Disturbances in the homeostasis of the elemental composition of thyroid tissue may have serious metabolic and health consequences. It is believed that the accumulation of some metals or the deficiency of others may even cause lethal tumours. Due to the fact that metallomics most often uses human serum to analyse macro and microelements as well as trace elements, it was decided to use material that is more difficult to obtain, but also adds credibility to the research - thyroid tissue samples biopsy. The experiments were conducted on 17 patients diagnosed with: nodular (10) and colloidal goitre (2), chronic thyroiditis (2), follicular adenoma (2) and papillary carcinoma (1). They were recruited by collecting a tumour fragment, control fragment and serum from each of them. The content of Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Zn was examined using ICP-OES (Inductively Coupled Plasma - Optical Emission Spectrometers). Simultaneously, biochemical methods were used to determine the markers of inflammation, glycation and peroxidation: malondialdehyde, pentosidine, reactive free amine content, compounds with thiol groups and galectin 3 in the sera of the examined patients. Three statistically significant correlations were identified: Ca-Mg and Cu-Zn in control tissues (p < 0.05) and Cr-Mn in pathological tissues (p < 0.05). A comparison of individual groups of patients shows that there are some potentail tendencies to increase or decrease in the concentration of certain elements or markers of inflammation and glycation, therefore we discuss potential relationships between a given parameter and a thyroid disorder. The pilot study is an introduction to a deeper analysis aimed at tracing the pathomechanism of the development of thyroid diseases, so that the risk of developing these diseases can be effectively minimized.

BackgroundHyalinizing trabecular tumor (HTT) is an uncommon follicular cell-derived thyroid tumor classified as a low-risk neoplasm by the World Health Organization Classification of Tumors of Endocrine Organs, 5th edition. The PAX8-GLIS3 gene fusion is reportedly a pathognomonic genetic alteration of HTT.Case presentationA 43-year-old Japanese female was incidentally discovered to have an 8-mm, well-defined, hypoechoic mass in the left lobe of the thyroid gland by ultrasound examination. Contrast-enhanced computed tomography scan revealed a solid mass exhibiting slight homogeneous enhancement in the lower pole of the thyroid gland. The mass was diagnosed as atypia of undetermined significance by fine-needle aspiration cytology. The patient underwent left hemithyroidectomy with routine central compartment dissection. Histologic findings revealed tumor cells with elongated nuclei and intranuclear pseudoinclusions arranged with trabeculae architecture or small nests in hyalinized stroma. Weak membranous and cytoplasmic staining was found by MIB1 (Ki-67) immunostaining. The final diagnosis was HTT of the thyroid gland. Next-generation sequencing genetic analysis of a surgical specimen revealed no pathologic mutations, including BRAF, H/K/NRAS, or RET-PTC fusions. The PAX8-GLIS3 fusion was detected by RT-PCR.ConclusionsA rare case of HTT was demonstrated through imaging, cytologic, histologic and molecular investigations. PAX8-GLIS3 fusion detected by RT-PCR and Sanger sequencing was confirmed to be a genetic hallmark of HTT.

Sub-centrimetric papillary thyroid carcinomas usually have a good prognosis with a cancer specific survival of > 99%, however in up to 65% of patients, lymph node metastases can be observed. Molecular alterations in BRAF, TERT and TP53 are associated with worse clinicopathological outcome in patients with papillary thyroid carcinoma. Twenty-two cases of papillary thyroid carcinomas measuring ≤ 1cm with synchronous lymph node metastases were examined regarding morphological patterns and immunohistochemical status of p53, Ki-67, and BRAF V600E status. TERT RNA expression in lymph node metastases were evaluated by RNAScope®. Morphological patterns were heterogeneous in both primary tumors and lymph node metastases. Proliferation indices measured by Ki-67 were low. Both primary and lymph node metastases were wild type for p53 by immunohistochemical analysis. No lymph node metastasis showed TERT expression by RNAScope®. Our data indicate that TERT expression is not involved in the development early lymph node metastasis in patients with sub-centimetric PTC.

BackgroundPapillary thyroid cancer (PTC) is an indolent disease with a favorable prognosis but characterized by a high recurrence rate. We aimed to improve precise stratification of recurrence risk in PTC patients with early stage using multi-gene signatures.Patients and methodsThe present study was performed using data from The Cancer Genome Atlas (TCGA) and multi-center datasets. Unsupervised consensus clustering was used to obtain the optimal molecular subtypes and least absolute shrinkage and selection operator (LASSO) analysis was performed to identify potential genes for the construction of recurrence signature. Kaplan-Meier survival analysis and the log-rank test was used to detect survival differences. Harrells concordance index (C-index) was used to assess the performance of the DNA damage repair (DDR) recurrence signature.ResultsThrough screening 8 candidate gene sets, the entire cohort was successfully stratified into two recurrence-related molecular subtypes based on DDR genes: DDR-high subtype and DDR-low subtype. The recurrence rate of DDR-high subtype was significantly lower than DDR-low subtype [HR = 0.288 (95%CI, 0.084–0.986), P = 0.047]. Further, a two-gene DDR recurrence signature was constructed, including PER1 and EME2. The high-risk group showed a significantly worse recurrence-free survival (RFS) than the low-risk group [HR = 10.647 (95%CI, 1.363–83.197), P = 0.024]. The multi-center data demonstrated that proportion of patients with low expression of PER1 and EME2 was higher in the recurrence group than those in the non-recurrence group.ConclusionsThese findings could help accurately and reliably identify PTC patients with high risk of recurrence so that they could receive more radical and aggressive treatment strategies and more rigorous surveillance practices.

Background Abnormal preconception thyrotropin levels were associated with fecundability and adverse fetomaternal outcomes, however, little is known regarding the natural change of serum thyrotropin in euthyroid preconception women. Thus, we performed a population-based study to evaluate the progression to abnormal thyrotropin in euthyroid preconception women.Methods This retrospective cohort study used data from the National Free Prepregnancy Checkups Project (NFPCP) collected between 2010 and 2020. Female Han Chinese participants aged 20–49 years who had two repeated NFPCP participations with a time interval of 1.5–3.0 years, confirmed non-pregnant status within this duration, and normal thyrotropin levels during their first participation were included for the analysis of thyrotropin abnormalities during the second NFPCP examination. Data were analyzed between June 1 and October 1, 2023.ResultsThis study included 186,095 euthyroid women of reproductive age (mean ± SD, 26.72 ± 4.70 years) whose preconception thyrotropin levels were between 0.37 and 4.87 mIU/L. The median follow-up time was 2.13 (IQR, 1.85–2.54) years. A total of 8,497 (4.57%) women developed abnormal thyrotropin, including 4,118 (2.21%) subnormal thyrotropin and 4,379 (2.35%) supranormal thyrotropin. Compared with the reference group (thyrotropin 1.01–2.00 mIU/L), the lower baseline thyrotropin group had greater risk of developing subnormal thyrotropin, and the higher baseline thyrotropin group had greater risk of developing supranormal thyrotropin. Moreover, the restricted cubic spline analysis revealed a U-shaped dose–response association of baseline thyrotropin levels or thyrotropin multiples of the median (MOM) levels against risk of subnormal thyrotropin in the follow-up, and a J-shaped dose–response association against risk of supranormal thyrotropin levels in the follow-up. We further found that baseline thyrotropin outside of 1.43–1.93 mIU/L or baseline thyrotropin MOM outside 0.59–1.36 would hava a higher risk of developing of abnormal thyrotropin.ConclusionsBoth low and high baseline thyrotropin were associated with a significantly increased risk of developing abnormal thyrotropin outcomes. The optimal preconception baseline thyrotropin levels may be between 1.43 mIU/L and 1.93 mIU/L or baseline thyrotropin MoM between 0.59 and 1.36 to minimize progression toward abnormal thyrotropin after 1.5–3.0 years. These findings may help with counseling of preconception thyroid function monitoring.

Spindle epithelial tumor with thymic like elements (SETTLE) is a biphasic tumor composed of epithelial and spindle cell components. It is an uncommon indolent tumor arising in the thyroid gland and most commonly affects the children and young adults. This entity is mostly overlooked because of its rarity and diagnostic difficulty on morphology. We discuss two cases of SETTLE with varied presentation, diagnostic challenges and lessons learnt from them.SETTLE should be considered as a differential especially when dealing with a thyroid lesion in young and adolescent. The article discusses the histologic details and common mimickers to be borne in mind aiding in arrival at the final diagnosis on biopsy specimens.

BackgroundWhether prophylactic central lymph node dissection is necessary for patients with clinically node-negative (cN0) papillary thyroid microcarcinoma (PTMC) remains controversial. Herein, we aimed to establish an ultrasound (US) radiomics (Rad) score for assessing the probability of central lymph node metastasis (CLNM) in such patients.Methods480 patients (327 in the training cohort, 153 in the validation cohort) who underwent thyroid surgery for cN0 PTMC at two institutions between January 2018 and December 2020 were included. Radiomics features were extracted from the US images. Least absolute shrinkage and selection operator logistic regression were utilized to generate a Rad score. A nomogram consisting of the Rad score and clinical factors was then constructed for the training cohort. Both cohorts assessed model performance using discrimination, calibration, and clinical usefulness.ResultsBased on the six most valuable radiomics features, the Rad score was calculated for each patient. A multivariate analysis revealed that a higher Rad score (P < 0.001), younger age (P = 0.006), and presence of capsule invasion (P = 0.030) were independently associated with CLNM. A nomogram integrating these three factors demonstrated good calibration and promising clinical utility in the training and validation cohorts. The nomogram yielded areas under the curve of 0.795 (95% confidence interval [CI], 0.745–0.846) and 0.774 (95% CI, 0.696–0.852) in the training and validation cohorts, respectively.ConclusionsThe radiomics nomogram may be a clinically useful tool for the individual prediction of CLNM in patients with cN0 PTMC.

BackgroundCoexistence of TSH-secreting pituitary adenoma (TSHoma) and Graves’ disease (GD) is rare and complicates the management decision.MethodsWe present a case of the co-existence of TSHoma and GD. In addition, we systematically searched articles describing TSHoma and GD in the same patient published until 20th March 2023, using Pubmed, Scopus and Embase.Case presentationA 46-year-old man presented with symptoms of thyrotoxicosis. His thyroid function tests showed serum TSH 3.35 (reference range 0.3–4.2) mIU/L, FT3 19.7 (3.7–6.4) pmol/L, and FT4 68.9 (11-23.3) pmol/L. The serum TSH receptor antibody was 11.5 mIU/L (positive at ≥ 1.75 mIU/L). Pituitary magnetic resonance imaging showed macroadenoma compressing the optic chiasm. The patient underwent trans-sphenoidal resection of pituitary adenoma. Postoperatively, he remained on maintenance carbimazole and octreotide.ResultsFourteen articles comprising 15 patients were identified from the systemic search. A total of 16 patients (including the current case) were included in the systematic review. The mean (± SD) age at diagnosis was 41 ± 13.6 years. The majority were females (75%). The median (IQR) TSH was 1.95 (0.12–5.5) mIU/L, the median (IQR) free T3 was 11.7 (7.6–19.7) pmol/L and the median (IQR) free T4 level was 47.6 (33.3–64.4) pmol/L. Ten (76.9%) patients had positive TSH receptor antibody levels. 84.6% had pituitary macroadenoma. Pituitary surgery was performed in 12 (75%) patients. At the last follow-up, 4 (25%) patients had complete resolution of symptoms after pituitary surgery, 3 (18.7%) were on maintenance treatment with thionamides for GD, 1 (6.25%) on beta-blockers and 1 (6.25%) on somatostatin analog.ConclusionTSHoma and GD can co-exist, and it is essential to identify this rare association as it can significantly impact treatment strategies.

BackgroundThyroid storm is a state of circulating thyroid hormone excess leading to multiorgan dysfunction and systemic decompensation. It typically occurs in the setting of poorly controlled hyperthyroidism and a precipitating illness or event. Management of thyroid storm in pregnancy poses unique diagnostic and therapeutic challenges.Main bodyThyroid storm is a clinical diagnosis characterized by hyperpyrexia, tachyarrhythmias, congestive heart failure, gastrointestinal and neuropsychiatric disturbances. However, diagnostic scoring systems have not been validated in pregnancy.Treatment involves specialist consultation, supportive care, and pharmacological options such as anti-thyroid medications, beta blockers, iodine solutions, glucocorticoids, and cholestyramine. These must be adapted and modified in pregnancy to prevent fetal and maternal complications.ConclusionThere is a critical need to recognize thyroid storm during pregnancy and initiate proper medical interventions promptly.

ObjectivesTo describe the demographic characteristics and clinical outcomes following the first cohort of patients with Bening Thyroid Nodule (BTN) and (Papillary Thyroid Microcarcinoma) (PTMC) treated with Radiofrequency Ablation (RFA)in Ecuador.MethodsSingle-center, cross-sectional study. We included adults undergoing RFA for BTN and PTMC between July 2019 and May 2022. Descriptive statistics and the Wilcoxon signed-rank test were used to compare some pre- and post-intervention outcomes.ResultsWe included 44 patients with 36 BTNs and eight PTMCs. The median age was 45.80 years (IQR 16–79 years), and most patients had normal thyroid function (72.72%). The median follow-up time was 7.80 months (IQR1.0-34.0). Nodules were primarily solid (43.21%) or predominantly solid (56.81%). The pre-RFA median volume in the benign lesions group was 10.30 ml (IQR 1.86–18.97). After ablation, the 1-month, 3-month, 6-month, and 12-month median volumes were 6.90 (IQR 0.48–10.15; p < 0.01) mL, 5.72 (IQR 0.77–7.25; p = 0.045); 0.98 (IQR 0.25–3.64; p < 0.01), and 0.11 (IQR 0.07–11.26; p = 0.026), respectively. The volume rate reduction was 47.20%, 72.20%, 74.00%, and 96.20% at 1, 3, 6, and 12-month follow-ups, respectively. The pre-RFA median volume in the PTMC group was 0.25 ml (IQR 0.19–0.48). After ablation, the 1-month, 3-month, and 6-month mean volumes were 0.19 (range 0.12–0.31; p = 0.120) mL, 0.10 (IQR 0.05–0.15; p = 0.13), and 0.01 (IQR 0.005–0.04; p = 0.364), respectively.ConclusionsIn this first report from Ecuador, we found that RFA may be a feasible alternative for treating benign and malignant thyroid nodules in the short term. Long-term data are needed to evaluate oncologic outcomes in PTMC patients.