Spectrum and Prevalence of Thyroid Diseases at a Tertiary Referral Hospital in Mogadishu, Somalia: A Retrospective Study of 976 Cases

Background. Thyroid disorder is one of the most common noncommunicable diseases worldwide and neglected public health issues in Somalia. The aim of the study thus was to investigate the thyroid disorders in patients attending to the largest tertiary referral hospital in Somalia. Methods. This retrospective study was conducted on patients admitted to the internal department of Somalia Mogadishu-Turkey Education and Research Hospital, Somali, between January 2017 and December 2019. Patients who were tested for thyroid function tests and had complete data were included. Patients with incomplete data and currently treated for any thyroid disorder were excluded from the study. Abstracted data including patients’ sociodemographic characteristics, thyroid function tests, and histopathological findings were retrieved from the hospital database system. Results. A total of 976 patients with thyroid disorders were enrolled, of whom 66.6% (n = 650) were female and 33.4% (n = 326) were male. The mean age of the patients was 47 ± 18.5 years. The majority of the patients were reported in the 31–50 (35.9%) age range. The most reported thyroid function disorders were 58.8% euthyroid sick syndrome followed by 15.4% hypothyroidism, 12.5% subclinical hypothyroidism, 7.6% hyperthyroidism, and 5.7% subclinical hyperthyroidism. The distribution of comorbidity indicated that 13.4% had diabetes mellitus, 10.4% had HIV, 4.9% had malaria, and 4.5% had HIV and malaria coinfection. Thyroid malignancies were detached in 22 (2.2%) patients including eleven papillary thyroid cancer, nine patients had follicular thyroid cancer, and two patients had differentiated thyroid cancer. Conclusions. Euthyroid sick syndrome was the most common type of thyroid disease in our setup. Hypothyroidism is the second most common, followed by subclinical hypothyroidism. Papillary thyroid cancer was the predominant histology among thyroid malignancies, followed by follicular thyroid cancer. This study revealed that thyroid diseases emerge as an important endocrine disorder encountered in Somali, necessitating a major public health response.

Squamous Differentiation in the Thyroid: Metaplasia, Neoplasia, or Bystander?

Background. Squamous differentiation within the thyroid is seen in a variety of settings. Squamous epithelium is non-native to the thyroid, and its debated origins span reactive metaplasia and developmental/embryologic remnants. Despite a lack of clarity as to its evolution, squamous epithelium may be associated with both neoplastic and non-neoplastic processes. Methods. Thyroid pathology reports spanning a 30-year period were reviewed for terms indicating squamous features. Associated diagnostic and clinical information was collated. Results. Four hundred and twenty seven of 17,452 (2.4%) thyroid surgical pathology cases during this period utilized terminology indicating squamous differentiation including 243 malignant (58%) and 178 benign (42%) diagnoses. There were 111 (26%) primary thyroid malignancies with squamous differentiation, 116 (28%) malignancies of non-thyroid origin including local extension from nearby cancers, and 16 (4%) malignancies of uncertain primary. Most benign lesions were non-neoplastic (84%). The minor subset representing benign neoplasia was interpreted as secondary reactive changes. Conclusion. While squamous differentiation is seen routinely in the thyroid, it is most commonly reported in malignancy. For primary thyroid malignancies reported to demonstrate a squamous component, biologically aggressive tumors were overrepresented. Available evidence suggests that multiple pathways may contribute to the presence of squamous epithelium in the thyroid including metaplasia of mature follicular cells, development from established embryonic remnants, or inception in putative, incompletely characterized stem-like cells. Our retrospective review presents an institutional landscape from which further investigation into the frequency and unique histologic and molecular context of intrathyroidal squamous differentiation as a driver or terminal event in thyroid pathophysiology.

Promoter Methylation of Tumor Suppressors in Thyroid Carci-noma: A Systematic Review

Background: The tumor suppressor genes play a critical role in cellular and molecular mechanisms such as cell cycle processes, cell differentiation and apoptosis. Aberrant DNA methylation of tumor suppressor genes and subsequent gene expression changes have shown to be involved in the initiation and progression of various malignancies including thyroid malignancies. In this review, we investigated what is known about the impact of promoter hypermethylation on the key tumor suppressor genes known to be involved in cell growth and/or apoptosis of thyroid cancer. Methods: The most important databases were searched for research articles until June 2020 to identify reported tumor suppressor genes that are modulated by methylation modulation changes in thyroid carcinoma. Following the inclusion and exclusion criteria, 26 studies were reviewed using the full text to meet the inclusion and exclusion criteria. Results: The tumor suppressor genes reviewed here are suggestive biomarkers and potential targetable drugs. Inactivation of RASSF1A, DAPK1, SLCFA8, and TSHR through aberrant epigenetic methylation could activate BRAF/MEK/ERK kinase pathways with potential clinical implications in thyroid cancer patients. RARβ2 and RUNX3 could suppress cell cycle and induce apoptosis in malignant cells. TIMP3 and PTEN could prevent angiogenesis and invasion through PIP3 pathway and arrest VEFG activity. Conclusion: The methylation status of key genes in various types of thyroid malignancies could be used in early diagnosis as well as differentiation of malignant and benign thyroid. This is valuable in drug repurposing and discovering alternative treatments or preventions in thyroid cancer.

Is Hashimoto thyroiditis associated with increasing risk of thyroid malignancies? A systematic review and meta-analysis

Background and purpose Hashimoto thyroiditis (HT) is the most common inflammatory autoimmune thyroid disease and also the most common cause of hypothyroidism in developed countries. There is evidence of the role of HT in developing thyroid cancers (TCs). This study investigated the association between HT and different types of TCs. Methods Results of a comprehensive search in three major databases, as well as hand searching, were screened in title/abstract and full-text stages and the relevant data were extracted from the studies that met the inclusion criteria. Risk of bias (RoB) was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools and the meta-analysis was conducted with Comprehensive Meta-Analysis software. Results Out of 4785 records, 50 studies were included in the systematic review, and 27 of them met the criteria for quantitative synthesis. The results indicated a significant role for HT in developing papillary TC (OR: 1.65; 95% CI: 1.04 to 2.61), medullary TC (OR: 2.70; 95% CI: 1.20 to 6.07) and lymphoma (OR:12.92; 95% CI: 2.15 to 77.63); but not anaplastic TC (OR: 1.92; 95% CI: 0.29 to 1.90) and follicular TC (OR: 0.73; 95% CI: 0.41 to 1.27). Also, this study found a significant association between HT and thyroid malignancies (OR: 1.36; 95% CI: 1.05 to 1.77). Conclusion Although we found a significant association between HT and some types of TCs, High RoB studies, high level of heterogeneity, and the limited number of well-designed prospective studies, suggested the need for more studies to reach more reliable evidence.

Preoperative Ultrasonography in the Evaluation of Suspected Familial Non-Medullary Thyroid Cancer: Are We Able to Predict Multifocality and Extrathyroidal Extension?

Family history of thyroid cancer increases the risk of harboring thyroid malignancies that end up having extrathyroidal extension (ETE) and multifocality on histology; some authors suggest a more aggressive surgical approach. Their pre-operative identification could allow more conservative surgical procedures if none of these features are suspected. Our aim was to assess if neck ultrasonography could identify or exclude multifocality or ETE in these patients to tailor the extent of surgery. This retrospective study included patients with previous thyroid surgery, ≥1 first-grade relative with thyroid cancer, and who had undergone pre-surgical ultrasound. ETE was suspected in the case of thyroid border interruption or gross invasion of perithyroidal tissues. Multiple suspicious nodules were defined as suspicion of multifocal cancer. The cohort consisted of 45 patients (median age 49 years, 40 with thyroid cancer, 30 females). The positive predictive value of ultrasonography in predicting multifocality and ETE was 57.14% (25.25–84.03) and 41.67% (21.5–65.1%), respectively, while the negative predictive values were 63.2% (56.4–69.4%) and 72.7% (63.3–80.5%). Pre-operative ultrasound examination is unable to reliably identify or exclude multifocal disease or extrathyroidal extension. In patients scheduled for surgery and with a first-degree relative affected by DTC, a “negative” pre-operative US report does not exclude the potential finding of multifocality and ETE at final histopathology.

SREBP1 promotes invasive phenotypes by upregulating CYR61/CTGF via the Hippo-YAP pathway

Aberrant lipid metabolism provides bioenergetic, biosynthetic, and redox supplies to cancer cells. Previous studies have reported differential lipid profiling in thyroid malignancies. Sterol regulatory element-binding protein 1 (SREBP1), encoded by the SREBF1 gene, is a master regulator of cellular lipid homeostasis. The clinical and functional significance of SREBP1 in thyroid cancer is not well understood. Here, we showed that SREBP1 expression is significantly upregulated in invasive thyroid cancer than in normal thyroid tissue or benign thyroid nodules. High tumoral SREBP1 expression was associated with extrathyroidal extension, advanced disease stage, and shorter disease-specific survival in patients with differentiated thyroid cancer. SREBP1 overexpression significantly increased the oxygen consumption rate, filopodia formation, and migratory and invasive capacities of thyroid cancer cells. Knockdown of SREBF1 or treatment with an SREBP1 activation inhibitor fatostatin had the opposite effect. RNA-Seq analysis showed that modulation of SREBP1 expression was accompanied by corresponding changes in the expression of epithelial-mesenchymal transition markers and CYR61/CTGF. SREBP1-facilitated cell invasion could be abrogated by treatment with a YAP inhibitor such as verteporfin or genetic silencing of CYR61 or CTGF. In summary, SREBP1 upregulation can be used as a prognostic indicator for thyroid cancer, and SREBP1 overexpression is involved in cancer invasiveness, at least partly, through upregulation of CYR61/CTGF via the Hippo-YAP pathway.

Endocrine surgery

This chapter outlines the clinically relevant anatomy and physiology of the thyroid and parathyroid glands. The assessment and management of a patient with a thyroid goitre and post-operative complications are described in detail. Conditions such as thyrotoxicosis, thyroid malignancies, hyperparathyroidism, adrenal incidentaloma, cushing’s syndrome, conn’s syndrome, phaeochromocytoma and multiple endocrine neoplasia are discussed in this chapter.

Malignancy Rate of Bethesda Class III Thyroid Nodules Based on the Presence of Chronic Lymphocytic Thyroiditis in Surgical Patients

BackgroundHashimoto’s thyroiditis (HT), also known as chronic lymphocytic thyroiditis (CLT), may interfere with the accurate cytological diagnosis of thyroid nodules. Recently, HT has been considered a premalignant condition for thyroid cancer development. The diagnosis of atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS) thyroid nodules is challenging and evidence for the malignancy risk of AUS/FLUS thyroid nodules coexisting with CLT is scarce. Therefore, we assessed the malignancy risk of AUS/FLUS thyroid nodules according to the presence of background CLT.MethodsThis study included 357 surgically resected thyroid nodules with AUS/FLUS cytology. Cases with concomitant malignant nodules were excluded. CLT was defined based on the pathologic report after thyroid surgery.ResultsAmong 357 tumors, 130 tumors (36%) were confirmed to have coexisting CLT, and 170 tumors (48%) were determined to be malignant after thyroidectomy. Malignancy rates were similar in both groups (48% in each) regardless of background CLT (62/130 with CLT vs. 108/227 without CLT). In the group with CLT, thyroiditis was more frequent in the final pathology (12% with CLT vs. 1% without CLT, P = 0.003). In multivariate analysis, positive BRAFV600E mutation, highly suspicious sonographic features (K-TIRADS 5), and smaller thyroid nodules were significant factors for thyroid malignancies.ConclusionThe malignancy rate of thyroid nodules with AUS/FLUS cytology was comparable irrespective of the presence of underlying CLT.

Comparative evaluation of BMI-1 proto-oncogene expression in normal tissue, adenoma and papillary carcinoma of human thyroid in pathology samples

Objective Papillary Thyroid carcinoma accounts for more than 60% of adult thyroid carcinomas. Finding a helpful marker is vital to determine the correct treatment approach. The present study was aimed to evaluate the expression of the B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) gene in papillary carcinoma, adenoma, and adjacent healthy thyroid tissues. Pathology blocks of thyroid tissues at the pathology department of patients who have undergone thyroid surgery between 2015 and 2019 were examined; papillary carcinoma, adenoma, and healthy tissues were selected and sectioned. Total RNA was extracted, and the relative expression level of the BMI-1 gene was examined using the Real-Time qPCR method. Results In the papillary and adenoma tissues, BMI-1 was overexpressed (1.047-fold and 1.042-fold) in comparison to healthy tissues (p < 0.05 for both comparisons). However, no statistically significant differences were observed between adenoma and papillary carcinoma tissues regarding BMI-1 gene expression. This study demonstrated a new biomarker for thyroid malignancies and found that the mRNA levels of the BMI-1 gene were higher in tumor tissues compared with healthy tissues. Further studies are needed to evaluate the BMI1 gene expression in other thyroid cancers.