Telomere length is shorter in affected members of families with familial nonmedullary thyroid cancer.

Background: The theory that short telomere length and genetic defects in maintaining telomere length are associated with familial nonmedullary thyroid cancer (FNMTC) is controversial. Thus, the aim of this study was to determine whether telomere length and genes involved in maintaining telomere length are altered in FNMTC.

Methods: Blood samples were collected from 44 members (13 affected and 31 unaffected) of six families with FNMTC and from 60 controls.

Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening.

Background: Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique.

Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia.

Hypoxia-inducible factors are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. When these proteins are dysregulated, they contribute to tumorigenesis and cancer progression. However, mutations in genes encoding α subunits of hypoxia-inducible factors (HIF-α) have not previously been identified in any cancer.

Cancer: thyroid cancer bone metastases and high morbidity rates.

Skeletal-related events (SREs) are important measures of morbidity and mortality in patients with solid tumour bone metastases. The high rate of SREs in patients with differentiated thyroid cancer bone metastases reported by Farooki indicates that routine use of antiresorptive therapy in these patients could result in reduced SREs.

Interleukin-13 receptor alpha2 is a novel therapeutic target for human adrenocortical carcinoma.

Background: Adrenocortical carcinoma (ACC) is a relatively rare but aggressive malignancy with limited therapeutic options. Previous genome-wide expression studies have demonstrated the overexpression of interleukin-13 receptor alpha2 (IL13Rα2) in some human malignancies.

Methods: The authors evaluated IL13Rα2 mRNA and protein expression in 21 normal samples, 78 benign samples, 10 primary malignant samples, and 25 metastatic/recurrent samples and performed functional analyses with IL13 ligand and IL13 Rα2 knockdown in vitro.

Rate of clinically significant postoperative pancreatic fistula in pancreatic neuroendocrine tumors.

Background: In 2005, the International Study Group of Pancreatic Fistula (ISGPF) developed a definition and grading system for postoperative pancreatic fistula (POPF). The authors sought to determine the rate of POPF after enucleation and/or resection of pancreatic neuroendocrine tumors (PNET) and to identify clinical, surgical, or pathologic factors associated with POPF.

Methods: A retrospective analysis of pancreatic enucleations and resections performed from March 1998 to April 2010.

Sleeping parathyroid tumor: rapid hyperfunction after removal of the dominant tumor.

Context: Due to frequent multiplicity of tumors in multiple endocrine neoplasia type 1, it may be difficult to decide when to stop a parathyroid exploration. A fall of intraoperative serum PTH by a certain percentage during parathyroid surgery is often used as one criterion for ending the operation.

Results: We report two patients with primary hyperparathyroidism due to multiple endocrine neoplasia type 1 who had their first parathyroidectomy at the National Institutes of Health.

Molecular markers of adrenocortical tumors.

Adrenocortical tumors are common and incidentally discovered in up to 14% of axial imaging studies performed for other indications. Most of these tumors are nonfunctioning but may require removal because of the risk of adrenocortical carcinoma. Unfortunately, most clinical and imaging features are still not accurate enough to allow definitive diagnosis and an increasing number of patients undergo adrenalectomy to exclude a cancer diagnosis.

DNA methylation profiling identifies global methylation differences and markers of adrenocortical tumors.

Context: It is not known whether there are any DNA methylation alterations in adrenocortical tumors.

Objective: The objective of the study was to determine the methylation profile of normal adrenal cortex and benign and malignant adrenocortical tumors.

Methods: Genome-wide methylation status of CpG regions were determined in normal (n = 19), benign (n = 48), primary malignant (n = 8), and metastatic malignant (n = 12) adrenocortical tissue samples.

Preoperative localizing studies for initial parathyroidectomy in MEN1 syndrome: is there any benefit?

Background: The objective of the present study was to evaluate the utility of preoperative localizing studies in patients with MEN1 undergoing initial bilateral neck exploration (BNE) and parathyroidectomy for pHPT.

Methods: We performed a retrospective analysis of patients diagnosed with MEN1 who underwent initial parathyroidectomy between December 1993 and December 2010. Results of preoperative localizing studies were compared with intraoperative findings and outcome.

KCNJ5 mutations in the National Institutes of Health cohort of patients with primary hyperaldosteronism: an infrequent genetic cause of Conn's syndrome.

KCNJ5 mutations were recently described in primary hyperaldosteronism (PH or Conn's syndrome). The frequency of these mutations in PH and the way KCNJ5 defects cause disease remain unknown. A total of 53 patients with PH have been seen at the National Institutes of Health over the last 12 years.

Evaluation of candidate diagnostic microRNAs in thyroid fine-needle aspiration biopsy samples.

Background: Thyroid cancer diagnosis in the United States has increased by 2.3-folds in the last three decades. Up to 30% of thyroid fine-needle aspiration biopsy (FNAB) results are inconclusive.

Clinical utility of functional imaging with ¹⁸F-FDOPA in Von Hippel-Lindau syndrome.

Context: Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome in which patients are at risk of developing multiple tumors in different organs. 6-L-¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-FDOPA) positron emission tomography (PET) is a relatively new metabolic imaging tracer proposed for the use of localizing sites of neuroendocrine tumors. There are limited data on the clinical utility of using ¹⁸F-FDOPA PET for identifying neuroendocrine tumors in a high-risk population such as VHL.

The microRNA expression changes associated with malignancy and SDHB mutation in pheochromocytoma.

Currently, the diagnosis of malignant pheochromocytoma can only be made when there is clinical evidence of metastasis or extensive local invasion. Thus, there is a need for new diagnostic marker(s) to identify tumors with malignant potential. The purpose of this study was to identify microRNAs (miRNAs) that are differentially expressed between benign and malignant pheochromocytomas and assess their diagnostic accuracy.

Quantitative high-throughput drug screening identifies novel classes of drugs with anticancer activity in thyroid cancer cells: opportunities for repurposing.

Context: Despite increased understanding of the pathogenesis and targets for thyroid cancer and other cancers, developing a new anticancer chemical agent remains an expensive and long process. An alternative approach is the exploitation of clinically used and/or bioactive compounds.

Objective: Our objective was to identify agents with an anticancer effect in thyroid cancer cell lines using quantitative high-throughput screening (qHTS).

Comparison of clinical and imaging features in succinate dehydrogenase-positive versus sporadic paragangliomas.

Background: Limited data exist concerning the clinical and imaging features that distinguish sporadic from familial paragangliomas (PGLs).

Methods: Clinical, genetic (succinate dehydrogenase [SDHB] vs no SDHx), and imaging (computed tomography [CT], magnetic resonance imaging, (18)F-fluoro-deoxy-glucose positron emission tomography [(18)F-FDG-PET]) features obtained during a decade in 124 PGL patients were studied. Data were analyzed by Fisher's exact test or Wilcoxon rank-sum test.

Comparison of 6-18F-fluoro-L-DOPA, 18F-2-deoxy-D-glucose, CT, and MRI in patients with pancreatic neuroendocrine neoplasms with von Hippel-Lindau disease.

Introduction: There are limited data on the utility of 6-(18)F-fluoro-l-3,4-dihydroxyphenylalanine ((18)F-DOPA) and (18)F-2-deoxy-d-glucose ((18)F-FDG) in the workup of patients with pancreatic neuroendocrine tumors (PNETs). The aim of our study was to determine the accuracy of (18)F-DOPA and (18)F-FDG to detect PNETs in patients with von Hippel-Lindau disease (vHL).

Methods: We studied prospectively 69 patients with a diagnosis of vHL and pancreatic lesion(s) using computed tomography (CT), magnetic resonance imaging (MRI), (18)F-FDG, and (18)F-DOPA.

Molecular pathways associated with mortality in papillary thyroid cancer.

Background: A better understanding of the molecular mechanisms involved in papillary thyroid cancer (PTC)-associated adverse outcome is needed to manage these patients effectively. Our objectives were to identify molecular pathways associated with unfavorable features and outcomes in patients with PTC.

Methods: We performed genome-wide expression (GWE) analysis in 64 human tissue samples affected by PTC.

KIAA0101 is overexpressed, and promotes growth and invasion in adrenal cancer.

Background: KIAA0101 is a proliferating cell nuclear antigen-associated factor that is overexpressed in some human malignancies. Adrenocortical neoplasm is one of the most common human neoplasms for which the molecular causes are poorly understood. Moreover, it is difficult to distinguish between localized benign and malignant adrenocortical tumors.

What is the best criterion for the interpretation of adrenal vein sample results in patients with primary hyperaldosteronism?

Background: In patients with primary hyperaldosteronism, adrenal vein sampling (AVS) has emerged as a gold standard for distinguishing between unilateral and bilateral disease, but multiple criteria have been used and no consensus exists as to the most accurate criterion. The objective of this study was to determine which AVS criteria most accurately identify patients with unilateral surgical disease and are associated with significant clinical improvement after adrenalectomy.

Methods: This is a retrospective analysis of AVS results in 108 patients with primary hyperaldosteronism treated at a single institution.