CircRNA circTIAM1 promotes papillary thyroid cancer progression through the miR-646/HNRNPA1 signaling pathway

Papillary thyroid cancer (PTC) is a common endocrine tumor with a rapidly increasing incidence in recent years. Although the majority of PTCs are relatively indolent and have a good prognosis, a certain proportion is highly aggressive with lymphatic metastasis, iodine resistance, and easy recurrence. Circular RNAs (circRNAs) are a class of noncoding RNAs that are linked to a variety of tumor processes in several cancers, including PTC. In the current study, circRNA high-throughput sequencing was performed to identify alterations in circRNA expression levels in PTC tissues. circTIAM1 was then selected because of its increased expression in PTC and association with apoptosis, proliferation, and migration of PTC cells in vitro and in vivo. Mechanistically, circTIAM1 acted as a sponge of microRNA-646 and functioned in PTC by targeting miR-646 and heterogeneous ribonucleoprotein A1. Fluorescence in situ hybridization and dual-luciferase reporter assays further confirmed these connections. Overall, our results reveal an important oncogenic role of circTIAM1 in PTC and may represent a potentially therapeutic target against PTC progression.

Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin

The adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at such approaches are lacking for endocrine diseases - with the exception of type-I-diabetes. Moreover, tumor formation is very common, however, appropriate high-throughput applications reflecting the high heterogeneity and furthermore relevant 3D-structures in vitro are still widely lacking. Recently, we have initiated the development of standardized multidimensional models of a variety of endocrine cell/tissue sources in a new multiwell-format. Firstly, we confirmed common applicability for pancreatic pseudo-islets. Next, we translated applicability for spheroid establishment to adrenocortical cell lines as well as patient material to establish spheroids from malignant, but also benign adrenal tumors. We aimed furthermore at the development of bovine derived adrenal organoids and were able to establish steroidogenic active organoids containing both, cells of cortical and medullary origin. Overall, we hope to open new avenues for basic research, endocrine cancer and adrenal tissue-replacement therapies as we demonstrate potential for innovative mechanistic insights and personalized medicine in endocrine (tumor)-biology.

Weight management in youth with rapid-onset obesity with hypothalamic dysregulation, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD-NET): literature search and case report

Objectives Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural endocrine tumor (ROHHAD-NET) syndrome is a youth-onset constellation of symptoms including rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. Despite growing understanding of the clinical classification of this syndrome there is limited investigation into treatment of the rapid-onset obesity which can be progressive and life-limiting. The purpose of this case report is to describe the clinical timeline and treatment of severe obesity in a patient with of ROHHAD-NET and propose recommendations for the treatment of associated obesity. Case presentation We present the case of a 10-year-old female with a clinical presentation consistent with ROHHAD-NET who achieved clinically meaningful weight loss with a combination of lifestyle modification and anti-obesity pharmacotherapies. We report on the use of three separate pharmacological agents and ultimately the referral for bariatric surgery. Conclusions Given that early-onset obesity and hypoventilation are life-limiting components of this condition, early recognition and treatment are essential to improve health outcomes.

Progression of Carcinoid Heart Disease in the Modern Management Era

Background The development of carcinoid heart disease (CaHD) is still relatively unclear. It is difficult to define an optimal follow‐up for patients without any cardiac involvement at baseline. The aim of this study was to assess the prevalence and natural history of CaHD by annual echocardiographic examinations. Methods and Results We studied 137 consecutive patients (61±12 years, 53% men) with proven digestive endocrine tumor and carcinoid syndrome between 1997 and 2017. All patients underwent serial conventional transthoracic echocardiographic studies. Right‐sided and left‐sided CaHD were systematically assessed. We used a previous validated echocardiographic scoring system of severity for the assessment of CaHD. An increase of 25% of the score was considered to be significant. Mean follow‐up was 54±45 months. Prevalence of CaHD was 27% at baseline and 32% at 5‐year follow‐up. Disease progression was reported in 28% of patients with initial CaHD followed up for >2 years (n=25). In patients without any cardiac involvement at baseline, occurrence of disease was 21%. CaHD occurred >5 years from the initial echocardiographic examination in 42% of our cases, especially in patients presenting with new recurrence of a digestive endocrine tumor. An increase of urinary 5‐hydroxyindoleacetic acid by 25% during follow‐up was identified as an independent predictor of CaHD occurrence during follow‐up (hazard ratio [HR], 5.81; 95% CI, 1.19–28.38; P =0.03), as well as a maximum value of urinary 5‐hydroxyindoleacetic acid >205 mg/24 h during follow‐up (HR, 8.41; 95% CI, 1.64–43.07; P =0.01). Conclusions Our study demonstrates that in patients without initial CaHD, cardiac involvement may occur late and is related to serotonin. Our data emphasize the need for cardiologic follow‐up in patients with recurrence of the tumor process.

A rare entity of malignant insulinoma diagnosed after 30 years of clinical manifestation of hypoglycemia: A case report and literature review

Malignant insulinomas, a rare life threatening pathology, exists in literature as an entity that constitutes 10% of all insulinomas and often present as multi-centric macro nodules with multiple lymph nodes or liver metastases before diagnosis. We report a rather rare case of a 68 year old male with a 30 years history of uninvestigated severe hypoglycemic attacks that improved on glucose intake. Blood tests showed a decreased value of glycemia (45 mg/dL) associated with increased insulin level (54 μU/ml) and an increased glycemia/ insulinemia ratio of 0.83 supporting the diagnosis of insulinoma. Abdominal CT showed a 4 cm mass localized in the head of the pancreas with atrophic body and tail, no signs of distant metastatic disease. A concomitant diagnosis of primary hyperparathyroidism raised, based on elevation of calcium associated and high level of PTH. The coexistence of the two endocrinopathies suggested the presence of type 1 multiple endocrine neoplasia (MEN I). Based on the workup suggesting a benign insulinoma with no signs of metastatic disease, co-existing with debilitating symptoms of hypoglycemia, pancreatectomy with lymph node dissection was performed. Histo-pathological examination returned surprisingly positive for malignant neuro-endocrine tumor with positive lymph nodes. In that domain, we summarized the literature discussion of neuroendocrine tumors, elaborating on malignant insulinoma diagnosis and management. Furthermore, what our article is trying to lay upon existing literature is a case of a long standing existent MEN 1 malignant insulinoma manifesting as a remarkably slow progressive disease of 30 years’ timeline versus a less likely chance of a transformation from benign insulinoma to malignant Keywords: neuroendocrine neoplasm; pancreatectomy; MENI; malignant insulinoma; chronic hypoglycemia.

LBX2-AS1 Activates FSTL3 by Binding to Transcription Factor RARα to Foster Proliferation, Migration, and Invasion of Thyroid Cancer

Background: Thyroid cancer is a frequent endocrine tumor in women. It is of great significance to investigate the molecular mechanism of progression of thyroid cancer.Methods: Gene expression data set and clinical data were downloaded from The Cancer Genome Atlas database for differential expression analysis. The triplet of downstream transcription factors (TFs) and modulatory genes of target lncRNA in thyroid cancer was predicted by the lncMAP database. mRNA and protein expression of lncRNA LBX2-AS1, RARα, and FSTL3 were detected by qRT-PCR and western blot. The localization of lncRNA LBX2-AS1 in cells was tested by Fluorescence in situ hybridization assay. The RNA immunoprecipitation assay was applied to verify the binding relationship between lncRNA LBX2-AS1 and FSTL3. ChIP and dual-luciferase assays were used to prove the binding relationship between RARα and FSTL3. Cell function experiments were used to test cell proliferation, migration and invasion in each treatment group. The role of lncRNA LBX2-AS1 in thyroid cancer progression was also confirmed in nude mice.Results: Bioinformatics analysis indicated that lncRNA LBX2-AS1, RARα, FSTL3 were remarkably fostered in thyroid cancer tissue, and LBX2-AS1 was evidently correlated with clinical features. The LncMAP triplet prediction showed that LBX2-AS1 recruited TF RARα to modulate FSTL3. RIP assay confirmed that LBX2-AS1 was prominently enriched on RARα. ChIP and dual-luciferase report assays unveiled that RARα bound to the promoter region of FSTL3 and functioned as a TF. Cell function experiments uncovered that LBX2-AS1 boosted the progression of thyroid cancer. The rescue experiments showed that LBX2-AS1 recruited the TF RARα to hasten the transcription activity of FSTL3 and thus promoted the development of thyroid cancer.Conclusion: The integrative results demonstrated that LBX2-AS1 activated FSTL3 by binding to TF RARα to hasten proliferation, migration and invasion of thyroid cancer.

Multiple endocrine neoplasia type 1 with a frameshift mutation in its gene accompanied by a giant cervical lipoma and multiple fatty deposits in the pancreas: case report

Background Multiple endocrine neoplasia type 1 (MEN1) is a syndrome characterized by pituitary neoplasia, primary hyperparathyroidism and pancreatic endocrine tumor. Here we show a case of MEN1 with a germline frameshift mutation in its gene accompanied by a giant cervical lipoma and multiple fatty deposits in the pancreas. Case presentation A 28-year-old man noticed the decreased visual acuity of both eyes and visited our institution. Since he was diagnosed as visual disturbance and brain computer tomography (CT) showed a mass in the pituitary fossa, he was hospitalized in our institution. Endoscopic trans-sphenoidal hypophysectomy and total parathyroidectomy with auto-transplantation were performed, and a giant cervical lipoma was resected. Furthermore, in genetic search, we found a germline frameshift mutation in MEN1 gene leading to the appearance of a new stop codon. Conclusions We should bear in m ind that giant skin lipoma and multiple abnormal fatty deposits in the pancreas could be complicated with MEN1.