Publications by authors named "Chris J Thompson"

24 Publications

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ENDOCRINOLOGY IN THE TIME OF COVID-19-2021 UPDATES: The management of diabetes insipidus and hyponatraemia.

Eur J Endocrinol 2021 Aug 27;185(4):G35-G42. Epub 2021 Aug 27.

Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counselling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of postoperative SIAD. They should know hyponatraemia symptoms. Hyponatraemia in COVID-19 is common with a prevalence of 20-30% and is mostly due to SIAD or hypovolaemia. It mirrors disease severity and is an early predictor of mortality. Hypernatraemia may also develop in COVID-19 patients, with a prevalence of 3-5%, especially in ICU, and derives from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.
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http://dx.doi.org/10.1530/EJE-21-0596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428073PMC
August 2021

Cardiometabolic and psychological effects of dual-release hydrocortisone: a cross-over study.

Eur J Endocrinol 2021 Feb;184(2):253-265

Academic Department of Endocrinology, Beaumont Hospital/RCSI.

Background: Adrenal insufficiency (AI) is associated with increased cardiovascular morbidity and mortality and reduced quality of life (QoL). Optimum glucocorticoid (GC) dosing and timing are crucial in the treatment of AI, yet the natural circadian secretion of cortisol is difficult to mimic. The once-daily dual-release hydrocortisone (DR-HC) preparation (Plenadren®), offers a more physiological cortisol profile and may address unmet needs.

Methods: An investigator-initiated, prospective, cross-over study in patients with AI. Following baseline assessment of cardiometabolic risk factors and QoL, patients switched from their usual hydrocortisone regimen to a once-daily dose equivalent of DR-HC and were reassessed after 12 weeks of treatment.

Results: Fifty-one patients (21 PAI/30 SAI) completed the study. Mean age was 41.6 years (s.d. 13), and 58% (n = 30) were male. The median daily HC dose before study entry was 20 mg (IQR 15-20 mg). After 3 months on DR-HC, the mean SBP decreased by 5.7 mmHg, P = 0.0019 and DBP decreased by 4.5 mmHg, P = 0.0011. There was also a significant reduction in mean body weight (-1.23 kg, P = 0.006) and BMI (-0.3 kg/m2, P = 0.003). In a sub-analysis, there was a greater reduction in SBP observed in patients with SAI when compared to PAI post-DR-HC. Patients reported significant improvements in QoL using three validated QoL questionnaires, with a greater improvement in PAI.

Conclusion: Dual-release hydrocortisone decreases BP, weight and BMI compared with conventional HC treatment, even at physiological GC replacement doses. Additionally, DR-HC confers significant improvements in QoL compared to immediate-release HC, particularly in patients with PAI, which is also reflected in the patient preference for DR-HC.
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http://dx.doi.org/10.1530/EJE-20-0642DOI Listing
February 2021

Active management of hyponatraemia and mortality in older hospitalised patients compared with younger patients: results of a prospective cohort study.

Age Ageing 2021 06;50(4):1144-1150

Academic Department of Endocrinology, RCSI Medical School and Beaumont Hospital, Dublin, Ireland.

Introduction: Hyponatraemia is associated with increased morbidity and mortality; the aetiology and outcomes of hyponatraemia in older patients have not been defined in prospective studies.

Methods: A single-centre 9-month prospective observational study in which clinical outcomes in hospitalised patients ≥ 65 years (older patients with hyponatraemia (OP-HN)) and those <65 years (young patients with hyponatraemia (YP-HN)) with hyponatraemia were analysed, and compared with eunatraemic controls (older patients with normonatraemia (OP-NN) and young patients with normonatraemia (YP-NN)).

Results: In total, 1,321 episodes of hyponatraemia in 1,086 patients were included; 437 YP-HN, median age 54 years (IQR 44,60) and 884 OP-HN, median age 77 years (IQR 71,82). A total of 1,120 consecutive eunatraemic control patients were simultaneously recruited; 690 OP-NN, median age 77 years (IQR 71,83) and 430 YP-NN, median age 52 years (IQR 41,58). Euvolaemic hyponatraemia was the commonest cause of hyponatraemia in both age groups (48% in YP-HN and 46% in OP-HN). Sixty-two percent of OP-HN received hyponatraemia-directed treatment within the initial 48 h, compared with 55% of YP-HN, P = 0.01. Despite the greater treatment rates in OP-HN, younger patients were 24% more likely to be discharged with normal plasma sodium concentration (pNa) compared with older patients, relative risk (RR) 1.24 (95% confidence interval (CI) 1.12-1.37), P < 0.001.Using OP-NN as the reference group, the RR of in-hospital death in OP-HN was 2.15 (95% CI 1.3-3.56), P = 0.002. Using YP-NN as the reference group, the RR of in-hospital death in YP-HN was 4.34 (95% CI 1.98-9.56), P < 0.001.

Conclusion: Despite greater rates of HN-targeted treatment, the risk of in-hospital death is increased in older hyponatraemic patients compared with older eunatraemic controls. The impact of hyponatraemia on mortality is even greater in younger patients.
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http://dx.doi.org/10.1093/ageing/afaa248DOI Listing
June 2021

Active management of severe hyponatraemia is associated with improved mortality.

Eur J Endocrinol 2021 Jan;184(1):9-17

Academic Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin, Ireland.

Objective: Severe hyponatraemia (plasma sodium concentration, pNa <120 mmol/L) is reported to be associated with mortality rates as high as 50%. Although there are several international guidelines for the management of severe hyponatraemia, there are few data on the impact of treatment.

Design And Methods: We have longitudinally reviewed rates of specialist input, active management of hyponatraemia, treatment outcomes and mortality rates in patients with severe hyponatraemia (pNa <120 mmol/L) in 2005, 2010 and 2015, and compared the recent mortality rate with that of patients with pNa 120-125 mmol/L.

Results: Between 2005 and 2010 there was a doubling in the rate of specialist referral (32 to 68%, P = 0.003) and an increase in the use of active management of hyponatraemia in patients with pNa <120 mmol/L (63 to 88%, P = 0.02), associated with a reduction in mortality from 51 to 15% (P < 0.001). The improved rates of intervention were maintained between 2010 and 2015, but there was no further reduction in mortality. When data from all three reviews were pooled, specialist consultation in patients with pNa <120 mmol/L was associated with a 91% reduction in mortality risk, RR 0.09 (95% CI: 0.03-0.26), P < 0.001. Log-rank testing on in-hospital survival in 2015 found no significant difference between patients with pNa <120 mmol/L and pNa 120-125 mmol/L (P = 0.56).

Conclusion: Dedicated specialist input and active management of severe hyponatraemia are associated with a reduction in mortality, to rates comparable with moderate hyponatraemia.
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http://dx.doi.org/10.1530/EJE-20-0577DOI Listing
January 2021

Fluid Restriction Therapy for Chronic SIAD; Results of a Prospective Randomized Controlled Trial.

J Clin Endocrinol Metab 2020 12;105(12)

Academic Department of Endocrinology, RCSI Medical School and Beaumont Hospital, Dublin, Ireland.

Context: Fluid restriction (FR) is the recommended first-line treatment for syndrome of inappropriate antidiuresis (SIAD), despite the lack of prospective data to support its efficacy.

Design: A prospective nonblinded randomized controlled trial of FR versus no treatment in chronic SIAD.

Interventions And Outcome: A total of 46 patients with chronic asymptomatic SIAD were randomized to either FR (1 liter/day) or no specific hyponatremia treatment (NoTx) for 1 month. The primary endpoints were change in plasma sodium concentration (pNa) at days 4 and 30.

Results: Median baseline pNa was similar in the 2 groups [127 mmol/L (interquartile range [IQR] 126-129) FR and 128 mmol/L (IQR 126-129) NoTx, P = 0.36]. PNa rose by 3 mmol/L (IQR 2-4) after 3 days FR, compared with 1 mmol/L (IQR 0-3) NoTx, P = 0.005. There was minimal additional rise in pNa by day 30; median pNa increased from baseline by 4 mmol/L (IQR 2-6) in FR, compared with 1 mmol/L (IQR 0-1) NoTx, P = 0.04. After 3 days, 17% of FR had a rise in pNa of ≥5 mmol/L, compared with 4% NoTx, RR 4.0 (95% CI 0.66-25.69), P = 0.35. After 3 days, 61% of FR corrected pNa to ≥130 mmol/L, compared with 39% of NoTx, RR 1.56 (95% CI 0.87-2.94), P = 0.24.

Conclusion: FR induces a modest early rise in pNa in patients with chronic SIAD, with minimal additional rise thereafter, and it is well-tolerated. More than one-third of patients fail to reach a pNa ≥130 mmol/L after 3 days of FR, emphasizing the clinical need for additional therapies for SIAD in some patients.
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http://dx.doi.org/10.1210/clinem/dgaa619DOI Listing
December 2020

Treatment Outcomes in Syndrome of Inappropriate Antidiuresis: Improvements in Hyponatremia May Reflect Successful Treatment or Resolution of the Underlying Cause.

Am J Kidney Dis 2020 10 20;76(4):599. Epub 2020 Jun 20.

Academic Department of Endocrinology, Beaumont Hospital and RCSI, Dublin, Ireland.

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http://dx.doi.org/10.1053/j.ajkd.2020.04.011DOI Listing
October 2020

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of diabetes insipidus and hyponatraemia.

Eur J Endocrinol 2020 Jul;183(1):G9-G15

Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counseling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of the postoperative syndrome of inappropriate antidiuresis (SIAD). They should know hyponatraemia symptoms. The prevalence of hyponatraemia in patients with pneumonia due to COVID-19 is not yet known, but seems to be low. In contrast, hypernatraemia may develop in COVID-19 patients in ICU, from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.
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http://dx.doi.org/10.1530/EJE-20-0338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938013PMC
July 2020

Understanding the presence of mental fatigue in English academy soccer players.

J Sports Sci 2020 Jul 25;38(13):1524-1530. Epub 2020 Mar 25.

Institute of Sport and Preventive Medicine, Saarland University , Saarbrücken, Germany.

Research has demonstrated that induced mental fatigue impairs soccer-specific technical, tactical and physical performance in soccer players. The findings are limited by the lack of elite players and low ecological validity of the tasks used to induce mental fatigue, which do not resemble the cognitive demands of soccer. The current study collected survey data from English academy soccer players (n = 256; age groups - U14 - U23), with questions comprising of five themes (descriptors of physical and mental fatigue, travel, education, match-play and fixture congestion). The survey consisted of multiple choice responses, checkboxes and blinded/unblinded (for duration based questions) 0-100 arbitrary unit (AU) slider scales. Listening to music (81.6% of players), using social media (58.3%) and watching videos (34.3%) were the most common pre-match activities. Pre-match subjective mental fatigue was low (18.7±18.8 AU), and most frequently reported at the end of a match (47±26 AU) and remained elevated 24-hours post-match (36±27 AU). Travel (29±24 AU), fixture congestion (44±25 AU) and education (30±26 AU) demonstrated a low to moderate presence of subjective mental fatigue. These findings provide an overview of activities performed by English academy soccer players pre-match, and demonstrate that mental fatigue is experienced as a result of match-play.
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http://dx.doi.org/10.1080/02640414.2020.1746597DOI Listing
July 2020

Hyponatremia and Glucocorticoid Deficiency.

Front Horm Res 2019 15;52:80-92. Epub 2019 Jan 15.

Hyponatremia is the commonest electrolyte deficiency in clinical practice. Of the many causes of hyponatremia, syndrome of inappropriate antidiuresis (SIAD) is the commonest. Glucocorticoid deficiency, due to central/secondary adrenal insufficiency, is the key differential diagnosis for SIAD, as it presents with a similar biochemical picture of euvolemic hyponatremia and inappropriate urinary concentration. The underlying mechanisms for the development of hyponatremia in glucocorticoid deficiency are: (1) impaired renal water handling in the absence of circulating cortisol and (2) increased plasma concentrations of arginine vasopressin (AVP), despite hypo-osmolality. The original diagnostic criteria for SIAD emphasized that normal adrenal reserve was essential for its diagnosis, in recognition of the similar biochemical presentation of SIAD and glucocorticoid deficiency. This has been emphasized in all of the recently published clinical guidelines. However, data from the literature suggest that clinicians ignore the measurement of plasma cortisol concentration in both clinical practice and research protocols. The reported prevalence of glucocorticoid deficiency in patients presenting with euvolemic hyponatremia may, therefore, be underestimated and patients with a dangerous, but treatable cause of hyponatremia are inevitably missed. In this chapter, we will review the physiopathology of hyponatremia in the setting of glucocorticoid deficiency. We will discuss the differential diagnosis of euvolemic hyponatremia and review the prevalence of glucocorticoid deficiency in patients with hyponatremia.
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http://dx.doi.org/10.1159/000493239DOI Listing
June 2020

Historical Aspects of Hyponatremia.

Front Horm Res 2019 15;52:1-7. Epub 2019 Jan 15.

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http://dx.doi.org/10.1159/000493216DOI Listing
June 2020

Future of Hyponatremia Research.

Front Horm Res 2019 15;52:200-203. Epub 2019 Jan 15.

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http://dx.doi.org/10.1159/000493249DOI Listing
June 2020

Continuous Versus Bolus Infusion of Hypertonic Saline in the Treatment of Symptomatic Hyponatremia Caused by SIAD.

J Clin Endocrinol Metab 2019 09;104(9):3595-3602

Academic Department of Endocrinology, Beaumont Hospital/RCSI, Dublin, Ireland.

Background: Acute hyponatremia is a medical emergency that confers high mortality, attributed primarily to cerebral edema. Expert guidelines advocate the use of intravenous boluses of hypertonic saline rather than traditional continuous infusion to achieve a faster initial rise in plasma sodium (pNa) concentration. However, there is a limited evidence base for this recommended policy change.

Methods: We prospectively assessed the clinical and biochemical outcomes in patients treated for symptomatic hyponatremia caused by syndrome of inappropriate antidiuresis in response to intravenous bolus treatment with 3% saline (100 mL, repeated up to two more times) and compared the outcomes to retrospective data from patients treated with continuous intravenous infusion of low-dose (20 mL/h) 3% saline.

Results: Twenty-two patients were treated with bolus infusion and 28 with continuous infusion. Three percent saline bolus caused more rapid elevation of pNa at 6 hours [median (range) 6 (2 to11) vs 3 (1 to 4) mmol/L, P < 0.0001], with a concomitant improvement in Glasgow Coma Scale (GCS) [median (range) 3 (1 to 6) vs 1 (-2 to 2), P < 0.0001] at 6 hours. Median pNa concentration was similar at 24 hours in the two treatment groups. The administration of a third saline bolus was associated with greater need for dextrose/dDAVP to prevent overcorrection (OR 24; P = 0.006). There were no cases of osmotic demyelination in either group.

Conclusion: Three percent saline bolus produces faster initial elevation of pNa than continuous infusion with quicker restoration of GCS, and without osmotic demyelination. Frequent electrolyte monitoring, and judicious intervention with dDAVP is required to prevent overcorrection with bolus therapy.
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http://dx.doi.org/10.1210/jc.2019-00044DOI Listing
September 2019

Mental Fatigue in Football: Is it Time to Shift the Goalposts? An Evaluation of the Current Methodology.

Sports Med 2019 02;49(2):177-183

Sport and Exercise Discipline Group, Faculty of Health, University of Technology Sydney, Moore Park, NSW, Australia.

Research in football for a long time has focused on the physical nature of fatigue as opposed to its mental aspects. However, since 2016, six original articles have investigated the effects of induced mental fatigue in football on isolated physical, skill and decision-making performance tests, along with physical, technical and tactical performance outcomes in small-sided games. Whilst these studies have overall shown a negative impact of mental fatigue on task performance, this current opinion aims to critically examine the methodological approach to this problem, most notably the lack of ecological validity when inducing mental fatigue and the present approach to measuring mental fatigue using visual analogue scales (VAS). It is suggested that future research on mental fatigue in football may benefit from the use of surveys/interviews to understand the true cognitive demands of elite football players. Additionally, future research should aim to reduce the reliance on using VAS to measure mental fatigue as results from this tool may be confounded by several response biases. In conclusion, this article highlights the need for mentally fatiguing tasks that adequately represent football-associated mental fatigue and assessments of mental fatigue that minimise the confounding effect of response bias.
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http://dx.doi.org/10.1007/s40279-018-1016-zDOI Listing
February 2019

Syndrome of inappropriate antidiuresis should it be managed by specialised endocrinologists?

Endocrine 2017 08 28;57(2):193-195. Epub 2017 Apr 28.

Academic Dept of Endocrinology, Beaumont Hospital/RCSI Medical School, Dublin, Ireland.

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http://dx.doi.org/10.1007/s12020-017-1304-7DOI Listing
August 2017

Increased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland.

Hum Mutat 2017 01 4;38(1):78-85. Epub 2016 Oct 4.

Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304 (or p.R304 ; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304 carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304 prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) versus non-Irish patients (0-2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1,275-5,000) years. tMRCA-based simulations predicted 432 (90-5,175) current carriers, including 86 affected (18-1,035) for 20% penetrance. In conclusion, R304 is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease.
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http://dx.doi.org/10.1002/humu.23121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215436PMC
January 2017

Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort.

J Clin Endocrinol Metab 2015 Mar 12;100(3):E531-41. Epub 2014 Dec 12.

Department of Endocrinology (J.D., U.S., M.D., P.G., W.M.D., M.K.), Barts and the London School of Medicine, Queen Mary University of London, London EC1M 6BQ, United Kingdom; Semmelweis University, School of PhD studies, Doctoral School of Clinical Medicine, Budapest, Hungary (J.D.), Endocrinology Directorate (F.S.), Norfolk and Norwich University Hospital, Norwich NR4 7UZ, United Kingdom; Department of Medical and Molecular Genetics (E.R., E.R.M.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Department of Molecular Genetics (K.S., M.O., S.E.), Royal Devon and Exeter National Health Service Foundation Trust, Exeter EX2 5DW, United Kingdom; University of Exeter Medical School (S.E.), Exeter EX4 4PY, United Kingdom; Oxford Medical Genetics Laboratories (T.C.), Oxford University Hospitals National Health Service Trust, The Churchill Hospital, Oxford OX3 7LJ, United Kingdom; Section on Endocrinology and Genetics (P.X., C.A.S.) and Section on Molecular Dysmorphology (C.W.), Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Electron Microscopy Unit (L.M.), Department Histopathology, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London W6 8RF, United Kingdom; Department of Clinical Genetics (A.K.), Great Ormond Street Hospital, London WC1N 1LE, United Kingdom; Departments of Oncology (N.F.) and Endocrinology (S.E.B.), University College London Hospitals, London WC1E 6BT, United Kingdom; Department of Diabetes and Endocrinology (D.M.), The Ipswich Hospital National Health Service Trust, Ipswich IP4 5PD, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS1 3NY, United Kingdom; Department of Endocrinology (A.Ag., C.J.T.), Beaumont Hospital, Dublin 9, Ireland; Institute of Molecular and Experimental Medicine (A.R.), Cardiff University, Cardiff CF10 3US, United Kingd

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence.

Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL.

Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples.

Setting: The study was conducted at university hospitals.

Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study.

Outcome: Outcomes included genetic screening and clinical characteristics.

Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context.

Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.
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http://dx.doi.org/10.1210/jc.2014-3399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333031PMC
March 2015

The reply.

Am J Med 2014 Jul;127(7):e31-2

Royal College of Surgeons in Ireland, Dublin, Ireland.

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http://dx.doi.org/10.1016/j.amjmed.2014.03.022DOI Listing
July 2014

Mineralization of basalts in the CO2-H2O-SO2-O2 system.

Environ Sci Technol 2014 May 17;48(9):5298-305. Epub 2014 Apr 17.

Pacific Northwest National Laboratory , Richland, Washington 99352, United States.

Sequestering carbon dioxide (CO2) containing minor amounts of co-contaminants in geologic formations was investigated in the laboratory through the use of high pressure static experiments. Five different basalt samples were immersed in water equilibrated with supercritical CO2 containing 1 wt % sulfur dioxide (SO2) and 1 wt % oxygen (O2) at reservoir conditions (∼ 100 bar, 90 °C) for 48 and 98 days. Gypsum (CaSO4) was a common precipitate, occurred early as elongated blades with striations, and served as substrates for other mineral products. In addition to gypsum, bimodal pulses of water released during dehydroxylation were key indicators, along with X-ray diffraction, for verifying the presence of jarosite-alunite group minerals. Well-developed pseudocubic jarosite crystals formed surface coatings, and in some instances, mixtures of natrojarosite and natroalunite aggregated into spherically shaped structures measuring 100 μm in diameter. Reaction products were also characterized using infrared spectroscopy, which indicated OH and Fe-O stretching modes. The presences of jarosite-alunite group minerals were found in the lower wavenumber region from 700 to 400 cm(-1). A strong preferential incorporation of Fe(III) into natrojarosite was attributed to the oxidation potential of O2. Evidence of CO2 was detected during thermal decomposition of precipitates, suggesting the onset of mineral carbonation.
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http://dx.doi.org/10.1021/es404964jDOI Listing
May 2014

A comparison of osteoprotegerin with adiponectin and high-sensitivity C-reactive protein (hsCRP) as a marker for insulin resistance.

Metabolism 2013 Jan 27;62(1):34-8. Epub 2012 Jul 27.

Department of Diabetes and Endocrinology, Royal College of Surgeons in Ireland Medical School, Beaumont Hospital, Dublin 9, Ireland.

Objective: Insulin resistance (IR) is associated with low adiponectin and elevated high sensitivity C-reactive protein (hsCRP). Osteoprotegerin (OPG) has been shown to be elevated in type 2 diabetes, but whether it reflects underlying IR is unclear. We aimed to compare the ability of serum OPG with adiponectin and hsCRP to act as a marker for IR in individuals with normal and abnormal glucose tolerance.

Materials/methods: 115 men underwent a 75 g oral glucose tolerance test. OPG, hsCRP and adiponectin were measured using ELISA. IR was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR).

Results: Men with abnormal glucose tolerance (n=38) were older (58.3±11.2 vs 47.3±11.4 years, P<.001), had higher body mass index (BMI) (31.1±2.9 vs 27.9±3.2 kg/m(2), P<.001) and were more insulin resistant (median (I.Q.) HOMA-IR 5.88 (3.38) vs 1.13 (1.14), P<.001) than those with normal glucose tolerance (n=77). After adjustment for age and BMI, OPG (6.28 (2.32) vs 5.16 (1.86) pmol/L, P<.001) and hsCRP (2.07 (5.47) vs 0.78 (1.05) mg/L, P<.001) were higher and adiponectin (3.02±1.17 vs 4.78±2.38 μg/mL, P<.001) was lower in those with AGT. After adjustment for age and BMI, adiponectin (r=-0.317, P<.001) and hsCRP (r=0.318, P<.001), but not OPG (r=0.126, P=.196) correlated with HOMA-IR. On multiple linear regression analysis, adiponectin and hsCRP but not OPG were independent predictors of HOMA-IR.

Conclusions: OPG is higher in individuals with abnormal glucose tolerance, but unlike adiponectin and hsCRP, does not correlate with HOMA-IR, suggesting its elevation within this cohort of individuals is due to factors other than insulin resistance.
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http://dx.doi.org/10.1016/j.metabol.2012.06.005DOI Listing
January 2013

The syndrome of inappropriate antidiuretic hormone: current and future management options.

Eur J Endocrinol 2010 Jun 17;162 Suppl 1:S13-8. Epub 2010 Feb 17.

Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, UK.

Hyponatraemia is the commonest electrolyte abnormality, and syndrome of inappropriate antidiuretic hormone (SIADH) is the most frequent underlying pathophysiology. Hyponatraemia is associated with significant morbidity and mortality, and as such appropriate treatment is essential. Treatment options for SIADH include fluid restriction, demeclocycline, urea, frusemide and saline infusion, all of which have their limitations. The introduction of the vasopressin-2 receptor antagonists has allowed clinicians to specifically target the underlying pathophysiology of SIADH. Initial studies have shown good efficacy and safety profiles in the treatment of mild to moderate hyponatraemia. However, studies assessing the efficacy and safety of these agents in acute severe symptomatic hyponatraemia are awaited. Furthermore, the cost of these agents at present may limit their use.
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http://dx.doi.org/10.1530/EJE-09-1057DOI Listing
June 2010

The natural history of surgically treated but radiotherapy-naïve nonfunctioning pituitary adenomas.

Clin Endocrinol (Oxf) 2009 Nov 19;71(5):709-14. Epub 2009 Mar 19.

Division of Neuro-endocrinology, Beaumont Hospital and the RCSI Medical School, Dublin, Ireland.

Background And Objectives: Transsphenoidal surgery is indicated for patients with nonfunctioning pituitary adenomas (NFPAs) causing compressive symptoms. Previous studies attempting to define the rate of recurrence/regrowth of surgically treated but radiation-naïve NFPAs were somewhat limited by selection bias and/or small numbers and/or lack of consistency of findings between studies. A better understanding of the natural history of this condition could allow stratification of recurrence risk and inform future management. We aimed to define the natural history of a large, mainly unselected cohort with surgically treated, radiotherapy (RT)-naïve NFPAs and to try to identify predictors of recurrence/regrowth.

Design: Case-note analysis of all patients who underwent surgery for NFPA in our hospital between 1980 and 2006 was undertaken. Median follow-up was 5.7 (range 1-25) years.

Patients: A total of 212 patients were identified of which 159 were suitable for analysis. 93% did not receive post-operative RT.

Measurement: Post-operative recurrent/regrowth was defined by any increase in tumour remnant size on serial post-operative pituitary imaging.

Results: Recurrence/regrowth was documented in 53 patients (33.5%). Multivariate analysis revealed size of the post-operative tumour remnant and length of follow-up to be the two major determinants of recurrence/regrowth. The presence of a tumour with an extrasellar remnant was associated with the highest risk of recurrence (odds ratio 3.73 [CI: 1.97-7.09]), while no recurrence was seen in those with no residual tumour post-operatively and regrowth risk was intermediate for those with remaining intrasellar remnant.

Conclusion: These results indicate that patients with post-operative tumour with an extrasellar remnant should be considered routinely for adjuvant RT to reduce the risk of tumour regrowth while those with no residual tumour can be safely observed. Individualized decisions should be made for patients with an intrasellar remnant.
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http://dx.doi.org/10.1111/j.1365-2265.2009.03583.xDOI Listing
November 2009

Central pontine myelinolysis complicating treatment of the hyperglycaemic hyperosmolar state.

Ann Clin Biochem 2008 Jul;45(Pt 4):440-3

Division of Endocrinology and Diabetes, Beaumont Hospital, Dublin, Ireland.

Central pontine myelinolysis (CPM) is well recognized to occur in a variety of clinical settings, but particularly following rapid correction of severe hyponatraemia. The development of CPM as a result of rapid shifts in plasma osmolality during the treatment of the hyperglycaemic hyperosmolar state (HHS) has hitherto been described in only one case. We report a second case in which this complication occurred in association with treatment of the HHS. The patient was a 49-year-old woman who presented to another hospital with drowsiness and a plasma glucose of 106 mmol/L. Her admission plasma sodium was 135 mmol/L. She received treatment with intravenous insulin and 0.9% normal saline, and there was a rapid drop in plasma glucose by 60 mmol/L within 6 h, which was associated with a rebound rise of plasma sodium to 159 mmol/L. Her plasma glucose and sodium were later stabilized. When the patient was transferred to our hospital a few days later, she was noted to have flaccid quadraparesis and pseudobulbar palsy. A magnetic resonance imaging scan revealed a pontine lesion consistent with CPM. She made a gradual recovery over several months with intensive rehabilitation and eventually returned to near normal functional capacity. This is the second case report in the literature of CPM complicating the management of HHS and highlights the importance of the judicious and measured correction of hyperglycaemia and the appropriate management of fluid replacement and electrolyte balance when treating this condition.
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http://dx.doi.org/10.1258/acb.2008.007171DOI Listing
July 2008

Risk of diabetes insipidus after pituitary surgery.

Expert Rev Endocrinol Metab 2008 Jan;3(1):23-27

b Academic Department of Diabetes and Endocrinology, Beaumont Hospital/RCSI Medical School, Dublin 9, Ireland.

Diabetes insipidus is a common complication of pituitary surgery, occurring acutely in 18-30% of operations. Most patients recover full posterior function but a minority sustain sufficient damage to vasopressin-secreting neurons to develop permanent diabetes insipidus. The triplephase response, comprising early transient diabetes insipidus, followed by a period of antidiuresis and hyponatremia, before resolving into permanent diabetes insipidus, is an uncommon but important variant. Diabetes insipidus is more common following surgery for craniopharyngioma compared with pituitary adenoma, and craniopharyngioma patients may develop the dangerous complication of adipsic diabetes insipidus. Diabetes insipidus is also more common following pituitary surgery for Rathke's cleft cysts and possible adrenocorticotropic hormone-secreting adenomas. The data on tumor size are conflicting but our own experience would suggest that diabetes insipidus is more common after surgery for large suprasellar tumors, particularly those with hypothalamic extension. The experience and skill of the neurosurgeon also determines the likelihood of developing diabetes insipidus. The diagnosis of postsurgical diabetes insipidus depends on excluding other forms of polyuria, including diabetes mellitus, excess intravenous fluids and therapy with diuretics or mannitol. Treatment with vasopressin analogues is almost always effective in controlling renal water excretion and normalizing plasma sodium concentrations.
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http://dx.doi.org/10.1586/17446651.3.1.23DOI Listing
January 2008

Is hypopituitarism predictable after traumatic brain injury?

Nat Clin Pract Endocrinol Metab 2008 Mar 4;4(3):126-7. Epub 2007 Dec 4.

Department of Endocrinology, Beaumont Hospital, Dublin, Ireland.

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http://dx.doi.org/10.1038/ncpendmet0719DOI Listing
March 2008
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