Thyroxine treatment with softgel capsule formulation. Usefulness in hypothyroid patients without malabsorption

Background: Levothyroxine sodium (LT4) is the therapy of choice for hypothyroidism. In the last decade, new LT4 formulations, such as liquid and softgel capsules, became available. Even if some evidence has been reached in the efficacy of liquid LT4 in patients with suboptimal TSH on tablet LT4, the usefulness of softgel LT4 has been rarely studied. This study aimed at evaluating the effect of switching from tablet to softgel LT4 patients without increased need for LT4. TSH was used as proxy of LT4 bioavailability and effectiveness. Methods: During the period from April to August 2017, 19 patients on tablet LT4 treatment for hypothyroidism, mostly due to autoimmune thyroiditis, were enrolled. Subjects with causes of malabsorption or increased requirement of LT4 were previously excluded. Patients finally included were asked to switch from tablet to softgel LT4 formulation at unchanged dose and ingestion fashion (30 min before breakfast). TSH was measured with chemiluminescence immunoassays. results: According to exclusion and inclusion criteria, 19 patients were finally selected. One of these had headache 4 days later and come back to tablet LT4, and 18 of them (16W/2M; mean age = 55 years; BMI 22.7 kg/m2) completed the study. They were treated with a median LT4 dose of 88 μg/day and showed a median TSH value of 3.33 mIU/L. The rate of cases with TSH ≤ 4.0 mIU/L was 61.1% (11/18 cases). When patients were re-evaluated after 3 months of softgel LT4, we observed that TSH reached levels under 4.0 mIU/L in 16/18 (88.9%) patients, TSH was lower in 11 cases, and in 6 out of 7 patients with pre-switch TSH values over the normal range. Overall, TSH values on softgel LT4 (median 1.90 mIU/L) was significantly lower from that observed during tablet LT4 (p = 0.0039). conclusion: These data show that hypothyroid patients with no proven malabsorption may have an improved TSH following 3 months from the switch from tablet to softgel LT4 preparation at unchanged dose

Lymph Node Thyroglobulin Measurement in Diagnosis of Neck Metastases of Differentiated Thyroid Carcinoma

Aim. Enlarged cervical lymph nodes (LNs) in patients with thyroid cancer are usually assessed by fine-needle aspiration cytology (FNAC). Thyroglobulin (Tg) is frequently elevated in malignant FNAC needle wash specimens (FNAC-Tg). The objectives of the study were to (1) determine an appropriate diagnostic cut-off for FNAC-Tg levels (2) compare FNAC and FNAC-Tg results in a group of 108 patients affected by differentiated thyroid carcinoma (DTC). Methods. A total of 126 consecutive FNACs were performed on enlarged LNs and the final diagnosis was confirmed by surgical pathology examination or clinical follow-up. The best FNAC-Tg cut-off level was selected by receiver operating curve analysis, and diagnostic performances of FNAC and FNAC-Tg were compared. Results. The rate of FNAC samples adequate for cytological examination was 77% in contrast FNAC-Tg available in 100% of aspirates (<.01). The sensitivity, specificity, and accuracy of FNAC were 71%, 80%, 74%, 100%, 80%, and 94%, respectively. The most appropriate cut-off value for the diagnosis of thyroid cancer metastatic LN was 1.1 ng/mL (sensitivity 100%, specificity 100%). Conclusions. The diagnostic performance of needle washout FNAC-Tg measurement with a cut-off of 1.1 ng/mL compared favorably with cytology in detecting DTC node metastases

Galectin-3 performance in histologic and cytologic assessment of thyroid nodules. A systematic review and meta-analysis

The literature on Galectin-3 (Gal-3) was systematically reviewed to achieve more robust information on its histologic reliability in identifying thyroid cancers and on the concordance between Gal-3 test in histologic and cytologic samples. A computer search of the PubMed and Scopus databases was conducted by combinations of the terms thyroid and Gal-3. Initially, 545 articles were found and, after their critical review, 52 original papers were finally included. They reported 8172 nodules with histologic evaluation of Gal-3, of which 358 with also preoperative FNAC Gal-3 assessment. At histology, Gal-3 sensitivity was 87% (95% confidence intervals [CI] from 86% to 88%), and specificity 87% (95% CI from 86% to 88%); in both cases, we found heterogeneity (I285% and 93%, respectively) and significant publication bias (p &lt; 0.001). The pooled rate of positive Gal-3 at fine needle aspiration (FNAC) among cancers with histologically proven Gal-3 positivity was 94% (95% CI from 89% to 97%), with neither heterogeneity (I214.5%) nor bias (p = 0.086). These data show high reliability of Gal-3 for thyroid cancer at histology, while its sensitivity on FNAC samples is lower. The limits of cytologic preparations and interpretation of Gal-3 results have to be solved

Molecular Imaging and Theragnostics of Thyroid Cancers

SIMPLE SUMMARY: According to the American Cancer Society, approximately 53,000 new cases of thyroid cancer were diagnosed and more than 2200 people died from the disease in 2020. New developments in molecular imaging are significantly improving thyroid cancer diagnostics and therapy. Continuous research in molecular imaging techniques additionally contributes to an understanding of a variety of diseases and enables more efficient care of thyroid cancer patients. Molecular imaging-based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theragnostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contributes to the success of personalized medicine. This review details the inception of molecular imaging and theragnostic applications for thyroid cancer management. ABSTRACT: Molecular imaging plays an important role in the evaluation and management of different thyroid cancer histotypes. The existing risk stratification models can be refined, by incorporation of tumor-specific molecular markers that have theranostic power, to optimize patient-specific (individualized) treatment decisions. Molecular imaging with varying radioisotopes of iodine (i.e., (131)I, (123)I, (124)I) is an indispensable component of dynamic and theragnostic risk stratification of differentiated carcinoma (DTC) while [(18)F]F-fluorodeoxyglucose ([(18)F]FDG) positron emission tomography/computed tomography (PET/CT) helps in addressing disease aggressiveness, detects distant metastases, and risk-stratifies patients with radioiodine-refractory DTC, poorly differentiated and anaplastic thyroid cancers. For medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells, [(18)F]F-dihydroxyphenylalanine (6-[(18)F]FDOPA) PET/CT and/or [(18)F]FDG PET/CT can be used dependent on serum markers levels and kinetics. In addition to radioiodine therapy for DTC, some theragnostic approaches are promising for metastatic MTC as well. Moreover, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC while new theragnostic approaches showed promising preliminary results for advanced and aggressive forms of follicular-cell derived thyroid cancers (i.e., peptide receptor radiotherapy). In order to help clinicians put the role of molecular imaging into perspective, the appropriate role and emerging opportunities for molecular imaging and theragnostics in thyroid cancer are discussed in our present review

Detection rate of FNA cytology in medullary thyroid carcinoma. a meta-analysis

Background: The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. Research Design and Methods: A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. Results: Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as 'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: -3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. Conclusions: The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results. © 2014 John Wiley & Sons Ltd

The ultrasound risk stratification systems for thyroid nodule have been evaluated against papillary carcinoma: a meta-analysis

Thyroid imaging reporting and data systems (TIRADS) are used to stratify the malignancy risk of thyroid nodule by ultrasound (US) examination. We conducted a meta-analysis to evaluate the pooled cancer prevalence and the relative prevalence of papillary, medullary, follicular thyroid cancer (PTC, MTC, and FTC) and other malignancies among nodules included in studies evaluating their performance. Four databases were searched until February 2020. Original articles with at least 1000 nodules, evaluating the performance of at least one TIRADS among AACE/ACE/AME, ACR-TIRADS, ATA, EU-TIRADS, or K-TIRADS, and reporting data on the histological diagnosis of malignant lesions were included. The number of malignant nodules, PTC, FTC, MTC and other malignancies in each study was extracted. For statistical pooling of data, a random-effects model was used. Nine studies were included, evaluating 19,494 thyroid nodules. The overall prevalence of malignancy was 34% (95%CI 21 to 49). Among 6162 histologically proven malignancies, the prevalence of PTC, FTC, MTC and other malignancies was 95%, 2%, 1%, and 1%, respectively. A high heterogeneity was found for all the outcomes. A limited number of studies generally conducted using a retrospective design was found, with possible selection bias. Acknowledging this limitation, TIRADSs should be regarded as accurate tools to diagnose PTC only. Proposed patterns and/or cut-offs should be revised and other strategies considered to improve their performance in the assessment of FTC, MTC and other malignancies

Levothyroxine therapy: Changes of TSH levels by switching patients from tablet to liquid formulation. A systematic review and meta-analysis

Background: In the last years, levothyroxine (LT4) has been commercialized also in liquid formulation, which is less sensitive to the factors known to reduce the absorption of tablet LT4. To date, there is no robust information that liquid LT4 can improve pharmacologic thyroid homeostasis of patients with reduced efficacy of tablet LT4. This analysis aimed at achieving solid evidence that switching thyroxine treatment from tablet to liquid preparation improves patients' TSH levels. Methods: The search was performed in PubMed/MEDLINE and Scopus database based on the terms "thyroid," "levothyroxine," and "liquid," and updated until September 25, 2017. Studies were included only if they described patients with suboptimal TSH on tablet LT4, subsequently switched to liquid LT4. Results: The literature search retrieved 462 articles and six were finally included. The pooled mean difference of TSH value between tablet and liquid LT4 was 4.23 mIU/L (95% CI from 3.69 to 4.77). Mild heterogeneity was found (I260%). Overall mean difference of TSH was significant (p &lt; 0.0001). Conclusion: The present meta-analysis showed that patients with suboptimal TSH on tablet LT4 can have a significantly improved TSH by switching to liquid LT4 formulation at unchanged dose

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