Quality of patient-reported outcome reporting in trials of diabetes in pregnancy: A systematic review.

AIMS: Patient-reported outcomes (PROs) are reports of the patient's health status that come directly from the patient without interpretation by the clinician or anyone else. They are increasingly used in randomised controlled trials (RCTs). In this systematic review we identified RCTs conducted in women with diabetes in pregnancy which included PROs in their primary or secondary outcomes. We then evaluated the quality of PRO reporting against an internationally accepted reporting framework (Consolidated Standards of Reporting Trials (CONSORT-PRO) guidelines). METHODS: We searched online databases for studies published 2013-2021 using a combination of keywords. Two authors reviewed all abstracts independently. Data on study characteristics and the quality of PRO reporting were extracted from relevant studies. We conducted a multiple regression analysis to identify factors associated with high quality reporting. RESULTS: We identified 7122 citations. Thirty-five articles were included for review. Only 17% of RCTs included a PRO as a primary or secondary outcome. Out of a maximum score of 100 the median score was 46, indicating sub-optimal reporting. A multiple regression analysis did not reveal any factors associated with high quality reporting. CONCLUSIONS: Researchers should be mindful of the importance of PRO inclusion and reporting and include reliable PROs in trials.

Approach to the Management of Hypernatraemia in Older Hospitalised Patients.

Hypernatraemia is associated with high morbidity and mortality and is more common in patients of older age, nursing home residents and those with cognitive impairment and restricted mobility. The most common cause in hospital settings is water dehydration due to reduced intake although other causes should be identified. Once identified, prompt management is necessary to avoid delayed correction as prolonged hypernatremia is associated with increased hospital stay and mortality. Comprehensive history-taking and physical examination, basic investigations and medication review are essential to identify causative and remediable factors in those admitted with hypernatraemia. Accurate calculation of fluid deficit and ongoing losses is essential in order to ensure adequate fluid replacement, The administration of appropriate, usually hypotonic, fluids is also essential to the timely restoration of eunatraemia. Although evidence of definite harm resulting from rapid correction is lacking, a serum sodium reduction rate of <12 mmol/l day is advised with the caveat that close monitoring of electrolytes is required to ensure the desired correction rate is being achieved. Medical and nursing professionals should have access to a local hospital protocol to guide management of patients with hypernatraemia to improve patient outcomes and mitigate the risk of harm, particularly from under-recognition and slow correction.

A Comparison of Community-Acquired and Hospital-Acquired Hypernatraemia in Patients who are Acutely Admitted to Hospital.

Background Hypernatraemia is associated with a short-term mortality of 20-60%. Age-related physiological changes predispose patients to hypernatraemia. This study reviewed acutely admitted patients comparing those with community-acquired (CAH) and hospital-acquired hypernatraemia (HAH). Methods A retrospective study of 102 consecutive acute medical in-patients with serum [Na]>145 mmol/L was conducted. Baseline characteristics, clinical presentation, laboratory values, monitoring, management and outcomes were compared between CAH and HAH groups. Results Patients were exclusively older (>69 years). Forty patients (39.2%) had CAH and sixty-two (61.8%) had HAH. Those with CAH were more likely to be NH residents, have dementia and reduced mobility. Most HAH patients had mild hypernatraemia initially (75.8%, n=47), and higher rates of acute kidney injury (27% (n=11) vs 8% (n=3)/p=0.02) were observed. Monitoring was inadequate and no patient had a free water deficit documented. Medication review and intravenous fluid prescribing was similar between groups. The median length of stay of discharged HAH patients was longer (22.5 vs 8 days/p=0.005). Mortality rates were similar (47% (n=29) vs 37% (n=15)/p=0.416). Time from admission to death was higher in HAH patients (16 vs 8 days/p=0.008). Conclusions Both CAH and HAH present similarly, however, older patients with cognitive/physical impairments are at an increased risk. Early identification of high-risk patients and adherence to best practice guidelines is required.

A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

A systematic review on outcome reporting in randomised controlled trials assessing treatment interventions in pregnant women with pregestational diabetes.

BACKGROUND: Pregestational diabetes mellitus (PGDM) is associated with adverse pregnancy outcomes. Studies assessing interventions to improve maternal and infant outcomes have increased exponentially over recent years. Several outcomes in this field of maternal diabetes are rare, making it difficult to synthesise evidence. OBJECTIVES: To collect outcomes reported in studies assessing treatment interventions in pregnant women with PGDM. SEARCH STRATEGY: CENTRAL, Web of Science, Medline, CINAHL, Embase and ClinicalTrials.gov from their inception until 27 January 2020. SELECTION CRITERIA: Any randomised controlled trial assessing treatment interventions in pregnant women with PGDM reported in English. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed the suitability of articles and retrieved the data. Outcomes extracted from the literature were broadly categorised into maternal, fetal/infant or other outcomes by the study advisory group. MAIN RESULTS: Sixty-seven of the 1475 studies identified fulfilled the inclusion criteria. The median number of outcomes reported per study was 15 (range 1-46). The majority of studies were from North America and Europe. Insulin and metformin were the most commonly investigated pharmacological interventions. Glucose monitoring was the most assessed technological intervention. In all, 131 unique outcomes were extracted: maternal (n = 69), fetal/infant (n = 61) and other (n = 1). CONCLUSIONS: Outcome reporting in treatment interventions trials of pregnant women with PGDM is varied, making it difficult to synthesise evidence, especially for rare outcomes. Systems are needed to standardise outcome reporting in future clinical trials and so facilitate evidence synthesis in this area of maternal diabetes. REGISTRATION: The systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO) database (Registration number CRD42020173549). TWEETABLE ABSTRACT: Outcome reporting is heterogeneous in intervention trials of pregnant women with diabetes existing before pregnancy.

Early gestational diabetes mellitus (GDM) is associated with worse pregnancy outcomes compared with GDM diagnosed at 24-28 weeks gestation despite early treatment.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated+ with adverse pregnancy outcomes compared with women with normal glucose tolerance in pregnancy. The WHO recommends screening at 24-28 weeks gestation for GDM. Women who are diagnosed before 24-28 weeks gestation have a longer intervention period which may impact positively on pregnancy outcomes. AIM: This study aimed to examine pregnancy outcomes of women with GDM diagnosed <24 weeks gestation compared with those diagnosed at 24-28 weeks in a large Irish cohort. METHODS: A retrospective cohort study of 1471 pregnancies in women with GDM diagnosed using IADPSG criteria between September 2012 and April 2016 was conducted. At GDM diagnosis, women were classified as early GDM <24 weeks or standard GDM 24-28 weeks gestation. RESULTS: Women with early GDM had a significantly greater risk of pregnancy-induced hypertension (12.4% vs. 5.3%; P < 0.05), post-partum haemorrhage (8.7% vs. 2.4%; P < 0.05) and post-partum glucose abnormalities (32% vs. 15.6%; P < 0.05). Their offspring had a greater risk of pre-maturity (10.9% vs. 6.6%; P < 0.05), stillbirth (1.4% vs. 0.5%; P < 0.05), large for gestational age (19.1% vs. 13.4% P < 0.05) and need neonatal intensive care (30.7% vs. 22.1%; P < 0.05) compared with offspring of women with standard GDM. Rates of C-section and pre-maturity were still higher in the early GDM group when the two groups where compared based on their post-natal OGTT. CONCLUSION: Early GDM women and their offspring are at greater risk of an adverse pregnancy outcome compared with those diagnosed at 24-28 weeks. In view of the abnormal post-natal glucose findings, early GDM may reflect a more advanced state in diabetes pathogenesis.

Establishing Benefit from Vitamin D Supplementation - Adherence to Defined Criteria and Targeting of High-Risk Groups Essential?

BACKGROUND: Vitamin D is the one of the most common nutritional deficiencies worldwide, and insufficiency or deficiency can be associated with musculoskeletal and non-skeletal conditions such as cancer, cardiovascular disease and diabetes mellitus. OBJECTIVE: Recent data suggests that Vitamin D is relatively safe and toxicity is rarer than previously indicated. However, international guidelines regarding dosage and target plasma levels are conflicting. Moreover multiple well-designed studies of healthy older adults, unselected in terms of Vitamin D status, have revealed largely negative results (with the possible exception of older patients in care homes/hospitals) in terms of improvement in musculoskeletal and non-skeletal conditions to date. CONCLUSION: On that basis, it is suggested that future trials regarding Vitamin D supplementation should be carried out in high-risk groups. The use of published criteria for evaluating the effect of nutrients and targeting of individuals with Vitamin D insufficiency and deficiency for inclusion in such studies is also proposed. The identification of specific subgroups that will benefit from supplementation and replacement, and the establishment of a scientific basis for such therapy, should be possible with this approach.

Plasma glycated CD59 (gCD59), a novel biomarker for the diagnosis, management and follow up of women with Gestational Diabetes (GDM) - protocol for prospective cohort study.

BACKGROUND: The prevalence of Gestational Diabetes (GDM) is rising and with it the number of mothers and children at risk of adverse outcomes. As treatment has been shown to reduce adverse events, it is imperative that we identify all at-risk pregnant women. In Ireland, the national standard of care is selective screening with a 2-hour 75 g oral glucose tolerance test (OGTT). Aiming for universal screening is of utmost importance but this is difficult given the length, the unfeasibility and impracticability of the OGTT. We aim to assess if the novel biomarker glycated CD59 (gCD59) is a suitable contender for the OGTT in identifying women with GDM. METHODS: In this prospective cohort study, the study participants will be consecutive pregnant women at Galway University Hospital, Galway, Ireland. Samples for the plasma gCD59 biomarker will be taken together with routine bloods at the first antenatal visit, at weeks 24-28 at the time of routine 75 g OGTT, in trimester 3- and 12-weeks post-partum for women with GDM while having their routine post-partum 75 g OGTT. The constructed database will contain baseline information on each study participant, baseline laboratory data, follow-up laboratory data and pregnancy related outcomes. We aim to recruit a total of 2,000 participants over the project period and with a national GDM prevalence of 12-13%, we will have 240-260 subjects who meet OGTT criteria for GDM. Following regional prevalence, we expect to have 34-37 women who will develop either diabetes or pre-diabetes in the early post-partum period. The sensitivity and specificity of plasma gCD59 to predict the results of the OGTT will be assessed using nonparametric estimates of the receiver operating characteristic (ROC) curves and respective area under the ROC curve (AUROC). DISCUSSION: A body of clinical and experimental evidence supports a link between the complement system, complement regulatory proteins, and the pathogenesis of diabetes complications. Building on this research, our study plans to look at the plasma gCD59 capacity to classify pregnant women with normal or abnormal glucose tolerance but also to assess if plasma gCD59 can be used as an early predictor for GDM, for adverse pregnancy outcomes and/or post-partum glucose intolerance.

Increased rates of hypernatraemia during modest heatwaves in temperate climates.

BACKGROUND: Hypernatraemia is associated with morbidity and mortality, particularly in the older person. Last summer, Ireland experienced prolonged periods of excessive heat. The Irish meteorological service defines a heatwave as temperatures exceeding 25°C for five consecutive days. AIM: This study sought to compare the frequency of hypernatraemia (sodium (Na+) >145 mmol/l) observed during a modest heatwave with that during average ambient temperature in the temperate Irish climate. DESIGN: Retrospective cross-sectional analysis with nested case-control study. METHODS: The 10-day period from 24 June to 3 July in 2017 and 2018 were chosen as the control and heatwave periods, respectively. Patients aged >65 with at least one Na+ value recorded on the laboratory information system were included. Local meteorological data, age, gender and Na+ levels were evaluated. RESULTS: Maximum air temperatures were significantly higher during the heatwave period (mean 27°C vs. 16.8°C, P < 0.0001). Hypernatraemia was present in 3.6% (66/1840) of samples collected during the heatwave compared to 1.4% (23/1593) in the control period. The mean age of affected patients was similar in both groups, 75 years ±7 (P = 1.000). Almost half of participants (49.5%) were male. The frequency of hypernatraemia observed was not influenced by gender, P = 0.33. The median sodium concentrations were similar in both groups, P = 1.00. CONCLUSION: Hypernatraemia was 2.5 times more frequent in samples drawn during the heatwave compared to the control period. In this study, neither age nor gender impacted the profile of patients diagnosed with hypernatraemia. A modest rise in temperatures increases hypernatraemia rates in temperate climates.

Fulminant Skeletal Failure in a Centenarian: The Impact of Nutrition and Immobility.

This case describes a 103-year-old lady who presented from home with an incidental diagnosis of a left femoral fracture. She had no history of trauma and denied pain. She had a known diagnosis of osteoporosis, and sustained a fracture of the contralateral femur aged 93 which was managed conservatively. She was bed-bound with fixed contractures, poor oral intake and was non-compliant with prescribed calcium/vitamin D supplementation. Clinical biochemical measurements showed severe vitamin D deficiency and mild hypocalcaemia. Secondary hyperparathyroidism in the setting of an inappropriately normal phosphate suggested concurrent renal bone disease. Biomarkers of bone turnover were also consistent with bone remodelling. The history of prior fragility fractures, severe vitamin D deficiency and immobility supports a diagnosis of osteoporotic fracture, however other causes of spontaneous fracture were also considered. This case highlights the complexity of interpreting clinical biochemistry results in the setting of multi-morbidity and addresses the challenges of bone health management in the frail older person.

Spontaneous Insufficiency Fractures.

Spontaneous insufficiency fractures are caused by normal or physiological stress on weakened bone. The leading cause of insufficiency fractures is osteoporosis which has a propensity to affect older patients. Other causes or associated factors are disorders which affect bone metabolism, collagen formation, bone remodelling and medications such as bisphosphonates and glucocorticoids. Pathological fractures and abuse are important causes of unexplained fractures which warrant careful consideration. Spontaneous fractures of the long bones affect on average 1% of nursing home residents per year and tend to occur in patients who are bed-bound with joint contractures. Preventative measures for spontaneous insufficiency fractures include optimising nutrition to include an adequate intake of protein, calcium and vitamin D, maintaining mobility and preventing long periods of bed-rest and treatment of underlying pre-disposing conditions.

Associations between glycaemic control and activation of the renin-angiotensin-aldosterone system in participants with type 2 diabetes mellitus and hypertension.

Introduction Hyperglycaemia increases succinate concentrations and succinate receptor activation in the kidney resulting in renin release. The aim of our study was to determine if there is an association between glycaemic control as evidenced by glycated haemoglobin values and activation of the renin-angiotensin-aldosterone system in patients with type 2 diabetes mellitus and hypertension. Methods A cross-sectional study was conducted at Galway University Hospitals between December 2014 and March 2015. Participants ( n = 66) were identified following interrogation of the electronic database for patients with type 2 diabetes mellitus. Baseline clinical demographics, aldosterone, plasma renin activity, direct renin concentration, urea and electrolytes, glycated haemoglobin, cholesterol, urine sodium and albumin creatinine ratio were recorded. Results There was a significant positive linear correlation between glycated haemoglobin and renin (both plasma renin activity [ P = 0.002] and direct renin concentration [ P = 0.008]) and between serum creatinine and aldosterone measured using both radioimmunoassay ( P = 0.008) and immunochemiluminometric assay ( P = 0.008). A significant negative linear correlation was demonstrated between serum sodium and plasma renin activity ( P = 0.005) and direct renin concentration ( P = 0.015) and between estimated glomerular filtration rate and aldosterone measured using radioimmunoassay ( P = 0.02) and immunochemiluminometric assay ( P = 0.016). A significant negative linear correlation existed between urine sodium and plasma renin activity ( P = 0.04) and aldosterone measured using radioimmunoassay ( P = 0.045). Conclusions There is a direct positive association between glycaemic control and renin. We advocate for renin measurement to be part of the diabetologist's armamentarium to assess, guide and optimize therapeutic strategies in patients with diabetes.

Screening for primary aldosteronism using the newly developed IDS-iSYS® automated assay system.

BACKGROUND: The recommended approach to screening for primary aldosteronism (PA) in at-risk populations is to determine the ratio of aldosterone concentration (serum (SAC)/plasma (PAC)) to renin measured in plasma as activity (PRA) or concentration (DRC). However, lack of assay standardisation mandates the need for method-specific decision thresholds and clinical validation in the local population. AIM: The study objective was to establish method-specific aldosterone: renin ratio (ARR) cut-offs for PA in men and women using the IDS-iSYS® assay system (IDS plc). METHODS: A prospective cohort study design was used. PAC and DRC were measured immunochemically in ethylenediamine-tetraacetic acid (EDTA) plasma on the IDS-iSYS® instrument. RESULTS: A total of 437 subjects (218 men, 219 women) were recruited including: healthy normotensive volunteers (n=266) and women taking the oral contraceptive pill (OCP; n=15); patients with essential hypertension (EH; n=128); confirmed PA (n=16); adrenal cortical carcinoma (ACC; n=3); Addison's disease (AD; n=4) and phaeochromocytoma/paraganglioma (PPGL; n=5). In this population, an ARR cut-off at >37.4 pmol/mIU provided 100% diagnostic sensitivity, 96% specificity and positive likelihood ratio for PA of 23:1. When the ARR decision threshold was stratified according to gender, a cut-off of >26.1 pmol/mIU in men and >113.6 pmol/mIU in women resulted in diagnostic sensitivity and specificity of 100%. CONCLUSION: This study demonstrates that decision thresholds for PA should not only be method-specific but also gender-specific. However, given the small number of PA patients (n=16), particularly women (n=4), further validation through a prospective study with a larger PA cohort is required before the thresholds presented here could be recommended for routine clinical use.

Hypertension: The role of biochemistry in the diagnosis and management.

Hypertension is defined as a persistently elevated blood pressure ≥140/90mmHg. It is an important treatable risk factor for cardiovascular disease, with a high prevalence in the general population. The most common cause, essential hypertension, is a widespread disease - however, secondary hypertension is under investigated and under diagnosed. Collectively, hypertension is referred to as a "silent killer" - frequently it displays no overt symptomatology. It is a leading risk factor for death and disability globally, with >40% of persons aged over 25 having hypertension. A vast spectrum of conditions result in hypertension spanning essential through resistant, to patients with an overt endocrine cause. A significant number of patients with hypertension have multiple cardiovascular risk factors at the time of presentation. Both routine and specialised biochemical investigations are paramount for the evaluation of these patients and their subsequent management. Biochemical testing serves to identify those hypertensive individuals who are at higher risk on the basis of evidence of dysglycaemia, dyslipidaemia, renal impairment, or target organ damage and to exclude identifiable causes of hypertension. The main target of biochemical testing is the identification of patients with a specific and treatable aetiology of hypertension. Information gleaned from biochemical investigation is used to risk stratify patients and tailor the type and intensity of subsequent management and treatment. We review the approach to the biochemical investigation of patients presenting with hypertension and propose a diagnostic algorithm for work-up.

Screening for phaeochromocytoma and paraganglioma: impact of using supine reference intervals for plasma metanephrines with samples collected from fasted/seated patients.

Background The Endocrine Society Clinical Practice Guideline on Phaeochomocytoma and Paraganglioma recommends phlebotomy for plasma-free metanephrines with patients fasted and supine using appropriately defined reference intervals. Studies have shown higher diagnostic sensitivities using these criteria. Further, with seated-sampling protocols, for result interpretation, reference intervals that do not compromise diagnostic sensitivity should be employed. Objective To determine the impact on diagnostic performance and financial cost of using supine reference intervals for result interpretation with our current plasma-free metanephrines fasted/seated-sampling protocol. Methods We conducted a retrospective cohort study of patients who underwent screening for PPGL using plasma-free metanephrines from 2009 to 2014 at Galway University Hospitals. Plasma-free metanephrines were measured using liquid chromatography-tandem mass spectrometry. Supine thresholds for plasma normetanephrine and metanephrine set at 610 pmol/L and 310 pmol/L, respectively, were used. Results A total of 183 patients were evaluated. Mean age of participants was 53.4 (±16.3) years. Five of 183 (2.7%) patients had histologically confirmed PPGL (males, n=4). Using seated reference intervals for plasma-free metanephrines, diagnostic sensitivity and specificity were 100% and 98.9%, respectively, with two false-positive cases. Application of reference intervals established in subjects supine and fasted to this cohort gave diagnostic sensitivity of 100% with specificity of 74.7%. Financial analysis of each pretesting strategy demonstrated cost-equivalence (€147.27/patient). Conclusion Our cost analysis, together with the evidence that fasted/supine-sampling for plasma-free metanephrines, offers more reliable exclusion of PPGL mandates changing our current practice. This study highlights the important advantages of standardized diagnostic protocols for plasma-free metanephrines to ensure the highest diagnostic accuracy for investigation of PPGL.

Abnormal glucose tolerance post-gestational diabetes mellitus as defined by the International Association of Diabetes and Pregnancy Study Groups criteria.

OBJECTIVE: An increase in gestational diabetes mellitus (GDM) prevalence has been demonstrated across many countries with adoption of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria. Here, we determine the cumulative incidence of abnormal glucose tolerance among women with previous GDM, and identify clinical risk factors predicting this. DESIGN: Two hundred and seventy women with previous IADPSG-defined GDM were prospectively followed up for 5years (mean 2.6) post-index pregnancy, and compared with 388 women with normal glucose tolerance (NGT) in pregnancy. METHODS: Cumulative incidence of abnormal glucose tolerance (using American Diabetes Association criteria for impaired fasting glucose, impaired glucose tolerance and diabetes) was determined using the Kaplan-Meier method of survival analysis. Cox regression models were constructed to test for factors predicting abnormal glucose tolerance. RESULTS: Twenty-six percent of women with previous GDM had abnormal glucose tolerance vs 4% with NGT, with the log-rank test demonstrating significantly different survival curves (P<0.001). Women meeting IADPSG, but not the World Health Organization (WHO) 1999 criteria, had a lower cumulative incidence than women meeting both sets of criteria, both in the early post-partum period (4.2% vs 21.7%, P<0.001) and at longer-term follow-up (13.7% vs 32.6%, P<0.001). Predictive factors were glucose levels on the pregnancy oral glucose tolerance test, family history of diabetes, gestational week at testing, and BMI at follow-up. CONCLUSIONS: The proportion of women developing abnormal glucose tolerance remains high among those with IADPSG-defined GDM. This demonstrates the need for continued close follow-up, although the optimal frequency and method needs further study.

Evaluating the optimum rest period prior to blood collection for fractionated plasma free metanephrines analysis.

INTRODUCTION: The high diagnostic accuracy of plasma metanephrines (PMets) in the diagnosis of Phaeochromocytoma/Paraganglioma (PPGL) is well established. Considerable controversy exists regarding optimum sampling conditions for PMets. The use of reference intervals that do not compromise diagnostic sensitivity is recommended. However, the optimum rest period prior to sampling has yet to be clearly established. The aim of this study was to evaluate PMets concentrations in paired blood samples collected following 30 and 40 min seated-rest prior to sampling, in patients in whom it was clinically reasonable to suspect that PPGL may be present. DESIGN AND METHODS: A retrospective cross-sectional study design was used. PMets results from paired blood samples collected after 30 and 40 min seated-rest between January 2009 and June 2015 were recorded. Results were interpreted using reference intervals established in subjects seated and supine. RESULTS: A total of 410 patient results were eligible for analysis. There was no statistical difference between plasma normetanephrine (NMN) or metanephrine (MN) concentrations in samples collected following 30 and 40 min seated-rest in subjects with PPGL (n=11), post-resection of PPGL (n=20) or in whom PPGL was excluded (n=379). Using reference intervals established in the seated position, diagnostic sensitivity was 100% at 30 min and 90.9% at 40 min. Diagnostic specificity was approximately 95% at both time points. When supine reference intervals were used, diagnostic sensitivity was 100% and diagnostic specificity was reduced by ≈22% at both time points. CONCLUSION: Based on these data, we recommend at most 30 min continuous rest prior to sampling for PMets measurement.