Lincango-Naranjo, Eddy

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 >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 <30 mIU/L versus ≥30 mIU/L, and subgroup analysis on <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% >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 <30 mIU/L group and 1788 patients in the TSH ≥30 mIU/L group. Comparing stimulated TSH threshold before RAI (<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 <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 <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 >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 Introduction: Optimal initial antithyroid drugs (ATD) dosing may achieve rapid improvement in thyroid hormone levels while minimizing risk of adverse events. As ATD have become the most common first line therapy for the treatment of Graves’ disease (GD), we examined trends over time in initial ATD dosing, and the association between guideline-based ATD dosing with time to normalization of FT4 and frequency of adverse events. Methods: This is a single cohort retrospective study in Mayo Clinic, Rochester, MN. We identified adults (≥18 years old) diagnosed with new onset GD between January 1, 2002-December 31, 2019 treated with at least 14 days of ATD and with available initial follow up data within 3 months prior to a dose change. Propylthiouracil (PTU) doses were converted to Methimazole (MMI) equivalents at 10:1 ratio. Guideline concordant care was defined as initial ATD dosed based on 2016 American Thyroid Association guidelines (i.e. 5-10 mg for presenting FT4 between >1.7-2.55 ng/dL, 10-20 mg for 2.56-3.40 ng/dL, and 30-40 mg for 3.41 ng/dL and above). Based on the first follow up FT4 values, patients were grouped into categories of: normal range (FT4 0.9-1.7 ng/dL) and under treated (FT4 >1.7 ng/dL). Results: 398 patients were included; mean (SD) age was 49 years (16.6), and 75% were women. Mean initial (SD) Free T4 value was 3.9 ng/dL (2.8), with patients treated with ATD at mean (SD) starting dose of 21.9 mg (13.3) MMI equivalent. Over time there was a decrease in the starting ATD dose from 30 mg MMI equivalent in 2002-2004 to 20 mg in 2017-2019, despite steady presenting FT4 values (2.7 ng/dL in 2002-2005 and 3.1 ng/dL in 2017-2019). In the subset of 340 patients with overt hyperthyroidism, 181 (53%) received guideline concordant (GC) dosing. Patients receiving GC care had a higher initial FT4 (4.9 vs. 3.6 ng/dL, p=0.002), larger goiters (40 vs. 30 g, p<0.001) and higher initial ATD mean dose (SD) 25 mg (15.7) vs. 21.3 mg (9.9), p= 0.05. However at follow up (median 32 days vs 35 days respectively), both groups had similar proportion of patients with normal FT4 values (43% vs. 42%, p=0.79); undertreated patients (45% vs. 45%, p=0.99) and frequency of adverse events (4% vs. 6%, p=0.40). Conclusion: The initial dose of ATD for the treatment of GD has decreased over the past 2 decades. Most clinicians initiate ATD at a dose concordant to guidelines. Despite this, a significant proportion of patients have persistent hyperthyroidism on initial follow up. In light of evidence of risks associated with duration of hyperthyroidism, strategies to improve optimization of initial dosing are needed. Pending further subgroup analysis by presenting FT4 severity, these preliminary results suggest and approach factoring other variables apart from guideline based initial ATD dose is needed to optimize response. Our data will be utilized to pilot an individualized, patient specific predictive model to guide initial dosing to this end.

Abstract Introduction: Anti-thyroid Drugs (ATD) have become the most frequently used treatment for Graves’ disease (GD) in the United States. However, the response to this therapy is variable. Factors that predict biochemically responsive vs. biochemically persistent disease remain unknown. Identifying predictors of disease poorly responsive to ATD can help guide treatment decision making, follow up planning and prognosis. Methods: From a database of patients with GD treated with ATD and receiving care at an academic medical center between 2009–2019, we selected adults with incident GD treated with ≥14 days of ATD. Results: 172 patients (from a database of 730 patients with GD on ATD) were sampled for the purpose of this pilot and 97 of these met inclusion criteria. Patients had a median age of 50 (18–90); female, 70.1%; never smokers, 64.9%; median goiter size of 40 g (15–100); and median TRAb on presentation of 8.1 mIU/L (1.0- 60). Graves’ orbitopathy (GO) was present in 13.4% at baseline. Patients (100%) were started on methimazole at a median dose of 20 mg (2.5–60). The median time from presentation until biochemical improvement (defined as the first instance of FT4 ≤1.7 ng/dL) was 120.9 days (18–1525), and to biochemical euthyroidism (normal TSH & FT4) was 251 days (41–1259) including a median of 3 (0–17) dose adjustments. In a univariate analysis, response to ATD was divided into two groups; biochemically responsive and biochemically persistent disease (based on reaching biochemical improvement in ≤6 months, or >6 months respectively). Biochemically persistent disease was more common in those with GO at presentation (38.5% vs.11.1%) (p .024). There was a trend towards greater prevalence of biochemically persistent disease in those with TRAb ≥ 8.0 mIU/L (46.2% vs. 27.8%) (p .204), and goiter estimated 30 grams or above by physical examination (30.8% vs. 19.4%) (p .460). Biochemically responsive disease was associated with higher frequency of hypothyroidism during treatment (p .047). Conclusion: Our preliminary results illustrate the spectrum of response to ATD and predictors of biochemically persistent disease. We aim to expand this analysis utilizing a large database. As use of ATD increases, clinicians and patients can apply this data to estimate response to therapy, and identify patients that may require more aggressive therapy, thereby tailoring management plans.

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.