BACKGROUND AND OBJECTIVE

Transient congenital hypothyroidism (TCH) refers to temporary deficiency of thyroid hormone identified after birth which later recovers to improved thyroxine production. Its prevalence in the Philippines has not been reported in a large-scale study. Its diagnosis remains difficult due to its numerous possible etiologies. Identifying the predictive factors of TCH may aid in earlier diagnosis and decreased risk of overtreatment. This study aimed to determine the predictive factors for TCH in children with congenital hypothyroidism (CH) detected by newborn screening (NBS) in the Philippines from January 2010 to December 2017.

In this multicenter retrospective cohort study involving 15 NBS continuity clinics in the Philippines, medical records were reviewed, and clinical and laboratory factors were compared between children with TCH and those with permanent congenital hypothyroidism (PCH). Of the 2,913 children diagnosed with CH in the Philippines from 2010 to 2017, 1,163 (39.92%) were excluded from the study due to an unrecalled or lost to follow-up status, or a concomitant diagnosis of Down Syndrome.

Among the 1,750 patients included in analysis, 6.97% were diagnosed with TCH, 60.80% were female, mean gestational age at birth was 38 weeks, and mean birth weight was 2,841 grams. Confirmatory thyrotropin (TSH) was lower and confirmatory free thyroxine (FT4) was higher in the TCH group compared to those with PCH (TSH 32.80 vs 86.65 µIU/mL [p < 0.0001]; FT4 9.90 vs 7.37 pmol/L [p 0.001]). The TCH group required lower L-thyroxine doses compared to the PCH group at treatment initiation and at 1, 2, and 3 years of age (initial 6.98 vs 12.08 µg/ kg/day [p < 0.0001]; at 1 year 1.89 vs 4.11 µg/kg/day [p < 0.0001]; at 2 years 1.21 vs 3.72 µg/kg/day [p < 0.0001]; at 3 years 0.83 vs 3.45 µg/kg/day [p < 0.0001]). Among those with TCH, mean serum TSH decreased significantly after treatment with L-thyroxine (32.80 vs. 6.55 µIU/ mL, p 0.0001). Other factors associated with TCH were results of thyroid ultrasonography (p 0.007), gestational age at birth (p 0.02), and maternal history of thyroid illness (p < 0.0001).

Of all the patients with confirmed congenital hypothyroidism via the newborn screening, 6.97% were diagnosed with transient CH. Factors associated with TCH are confirmatory TSH and FT4, L-thyroxine dose requirements, thyroid ultrasound findings, gestational age at birth, and a maternal history of thyroid illness.

A 61-year-old woman presented with a 2-month history of non-painful left eye proptosis. Imaging studies showed a superotemporal mass in the left orbit with intracranial extension. Surgical excision of the orbitocranial mass was performed and histopathologic examination revealed metastatic papillary thyroid carcinoma. She subsequently underwent total thyroidectomy. Orbital metastasis from thyroid carcinoma is rare and can be the initial manifestation of occult disease in 63% of cases.

Objective To investigate the value of the novel lymphatic contrast-enhanced ultrasound(LCEUS)and conventional venous contrast-enhanced ultrasound(VCEUS)in the differential diagnosis of benign and malignant cervical lymph nodes in patients with thyroid cancer. Methods Patients with suspected thyroid cancer underwent conventional ultrasound,VCEUS,and LCEUS examinations of cervical lymph nodes before biopsy.The diagnostic abilities of conventional ultrasound,VCEUS,and LCEUS were compared with pathological results as the golden standard. Results Forty-four patients with 52 lymph nodes were included in the final data.Thirty-eight metastatic lymph nodes were confirmed by pathological results,and 14 were benign.The diagnostic sensitivity,specificity,and accuracy were 97.37%,71.43%,and 90.38% for LCEUS,92.11%,35.71%,and 76.92% for VCEUS,and 94.74%,21.43%,and 75.00% for conventional ultrasound,respectively.The area under the curve of LCEUS analyzed by the receiver operating characteristic curve was greater than that of VCEUS(P=0.020)and conventional ultrasound(P<0.001). Conclusion LCEUS could significantly improve the differential diagnosis of cervical lymph node metastasis in the patients with thyroid cancer,providing a basis for precise clinical treatment.
Humans ; Thyroid Neoplasms/diagnostic imaging* ; Lymphatic Metastasis/diagnostic imaging* ; Diagnosis, Differential ; Female ; Male ; Middle Aged ; Ultrasonography ; Adult ; Lymph Nodes/pathology* ; Contrast Media ; Neck ; Aged ; Young Adult ; Adolescent ; Sensitivity and Specificity

Objective To analyze the cellular and histopathological characteristics of underdiagnosed thyroid nodules of Chinese thyroid imaging reporting and data system(C-TIRADS) categories 3 and 4a,thus improving the understanding of these lesions. Methods The data of ultrasound and fine needle aspiration cytology were collected from 683 nodules diagnosed based on pathological evidence in 549 patients undergoing thyroid surgery.The cellular and histopathological characteristics of C-TIRADS 3 and 4a nodules were analyzed. Results Two hundred and sixty-eight nodules were classified as C-TIRADS category 3,including 236 benign nodules,12 low-risk ones,and 20 (7.46%) malignant ones.Two hundred and twenty-one nodules were classified as C-TIRADS category 4a,including 133 benign nodules,7 low-risk ones,and 81 (36.65%) malignant ones.The malignancy rates differed between C-TIRADS 3 and 4a nodules (χ²=58.93,P<0.001),and both were higher than the recommended malignancy rate in the guidelines for malignancy risk stratification of thyroid nodules (C-TIRADS) (both P<0.001).According to the pathological evidence,the underdiagnosed C-TIRADS 3/4a nodules were mainly papillary thyroid carcinoma,especially in patients with Hashimoto thyroiditis.There was not a consistent one-to-one match between each ultrasound result and each cytological classification of low-risk thyroid nodules.Conclusions When the malignant features in preoprative ultrasound imaging are atypical or absent,papillary thyroid carcinoma (especially with Hashimoto thyroiditis),follicular carcinoma,and medullary carcinoma are likely to be underdiagnosed as C-TIRADS 3 or 4a nodules.Therefore,efforts should be made to fully understand the cellular and pathological characteristics of these lesions.
Humans ; Thyroid Nodule/diagnostic imaging* ; Female ; Male ; Middle Aged ; Adult ; Ultrasonography ; Biopsy, Fine-Needle ; Aged ; Young Adult ; Thyroid Neoplasms/diagnostic imaging* ; Adolescent

Objective To analyze the ultrasonographic features of secondary squamous cell carcinoma of the thyroid(SSCC-T)and evaluate the diagnostic value of ultrasound.Methods A retrospective analysis was conducted on clinical and ultrasonographic data from 12 patients with pathologically confirmed SSCC-T treated at Beijing Friendship Hospital,Capital Medical University between January 2016 and January 2025.Evaluated parameters included lesion size,echogenicity,edge,vascularity,calcification,and cervical lymph node metastasis.Descriptive statistical analysis was performed to analyze the ultrasonographic features of SSCC-T,and Fisher's exact test was conducted to analyze the correlation between different ultrasound classifications and thyroid dysfunction.Results The 12 patients showed the following ultrasound classifications:nodular type(50.0%,6/12),diffuse type(33.3%,4/12),and mixed type(16.7%,2/12).All diffuse-type patients exhibited a characteristic cord-like hypoechoic pattern.Cervical lymph node metastasis was observed in all the patients,with 75.0%(9/12)showing lymph nodes >2 cm in maximum diameter.Thyroid dysfunction occurred in 66.7%(8/12)of patients,including 2 patients with dynamic shifts from hyperthyroidism to hypothyroidism.Diffuse and mixed types were associated with hypothyroidism(P=0.038).Conclusions SSCC-T demonstrates specific ultrasonographic features,particularly the cord-like hypoechoic pattern in the diffuse type.For patients with squamous cell carcinoma,regular ultrasound examinations of the thyroid and cervical lymph nodes combined with changes in thyroid function are conducive to the timely detection of thyroid metastasis of squamous cell carcinoma.
Humans ; Retrospective Studies ; Ultrasonography ; Carcinoma, Squamous Cell/diagnostic imaging* ; Thyroid Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Male ; Female ; Middle Aged ; Thyroid Gland/diagnostic imaging* ; Adult

The incidence of thyroid cancer keeps rising globally,with the majority being papillary thyroid carcinoma (PTC),which has a favorable prognosis.However,some aggressive PTCs exhibit different clinical behaviors and higher mortality risks,with the growth rate surpassing that of well-differentiated PTC and undifferentiated cancers.Therefore,achieving precise diagnosis and treatment of thyroid carcinoma presents a significant challenge.Photoacoustic imaging is a molecular imaging technology that integrates optical imaging and ultrasound,providing imaging information on structure,function,and molecules.Moreover,it can utilize exogenous contrast agents to realize tumor treatment,such as photothermal therapy,serving as a promising technology for precise diagnosis and treatment of thyroid carcinoma.Researchers both domestically and internationally have explored the application of photoacoustic imaging in the precise diagnosis and treatment of thyroid tumors.This article reviews the research progress,elucidates the advantages and limitations of photoacoustic imaging in the diagnosis and treatment of thyroid carcinoma,and prospects on the precise diagnosis and treatment of this disease.
Humans ; Thyroid Neoplasms/diagnostic imaging* ; Photoacoustic Techniques/methods* ; Precision Medicine

OBJECTIVES: To investigate the role of nucleolar pre-rRNA processing protein NIP7 (NIP7) in maintaining the malignant phenotype of anaplastic thyroid cancer (ATC) and its molecular mechanisms. METHODS: NIP7 expression in ATC tissues and its gene knock-out effects in ATC cells were analyzed using gene expression microarray (GSE33630), proteome database (IPX0008941000) and the Dependency Map database, respectively. Expression and localization of NIP7 in normal thyroid cells, papillary thyroid cancer cells, and ATC cells were detected by Western blotting. Small interfering RNA (siRNA) was transfected into ATC cells, and the knockdown efficiency of NIP7 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Cell proliferation was assessed by CCK-8 assay, colony formation was evaluated by colony formation assay, and tumor growth was assessed by xenograft tumor model in nude mice. SUnSET (surface sensing of translation) assay combined with co-immunoprecipitation were employed to evaluate the effect of NIP7 silencing on ubiquitin-conjugating enzyme E2 C (UBE2C) translation. Finally, gene set enrichment analysis was used to identify shared pathways of NIP7 and UBE2C, which were validated by qRT-PCR. RESULTS: Compared with normal tissues and papillary thyroid cancer, NIP7 was significantly upregulated in ATC tissues, and had a gene knock-out fitness effect on different ATC cell lines. The relative protein levels of NIP7 in ATC cells were significantly higher than those in normal thyroid follicular cells, and the protein was mainly expressed in the nucleus. NIP7 silencing significantly inhibited cell proliferation and reduced colony formation. Xenograft tumor model showed that NIP7 knockdown significantly slowed down the growth of ATC xenograft, and the tumor volume and weight were significantly lower than those in the control group (all P<0.05). NIP7 silencing downregulated the protein level of UBE2C, but did not affect the expression of UBE2C mRNA. Compared to the control group, UBE2C silencing significantly inhibited ATC cells proliferation (P<0.01) and colony formation (P<0.05). UBE2C overexpression reversed the proliferation-inhibitory effect induced by NIP7 silencing (P<0.01). Gene set enrichment analysis indicated that NIP7 and UBE2C were both involved in DNA replication. NIP7 or UBE2C silencing could significantly downregulate the expression levels of DNA polymerase epsilon, catalytic subunit 2 and replication factor C4 in DNA replication pathway. CONCLUSIONS NIP7 promotes ATC tumor growth by upregulating UBE2C to mediate DNA replication.
Humans ; Ubiquitin-Conjugating Enzymes/genetics* ; Thyroid Neoplasms/genetics* ; Thyroid Carcinoma, Anaplastic/genetics* ; Animals ; Mice, Nude ; Mice ; Cell Line, Tumor ; Cell Proliferation ; Up-Regulation ; RNA, Small Interfering/genetics* ; Nuclear Proteins/metabolism* ; Gene Expression Regulation, Neoplastic

INTRODUCTION

Papillary thyroid cancer (PTC) is generally considered to be an indolent disease with relatively good prognosis. However, some studies have shown that the Filipino population has a higher risk for disease recurrence compared to non-Filipino patients and hence early identification and management during the follow-up period would be beneficial, especially those in whom risk factors for recurrence were identified.

This study aims to identify determinants for disease recurrence of patients with papillary thyroid carcinoma (as defined by the American Thyroid Association (ATA) guidelines 2015) diagnosed from January 1, 2013-December 31, 2017, seen at the University of Santo Tomas Hospital (USTH) outpatient endocrine clinic and underwent total thyroidectomy with or without radioactive iodine ablation therapy.

Retrospective review of outpatient medical records of 82 patients with PTC who underwent total thyroidectomy with or without radioactive iodine (RAI) therapy and achieved excellent response (ER) to therapy was performed. Baseline clinical profile such as age at diagnosis, sex, family history of thyroid cancer, family history of goiter, histopathology result, serial thyroglobulin (Tg), anti-thyroglobulin (anti-Tg) levels, whole body scan reports, neck ultrasound reports and RAI doses were collected. Logistic regression analysis was used to identify determinants to the development of worsening response.

Of the 82 patients, 18 (21.9%) developed worsening response to therapy. Predictors of poor outcomes identified from previous studies such as age, sex, extent of disease, size and multifocality of tumors, ATA risk classification and initial dynamic risk assessment, RAI therapy, level of thyroid-stimulating hormone (TSH) suppression were analyzed. After logistic regression analysis, there was no significant association between variables and progression to worsening response that were previously identified in other studies.

Even though no significant association between investigated variables and worsening response were identified in this study, previous studies with larger populations that had exhibited positive association should be considered and hence current Philippine guidelines for the management of PTC must still be applied.

BACKGROUND

Thyroid fine-needle aspiration biopsy (FNAB) is widely used for thyroid nodule characterization, with approximately 2.7% of samples classified as "inadequate." Non-diagnostic samples pose limitations, resulting in repeated procedures, and unnecessary diagnostic thyroidectomies. Conventional smear (CS) is commonly the method of choice for cytologic preparation of thyroid FNAB. The cell block technique is an alternative that concentrates cells providing additional material for better evaluation and ancillary testing. While conventional smears are commonly used, introducing routine complementary cell blocks could potentially lower costs associated with repeat procedures and improve patient management.

The study aimed to investigate the diagnostic value of incorporating the cell block technique as adjunct to conventional smear technique in reducing nondiagnostic rates (Bethesda Category I) in thyroid-fine needle aspiration biopsies (FNAB) conducted in 2 private hospitals.

This is a multi-center, retrospective cross-sectional study with 701 samples from 528 adult patients, who underwent thyroid FNAB between January 2020 - September 2022. The primary outcome of interest is the reduction in non-diagnostic rates with the combined use of conventional smears and cell block.

The non-diagnostic rates were significantly higher with cell block technique (28.10%) as compared to conventional smears (16.26%), p-value < .01. The results show that conventional smears have lower non-diagnostic rates. With smear cytology alone, 114 (16.3%) of all samples were nondiagnostic. With the addition of cell block technique, 15 of these samples were reclassified as benign (n = 13), Bethesda III (n = 1) or Bethesda IV (n = 1). The rest of the non-diagnostic samples (n = 99) remained Bethesda I. Overall, the equivalent decrease in non-diagnostic rate was 2.1%.

The combined use of cell block and conventional smears did not significantly decrease nondiagnostic rates in thyroid FNAB. In general, conventional smears demonstrated superior diagnostic efficacy across all Bethesda categories, establishing it as the preferred sampling preparation method for thyroid FNAB. Cell blocks should be considered a supplementary technique, particularly in cases where ancillary methods like immunohistochemistry or molecular testing are needed.

INTRODUCTION

Hyperthyroidism was thought to lower thyroid cancer risk due to TSH suppression, potentially leading to overlooked diagnoses. This study examines clinical factors linked to thyroid cancer in hyperthyroid patients who have undergone thyroidectomy.

This study determined the clinical factors associated with malignancy among patients with hyperthyroidism who underwent thyroidectomy in a tertiary hospital.

This analytical cross-sectional study reviewed electronic biopsy results of adult patients who underwent thyroidectomy from January 2009 to December 2019 for hyperthyroidism secondary to Graves’ Disease, Solitary Toxic Adenoma or Multinodular Toxic Goiter. It considered factors linked to thyroid cancer, its prevalence, and clinical features associated with aggressive tumor behavior.

Sixty hyperthyroid patients who underwent thyroidectomy were included, 12 of whom have thyroid cancer. Each increase in the initial free thyroxine (FT4) leads to increased likelihood of thyroid cancer by 1.02 times (95% CI 1.001-1.03, p=0.044). The presence of thyroid nodule is associated with 24 times (95% CI 2.67-3275.62, p=0.002) higher risk of thyroid cancer, while every unit increase in mm for nodule diameter increases thyroid cancer odds by 1.04 times (95% CI 1.01-1.07, p=0.022). An FNAB pre-op diagnosis of malignancy is associated with having histopathologic diagnosis of thyroid cancer increased by 40 times (95% CI 2.42-6668.98, p=0.007). Although aggressive tumor behavior was noted among those with a younger age on average (36.35 vs 46.75 years), higher initial FT4 (95.97 vs 23.55 pmol/L), and those with sizeable diameter of multinodular goiter (95 mm vs 20 mm), only the high FT4 was statistically significant.

Initial FT4, thyroid nodules, nodule size, and pre-operative FNAB finding of a malignancy were the factors associated with thyroid cancer in hyperthyroid patients who underwent thyroidectomy. Furthermore, those with aggressive tumor behavior had higher initial FT4 levels.