Alvarado-Mafla, Benjamin

Background: Preparation for radioiodine (RAI) therapy in differentiated thyroid cancer (DTC) often requires thyroid hormone withdrawal (THW) to achieve thyrotropin (TSH) stimulation. Current guidelines recommend TSH ≥30 mIU/L, a target that prolongs hypothyroidism and worsens quality of life, yet rests on limited evidence. Objective: To evaluate the association between pre-RAI TSH levels and oncologic outcomes in adults with DTC prepared by THW. Methods: We conducted a systematic review and meta-analysis of studies comparing outcomes across pre-RAI TSH thresholds (<30 vs. ≥30, <60 vs. ≥60, and <90 vs. ≥90 mIU/L) in adults with DTC prepared by THW. Primary outcomes included disease-specific mortality, recurrence, and response to therapy. Searches in MEDLINE, Embase, Cochrane, and Scopus (inception to March 2025) identified eligible studies. Risk of bias was assessed using the CLARITY tool and certainty of evidence using GRADE. Pooled relative risks (RRs) were calculated using random-effects models. This systematic review was registered in PROSPERO (CRD42020158354). Results: This meta-analysis included eight retrospective cohort studies comprising a total of 4651 DTC patients, predominantly women (68.5%) with a mean age of 46 years. All patients underwent THW before RAI. Across all TSH thresholds examined (<30, <60, and <90 mIU/L), higher pre-RAI TSH levels were not associated with better treatment response, lower recurrence, or reduced mortality. Specifically, patients with higher pre-RAI TSH levels (≥30 mIU/L) did not have better oncologic outcomes compared with those with lower levels (<30 mIU/L). At 2- and 3-year follow-up, no significant differences were observed in excellent (pooled RR = 0.87; confidence interval [CI] 0.68–1.11) or indeterminate (RR = 1.28; CI 0.72–2.27) response rates. Similarly, recurrence rates did not differ (RR = 1.45; CI 0.83–2.55), and no study demonstrated a difference in disease-specific mortality across follow-up periods extending up to 10 years. The certainty of evidence for all outcomes was rated very low due to risk of bias, heterogeneity, and imprecision. Conclusions: The current evidence base is insufficient to support or refute the routine use of a specific TSH threshold before RAI administration. These findings question the recommendation to achieve TSH ≥30 mIU/L before RAI and highlight the need for trials to define the minimal effective level of TSH stimulation.

Abstract Background: Patients with differentiated thyroid cancer (DTC) may benefit of radioiodine ablation (RAI) to reduce the probability of thyroid cancer recurrence. Guidelines recommend that thyroid stimulating hormone (TSH) of &gt;30mIU/L before RAI to optimize treatment response. However, evidence regarding this recommendation is conflicting. We conducted a systematic review and meta-analysis to compare outcomes (thyroid cancer recurrence and survival at 10 years of follow up) of stimulated TSH threshold before RAI with primary analysis focus on &lt;30 mIU/L versus ≥30 mIU/L, and subgroup analysis on &lt;90 mIU/L versus ≥90 mIU/L in patients with DTC after initial total thyroidectomy. Methods: The protocol for this study is registered and available online (CRD42020158354). Briefly, we searched several databases from their inception to April 2020. Reviewers, working independently and in duplicate selected studies for inclusion, extracted data, and evaluated each study’s risk of bias. We excluded studies that used recombinant human thyroid stimulating hormone before ablation. Results: We included five retrospective cohort studies, which enrolled a total of 2,514 patients. Risk of bias was low in four studies and high in one study. Mean age was 47 years old (ranged from 40.7 to 47.9) and most of them were female (69%). The most common DTC type was papillary thyroid cancer (78%). From those articles that reported tumor characteristics, 48% had a size ≤2cm (T1b) and 47% &gt;2cm. Moreover, 73% of the patients had no regional lymph metastasis (N0). Two studies reported radioiodine mean dose given of 30 and 100 mci. A total of 301 patients were included in the TSH threshold &lt;30 mIU/L group and 1788 patients in the TSH ≥30 mIU/L group. Comparing stimulated TSH threshold before RAI (&lt;30 mIU/L versus ≥30 mIU/L), there was difference in recurrence at 1 year (RR 2.46 (C.I. 1.09-5.55) and at 20 years (RR 1.71 (C.I. 1.19 – 2.47). However, there was no difference in mortality at 20 years (RR 0.53 (Confidence Interval (C.I.) 0.12-2.23). In addition, 10-years recurrence was not different when we compared &lt;90 mIU/L versus ≥90 mIU/L TSH (RR 1.06; 95%CI: 0.88 – 1.27). Conclusions: Mortality do not differ between recommended TSH goal (≥30 mIU/L) vs &lt;30 mIU/L in thyroid hormone withdrawal-aided radioiodine ablation in DTC patients. However, the risk of recurrence is reduced when patients achieved a TSH level &gt;30 UI/mL. These results suggest that patients may need to reach a stimulated TSH ≥30 mIU/L stimulated TSH threshold to be treated. Randomized trials are needed to confirm these findings.

Abstract Background: In contrast to the rapid increase in thyroid cancer incidence, the mortality has remained low and stable over the last decades. In Ecuador, however, thyroid cancer mortality has increased. The objective of this study is to determine possible drivers of high rates of thyroid cancer mortality, through a cross-sectional analysis of all patients attending a thyroid cancer referral center in Ecuador.Methods: From June 2014 to December 2017, a cross-sectional study was conducted at the Hospital de Especialidades Eugenio Espejo, a regional reference public hospital for endocrine neoplasia in adults in Quito, Ecuador. We identified the mechanism of detection, histopathology and treatment modalities from a patient interview and review of clinical records. Results: Among 452 patients, 74.8% were young adults and 94.2% (426) were female. 13.7% had a family history of thyroid cancer, and patients’ median tumor size was 2 cm. The incidental finding was 54.2% whereas 45.8% was non-incidental. Thyroid cancer histology reported that 93.3% had papillary thyroid cancer (PTC), 2.7% follicular, 1.5% Hurtle cells, 1.6% medullary, 0.7% poor differentiated, and 0.2% anaplastic carcinoma. The mean MACIS (metastasis, age, completeness, invasion, and size) score was 4.95 (CI 4.15-5.95) with 76.2% of the thyroid cancer patients having MACIS score less than or equal to 6. The very low and low risk of recurrence was 18.1% (79) and 62% (271) respectively. An analysis of 319 patients with non-metastatic thyroid cancer showed that 10.7% (34) of patients had surgical complications. Moreover, around 62.5% (80 from 128 patients with thyroglobulin laboratory results) of TC patients had a stimulated-thyroglobulin value equal or higher than 2 ng/ml. Overall, a poor surgical outcome was present in 35.1% (112) patients. Out of 436 patients with differentiated thyroid carcinoma, 86% (375) received radioactive iodine. Conclusion: Thyroid cancer histological characteristics and method of diagnosis are like those described in other reports without any evidence of the high frequency of aggressive thyroid cancer histology. However, we observed evidence of overtreatment and poor surgical outcomes that demand additional studies to understand their association with thyroid cancer mortality in Ecuador.

Abstract Background: In contrast to the rapid increase in thyroid cancer (TC) incidence, thyroid cancer mortality has remained low and stable over the last decades. In Ecuador, however, TC mortality has increased. The objective of this study is to determine possible drivers of high rates of thyroid cancer mortality, through a cross-sectional analysis of all patients attending a thyroid cancer referral center in Ecuador.Methods: From June 2014 to December 2017, a cross-sectional study was conducted at the Hospital de Especialidades Eugenio Espejo (HEEE), a regional reference public hospital for endocrine neoplasia in adults in Quito, Ecuador. We identified the mechanism of detection, histopathology and treatment modalities from a patient interview and review of clinical records. Results: Among 452 patients, 74.8% were young adults and 94.2% (426) were female. 13.7% had a family history of thyroid cancer, and patients’ median tumor size was 2 cm. The incidental finding was 54.2% whereas 45.8% was non-incidental. Thyroid cancer histology reported that 93.3% had papillary thyroid cancer (PTC), 2.7% follicular, 1.5% Hurtle cells, 1.6% medullary, 0.7% poor differentiated, and 0.2% anaplastic carcinoma. The mean MACIS (metastasis, age, completeness, invasion, and size) score was 4.95 (CI 4.15-5.95) with 76.2% of the thyroid cancer patients having MACIS score less than or equal to 6. The very low and low risk of recurrence was 18.1% (79) and 62% (271) respectively. An analysis of 319 patients with non-metastatic thyroid cancer showed that 10.7% (34) of patients had surgical complications. Moreover, around 62.5% (80 from 128 patients with thyroglobulin laboratory results) of TC patients had a stimulated-thyroglobulin (sTg) value equal or higher than 2 ng/ml. Overall, a poor surgical outcome was present in 35.1% (112) patients. Out of 436 patients with differentiated thyroid carcinoma (DTC), 86% (375) received radioactive iodine (RAI). Conclusion: Thyroid cancer histological characteristics and method of diagnosis are like those described in other reports without any evidence of the high frequency of aggressive thyroid cancer histology. However, we observed evidence of overtreatment and poor surgical outcomes that demand additional studies to understand their association with thyroid cancer mortality in Ecuador.

Abstract Background: In contrast to the rapid increase in thyroid cancer (TC) incidence, thyroid cancer mortality rates have remained low and stable over the last decades. In Ecuador, however, TC mortality has increased and to determine possible drivers, a retrospective analysis of all patients attending a thyroid cancer referral center in Ecuador was conducted. Methods: From June 2014 to December 2017, a cross-sectional study was conducted at the Hospital de Especialidades Eugenio Espejo (HEEE), a regional reference public hospital for endocrine neoplasia in adults in Quito, Ecuador. We identified the mechanism of detection, histopathology and treatment modalities from a patient interview and review of clinical records. Results: Among 452 patients, 74.8% were young adults and 94.2% (426) of patients were female. 13.7% had a family history of thyroid cancer, and median of tumor size was 2 cm. The incidental finding was 54.2% whereas 45.8% was non-incidental. Thyroid cancer histology reported that 93.3% had papillary thyroid cancer (PTC), 2.7% follicular, 1.5% Hurtle cells, 1.6% medullary, 0.7% poor differentiated, and 0.2% anaplastic carcinoma. The mean MACIS (metastasis, age, completeness, invasion, and size) score was 4.95 (CI 4.15-5.95) with 76.2% of the thyroid cancer patients having MACIS score equal or less than 6. The very low and low risk of recurrence was 18.1% (79) and 62% (271) respectively. An analysis of 319 patients with non-metastatic thyroid cancer showed that 10.7% (34) of patients had surgical complications. Moreover, around 62.5% (80 from 128 patients with thyroglobulin laboratory results) of TC patients had a stimulated-thyroglobulin (sTg) value equal or higher than 2 ng/ml. Overall, a poor surgical outcome was present in 35.1% (112) patients. Out of 436 patients with differentiated thyroid carcinoma (DTC), 86% (n=375) received radioactive iodine (RAI). Conclusion: Thyroid cancer histological characteristics and method of diagnosis are like the ones described in other reports without any evidence of the high frequency of aggressive thyroid cancer histology. However, we observed evidence of overtreatment and poor surgical outcomes that demand additional studies to understand their association with thyroid cancer mortality in Ecuador.