Interleukin-6 producing pheochromocytoma/paraganglioma: case series from a tertiary referral centre for pheochromocytomas and paragangliomas

Introduction In addition to catecholamines, pheochromocytomas and paragangliomas (PPGL) may secrete interleukin-6 (IL-6). IL-6 contributes to the development of unusual symptoms, which may hinder the diagnosis. Patients and methods We report the clinical course and subsequent treatment of IL-6 producing PPGL in three patients from a single tertiary referral centre for PPGL patients in the Netherlands. Conclusion PPGL combined with persistent elevated inflammatory markers, either in the presence or absence of pyrexia, raised suspicion of IL-6 overproduction in these three patients. Although surgical resection of the tumour is the only curative treatment option, our case series adds to the accumulating evidence that alpha-blockers might be effective in these patients.Diabetes mellitus: pathophysiological changes and therap

Chronic nonbacterial osteomyelitis of the sternocostoclavicular region in adults: a single-center Dutch cohort study

Sternocostoclavicular hyperostosis (SCCH) is a rare autoinflammatory bone disorder caused by chronic nonbacterial osteomyelitis (CNO), which is associated with sclerosis and hyperostosis primarily affecting the sternum, the medial end of the clavicles, and the first ribs. Other areas of the axial skeleton may also be affected. The more severe synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is additionally associated with dermatoses and joint manifestations. This Dutch retrospective cross-sectional single-center cohort study characterizes the spectrum of clinical features in adult CNO/SCCH patients at the time of diagnosis. The only inclusion criteria was the availability of complete sets of clinical and imaging data systematically collected over three decades using in-house protocols. Data from 213 predominantly female patients (88%) with a median age of 36 years at presentation were studied. The mean diagnostic delay was 5 +/- 5 years. The main symptoms were chronic pain (92%), bony swelling (61%), and restricted shoulder girdle function (46%); 32% had palmoplantar pustulosis and 22% had autoimmune disease. The majority (73%) had isolated SCCH; 59 (27%) had additional localizations in vertebrae (19%), the mandible (9%), or both (2%); 4 had SAPHO. The prevalence of current or past smoking was high (58%), particularly for patients with palmoplantar pustulosis (76%). There was a significant relationship between delay in diagnosis and both the extent of affected skeletal sites (p = 0.036) and erythrocyte sedimentation rate levels (p = 0.023). Adult-onset CNO is characterized by distinctive clinical and radiological features, but diverse aspects of its spectrum are currently not fully captured by a comprehensive classification. Delayed diagnosis is still common and potentially associated with irreversible structural changes and debilitating chronic symptoms, increasing the burden of illness and negatively impacting on quality of life. It is hoped that findings from this study will dispel confusion about nomenclature and classification of adult-onset CNO and increase awareness of its distinctive clinical and radiological features, and thus facilitate early diagnosis and referral for treatment, which should positively impact prognosis by preventing disease progression, although this remains to be established. (c) 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.Diabetes mellitus: pathophysiological changes and therap

The association of glucose metabolism and kidney function in middle-aged adults

Background. Previous clinical studies have shown that various measures of glucose metabolism are associated with a risk of chronic kidney disease in different populations, but results were not consistent. In this study we assessed measures of glucose metabolism and their association with kidney function in a population-based study.Methods. The Netherlands Epidemiology of Obesity study is a population-based cohort study of middle-aged men and women. We categorized the study population according to glycaemic levels into normoglycaemia (reference group), pre-diabetes mellitus (pre-DM), known DM and newly diagnosed DM. Outcome variables were serum creatinine, estimated glomerular filtration rate (eGFR), glomerular hyperfiltration (defined as an eGFR >90th percentile; >102mL/min/1.73m(2)) and micro-albuminuria. We examined the association between measures of glucose metabolism [fasting glucose, haemoglobin A1c (HbA1c), fasting insulin, glucose area under the curve (AUC), insulin AUC, Homoeostatic Model Assessment of Insulin Resistance (HOMA-IR), HOMA of beta-cell function (HOMA-B) and disposition index] and measures of kidney function.Results. Of the total population (N=6338), 55% of participants were classified as normoglycaemic (reference), 35% as pre-DM, 7% as DM and 4% as newly diagnosed DM. Compared with the reference group, diagnosed and newly diagnosed DMs were associated with a slightly higher trend in eGFR {+2.1mL/min/1.73m(2) [95% confidence interval (CI) -0.2-4.4] and +2.7mL/min/1.73m(2) [95% CI -0.3-5.7], respectively}. A 1% higher HbA1c was associated with increased odds of hyperfiltration [odds ratio (OR) 1.41 (95% CI 1.06-1.88)]. Higher levels of fasting plasma glucose, AUC glucose and HOMA-B were associated with hyperfiltration. Fasting insulin, AUC insulin and HOMA-IR were not associated with hyperfiltration. The OR of microalbuminuria was 1.21 (95% CI 1.04-1.42) per mmol/L higher fasting glucose concentrations.Conclusions. Both fasting and post-prandial glucose and HOMA-B, but not measures of insulin resistance, were associated with glomerular hyperfiltration, while fasting glucose was also associated with microalbuminuria.Nephrolog

Clinical aspects of the relation between diabetes mellitus and kidney disease: From hyperfiltration to dialysis

Patients with diabetes mellitus have the highest mortality risk within the dialysis population. The presence of chronic kidney disease (CKD) in patients with diabetes is also strongly related to impaired quality of life. Research is warranted to prevent progressive diabetic kidney disease, improve quality of life and reduce mortality in this vulnerable population. In order to improve survival, more knowledge about which patients have the highest mortality risk and which risk factors and co-morbid conditions contribute to this increased mortality risk is essential. In this thesis we focussed on clinical aspects of the relation between diabetes mellitus and kidney disease, from hyperfiltration to dialysis. In chapter 2 we assessed many different measures of glucose metabolism and their association with kidney function among Dutch middle-aged adults. In chapter three and four we compared survival of dialysis patients with diabetes mellitus as underlying cause of the renal failure versus dialysis patients with diabetes mellitus as a co-morbid condition only. In chapter five we aimed to develop a prediction model for 1-year mortality in diabetic dialysis patients. Furthermore in chapter six we compared survival after amputation in diabetic dialysis patients to non-diabetic dialysis patients.LUMC / Geneeskund

Clinical aspects of the relation between diabetes mellitus and kidney disease: From hyperfiltration to dialysis

Patients with diabetes mellitus have the highest mortality risk within the dialysis population. The presence of chronic kidney disease (CKD) in patients with diabetes is also strongly related to impaired quality of life. Research is warranted to prevent progressive diabetic kidney disease, improve quality of life and reduce mortality in this vulnerable population. In order to improve survival, more knowledge about which patients have the highest mortality risk and which risk factors and co-morbid conditions contribute to this increased mortality risk is essential. In this thesis we focussed on clinical aspects of the relation between diabetes mellitus and kidney disease, from hyperfiltration to dialysis. In chapter 2 we assessed many different measures of glucose metabolism and their association with kidney function among Dutch middle-aged adults. In chapter three and four we compared survival of dialysis patients with diabetes mellitus as underlying cause of the renal failure versus dialysis patients with diabetes mellitus as a co-morbid condition only. In chapter five we aimed to develop a prediction model for 1-year mortality in diabetic dialysis patients. Furthermore in chapter six we compared survival after amputation in diabetic dialysis patients to non-diabetic dialysis patients.</p

Predicting Mortality in Patients with Diabetes Starting Dialysis

Nephrolog

Mortality after amputation in dialysis patients is high but not modified by diabetes status

Background: Survival among dialysis patients with diabetes mellitus (DM) is inferior to survival of non-diabetic dialysis patients, probably due to the higher prevalence of diabetes-related comorbid conditions. One could hypothesize that these comorbid conditions also contribute to a decreased survival after amputation in diabetic patients compared with non-diabetic patients on dialysis.Methods: Data were collected from the Netherlands Cooperative Study on the Adequacy of Dialysis, a multicentre, prospective cohort study in which new patients with end-stage renal disease were monitored until transplantation or death. Amputation rates (incident cases) were calculated in patients with and without DM. The primary endpoint was all-cause survival after first amputation during dialysis therapy in diabetic patients compared with non-diabetic dialysis patients with an amputation. This was formally assessed using interaction analysis (Poisson regression).Results: During follow-up (mean duration 2.9 years), 50 of the 413 diabetic patients had a new amputation (12.1%), compared with 20 of 1553 non-diabetic patients (1.2%). Amputation rates/1000 person-years were 47.9 [95% confidence interval (CI) 36.3-63.2] and 4.1 (95% CI 2.7-6.4), respectively, for diabetic patients and non-diabetic patients. Amputation increased mortality risk more than 4-fold in patients without diabetes [hazard ratio (HR) 4.6 (95% CI 2.8-7.6)] as well as in patients with diabetes [HR 4.6 (95% CI 3.3-6.4)]. No formal interaction between diabetes and amputation was found (P = 0.12).Conclusions: Amputation in dialysis patients is associated with a 4-fold increased mortality risk; this mortality risk was similar for diabetes and non-diabetes patients. Importantly, the risk for amputation is 10-fold higher in DM compared with non-diabetic dialysis patients.Vascular Surger