UNASSIGNED: Pituitary metastasis (PM) from differentiated thyroid cancer (DTC) is extremely rare and may adversely affect outcomes. We aimed to assess the characteristics and outcomes of patients with PM from DTC.
UNASSIGNED: We systematically reviewed the literature on publications on PM and the different DTC histologic types (papillary, follicular, and Hurthle cell cancers). Three databases (PubMed, Embase, and Scopus) were searched for articles published from 1967 to 2022. Survival time was estimated as the period from the first treatment of PM to the time of death or last follow-up.
UNASSIGNED: Twenty-five articles comprising 27 cases that met the eligibility criteria were identified using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The median age of the patients was 60 years (23 - 86). A preponderance of females (66.7%) with PM most commonly reported papillary thyroid cancer (55.6%). This was followed by follicular thyroid cancer (37.0%) and Hurthle cell cancer (7.4%). The most common presentations were headache, nausea, and vomiting, with visual symptoms in 44.4%. Diabetes insipidus was an infrequent finding (7.4%). The median time from diagnosis or first treatment of DTC to the diagnosis of PM was 3 years (0 - 25). The most common endocrine abnormality was hyperprolactinemia (63.2%), while the most frequently deficient hormone was luteinizing hormone (50%). The most common treatment modality for PM was a combination of radiotherapy and surgery with or without radio-iodine. At the end of the follow-up, 30% of the patients died. Only 33.3% of the patients achieved complete resolution of symptoms. The overall median survival time was 12 months (3 - 108). There was a moderate inverse correlation between the age of patients and survival, which was, however, not statistically significant (rs = -0.45, P = 0.103).
UNASSIGNED: PM from DTC is extremely rare, and Hurtle cell cancer appears to be the least associated with PM. Diabetes insipidus is a rare initial manifestation of PM from DTC. Complete resolution of symptoms is less likely to be achieved in PM from DTC. Older age may confer an increased survival tendency, probably due to more intracranial space volume in older people compared to the younger population. Larger studies are needed to examine the relationship between age and survival in PM from DTC. Also, more observational data are required to determine the predictors of survival and compare the efficacy of the different treatment modalities in patients with PM from DTC.

BACKGROUND: Gene silence via methylation of the CpG islands is cancer\'s most common epigenetic modification. Given the highly significant role of NIS in thyroid cancer (TC) differentiation, this cross-sectional study aimed to investigate the DNA methylation pattern in seven CpG islands (CpG1-7 including +846, +918, +929, +947, +953, +955, and +963, respectively) of the NIS promoter in patients diagnosed with papillary (PTC), follicular (FTC), and multinodular goiter (MNG). Additionally, a systematic review of the literature was conducted to compare our results with studies concerning methylation of the NIS gene promoter.
METHODS: Thyroid specimens from 64 patients met the eligibility criteria, consisting of 28 PTC, 9 FTC, and 27 benign MNG cases. The mRNA of NIS was tested by qRT-PCR. The bisulfite sequencing PCR (BSP) technique was performed to evaluate the promoter methylation pattern of the NIS gene. Sequencing results were received in chromatograph, FASTA, SEQ, and pdf formats and were analyzed using Chromas. The methylation percentage at each position and for each sample was calculated by mC/(mC+C) formula for all examined CpGs; following that, the methylation percentage was also calculated at each CpG site. Besides, a literature search was conducted without restricting publication dates. Nine studies met the eligibility criteria after removing duplicates, unrelated articles, and reviews.
RESULTS: NIS mRNA levels decreased in tumoral tissues of PTC (P = 0.04) and FTC (P = 0.03) patients compared to their matched non-tumoral ones. The methylation of NIS promoter was not common in PTC samples, but it was frequent in FTC (P < 0.05). Significant differences were observed in the methylation levels in the 4th(+ 947), 6th(+ 955), and 7th(+ 963) CpGs sites in the forward strand of NIS promoter between FTC and MNG tissues (76.34 ± 3.12 vs 40.43 ± 8.42, P = 0.004, 69.63 ± 3.03 vs 23.29 ± 6.84, P = 0.001 and 50.33 ± 5.65 vs 24 ± 6.89, P = 0.030, respectively). There was no significant correlation between the expression and methylation status of NIS in PTC and FTC tissues.
CONCLUSIONS: Perturbation in NIS promoter\'s methylation individually may have a potential utility in differentiating MNG and FTC tissues. The absence of a distinct methylation pattern implies the importance of other epigenetic processes, which may alter the production of NIS mRNA. In addition, according to the reversibility of DNA methylation, it is anticipated that the design of particular targeted demethylation medicines will lead to a novel cancer therapeutic strategy.

Ultrasound has been established as a baseline imaging technique for thyroid nodules. The main advantage of adding CEUS is the ability to assess the sequence and intensity of vascular perfusion and hemodynamics in the thyroid nodule, thus providing real-time characterization of nodule features, considered a valuable new approach in the determination of benign vs. malignant nodules. Original studies, reviews and six meta-analyses were included in this article. A total of 624 studies were retrieved, and 107 were included in the study. As recognized for thyroid nodule malignancy risk stratification by US, for acceptable accuracy in malignancy a combination of several CEUS parameters should be applied: hypo-enhancement, heterogeneous, peripheral irregular enhancement in combination with internal enhancement patterns, and slow wash-in and wash-out curve lower than in normal thyroid tissue. In contrast, homogeneous, intense enhancement with smooth rim enhancement and \"fast-in and slow-out\" are indicative of the benignity of the thyroid nodule. Even though overlapping features require standardization, with further research, CEUS may achieve reliable performance in detecting or excluding thyroid cancer. It can also play an operative role in guiding ablation procedures of benign and malignant thyroid nodules and metastatic lymph nodes, and providing accurate follow-up imaging to assess treatment efficacy.

Background: In risk assessment of recurrence, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) are often grouped together as differentiated thyroid cancer (DTC). However, while risk factors affecting recurrence of PTC are well established, risk factors for recurrence of FTC are not. This systematic review examines risk factors for recurrence of FTC and evaluates their significance. Methods: A systematic search on PubMed and Embase was performed in September 2020, including studies evaluating risk factors for recurrence of FTC. A quality assessment of the enrolled studies was performed. Results: Nine studies (n = 1544 patients) from eight countries were included. The average recurrence rate was 13.6%, and distant metastasis (DM) constituted 64.8% of the recurrent cases. The risk factors examined were sex, age at diagnosis, primary tumor size, degree of invasiveness, focality, positive resection margin, lymph node (LN) metastasis, and DM at diagnosis. Risk factors correlated with recurrence of FTC were age older than 45 years, primary tumor size above 40 mm, widespread invasion, multifocality, positive resection margin, LN metastasis, and DM at diagnosis. Sex was not a statistically significant risk factor. Conclusions: We identified seven risk factors associated with recurrence of FTC. Age and multifocality were found to be of greater impact regarding recurrence risk of FTC compared with PTC. Future research needs to address the impact of different risk factors for recurrence of FTC particularly including age, primary tumor size, angioinvasion, and mutational status.

An increasing number of patients with low and moderate risk differentiated thyroid cancer (DTC) are now managed with lobectomy alone. The value of serum thyroglobulin (Tg) in the follow up of these patients remains poorly defined.
A review of the MEDLINE and EMBASE databases was performed to assess the utility of Tg in the follow up of patients undergoing thyroid lobectomy for DTC.
A total of five retrospective reviews were identified including 1136 patients undergoing hemithyroidectomy with or without prophylactic central neck dissection. The overall locoregional recurrence rate was 3.7%. Changes in serum Tg following hemithyroidectomy for cancer were found to be clinically useful in one study only. The proposed cut-off value of 30 ng/mL following hemithyroidectomy as a predictor of recurrent disease was not validated by any study.
Serum Tg values are not useful in the follow up of DTC patients managed with lobectomy alone. Good quality neck ultrasound appears to be an effective modality in the detection of locoregional recurrence in these patients while research efforts continue to identify and validate novel biomarkers.

Background: Serum thyroglobulin (Tg) is used in the follow-up of patients with differentiated thyroid cancers (DTC), but the presence of antithyroglobulin antibodies (TgAbs) makes Tg measurements unreliable. TgAb decline after total thyroidectomy and persistent/increasing levels may indicate cancer persistence/recurrence. Hence, we aimed to determine whether TgAb might be a reliable prognostic marker for DTC. Methods: We conducted a meta-analysis and systematic review. A comprehensive literature search was performed to identify studies of patients with DTC with known TgAb status and prognostic outcomes in five databases (Medline, Embase, PubMed, Google Scholar, and Scopus). We used a random-effects model to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs) for TgAb status and its association with DTC prognosis. Results: After analysis of 34 studies, we found that TgAb+ patients have a higher risk of lymph node metastasis (OR = 1.18 [CI 1.47-2.25]) and cancer persistence/recurrence (OR = 2.78 [CI 1.55-4.98]) than TgAb- patients. However, no significant differences in mean/median tumor size, risk of extrathyroidal extension, tumor multifocality, and cancer mortality were found between the two groups. In a comparison of TgAb trends, patients with persistent/increasing TgAb levels were found to have a higher risk of cancer persistence/recurrence (OR = 9.90 [CI 4.36-22.50]) and cancer mortality (OR = 15.18 [CI 2.99-77]) than patients with decreasing TgAb levels. Conclusions: TgAb positivity and persistent/increasing trends were associated with compromised DTC prognosis. These results suggest that TgAb may be used as a prognostic marker in the follow-up of patients with DTC.

Endobronchial metastasis is a rare manifestation of differentiated thyroid cancer. A 79-year-old male was admitted to the hospital with shortness of breath, chest pain, anemia, and weight loss. Computed tomography of chest revealed multiple lung nodules. Bronchoscopy showed an endobronchial lesion in the right upper lobe. The biopsy of the lesion demonstrated neoplastic cells stained positive for thyroglobulin, thyroid transcription factor-1, and cytokeratin-7, consistent with metastatic follicular thyroid cancer. Physical examination revealed a firm fixed thyroid nodule, which was confirmed by thyroid ultrasound. He subsequently underwent total thyroidectomy and neck exploration. Thyroid gland pathology revealed a nodule with features of high-grade follicular thyroid carcinoma. Metastatic thyroid cancer should be considered in workup of pulmonary nodules. We recommend an examination of thyroid gland in patients who present with pulmonary nodules associated with signs and symptoms of malignancy.

BACKGROUND: Follicular thyroid cancers constitute 15-20% of all thyroid tumors. The usual mode of dissemination is via the hematogenous route. The most common sites of distant metastasis are to the lungs and bones.
OBJECTIVE: A case is presented to demonstrate the unusual presentation of follicular cancer with synchronous digital (distal phalanx of the little finger) and choroidal metastasis that was responsive to radioiodine treatment.
METHODS: A 54-year-old female presented with swelling over the terminal part of the left little finger with thyromegaly. Investigations revealed metastasis from follicular thyroid cancer to the little finger along with pulmonary metastases. She underwent total thyroidectomy with central compartment clearance followed by (131)I therapy. Subsequent follow-up demonstrated complete regression of the digital metastasis and partial regression of the choroidal metastasis which was evaluated after the radioiodine scan that picked up the choroidal metastasis.
CONCLUSIONS: Follicular thyroid cancers can rarely spread to unusual sites like the digits and choroid. This report highlights the synchronous presentation of digital and choroidal metastasis which responded to (131)I therapy.