Endocrine Abstracts

Nicotinamide nucleotide transhydrogenase (NNT) is a NADPH-generating mitochondrial proton pump with a central role in mitochondrial antioxidant pathways. Recent studies revealed inactivating NNT mutations in patients with familial glucocorticoid deficiency, indicating a selective susceptibility of the adrenal cortex to NNT deficiency and oxidative stress. Here we explored the potential value of NNT as a therapeutic target in adrenocortical cancer. We delineated the distinct ef...

Improved therapies for pancreatic and pituitary neuroendocrine tumors (NETs), which may occur in Multiple Endocrine Neoplasia type 1 (MEN1), are needed. We assessed the effects of pasireotide, a somatostatin analogue with high affinity for somatostatin receptors (SSTRs) −1, −2, −3 and −5, in a mouse model of MEN1. Men1+/− mice treated from 12 months of age with 40 μg/g pasireotide (n=71), or phosphate-buffered sal...

Steroid sulphatase (STS) liberates sulphated oestrogens into their active forms. In the colon, evidence suggests that although initially pro-apoptotic in healthy mucosa, once malignancy occurs, oestrogens may stimulate colorectal cancer (CRC) proliferation. Moreover, greater intratumoural oestrogen synthesis is negatively associated with survival outcomes in CRC patients. However, little is known about oestrogen metabolism pathways in CRC, and whether alterations in local oest...

PTTG is a multifunctional proto-oncogene, overexpressed in thyroid, pituitary and other endocrine cancers. PTTG is also implicated in the pathogenesis of head and neck cancer, where high PTTG expression independently correlates with advanced tumour stage and reduced disease-free survival. Recently, abrogation of residue threonine-60 (T60) has been associated with altered PTTG half-life, chromosomal instability and cell invasion. We therefore generated a phospho-specific antibo...

Functional disruption of the tumour suppressor p53 has a critical role in promoting the development of most cancers. The proto-oncogenes PBF and PTTG1 both regulate p53 activity, but the relative contribution of each gene in influencing p53 function has not been delineated, especially in thyroid cancer where both proto-oncogenes are commonly overexpressed. To better understand the interplay between PTTG1, PBF and p53 in vivo, we examined p53 responses in primary thyrocytes cul...

Differentiated thyroid cancer (DTC) is common in female patients of reproductive age and generally has a good prognosis and so many patients may become pregnant following treatment. Progression of DTC during pregnancy has been reported and may relate to thyroid stimulation by human chorionic gonadotropin (hCG). Until recently suppression of thyrotropin (TSH) by supraphysiological doses of levothyroxine was indicated for all patients following thyroidectomy and radioiodine abla...

Introduction: Radiation-induced hypopituitarism has been well-described in childhood-onset brain tumour survivors, however in adults has received less attention. The aim of this study was to assess the pituitary-related outcomes following cXRT in adults with extra-sellar gliomas.Methods: We retrospectively collected longitudinal data regarding pituitary-related outcomes from medical records of 59 patients, diagnosed with extra-sellar gliomas in adulthood...

Context: Pancreatic neuroendocrine tumours (NETs) overexpressing glucagon are associated with phenotypic heterogeneity. Objective: To correlate clinical phenotype with detailed analysis of plasma levels of proglucagon-derived peptides (PGDPs) in subjects with proglucagon-expressing tumours using specific immunoassays and gel filtration profiles to elaborate molecular heterogeneity of PGDPs, before and after somatostatin analogues.Case 1: A 57 year old wo...

Background: Olfactory neuroblastoma (ONB), a neuroendocrine nasal tumour, exhibits a range of phenotypes from indolent to very aggressive. Even early disease is associated with high (60%) recurrence rates, while advanced disease has 1.5y disease-free and 2.5y overall mean survival. Medical treatments against primary and recurrent disease as well as prognostic biomarkers are urgently required. The few studies available suggest that mTOR/MAPK and Sonic Hedgehog signalling has a ...

Primary pigmented nodular adrenal disease (PPNAD) is a form of bilateral adrenocortical hyperplasia characterised by small to normal sized adrenal glands containing multiple small cortical pigmented nodules1. It may occur independently, but 90% of cases are a manifestation of the Carney complex. Most cases of PPNAD are diagnosed before age 30, and are the result of a germline mutation in PRKAR1A or PDE11A, leading to upregulation of cAMP signalling. It is a cause of...

Introduction: Primary, non-motile, cilia are microtubule-based organelles that protrude from the cell membrane into the extracellular environment of virtually all nucleated mammalian cells. They function as signalling platforms involved in the transduction of extracellular stimuli and have an important role in cell cycle regulation. Disruption of primary cilia structure and therefore function has been identified in a range of cancers including kidney, breast, pancreatic and pr...

Introduction: Childhood-onset brain tumour (CO-BT) survivors demonstrate elevated standardized mortality rates for cardiac disease. Adverse lipid profile and body composition contribute to the increased cardiovascular risk. Little is known about the metabolic changes in long-term survivors of adult-onset brain tumours (AO-BT).Methods: We performed a cross-sectional study to compare cardiovascular risk parameters in CO-BT with AO-BT survivors and healthy ...

Introduction: Perhaps due to a current global epidemic of “overdiagnosis”, papillary thyroid microcarcinoma (PTM) is now the commonest endocrine malignancy (BMJ 348: 3045, 2014). Current management options vary from lobectomy or total thyroidectomy to “active surveillance”. An alternative approach, used successfully for eliminating neck nodal metastases (JCEM 96: 2717, 2011), is ultrasound-guided percutaneous ethanol ablation (UPEA). Here we present our exp...

Introduction: Childhood-onset cancer survivors demonstrate increased mortality rates due to cardiovascular and cerebrovascular events. Studies suggest that leukaemia and brain tumour survivors have a relative risk of 6.4 and 29.0 respectively for stroke. Adverse lipid profile, body composition, insulin resistance and hypertension have been implicated to the increased cardiovascular risk in these patients, however little is known about procoagulant factors and markers of vascul...

: The orally administered targeted therapies, Sunitinib and Everolimus lengthen progression free survival in pancreatic neuroendocrine tumours (pNETs). Choice of therapy has traditionally been on avoidance of deterioration in established co-morbidities. Sunitinib has been recognised to induce hypocalcaemia and the subsequent need for calcium supplementation has been reported. However, little has been documented about the utility and therapeutic significance of this effect....

Neuroendocrine tumours (NETs) are rare tumours that originate from neuroendocrine cells and their incidence has increased for the last 20 decades; partly because of advances in diagnostic tools, which have improved detection rates. Chromogranin A (CgA) is the most widely used biochemical tumour marker for NETs, however, its prognostic utility has been questioned due to several non-neuroendocrine causes of elevated CgA. This is the first study to assess the prognostic utility o...

Androgens are required for normal development and fertility. They have a vital role in tissues such as the reproductive tract, the brain, muscle and bone. Prostate cancer (PCa) is the most prevalent malignancy in western males: it is dependent upon circulating androgens and the therapies currently available aim to reduce synthesis of circulating androgens and/or inhibit the pathway using antiandrogens. Therapies inhibiting androgen signalling, and in particular the androgen re...

Background: Insulinomas, the most common functional neuroendocrine tumours of the pancreas, are usually sporadic, benign and solitary.Aims: To assess biochemical data, localisation and treatment outcome of insulinomas diagnosed in a tertiary endocrine centre.Patients and methods: Twenty-five patients (14 F/11 M), aged 49.1±14.1 years, diagnosed with insulinoma in a Neuroendocrine Tumours centre between 2000 and 2014 were retro...

59-year-old gentleman with known succinate dehydrogenase complex subunit C (SDHC) gene mutation attended endocrine clinic with non-specific symptoms. Past medical history included glomus jugulare paraganglioma (PGL) surgically treated (1993, 2003) with residual disease, macroprolactinoma treated with cabergoline since 2010, and BPH treated with finasteride and tamsulosin. His brother has glomus vagale. Clinical examination was unremarkable. Plasma metanephrine ranged between 3...

Phaeochromocytomas are rare neuroendocrine tumours with an incidence of 2–8/million persons per year. They occur as a sporadic entity or form part of a complex autosomal dominant familial genetic syndrome, mainly MEN2A, MEN2B, Neurofibromatosis Type1, Von Hippel-Lindau disease (VHL) and mutations in succinyl dehydrogenase. The mean age at diagnosis is in the third decade in the familial cases and the risk of recurrence has been described as high as 23%.<p class="abste...

We present the case of a 53 year old gentleman with recurrent bladder paraganglioma. He presented initially in 2010 with headache and blurred vision when passing urine. The tumour was surgically removed, BP normalized and his postoperative MIBG-scan was normal. The patient presented with hypertensive crisis 4 years later with a suspicion of tumor recurrence, confirmed biochemically and radiologically. Treatment with phenoxybenzamine and bisoprolol resulted in adequate BP contr...

Introduction/Background: ACTH production from a midgut mesentery NET is extremely rare (1). A 62y old woman presented with hypokalaemia (2mmol/L) and hyperpigmentation, 11y after surgery of a pT3N1Mx non-functional G1 NET with SRS positive, non-resectable but stable, residual mass encasing mesenteric vessels. Serum cortisol (3261 nmol/L), ACTH (796 ng/L), CgA (530 pmol/L) and urine total cortisol metabolites (33920 μg/24h) including 14 sub-products indicated change of bio...

A 68 year old man presented with shortness of breath and was found to have a pulmonary embolus. During work up of the underlying aetiology he was noted to have bilateral adrenal masses. He was subsequently readmitted with pyrexia and feeling generally unwell. Imaging revealed the progression of adrenal masses and there was biochemical evidence of adrenal insufficiency with a random cortisol at the low end of normal. CT guided biopsy was consistent with the diagnosis of a high ...

A 63-year-old Caucasian female was admitted with a 12-month history of exertional breathlessness, anxiety attacks, syncopal episodes, diarrhoea, fatigue, reduced appetite, two stones weight loss, and dry facial and truncal flushing. Investigations revealed raised Urine 5-HIAA of 116 (RR <50 μmol/24 h) and raised Chromogranin A of 48 (RR <6 nmol/l). CT scan revealed an extensive soft tissue mass encasing the upper abdominal aorta, compressing the inferior vena cava...

Case history: A 42 year old female presented with a history of collapse and seizure activity. Her blood glucose was noted to be 3.1 with the paramedics and subsequent hypoglycaemia was demonstrated on several occasions whilst in hospital. She described a family history of insulinoma in her mother. A 72 h fast was performed as an inpatient to look for insulinoma. The nadir serum glucose was 2.0 mmol/l with an inappropriate C-peptide level of 1006 pmol/l and an insulin level of ...

18 year old female referred with 2 years history of hirsutism and secondary amenorrhoea. She was born at 37 weeks and was found to have neonatal hypothermia, hypoglycaemia and crossed hemihypertrophy, but no macroglossia. Due to the increased risk of Wilm’s tumour she had regular ultrasound scans up to the age of 11 years. She attained menarche at the age of 13 but had only two periods within 18 months. By the age of 15 she developed hirsutism and acne. Biochemistry revea...

Bronchial carcinoid tumours are uncommon pulmonary neoplasms. Manifestation of a bronchial carcinoid with acromegaly secondary to extra-pituitary growth hormone releasing hormone (GHRH) production is rare, but bronchial carcinoid tumours are the most common cause of ectopic GHRH secretion.We report the case of 60 year old female, ex-smoker with hypertension presenting with cough, dyspnoea and right lower lobe opacity on the chest X-ray. Patient was noted...

Introduction: Glucagonoma syndrome is a rare paraneoplastic phenomenon characterised by necrolytic migratory erythema, diabetes mellitus and symptoms of gastrointestinal upset. It is often diagnosed late leading to a poor prognosis.Case report: A 70 year old lady with type two diabetes mellitus and fibromyalgia presented in late 2011 to Gynaecology with an itchy erythematous vulval rash. Skin biopsy suggested lichen sclerosis and she was discharged with ...

A 27 year old male patient with severe cardiomyopathy secondary to Epirubicin chemotherapy for rhabdomyosarcoma in infancy was noted to be hypercalcaemic during the course of admission for severe inotrope dependant congestive cardiac failure. Biochemical investigations confirmed a diagnosis of primary hyperparathyroidism (corrected Calcium 3.10 mmol/l, PTH 22 pmol/l, Vitamin D 77 nmol/l).His brother had undergone trans-sphenoidal pituitary surgery for ac...

The prevalence of new cases of cancer in developing countries even though less than the developed countries have greater mortality rate, due to lack of access to treatment and early detection of the disease. Epigenetic alterations in BRCA2 and TP53, such as DNA methylation, maybe an effective approach in diagnosis, prognosis and therapy in breast cancer. This study examines the DNA methylation signature of BRCA2 and TP53 in Nigerian breast cancer patients. In this study, thirt...

A 64 year old lady was admitted with a 2 day history of feeling generally unwell. Her relatives also reported new onset confusion over these 2 days. Her bloods showed raised inflammatory markers (CRP 110.3 mg/l, WCC 18.2×109/l) hypoalbuminemia (17 g/l), bilirubinemia (55 μmol/l) and a raised alkaline phosphatase (917 IU/l). She had recently been diagnosed with carcinoid syndrome; primary tumour situated in the terminal ileum with liver metastasis and had b...