Endocrine Abstracts

CNP belongs to a family of peptides best known for their role in blood pressure regulation and cardiac remodeling. However CNP differs from the cardiac hormones (ANP and BNP) in showing more diverse expression and low circulating plasma concentrations. Genetic studies, as well as showing cardioprotective roles for all three hormones, have revealed a critical role for CNP in promoting linear growth in both rodents and humans. Finding that the aminoterminal bio-inactive fragment...

Numerous growth factors, oncogenes, tumour suppressor genes and hormonal influences have been implicated in pituitary tumorigenesis. We have demonstrated that the PI3K-Akt pathway is upregulated in pituitary tumours and since Akt is a major downstream signalling molecule of growth factor-liganded tyrosine kinase receptors it is possible that an abnormality at this level could be the primary driver of pituitary tumorigenesis. The serine/threonine kinase B-Raf functions as a dow...

Glucocorticoid (GC) hormone action can be modulated at the pre-receptor level by the endoluminal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). 11βHSD1 is a bidirectional enzyme that primarily acts as an oxo-reductase in vivo, converting the pro-hormone cortisone to its active form cortisol, while its dehydrogenase activity results in inactivation of cortisol to cortisone. 11βHSD1 oxo-reductase activity allows GC reactivation in a tissue s...

Recent advances in the molecular classification of papillary thyroid cancer (PTC) have improved the diagnostic work-up and the care of patients with thyroid nodules and cancer, highlighting the need to routinely add information on the genetic pattern to the classification of cancer. The genomic background of a large series of 208 PTCs followed at a single Center was analysed by a custom MA genotyping platform (PTC-MA), which allows the simultaneous detection of 19 genetic alte...

There are three main applications for molecular genetic testing in thyroid pathology:1. As part of an integrated approach of careful clinical, ultrasound and FNBC assessment with local outcome data molecular analysis of fine needle biopsy cytology is able able to improve diagnostic outcomes for thyroid nodules by identifying patients with an indeterminate FNBC as most likely benign with < 5% false negatives and thus obviating diagnostic lobectomy or ...

Introduction Vascular adhesion protein-1 (VAP-1) is a known driver of hepatic inflammation and fibrosis, with elevated levels detected in the circulation in disease. We studied the tissue expression of VAP-1 in midgut NETs and carcinoid heart disease (CHD) alongside circulating soluble VAP-1 (sVAP-1) to determine the role of VAP-1 in NETs.Methods Expression of VAP-1 and inflammatory and stromal markers in midgut NETs tissue, CHD valves and control valves...

Objectives: Thyroid eye disease (TED) is considered a fibroinflammatory disease with pathology related to both inflammatory and fibrotic disease processes. IL-11 is a fibroinflammatory cytokine that is linked to tissue fibrosis of the lung, skin, heart, kidney and liver. Recently, IL-11 was identified as a possible disease modifier in TED. IL-11 levels are increased in TED patient plasma, in correlation with disease severity, and IL-11 stimulates phenotypic switching of orbita...

Background: Struma ovarii is a germ cell tumor of the ovary containing ≥ 50% thyroid tissue and malignant struma ovarii (MSO) is a very rare disease containing papillary or follicular thyroid carcinomas (FTC). There is no consensus on optimal management for patients with MSO and no data on radioactive iodine (RAI) responsiveness. Here, we report two cases with RAI refractory MSO with NRAS mutation detected by next-generation sequencing (NGS). Case ...

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive malignancy with only limited effective systemic treatment options. The identification of actionable genetic lesions and its exploitation has expanded therapeutic approaches and especially for the subset of BRAFV600E mutated ATC (11-25%) combined BRAF- and MEK-inhibition indicated meaningful activity. Still, further effective therapeutic options are required for patients without identifiable driver mutations. The role ...

IntroductionAromatase Inhibitors (AI) are standard therapy for hormone receptor positive breast cancers in post-menopausal patients. Unfortunately, resistance is common and previous studies from our lab suggest that the altered steroid environment may be a driver. Using label-free mass spectrometry we set out to explore the unique androgen receptor (AR) interactome that supervenes in AI resistant breast cancer and associated hyper-androgenic environment....