ratio; PSM = propensity score matching; Ps-Tg = pre-ablation stimulated thyroglobulin; PTC = papillary thyroid cancer; RAI = radioactive iodine; SIR = structural incomplete response; Tg = thyroglobulin; TgAb = thyroglobulin antibody; TSH = thyroid-stimulating hormone     

Ultrasonographic Differentiation of Cervical Lymph Nodes in Patients with Papillary Thyroid Carcinoma After Thyroidectomy and Radioiodine Ablation: A Prospective Study

ObjectiveThe objective of the present study was to validate an ultrasound (US) classification of cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC) after thyroidectomy and radioactive iodine (¹³¹I) ablation.MethodsWe performed a prospective study in which the patients were submitted to thyroidectomy and ¹³¹I ablation and then followed until neck US revealed LN(s) ≥ 5 mm. A total of 288 LNs from 112 patients with PTC were evaluated. Patient management was based on LN characteristics grouped according to the classification system studied here.ResultsThe presence of microcalcifications and/or cystic degeneration of cervical LNs were highly suggestive of a metastatic etiology (specificity of 99.4%). In contrast, the most sensitive finding for LNs affected by PTC was the absence of an echogenic hilum (sensitivity of 100%). In the absence of these findings (microcalcifications, cystic degeneration, echogenic hilum), a metastatic etiology was the most likely in the case of a round LN (specificity of 89%). The differentiation of a spindle-shaped LN without a visible hilum by Doppler analysis permitted us to dichotomize an initial probability of metastases of 13% in 25% (with peripheral vascularization) versus 3.3% (without peripheral vascularization).ConclusionsOur results confirm that the classification proposed for cervical LNs in patients with PTC is valid for determining patient management following initial therapy. (Endocr Pract. 2014;20:293-298)     

Radioiodine therapy of thyroid disease

Ten “ideal” steps used at the University of Michigan to treat well-differentiated thyroid cancer are presented. Using this in 103 patients with well-differentiated thyroid carcinoma and metastases outside their neck, those that were freed of their disease after ¹³¹I therapy survived three times as long as those not cured of their disease. Patients successfully cured of their metastases showed better conformity to the “ideal” steps than the patients with residual metastases. Each of the most commonly asked questions about ¹³¹I treatment of thyroid carcinoma following surgical treatment are discussed.