Endocrine Abstracts

We previously reported that calycosin, a natural phytoestrogen structurally similar to estrogen, successfully triggered apoptosis of ER-positive breast cancer cell line, MCF-7. To better understand the antitumor activities of calycosin against breast cancer, besides MCF-7 cells, another ER-positive cell line T-47D was analyzed here, with ER-negative cell lines (MDA-231 and MDA-435) as control. Notably, calycosin led to inhibited cell viability and apoptosis only in ER-positive...

Background: Cushing’s syndrome derived from paraneoplastic ectopic ACTH production can present in dramatic fashion. We describe such a case that presented with severe hypokalaemia, involving significant diagnostic and management challenges.The case: A 66-year-old female was referred acutely to hospital by her GP after feeling weak and lethargic. She had profound hypokalaemia of 1.5 mmol/l (3.5–5.3) with normal renal function and had been normok...

Small cell lung cancer (SCLC) is a common and devastating disease. SCLC tumours contain a neuroendocrine cell population that exhibit ectopic hormone production in a minority of patients. The aim of this study was to investigate a panel of neuroendocrine peptides as potential biomarkers of SCLC, including pro-opiomelanocortin, neuron specific enolase, chromogranin A and neural-cell adhesion molecule. Immunohistochemistry methods were used to examine neuroendocrine peptides in ...

Background: Bone marrow transplant (BMT) survivors are at increased risk of metabolic syndrome and developing type 2 diabetes (T2DM). Measurement of HbA1c is increasingly used in recent years for the diagnosis of T2DM. An HbA1c level of ≥6.5% (48 mmol/mol) is considered as a diagnostic cut-off for T2DM and an HbA1c between 6.0–6.4% (42–47 mmol/mol) is considered as at risk of T2DM. We aimed to look at the diagnostic performance of HbA1c and oral glucose toleran...

Small cell lung cancer (SCLC) is distinguished by its neuroendocrine phenotype and secretion of hormone biomarkers. Tumours initially respond well to therapy but almost invariably relapse with a therapy-resistant phenotype. We have previously described pro-opiomelanocortin (POMC) as a potential biomarker of SCLC. In this study, we investigated how POMC acts as a biomarker of tumour response to treatment.SCLC cells (DMS 79) were injected subcutaneously in...

Introduction: Langerhans cell histiocytosis (LCH) is a rare condition primarily affecting children. It is characterised by clonal proliferation of Langerhans cells. Disease severity is dependent on the type and number of organs involved in addition to focality. Disease aetiology remains unclear. We aimed to record the incidence and characteristics of West of Scotland LCH patients with a focus on predictive factors for endocrine dysfunction.Method: Consec...

PBF is a ubiquitous glycoprotein which is over-expressed particularly in endocrine and endocrine-related cancers. Previously classified as a proto-oncogene, 11 substitution-missense mutations of PBF have now been reported in tumours from patients with ovarian, prostate and colorectal cancers via the COSMIC database, suggesting PBF may in fact be an oncogene. We have therefore examined the biological implications of all 11 mutations. Substitution mutations, which occurred acros...

Pancreatic neuroendocrine tumours (NETs) are reported to show frequent mutations in chromatin remodelling genes, while pituitary NETS have alterations in histone modification. Histone modifications, and specifically acetylated residues on histone tails are recognised by members of the bromo and extra terminal (BET) protein family, via their bromodomains, causing alterations in the transcription of growth stimulating genes. BET bromodomain inhibitors have been demonstrated to s...

We present a case of 50-year-old female who presented to a local hospital with sudden onset severe sharp left flank pain. Urgent CT revealed a mass in the left adrenal gland which was thought to be a supra-renal bleed. It measured 6 cm at this point. She was discharged with paracetamol and re-assured. As she was not feeling well, she had an US kidney in private sector 1 month later revealing static appearance of presumed haematoma. Following the period of observation to allow ...

We present a family of a 45-year-old patient who presented to hospital acutely unwell with metastatic paragangliomas. Unfortunately due to rapidity of his presentation, no genetic testing was performed. He was found to have 5 cm right carotid body tumour. His urine collections confirmed raised (seven times normal) 24 h urine metanephrines 24.55 μmol (normal <3.47 μmol). Shortly after the initial diagnosis he was found to have extensive vertebral body metastases i...

A 43-year-old gentleman was referred from a local hospital with biochemical and radiological suspicion of pheochromocytoma. He admitted to a 10-year history of palpitations, flushing, sweating, and tremors. He was intermittently feeling stressed, anxious and angry with mood swings. He had difficulty sleeping and suffered from headaches. He was treated for hypertension and 10 years prior he was admitted to the local hospital with malignant hypertension. He was drinking up to 40...

Whilst, radioiodine ablation is an effective therapy for many patients with thyroid cancer, a subset of patients are incapable of accumulating sufficient iodide-131 for effective treatment, due to low sodium–iodide symporter (NIS) activity. Previous work has identified that the overexpression of pituitary tumor transforming gene (PTTG) binding factor (PBF) in thyroid cells leads to the redistribution of NIS from the plasma membrane into intracellular vesicles, thereby red...

The use of herbal intervention in the treatment of tumors is widely spread in all regions of the developing world even though there are insufficient data on their possible molecular mechanism of action. Thirty percent of all cancers in women occur in the breast making it the most commonly diagnosed female cancer. The cytotoxic properties of the 80% aqueous-ethanol crude, n-hexane, chloroform, ethylacetate, detannified, and tannin fractions of Curculigo pilosa&#146...

Background: The glands most commonly affected in MEN1 are parathyroid, pituitary and pancreas. Pancreatic neuroendocrine tumours (pNETs) are of foregut origin, but a number of other so-called ’foregut carcinoid tumours’ may also occur in MEN1, including tumours of bronchial, thymic, and gastrointestinal origin. Reported rates of prevalence of these latter tumours vary from 2% for thymic and bronchial carcinoids, to 10% for gastric carcinoids. Thymic carcinoids have b...

Phaeochromocytomas (PCC) and paraganglioma (PGL) are neural crest tumours arising from the chromaffin producing cells of the adrenal medulla or sympathetic/parasympathetic system respectively. Recently, in part due to advances in high throughput sequencing, our understanding of the genetic predisposition to these tumours has greatly increased. To date, 13 genes have been implicated in the pathogenesis of these conditions (ten available for testing at our centre). Recent studie...

Introduction: Adrenocortical carcinoma (ACC) has a poor prognosis and limited therapeutic options. The epidermal growth factor receptor (EGFR) expression was found to be a good discriminator between malignant and benign adrenal tumours, but was mutated only in 3–10% of ACC cases.Aim: The aim of this study was to assess the effect of inhibition of EGFR with targeted therapies, i.e. Erlotinib (with and without EGF stimulation) on ACC cell proliferatio...

Aim: The aim of this study was to examine the incidence of metabolic abnormalities in adults getting treatments of brain tumors (BT) and acute lymphoblastic leukemia (ALL) in their childhood or adolescence.Methods: patients were divided in two groups. In group 1: 31 BT survivors (13 women and 18 men) were included. All patients received craniospinal irradiation up to 36 Gy and boost to the tumor up to 55 Gy and chemotherapy. The group 2: 18 ALL survivors...

Introduction: Gas chromatography/mass spectrometry based steroid profiling has been proposed as a tool for differentiating adrenocortical carcinoma (ACC) from benign adrenocortical adenoma (ACA). We retrospectively examined urinary steroid profiles from ten patients with ACC and 14 patients with ACA to determine, if the steroid profiles were predictive in distinguishing benign from malignant disease.Methods: Patients who had undergone adrenalectomy for r...

Introduction: Adrenal incidentalomas (AI) are mostly benign and non secretory, but some are malignant. Current diagnostic and management algorithms are not fail safe when assessing malignant potential, although functional status is much easier to assess. We present a subject with multiple comorbidities whose AI was a very rare adrenal leiomyosarcoma (AL)Case presentation: A 40-year-old woman with SLE and the antiphospholid syndrome on lifelong warfarin t...

Introduction: Mutations in the RET gene cause multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma (FMTC). The identification of a germline RET mutation aids clinical management, enables the identification and predictive testing of at risk family members and provides reassurance for mutation-negative family members. In the research setting, mutations in exons 5, 8, 10, 11, 13–16 of the RET gene have been ...

Phaeochromocytomas (PHAEOs) and extra-adrenal paragangliomas (PGLs) are rare neuroendocrine tumours. As many as 35% may have an identifiable germline mutation, most commonly in the genes encoding RET, VHL or subunits of succinate dehydrogenase (SDHx).[123I]-labelled metaiodobenzylguanidine (123I-MIBG) scintigraphy is used to localise PHAEOs/PGLs, while 131I-MIBG is used as therapy in malignant disease. Uptake of radioisot...

Background: Succinate dehydrogenase B (SDHB) associated disease has been characterised by the presence of extra-adrenal paragangliomas with a high rate of metastatic transformation. There is currently no consensus as to the appropriate surveillance regimes for these subjects. We present the surveillance data from a single UK institution with an SDHB surveillance regime which includes annual MR imaging of the abdomen, biennial imaging of the neck, thorax and pelvis and annual u...

Introduction: Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant multi-glandular tumour syndrome, caused by RET germline mutations.We present a family with three affected generations identified by predictive testing.Index case and cohort details: A 40-year-old lady referred to ENT clinic with a swelling in the neck. Ultrasound confirmed multinodular goitre with FNAC-THY3. Diagnostic hemithyroidectomy was followed by total thyroidectomy f...

MEN2a is a rare genetic endocrine disorder associated with mutation of RET oncogene on chromosome 10. It involves lesions in thyroid, parathyroid and adrenal glands. Medullary thyroid carcinoma is the pathological hallmark and usually the first presentation of this syndrome.Clinical case: A 64-year-old lady with previous history of hypertension, IHD, and hypercholesterolemia was referred to Endocrine clinic after she was incidentally found to have high c...

Disruption of DNA damage response pathways results in an accumulation of genetic mutations, gene amplifications and chromosome alterations, which are key initiating factors in cellular transformation and oncogenesis. PBF is a multifunctional proto-oncogene which is overexpressed in thyroid, pituitary and breast cancers, with roles in cell transformation, invasion and transporter regulation. Recently, we reported that targeted transgenic expression of PBF promotes genetic insta...