Imperial College London

Professor Karim Meeran

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Endocrinology
 
 
 
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Contact

 

+44 (0)20 8846 1065k.meeran

 
 
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Location

 

9E05Charing Cross HospitalCharing Cross Campus

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Summary

 

Publications

Publication Type
Year
to

226 results found

Almazrouei R, Zaman S, Wernig F, Meeran Ket al., 2022, Utility of cannulated prolactin to exclude stress hyperprolactinemia in patients with persistent mild hyperprolactinemia, Clinical Medicine Insights: Endocrinology and Diabetes, Vol: 14, ISSN: 1178-1173

Background:Stress-induced hyperprolactinemia can be difficult to differentiate from true hyperprolactinema and may result in patients having unnecessary investigations and imaging. We report the results of cannulated prolactin tests with serial prolactin measurements from an indwelling catheter to differentiate true from stress-induced hyperprolactinemia in patients with persistently mildly elevated prolactin levels in both referral and repeat samples.Methods:Data were collected for 42 patients who had a cannulated prolactin test between January 2017 and May 2018. After cannula insertion, prolactin was measured at 0, 60, and 120 minutes. Normalization is defined as a decline in prolactin to gender-defined normal ranges.Results:The mean age was 33.8 years (SD ± 9.9), and 37 (88%) were female. Menstrual irregularities were the main presenting symptom in 28.57% of the patients. Prolactin normalized in 12 (28.6%) patients of whom cannulated prolactin test was done. Repeat random prolactin levels were significantly higher in patients whose prolactin did not normalize during the cannulated prolactin test. MRI of the pituitary gland showed an abnormality in 23 out of 28 (82%) patients who did not normalize prolactin, a microadenoma in the majority of patients (18 patients).Conclusion:The cannulated prolactin test was useful in excluding true hyperprolactinemia in 28.6% of patients with previously confirmed mildly elevated random prolactin on two occasions, thus avoiding over-diagnosis and unnecessary imaging.

Journal article

Ramadoss V, Lazarus K, Prevost AT, Tan T, Meeran K, Choudhury Set al., 2021, Improving the interpretation of afternoon cortisol levels and SSTs to prevent misdiagnosis of Adrenal Insufficiency, Journal of the Endocrine Society, Vol: 5, Pages: 1-14, ISSN: 2472-1972

IntroductionAdrenal Insufficiency (AI), especially iatrogenic-AI, is a treatable cause of mortality. The difficulty in obtaining 9am cortisol levels means samples are taken at suboptimal times, including a substantial proportion in the afternoon. Low afternoon cortisol levels often provoke short Synacthen Tests (SSTs). It is important that this does not lead to patients misdiagnosed with AI, exposing them to the excess mortality and morbidity of inappropriate steroid replacement therapy.MethodsThis retrospective study collected 60,178 cortisol results. Medical records, including subsequent SSTs of initial cortisol results measured after midday were reviewed.ResultsROC analysis (AUC- 0.89) on 6531 suitable cortisol values showed that a limit of <201.5nmol/L achieved a sensitivity and specificity of 95.6% and 72.6%, whilst a limit of <234nmol/L had a sensitivity of 100% and a specificity of 59.5%. Out of 670 SSTs, 628 patients passed. Of these, 140 would have otherwise failed if only their 30-minute cortisol was assessed without the 60-minute value.A 30-minute and 60-minute SST cortisol cut-off of 366.5nmol/L and 418.5nmol/L respectively, can achieve a sensitivity of >95% on the Abbott analyser platform.ConclusionAn afternoon cortisol >234nmol/L excludes AI on Abbott analyser platforms. In patients who have an afternoon cortisol <234nmol/L, including both a 30-minute and a 60-minute SST cortisol values prevents unnecessary glucocorticoid replacement therapy in 22.3% of individuals in this study. The Abbott analyser SST cortisol cut-offs used to define AI should be 366.5nmol/L and 418.5nmol/L at 30- and 60-minutes respectively. All patients remained well subsequently with at least one year longitudinal follow up.

Journal article

Clarke S, Phylactou M, Patel B, Mills E, Muzi B, Izzi-Engbeaya C, Choudhury S, Khoo B, Meeran K, Comninos A, Abbara A, Tan T, Dhillo Wet al., 2021, Normal adrenal and thyroid function in patients who survive COVID-19 infection, Journal of Clinical Endocrinology and Metabolism, Vol: 106, Pages: 2208-2220, ISSN: 0021-972X

ContextThe COVID-19 pandemic continues to exert an immense burden on global health services. Moreover, up to 63% of patients experience persistent symptoms, including fatigue, after acute illness. Endocrine systems are vulnerable to the effects of COVID-19 as many glands express the ACE2 receptor, used by the SARS-CoV-2 virion for cellular access. However, the effects of COVID-19 on adrenal and thyroid gland function after acute COVID-19 remain unknown. ObjectivesOur objectives were to evaluate adrenal and thyroid gland function in COVID-19 survivors. DesignA prospective, observational study was undertaken. SettingClinical Research Facility, Imperial College NHS Healthcare Trust. ParticipantsSeventy patients ≥ 18 years at least 3 months after diagnosis of COVID-19 were included. InterventionParticipants attended a research study visit (08:00-09:30), during which a short Synacthen test (250 µg IV bolus), and thyroid function assessments were performed.ResultsAll patients had a peak cortisol ≥450 nmol/l after Synacthen, consistent with adequate adrenal reserve. Basal and peak serum cortisol did not differ according to disease severity or history of dexamethasone treatment during COVID-19. There was no difference in baseline or peak cortisol after Synacthen or in thyroid function tests, or thyroid status, in patients with fatigue (n=44) compared to those without (n=26).ConclusionsAdrenal and thyroid function ≥3 months after presentation with COVID-19 was preserved. Whilst a significant proportion of patients experienced persistent fatigue, their symptoms were not accounted for by alterations in adrenal or thyroid function. These findings have important implications for the clinical care of patients after COVID-19.

Journal article

Zaman S, Almazrouei R, Sam AH, DiMarco AN, Todd JF, Palazzo FF, Tan T, Dhillo WS, Meeran K, Wernig Fet al., 2021, Synacthen stimulation test following unilateral adrenalectomy needs to be interpreted with caution, Frontiers in Endocrinology, Vol: 12, Pages: 1-7, ISSN: 1664-2392

Background: Cortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center.Methods: Data were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing’s syndrome were excluded.Results: The median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement.Conclusions: Synacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.

Journal article

Lee V, 2021, A ‘Real Life’ service evaluation model for multidisciplinary thyroid eye services, Frontiers in Endocrinology, Vol: 12, Pages: 1-9, ISSN: 1664-2392

Background/Aims: There is no universal consensus on the practical implementation and evaluation of the Amsterdam Declaration on Graves Orbitopathy in a Multidisciplinary Thyroid Eye Disease (MDTED) pathway. Recent recommendations from the UK TEAMeD-5 and BOPSS initiative highlight the importance of prevention, screening, and prompt referral of patients with moderate to severe and sight-threatening thyroid eye disease to multidisciplinary (MDTED) clinics and recommends annual auditing. We propose a practical service evaluation model with Key Performance Indicators (KPI) that are achievable and could be implemented across most TED pathways.Material and Methods: We conducted a service evaluation from an integrated TED pathway in London with three MDTED clinics. Data was collected retrospectively from consecutive TED patients included: 1) Patient demographics, 2) Referral to first appointment time, 3) Documented smoking cessation and selenium supplementation advice, 4) Presenting disease activity and severity, 5) Investigations and treatments, including radio-iodine, 6) Time from decision to treatment initiation, 7) Initial and subsequent thyroid status.Results: The median age was 49.0 yrs, 77.5% (183/236) were female and 49.5% (101/204) Afro-Caribbean or Asian. At their first clinic attendance, 47.6% (110/231) were biochemically euthyroid and 76.7% (79/103) at discharge. All 23.1% (52/225) current smokers received smoking cessation advice and 64.8% (153/236) received selenium supplementation advice. Intravenous methylprednisolone was given to 33.9% (80/236) patients and 12.7% (30/236) received second-line immunosuppression. All 7.2% (17/236) patients with sight-threatening disease received treatment within two weeks of diagnosis.Conclusions: This study forms a waymark for other units using TEAMeD-5 and BOPSS audit criteria. Dedicated electronic patient records with ongoing data capture, including quality of life assessments, and diagnostic coding would significantly ai

Journal article

Boharoon H, Tomlinson J, Limback-Stanic C, Gontsarova A, Martin N, Hatfield E, Meeran M, Nair R, Mendoza N, Levy J, McAdoo S, Pusey C, Wernig Fet al., 2021, A case series of patients with isolated IgG4-related hypophysitis treated with rituximab, Journal of the Endocrine Society, Vol: 4, Pages: 1-9, ISSN: 2472-1972

ContextThe 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 descriptionWe 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.ConclusionRTX 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.

Journal article

Kelada M, Avari P, Farag S, Akashar R, Jain R, Aziz A, Feeney C, Bravis V, Meeran K, Lee Vet al., 2021, Association of other autoimmune diseases in thyroid eye disease, Frontiers in Endocrinology, Vol: 12, ISSN: 1664-2392

Background: Thyroid eye disease (TED) is a potentially disfiguring and sight-threatening autoimmune (AI) orbitopathy, affecting up to 400,000 people in the UK. There are no accurate early predictors of TED severity. Although polyautoimmunity has been shown to affect AI disease severity, its influence on TED severity has never been investigated. The prevalence of polyautoimmunity among TED patients is also unclear, with discordant results reported in the literature. This study evaluates the prevalence of non-thyroid/“other” AI (OAI) conditions in an ethnically diverse TED cohort and assesses how polyautoimmunity affects TED severity and activity.Methods: A retrospective study of patients presenting to multidisciplinary TED clinics across three North-West London hospitals between 2011 and 2019. Data collected included: 1) demographics; 2) OAI conditions and management; 3) endocrine management of thyroid dysfunction; 4) details of TED and clinical activity score at presentation.Results: Two hundred and sixty-seven patients with a median age of 46 (35–54) years were included, 79.4% were female and 55% were Black, Asian and minority ethnic (BAME). Thirty-seven patients (13.9%) had OAI conditions, with rheumatoid arthritis (3.7%), vitiligo (3.0%) and psoriasis (3.0%) among the most prevalent. Of patients with OAI conditions, 43.2% (16/37) required immunosuppression prior to TED onset. Non-immunosuppressed patients with OAI conditions had a significantly higher clinical activity score at presentation than TED-only and previously immunosuppressed patients (p=0.02). No significant differences were observed in thyroid receptor antibody titers between these groups.Conclusions: This study finds a 13.9% prevalence of OAI conditions among TED patients. Patients with OAI conditions overall have a tendency for more severe and significantly more clinically active TED than those without OAI conditions. Larger, prospective studies are warranted to further evaluate po

Journal article

Meeran M, Zaman S, 2021, The Vanishing Adrenal Glands: A transient regression of adrenal lymphoma after a single dose of 1 mg dexamethasone, AACE Journal, Vol: 7, Pages: 109-112, ISSN: 1551-3696

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.

Journal article

Mehta P, Meeran K, Macphie E, Abbas A, Rippin J, Jeffery RC, Reddy V, Leandro MJ, Ciurtin C, Simpson HL, Mackie SLet al., 2021, Variability in counselling for adrenal insufficiency in COVID-19 and beyond: a survey of rheumatology practice, The Lancet Rheumatology, Vol: 3, Pages: E92-E94, ISSN: 2665-9913

Journal article

Khoo B, Tan T, Clarke S, Mills E, Patel B, Modi M, Phylactou M, Eng PC, Thurston L, Alexander E, Meeran K, Comninos A, Abbara A, Dhillo Wet al., 2021, Thyroid function before, during and after COVID-19, Journal of Clinical Endocrinology and Metabolism, Vol: 106, Pages: e803-e811, ISSN: 0021-972X

Context: The effects of COVID-19 on the thyroid axis remain uncertain. Recent evidence has been conflicting, with both thyrotoxicosis and suppression of thyroid function reported. Objective: We aimed to detail the acute effects of COVID-19 on thyroid function and determine if these effects persisted upon recovery from COVID-19. Design: Cohort observational study. Participants and setting: Adult patients admitted to Imperial College Healthcare National Health Service Trust, London, UK with suspected COVID-19 between March 9 to April 22, 2020 were included, excluding those with pre-existing thyroid disease and those missing either free thyroxine (FT4) or TSH measurements. Of 456 patients, 334 had COVID-19 and 122 did not.Main Outcome Measures: TSH and FT4 measurements at admission, and where available, those taken in 2019 and at COVID-19 follow-up. Results: Most patients (86·6%) presenting with COVID-19 were euthyroid, with none presenting with overt thyrotoxicosis. Patients with COVID-19 had a lower admission TSH and FT4 compared to those without COVID-19. In the COVID-19 patients with matching baseline thyroid function tests from 2019 (n=185 for TSH and 104 for FT4), both TSH and FT4 were reduced at admission compared to baseline. In a complete cases analysis of COVID-19 patients with TSH measurements at follow-up, admission and baseline (n=55), TSH was seen to recover to baseline at follow-up. Conclusions: Most patients with COVID-19 present with euthyroidism. We observed mild reductions in TSH and FT4 in keeping with a non-thyroidal illness syndrome. Furthermore, in survivors of COVID-19, thyroid function tests at follow-up returned to baseline.

Journal article

Choudhury SM, Tan TMM, Lazarus K, Meeran Ket al., 2021, The use of prednisolone versus dual-release hydrocortisone in the treatment of hypoadrenalism, Endocrine Connections, Vol: 10, Pages: R66-R76, ISSN: 2049-3614

The introduction of adrenocortical extract in 1930 improved the life expectancy of hyhpoadrenal patients, with further increases seen after the introduction of cortisone acetate from 1948. Most patients are now treated with synthetic hydrocortisone, and incremental advances have been made with optimisation of daily dosing and the introduction of multidose regimens. There remains a significant mortality gap between individuals with treated hypoadrenalism and the general population. It is unclear whether this gap is a result of glucocorticoid over-replacement, under-replacement or loss of the circadian and ultradian rhythm of cortisol secretion, with the risk of detrimental excess glucocorticoid exposure at later times in the day. The way forwards will involve replacement of the diurnal cortisol rhythm with better glucocorticoid replacement regimens. The steroid profile produced by both prednisolone and dual-release hydrocortisone (Plenadren), provide a smoother glucocorticoid profile of cortisol than standard oral multidose regimens of hydrocortisone and cortisone acetate. The individualisation of prednisolone doses and lower bioavailability of Plenadren offer reductions in total steroid exposure. Although there is emerging evidence of both treatments offering better cardiometabolic outcomes than standard glucocorticoid replacement regimens, there is a paucity of evidence involving very low dose prednisolone (2–4 mg daily) compared to the larger doses (~7.5 mg) historically used. Data from upcoming clinical studies on prednisolone will therefore be of key importance in informing future practice.

Journal article

Hameed S, Salem V, Alessimii H, Scholtz S, Dar O, Miras AD, Meeran K, Bloom SR, Ahmed AR, Purkayastha S, Chahal H, Tan Tet al., 2020, Imperial Satiety Protocol: A new non-surgical weight-loss programme, delivered in a health care setting, produces improved clinical outcomes for people with obesity, Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 23, Pages: 270-275, ISSN: 1462-8902

‘Imperial Satiety Protocol’ (I-SatPro) is a new multifaceted approach to weight loss for people with obesity (PwO), encompassing dietary advice, time-restricted eating, physical activity and coaching to support behaviour change. Participants (n = 84) attended fortnightly I-SatPro group sessions for 30 weeks, with 70% of participants completing. On completion at 30 weeks, the mean weight loss was 15.2 ± 1.1 kg (13.2 ± 0.8% from baseline, P < .0001), which was maintained to 52 weeks (16.6 ± 1.5 kg, 14.1 ± 1.2%, P < .0001). Weight loss was not associated with reduced energy expenditure. In participants with type 2 diabetes and pre-diabetes (n = 16), glycated haemoglobin fell from 50 to 43 mmol/mol (P < .01). Systolic blood pressure fell by 12 mmHg (P < .0001). Triglycerides fell by 0.37 mmol/L (P < .01) and high-density lipoprotein rose by 0.08 mmol/L (P < .01). Short Form-36 (SF-36) functioning and wellbeing scores increased in all domains post I-SatPro intervention. For selected PwO, I-SatPro delivers clinically meaningful weight loss, and the potential for long-term health and wellbeing improvements.

Journal article

Tan T, Khoo B, Mills EG, Phylactou M, Patel B, Eng PC, Thurston L, Muzi B, Meeran K, Prevost AT, Comninos AN, Abbara A, Dhillo WSet al., 2020, Cortisol concentrations and mortality from COVID-19 - Authors' reply, The Lancet Diabetes and Endocrinology, Vol: 8, Pages: 809-810, ISSN: 2213-8595

Journal article

Tan T, Khoo B, Mills EG, Phylactou M, Patel B, Eng PC, Thurston L, Muzi B, Meeran K, Prevost AT, Comninos AN, Abbara A, Dhillo WSet al., 2020, Association between high serum total cortisol concentrations and mortality from COVID-19, The Lancet Diabetes and Endocrinology, Vol: 8, Pages: 659-660, ISSN: 2213-8595

Journal article

Hussain S, Hussain S, Mohammed R, Meeran K, Ghouri Net al., 2020, Fasting with adrenal insufficiency: Practical guidance for healthcare professionals managing patients on steroids during Ramadan, Clinical Endocrinology, Vol: 93, Pages: 87-96, ISSN: 0300-0664

There are limited recommendations for fasting in many chronic diseases such as adrenal insufficiency (AI). Research in such situations highlights potential for complications and need for education for patients with AI undertaking fasting during Ramadan. This article aimed to provide up-to-date guidance for healthcare professionals to educate, discuss and manage patients with AI who are considering fasting in Ramadan and is religiously compatible. Latest guidance on this topic and the evidence base for steroid dosing are reviewed and discussed. Risk stratification for patients with AI and optimal strategies for management, including steroid dosing, are detailed. Our review highlights that patients with AI wishing to fast should undergo a thorough risk assessment ideally several months before Ramadan. ‘High risk’ and ‘Very high risk’ patients should be encouraged to explore alternative options to fasting discussed below. Prior to the commencement of Ramadan, all patients must receive up-to-date education on sick day rules, instructions on when to terminate their fast or abstain from fasting, carry steroid warning information and must have a valid intramuscular (IM) hydrocortisone pack and know how to administer this. Switching patients with AI desiring to fast from multiple daily hydrocortisone replacement to prednisolone 5 mg once daily at dawn (during Suhoor or Sehri) is recommended and discussed. Patients on fludrocortisone for AI should be advised to take their total dose at dawn. We provide practically relevant case-based scenarios to help with the application of this guidance. Future efforts need to focus on healthcare professional awareness and further research in this setting.

Journal article

Abbara A, Clarke S, Brewster R, Simmonard A, Eng PC, Phylactou M, Papadopoulou D, Izzi-Engbeaya C, Sam A, Wernig F, Jonauskyte E, Comninos A, Meeran K, Kelsey T, Dhillo Wet al., 2020, Pharmacodynamic response to anti-thyroid drugs in Graves’ hyperthyroidism, Frontiers in Endocrinology, Vol: 11, ISSN: 1664-2392

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.

Journal article

Almazrouei R, Meeran K, Palazzo FF, 2020, Visual Vignette, ENDOCRINE PRACTICE, Vol: 26, Pages: 252-252, ISSN: 1530-891X

Journal article

Sam AH, Wilson RK, Lupton M, Melville C, Halse O, Harris J, Meeran Ket al., 2019, Clinical prioritisation questions: A novel assessment tool to encourage tolerance of uncertainty?, Medical Teacher, Pages: 1-6, ISSN: 0142-159X

Uncertainty is a common and increasingly acknowledged problem in clinical practice. Current single best answer (SBA) style assessments test areas where there is one correct answer, and as the approach to assessment impacts on the approach to learning, these exams may poorly prepare our future doctors to handle uncertainty. We therefore, need to modify our approach to assessment to emphasize reasoning and introduce the possibility of more than one ‘correct’ answer. We have developed clinical prioritization questions (CPQs), a novel formative assessment tool in which students prioritize possible responses in order of likelihood. This assessment format was piloted with a group of medical students and evaluated in comparison with the more traditional SBA question format in a team-based learning setting. Students reported that they felt ongoing use would help improve their tolerance of uncertainty (p < 0.01). Furthermore, over 80% of students felt that CPQs were more reflective of real-life clinical practice. Group based discussions were significantly longer when answering CPQs (p < 0.01), suggesting they may promote richer discourse. CPQs may have a role in formative assessment to help equip students with the skills to cope with ambiguity and strengthen clinical reasoning and decision-making. Institutions may find them more practical to implement compared with other clinical reasoning assessment tools.

Journal article

Meeran K, 2019, Optimising glucocorticoid replacement in adrenal insufficiency, BRITISH JOURNAL OF DIABETES, Vol: 19, Pages: 131-132, ISSN: 2397-6233

Journal article

Farag S, Feeney C, Lee V, Akishar R, Nagendran S, Jain R, Aziz A, Robinson S, Meeran K, Bravis Vet al., 2019, Identifying risk factors for severity & activity of Graves Orbitopathy - a multi-centre analysis of the characteristics and treatment of patients with Thyroid Eye Disease, The 2019 European Association for Vision and Eye Research Conference, Publisher: European Association for Vision and Eye Research (EVER), Pages: 1-2, ISSN: 1395-3907

PurposeEarly diagnosis and treatment of Graves Orbitopathy (GO) is essential to prevent sight-threatening complications and long-term disability and therefore establishing a standard of care is highly desirable. Establishing predictors of a severe disease course are also vital to allow for early intervention.MethodsA retrospective patient-cohort study of 236 patients referred to three GO multidisciplinary (MDT) clinics between 2012–2019. Derived from this cohort, audit standards were compared against TEAMeD-5 guidelines, looking in particular at; (i) time between referral and specialist review (ii) offering of smoking cessation and selenium supplementation where appropriate (iii) time from referral to treatment for moderate-severe active disease. Patient characteristics were also analysed to investigate for any groupwise differences and correlations between variables collected at baseline to help predict subsequent disease activity.ResultsMedian patient age was 48.0 years, 77.5% female, 30.1% White Caucasian. Median initial clinical activity score (CAS) was 1 (range 0–7). Additionally, 80.5% had positive TSH antibody titre. The median time between referral and first MDT clinic was 50.0 days. Of the 254 patients, 80/236 received IVMP for active moderate-severe GO and the mean time to treatment was 9.3 days. All patients with sight-threatening GO were seen and treated within 2 weeks. There were 52/236 (22.0%) current smokers, all of whom received documented smoking cessation advice. A positive correlation was found between TSH antibody titre (R = −0.2902, p = 0.0545).ConclusionThe increasing recognition that an MDT approach is optimal for the management of GO requires a strong clinical governance framework. This work will further define the TEAMeD guidelines before the national implementation. Novel findings relating to the association of disease activtiy with biomarkers of diabetes and antibody titres are worth further investigation.

Conference paper

Sam SA, Peleva E, Fung CY, Cohen N, Benbow EW, Meeran Ket al., 2019, Very short answer questions: a novel approach to summative assessments in pathology, Advances in Medical Education and Practice, Vol: 10, Pages: 943-948, ISSN: 1179-7258

BackgroundA solid understanding of the science underpinning treatment is essential for all doctors. Pathology teaching and assessment are fundamental components of the undergraduate medicine curriculum. Assessment drives learning and the choice of assessments influences students’ learning behaviours. The use of multiple-choice questions is common but is associated with significant cueing and may promote ‘rote learning’. Essay-type questions and Objective Structured Clinical Examinations (OSCEs) are resource-intensive in terms of delivery and marking, and do not allow adequate sampling of the curriculum. To address these limitations, we used a novel online tool to administer Very Short Answer questions (VSAQs) and evaluated the utility of the VSAQs in an undergraduate summative pathology assessment.MethodsA group of 285 medical students took the summative assessment, comprising 50 VSAQs, 50 single best answer questions (SBAQs), and 75 extended matching questions (EMQs). The VSAQs were machine-marked against pre-approved responses, and subsequently reviewed by a panel of pathologists, with the software remembering all new marking judgements.ResultsThe total time taken to mark all 50 VSAQs for all 285 students was 5 hours, compared to 70 hours required to manually mark an equivalent number of questions in a paper-based pathology exam. The median percentage score for the VSA test (72%) was significantly lower than that of the SBAQs (80%) and EMQs (84%), p <0.0001. VSAQs had a higher Cronbach alpha (0.86) than SBAQs (0.76), and EMQs (0.77). VSAQs, SBAQs and EMQs had a mean point-biserial of 0.35, 0.30 and 0.28, respectively.ConclusionsVSAQs are an acceptable, reliable and discriminatory method for assessing pathology, and may enhance students’ understanding of how pathology supports clinical decision-making and clinical care by changing learning behaviour.

Journal article

Meeran K, 2019, In reply to quinkler and Murray: prednisolone replacement therapy mimics the circadian rhythm more closely than other glucocorticoids, The Journal of Applied Laboratory Medicine, Vol: 1, Pages: 755-757, ISSN: 2576-9456

Journal article

Almazrouei R, Model D, Meeran K, 2019, Sheehan's like syndrome in a man, QJM: An International Journal of Medicine, Vol: 112, Pages: 811-812, ISSN: 1460-2393

An 84-year-old physician self-diagnosed that he had a pituitary tumour when he was found to have a bilateral upper quadrantanopia on routine eye testing. Magnetic resonance imaging (MRI) confirmed a large non-functioning pituitary macroadenoma associated with chiasmal compression. Investigation showed partial hypopituitarism with disconnection hyperprolactinaemia [prolactin 1095 mU/L (60–300)]. He was treated with hormonal replacement consisting of thyroxin 100 µg and prednisolone 3 mg and was offered transphenoidal hypophysectomy, but chose a conservative approach. Two years later, his visual fields worsened (Figure 1A) corresponding to an increase in macrodenoma size. Subsequently, he fell and fractured his left shoulder, which became infected, requiring surgery. Immediately after the shoulder surgery, he became hypotensive and vomited several times, and his visual fields became restricted. MRI showed pituitary infarction (Figure 1B), and he did not require surgical intervention. A few weeks later, he noticed dramatic improvement in his vision. His prolactin level dropped from a peak level of 1095 to 48 mU/L (60–300), suggesting lactotroph infarction. Repeated pituitary MRI showed dramatic reduction in the height of the pituitary macroadenoma consistent with the improvement in his visual fields (Figure 1C).

Journal article

Sam AH, Westacott R, Gurnell M, Wilson R, Meeran K, Brown Cet al., 2019, Comparing single-best-answer and very-short-answer questions for the assessment of applied medical knowledge in 20 UK medical schools: Cross-sectional study, BMJ Open, Vol: 9, Pages: 1-7, ISSN: 2044-6055

Objectives The study aimed to compare candidate performance between traditional best-of-five single-best-answer (SBA) questions and very-short-answer (VSA) questions, in which candidates must generate their own answers of between one and five words. The primary objective was to determine if the mean positive cue rate for SBAs exceeded the null hypothesis guessing rate of 20%.Design This was a cross-sectional study undertaken in 2018.Setting 20 medical schools in the UK.Participants 1417 volunteer medical students preparing for their final undergraduate medicine examinations (total eligible population across all UK medical schools approximately 7500).Interventions Students completed a 50-question VSA test, followed immediately by the same test in SBA format, using a novel digital exam delivery platform which also facilitated rapid marking of VSAs.Main outcome measures The main outcome measure was the mean positive cue rate across SBAs: the percentage of students getting the SBA format of the question correct after getting the VSA format incorrect. Internal consistency, item discrimination and the pass rate using Cohen standard setting for VSAs and SBAs were also evaluated, and a cost analysis in terms of marking the VSA was performed.Results The study was completed by 1417 students. Mean student scores were 21 percentage points higher for SBAs. The mean positive cue rate was 42.7% (95% CI 36.8% to 48.6%), one-sample t-test against ≤20%: t=7.53, p<0.001. Internal consistency was higher for VSAs than SBAs and the median item discrimination equivalent. The estimated marking cost was £2655 ($3500), with 24.5 hours of clinician time required (1.25 s per student per question).Conclusions SBA questions can give a false impression of students’ competence. VSAs appear to have greater authenticity and can provide useful information regarding students’ cognitive errors, helping to improve learning as well as assessment. Electronic delivery

Journal article

Bhatt PS, Sam AH, Meeran KM, Salem Vet al., 2019, The relevance of cortisol co-secretion from aldosterone-producing adenomas, Hormones (Athens, Greece), Vol: 18, Pages: 307-313, ISSN: 1109-3099

AIMS AND OBJECTIVES: Adrenal adenomas are usually non-functioning, but can secrete aldosterone or cortisol. It has recently been suggested that many more adenomas than previously thought secrete more than one hormone. This has important implications for their clinical management. Our aim was to determine the frequency of cortisol co-secretion in primary hyperaldosteronism at our institution and investigate the difference in metabolic profiles and clinical outcomes between co-secreting and non-co-secreting patients. DESIGN AND PATIENTS: A retrospective study of 25 patients with primary hyperaldosteronism who also underwent formal dexamethasone suppression tests to determine cortisol co-secretion. MEASUREMENTS: Post-dexamethasone suppression test cortisol, serum ALT, total cholesterol, HDL-cholesterol, LDL-cholesterol, HbA1C (were recorded) and mean arterial pressure are reported in this cohort of patients with primary hyperaldosteronism. RESULTS: Four out of 25 patients with primary hyperaldosteronism failed dexamethasone suppression tests. This suggests a frequency of co-secretion ranging between 4 and 16%. No significant difference was found in serum ALT, total cholesterol, serum HDL-cholesterol, LDL-cholesterol and mean arterial blood pressure at presentation between co-secretors and non-co-secretors. CONCLUSION: A frequency range of 4-16% suggests that a significant proportion of patients with primary hyperaldosteronism co-secrete cortisol. Co-secretors did not have a worse metabolic profile than non-secretors. The impact of co-secretion on metabolic profile and surgical management remains unclear and warrants further study.

Journal article

Choudhury S, Lightman S, Meeran K, 2019, Improving glucocorticoid replacement profiles in adrenal insufficiency, Clinical Endocrinology, Vol: 91, Pages: 367-371, ISSN: 1365-2265

There is an increased mortality associated with adrenal insufficiency despite glucocorticoid replacement therapy with a standardized mortality ratio greater than two. The cause of the increased mortality is yet to be definitively elucidated, but may be due to excess steroid exposure, or replacement regimens that are uncoupled from the normal physiological cortisol profile. Cortisol secretion follows an ultradian pattern which is not possible to reproduce using oral replacement. With the advent of new pumps, it is now possible to mimic the pulsatility of the adrenal glands. While the cognitive and emotional benefits of reproducing the ultradian rhythm are known, the presence of long-term benefits is not yet clear. There is a dearth of evidence and high-quality studies to underline our current understanding of the pathophysiology of adrenal insufficiency and replacement therapy. There is a particular lack of research comparing objective outcomes between patients receiving hydrocortisone replacement (either standard therapy or new sustained release preparations), prednisolone replacement and ultradian pumps. Direct comparative studies are now warranted to understand the optimal approach.

Journal article

Sam SA, Fung CY, Wilson R, Peleva E, Kluth D, Lupton M, Owen D, Melville C, Meeran Met al., 2019, Using prescribing very short answer questions to identify sources of medication errors: a prospective study in two UK medical schools, BMJ Open, Vol: 9, Pages: 1-5, ISSN: 2044-6055

Objective To assess the utility and ability of the novel prescribing very short answer (VSA) question format to identify the sources of undergraduate prescribing errors when compared with the conventional single best answer (SBA) question format and assess the acceptability of machine marking prescribing VSAs.Design A prospective study involving analysis of data generated from a pilot two-part prescribing assessment.Setting Two UK medical schools.Participants 364 final year medical students took part. Participation was voluntary. There were no other inclusion or exclusion criteria.Outcomes (1) Time taken to mark and verify VSA questions (acceptability), (2) differences between VSA and SBA scores, (3) performance in VSA and (4) SBA format across different subject areas and types of prescribing error made in the VSA format.Results 18 200 prescribing VSA questions were marked and verified in 91 min. The median percentage score for the VSA test was significantly lower than the SBA test (28% vs 64%, p<0.0001). Significantly more prescribing errors were detected in the VSA format than the SBA format across all domains, notably in prescribing insulin (96.4% vs 50.3%, p<0.0001), fluids (95.6% vs 55%, p<0.0001) and analgesia (85.7% vs 51%, p<0.0001). Of the incorrect VSA responses, 33.1% were due to the medication prescribed, 6.0% due to the dose, 1.4% due to the route and 4.8% due to the frequency.Conclusions Prescribing VSA questions represent an efficient tool for providing detailed insight into the sources of significant prescribing errors, which are not identified by SBA questions. This makes the prescribing VSA a valuable formative assessment tool to enhance students’ skills in safe prescribing and to potentially reduce prescribing errors.

Journal article

Choudhury S, Machenahalli P, Tan T, Meeran Ket al., 2019, Inadvertent treatment of hypoadrenalism with prednisolone in pemphigus: a case report, Clinical Case Reports, Vol: 7, Pages: 987-989, ISSN: 2050-0904

Pituitary and adrenal insufficiency must not be overlooked when weaning patients down from high‐dose steroids. Prednisolone can be used as glucocorticoid replacement therapy, with most patients needing 3‐4 mg once daily.

Journal article

Di Marco A, Meeran K, Christakis I, Sodhi V, Nelson-Piercy C, Tolley N, Palazzo Fet al., 2019, Seventeen cases of primary hyperparathyroidism in pregnancy: a call for management guidelines, Journal of the Endocrine Society, Vol: 3, Pages: 1009-1021, ISSN: 2472-1972

IntroductionThe risks of primary hyperparathyroidism (pHPT) to pregnant women and their fetuses are well-reported and appear to increase commensurate with serum calcium. The management strategy of pHPT must be adapted in pregnancy and should reflect the severity of hypercalcaemia. However, no guidelines exist to assist clinicians facing this dilemma.MethodsThe experience of a high-volume multidisciplinary endocrine surgical service in managing a consecutive series of pregnant women with pHPT referred for parathyroidectomy is presented and compared to a non-pregnant cohort with pHPT. Evidence in the published literature is explored via a review on pHPT and pregnancy outcomes.ResultsSeventeen pregnant women and 247 age range-matched non-pregnant women with pHPT were referred for surgery over 11 years. Serum calcium was higher in the pregnant cohort 2.89mmol/l vs 2.78mmol/l (p=0.03). Pre-operative localisation with ultrasound succeeded in 8(47%) pregnant women and SestaMIBI in 2/6(33% imaged pre-conception) compared to 84(34%) and 102(42%) controls (NS at 0.36 and 0.59). Parathyroidectomy was performed under general anaesthesia between 12 and 28 weeks gestation, with no adverse pregnancy outcomes resulting. Cure rate was 100% vs 96% in controls.ConclusionspHPT in pregnancy is a threat to mother and child. Medical management may be appropriate in mild disease (serum calcium <0.25mmol/l above the normal range) but in moderate-severe disease, parathyroidectomy under general anaesthesia in the second trimester is safe. Localisation using ionising radiation/MRI is unnecessary as surgical intervention in a high-volume multi-disciplinary setting has excellent outcomes. Guidelines on the topic would assist clinicians in this complex decision-making process.

Journal article

Almazrouei RA, Sam AH, Meeran K, Palazzo Fet al., 2019, PARATHYROID SESTAMIBI REVEALS MENINGIOMA., Endocr Pract, ISSN: 1530-891X

Journal article

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