The Vanishing Adrenal Glands: A transient regression of adrenal lymphoma after a single dose of 1 mg dexamethasone

Objective: Dexamethasone is a known treatment for lymphoma, but it’s potency and rapidity of its effect has not been recognised. Our objective is to present a case of bilateral adrenal lymphoma, which significantly reduced in size after a single dose of dexamethasone. Methods: Clinical course and investigations including Adrenocorticotropic hormone (ACTH), cortisol, short synacthen test, computed tomography (CT) and adrenal biopsy are presented. Results: A 52-year-old man had a fall and was incidentally found to have bilateral adrenal masses (6 cm on left and 5 cm on right) on CT. His adrenal function tests included plasma metanephrines (normetanephrine 830 pmol/L (0-1180); metanephrine <100 pmol/L (0-510); 3-methoxytyramine <100 pmol/L (0-180), aldosterone 270 pmol/L( 90-700) and random cortisol 230 nmol/L (160-550). Overnight dexamethasone suppression test (ONDST), with 1 mg of dexamethasone, showed cortisol of <28 nmol/L (0-50).. A repeat CT, eight days following ONDST, showed adrenal masses of 4.5 cm and 3.5 cm on left and right respectively. He had a follow-up CT three months later, which showed adrenal lesions measuring 8 cm (left) and 9 cm (right). He subsequently presented with fatigue and dizziness. Morning cortisol of 201 nmol/L (160-550) with ACTH of 216 ng/L (10-30) indicated primary adrenal insufficiency. Mineralocorticoid and glucocorticoid replacement was commenced. Adrenal biopsy showed abnormal enlarged B-cells consistent with a diagnosis of diffuse large B-cell lymphoma. Conclusion: A diagnosis of lymphoma should be considered when adrenal lesions shrink, following even a single low dose of dexamethasone administered as a part of a diagnostic test

COVID-19 catalysing assessment transformation: A case of the online open book examination

Under COVID-19 lockdown conditions, the imposition of social distancing and restricted mobility, disrupted the traditional way of assessment in higher education. The closed book examination, conducted under proctored conditions, had to be substituted for the online open book examination (OOBE), posing challenges to both conventional and Open Distance Learning (ODL) institutions. The OOBE became a new experience to lecturers and students. Considering COVID-19 as a potential catalyst for educational transformation, the experiences gained in this format of assessment presents a valuable frame of reference for future learning. The aim is to extract lessons from this innovative learning experience to inform future assessment practices. The study is set in the context of a B.Ed. (Hons) compulsory module, offered at an Open Distance Learning (ODL) institution in South Africa. It is guided by the research question: “what were students’ experiences of their first online, open-book final examination and what are the implications for policy, practice and research?” This is a qualitative study, using as data, student emails on their experiences of the OOBE. The results show that the OOBE is an innovative assessment practice in higher education, in need of deeper understanding and (re)training. We conclude that the OOBE offers transformational opportunities in higher education assessment practices, to replace the traditional closed-book examination. We make recommendations to assist lecturers and students in approaching the OOBE in future

Sulforaphane Causes Epigenetic Repression of hTERT Expression in Human Breast Cancer Cell Lines

Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is a common dietary component that has histone deacetylase inhibition activity and exciting potential in cancer prevention. The mechanisms by which SFN imparts its chemopreventive properties are of considerable interest and little is known of its preventive potential for breast cancer. expression facilitated the induction of cellular apoptosis in human breast cancer cells.Collectively, our results provide novel insights into SFN-mediated epigenetic down-regulation of telomerase in breast cancer prevention and may open new avenues for approaches to SFN-mediated cancer prevention

A case series of patients with isolated IgG4-related hypophysitis treated with rituximab

Context The acute presentation of Immunoglobulin G4 (IgG4)-related hypophysitis can be indistinguishable from other forms of acute hypophysitis and histology remains the diagnostic gold standard. The high recurrence rate necessitates long term immunosuppressive therapy. Rituximab (RTX) has been shown to be effective in systemic IgG4-related disease (IgG4-RD), but experience with isolated pituitary involvement remains limited. Case description We report three female patients with MRI findings suggestive of hypophysitis. All patients underwent transsphenoidal biopsy and fulfilled diagnostic criteria for IgG4-related hypophysitis. Treatment with GCs (GC) resulted in good therapeutic response in patients 1 and 2, but the disease recurred on tapering doses of GCs. GC treatment led to emotional lability in Patient 3 necessitating dose reduction. All three patients received RTX and Patients 2 and 3 received further courses when symptoms returned and B-cells repopulated. Patient 3 did not receive RTX until 12 months from onset of symptoms. Patient 1 was not able to have further RTX treatments due to an allergic reaction when receiving the second dose. RTX treatment resulted in sustained remission and full recovery of anterior pituitary function in Patients 1 and 2 with complete resolution of pituitary enlargement. By contrast, Patient 3 only showed symptomatic response following RTX treatment, but pituitary enlargement and hypofunction persisted. Conclusion RTX treatment for IgG4-related hypophysitis resulted in sustained remission in two patients treated early in the disease process, but only achieved partial response in a patient with chronic disease suggesting that early therapeutic intervention may be crucial to avoid irreversible changes

Pharmacodynamic response to anti-thyroid drugs in Graves’ hyperthyroidism

The Section of Endocrinology and Investigative Medicine was funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009- 241592 EuroCHIP grant and was supported by the NIHR Biomedical Research Centre Funding Scheme. AA was supported by an NIHR Clinician Scientist award. SC was supported by an NIHR Clinical Lectureship. AC was supported by the NHS and BRC. WD was supported by an NIHR Research Professorship (RP-2014-05-001).Objective: Graves' disease is the commonest cause of hyperthyroidism in populations with sufficient dietary iodine intake. Anti-thyroid drugs (ATD) are often used as the initial treatment for Graves' hyperthyroidism, however there is a paucity of data relating the dose of ATD therapy to the effect on thyroid hormone levels, increasing the risk of both over- and under-treatment. We aimed to determine the pharmacodynamic response to the ATD carbimazole. Design: Retrospective cohort study. Methods: Participants were patients (n = 441) diagnosed with Graves' disease at Imperial College Healthcare NHS Trust between 2009 and 2018. The main outcome measure was change in thyroid hormone levels in response to ATD. Results: Baseline thyroid hormone levels were positively associated with TSH receptor antibody titres (P < 0.0001). Baseline free triiodothyronine (fT3) were linearly related to free thyroxine (fT4) levels in the hyperthyroid state (fT3 = fT4*0.97–11), and fell proportionately with carbimazole. The percentage falls in fT4 and fT3 per day were associated with carbimazole dose (P < 0.0001). The magnitude of fall in thyroid hormones after the same dose of carbimazole was lower during follow up than at the initiation visit. The fall in thyroid hormone levels approximated to a linear response if assessed at least 3 weeks after commencement of carbimazole. Following withdrawal of antithyroid drug treatment, the risk of relapse was greater in patients with higher initial fT4, initial TSH receptor antibody titre, males, smokers, and British Caucasian ethnicity. Conclusion: We identify a dose-response relationship for fall in thyroid hormones in response to carbimazole to aid in the selection of dose for Graves' hyperthyroidism.Publisher PDFPeer reviewe

An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs. METHODS: Tissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1α (Hif-1α), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1–5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan–Meier and Cox regression methods. RESULTS: Eighty-six consecutive cases were included: 51% male, median age 51 (range 16–82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1α and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1α expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1α-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1α+ GEP-NETs had a median survival of only 4.2 years (P=0.006). CONCLUSION: We have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif-1α expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up

A consensus process to agree best practice for managing physical wellbeing in people with a prolonged disorder of consciousness.

BACKGROUND: Current practice for physical wellbeing of people in a Prolonged Disorder of Consciousness (PDOC) is variable. A scoping literature review identified no agreed standard of care for physical management of those in a PDOC. This study addressed this deficit using a consensus process applied using nominal group technique. AIM: The aims of this project were to promote best practice for physical management in PDOC, by identifying consensus for: 1) a pathway of care; and 2) current best practice recommendations. DESIGN: A consensus process using nominal group technique. SETTING: Representation from national, purposively selected, rehabilitation services assessing and managing people in a PDOC in the UK. POPULATION: The population to whom the consensus process relates are people in a PDOC, requiring physical management. METHODS: An initial meeting with selected clinical experts from national centres was conducted to set terms of reference. A consensus meeting using nominal group technique (N.=33) then followed. Experts were initially asked to review systematic review findings reproduced as statements. Following systematic refinement, they were then asked to vote on the importance and relevance of statements. RESULTS: Following the nominal group process, 25 initial recommendations were refined to 19, which expressed the principles of physical management for people with a Prolonged Disorder of Consciousness. Statements are grouped into "acute-care" (6-recommendations), "postacute care" (10-recommendations) and "long-term care" (3-recommendations). Across the participants, agreement with the final recommendation statements ranged from 100-61% (N.=33-20), 15 of the statements were supported by 85% or more experts (N.=29). In addition, a clinical pathway of care, incorporating the recommendation principles was produced (agreement from 28 experts, 83%). CONCLUSIONS: The recommendations provide a basis for standardising current practice. They provide a standard against which care, and effectiveness can be evaluated. An accessible guideline document is planned for publication to enable implementation into practice, supported by online resources. CLINICAL REHABILITATION IMPACT: Recommendations have been produced under the headings of "acute care," "postacute care" and "long-term care." In addition, a pathway for provision of care interventions has been identified for the physical management of people in a prolonged disorder of consciousness

Grape Seed Proanthocyanidins Inhibit the Invasiveness of Human HNSCC Cells by Targeting EGFR and Reversing the Epithelial-To-Mesenchymal Transition

Head and neck squamous cell carcinoma (HNSCC) is responsible for approximately 20,000 deaths per year in the United States. Most of the deaths are due to the metastases. To develop more effective strategies for the prevention of metastasis of HNSCC cells, we have determined the effect of grape seed proanthocyanidins (GSPs) on the invasive potential of HNSCC cell and the mechanisms underlying these effects using OSC19 cells as an in vitro model. Using cell invasion assays, we established that treatment of the OSC19 cells with GSPs resulted in a dose-dependent inhibition of cell invasion. EGFR is over-expressed in 90% of HNSCCs and the EGFR inhibitors, erlotinib and gefitinib, are being explored as therapies for this disease. We found that GSPs treatment reduced the levels of expression of EGFR in the OSC19 cells as well as reducing the activation of NF-κB/p65, a downstream target of EGFR, and the expression of NF-κB-responsive proteins. GSPs treatment also reduced the activity of ERK1/2, an upstream regulator of NF-κB and treatment of the cells with caffeic acid phenethyl ester, an inhibitor of NF-κB, inhibited cell invasion. Overexpression of EGFR and high NF-κB activity play a key role in the epithelial-to-mesenchymal transition, which is of critical importance in the processes underlying metastasis, and we found treatment with GSPs enhanced the levels of epithelial (E-cadherin, cytokeratins and desmoglein-2) and reduced the levels of mesenchymal (vimentin, fibronectin, N-cadherin and Slug) biomarkers in the OSC19 cells. These results indicate that GSPs have the ability to inhibit HNSCC cell invasion, and do so by targeting the expression of EGFR and activation of NF-κB as well as inhibiting the epithelial-to-mesenchymal transition

Pituitary macroadenomas: are combination antiplatelet and anticoagulant therapy contraindicated? A case report

<p>Abstract</p> <p>Background</p> <p>Pituitary apoplexy is a life-threatening endocrine emergency that is caused by haemorrhage or infarction of the pituitary gland, commonly within a pituitary adenoma. Patients classically present with headache, ophthalmoplegia, visual field defects and altered mental state, but may present with a typical symptoms such as fever and altered conscious level.</p> <p>Case presentation</p> <p>A 57-year-old female with a known pituitary macroadenoma was treated for suspected acute coronary syndrome with aspirin, clopidogrel and full dose enoxaparin. She developed a severe and sudden headache, nausea and vomiting and visual deterioration. A CT scan showed haemorrhage into the pituitary macroadenoma. She underwent neurosurgical decompression. Post-operatively her visual fields and acuity returned to baseline. She was continued on hydrocortisone and thyroxine replacement on discharge.</p> <p>Conclusion</p> <p>This case illustrates the risks of anticoagulation in a patient with a known pituitary macroadenoma, and raises the issue of whether these tumours present a relative contraindication to the use of dual antiplatelet and anticoagulation in acute coronary syndrome.</p