Publications by authors named "John Wass"

132 Publications

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

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

J Endocr Soc 2021 Mar 9;5(3):bvaa205. Epub 2021 Feb 9.

Royal Veterinary College, University of London, London, UK.

The designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.
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http://dx.doi.org/10.1210/jendso/bvaa205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874572PMC
March 2021

Multidisciplinary management of acromegaly: A consensus.

Rev Endocr Metab Disord 2020 12 10;21(4):667-678. Epub 2020 Sep 10.

Medical Research Unit in Endcrine Diseases, Hospital de Especialidades, Centro Médico Nacional, Siglo XXI, IMSS, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.
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http://dx.doi.org/10.1007/s11154-020-09588-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942783PMC
December 2020

Guidance for the prevention and emergency management of adult patients with adrenal insufficiency.

Clin Med (Lond) 2020 07;20(4):371-378

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.

Adrenal insufficiency (AI) is an often-unrecognised endocrine disorder, which can lead to adrenal crisis and death if not identified and treated. Omission of steroids in patients with AI, particularly during physiological stress such as an intercurrent illness or surgery, can also lead to an adrenal crisis. The National Reporting and Learning System (NRLS) identified 78 incidents including two deaths and six incidents of severe harm to patients in a recent 4-year period. This guidance will go through causes of adrenal insufficiency, groups at risk of an adrenal crisis, emergency management and management for surgical procedures. A new NHS Steroid Emergency Card has been developed to be carried by patients at risk of adrenal crisis. We hope the new emergency card and this guidance will increase awareness of the need to start steroids promptly in patients at risk of an adrenal crisis, particularly those presenting in the emergency department or to acute medicine teams and those undergoing surgery or invasive procedures.
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http://dx.doi.org/10.7861/clinmed.2019-0324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385786PMC
July 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

Prevention of Adrenal Crisis: Cortisol Responses to Major Stress Compared to Stress Dose Hydrocortisone Delivery.

J Clin Endocrinol Metab 2020 07;105(7)

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.

Context: Patients with adrenal insufficiency require increased hydrocortisone cover during major stress to avoid a life-threatening adrenal crisis. However, current treatment recommendations are not evidence-based.

Objective: To identify the most appropriate mode of hydrocortisone delivery in patients with adrenal insufficiency who are exposed to major stress.

Design And Participants: Cross-sectional study: 122 unstressed healthy subjects and 288 subjects exposed to different stressors (major trauma [N = 83], sepsis [N = 100], and combat stress [N = 105]). Longitudinal study: 22 patients with preserved adrenal function undergoing elective surgery. Pharmacokinetic study: 10 patients with primary adrenal insufficiency undergoing administration of 200 mg hydrocortisone over 24 hours in 4 different delivery modes (continuous intravenous infusion; 6-hourly oral, intramuscular or intravenous bolus administration).

Main Outcome Measure: We measured total serum cortisol and cortisone, free serum cortisol, and urinary glucocorticoid metabolite excretion by mass spectrometry. Linear pharmacokinetic modeling was used to determine the most appropriate mode and dose of hydrocortisone administration in patients with adrenal insufficiency exposed to major stress.

Results: Serum cortisol was increased in all stress conditions, with the highest values observed in surgery and sepsis. Continuous intravenous hydrocortisone was the only administration mode persistently achieving median cortisol concentrations in the range observed during major stress. Linear pharmacokinetic modeling identified continuous intravenous infusion of 200 mg hydrocortisone over 24 hours, preceded by an initial bolus of 50-100 mg hydrocortisone, as best suited for maintaining cortisol concentrations in the required range.

Conclusions: Continuous intravenous hydrocortisone infusion should be favored over intermittent bolus administration in the prevention and treatment of adrenal crisis during major stress.
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http://dx.doi.org/10.1210/clinem/dgaa133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241266PMC
July 2020

Thyroid Screening During Early Pregnancy and the Need for Trimester Specific Reference Ranges: A Cross-Sectional Study in Lahore, Pakistan.

Cureus 2019 Sep 15;11(9):e5661. Epub 2019 Sep 15.

Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, GBR.

Background Derangements in thyroid hormone levels can cause multiple complications in the mother and the foetus. Thyroid stimulating hormone (TSH) and free thyroxine (free T4 or FT4) levels are used to screen for maternal thyroid dysfunction; these should be compared with population based trimester-specific reference ranges. Our goal was: to determine the prevalence of various thyroid derangements, in early pregnancy, according to the current reference ranges available; to determine the need for trimester specific reference ranges for the local population. Methods A multi-centric, cross sectional population survey was conducted in Lahore, Pakistan. Serum TSH and FT4 levels were measured at the hormone lab of the Pathology department of Combined Military Hospital (CMH) Lahore. The results were entered and analysed using Statistical Package for the Social Sciences (SPSS) version 23.  Results In the 293 women sampled, mean FT4 and TSH levels were 15.03 (±5.62) pmol/L and 2.53 (±6.82) mIU/L respectively. According to the laboratory specific reference ranges, the prevalence of overt hyperthyroidism was 4.10%, (mean TSH= 0.03mIU/L); subclinical hyperthyroidism was 16.38%, (mean TSH= 0.17mIU/L); normal 70.65%, (mean TSH = 1.29mIU/L); subclinical hypothyroidism 4.44%, (mean TSH= 15.11mIU/L); overt hypothyroidism 4.44%, (mean TSH = 20.60mIU/L). Conclusion Our study showed a significant prevalence of thyroid dysfunction in the first trimester of pregnancy, and therefore highlights the need for more rigorous thyroid screening of women, in early pregnancy. There is a need to monitor these women in order to reduce maternal and foetal complications. Trimester specific reference ranges for thyroid hormones need to be developed in Pakistan.
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http://dx.doi.org/10.7759/cureus.5661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823014PMC
September 2019

A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Medicine, CIBERER, Universidad Autónoma de Madrid, Madrid, Spain.

Objective: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.

Participants: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration.

Evidence: This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities.

Consensus Process: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system.

Conclusions: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.
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http://dx.doi.org/10.1210/clinem/dgz096DOI Listing
April 2020

Increased Infection Risk in Addison's Disease and Congenital Adrenal Hyperplasia.

J Clin Endocrinol Metab 2020 02;105(2)

Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

Context: Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI). However, the risk of primary care-managed infections in patients with PAI is unknown.

Objective: To estimate infection risk in PAI due to Addison's disease (AD) and congenital adrenal hyperplasia (CAH) in a primary care setting.

Design: Retrospective cohort study using UK data collected from 1995 to 2018.

Main Outcome Measures: Incidence of lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), gastrointestinal infections (GIIs), and prescription counts of antimicrobials in adult PAI patients compared to unexposed controls.

Results: A diagnosis of PAI was established in 1580 AD patients (mean age 51.7 years) and 602 CAH patients (mean age 35.4 years). All AD patients and 42% of CAH patients were prescribed glucocorticoids, most frequently hydrocortisone in AD (82%) and prednisolone in CAH (50%). AD and CAH patients exposed to glucocorticoids, but not CAH patients without glucocorticoid treatment, had a significantly increased risk of LRTIs (adjusted incidence rate ratio AD 2.11 [95% confidence interval (CI) 1.64-2.69], CAH 3.23 [95% CI 1.21-8.61]), UTIs (AD 1.51 [95% CI 1.29-1.77], CAH 2.20 [95% CI 1.43-3.34]), and GIIs (AD 3.80 [95% CI 2.99-4.84], CAH 1.93 [95% CI 1.06-3.52]). This was mirrored by increased prescription of antibiotics (AD 1.73 [95% CI 1.69-1.77], CAH 1.77 [95% CI 1.66-1.89]) and antifungals (AD 1.89 [95% CI 1.74-2.05], CAH 1.91 [95% CI 1.50-2.43]).

Conclusions: There is an increased risk of infections and antimicrobial use in PAI in the primary care setting at least partially linked to glucocorticoid treatment. Future studies will need to address whether more physiological glucocorticoid replacement modes could reduce this risk.
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http://dx.doi.org/10.1210/clinem/dgz006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046014PMC
February 2020

Pituitary adenomas.

BMJ 2019 06 6;365:l2091. Epub 2019 Jun 6.

Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

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http://dx.doi.org/10.1136/bmj.l2091DOI Listing
June 2019

Diabetes insipidus.

BMJ 2019 Feb 28;364:l321. Epub 2019 Feb 28.

Department of Endocrinology, Oxford University Hospital NHS Foundation Trust, Oxford, UK.

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http://dx.doi.org/10.1136/bmj.l321DOI Listing
February 2019

Liothyronine cost and prescriptions in England.

Lancet Diabetes Endocrinol 2019 01;7(1):11-12

Institute of Metabolism and Systems Research, School of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

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http://dx.doi.org/10.1016/S2213-8587(18)30334-6DOI Listing
January 2019

Gathering momentum for the way ahead: fifth report of the Lancet Standing Commission on Liver Disease in the UK.

Lancet 2018 12 22;392(10162):2398-2412. Epub 2018 Nov 22.

King's College Hospital, London, UK.

This report presents further evidence on the escalating alcohol consumption in the UK and the burden of liver disease associated with this major risk factor, as well as the effects on hospital and primary care. We reiterate the need for fiscal regulation by the UK Government if overall alcohol consumption is to be reduced sufficiently to improve health outcomes. We also draw attention to the effects of drastic cuts in public services for alcohol treatment, the repeated failures of voluntary agreements with the drinks industry, and the influence of the industry through its lobbying activities. We continue to press for reintroduction of the alcohol duty escalator, which was highly effective during the 5 years it was in place, and the introduction of minimum unit pricing in England, targeted at the heaviest drinkers. Results from the introduction of minimum unit pricing in Scotland, with results from Wales to follow, are likely to seriously expose the weakness of England's position. The increasing prevalence of obesity-related liver disease, the rising number of people diagnosed with type 2 diabetes and its complications, and increasing number of cases of end-stage liver disease and primary liver cancers from non-alcoholic fatty liver disease make apparent the need for an obesity strategy for adults. We also discuss the important effects of obesity and alcohol on disease progression, and the increased risk of the ten most common cancers (including breast and colon cancers). A new in-depth analysis of the UK National Health Service (NHS) and total societal costs shows the extraordinarily large expenditures that could be saved or redeployed elsewhere in the NHS. Excellent results have been reported for new antiviral drugs for hepatitis C virus infection, making elimination of chronic infection a real possibility ahead of the WHO 2030 target. However, the extent of unidentified cases remains a problem, and will also apply when new curative drugs for hepatitis B virus become available. We also describe efforts to improve standards of hospital care for liver disease with better understanding of current service deficiencies and a new accreditation process for hospitals providing liver services. New commissioning arrangements for primary and community care represent progress, in terms of effective screening of high-risk subjects and the early detection of liver disease.
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http://dx.doi.org/10.1016/S0140-6736(18)32561-3DOI Listing
December 2018

Correction to: Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement.

Pituitary 2018 12;21(6):663

Division of Endocrinology, San Raffaele University Hospital, Milan, Italy.

The original version of this article unfortunately contained an affiliation error in 'Collaborators for The Pituitary Society, Expert Group on Pituitary Tumors' section. Dr. Misa Pfeifer is affiliated with Medical Faculty, University of Ljubljana, Slovenia and the correct email address to contact is [email protected]
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http://dx.doi.org/10.1007/s11102-018-0912-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828177PMC
December 2018

A Consensus Statement on acromegaly therapeutic outcomes.

Nat Rev Endocrinol 2018 09;14(9):552-561

Department of Endocrinology and Metabolism, San Raffaele University Hospital Milan, Milan, Italy.

The 11th Acromegaly Consensus Conference in April 2017 was convened to update recommendations on therapeutic outcomes for patients with acromegaly. Consensus guidelines on the medical management of acromegaly were last published in 2014; since then, new pharmacological agents have been developed and new approaches to treatment sequencing have been considered. Thirty-seven experts in the management of patients with acromegaly reviewed the current literature and assessed changes in drug approvals, clinical practice standards and clinical opinion. They considered current treatment outcome goals with a focus on the impact of current and emerging somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists on biochemical, clinical, tumour mass and surgical outcomes. The participants discussed factors that would determine pharmacological choices as well as the proposed place of each agent in the guidelines. We present consensus recommendations highlighting how acromegaly management could be optimized in clinical practice.
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http://dx.doi.org/10.1038/s41574-018-0058-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136157PMC
September 2018

The cortisol stress response induced by surgery: A systematic review and meta-analysis.

Clin Endocrinol (Oxf) 2018 11 23;89(5):554-567. Epub 2018 Aug 23.

Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Objective: Surgery is a stressor that can be categorized by duration and severity and induces a systemic stress response that includes increased adrenal cortisol production. However, the precise impact of surgical stress on the cortisol response remains to be defined.

Design: We performed a systematic review and meta-analysis to assess the cortisol stress response induced by surgery and to stratify this response according to different parameters.

Methods: We conducted a comprehensive search in several databases from 1990 to 2016. Pairs of reviewers independently selected studies, extracted data and evaluated the risk of bias. Cortisol concentrations were standardized, pooled in meta-analysis and plotted over time.

Results: We included 71 studies reporting peri-operative serum cortisol measurements in 2953 patients. The cortisol response differed substantially between moderately/highly invasive and minimally invasive surgical procedures. Minimally invasive procedures did not show a peri-operative cortisol peak, whereas more invasive surgeries caused a cortisol surge that was more pronounced in older subjects, women and patients undergoing open surgery and general anaesthesia. The duration of the procedure and the use of etomidate for induction of anaesthesia did not affect the cortisol response.

Conclusions: The peri-operative cortisol stress response is dynamic and influenced by patient-specific, surgical and anaesthetic features. However, the available evidence is derived from highly heterogeneous studies, with only two of 71 studies measuring cortisol by mass spectrometry, which currently prevents a precise and reproducible definition of this response.
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http://dx.doi.org/10.1111/cen.13820DOI Listing
November 2018

Worse Health-Related Quality of Life at long-term follow-up in patients with Cushing's disease than patients with cortisol producing adenoma. Data from the ERCUSYN.

Clin Endocrinol (Oxf) 2018 06 16;88(6):787-798. Epub 2018 Apr 16.

Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and the Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Objective: Hypercortisolism in Cushing's syndrome (CS) is associated with impaired health-related quality of life (HRQoL), which may persist despite remission. We used the data entered into the European Registry on Cushing's syndrome (ERCUSYN) to evaluate if patients with CS of pituitary origin (PIT-CS) have worse HRQoL, both before and after treatment than patients with adrenal causes (ADR-CS).

Methods: Data from 595 patients (492 women; 83%) who completed the CushingQoL and/or EQ-5D questionnaires at baseline and/or following treatment were analysed.

Results: At baseline, HRQoL did not differ between PIT-CS (n = 293) and ADR-CS (n = 120) on both EuroQoL and CushingQoL. Total CushingQoL score in PIT-CS and ADR-CS was 41 ± 18 and 44 ± 20, respectively (P = .7). At long-time follow-up (>1 year after treatment) total CushingQoL score was however lower in PIT-CS than ADR-CS (56 ± 20 vs 62 ± 23; P = .045). In a regression analysis, after adjustment for baseline age, gender, remission status, duration of active CS, glucocorticoid dependency and follow-up time, no association was observed between aetiology and HRQoL. Remission was associated with better total CushingQoL score (P < .001), and older age at diagnosis with worse total score (P = .01). Depression at diagnosis was associated with worse total CushingQoL score at the last follow-up (P < .001).

Conclusion: PIT-CS patients had poorer HRQoL than ADR-CS at long-term follow-up, despite similar baseline scoring. After adjusting for remission status, no interaetiology differences in HRQoL scoring were found. Age and presence of depression at diagnosis of CS may be potential predictors of worse HRQoL regardless of CS aetiology.
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http://dx.doi.org/10.1111/cen.13600DOI Listing
June 2018

Preoperative medical treatment in Cushing's syndrome: frequency of use and its impact on postoperative assessment: data from ERCUSYN.

Eur J Endocrinol 2018 Apr 12;178(4):399-409. Epub 2018 Feb 12.

Centre Hospitalier Universitaire de BordeauxBordeaux, France.

Background: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial.

Objective: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS).

Patients And Methods: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS).

Results: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS ( < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) ( < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol ( < 0.01) and a lower remission rate ( < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups.

Conclusions: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.
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http://dx.doi.org/10.1530/EJE-17-0997DOI Listing
April 2018

Consider Addison's disease in differential diagnosis of eating disorders in children and young people.

BMJ 2018 01 26;360:k277. Epub 2018 Jan 26.

University of Birmingham, Birmingham, UK.

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http://dx.doi.org/10.1136/bmj.k277DOI Listing
January 2018

Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas.

Pituitary 2018 Apr;21(2):111-118

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

Purpose: Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms that do not cause a hormonal hypersecretory syndrome. An improved understanding of their epidemiology, clinical presentation and diagnosis is needed.

Method: A literature review was performed using Pubmed to identify research reports and clinical case series on NFPAs.

Results: They account for 14-54% of pituitary adenomas and have a prevalence of 7-41.3/100,000 population. Their standardized incidence rate is 0.65-2.34/100,000 and the peak occurence is from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from being completely asymptomatic to causing significant hypothalamic/pituitary dysfunction and visual field compromise due to their large size. Most patients present with symptoms of mass effect, such as headaches, visual field defects, ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning pituitary incidentalomas are found on brain imaging performed for an unrelated reason. Diagnostic approach includes magnetic resonance imaging of the sellar region, laboratory evaluations, screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm.

Conclusion: This article reviews the epidemiology, clinical behaviour and diagnostic approach of non-functioning pituitary adenomas.
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http://dx.doi.org/10.1007/s11102-018-0869-3DOI Listing
April 2018

Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK.

Lancet 2018 03 29;391(10125):1097-1107. Epub 2017 Nov 29.

Fulcrum Practice, Middlesbrough, UK.

This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcohol dependence, damage to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government's soft drinks industry levy have been seen, but the government cannot continue to ignore the number of adults being affected by diabetes, hypertension, and liver disease. New direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection have reduced mortality and the number of patients requiring liver transplantation, but more screening campaigns are needed for identification of infected people in high-risk migrant communities, prisons, and addiction centres. Provision of care continues to be worst in regions with the greatest socioeconomic deprivation, and deficiencies exist in training programmes in hepatology for specialist registrars. Firm guidance is needed for primary care on the use of liver blood tests in detection of early disease and the need for specialist referral. This report also brings together all the evidence on costs to the National Health Service and wider society, in addition to the loss of tax revenue, with alcohol misuse in England and Wales costing £21 billion a year (possibly up to £52 billion) and obesity costing £27 billion a year (treasury estimates are as high as £46 billion). Voluntary restraints by the food and drinks industry have had little effect on disease burden, and concerted regulatory and fiscal action by the UK Government is essential if the scale of the medical problem, with an estimated 63 000 preventable deaths over the next 5 years, is to be addressed.
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http://dx.doi.org/10.1016/S0140-6736(17)32866-0DOI Listing
March 2018

Males with prolactinoma are at increased risk of incident cardiovascular disease.

Clin Endocrinol (Oxf) 2018 Jan 8;88(1):71-76. Epub 2017 Nov 8.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Objective: To investigate whether the risk of incident cardiovascular disease (CVD) is increased in patients with prolactinoma.

Design: Population-based, retrospective, open-cohort study using The Health Improvement Network (THIN) database.

Patients: A total of 2233 patients with prolactinoma and 10 355 matched controls (1:5 ratio) from UK General Practices contributing to THIN were included. Sex, age, body mass index and smoking status were used as matching parameters. The primary outcome was any incident CVD, defined by Read codes suggesting myocardial infarction, angina pectoris, stroke, transient ischaemic attack or heart failure. Sex-specific-adjusted incidence rate ratios (aIRRs) were calculated with Poisson regression, using clinically relevant parameters as model covariates. Sensitivity analyses were performed to check whether a change in the initial assumptions could have an impact on the findings.

Results: During the 6-year observation period, the composite CVD outcome was recorded in 54 patients with prolactinoma and 180 "nonexposed" individuals. The incidence rate was 1.8 and 14.8 per 1000 person-years for the females and males with prolactinoma, respectively. The aIRRs for CVD were estimated at 0.99 [95% confidence interval (CI): 0.61-1.61, P = .968)] in female patients and 1.94 (95% CI: 1.29-2.91, P = .001) in male patients. These findings remained robust in sensitivity analyses restricting to patients with documented record of dopamine agonist treatment and those with newly diagnosed prolactinoma.

Conclusions: In contrast to females, men with prolactinoma have increased risk for incident CVD; the aetiology of this gender-specific finding remains to be elucidated.
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http://dx.doi.org/10.1111/cen.13498DOI Listing
January 2018

Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement.

Pituitary 2017 Oct;20(5):489-498

Division of Endocrinology, San Raffaele University Hospital, Milan, Italy.

Introduction: With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE).

Methods: To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement.

Results: After five years of iterative work a document with the ideal criteria for a PTCOE is presented.

Conclusions: Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.
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http://dx.doi.org/10.1007/s11102-017-0838-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606938PMC
October 2017

Diagnostic tests for Cushing's syndrome differ from published guidelines: data from ERCUSYN.

Eur J Endocrinol 2017 05;176(5):613-624

Department of EndocrinologyChristie Hospital, Manchester, UK.

Objective: To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing's syndrome (ERCUSYN), and to examine if their use differs from the current guidelines.

Patients And Methods: We analyzed data on the diagnostic tests performed in 1341 patients with Cushing's syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS).

Results: Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years ( < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years ( < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC ( < 0.05).

Conclusions: Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.
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http://dx.doi.org/10.1530/EJE-16-0967DOI Listing
May 2017

Outcome of Nonfunctioning Pituitary Adenomas That Regrow After Primary Treatment: A Study From Two Large UK Centers.

J Clin Endocrinol Metab 2017 06;102(6):1889-1897

Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham B15 2TT, Birmingham, United Kingdom.

Context: Despite the major risk of regrowth of clinically nonfunctioning pituitary adenomas (CNFAs) after primary treatment, systematic data on the probability of further tumor progression and the effectiveness of management approaches are lacking.

Objective: To assess the probability of further regrowth(s), predictive factors, and outcomes of management approaches in patients with CNFA diagnosed with adenoma regrowth after primary treatment.

Patients, Design, And Setting: Retrospective cohort study of 237 patients with regrown CNFA managed in two UK centers.

Results: Median follow-up was 5.9 years (range, 0.4 to 37.7 years). The 5-year second regrowth rate was 35.3% (36.2% after surgery; 12.5% after radiotherapy; 12.7% after surgery combined with radiotherapy; 63.4% with monitoring). Of those managed with monitoring, 34.8% eventually were offered intervention. Type of management and sex were risk factors for second regrowth. Among those with second adenoma regrowth, the 5-year third regrowth rate was 26.4% (24.4% after surgery; 0% after radiotherapy; 0% after surgery combined with radiotherapy; 48.3% with monitoring). Overall, patients with a CNFA regrowth had a 4.4% probability of a third regrowth at 5 years and a 10.0% probability at 10 years; type of management of the first regrowth was the only risk factor. Malignant transformation was diagnosed in two patients.

Conclusions: Patients with regrown CNFA after primary treatment continue to carry considerable risk of tumor progression, necessitating long-term follow-up. Management approach to the regrowth was the major factor determining this risk; monitoring had >60% risk of progression at 5 years, and a substantial number of patients ultimately required intervention.
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http://dx.doi.org/10.1210/jc.2016-4061DOI Listing
June 2017

The scandal of generic drug pricing: drug regulation policies need review.

BMJ 2017 02 23;356:j947. Epub 2017 Feb 23.

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

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http://dx.doi.org/10.1136/bmj.j947DOI Listing
February 2017
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