Endocrine Abstracts

Triple negative breast cancer (TNBC) represents 10–20% of all breast cancers diagnosed, affects young people and is highly aggressive. These tumours lack expression of the receptors that bind estrogen and progesterone and stratify patients for hormonal therapy. The only current therapeutic option for TNBC is chemotherapy which has limited efficacy, and therefore novel therapies are desperately needed. The receptors for estrogen and progesterone belong to the nuclear recep...

Colorectal cancer (CRC) is the third most common cancer and is one of the highest incidences and mortality tumours worldwide. Our group has previously shown that CRC favours oestradiol synthesis by increasing steroid sulfatase (STS) activity and altering 17β-hydroxysteroid dehydrogenases (HSD17Bs) expression. However, what regulates STS activity and HSD17Bs expression and activity in CRC remains unknown. In breast and prostate cancer inflammatory mediators, such as TNF&#9...

Background: Identifying individuals harbouring germline mutations in hereditary cancer genes provides opportunities for tumour surveillance programs, disease-specific treatment and cascade testing in family members but is reliant on accurate variant interpretation, which may be confounded by imprecise methods for ascribing pathogenicity. Where insufficient evidence supports a definitive classification, ‘variant of uncertain significance’ (VUS) status is applied, whic...

Background: Pathogenic variants in genes encoding Succinate Dehydrogenase subunits B and D (SDHB/SDHD) predispose to Phaeochromocytoma and Paraganglioma (PPGL). Cascade genetic screening identifies relatives at risk and allows surveillance screening to enable early detection of PPGLs.Methods: Retrospective analysis of genetic databases and hospital records between January 2000 and December 2018 identified relatives carrying SDHB and <em...

Background: Adrenocortical carcinoma (ACC) is a rare aggressive cancer with limited treatment options for advanced stages. By targeted RNA expression screening, we identified polo-like kinase 1 (PLK1) as one of most overexpressed genes, thus representing a potential drug target for ACC. PLK1 inhibitors are under evaluation in clinical trials for other solid cancers and seem to be more effective in TP53 mutated tumours. The aim of the study was to evaluate PLK1 protein levels i...

Introduction: Besides medullary thyroid carcinoma and other endocrinopathies, people with MEN 2B have intestinal ganglioneuromatosis. A recent MEN2B cohort study reported high rates of gastrointestinal (GI) symptoms: we hypothesized these might have a major impact on patients’ daily lives.Methods: An online survey was conducted among patients from Association for Multiple Endocrine Neoplasia Disorders (AMEND). This incorporated relevant elements fro...

Pancreatic neuroendocrine tumours (PNETs) may occur as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome, or as a non-familial isolated endocrinopathy. Current medical treatments for PNETs are largely ineffective in preventing tumour progression, so there is a need for better therapies, which will develop from an improved understanding of the mechanisms driving PNET tumorigenesis. Cytokine-driven inflammation has been implicated in the development and progression...

Primary hyperparathyroidism (PHP), usually due to multigland hyperplasia, occurs in >90% of patients with multiple endocrine neoplasia type 1 (MEN1). The literature is divided on the optimal surgical management for such patients. We report a retrospective cohort study on the long-term outcomes associated with limited, subtotal, or total parathyroidectomy as initial surgery for PHP in MEN1. The primary endpoint was recurrent PHP defined as an adjusted serum calcium >2.6 mmol/l ...

Colorectal cancers (CRC) represent 9.4% of all cancers, with about 42 000 new UK cases per year. Current treatment involves surgical resection followed by radio- and chemo-therapy. 5-Fluorouracil is the standard post-operative chemotherapy although tolerance is poor due to dose-limiting toxicities and drug-resistance. New treatment strategies are therefore sorely needed. One emerging chemotherapeutic option is to target oestrogen metabolism. Our novel work rev...

Introduction: Checkpoint inhibitor (CPI) related endocrine toxicities are increasingly commonly with the use of these new cancer agents. With one of the largest cancer departments in UK, we studied the clinical management and outcome of patients who developed different endocrine toxicities over the last five years, with the use of CTLA-4, PD-1 and PDL-1 agents.Methods: All patients treated with CPI between 1 Jan 2014 to 31 Jan 2019 were included for the ...

Mutations in cyclin dependent kinase inhibitor 1B (CDKN1B) are associated with multiple endocrine neoplasia type 4 (MEN4), in which patients typically develop parathyroid and anterior pituitary tumours, and occasionally tumours of the pancreas, adrenals, kidneys and reproductive organs. Here, we report a family with a missense mutation of CDKN1B (p.Pro69Leu) that did not have MEN4-associated tumours, but instead had hypomagnesaemia. The proband, presented wit...

Background: Immune checkpoint inhibitors (ICIs), approved in the UK for the treatment of increasingly numerous malignancies, are commonly associated with endocrine sequelae, some of which may be life threatening. Society for Endocrinology guidelines detail management protocols for acute endocrinopathies, however widely accepted standards for their routine detection are lacking. Hypophysitis, clinically and radiologically silent in many, is seen in up to 15% of patients on ICIs...

Objective: To review impact of childhood cancer treatment on endocrine, gonadal and thyroid function.Methods: Retrospective review of electronic records of 79 females, 90 males over 6 months of clinic visits from a Late Effects of childhood cancer clinic. Age at diagnosis: 8.5 years (range 5 months–9 years); time from treatment 23.5 years (range 10–40). Diagnoses: ALL, AML, Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma, sarcomas, Wilms, ...

Introduction: Ipilimumab is a human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) that has been shown to significantly improve survival in patients with metastatic melanoma. Immune-related adverse events (irAEs) occur in some patients with increased T-cell activation, of which ipilimumab-related hypophysitis (IH) is an important treatment complication. The aim of this study is to determine the incidence of IH and characterise clinical presentat...

Introduction: Patients with the familial cancer syndrome von Hippel–Lindau disease (VHL) are enrolled in radiological screening programmes which aim to identify tumour development at an early stage. This facilitates timely intervention to lesions when the risk of metastatic spread is low and when they are conducive to less-invasive and parenchymal-sparing interventions, thereby minimising treatment-related morbidity. A number of international screening protocols exist, al...

Aims: To discover the views of patients with Diabetes Insipidus (DI) on difficulties they encounter with managing DI in different circumstances; the possible causes of these difficulties and how these might be improved for their safety.Background: Between 2009 and 2015 there were 471 serious adverse inpatient incidents and 2 deaths involving DDAVP administration1. The analysis of one death resulted in a suggestion that the name of the conditio...

Background: Advances in next-generation sequencing facilitate the simultaneous evaluation of large numbers of cancer predisposition genes (CPGs) in patients with cancer irrespective of family history or tumour phenotype. Several studies have reported the frequent occurrence of germline mutations in CPGs in patients with discordant cancer types raising the possibility of novel gene-cancer associations. The current study aimed to evaluate the significance of germline mutations i...

Background: The accuracy of thyroglobulin (Tg) as a tumour marker following lobectomy for differentiated thyroid cancer (DTC) remains controversial. A Tg (<10 µg/l) looked promising in identifying those without clinically apparent recurrence after median 51 months of follow-up. Longer term follow up allows assessment of the diagnostic utility of thyroglobulin in predicting relapse.Methods: Ninety-nine patients who underwent lobectomy for DTC wer...

Introduction: Due to improved cancer survival rates, a rising number of CNS cancer survivors face late effects of therapy, such as hormone deficiencies. During adolesecence and young adulthood, specialised transition services are needed to cater for young peoples complex health needs and general needs, such as achieving independence. This study therefore audited a Teenage & Young Adult (TYA) neuro-oncology late effects clinic to identify areas of good practice and areas fo...

Introduction: Insulinoma a neuroendocrine tumour is diagnosed by inappropriately raised Insulin concentrations during a spontaneous or induced episode of hypoglycaemia. A provocative 72-h supervised fast is done to evaluate suspected inappropriate insulin secretion. Our aim is to see if it is feasible for a shorter duration of fast is enough to confirm Insulinoma.Method and results: In our Trust we analysed retrospectively in the last 10 years, ...

A 38 year old female was identified as carrying a heterozygous pathogenic MEN1 variant (c.13404delG) through predictive testing, following a diagnosis of familial hyperparathyroidism. Routine screening for hyperparathyroidism and pituitary disease was negative. However, a CT thorax-abdomen-pelvis revealed a 41 mm pancreatic tail mass. Biopsy via endoscopic ultrasound confirmed a well-differentiated (grade 1) pancreatic neuroendocrine tumour (pNET) with MIB1<1%. Bi...

Background: Neuroendocrine tumours are rare tumours that arise from neuroendocrine cell types which are widespread throughout the body. These tumours can develop in many different organs and secrete a variety of hormones making biochemical monitoring of treatment/progression challenging. Previously patients at Beatson West of Scotland Cancer Centre were monitored using either a full gut hormone profile (GHP) or chromogranin A and B (CGs) measured at Charing Cross Hospital. A n...

Current challenges in the management of breast cancer includes a continuous search for sensitive and specific minimally invasive biomarkers that can be exploited to detect early neoplastic changes, thus facilitating the detection of breast cancer at an early stage, as well as for monitoring the progress of patients with breast cancer and their response to treatments. This study investigated the expression pattern of miR-16, 21, 145, and 375 in plasma of breast cancer patients ...

Introduction: Hypophysitis has been recognised as a frequent endocrine related side effect of immunotherapy with the CLTA-4 inhibitor Ipilimumab, with a prevalence of upto 17.4%. The most common symptoms of hypophysitis are headache and signs/symptoms of hypopituitarism. Whilst some patients have an enlarged pituitary on MRI, this is frequently normal. ACTH and TSH deficiencies are most common, but all anterior and posterior pituitary hormonal axis may be affected. Hypopituita...

Introduction: Checkpoint inhibitors (CPi) are finding a place in the treatment algorithm of an increasing number of cancers. Immune-related (ir) endocrinopathies are frequent side-effects. Diabetes mellitus (irDM) is infrequent, but often presents acutely and can be potentially life-threatening There are ˜60–70 cases characterising irDM in the literature. We describe 4 cases of irDM to add to the understanding of this condition. All four patients were undergoing trea...

Carney’s triad; a diagnosis based on the presence of three associated neoplasms; epithelioid leiomyosarcoma, pulmonary chondroma, and extra-adrenal paraganglioma remains a rare diagnosis. Here we report a 52-year-old female investigated for chronic cough. Initial chest X-ray demonstrated calcified masses, and CT thorax confirmed a left pulmonary lesion measuring 41 mm in diameter with 3 adjacent smaller nodules up to 20 mm. A chondroid pattern o...

We present the case of a 77-year-old woman with a medical history of diabetes mellitus type 2 and hypothyroidism who was admitted to hospital after having had episodes of recurrent symptomatic hypoglycaemia. The patient had diabetes mellitus type 2 for 26 years and this had gone into remission over the previous 2 years: she had been having recurrent hypoglycaemia necessitating reduction in insulin doses and then subsequent discontinuation of therapy altogether. There was a his...

Background: Pancreatic Neuroendocrine Tumours (pNETs) can be associated with cancer susceptibility syndromes such as Multiple Endocrine Neoplasia type 1 (MEN1). MEN1 increases a person’s chance of developing pNETs, which are the main cause of mortality in this cohort. A diagnosis of pNETs, therefore, provides the opportunity for detection of associated MEN1 and subsequent identification of asymptomatic relatives who would then undergo relevant clinical, biochemical and ra...

Advanced papillary thyroid carcinoma (PTC) with cutaneous metastases may cause pain, ulceration and bleeding. Electrochemotherapy (ECT) is a minimally invasive oncologic treatment of tumours located in the skin and subcutaneous tissue. The electric pulses potentiates the toxicity of a cytostatic agent entering the tumour cell. It is highly effective especially to relieve pain and improve quality of life. The adverse events are local and transient. A case of progressive metasta...

Total parathyroidectomy with autotransplantation of parathyroid tissue is one of the treatment modalities for primary hyperparathyroidism in Multiple endocrine neoplasia type 1 (MEN1). Many of these patients are young and recurrence may take decades to emerge. We present a case of a 45-year-old woman who was diagnosed with MEN syndrome type 1 at the age of 12. Over the years, she underwent multiple surgical interventions including pituitary macroprolactinoma resection resultin...

Endocrinopathies are common complications following cancer therapy and may occur decades later. We present a case of 37 year old lady with a background of chronic myeloid leukaemia (CML) which was treated with sibling allogenic stem cell transplant and total body irradiation in 2002. She was noted to have elevated calcium levels with raised PTH 10 years later. In view of young age, she underwent genetic screening for MEN1 through buccal swab as her lymphocytes were not suitabl...

This is a case of a patient diagnosed with small cell lung carcinoma after presenting with severe hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) who was readmitted 7 months later with refractory hypokalemia and hyperglycaemia due to ectopic adrenocorticotrophic hormone secretion (EAS). A 65 year-old man presented in November 2018 with symptoms of nausea, vomiting, headaches and blurred vision. On examination he was clinically euvolemic. La...

A 45-year-old man with obesity (BMI 36 kg/m2) was admitted with a 12-hour history of headache and confusion and managed for viral meningitis. Treatment was discontinued after CSF viral PCR was negative. At presentation, he was hypoglycaemic with a capillary glucose of 1.6 mmol/l. Past medical history was not significant and there were no similar episodes previously. He denied taking insulin, other medications, illicit drugs or alcohol. Initial investigations reveale...

Diabetes education plays a vital role especially in newly diagnosed patients to prevent long-term complications and hospital admissions. We present a 68-year old female who was admitted with nausea, vomiting and poor oral intake. She was discharged two weeks ago after having complete pancreatectomy, splenectomy and left adrenalectomy for pancreatic cancer and a left adrenal mass. She did not have past medical history of diabetes and was commenced on basal bolus insulin after s...

63 year old gentleman, admitted in Nov 2018. Feeling generally unwell, decreased appetite, lethargy and poor mobility. Known lung cancer (diagnosed January 2018) On Immunotherapy last received in October 2018CT scan (September 2018) after 4 cycles of Pembrolizumab–excellent response to treatment. Routine blood tests were normal apart from a raised CRP at 551 and white cell count. A random cortisol level was done and found to be low at 135. Blood, urine, sputum and stool c...

Introduction: Metastatic lesion in the pituitary is a rare condition with most of them being asymptomatic. Breast cancer is the most frequent primary location and the overall prognosis is poor. We describe the case of a lady with this condition, who presented to our unit with bitemporal hemianopia.Case: A 65 year old lady with history of breast cancer (surgical excision with chemoradiotherapy 4 years ago, HER2 negative, currently in remission) presented ...