Etomidate in the management of severe Cushing's disease and MRSA bacteraemia in a district general hospital in the United Kingdom.

SUMMARY: We report our experience on managing a case of florid Cushing's disease with Methicillin-resistant Staphylococcus aureus (MRSA) sepsis using intravenous etomidate in the intensive care unit of a UK district general hospital. LEARNING POINTS: Severe Cushing's syndrome is associated with high morbidity and mortality. Etomidate is a safe and effective medical therapy to rapidly lower cortisol levels even in the context of severe sepsis and immunosuppression. Etomidate should ideally be administered in an intensive care unit but is still feasible in a district general hospital. During treatment with etomidate, accumulation of serum 11ß-deoxycortisol (11DOC) levels can cross-react with laboratory cortisol measurement leading to falsely elevated serum cortisol levels. For this reason, serum cortisol measurement using a mass spectrometry assay should ideally be used to guide etomidate prescription.

Assessment of global long interspersed nucleotide element-1 (LINE-1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2DM) individuals.

INTRODUCTION: Recent studies have indicated that methylation of the LINE-1 elements is associated with an increased risk of worsening carbohydrate metabolism. It has been shown that overall DNA methylation of LINE-1 elements could be considered as a risk factor for T2DM and its complications, independent of other established risk factors. METHODS: A total of 794 T2DM individuals from Salford, UK were included in this study (60% men n = 470). All patients had clinical and metabolic variables measured in 2002 (baseline outcomes) and annually through to 2016. Global LINE-1 DNA methylation was measured at four CpG sites. The QIAGEN PyroMark Q96 MD pyrosequencer was used to quantify methylation. RESULTS: The overall mean ± SD global LINE-1 methylation was 75.81 ± 3.25%. Cross-sectional linear regression analysis at baseline year 2002 showed that LINE-1 methylation was a significant predictor of diastolic BP (adjusted beta coefficient ß = -0.25), estimated glomerular filtration rate (eGFR) (ß = -0.48) and cholesterol HDL ratio (ß = -0.04). A 10% increase in LINE-1 methylation was associated with a lower diastolic BP by 2.5 mm Hg, a lower eGFR by 4.8 ml/min/1.73 m2 and decreased cholesterol/HDL ratio by 0.4 mmol/L. Longitudinal analysis over the 14-year-follow-up periods showed that global LINE-1 methylation at baseline was associated with lower BMI in women [ß = -0.25] and lower cholesterol: HDL ratio [ß = -0.07]. A 10% increase in LINE-1 methylation was associated with reduction in BMI by 2.5 kg/m2 in women and reduction in cholesterol:HDL ratio by 0.7 mmol/L. CONCLUSION: In a 14-year longitudinal cohort of T2DM individuals, relations between global LINE-1 DNA methylation status and specific metabolic markers were seen. Also, a higher degree of DNA methylation was predictive of less weight gain over time in women.

Pregnancy Following Bariatric Surgery-Medical Complications and Management.

Bariatric surgery is most commonly carried out in women of childbearing age. Whilst fertility rates are improved, pregnancy following bariatric surgery poses several challenges. Whilst rates of many adverse maternal and foetal outcomes in obese women are reduced after bariatric surgery, pregnancy is best avoided for 12-24 months to reduce the potential risk of intrauterine growth retardation. Dumping syndromes are common after bariatric surgery and can present diagnostic and therapeutic challenges in pregnancy. Early dumping occurs due to osmotic fluid shifts resulting from rapid gastrointestinal food transit, whilst late dumping is characterized by a hyperinsulinemic response to rapid absorption of simple carbohydrates. Dietary measures are the mainstay of management of dumping syndromes but pharmacotherapy may sometimes become necessary. Acarbose is the least hazardous pharmacological option for the management of postprandial hypoglycemia in pregnancy. Nutrient deficiencies may vary depending on the type of surgery; it is important to optimize the nutritional status of women prior to and during pregnancy. Dietary management should include adequate protein and calorie intake and supplementation of vitamins and micronutrients. A high clinical index of suspicion is required for early diagnosis of surgical complications of prior weight loss procedures during pregnancy, including small bowel obstruction, internal hernias, gastric band erosion or migration and cholelithiasis.

Screening for hypogonadism in diabetes 2008/9: results from the Cheshire Primary Care cohort.

AIM: There is increasing awareness of hypogonadism in men with type 2 diabetes but limited data from Primary Care. SUBJECTS AND METHODS: The anonymised records of 6457 male patients aged 18-80 years with diabetes were accessed. Within the last 2 years 391 men (6.0% of total) underwent measurement of serum testosterone. Data search was performed through the centralised data facility afforded by EMIS®, the majority GP systems provider in Cheshire. RESULTS: 4.4% of type 2 diabetes men screened were frankly hypogonadal with a serum total testosterone of less than 8.0 nmol/l. For borderline hypogonadism (serum total testosterone 8-11.99 nmol/l) the proportion of type 2 diabetes men rose to 32.1%. Age adjusted mean (geometric) testosterone was lower in men with type 2 diabetes (13.6 nmol/l 95%CI: 13.1-14.2) vs type 1 diabetes (17.9 nmol/l; 95%CI 15.2-21.0), F=10.3; p=0.0014. For those screened age adjusted body mass index (BMI) was greater in type 2 diabetes at 30.7 (30.1-31.3) vs 28.4 (26.1-30.6)kg/m(2) in type 1 diabetes (F=4.3; p=0.04). Multiple linear regression analysis indicated that there was a statistically significant interaction (P=0.014) between BMI and diabetes type in their relation with log testosterone. For persons with type 1 DM and type 2 DM, testosterone can be expected to decrease by 6% (P=0.002) and by 1% (P=0.002) respectively, for every one unit increment in BMI. CONCLUSIONS: There is manifestly a subset of men with diabetes and androgen deficiency who could benefit from testosterone replacement. BMI has an independent influence on androgen status.