Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study.

PURPOSE: This multicentric study aimed to investigate the main prognostic factors associated with treatment response at 1 year after radioactive iodine therapy (RAIT) and the last disease status in pediatric patients affected by differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: In the period 1990-2020, all consecutive patients ≤ 18 years from six different centers were retrospectively included. Patients were classified as low, intermediate, and high risk for persistence/recurrence. The response to RAIT was evaluated and scored 1 year later according to 2015 ATA guidelines. Moreover, at the last follow-up, the disease status was evaluated and dichotomized as no evidence of disease (NED) or persistent disease. RESULTS: Two hundred and eighty-five patients (197 female, 88 male; mean age 14.4 years) were recruited. All, except nine, underwent near-total thyroidectomy followed by RAIT. One-year after first RAIT, 146/276 (53%) patients had excellent response, 37/276 (14%) indeterminate response, and 91/276 (33%) incomplete response. One-year after RAIT, children with excellent response had significantly lower stimulated thyroglobulin (sTg) compared to not excellent group (median sTg 4.4 ng/ml vs 52.5 ng/ml, p < 0.001). ROC curve showed sTg higher than 27.2 ng/ml as the most accurate to predict 1-year treatment response. After a median follow-up of 133 months, NED was present in 241 cases (87%) while persistent disease in 35 (13%). At multivariate analysis, sTg and 1-year treatment response categories were both significantly associated with the last disease status (p value 0.023 and < 0.001). CONCLUSIONS: In pediatric DTC, sTg is significantly associated with 1-year treatment response and final outcome. However, 1-year response is the principal prognostic factor able to predict pediatric DTCs outcome.

Early preablation rhTSH-stimulated thyroglobulin predicts outcome of differentiated thyroid cancer (DTC) patients.

AIM: Total thyroidectomy and risk-adapted 131-radioiodine therapy (RaIT) are the treatments of choice in differentiated thyroid cancer (DTC) patients. The response to treatments is assessed 6-12 months after RaIT. However, thyroglobulin (Tg) values obtained just before RaIT also provide reliable informations on patients'outcome. As available data were mostly obtained in hypothyroid status, we evaluated the predictive role of preablation-Tg in patients underwent RaIT after rhTSH stimulation. MATERIAL AND METHODS: We enrolled 299 low-to-intermediate risk DTC patients underwent rhTSH-stimulated RaIT (standard protocol). Serum Tg levels were measured before rhTSH administration (basal Tg), before RaIT (early-stimulated Tg), and 2 days after RaIT (late-stimulated Tg). The early response assessment was done 12 months after RaIT according to 2015 American Thyroid Association (2015 ATA) criteria. RESULTS: Most patients (277/299, 92.6%) had an excellent response (ER) to RaIT, while 15/299 (5.1%) and 7/299 (2.3%) patients showed biochemical incomplete/indeterminate response or persistent structural disease, respectively. At receiver operating characteristic analysis, the optimal cutoff to predict ER was set at 1.55 (AUC = 0.792), 2.6 (AUC = 0.931), and 4.9 (AUC = 0.874) ng/mL, for basal, early-, and late-stimulated Tg, respectively. The overall sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for basal, early-, and late-stimulated Tg were 50%, 96.7%, 93.3%, 55%, and 96.1%; 90.9%, 84.5%, 84.9%, 31.7%, and 99.1%; and 90.9%, 71.8%, 73.2%, 20.4%, and 99%, respectively. In univariate and multivariate logistic regression analysis, early-stimulated Tg cutoff resulted as an independent prognostic marker for predicting ER regardless of gender, age, histotype, histological variant, tumor size, risk classification, and stage of disease. CONCLUSION: Early-stimulated Tg is a reliable diagnostic tool for predicting the response to primary treatment of DTC.

HER2 Analysis in Sporadic Thyroid Cancer of Follicular Cell Origin.

The Epidermal Growth Factor Receoptor (EGFR) family member human epidermal growth factor receptor 2 (HER2) is overexpressed in many human epithelial malignancies, representing a molecular target for specific anti-neoplastic drugs. Few data are available on HER2 status in differentiated thyroid cancer (DTC). The present study was aimed to investigate HER2 status in sporadic cancers of follicular cell origin to better clarify the role of this receptor in the stratification of thyroid cancer. By immunohistochemistry and fluorescence in-situ hybridization, HER2 expression was investigated in formalin-fixed paraffin-embedded surgical specimens from 90 DTC patients, 45 follicular (FTC) and 45 papillary (PTC) histotypes. No HER2 immunostaining was recorded in background thyroid tissue. By contrast, overall HER2 overexpression was found in 20/45 (44%) FTC and 8/45 (18%) PTC, with a significant difference between the two histotypes (p = 0.046). Five of the six patients who developed metastatic disease during a median nine-year follow-up had a HER2-positive tumor. Therefore, we suggest that HER2 expression may represent an additional aid to identify a subset of patients who are characterized by a worse prognosis and are potentially eligible for targeted therapy.

Nodal metastasis in noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

The term noninvasive tumor with a follicular growth pattern and nuclear features of papillary thyroid cancer (NIFTP) is used to describe a tumor currently considered as a pre-malignant lesion for which a conservative therapeutic approach (i.e., lobectomy without radioiodine therapy) is strongly suggested. However, some patients with NIFTP and loco-regional or distant metastases have been already reported. We present an adult male patient with a final histological diagnosis of NIFTP and lymph node metastasis noted at post-therapy whole-body scintigraphy performed some days after radioiodine therapy.

mCRPC progression of disease after [177Lu]Lu-PSMA-617 detected on [18F]Choline: a case of PCa heterogeneity.

Radioligand therapy with [177Lu]Lu-PSMA is a theranostic approach for heavily treated mCRPC patients with positive PSMA PET in the absence of relevant PSMA-negative metastases assessed through CT, MRI, bone scan or FDG PET. In this case, we described a mCRPC patient treated with RLT with discordant PSA values and PSMA images, in which Choline PET confirmed a biochemically suspected disease progression (PD), showing metastatic lesions not revealed by PSMA imaging.

Thyroglobulin Value Predict Iodine-123 Imaging Result in Differentiated Thyroid Cancer Patients.

Background: In differentiated thyroid cancer (DTC) patients, the response to initial treatments is evaluated 6-12 months after radioiodine therapy (RIT) according to the 2015 American Thyroid Association (2015 ATA) criteria. In selected patients, diagnostic 131-radioiodine whole-body scintigraphy (Dx-WBS) is recommended. We evaluated the diagnostic performance of 123I-Dx-WBS-SPECT/CT imaging in detecting incomplete structural responses in the early follow-up of DTC patients and, additionally, derived optimized basal-Tg value as a yardstick for scintigraphic imaging. Methods: We reviewed the records of 124 low or intermediate-risk DTC patients with negative anti-thyroglobulin antibody. All patients had undergone (near)-total-thyroidectomy followed by RIT. The response to initial treatments was evaluated 6-12 months after RIT. Results: According to the 2015 ATA criteria, 87, 19 and 18 DTC patients were classified to have excellent response (ER), indeterminate/incomplete biochemical response (BIndR/BIR) or structural incomplete response (SIR), respectively. Among patients with less than ER, 18 had a positive 123I-Dx-WBS-SPECT/CT. Metastatic disease at 123I-Dx-WBS-SPECT/CT mainly involved lymph nodes within the central compartment, and corresponding neck ultrasound examinations were negative. The ROC curve analysis was performed to define the best basal-Tg cut-off (i.e., 0.39 ng/mL; AUC = 0.852) able to discriminate patients with and without positive 123I-Dx-WBS-SPECT/CT, respectively. The overall sensitivity, specificity, accuracy, PPV and NPV were 77.8%, 89.6%, 87.9%, 56.0% and 95.9%, respectively. Basal-Tg cut-off was an independent risk factor for having a positive 123I-Dx-WBS-SPECT/CT. Conclusion:123I-Dx-WBS-SPECT/CT identified lymph node metastases in 14/37 patients with less than ER and a negative neck ultrasound, thus modifying the management of such patients. The diagnostic performance of 123I-Dx-WBS-SPECT/CT significantly increased in patients with basal-Tg values ≥ 0.39 ng/mL.

Comparison of 1.1 GBq and 2.2 GBq Activities in Patients with Low-Risk Differentiated Thyroid Cancer Requiring Postoperative 131I Administration: A Real Life Study.

OBJECTIVES: To compare the efficacy of low and moderate 131I activities in low-risk differentiated thyroid carcinoma (DTC) patients requiring postoperative thyroid remnant ablation in a real-world clinical setting. METHODS: We retrospectively reviewed the records of 299 low-risk DTC patients (pT1-T2, Nx(0) Mx) who had undergone (near)-total thyroidectomy followed by 131I therapy, using either low (1.1 GBq) or moderate (2.2 GBq) radioiodine activities. The response to initial treatments was evaluated after 8-12 months, and patient responses were classified according to the 2015 American Thyroid Association guidelines. RESULTS: An excellent response was observed in 274/299 (91.6%) patients, specifically, in 119/139 (85.6%) and 155/160 (96.9%) patients treated with low and moderate 131I activities, respectively (p = 0.029). A biochemically indeterminate or incomplete response was observed in seventeen (22.2%) patients treated with low 131I activities and three (1.8%) patients treated with moderate 131I activities (p = 0.001). Finally, five patients showed an incomplete structural response, among which three and two received low and moderate 131I activities, respectively (p = 0.654). CONCLUSIONS: When 131I ablation is indicated, we encourage the use of moderate instead of low activities, in order to reach an excellent response in a significantly larger proportion of patients, including patients with the unexpected persistence of the disease.

Thyroid Cancer Persistence in Patients with Unreliable Thyroglobulin Measurement: Circulating microRNA as Candidate Alternative Biomarkers.

BACKGROUND: We aimed to evaluate the role of circulating miRNAs as a biomarker of the persistence of papillary thyroid cancer (PTC) in patients with an "uninformative" thyroglobulin (Tg) measurement. METHODS: We prospectively enrolled 49 consecutive PTC patients with Tg-positive antibodies (TgAb) who had undergone a (near)-total thyroidectomy and 131I therapy (RIT). The serum thyroid stimulating hormone (TSH), Tg, and TgAb levels were measured before and at 6 and 12 months after RIT, respectively. The serum miRNA (221, 222, 375, 155, and 146b) levels were measured simultaneously. RESULTS: The response to the initial therapy was assessed according to the 2015 ATA criteria. A decrease in 50% or more of serum miRNA over time was observed in 41/49 PTC patients, who showed an excellent response (ER), but six and two patients were classified to have an indeterminate/incomplete biochemical or incomplete structural response to initial therapy. CONCLUSION: Serum miRNA kinetics emerge as a promising biomarker for the early detection of a persistent disease in PTC patients with uninformative Tg results.

Subacute thyroiditis in a patient infected with SARS-COV-2: an endocrine complication linked to the COVID-19 pandemic.

PURPOSE: Subacute thyroiditis (SAT) is an inflammatory thyroid disorder of viral origin, generally preceded by an upper respiratory tract infection. Since the disorder is self-limiting, it is frequently underdiagnosed. However, the disease should not be overlooked since the associated thyrotoxicosis may worsen the clinical course of concomitant disorders (e.g., respiratory distress) and long-term sequelae, such as autoimmune hypothyroidism, have been reported. METHODS: Here we describe a woman who developed SAT with thyrotoxicosis after SARS-COV-2 infection. Coronavirus disease (COVID-19) symptoms were mild and the patient was managed with no specific treatment and recovered rapidly. RESULTS: Six weeks after the onset of the upper respiratory tract infection, the patient developed pain and tenderness in the anterior cervical region, fatigue, tremors, and palpitations. Physical examination revealed mild tremors of the extremities, a diffuse and painful goiter, and enlarged and tender cervical and submandibular lymph nodes. At biochemical evaluation, TSH was suppressed, FT3 and FT4 were high, and serum thyroglobulin was markedly increased (188 pg/mL; n.v. 0-40). Thyroid scintigraphy showed markedly reduced 99mTc-perthecnetate uptake in the gland. All findings were consistent with SAT, and treatment with oral prednisone (25 mg/day as the starting dose, gradually tapered) was started. Under the corticosteroid therapy, there was progressive resolution of symptoms and signs, and, within 4 weeks, all thyroid functional tests and inflammatory indexes normalized. CONCLUSION: Clinicians should be aware of thyroid manifestations potentially associated with COVID-19.

Initial results of the use of a novel semiquantitative parameter in three-phase bone scan to predict 99mTc-HMPAO-labeled leukocyte scintigraphy in patients with unilateral total knee replacement.

OBJECTIVES: The aim of the study was to predict the results of 99mTc-hexamethylpropyleneamine oxime (HMPAO)-labeled autologous leukocytes scintigraphy assessing count ratios in the perfusion (Pr) and blood-pool (BPr) phase images in three-phase bone scan (3PBSr) between the prosthetic knee and the 'healthy' knee and a novel semiquantitative parameter (P/BP ratio) in patients with unilateral knee arthroplasty. METHODS: Patients with unilateral knee arthroplasty and available 3PBS and 99mTc-HMPAO-labeled autologous leukocytes scintigraphic images were searched in two hospitals (A and B). In center A, the perfusion phase was not available. Regions of interest (ROI) were delineated in the perfusion (P) and blood-pool (BP) phase images, incorporating the prosthetic region and applying an isocontour (40% of the maximum pixel activity); corresponding mirror ROIs were placed on the healthy knee. The P/BP ratio was calculated as {[(Pr/BPr) × 100] - 100}. Receiver operator curves (ROCs) were generated for each semiquantitative parameter to identify the optimal cutoff for predicting the results of the autologous leukocytes scintigraphy. RESULTS: In the whole group (79 patients), BPr demonstrated an area under the curve (AUC) of 0.722 (optimal cutoff = 1.43). In center A (52 patients), BPr demonstrated an AUC of 0.737 (cutoff = 1.43), whereas, in center B (27 patients), AUC for BPr was 0.718 (cutoff = 1.6). A better diagnostic performance was obtained selecting Pr (AUC = 0.918; cutoff = 2.34) and P/BP ratio (AUC = 0.947; cutoff = 26.5%) for the discrimination between septic and aseptic loosening. CONCLUSIONS: The novel P/BP ratio seems to be a promising semiquantitative parameter to predict septic loosening. These findings warrant confirmation in larger patient samples.

SARS-COV-2-related immune-inflammatory thyroid disorders: facts and perspectives.

Introduction: During the COVID-19 pandemic thyroid gland alteration/dysfunction has been emerged as a possible endocrine complication. The present review is focused on inflammatory and autoimmune thyroid complications triggered by SARS-CoV-2 infection by searching through databases like MEDLINE and Scopus up to April 2021.Areas covered: Beside the occurrence of 'non-thyroidal illness' in severe clinical conditions, alterations of thyroid function and structure may occur during COVID-19 as a consequence of either direct or indirect effects of SARS-CoV-2 infection on the gland. On the one hand, SARS-CoV-2 uses ACE2 as a receptor to infect the host cells and ACE2 is highly expressed by follicular thyroid cells. On the other hand, COVID-19 is associated with a systemic inflammatory and immune response, involving Th1/Th17/Th2 lymphocytes and proinflammatory cytokines, which resembles the immune activation that occurs in immune-mediated thyroid diseases. COVID-19-related thyroid disorders include destructive thyroiditis and onset or relapse of autoimmune thyroid disorders, leading to a broad spectrum of thyroid dysfunction ranging from thyrotoxicosis to hypothyroidism, that may worsen COVID-19 clinical course and affect prognosis.Expert opinion: Physicians should be aware of the possible occurrence of thyroid dysfunction during and after SARS-CoV-2 infection. Further longitudinal studies are warranted to evaluate potential long-term sequelae.

BRAFV600E mutation is associated with increased prevalence of contralateral lymph-node metastases in low and low-to-intermediate risk papillary thyroid cancer.

OBJECTIVE: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. Despite good prognosis being generally associated with PTC, persistent/recurrent disease can be observed in a not negligible number of patients. Accurate postoperative management can lead to a significant improvement of risk stratification/staging of PTC patients identifying those at higher risk of a more aggressive clinical course. Molecular tests were introduced at the beginning of the 2000s to improve PTC risk stratification. METHODS: We reviewed the records of 354/1185 patients affected by low or low-to-intermediate risk unilateral-PTC. In these patients, BRAFV600E mutation was looked for and 131-radioiodine therapy was performed 3 months after thyroid surgery. A radioiodine post-therapeutic imaging was obtained in all patients. RESULTS: BRAFV600E mutation was found in 170/354 PTC patients (female = 126). Forty-two out of 170 BRAFV600E mutation +ve patients (female = 27) had ipsilateral (n = 24) or contralateral (n = 18) loco-regional metastases at post-therapeutic imaging. Significant differences in terms of 2015 American Thyroid Association risk stratification, Hashimoto thyroiditis prevalence, tumor size, multifocality, disease staging and aggressive variant were observed between BRAFV600E mutation +ve and BRAFV600E mutation -ve patients (P ≤ 0.001;P = 0.001; P ≤ 0.001; P = 0.026; P ≤ 0.001; P ≤ 0.001). Interestingly, the prevalence of contralateral lymph-node metastases was significantly higher in BRAFV600E mutation +ve than BRAFV600E mutation -ve patients (18/42 vs. 2/22, respectively; P = 0.013). CONCLUSION: This study suggests that BRAFV600E mutation represents a significant risk factor for developing contralateral lymph-node metastases and confirms that BRAFV600E mutation is associated with more aggressive PTC features and a higher prevalence of metastatic disease also in low or low-to-intermediate-risk PTC patients.

Isthmus topography is a risk factor for persistent disease in patients with differentiated thyroid cancer.

AIM: The risk of differentiated thyroid cancer (DTC) recurrence is widely evaluated according to the 2015 ATA Risk Stratification System. Topography of malignant nodules has been previously reported as an additional risk factor but is not included in the ATA system. Thus, our study aimed to evaluate the relationship between DTC topography and response to initial therapy. PATIENTS AND METHODS: We enrolled 401 low- to intermediate-risk patients with DTC who had undergone thyroidectomy and radioiodine therapy. DTC topography was recorded and compared with the response to therapy as assessed 12 months after the end of therapy. RESULTS: Overall, 366/401 (91.3%) patients had an excellent response to initial therapy while 22/401 (5.5%) and 13/401 (3.2%) had incomplete biochemical or structural responses, respectively. Incomplete response occurred in 10/36 (27.8%), 5/125 (4.0%), and 4/111 (3.6%) patients whose unifocal malignant nodules were located in the isthmus, right lobe, or left lobe. Incomplete response was also observed in 4/54 (7.4%) and 12/75 (16%) patients carrying multifocal cancers in one or both lobes, respectively. Patients with isthmic cancer more frequently demonstrated incomplete response compared with those who had cancer in other locations (P = 0.00). No significant relationship was found with age, gender, maximum size of malignant nodule, Hashimoto's thyroiditis, vascular invasion, and extrathyroidal extension (P = 0.78, P = 0.77, P = 0.52, P = 0.19, P = 0.73, and P = 0.26, respectively). The risk of incomplete response was about 65% higher in patients with isthmic lesions compared with other patients (odds ratio = 6.725). A log-rank test demonstrated that disease-free survival (DFS) of patients with isthmic lesions was significantly shorter than that of other patients (P = 0.02). CONCLUSION: Our data show that isthmus topography of malignant thyroid nodules is a risk factor for having both persistent disease 12 months after primary treatment and reduced DFS.

Sentinel Node Identification in Melanoma: Current Clinical Impact, New Emerging SPECT Radiotracers and Technological Advancements. An Update of the Last Decade.

BACKGROUND: Melanoma is the most lethal skin cancer with a mortality rate of 262 cases per 100.000 cases. The sentinel lymph node (SLN) is the first lymph node draining the tumor. SLN biopsy is a widely accepted procedure in the clinical setting since it provides important prognostic information, which helps patient management, and avoids the side effects of complete lymph node dissection. The rationale of identifying and removing the SLN relies on the low probability of subsequent metastatic nodes in case of a negative histological exam performed in the SLN. DISCUSSION: Recently, new analytical approaches, based on the evaluation of scintigraphic images are also exploring the possibility to predict the metastatic involvement of the SLN. 99mTc-labeled colloids are still the most commonly used radiotracers but new promising radiotracers, such as 99mTc- Tilmanocept, are now on the market. In the last decades, single photon emission computed tomography- computerized tomography (SPECT/CT) has gained wider diffusion in clinical departments and there is large evidence about its superior diagnostic accuracy over planar lymphoscintigraphy (PL) in the detection of SLN in patients with melanoma. Scientists are also investigating new hybrid techniques combining functional and anatomical images for the depiction of SLN but further evidence about their value is needed. CONCLUSION: This review examined the predictive and prognostic factors of lymphoscintigraphy for metastatic involvement of SLN, the currently available and emerging radiotracers and the evidence of the additional value of SPECT/CT over PL for the identification of SLN in patients with melanoma. Finally, the review discussed the most recent technical advances in the field.

Hepatocyte Growth Factor/C-Met Axis in Thyroid Cancer: From Diagnostic Biomarker to Therapeutic Target.

The hepatocyte growth factor (HGF)/c-met axis plays a crucial role in cancer development by promoting cellular proliferation, motility, and morphogenesis, as well as angiogenesis. Different cellular distributions of both the ligand and the receptor in benign vs malignant lesions indicate this biological system as a candidate for a diagnostic biomarker of malignancy occurring in endocrine glands, such as the thyroid and pituitary. Furthermore, the HGF/c-met expression may help to identify a subset of patients eligible for potential targeted therapies with HGF/c-met inhibitors or antagonists in thyroid tumour, as well as in other malignancies. This may be relevant for iodine-refractory cancers, the treatment of which is still a major challenge. With this in mind, HGF/c-met expression in thyroid cancer tissue may be useful for prognostic and therapeutic stratification of patients.

(99m)Tc-Methoxy-Isobutyl-Isonitrile Scintigraphy Is a Useful Tool for Assessing the Risk of Malignancy in Thyroid Nodules with Indeterminate Fine-Needle Cytology.

BACKGROUND: Thyroid nodular disease is a very common clinical problem. The diagnostic algorithm includes laboratory tests, thyroid ultrasound (US), thyroid scintigraphy, and, if necessary, US-guided fine-needle aspiration cytology. However, cytology results are reported as indeterminate in a not negligible number of patients. This is a central problem in the workup of patients, since about 55-85% of those undergoing surgery do not have thyroid cancer at final histology diagnosis. The aim of this study was to evaluate prospectively the role of (99m)Tc-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) thyroid scintigraphy in differentiating malignant from benign thyroid nodules with indeterminate cytology using quantitative analysis. METHOD: One hundred five patients affected by nodular thyroid goiter and with a euthyroid or hypothyroid functional status were prospectively evaluated. All patients had a suspicious nodule ≥15 mm in maximal diameter on US. All nodules were "cold" on (99m)Tc-pertechnetate scintigraphy and had a cytological diagnosis of class III or IV according to the Bethesda system. Planar images of the thyroid were acquired 10 and 60 minutes after (99m)Tc-MIBI administration. All cold nodules were MIBI-positive. Using quantitative analysis, the MIBI washout index (WOind) was calculated as a percentage reduction value of mean MIBI nodular uptake between early (+10 minutes) and late (+60 minutes) scans. RESULTS: Subdividing the patients into positive and negative for malignancy (either including or excluding patients with Hürthle cell adenoma) and performing receiver operating characterist curve analysis, the optimal WOind cutoff in differentiating malignant from benign follicular lesions was set at -19%. The overall sensitivity and specificity of (99m)Tc-MIBI quantitative analysis in identifying patients with malignant lesions was 100% and 90.9%, respectively. However, after excluding patients with Hürthle cell adenomas from the negative patient group, the overall sensitivity and specificity both reached 100%. CONCLUSION: The use of MIBI scintigraphy using quantitative analysis in the workup of cold nodules with indeterminate cytology is suggested in order to stratify patient risk for a malignant lesion better, thus reducing the number of patients referred to surgery. Surgical treatment should be planned in those patients with a WOind up to -19%.

Thyroid remnant ablation in differentiated thyroid cancer: searching for the most effective radioiodine activity and stimulation strategy in a real-life scenario.

OBJECTIVE: Differentiated thyroid cancer is rare, but the incidence has been increasing in the last few decades. Early treatment is based on surgery and thyroid remnant ablation (TRA) by means of radioiodine therapy. Despite radioiodine being widely used for decades, the choice of ablative activity is generally empirical and no consensus has been reached to date. The aim of our study was to compare the efficacy and safety of different radioiodine activities. In addition, we compared the ablation rate in patients treated in the hypothyroid state or after recombinant human thyroid-stimulating hormone (rhTSH) administration, retrospectively reviewing the records of 471 patients affected by differentiated thyroid cancer. PATIENTS AND METHODS: Patients were subdivided into three groups on the basis of the different activities of radioiodine administered and taking into account the different approaches used to perform the therapy: thyroid hormonal withdrawal or rhTSH stimulation. RESULTS: The success of TRA was evaluated 12 months later. TRA was obtained in 62/79 (78.5%) in group A (1110 MBq in the hypothyroid state), 183/190 (96.3%) in group B [2220 MBq in the hypothyroid state or after rhTSH administration: 87/90 (97%) and 96/100 (96%) patients, respectively], 199/202 (98.5%) in group C [3700 MBq in hypothyroid state or after rhTSH administration: 98/100 (98%) and 101/102 (99%) patients, respectively]. CONCLUSION: Our data demonstrate that 2220 and 3700 MBq radioiodine are more effective compared with 1110 MBq in TRA, without significant differences between 2220 and 3700 MBq or between hypothyroidism and euthyroidism. We suggest rhTSH-aided TRA with 2220 MBq iodine-131, as this approach permits efficacious treatment, thereby reducing side effects, absorbed dose to body and hospital stay.

Is malignant nodule topography an additional risk factor for metastatic disease in low-risk differentiated thyroid cancer?

BACKGROUND: Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. In recent decades, the incidence has been increasing, largely due to increased detection of patients with low-risk or very low-risk DTC. According to European Thyroid Association and American Thyroid Association guidelines, radioiodine (RAI) thyroid remnant ablation is not indicated in very low-risk patients, while its role is still debated in low-risk patients. Accordingly, risk stratification of DTC patients is pivotal when deciding for or against RAI ablation. Presently, risk stratification is based on pTNM staging integrated with clinical parameters. The aim of our study was to evaluate the relationship between location of malignant thyroid nodules within the thyroid gland and the presence of loco-regional and/or distant metastases in patients with pT1a-pT1b DTCs. METHODS: We reviewed the records of 246 patients (214 women, 32 men; female-to-male ratio 6.7:1) affected by unifocal DTC ≤ 2 cm, who had undergone RAI thyroid remnant ablation (activity ranged 555-4588 MBq) after levothyroxine withdrawal or after recombinant human TSH (rhTSH) stimulation. The majority of the patients (91.5%) were affected by papillary thyroid carcinoma. RESULTS: Metastases were discovered by posttreatment whole-body scintigraphy in 29 out of 246 (11.8%) patients. In patients with metastases, malignant thyroid nodules were located in the right lobe (14/123, 11.4%), left lobe (7/95, 7.4%), and isthmus (8/27, 29.6%). The prevalence of metastases was significantly higher in patients with DTC located in the isthmus, compared to other sites (χ(2) = 9.6, p = 0.002). CONCLUSIONS: Our data show for the first time that a location of a thyroid cancer in the isthmus is an additional risk factor for RAI avid metastatic disease in pT1a-pT1b DTC patients, regardless of the presence or absence of other risk factors.