Endocrine Abstracts

We describe a 35 year old man who was referred back to the endocrinology service with a chronically raised amylase. He had previously been seen for early onset type 2 diabetes and for primary hyperparathyroidism. He had undergone a single gland parathyroidectomy, aged 32, for primary hyperparathyroidism in 2013 after which his calcium had remained normal. In clinic he was found to be overweight but otherwise well, with normal blood pressure and an HbA1c 49 mmol/mol. The most s...

Multiple endocrine neoplasia (MEN) disorders are autosomal dominantly inherited syndromes characterised by multi-glandular adenomas/carcinomas. AMEND is a charity providing support and information resources to MEN patients. A recent anonymous online patient survey was conducted by AMEND into the psycho-social impact of the conditions. 219 patients participated (n101 MEN1, n60 MEN2a, n26 MEN2b, n32 other) with a mean age of 47.5 years. 57% felt that their condition had a negati...

Pancreatic neuroendocrine tumours (PNETs) may occur as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome or as non-familial (sporadic) tumours. PNETs, which include gastrinomas, insulinomas and non-functioning tumours occur in more than 80% of MEN1 patients and account for 50% of disease-specific deaths. This is because 25–40% of patients with PNETs will have metastasis at presentation, and current treatments, which include surgery, chemotherapy and radiothe...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of parathyroid tumours, and neuroendocrine tumours (NETs) of the pancreas and pituitary. Reliable biomarkers, ideally in plasma or serum, for the early detection and recurrence of MEN-1 associated tumours, and especially pancreatic NETs are required, and we explored the potential use of microRNAS (miRNAs), which are small non-coding RNAs that bind target mRNAs ...

The prolactin receptor (PRLR) is a type-I cytokine receptor that plays critical roles in mammary gland development, lactation and glucose metabolism, and PRLR mutations have been associated with breast cancer and familial hyperprolactinaemia. The PRLR signals via Janus kinase-2-signal transducer and activator of transcription-5 (JAK2-STAT5) or phosphoinositide 3-kinase-Akt (PI3K-Akt) pathways to mediate changes in transcription, differentiation and proliferation, and we hypoth...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the occurrence of parathyroid, pancreatic and pituitary tumours, and is due to mutations of the MEN1 gene, which encodes menin. We have investigated identical twins with MEN1, one of whom developed primary hyperparathyroidism (PHPT) and a prolactinoma that caused pubertal arrest, and the other had PHPT only. DNA sequence analysis of the MEN1 coding region had not ide...

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary condition characterised by the predisposition to hyperplasia or the development of solitary adenomas of multiple endocrine gland. MEN1 related disease is responsible for death in two thirds of patients with this hereditary condition and the mean age at death is 55 years. This associated mortality necessitates a vigorous surveillance protocol, however all recommendations for radiological surveillance are based on non-pr...

Phaeochromocytomas (PC) are tumours of the adrenal medulla and paragangliomas (PGL) refer to their extra-adrenal counterpart arising from sympathetic or parasympathetic tissue. Mutations in the citric acid cycle enzyme succinate dehydrogenase (SDH) predispose to PC/PGL. Clinical practice guidelines suggest that plasma metanephrine and normetanephrine levels measured in the supine position should be used in the first instance for biochemical diagnosis, and those with positive r...

Background: There is no consensus on the optimal timing of surgery for primary hyperparathyroidism (PHPT) in MEN1. Experienced centres recommend subtotal or total parathyroid surgery with three and a half gland surgery along with thymic removal as a favoured procedure; but long-term outcomes have rarely been reported.Objective: To investigate the indications and outcomes for surgery in patients with PHPT in MEN1Methods: Review of c...

Vitamin D deficiency is associated with the development of some cancers and in vitro 1,25-dihydroxyvitamin D (1,25D) reduces cell proliferation. We suggest that modification of tissue specific immune responses, as a consequence of local synthesis of 1,25D, may be key. To assess the impact of serum 25D on the risk of bladder cancer we conducted a systematic review. To test our hypothesis, expression of vitamin D signalling components and the synthesis of 1,25D were exa...

Objective: There is limited evidence on the diagnostic accuracy of imaging tests in patients at high risk for adrenal malignancy. Our objective was to determine the performance of computed tomography (CT) and 18FDG-PET/CT imaging in diagnosing a malignant adrenal mass in a high risk population of patients referred for CT-guided adrenal biopsy.Methods: We retrospectively reviewed the medical records of 378 patients who had percutaneous adrenal ...

Introduction: Metformin is used as a first line treatment in type 2 diabetes. Several studies suggest that patients with type 2 diabetes treated with metformin may have reduced cancer risk. Recently it has been shown that Metformin acts directly on mitochondria to alter cellular bioenergetics and reduce tumorigenesis. We have shown that anti-proliferative effect of Mitotane is related with changes of expression of the genes involved in mitochondrial metabolism in human adrenoc...

Somatotroph adenomas (SA) causing acromegaly exist as two major pathological variants: densely and sparsely granulated, according to the number and distribution of growth-hormone-containing secretory granules. These variants are increasingly recognised by neuropathologists and endocrinologists, but the consequences for tumour behaviour and patient outcome remain to be defined. Sparsely granulated SAs are associated with younger, female patients and are more invasive and prolif...

Introduction: Long-term survivors of childhood-onset brain tumours have increased risk of premature vascular disease by mechanisms that remain unclear. We hypothesised that a thrombotic fibrin network profile is one mechanism for the increased vascular risk in this population.Methods: We undertook a cross-sectional study in 33 patients with previous history of brain tumours and 33 age and sex-matched healthy controls. We performed clot structure analysis...

Background and aims: Immediate release somatostatin analogues (SAs) have routinely been administered to test tolerability prior to commencing long-acting SAs, though there is limited evidence to support this process. We aim to examine this practice at our centre.Methods: Patients who received SA therapy for a neuro endocrine tumours (NET) between December 2012 and December 2014 were identified. Records were used to identify; start date, duration of test-...

Peptide receptor radionuclide therapy (PRRT) is a targeted therapy using synthetic somatostatin analogues attached to a radionuclide, which binds to tumours expressing somatostatin receptors. The aim was to review the role of PRRT in a tertiary referral centre. We retrospectively reviewed a cohort of 25 patients (eight males, 17 females), with a median age of 65, who received Yttrium-90 DOTATATE or Lutetium-177 DOTATATE at Addenbrookes Hospital. The location of the primary tum...

Phaeochromocytomas are life-threatening catecholamine-producing tumours of the adrenal medulla. Our understanding of their pathogenesis is incomplete, with limited ability to predict malignant potential and disappointing treatment results in disseminated disease. Phaeochromocytomas occur in the inherited cancer syndrome von Hippel-Lindau (VHL). One function of VHL protein is in the formation and maintenance of primary cilia. These are microtubule-based organelles that protrude...

Introduction: Neuroendocrine tumours (NETs) comprise a heterogeneous group of tumours that constitute a diagnostic and therapeutic challenge. The most commonly used general NET circulating biomarker is Chromogranin A (CgA). CgA is elevated under other circumstances, notably by the use of Proton Pump Inhibitors (PPIs) and possibly via a gastrin-mediated mechanism. Chromogranin B (CgB) and Cocaine- and Amphetamine-Regulated transcript (CART) are two less commonly used NET biomar...