Autonomic regulation in different hypertensive phenotypes - the HELIUS study.

Background: Hypertension can be classified into different phenotypes based on systolic and diastolic blood pressure (BP) that carry a different prognosis and may therefore be differently associated with sympathetic activity. We assessed the association between cardiac autonomic function determined from continuous finger BP recordings and hypertensive phenotypes. Methods: We included 10,221 individuals aged between 18-70 years from the multi-ethnic HELIUS study. Finger BP was recorded continuously for 3-5 minutes from which cross-correlation baroreflex sensitivity (xBRS) and heart rate variability (HRV) were determined. Hypertension was classified into isolated systolic (ISH; ≥140/<90), diastolic (IDH; <140/≥90) and combined systolic and diastolic hypertension (SDH; ≥140/≥90). Differences were assessed after stratification by age (younger: ≤40, older: >40 years) and sex, using regression with correction for relevant covariates. For xBRS, values were log-transformed. Results: In younger adults with ISH, xBRS was comparable to normotensive individuals in men (ratio 0.92; 95%CI 0.84-1.01) and women (1.00; 95%CI 0.84-1.20), while xBRS was significantly lower in IDH and SDH (ratios between 0.67 and 0.80). In older adults, all hypertensive phenotypes had significantly lower xBRS compared to normotensives. We found a similar pattern for HRV in men, while in women HRV did not differ between phenotypes. Conclusions: In younger men and women ISH is not associated with a shift towards increased sympathetic control, while IDH and SDH in younger and all hypertensive phenotypes in older participants were associated with increased sympathetic control. This suggests that alterations in autonomic regulation could be a contributing factor to known prognostic disparities between hypertensive phenotypes.

Hypertension can be classified into different phenotypes based on systolic and diastolic blood pressure (BP) that carry a different prognosis. Impaired autonomic regulation is important in the pathogenesis of hypertension and independently associated with adverse cardiovascular outcomes.We analyzed 3-5 minutes continuous non-invasive finger blood pressure recordings performed in over 10.000 individuals participating in the HELIUS cohort study. From these measurements, short term heart rate variability (HRV) and cross correlation baroreflex sensitivity (xBRS) were determined using an automatic algorithm.In our analysis we observed pronounced differences in the relation between autonomic regulation and hypertensive phenotypes that depend on age and sex.Younger men and women (age 18-40 years) with isolated systolic hypertension had similar values for xBRS and HRV compared to normotensives, while isolated diastolic hypertension was associated with a shift towards increased sympathetic control. In contrast to our findings in younger individuals, all hypertensive phenotypes were associated with increased sympathetic control in older participants (age 40-70 years).This supports earlier studies showing prognostic differences and suggests that alterations in sympathovagal balance could be a contributing factor to the disparities between phenotypes.

Automated analysis of finger blood pressure recordings provides insight in determinants of baroreflex sensitivity and heart rate variability-the HELIUS study.

Sympathovagal balance is important in the pathogenesis of hypertension and independently associated with mortality. We evaluated the value of automated analysis of cross-correlation baroreflex sensitivity (xBRS) and heart rate variability (HRV) and its relationship with clinical covariates in 13,326 participants from the multi-ethnic HELIUS study. Finger blood pressure (BP) was continuously recorded, from which xBRS, standard deviation of normal-to-normal intervals (SDNN), and squared root of mean squared successive difference between normal-to-normal intervals (RMSDD) were determined. A subset of 3356 recordings > 300 s was used to derive the minimally required duration by comparing shortened to complete recordings, defined as intraclass correlation (ICC) > 0.90. For xBRS and SDNN, 120 s and 180 s were required (ICC 0.93); for RMSDD, 60 s (ICC 0.94) was sufficient. We included 10,252 participants (median age 46 years, 54% women) with a recording > 180 s for the regression. xBRS, SDNN, and RMSDD decreased linearly up to 50 years of age. For xBRS, there was a signification interaction with sex, with for every 10 years a decrease of 4.3 ms/mmHg (95%CI 4.0-4.6) for men and 5.9 ms/mmHg (95%CI 5.6-6.1) for women. Using splines, we observed sex-dependent nonlinearities in the relation with BP, waist-to-hip-ratio, and body mass index. Future studies can help unravel the dynamics of these relations and assess their predictive value. Panel 1 depicts automatic analysis and filtering of finger BP recordings, panel 2 depicts computation of xBRS from interpolated beat to beat data of systolic BP and interbeat interval, and (IBI) SDNN and RMSDD are computed directly from the filtered IBI dataset. Panel 3 depicts the results of large-scale analysis and relation of xBRS with age, sex, blood pressure and body mass index.

Intestinal microbiota and diabetic kidney diseases: the Role of microbiota and derived metabolites inmodulation of renal inflammation and disease progression.

Diabetic kidney disease (DKD) represents a growing public health burden and is the leading cause of end-stage kidney diseases. In recent years, host-gut microbiota interactions have emerged as an integral part for host homeostasis. In the context of nephropathies, mounting evidence supports a bidirectional microbiota-kidney crosstalk, which becomes particularly manifest during progressive kidney dysfunction. Indeed, in chronic kidney disease (CKD), the "healthy" microbiota structure is disrupted and intestinal microbes produce large quantities of uremic solutes responsible for renal damage; on the other hand, the uremic state, fueled by reduced renal clearance, causes shifts in microbial metabolism and composition, hence creating a vicious cycle in which dysbiosis and renal dysfunction are progressively worsened. In this review, we will summarize the evidence from clinical/experimental studies concerning the occurrence of gut dysbiosis in diabetic and non-diabetic CKD, discuss the functional consequences of dysbiosis for CKD progression and debate putative therapeutic interventions targeting the intestinal microbiome.

Soluble syndecan-1 and glycosaminoglycans in preeclamptic and normotensive pregnancies.

Preeclampsia, an important cause of maternal and fetal morbidity and mortality, is associated with increased sFLT1 levels and with structural and functional damage to the glycocalyx contributing to endothelial dysfunction. We investigated glycocalyx components in relation to preeclampsia in human samples. While soluble syndecan-1 and heparan sulphate were similar in plasma of preeclamptic and normotensive pregnant women, dermatan sulphate was increased and keratan sulphate decreased in preeclamptic women. Dermatan sulphate was correlated with soluble syndecan-1, and inversely correlated with blood pressure and activated partial thromboplastin time. To determine if syndecan-1 was a prerequisite for the sFlt1 induced increase in blood pressure in mice we studied the effect of sFlt1 on blood pressure and vascular contractile responses in syndecan-1 deficient and wild type male mice. The classical sFlt1 induced rise in blood pressure was absent in syndecan-1 deficient mice indicating that syndecan-1 is a prerequisite for sFlt1 induced increase in blood pressure central to preeclampsia. The results show that an interplay between syndecan-1 and dermatan sulphate contributes to sFlt1 induced blood pressure elevation in pre-eclampsia.

New diagnostic and treatment strategies in renal artery stenosis: a promising pursuit or disappointment foretold?

Clinical management of renal artery stenosis has seen a major shift, after randomised clinical trials have shown no group benefit of endovascular intervention relative to optimal medical control. However, the inclusion criteria of these trials have been criticised for focusing on a subset of patients with atherosclerotic renal artery stenosis where intervention was unlikely to be beneficial. Moreover, new imaging and computational techniques have become available, which have the potential to improve identification of patients that will respond to interventional treatment. This review addresses the challenges associated with clinical decision making in patients with renal artery stenosis. Opportunities for novel diagnostic techniques to improve patient selection are discussed, along with ongoing Dutch studies and network initiatives that investigate these strategies.

IgG4:IgG RNA ratio differentiates active disease from remission in granulomatosis with polyangiitis: a new disease activity marker? A cross-sectional and longitudinal study.

OBJECTIVES: An important limitation in granulomatosis with polyangiitis (GPA) is the lack of disease activity markers. Immunoglobulin G4-positive (IgG4+) B cells and plasma cells are implicated in the pathogenesis of GPA. We hypothesized that the presence of these cells in peripheral blood could serve as disease activity parameter in GPA. METHODS: We included 35 proteinase 3-antineutrophil cytoplasmic antibodies-positive patients with GPA in a cross-sectional study. Active disease was defined as Birmingham Vasculitis Activity Score (BVAS) ≥ 3 (n = 15), remission as BVAS of 0 (n = 17), and low disease activity (LDA) as BVAS of 1-2 and clinical remission (n = 3). Healthy subjects (n = 10), patients with systemic lupus erythematosus (n = 24), and patients with rheumatoid arthritis (n = 19) functioned as control subjects. An additional longitudinal study was performed in ten patients with GPA. Using a validated qPCR test, we measured the IgG4:IgG RNA ratio in all groups and compared the results with known biomarkers. RESULTS: The median qPCR score was higher in active GPA (21.4; IQR 12.1-29.6) than in remission/LDA (3.3; IQR 1.6-5.6) (Mann-Whitney U test, p < 0.0001) and outperformed other known disease activity parameters in detecting activity. A cutoff qPCR score of 11.2% differentiated active disease from remission/LDA accurately (AUC 0.993). The qPCR test correlated well with the BVAS (Spearman r = 0.77, p < 0.0001). In the longitudinal study, a decrease in BVAS correlated with qPCR score reduction (paired t test, p < 0.05). CONCLUSIONS: The IgG4:IgG RNA ratio in GPA accurately distinguishes active disease from remission and correlates well with disease activity in these single-center studies. If these results are confirmed in larger longitudinal studies, this test might help to steer treatment decisions in patients with GPA.

[Limits to the treatment of hypertension]. / Grenzen aan de behandeling van hypertensie.

According to the 2011 Dutch guideline on Cardiovascular risk management 1 in 5 hypertensive patients are eligible for blood pressure lowering treatment. The Dutch guideline recommends striving for a systolic blood pressure (SBP) of < 140 mmHg in adult patients who have no cardiovascular disease or diabetes mellitus, while the recent American guideline now recommends an SBP target value of < 130 mmHg for all adult patients. An important reason for using a stricter SBP target value are the results of randomised studies and meta-analyses that looked at the effect of intensive antihypertensive therapy on the risk of mortality and cardiovascular disease. Based on the literature, there appears to be sufficient evidence that intensive antihypertensive therapy (SBP target value of < 130 mmHg) is useful in patients with cardiovascular disease and in patients with high cardiovascular risk. Currently, there is insufficient evidence that intensive antihypertensive therapy is useful in patients who have diabetes mellitus or who are over 80 years old.

Prevalence and reproducibility of differences between home and ambulatory blood pressure and their relation with hypertensive organ damage.

Home and ambulatory blood pressure (BP) better predict cardiovascular disease than office BP, but are not interchangeable. We hypothesised that home BP may be higher than office BP because of anticipatory reactions to self-measurement and studied prevalence and reproducibility of incremental differences between home and daytime ambulatory BP and their relation with hypertensive organ damage. A total of 176 participants (mean age 57.1±12.8 years, 43.2% female) measured their BP for 2 weeks and received a 24-h ambulatory BP in between. Hypertensive organ damage was assessed by urinary albumin-to-creatinine ratio and electrocardiographic criteria for left ventricular hypertrophy. Thresholds of 10/5 and 20/10 mm Hg were used to define relevant systolic/diastolic differences between home and ambulatory BP. A higher home compared to ambulatory BP was present in 92 (52.3%) and 35 (19.1%) participants, while lower home BP values were present in 36 (20.4%) and 8 (4.5%) subjects for differences ⩾10/5 and ⩾20/10 mm Hg. Participants with higher home than ambulatory BP differences were older, had higher body mass index, higher office BP, more antihypertensive medication and lower glomerular filtration rate (P<0.01). Differences between home and ambulatory BP were highly reproducible (r=0.80 and 0.67 for systolic and diastolic BP, P<0.001). Both home and ambulatory BPs were associated with organ damage, but their difference was not. Many patients have a significantly higher home than ambulatory BP. Differences between home and ambulatory BP are reproducible, but not associated with hypertensive organ damage. Our findings suggest that ambulatory BP remains the standard of reference when positive differences between home and ambulatory BP exist.

Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry.

BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to efficacy, safety, predictors for success and long-term effects. To answer these important questions, we initiated a Dutch RDN registry aiming to collect data from all RDN procedures performed in the Netherlands. METHODS: The Dutch RDN registry is an ongoing investigator-initiated, prospective, multicentre cohort study. Twenty-six Dutch hospitals agreed to participate in this registry. All patients who undergo RDN, regardless of the clinical indication or device that is used, will be included. Data are currently being collected on eligibility and screening, treatment and follow-up. RESULTS: Procedures have been performed since August 2010. At present, data from 306 patients have been entered into the database. The main indication for RDN was hypertension (n = 302, 99%). Patients had a mean office blood pressure of 177/100 (±29/16) mmHg with a median use of three (range 0-8) blood pressure lowering drugs. Mean 24-hour blood pressure before RDN was 157/93 (±18/13) mmHg. RDN was performed with different devices, with the Simplicity™ catheter currently used most frequently. CONCLUSION: Here we report on the rationale and design of the Dutch RDN registry. Enrolment in this investigator-initiated study is ongoing. We present baseline characteristics of the first 306 participants.

Placental expression of heparan sulfate 3-O-sulfotransferase-3A1 in normotensive and pre-eclamptic pregnancies.

INTRODUCTION: The endothelial glycocalyx, consisting of membrane-bound proteoglycans and attached glycosaminoglycans plays an important role in vascular homeostasis. We aimed to assess whether glycocalyx mRNA transcripts are differentially expressed in placental tissue of pre-eclamptic and normotensive women. METHODS: We evaluated the expression of transcripts encoding for proteins involved in glycocalyx synthesis and degradation using a microarray analysis of placental mRNA obtained from pre-eclamptic and normotensive women. Participants were recruited from the department of obstetrics at a university hospital in Amsterdam, The Netherlands. The most prominent differentially expressed transcript was validated by qPCR on 112 additional placenta samples. RESULTS: Of 78 preselected genes involved in glycocalyx synthesis and degradation, only HS3ST3A1 mRNA was differentially expressed in placental tissue obtained from pre-eclamptic women (N = 12) compared to normotensive women (N = 12, fold change = 0.61, p = 0.02). Validation with qPCR in additional placental samples of 64 normotensive and 48 pre-eclamptic women confirmed that normalized mRNA expression of HS3ST3A1 was decreased by 27% (95% CI 14%-41%) in placental tissue obtained from pre-eclamptic compared to normotensive women (p < 0.001). HS3ST3A1 expression was positively correlated with neonatal birth weight in normotensive women (r = 0.35, p < 0.01) and inversely correlated with mean arterial pressure of women with pre-eclampsia (r = 0.32, p = 0.02). CONCLUSIONS: The mRNA expression of HS3ST3A1, which encodes for a 3-O sulfating enzyme of heparan sulfate (3-OST-3A1), is decreased in pre-eclamptic placental tissue. Expression of this glycocalyx synthesis transcript is correlated with maternal blood pressure and neonatal birth weight, suggesting a possible role in pre-eclampsia-associated placental dysfunction.

Dutch guideline for the management of hypertensive crisis -- 2010 revision.

Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.

Value of retinal examination in hypertensive encephalopathy.

The presence of grade III or IV hypertensive retinopathy (HRP) is considered to distinguish hypertensive urgencies from emergencies. However, case-reports suggest that these retinal changes may be lacking in patients with hypertensive encephalopathy. To assess the frequency of grade III and IV retinopathy in this hypertensive emergency, we conducted a retrospective cohort study. We retrieved 162 patients with malignant hypertension and 34 patients (17%) fulfilled the predefined criteria for hypertensive encephalopathy. Data on retinal examination were incomplete for 6 patients (18%), thus leaving 28 patients who were analysed for the presence or absence of grade III and IV HRP. In 9 (32%) patients with hypertensive encephalopathy, grade III or IV HRP was absent, 11 (39%) patients presented with grade III and 8 (29%) patients with grade IV retinopathy. Patients without retinal abnormalities were on average 13 years younger (P=0.05), more often black (P=0.02) and displayed lower blood pressure (BP) values (P=0.04 for systolic and diastolic BP). A substantial proportion of patients with hypertensive encephalopathy lack grade III or IV HRP. This suggests that the decision to admit these patients should not only rely on the presence of grade III and IV retinopathy alone, but should also include a careful neurological examination.

[Severe anaemia caused by Human Parvovirus B19 infection in a patient with autoimmune haemolytic anaemia and a B-cell non-Hodgkin lymphoma]. / Ernstige anemie door infectie met het Humaan parvovirus B19 bij een patiënt met een auto-immuun-hemolytische anemie en een B-cel-non-hodgkinlymfoom.

A 65-year-old man with a 15-year history of 'leukemicised' low-grade lymphocytic B-cell non-Hodgkin lymphoma with a low-titre of IgM kappa paraprotein was admitted with severe anaemia and reticulocytopenia. Treatment with prednisone and chlorambucil had been started two weeks earlier because of a recently diagnosed Coombs-positive haemolytic anaemia. He also received a blood transfusion at that time. During his stay in the hospital, a crista biopsy was performed that revealed no signs of bone marrow suppression but markedly enlarged pro-erythroblasts. Although a serologic test for Human Parvovirus-B19 was negative, PCR showed a sharply increased viral load with more than 1 x 10(11) copies/ml, compatible with a primary parvovirus infection. In retrospect, an earlier transfusion of blood that had not been screened for parvovirus was probably the culprit. Treatment with human immunoglobulin was effective in lowering the viral load and normalising the haemoglobin. This case illustrates that reticulocytopenia in a patient with a haematologic disorder accompanied by a shortened erythrocyte life-span is suggestive for a primary parvovirus infection, especially following a recent transfusion. To prevent transmission of Human Parvovirus B19 via blood transfusion, the Health Council of the Netherlands published a guideline indicating that patients at high risk for a complicated infection with Human Parvovirus B19 should be given 'virus-free' blood products.

[Clinical reasoning and decision making in practice. A 39-year-old woman with somnolence, hypertension and haemolysis]. / Klinisch denken en beslissen in de praktijk. Een 39-jarige vrouw met sufheid, hypertensie en hemolyse.

A 39-year-old woman was admitted with somnolence, severe hypertension and thrombotic microangiopathy. Both malignant hypertension and thrombotic thrombocytopenic purpura (TTP) were considered. Immediate therapy was instituted to treat both diseases because of severe clinical deterioration. Eventually, TTP was considered less likely due to the presence of grade IV hypertensive retinopathy (papilloedema and soft exudates) and a normal Von Willebrand factor-cleaving protease level. Differentiating TTP from malignant hypertension can be difficult as both diseases have similar clinical, laboratory and radiological features. In both diseases, hypertension, thrombotic microangiopathy and encephalopathy with white-matter lesions in the posterior regions of the brain may be apparent. Funduscopic abnormalities consistent with grade III and IV hypertensive retinopathy are rare in TTP, as are normal levels ofVon Willebrand factor-cleaving protease. Therefore, the diagnosis TTP was considered less likely and plasmapheresis was stopped. Hereafter, the laboratory values pointing towards haemolysis remained normal with adequate blood pressure control supporting the rejection of TTP as the cause of the symptoms.

[Clinical reasoning and decision making in practice: a 30-year-old man with unexplained coma]. / Klinisch denken en beslissen in de praktijk. Een 30-jarige man met een onverklaard coma.

A 30-year-old man known to have a factor-IX deficiency was presented at the emergency department with unexplained coma. After immediate treatment with factor IX, a CT-scan of the brain revealed no intracerebral haemorrhage. However, blood tests showed severe hyponatraemia, low serum osmolarity and high urine-sodium excretion consistent with the Syndrome of Inappropriate Antiduretic Hormone Secretion (SIADH). Therapy with hypertonic saline was instituted resulting in a gradual rise in the serum-sodium concentration. The cause of the hyponatraemia however remained unclear. After repeat history taking the patient mentioned the use of desmopressin for nocturia. Hyponatraemia as a complication of desmopressin use occurs in 8% of adult patients treated for nocturia. Direct availability of a patient's drug history, by means of an electronic record for instance, could avoid unnecessary tests and delay in diagnosis.

[Atenolol or metoprolol as beta-blocker in the treatment of hypertension]. / Atenolol en metoprolol beide geschikt als beta-blokker voor de behandeling van hypertensie.

Recently the guideline committee of the Dutch College of General Practitioners advocated the use of metoprolol instead of atenolol in patients with an indication for beta-blockers. This recommendation was based on a recent meta-analysis in The Lancet in which no effect was observed in favour ofatenolol compared with placebo on all-cause mortality, cardiovascular mortality and myocardial infarction. Atenolol also had a higher total mortality and stroke risk compared with other antihypertensive agents. Apart from the presence of statistical heterogeneity and the inappropriate use of a fixed-effect model, the studies referred to in this meta-analysis were also clinically heterogeneous. Furthermore, in most studies, only older patients were included. In older patients with hypertension, it is known that beta-blockers are less effective than diuretics or calcium antagonists. Comparative trials between atenolol and metoprolol in the treatment of hypertension have not been performed with regard to cardiovascular endpoints. We conclude that there is no evidence that atenolol is better or worse than metoprolol in the treatment of the hypertensive patient. For the treatment of patients with heart failure, however, lipophilic beta-blockers such as metoprolol may be preferred, as these drugs have been more thoroughly evaluated for this indication.

[Clinical reasoning and decision making in practice. Fever, purpura and hemiparesis in a 29-year old female]. / Klinisch denken en beslissen in de praktijk. Koorts, purpura en krachtsverlies bij een 29-jarige vrouw.

A 29-year-old female was admitted with fever, purpura and hemiparesis. She was treated for meningococcal sepsis after a Gram stain of a purpuric lesion showed Gram-negative diplococci. CT scan of the brain revealed multiple haemorrhagic lesions with obliteration of the sulci and basal cisterns. In the course of the disease she developed an acute myocardial infarction. Besides wall motion abnormalities, echocardiography revealed a bicuspid aortic valve with a vegetation on one of its cusps. Despite these findings, both the doctors who were involved in the treatment of this patient and the consulted physician in this article failed to reject the diagnosis 'meningococcal sepsis' and to replace it with a more likely diagnosis, namely Staphylococcus aureus endocarditis. The patient died one day after admission due to transtentorial herniation. Although purpuric lesions are common in meningococcal sepsis, they are not specific for this disease. The false-positive result of the Gram stain resulted in a process known as 'premature closure': the diagnosis of meningococcal sepsis was accepted before it was fully verified. In this case, the consequence was that other diagnostic tests and symptoms were misinterpreted with the result that inappropriate antibiotic therapy was instituted.

[Clinical thinking and decision making in practice. Unexplained rectal blood loss in a patient with multiple endocrine neoplasia type 1 syndrome]. / Klinisch denken en beslissen in de praktijk. Onverklaard rectaal bloedverlies bij een patiënte met het multipele-endocriene-neoplasie-1-syndroom.

A 55-year-old woman, known with multiple endocrine neoplasia (MEN) type 1, had rectal bleeding and later haematemesis but colonoscopy and gastroduodenoscopy revealed no abnormalities. Due to the normal results for serum gastrin concentration, gastroduodenoscopy and CT scanning of the pancreas, Zollinger-Ellison syndrome was considered to be less likely. Yet the diagnosis could be established on the basis of persistent symptoms and a positive somatostatin receptor scintigraphy. The patient was treated with high doses of a proton pump inhibitor and temporary tube feeding due to weight loss. Follow-up will take place at the endocrinology outpatients' department. Zollinger-Ellison syndrome is a relatively common feature of patients with MEN-1. The diagnosis and localisation of the gastrinoma can be difficult: serum gastrin concentrations can be normal and the sensitivity of CT scanning is low. The primary aim of treating gastrinoma is to control gastric acid hypersecretion by means of high doses of a proton pump inhibitor. The question as to whether surgery is indicated remains controversial.