Minimal Extrathyroidal Extension in Predicting 1-Year Outcomes: A Longitudinal Multicenter Study of Low-to-Intermediate-Risk Papillary Thyroid Carcinoma (ITCO#4)

Background: The role of minimal extrathyroidal extension (mETE) as a risk factor for persistent papillary thyroid carcinoma (PTC) is still debated. The aim of this study was to assess the clinical impact of mETE as a predictor of worse initial treatment response in PTC patients and to verify the impact of radioiodine therapy after surgery in patients with mETE. Methods: We reviewed all records in the Italian Thyroid Cancer Observatory (ITCO) database and selected 2237 consecutive patients with PTC who satisfied the inclusion criteria (PTC with no lymph node metastases and at least 1 year of follow-up). For each case, we considered initial surgery, histological variant of PTC, tumor diameter, recurrence risk class according to the American Thyroid Association (ATA) risk stratification system, use of radioiodine therapy, and initial therapy response, as suggested by ATA guidelines. Results: At 1-year follow-up, 1831 patients (81.8%) had an excellent response, 296 (13.2%) had an indeterminate response, 55 (2.5%) had a biochemical incomplete response, and 55 (2.5%) had a structural incomplete response. Statistical analysis suggested that mETE (odds ratio [OR] 1.16, p=0.65), tumor size >2 cm (OR 1.45, p=0.34), aggressive PTC histology (OR 0.55, p=0.15), and age at diagnosis (OR 0.90, p=0.32) were not significant risk factors for a worse initial therapy response. When evaluating the combination of mETE, tumor size, and aggressive PTC histology, the presence of mETE with a >2 cm tumor was significantly associated with a worse outcome (OR 5.27, 95% CI, p=0.014). The role of radioiodine ablation in patients with mETE was also evaluated. When considering radioiodine treatment, propensity score-based matching was performed, and no significant differences were found between treated and non-treated patients (p=0.24). Conclusions: This study failed to show the prognostic value of mETE in predicting initial therapy response in a large cohort of PTC patients without lymph node metastases. The study suggests that the combination of tumor diameter and mETE can be used as a reliable prognostic factor for persistence and could be easily applied in clinical practice to manage PTC patients with low-to-intermediate risk of recurrent/persistent disease

Role of age at diagnosis in defining potential familial nonmedullary thyroid cancer in kindreds with two affected members

Context The definition of familial nonmedullary thyroid cancer (FNMTC) in 2 or more first-degree relatives is controversial due to the high probability of observing a sporadic association when only 2 members of first-degree relatives are affected. Objective To evaluate the role of age at diagnosis in differentiating the true cases of FNMTC. Design, Setting, Participants, and Main Outcome From a group of 721 papillary thyroid cancer (PTC) patients, 95 familial PTC (FPTC) patients with 2 first-degree relatives have been identified. They were split in 2 groups: Group 1 consisted of both the proband and the affected relative, with age at diagnosis ≤ 45 years; Group 2 consisted of proband and/or the affected family member, with age at diagnosis > 45 years. The clinical-pathological features and outcome of both FPTC groups were compared with 626 sporadic PTC patients (SPTC). Results Familial PTC patients with age at diagnosis ≤ 45 years, compared with the matched group of sporadic PTCs, had a more frequent multifocal, bilateral, and extrathyroidal extension of tumor and showed worse outcome. No differences were found between FPTC and SPTC patients with age > 45 years. At multivariate analysis, distant metastases, American Thyroid Association (ATA) risk, and FPTC ≤ 45 years were independent predictors of outcome. Conclusions Based on the observation that PTC is more aggressive when the diagnosis is made in 2 family members, both with age < 45years, we suggest that the definition of FPTC in kindreds with 2 affected members should also take into account the age at diagnosis as a key element of familial cancer. © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved

Bariatric surgery reduces serum anti-mullerian hormone levels in obese women with and without polycystic ovarian syndrome

Obesity in fertile women has negative effect on fertility. Anti-mullerian hormone (AMH)represents a good index of fertility, and it is considered a marker of ovarian reserve and of polycystic ovarian syndrome (PCOS) gravity. Previous studies evaluated the relationship between obesity and AMH with contradictory results. The aim of the study was to investigate the relationship between obesity and AMH and the changes of AMH in obese women in reproductive age submitted to bariatric surgery. Fifty-five obese patients between 18 and 39 years with (29 patients) and without PCOS (26 patients) were compared with a control group of normal weight women with (24 patients) and without PCOS (19 patients). Fourteen obese women with PCOS and 18 without PCOS underwent to bariatric surgery. Serum AMH, testosterone, androstenedione, and DHEAS were performed in all patients before and 1 year after surgical intervention. AMH was significantly higher in the PCOS groups (p < 0.001), both in obese (5.84 ± 3.94 ng/ml) and non-obese women (7.35 ± 4.39 ng/ml). AMH was positively related to testosterone (p < 0.0001), androstenedione (p = 0.0005), and DHEAS(p=0.003).After bariatric surgery, AMH levels were reduced in the both PCOS (p = 0.02) and non-PCOS group (p = 0.04). AMH levels are elevated in PCOS patients regardless of the body weight. Bariatric surgery is effective in the normalization of AMH levels (a possible indirect marker of better fertility) only in obese patients with PCOS

Preliminary results from whole-genome expression analysis in patients with secondary adrenal insufficiency treated with modified-release hydrocortisone

Purpose Conventional (CONV) treatment of adrenal insufficiency (AI) is associated with risk of overtreatment: glyco-metabolic impairment, bone loss, and reduced quality of life. Recent findings suggest that modified-release hydrocortisone (MOD) may restore a more physiological cortisol profile. Our aims were: (1) to compare the gene expression profile of peripheral blood mononuclear cells derived from patients, with secondary AI (SAI), under CONV (cortisone acetate or hydrocortisone) or MOD versus healthy controls; and (2) to evaluate MOD effects on serum cortisol profile, glucose, lipid, bone, and clinical parameters.Methods Thirteen patients with SAI were switched from CONV to MOD at equivalent dose. Area under curve (AUC) of both formulations was calculated in six patients. Clinical, metabolic and bone parameters were measured at baseline and 3 months after MOD in all patients. In six patients and six age- and sex-matched healthy controls, a whole-genome expression analysis was performed at baseline, 1 month, and 3 months after MOD.Results (1) The number of genes differentially expressed (n = 235; mainly involved in immune response and metabolism) in SAI patients compared to controls progressively and significantly decreased switching from CONV to MOD (n = 78 at 3 months). (2) Under MOD: AUC of cortisol exposure tended to be smaller and cortisol levels showed a more physiological profile; no significant changes of clinical, metabolic and bone parameters were observed, likely due to the short follow-up, but triglycerides tended slightly to increase.Conclusions MOD may restore a normal gene expression profile as soon as 1 month after switching from CONV

Validation of American Thyroid Association Ultrasound Risk-Adapted Approach for Repeating Cytology in Benign Thyroid Nodules

Background:The 2015 American Thyroid Association (ATA) ultrasound (US) risk stratification system is used to identify thyroid nodules in which fine-needle aspiration cytology (FNAC) should be performed. In addition, this system is used to plan the long-term follow-up of patients with cytological benign thyroid nodules. The aim of our study was to evaluate the ATA US risk-adapted approach for repeating cytology in a large retrospective cohort of consecutive benign nodules with a second FNAC repeated after a median follow-up of 3.8 years (range 1.0-14.2 years). Methods:We retrospectively evaluated 1010 thyroid nodules, with an initial benign cytological diagnosis, that underwent at least one repeat FNAC during the follow-up. Results:The rate of missed cancer in the whole cohort of thyroid nodules was 1.0%, and it increased along by the US risk class (0.8% in very low/low-risk, 1.2% in intermediate-risk, and 3.1% in high-risk nodules). The 2015 ATA US risk stratification system showed a very high accuracy in selecting nodules that did not require a second FNAC (negative predictive value = 99.1%). In addition, the rate of missed cancer significantly increased along with the increase in the US risk class in nodules that showed an enlarged volume (0.4% in the low-risk class and 6.4% in the high-risk class,p = 0.005), while it was very low and not associated with the US features in the subgroup of thyroid nodules that did not grow during the follow-up (p = 0.96). Conclusions:Our results confirm the accuracy of the ATA recommendations in selecting benign nodules for FNAC repetition during the follow-up. An additional cytological evaluation maybe avoided in benign thyroid nodules with low-risk US features, regardless of the evidence of growth during the follow-up. While the utility of the routine repeat FNAC in all benign nodules with high-risk US features remains to be defined, based on our results, repetition of FNAC seems to be indicated in nodules with evidence of growth during the follow-up

Calcitonin Levels in Thyroid Disease Are Not Affected by Autoimmune Thyroiditis or Differentiated Thyroid Carcinoma

Introduction: Association between hypercalcitoninemia and pathological conditions such as autoimmune thyroiditis (AIT) or differentiated thyroid carcinoma (DTC) has been addressed, with conflicting results. We evaluated the prevalence and the clinical relevance of elevated basal serum calcitonin (CT) levels in non-neoplastic (nodular goiter [NG] and AIT) and neoplastic thyroid diseases (DTC). Methods: We retrospectively evaluated 3,250 consecutive patients with thyroid nodular disease who underwent fine-needle aspiration cytology with adequate sample. After exclusion of medullary thyroid cancer (MTC) patients were divided according to the presence/absence of thyroid autoimmunity into NG or nodular autoimmune thyroiditis (N-AIT) and, according to cytological results, in benign or suspicious/malignant nodules. Results: One hundred ninety-seven/3,250 patients (6.0%) showed CT level >10 pg/mL. In 11/3,250 (0.3%) cases, a final histological diagnosis of MTC was made, while the remaining 186/3,250 patients (5.7%) had non-MTC-related hypercalcitoninemia (CT > 10 pg/mL). According to cytological diagnosis, the rate of hypercalcitoninemia was similar in class II and class V-VI groups (5.4 vs. 6.9%, p = 0.4). The occurrence of hypercalcitoninemia was significantly higher in patients with NG (166/2,634 [6.3%]) than in patients with N-AIT (20/605 [3.3%]) (p = 0.004). However, after matching by sex, no difference was found between the 2 groups (NG and N-AIT). These results were confirmed in 598 patients submitted to surgery. Conclusions: AIT and DTC seem not to affect serum CT levels in patients with thyroid nodules. Therefore, hypercalcitoninemia, in these patients, should be submitted to the same diagnostic workup than patients without AIT or DTC. © 2020 European Thyroid Association Published by S. Karger AG, Base

Small papillary thyroid carcinoma with minimal extrathyroidal extension should be managed as ATA low-risk tumor

According to American Thyroid Association (ATA) guideline, papillary thyroid cancer (PTC) with minimal extrathyroidal extension (mETE) is classified at "intermediate risk" of persistent/recurrent disease. However, the impact of mETE per se on patients' outcome is not fully understood. The aim of our study was to evaluate the prognostic significance of mETE in patients with PTC not submitted to therapeutic or prophylactic lymph node dissection, according to tumor size and other prognostic factors