Publications by authors named "Rachel K Crowley"

44 Publications

Myxoedema coma caused by immunotherapy-related thyroiditis and enteritis.

Endocrinol Diabetes Metab Case Rep 2021 Oct 1;2021. Epub 2021 Oct 1.

Department of Endocrinology, St Vincent's University Hospital, Dublin, Ireland.

Summary: Thyroid dysfunction is among the most common immune-related adverse reactions associated with immune checkpoint inhibitors. It most commonly manifests as painless thyroiditis followed by permanent hypothyroidism. This usually causes mild toxicity that does not interfere with oncological treatment. In rare instances, however, a life-threatening form of decompensated hypothyroidism called myxoedema coma may develop. We present a case of myxoedema coma in a woman in her sixties who was treated with a combination of CTLA-4 and PD-1 immune checkpoint inhibitors; for stage four malignant melanoma. She became hypothyroid and required thyroxine replacement after an episode of painless thyroiditis. Six months after the initial diagnosis of malignant melanoma, she presented to the emergency department with abdominal pain, profuse diarrhoea, lethargy and confusion. She was drowsy, hypotensive with a BP of 60/40 mmHg, hyponatraemic and hypoglycaemic. Thyroid function tests (TFTs) indicated profound hypothyroidism with a TSH of 19 mIU/L, and undetectable fT3 and fT4, despite the patient being compliant with thyroxine. She was diagnosed with a myxoedema coma caused by immune-related enteritis and subsequent thyroxine malabsorption. The patient was treated with i.v. triiodothyronine (T3) and methylprednisolone in the ICU. While her clinical status improved with T3 replacement, her enteritis was refractory to steroid therapy. A thyroxine absorption test confirmed persistent malabsorption. Attempts to revert to oral thyroxine were unsuccessful. Unfortunately, the patient's malignant melanoma progressed significantly and she passed away four months later. This is the first reported case of myxoedema coma that resulted from two distinct immune-related adverse reactions, namely painless thyroiditis and enterocolitis.

Learning Points: Myxoedema coma, a severe form of decompensated hypothyroidism is a rare immunotherapy-related endocrinopathy. Myxedema coma should be treated with either i.v. triiodothyronine (T3) or i.v. thyroxine (T4). Intravenous glucocorticoids should be co-administered with thyroid hormone replacement to avoid precipitating an adrenal crisis. Thyroid function tests (TFTs) should be monitored closely in individuals with hypothyroidism and diarrhoea due to the risk of thyroxine malabsorption. A thyroxine absorption test can be used to confirm thyroxine malabsorption in individuals with persistent hypothyroidism.
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http://dx.doi.org/10.1530/EDM-21-0130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558892PMC
October 2021

Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension.

RMD Open 2021 09;7(3)

Department of Medicine and Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Objectives: To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks.

Methods: Adults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT).

Results: Subjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks.

Conclusions: Adults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function.

Trial Registration Number: NCT02526160.
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http://dx.doi.org/10.1136/rmdopen-2021-001714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458321PMC
September 2021

An evaluation of the process of informed consent: views from research participants and staff.

Trials 2021 Aug 18;22(1):544. Epub 2021 Aug 18.

School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

Background: The process of informed consent for enrolment to a clinical research study can be complex for both participants and research staff. Challenges include respecting the potential participant's autonomy and information needs while simultaneously providing adequate information to enable an informed decision. Qualitative research with small sample sizes has added to our understanding of these challenges. However, there is value in garnering the perspectives of research participants and staff across larger samples to explore the impact of contextual factors (time spent, the timing of the discussion and the setting), on the informed consent process.

Methods: Research staff and research participants from Ireland and the UK were invited to complete an anonymous survey by post or online (research participants) and online (research staff). The surveys aimed to quantify the perceptions of research participants and staff regarding some contextual factors about the process of informed consent. The survey, which contained 14 and 16 multiple choice questions for research participants and staff respectively, was analysed using descriptive statistics. Both surveys included one optional, open-ended question, which were analysed thematically.

Results: Research participants (169) and research staff (115) completed the survey. Research participants were predominantly positive about the informed consent process but highlighted the importance of having sufficient time and the value of providing follow-up once the study concludes, e.g. providing results to participants. Most staff (74.4%) staff reported that they felt very confident or confident facilitating informed consent discussions, but 63% felt information leaflets were too long and/or complicated, 56% were concerned about whether participants had understood complex information and 40% felt that time constraints were a barrier. A dominant theme from the open-ended responses to the staff survey was the importance of adequate time and resources.

Conclusions: Research participants in this study were overwhelmingly positive about their experience of the informed consent process. However, research staff expressed concern about how much participants have understood and studies of patient comprehension of research study information would seem to confirm these fears. This study highlights the importance of allocating adequate time to informed consent discussions, and research staff could consider using Teach Back techniques.

Trial Registration: Not applicable.
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http://dx.doi.org/10.1186/s13063-021-05493-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371296PMC
August 2021

No effect of calcium and vitamin D intake on maternal blood pressure in a healthy pregnant population.

Eur J Obstet Gynecol Reprod Biol 2021 Sep 7;264:8-14. Epub 2021 Jul 7.

Department of Endocrinology, St Vincent's University Hospital, Dublin, Ireland; UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland.

Objectives: Clinical studies have reported an inverse relationship between calcium and vitamin D intake and hypertensive disorders of pregnancy (HDP). The aim of this study was to investigate if there was an association between calcium/vitamin D intake, and vitamin D (25OHD) status, and maternal blood pressure (BP), during pregnancy and at 5-year follow-up.

Study Design: This was an observational study of 415 women who participated in the ROLO (Randomised cOntrolled trial of LOw glycaemic index diet for the prevention of recurrence of macrosomia) study. Maternal BP measurements were taken during each trimester and at 5-year follow-up. Calcium and vitamin D intake were determined at each trimester and 25OHD was measured in early and late pregnancy.

Results: Over two-thirds of the cohort were vitamin D sufficient (25OHD > 30 nmol/L) and had adequate calcium intake (>750 mg/day). There was no correlation between calcium intake or vitamin D intake and maternal BP in trimester 1 to 3 or at 5-year follow-up. Vitamin D status at 13 weeks' gestation negatively correlated with mean arterial pressure in trimester 1 (r = -0.152, p = 0.044). There was no correlation however between 25OHD at 28 weeks' gestation and BP at 28 or 34 weeks' gestation or 25OHD and BP at 5-year follow-up.

Conclusions: In a healthy population of women with adequate calcium and vitamin D intake, no clinically significant correlation existed between calcium and vitamin D and maternal BP.
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http://dx.doi.org/10.1016/j.ejogrb.2021.07.005DOI Listing
September 2021

Adherence with reporting of ethical standards in COVID-19 human studies: a rapid review.

BMC Med Ethics 2021 06 28;22(1):80. Epub 2021 Jun 28.

School of Medicine, University College Dublin, Dublin 4, D04 V1W8, Ireland.

Background: Patients with COVID-19 may feel under pressure to participate in research during the pandemic. Safeguards to protect research participants include ethical guidelines [e.g. Declaration of Helsinki and good clinical practice (GCP)], legislation to protect participants' privacy, research ethics committees (RECs) and informed consent. The International Committee of Medical Journal Editors (ICMJE) advises researchers to document compliance with these safeguards. Adherence to publication guidelines has been suboptimal in other specialty fields. The aim of this rapid review was to determine whether COVID-19 human research publications report compliance with these ethical safeguards.

Methods: A rapid systematic literature review was conducted in MEDLINE using the search term 'COVID-19'. The search was performed in April 2020 with no start date and repeated to include articles published in November 2020. Filters were 'Full free text available' and 'English Language'. Two reviewers assessed article title, abstracts and full texts. Non-COVID-19 articles and non-clinical studies were excluded. Independent reviewers conducted a second assessment of a random 20% of articles. The outcomes included reporting of compliance with the Declaration of Helsinki and GCP, REC approval, informed consent and participant privacy.

Results: The searches yielded 1275 and 1942 articles of which 247 and 717 were deemed eligible, from the April  search and November respectively. The majority of journals had editorial policies which purported to comply with ICMJE ethical standards. Reporting of compliance with ethical guidelines was low across all study types but was higher in the November search for case series and observational studies. Reporting of informed consent for case studies and observational studies was higher in the November search, but similar for case series. Overall, participant confidentiality was maintained but some case studies included a combination of details which would have enabled participant identification. Reporting of REC approval was higher in the November search for observational studies.

Conclusions: While the majority of journal's editorial policies purported to support the ethical safeguards, many COVID-19 clinical research publications identified in this rapid review lacked documentation of these important safeguards for research participants. In order to promote public trust, ethical declarations should be included consistently.
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http://dx.doi.org/10.1186/s12910-021-00649-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237766PMC
June 2021

Should denosumab treatment for osteoporosis be continued indefinitely?

Ther Adv Endocrinol Metab 2021 22;12:20420188211010052. Epub 2021 Apr 22.

Department of Endocrinology, St Vincent's University Hospital, Elm Park, Dublin, 4, Ireland.

Denosumab was approved for the treatment of postmenopausal osteoporosis in 2010, based on the FREEDOM study, which indicated a benefit in terms of increased bone mineral density and reduced risk of major osteoporotic fracture. In the initial clinical studies it was noted that discontinuation of denosumab can lead to a rebound of bone turnover markers and loss of accrued bone mineral density. An increased risk of fractures (multiple vertebral fractures in particular) associated with discontinuation was noted after approval and marketing of denosumab. For many patients experiencing gain in bone mineral density and fracture prevention while taking denosumab, there is no reason to stop therapy. However, discontinuation of denosumab may happen due to non-adherence; potential lack of efficacy in an individual; where reimbursement for therapy is limited to those with bone mineral density in the osteoporosis range, when assessment reveals this has been exceeded; or patient or physician concern regarding side effects. This review paper aims to discuss these concerns and to summarize the data available to date regarding sequential osteoporosis therapy following denosumab cessation to reduce the risk of multiple vertebral fracture.
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http://dx.doi.org/10.1177/20420188211010052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072936PMC
April 2021

Letter to the Editor from Martin-Grace and Crowley: "Myxedema Heart and Pseudotamponade".

J Endocr Soc 2021 May 2;5(5):bvab026. Epub 2021 Mar 2.

Department of Endocrinology, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland.

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http://dx.doi.org/10.1210/jendso/bvab026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041348PMC
May 2021

Renal Phosphate Handling: Independent Effects of Circulating FGF23, PTH, and Calcium.

JBMR Plus 2021 Feb 9;5(2):e10437. Epub 2020 Dec 9.

UCD School of Medicine University College Dublin Dublin Ireland.

Excess fibroblast growth factor 23 (FGF23), excess PTH, and an increase in extracellular calcium cause hypophosphatemia by lowering the maximum renal phosphate reabsorption threshold (TmP/GFR). We recently reported two cases of X-linked hypophosphatemia (XLH) with severe tertiary hyperparathyroidism who had normalization of TmP/GFR upon being rendered hypoparathyroid following total parathyroidectomy, despite marked excess in both C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23). We explored the effects of FGF23, PTH, and calcium on TmP/GFR in a cross-sectional study ( = 74) across a spectrum of clinical cases with abnormalities in TmP/GFR, PTH, and FGF23. This comprised three groups: FGF23-dependent hypophosphatemia ( = 27), hypoparathyroidism (HOPT; = 17), and chronic kidney disease ( = 30). Measurements included TmP/GFR, cFGF23, PTH, ionized calcium, vitamin D metabolites, and bone turnover markers. The combined effect of cFGF23, PTH, and ionized calcium on TmP/GFR was modeled using hierarchical multiple regression and was probed by moderation analysis with PROCESS. Modeling analysis showed independent effects on TmP/GFR by cFGF23, PTH, and ionized calcium in conjunction with a weak but significant effect of the interaction term for PTH and FGF23; probing showed that the effect was most prominent during PTH deficiency. Teriparatide 20 μg daily was self-administered for 28 days by one case of X-linked hypophosphatemia with hypoparathyroidism (XLH-HOPT) to assess the response of TmP/GFR, cFGF23, iFGF23, nephrogenous cyclic adenosine monophosphate (NcAMP), vitamin D metabolites, and bone turnover markers. After 28 days, TmP/GFR was lowered from 1.10 mmol/L to 0.48 mmol/L; this was accompanied by increases in NcAMP, ionized calcium, and bone turnover markers. In conclusion, the effect of FGF23 excess on TmP/GFR is altered by PTH such that the effect is ameliorated by hypoparathyroidism and the effect is augmented by hyperparathyroidism. © 2020 The Authors. published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872336PMC
February 2021

Primary hyperparathyroidism and Zollinger Ellison syndrome during pregnancy: a case report.

Endocrinol Diabetes Metab Case Rep 2021 Feb 17;2021. Epub 2021 Feb 17.

St. Vincent's University Hospital, Dublin, Ireland.

Summary: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited endocrine disorder with a high rate of penetrance. The incidence of MEN1 is 1/30,000 in the general population; however, it is quite rare for a patient to present for medical attention with MEN1 for the first time in pregnancy. Primary hyperparathyroidism (PHPT) is one of the most common features of MEN1. The incidence of PHPT occurring in pregnancy is 1%. Despite advances in the medical, surgical and obstetric care over the years, management of this condition during pregnancy may be challenging. It can be difficult to identify pregnant women with PHPT requiring intervention and to monitor safely. Hypercalcemia can result in significant maternal and fetal adverse outcomes including: miscarriage, intrauterine growth restriction, preterm delivery, neonatal hypocalcaemia, pre-eclampsia and maternal nephrolithiasis. Herein, we present a case study of a lady with a strong family history of MEN1, who was biochemically proven to have PHPT and evidence of Zollinger Ellison Syndrome (ZE) on endoscopy. This patient delayed her assisted pregnancy plans for in vitro fertilization (IVF) until completion of the MEN1 workup; nevertheless, she spontaneously achieved an unplanned pregnancy. As a result, she required intervention with parathyroidectomy in the second trimester of her pregnancy as her calcium level continued to rise. This case study highlights the workup, follow up and management of MEN1 presenting with PHPT and ZE in pregnancy.

Learning Points: Women of childbearing age who are suspected to have a diagnosis of primary hyperparathyroidism ideally should have genetic testing and avoid pregnancy until definitive plans are in place. Zollinger Ellison syndrome in pregnancy means off-label use of high dose of proton pump inhibitors (PPI). Use of PPI in pregnancy is considered to be safe based on retrospective studies. Omeprazole, however, is FDA class C drug because of lack of large prospective studies or large case series during pregnancy. Calcium supplements in the form of calcium carbonate must be converted to calcium chloride by gastric acid in order to be absorbed, however, patients rendered achlorhydric as a result of PPI use will have impaired absorption of calcium. Therefore, use of calcium citrate might be considered a better option in this case.
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http://dx.doi.org/10.1530/EDM-20-0130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923119PMC
February 2021

The effects of acute hyponatraemia on bone turnover in patients with subarachnoid haemorrhage: A preliminary report.

Clin Endocrinol (Oxf) 2021 04 26;94(4):616-624. Epub 2020 Dec 26.

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

Context: Animal data and cross-sectional human studies have established that chronic hyponatraemia predisposes to osteoporosis; the effects of acute hyponatraemia on bone turnover have not been determined. Our objective was to test the hypothesis that acute hyponatraemia leads to dynamic effects on bone turnover.

Design: A prospective observational pilot study.

Methods: Bone turnover markers [C-terminal crosslinking telopeptide of type 1 collagen (CTX-1), N-propeptide of type 1 collagen (P1NP) and osteocalcin] were measured prospectively over one week in 22 eunatraemic patients with subarachnoid haemorrhage. Patients treated with glucocorticoids were excluded.

Results: Eight patients developed acute hyponatraemia, median nadir plasma sodium concentration 131 mmol/L (IQR 128-132), and 14 remained eunatraemic, nadir plasma sodium concentration 136 mmol/L (IQR 133-137). Significant main effects of hyponatraemia were found for P1NP (p = .02) and P1NP:CTX-1 ratio (p = .02), both fell in patients with acute hyponatraemia, with significant interaction between hyponatraemia and time from baseline for P1NP (p = .02). Significant main effects of time from baseline (p < .001) but not hyponatraemia (p = .07) were found for osteocalcin. For CTX-1, significant main effects of time from baseline (p = .001) but not hyponatraemia (p = .65) were found. There was a positive correlation between change in P1NP:CTX-1 ratio and nadir plasma sodium concentration, r = +.43, p = .04. Median serum cortisol (measured on days 1, 3 and 7) was higher in the hyponatraemia group than in those who remained eunatraemic, 545 nmol/L (IQR 373-778) versus 444 nmol/L (IQR 379-542) p = .03.

Conclusion: These data suggest that acute mild hyponatraemia is associated with a reduction in bone formation activity.
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http://dx.doi.org/10.1111/cen.14367DOI Listing
April 2021

Ethical Considerations for safeguarding human participants in pandemic research: a rapid review protocol.

HRB Open Res 2020 20;3:22. Epub 2020 Jul 20.

UCD School of Medicine, University College Dublin, Dublin 4, Ireland.

COVID-19 is a respiratory disease caused by a coronavirus, designated SARS-CoV-2, which is responsible for a global pandemic in 2020. Public interest in this disease has led to the publication of thousands of articles in the medical literature in a very short timeframe. It is imperative that medical research into COVID-19 is conducted quickly and safely, and that due reference is given to the ethical considerations enshrined in the ICH GCP guidelines, according to the Declaration of Helsinki. In order to review the reporting of ethical considerations in these papers, we hereby propose a protocol for a systematic review of COVID-19 papers up to April 14 2020. The search criteria proposed for the review are based upon what would be a reasonable search conducted by a lay member of the public with access to PubMed.gov. Institutional Research Ethics Committees (RECs) face significant challenges in providing thorough and timely ethical review during the COVID-19 pandemic. It is proposed to publish the findings of this rapid review along with a summary of an institutional REC response to the challenges of reviewing and approving clinical research proposals in the time of a pandemic.
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http://dx.doi.org/10.12688/hrbopenres.13053.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424914PMC
July 2020

Alemtuzumab-related thyroid disease in people with multiple sclerosis is associated with age and brainstem phenotype at disease onset.

Mult Scler J Exp Transl Clin 2020 Apr-Jun;6(2):2055217320933928. Epub 2020 Jun 18.

Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland.

Background: Autoimmune thyroid disease (AITD) occurs in 40%-50% of alemtuzumab-treated persons with multiple sclerosis (pwMS), most of whom will develop Graves' Disease (GD).

Objective: To explore contributory factors for alemtuzumab-related AITD in pwMS.

Methods: A retrospective patient chart review was performed.

Results: Sixteen out of 52 (30.8%) pwMS developed AITD. GD occurred in 56.3% ( = 9), the majority ( = 7, 77.8%) symptomatic. All but one (85.7%) pwMS with symptomatic GD developed atypical, large and rapid fluctuations in thyroid hormone levels unexplained by effect of anti-thyroid medication alone. All symptomatic GD cases were age ≤32 years when starting alemtuzumab (ɸ = 0.60,  = 0.03). PwMS who started alemtuzumab at a younger age developed thyroid disease earlier ( = 0.51,  = 0.04). PwMS with clinical and radiological evidence of brainstem involvement at onset of multiple sclerosis were 11 times more likely to develop symptomatic GD compared with those with other phenotypes ( < 0.01).

Conclusion: Alemtuzumab-induced reconstitution GD may result from early and increased cross-reactivity between antigens common to the brainstem and thyroid, or presence of shared Human Leukocyte Antigen (HLA) alleles that determine brainstem and thyroid involvement. We suggest cautious use of alemtuzumab in younger (≤32 years) pwMS with early brainstem involvement, especially those actively planning pregnancy, where alternative therapies are readily available.
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http://dx.doi.org/10.1177/2055217320933928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307483PMC
June 2020

Characteristics of Early Paget's Disease in SQSTM1 Mutation Carriers: Baseline Analysis of the ZiPP Study Cohort.

J Bone Miner Res 2020 07 20;35(7):1246-1252. Epub 2020 Apr 20.

Department of Rheumatology, Hospital Clinic, CIBERehd, Barcelona, Spain.

Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p = .07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p = .17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p < .0001). Similar findings were observed for other biochemical markers of bone turnover, but the sensitivity of ALP and other markers in detecting lesions was poor. Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow-up of this cohort will provide important information on the natural history of early PDB and its response to treatment. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.4007DOI Listing
July 2020

The impact of diet, body composition, and physical activity on child bone mineral density at five years of age-findings from the ROLO Kids Study.

Eur J Pediatr 2020 Jan 1;179(1):121-131. Epub 2019 Nov 1.

UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland.

Bone health is extremely important in early childhood because children with low bone mineral density (BMD) are at a greater risk of bone fractures. While physical activity and intake of both calcium and vitamin D benefit BMD in older children, there is limited research on the determinants of good bone health in early childhood. The aim of this cross-sectional study was to investigate the impact of diet, physical activity, and body composition on BMD at five years of age. Dietary intakes and physical activity levels were measured through questionnaires. Whole body BMD was measured by dual-energy X-ray absorptiometry in 102 children. Child weight, height, circumferences, skinfolds and serum 25-hydroxyvitamin D (25OHD) concentrations were assessed. There was no association between BMD and dietary calcium, dietary vitamin D, 25OHD, physical activity, or sedentary behaviour. Several measures of body composition were significantly positively associated with BMD; however, neither fat mass nor lean body mass was associated with BMD.Conclusion: Although we found no association between self-reported dietary and lifestyle factors and bone health in early years, increased body size was linked with higher BMD. These findings are important as identifying modifiable factors that can improve bone health at a young age is of utmost importance.What is Known:• Bone health is extremely important in early childhood, as children with low bone mineral density (BMD) are at greater risk of bone fractures.• Physical activity has been found to be beneficial for bone health in adolescents, and body composition has also been associated with BMD in teenage years.• Limited research on the determinants of good bone health in early childhood.What is New:• No association between self-reported lifestyle and dietary factors with bone health in early childhood.• Increased body size was associated with higher BMD at five years of age.
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http://dx.doi.org/10.1007/s00431-019-03465-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942579PMC
January 2020

Blood pressure in pregnancy-A stress test for hypertension? Five-year, prospective, follow-up of the ROLO study.

Clin Endocrinol (Oxf) 2019 12 13;91(6):816-823. Epub 2019 Oct 13.

UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland.

Objective: To investigate whether maternal blood pressure (BP) below the diagnostic criteria of hypertensive disorders of pregnancy (HDP) is associated with maternal BP 5 years later.

Design: Prospective, observational study.

Setting: Dublin, Ireland (2007-2011).

Sample: Three hundred twenty-nine women from the ROLO study (Randomized cOntrol trial of LOw glycaemic index diet to prevent the recurrence of macrosomia).

Methods: Maternal BP measurements were taken during pregnancy (13, 28 and 34 weeks' gestation and day 1 postpartum) and at the 5-year follow-up. Systolic BP (SBP) and diastolic BP (DBP) were categorized as normal (SBP < 120 and DBP < 80 mm Hg), elevated (SBP 120-129 and DBP < 80 mm Hg), HTN stage 1 (SBP 130-139 or DBP 80-89 mm Hg) or HTN stage 2 (SBP ≥ 140 or DBP ≥ 90 mm Hg) at each timepoint.

Main Outcome Measures: Maternal blood pressure at the 5-year follow-up.

Results: Women with elevated BP at 28 and 34 weeks' gestation had 2.68 (95% CI: 1.36-5.26) and 2.45-fold (95% CI: 1.22-4.95) increased odds of HTN stage 1 respectively, at the 5-year follow-up, compared to those with normal BP in pregnancy.

Conclusion: Elevated BP at 28 and 34 weeks' gestation was associated with an increased risk of HTN stage 1 at 5 years later. Thus, raised BP, below the diagnostic criteria of HDP, could be flagged for follow-up postpartum.
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http://dx.doi.org/10.1111/cen.14102DOI Listing
December 2019

Zoledronate in the prevention of Paget's (ZiPP): protocol for a randomised trial of genetic testing and targeted zoledronic acid therapy to prevent -mediated Paget's disease of bone.

BMJ Open 2019 09 4;9(9):e030689. Epub 2019 Sep 4.

Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

Introduction: Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 () are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget's disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry mutations.

Methods And Analysis: People with a family history of PDB aged >30 years who test positive for mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events.

Ethics And Dissemination: The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable.

Trial Registration Number: ISRCTN11616770.
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http://dx.doi.org/10.1136/bmjopen-2019-030689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731944PMC
September 2019

The prevalence and incidence of thyroid dysfunction in patients with diabetes - a longitudinal follow-up study.

Ir J Med Sci 2020 Feb 20;189(1):171-175. Epub 2019 Aug 20.

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

Background: Thyroid dysfunction (TD) occurs in 13.4% of diabetic patients, which has prompted recommendations for annual thyroid screening in patients with diabetes. However, recommendations for annual screening should be based on disease incidence rather than prevalence.

Methods: In 1997-1998, seven hundred and thirty patients (618 type 2 diabetes, 55% male; 112 type 1 diabetes, 47% male) were sequentially screened for TD. The 639 patients with normal thyroid function were followed from 1999 to 2006, with annual thyroid function tests.

Results: A total of 21/112 (19%) with type 1 diabetes (T1DM) and 70/618 (11%) with type 2 diabetes (T2DM) had TD. TD was more frequent in females (p < 0.05) and T1DM (p = 0.04). The mean annual rate of conversion to abnormal tests was 2.1%. At 8 years, there were 100 new cases of TD representing 15.6% of the cohort (17 T1DM and 83 T2DM). TD was more frequent in females (p < 0.05), but there was no difference in the incidence of new TD between T1DM and T2DM (p = 0.39).

Conclusions: Our data confirms the high prevalence of TD in diabetic patients, in concordance with the results from other series. We found only 25 treatable cases of new thyroid disease from 639 patients in the 8-year follow-up, less than 0.5% per year. The low incidence of treatable thyroid disease challenges the need for annual screening for thyroid abnormalities in patients with type 2 diabetes.
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http://dx.doi.org/10.1007/s11845-019-02082-9DOI Listing
February 2020

Double trouble: two cases of dual adrenal pathologies in one adrenal mass.

Endocrinol Diabetes Metab Case Rep 2019 Mar 23;2019. Epub 2019 Mar 23.

St. Vincent's University Hospital and University College Dublin, Dublin, Ireland.

Context Adrenal incidentalomas (AI) represent an increasingly common problem in modern endocrine practice. The diagnostic approach to AIs can be challenging and occasionally reveals surprising features. Here we describe two rare cases of complex adrenal lesions consisting of phaeochromocytomas with synchronous metastases from extra-adrenal primaries. Case descriptions Patient 1 - a 65-year-old gentleman with a newly diagnosed malignant melanoma was found to harbour an adrenal lesion with suspicious radiographic characteristics. Percutaneous adrenal biopsy was consistent with adrenocortical adenoma. After excision of the skin melanoma and regional lymphatic metastases, he was followed up without imaging. Three years later, he presented with abdominal discomfort and enlargement of his adrenal lesion, associated with high plasma metanephrines. Adrenalectomy revealed a mixed tumour consisting of a large phaeochromocytoma with an embedded melanoma metastasis in its core. Patient 2 - a 63-year-old lady with a history of NF-1-related phaeochromocytoma 20 years ago and previous breast cancer presented with a new adrenal lesion on the contralateral side. Plasma normetanephrine was markedly elevated. Elective adrenalectomy revealed an adrenal tumour consisting of chromaffin cells intermixed with breast carcinoma cells. Conclusions Adrenal incidentalomas require careful evaluation to exclude metastatic disease, especially in the context of a history of previous malignancy. Adrenal biopsy provides limited and potentially misleading information. Phaeochromocytomas are highly vascularised tumours that may function as a sieve, extracting and retaining irregularly shaped cancer cells, thereby yielding adrenal masses with intriguing dual pathology. Learning points: Adrenal incidentalomas require careful evaluation focused on exclusion of underlying hormone excess and malignant pathology. Adrenal biopsy can be misleading and should only be considered in select cases. Phaeochromocytomas harbouring intratumoural metastases from other, extra-adrenal primary malignancies represent rare pathological entities that highlight the complexities that can be presented by adrenal tumours.
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http://dx.doi.org/10.1530/EDM-18-0151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6432979PMC
March 2019

Author's Reply: Does increased 11 β HSD-1 activity induce adverse metabolic phenotype only in lean?

Clin Endocrinol (Oxf) 2019 06 2;90(6):849-850. Epub 2019 Apr 2.

Division of Medical Sciences, University of Oxford, Oxford, UK.

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http://dx.doi.org/10.1111/cen.13964DOI Listing
June 2019

Increased central adiposity and decreased subcutaneous adipose tissue 11β-hydroxysteroid dehydrogenase type 1 are associated with deterioration in glucose tolerance-A longitudinal cohort study.

Clin Endocrinol (Oxf) 2019 07 17;91(1):72-81. Epub 2019 Apr 17.

Oxford Centre for Diabetes Endocrinology & Metabolism (OCDEM), NIHR Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, UK.

Objective And Context: Increasing adiposity, ageing and tissue-specific regeneration of cortisol through the activity of 11β-hydroxysteroid dehydrogenase type 1 have been associated with deterioration in glucose tolerance. We undertook a longitudinal, prospective clinical study to determine if alterations in local glucocorticoid metabolism track with changes in glucose tolerance.

Design, Patients, And Measurements: Sixty-five overweight/obese individuals (mean age 50.3 ± 7.3 years) underwent oral glucose tolerance testing, body composition assessment, subcutaneous adipose tissue biopsy and urinary steroid metabolite analysis annually for up to 5 years. Participants were categorized into those in whom glucose tolerance deteriorated ("deteriorators") or improved ("improvers").

Results: Deteriorating glucose tolerance was associated with increasing total and trunk fat mass and increased subcutaneous adipose tissue expression of lipogenic genes. Subcutaneous adipose tissue 11β-HSD1 gene expression decreased in deteriorators, and at study completion, it was highest in the improvers. There was a significant negative correlation between change in area under the curve glucose and 11β-HSD1 expression. Global 11β-HSD1 activity did not change and was not different between deteriorators and improvers at baseline or follow-up.

Conclusion: Longitudinal deterioration in metabolic phenotype is not associated with increased 11β-HSD1 activity, but decreased subcutaneous adipose tissue gene expression. These changes may represent a compensatory mechanism to decrease local glucocorticoid exposure in the face of an adverse metabolic phenotype.
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http://dx.doi.org/10.1111/cen.13939DOI Listing
July 2019

Management of hypothalamic disease in patients with craniopharyngioma.

Clin Endocrinol (Oxf) 2019 04 11;90(4):506-516. Epub 2019 Feb 11.

Department of Endocrinology, St Vincent's University Hospital, Dublin, Ireland.

Patients with craniopharyngioma experience excess morbidity and mortality when compared with the background population and with other hypopituitary patients. Large, suprasellar tumours which form micropapillae into surrounding structures can cause hypothalamic damage before any therapeutic intervention; attempted gross total resection can lead to hypothalamic obesity, sleep disorders, thirst disorders and dysregulation of temperature as well as panhypopituitarism. The management of tumour bulk and the pathophysiology of hypothalamic complications have been reviewed extensively. We present a practical, clinical approach to management of hypothalamic disease in a patient with craniopharyngioma and highlight potential targets for future pharmacological or surgical intervention.
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http://dx.doi.org/10.1111/cen.13929DOI Listing
April 2019

An exploratory analysis of associations of diet, sun exposure, and body composition with 25OHD at five years of age: Findings from the ROLO Kids Study.

J Steroid Biochem Mol Biol 2019 04 31;188:111-116. Epub 2018 Dec 31.

UCD Perinatal Research Centre, School of Medicine, National Maternity Hospital, University College Dublin, Dublin, Ireland.

Serum 25-hydroxyvitamin D (25OHD) is the main circulating form of vitamin D in the blood. Vitamin D status in adults is determined by numerous factors such as oral intake, skin generation, and body composition. However, there is limited understanding regarding determinants of 25OHD in young children. The aim of this study was to identify modifiable factors that may act as determinants of 25OHD at five years of age. Analysis conducted on 79 children from the ROLO Kids study. Dietary intakes and dietary habits were measured using a food frequency questionnaire and levels of sun exposure were assessed using a lifestyle questionnaire, both completed by the mother. Child weight, height, and skinfolds were measured. Vitamin D status was sufficient (25OHD > 50 nmol/L) in 61% of the participants. Neither reported dietary vitamin D nor calcium intake was significantly associated with 25OHD. Intakes of standard milk, eggs, and oily fish were not associated with 25OHD. However, reported consumption of fortified milk, and more than 7 bowls of cereal a week were independently associated with higher 25OHD (p < 0.001 and p = 0.049, respectively). Sun exposure (measured as obtaining at least half an hour of sun per day) was not significantly associated with 25OHD, but reported use of sunscreen was associated with higher 25OHD (p = 0.016). There was no association of body composition with 25OHD. These findings suggest the primacy of dietary and lifestyle habits as indicators of 25OHD in early childhood. This may have utility in identifying at-risk individuals for public health campaigns about education surrounding dietary habits, which may be useful to ensure sufficient vitamin D status within this age group.
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http://dx.doi.org/10.1016/j.jsbmb.2018.12.014DOI Listing
April 2019

Laboratory trend in vitamin D status in Ireland: Dual concerns about low and high 25OHD.

J Steroid Biochem Mol Biol 2019 02 5;186:105-109. Epub 2018 Oct 5.

Clinical Chemistry, St. Vincent's University Hospital, Dublin, Ireland.

Serum 25-hydroxyvitamin D (25OHD) is the pre-eminent estimate of vitamin D status that we have been measuring in a hospital laboratory setting since the 1970s. We previously evaluated the trend in 25OHD results in our laboratory from 1993 to 2013. Using a time series analysis of monthly average 25OHD results the trend was modelled, and this was used to forecast monthly average 25OHD from 2014 to 2016. In this study, all 25OHD results from 2014 to 2016 were retrieved (n = 67,922) and trimmed to 40,307 results after duplicates were excluded. The average monthly actual 25OHD was almost identical to the average monthly forecast 25OHD (p = 0.028) with a strong correlation between the actual 25OHD and forecast 25OHD (r = 0.69, p < 0.001). This upward trend is attributed to higher oral intake of vitamin D. We have a dual concern: policies to prevent hypovitaminosis D must be offset by strategies to avert hypervitaminosis D.
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http://dx.doi.org/10.1016/j.jsbmb.2018.10.001DOI Listing
February 2019

RESPONSE LETTER.

Endocr Pract 2018 Jan;24(1):127

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http://dx.doi.org/10.4158/1934-2403-24.1.127DOI Listing
January 2018

Atypia of Undetermined Significance in Thyroid Fine Needle Aspirates: a 4-Year Audit of Thy3a Reporting.

Eur Thyroid J 2017 Sep 17;6(5):271-275. Epub 2017 Jul 17.

Department of Pathology, St. Vincent's University Hospital, Dublin 4, Ireland.

Objective: Thyroid nodules are common within the general population. Cytological analysis of fine needle aspirates (FNAs) of these lesions allows for identification of those that require further surgery. A numerical classification system is in place to streamline reporting. The 3a category is used for lesions that are neither benign nor malignant but show atypia of undetermined significance. We reviewed our use and clinical outcomes of Thy3a over a 4-year period.

Methods: All thyroid FNAs performed at this institute from January 2012 to December 2015 were identified from our laboratory information system using SNOMED codes. Cytology was correlated with histology.

Results: Of the 1,259 FNAs reported at this institute, Thy3a constituted only 1.2% ( = 16) of all cases, with a malignancy rate of 7%. Five Thy3a cases had a repeat FNA that was reported as Thy2 (benign), 1 as Thy1c (cyst), 1 as Thy3f (follicular lesion), and 1 as Thy5 (malignant). Six cases without repeat FNA were follicular adenomas at resection. Two cases were lost to follow-up. Within all thyroid cytology categories in this 4-year period, we had a false-positive rate of 1.9% and a false-negative rate of 0.3%.

Conclusions: The Thy3a subclassification has varied diagnostic criteria and lacks reproducibility. Despite the rare use of the Thy3a category at our centre, our diagnostic accuracy remained high. At this time, further Thy3a cohort studies are required to assess the real benefits of this category.
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http://dx.doi.org/10.1159/000478773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5649310PMC
September 2017

DIABETIC KETOACIDOSIS IN PATIENTS WITH TYPE 2 DIABETES RECENTLY COMMENCED ON SGLT-2 INHIBITORS: AN ONGOING CONCERN.

Endocr Pract 2017 04;23(4):506-508

Objective: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly used as an adjunctive treatment for type 2 diabetes. We report the occurrence of diabetic ketoacidosis (DKA) in 3 patients with type 2 diabetes recently commenced on SGLT-2 inhibitors.

Methods: Clinical presentation, laboratory data, and treatment outcomes of all 3 cases are described.

Results: All 3 patients had documented history of longstanding type 2 diabetes. The presentation in all patients was that of hyperglycaemia, acidosis, and ketosis occurring within 4 weeks of commencing SGLT-2 inhibitors. The risk factors for developing DKA were infection, myocardial infarction, and alcohol excess. DKA resolved within 24 hours of initiating intravenous fluids and insulin in all cases.

Conclusion: This case series illustrates the importance of careful patient selection, education, and monitoring when starting this group of antidiabetic medications.

Abbreviations: DKA = diabetic ketoacidosis SGLT-2 = sodium-glucose cotransporter 2 T2D = type 2 diabetes.
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http://dx.doi.org/10.4158/EP161447.LTDOI Listing
April 2017

Getting to the heart of hypopituitarism.

Clin Med (Lond) 2017 Apr;17(2):140-142

St. Vincent's University Hospital and University College Dublin, Dublin, Ireland.

A 53-year-old woman was diagnosed with hypopituitarism following an acute presentation with cardiac tamponade and hyponatraemia, having recently been investigated for a pericardial effusion. Secondary hypothyroidism is a rare cause of pericardial effusion and tamponade, but an important differential to consider. Management requires appropriate hormone replacement and, critically, a low threshold for commencing stress dose steroids. Clinical signs classically associated with cardiac tamponade are frequently absent in cases of tamponade due to primary and secondary hypothyroidism, and the relatively volume deplete state of secondary hypoadrenalism in hypopituitarism may further mask an evolving tamponade, as the rise in right atrial pressure is less marked even in the presence of large effusion. Our case demonstrates the importance of a high index of suspicion for cardiac tamponade in this patient cohort, even in the absence of clinical signs, and for measuring both thyroid-stimulating hormone and thyroxine levels when evaluating a pericardial effusion.
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http://dx.doi.org/10.7861/clinmedicine.17-2-140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297610PMC
April 2017

SFRP2 Is Associated with Increased Adiposity and VEGF Expression.

PLoS One 2016;11(9):e0163777. Epub 2016 Sep 29.

Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, United Kingdom.

Aims: The aim of this study was to assess depot-specific expression and secretion of secreted frizzled-related protein 2 (sFRP2) by adipose tissue and its effect on adipocyte biology. We measured serum sFRP2 concentrations in 106 patients in vivo to explore its relationship to fat mass, glycaemia and insulin resistance.

Methods: Expression of sFRP2 in mouse and human tissues was assessed using polymerase chain reaction and Western blot. Western blot confirmed secretion of sFRP2 by adipose tissue into cell culture medium. Effects of recombinant sFRP2 on lipogenesis and preadipocyte proliferation were measured. Preadipocyte expression of the angiogenic genes vascular endothelial growth factor (VEGF) and nuclear factor of activated T-cells 3 (NFATC3) was measured after recombinant sFRP2 exposure. Complementary clinical studies correlating human serum sFRP2 with age, gender, adiposity and insulin secretion were also performed.

Results: sFRP2 messenger RNA (mRNA) was expressed in mouse and human adipose tissue. In humans, sFRP2 mRNA expression was 4.2-fold higher in omental than subcutaneous adipose. Omental adipose tissue secreted 63% more sFRP2 protein than subcutaneous. Treatment with recombinant sFRP2 did not impact on lipogenesis or preadipocyte proliferation but was associated with increased VEGF mRNA expression. In human subjects, circulating insulin levels positively correlated with serum sFRP2, and levels were higher in patients with abnormal glucose tolerance (34.2ng/ml) compared to controls (29.5ng/ml). A positive correlation between sFRP2 and BMI was also observed.

Conclusions: Circulating sFRP2 is associated with adipose tissue mass and has a potential role to drive adipose angiogenesis through enhanced VEGF expression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163777PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042473PMC
September 2016

Epidural pneumatosis associated with spontaneous pneumomediastinum: a rare complication of diabetic ketoacidosis.

BMJ Case Rep 2016 Jul 22;2016. Epub 2016 Jul 22.

St Vincent's University Hospital, Dublin, Ireland University College Dublin, Dublin, Ireland.

Pneumomediastinum and epidural pneumatosis are rare complications of diabetic ketoacidosis (DKA). These result from the emesis and hyperventilation associated with DKA which lead to alveolar rupture and air escape into the mediastinal and epidural spaces. These complications are often asymptomatic and resolve with the correction of the underlying metabolic abnormality. Oesophageal contrast studies are only required if oesophageal perforation is suspected in patients presenting with persistent vomiting and chest pain. We report the rare association of pneumomediastinum and epidural pneumatosis complicating DKA in a 19-year-old female patient.
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http://dx.doi.org/10.1136/bcr-2016-216295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964182PMC
July 2016

THERAPY OF ENDOCRINE DISEASE: Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing's syndrome: a systematic review and meta-analysis.

Eur J Endocrinol 2016 Dec 22;175(6):R283-R295. Epub 2016 Jul 22.

Evidence-based Practice CenterMayo Clinic, Rochester, Minnesota, USA.

Objective: Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushing's syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor.

Methods: MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate.

Results: We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3-27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5-9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97-7.2) or obesity (RR 3.4, 95% CI: 0.95-12). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS.

Conclusions: Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management.
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http://dx.doi.org/10.1530/EJE-16-0465DOI Listing
December 2016
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