Post-Surgical Indications to Radioiodine Treatment and Potential Risk Factors for Post-Treatment Recurrence in Patients with Intermediate-Risk Differentiated Thyroid Carcinoma.

In this multicentric retrospective observational study, we investigated the potential risk factors for radioiodine (RAI) indication and the post-treatment recurrence of intermediate-risk differentiated thyroid cancer (DTC) 1 and 3 years from diagnosis. We included 121 patients who underwent thyroidectomy for intermediate-risk DTC. The 92 patients (76.0%) who underwent RAI treatment had a higher prevalence of extra-thyroid micro-extension (mETE) (p = 0.03), pT3 staging (p = 0.03) and recourse to therapeutic central (p = 0.04) and lateral (p = 0.01) neck dissection, as well as higher numbers (p = 0.02) and greater dimensions (p = 0.01) of lymph node metastases, compared with untreated patients. Relapse was observed in 18.1% and 20.7% of cases 1 and 3 years from diagnosis, respectively, with no significant differences between groups. A lower age at diagnosis (p = 0.03) and higher levels of stimulated thyroglobulin (Tg) (p = 0.04) emerged as the only independent risk factors for tumour relapse at 1 year. Tumour relapse at 3 years was only independently predicted by the presence of tumour relapse at 1 year (p = 0.04). In conclusion, mETE, pT3 and the presence of large, multiple or clinically evident lymph node metastases represent the main indicators for referring patients to RAI treatment. Early recurrence may be considered the most relevant factor when planning further surveillance.

External Validation of Three Available Grading Systems for Medullary Thyroid Carcinoma in a Single Institution Cohort.

Medullary thyroid carcinoma (MTC) is a rare thyroid carcinoma with a variable clinical behavior. Potential clinical and pathological prognostic markers have been investigated, but studies are limited and controversial. In neuroendocrine neoplasms of various other sites, necrosis and proliferation (mitotic activity and/or Ki67 index) are integrated to provide a histological grade. Recently, an International Medullary Thyroid Carcinoma Grading System (IMTCGS) has been designed to define high- or low-grade MTC by combining proliferative activity and necrosis. This proposal integrates two previously published grading schemes by American (2-tiered grading, low- and high-grade MTC) and Australian authors (3-tiered grading, low-, intermediate-, and high-grade MTC). To validate the clinical role of these systems, their prognostic impact was evaluated in an independent cohort of 111 MTCs. Necrosis, which was the only parameter integrated into the 3 grading systems, proved to be individually correlate with tumor relapse, while no association was found with the proliferation (mitotic count and Ki67 index); however, by combining the different parameters according to all three grading systems, "high-grade" MTCs turned out to be significantly associated with the disease recurrence (p < 0.005) in all systems. In disease-free survival analysis, the IMTCGS stratification was the only one that demonstrated a significant impact at Cox regression analysis (p = 0.004), further confirmed by the Kaplan-Meier curves (p = 0.002). Similar findings were also reproduced when analysis was restricted to sporadic MTCs (68 cases). In conclusion, our results confirm the prognostic role of IMTCGS, supporting the importance of incorporating this information into the pathology report. However, none of the systems proved to predict the overall survival in this validation cohort.

Endocrine disrupting chemicals: effects on pituitary, thyroid and adrenal glands.

BACKGROUND: In recent years, scientific research has increasingly focused on Endocrine Disrupting Chemicals (EDCs) and demonstrated their relevant role in the functional impairment of endocrine glands. This induced regulatory authorities to ban some of these compounds and to carefully investigate others in order to prevent EDCs-related conditions. As a result, we witnessed a growing awareness and interest on this topic. AIMS: This paper aims to summarize current evidence regarding the detrimental effects of EDCs on pivotal endocrine glands like pituitary, thyroid and adrenal ones. Particularly, we directed our attention on the known and the hypothesized mechanisms of endocrine dysfunction brought by EDCs. We also gave a glimpse on recent findings from pioneering studies that could in the future shed a light on the pathophysiology of well-known, but poorly understood, endocrine diseases like hormone-producing adenomas. CONCLUSIONS: Although intriguing, studies on endocrine dysfunctions brought by EDCs are challenging, in particular when investigating long-term effects of EDCs on humans. However, undoubtedly, it represents a new intriguing field of science research.

Predictive factors of a worse response to radioactive Iodine-I131 treatment in hyperthyroidism: outcome analysis in 424 patients. A single centre experience.

PURPOSE: Aim of our study was to search for variables associated with worse outcomes in patients treated with radioactive iodine (RAI) for hyperthyroidism by a dosimetric-based approach. METHODS: Four hundred twenty-four patients with hyperthyroidism related to Toxic Multinodular Goiter (TMG; n = 213), Grave's disease (GD; n = 150) and toxic adenoma (TA; n = 61) treated with RAI between 2000 and 2018 and with at least 12 months follow-up were retrospectively evaluated. Association between outcomes (response vs. no response) at 6 and 12 months and baseline TSH values, anti-thyroid drugs (ATD) duration and posology, RAI absorbed dose and dimensional reduction of target mass at ultrasound was evaluated by Mann-Whitney test. Risk factors for response vs. no-response were analysed by binary logistic regression model. RESULTS: Overall response rate was 78.7 and 83% at 6 and 12 months, respectively. Both at 6 and 12 months higher TSH baseline values (p < 0.001), lower ATD duration (p = 0.004 and p = 0.043), lower ATD posology (p = 0.014 and p = 0.005), and lower dose to target (DT) (327 vs. 373 Gy, p = 0.003) were associated to response. Longer ATD duration and higher ATD posology were independent risk factors for no response at 6 and 12 months in GD and TMG, with no response at 6 months in TA subgroups. CONCLUSIONS: Low TSH levels, longer duration and higher posology of ATD were associated with worse response to RAI. These data confirm that RAI therapy should be considered earlier in patients' management to allow better outcome and avoid ATD toxicity.

Endocrine Autoimmunity in Down's Syndrome.

Since the mid 1900s, a significant increase of infectious, hematological, and autoimmune diseases has been reported in patients with Down's syndrome (DS), independent of sex, age, family history, and exposure to other risk factors, suggesting an intrinsic alteration of the immune system. Several in vitro and in vivo studies have demonstrated alterations of both cellular and humoral immunological response mainly, although not exclusively, secondary to alterations of the expression of autoimmune regulator gene (located on chromosome 21), leading to thymic structural and functional impairments. Autoimmune thyroid disorders (i.e. Hashimoto's thyroiditis and Graves' disease) and type 1 diabetes mellitus are the most common autoimmune endocrine disorders associated with DS, and present with some peculiar features. The underlying etiopathogenic mechanisms and clinical significance of some mild laboratory alterations are still poorly understood. For these aspects, together with the associated multiple comorbidities and intellectual impairment - that make DS patients dependent on care givers - and in the absence of definite guidelines, disease management is very challenging and should be patient-tailored.

Clinical challenges with calcitonin-negative medullary thyroid carcinoma.

PURPOSE: Medullary thyroid carcinoma (MTC) is a relatively uncommon malignant tumor of the parafollicular C cells of the thyroid, which distinguishing feature is the production of calcitonin (CT). CT is a well-recognized tool in the diagnosis and the postsurgical follow-up of patients with MTC with a high sensitivity and specificity, and represents a powerful prognostic indicator. Usually, there is a direct correlation between tumor size and basal CT levels. However, few cases of CT-negative MTCs have been reported in literature and criteria for diagnosis and follow-up are still controversial. METHODS: We performed a brief review on CT-negative MTC and reported our experience on this rare condition, focusing on the clinical characteristics at presentation, the histological and immunostaining features, and the management. RESULTS: Fifteen cases of large, palpable, CT-negative MTCs have been reported in the literature so far; moreover, we reported four cases followed at our center. CONCLUSIONS: Although CT-negative MTC is rare, normal/low serum levels of CT and CEA cannot completely exclude the possibility of the diagnosis, when suspected. It is well accepted that early diagnosis is crucial, but there is still no consensus on the optimal postoperative surveillance strategy. The ultrasound evaluation of the cervical region, together with abdominal computerized tomography scan, chest X-ray, and fluorine18-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (FDG-PET/CT), would be recommended in the follow-up of such cases.