European Endocrinology最新文献

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine tumour deriving from the adrenal cortex. A correct therapeutic strategy requires a multidisciplinary approach between endocrinologist, surgeon and oncologist. Surgery is the mainstay treatment in ACC while mitotane, deriving from the insecticide dichloro-diphenyl-trichloro-ethane, is the main base of the medical treatment of ACC in consideration of its adrenocytolitic activity. However, the use of mitotane as adjuvant therapy is still controversial, also in consideration of the retrospective nature of several studies. A prospective randomised trial (ADIUVO), recruiting patients with low-intermediate risk of recurrence, is evaluating the utility of adjuvant treatment with mitotane in this setting. The therapeutic response is observed with plasma levels of mitotane >14 mg/L. However, the major difficulty in the management of mitotane treatment is related to side effects and to the risk of toxicity, which is related to plasmatic levels >20 mg/L, that is considered the upper limit of the therapeutic window. Mitotane therapy results in adrenal insufficiency, and glucocorticoid replacement therapy has to be administered at higher doses than those used in other aetiologies of primary adrenal insufficiency. Furthermore, other endocrine side effects related to mitotane should be considered, in particular on thyroid hormone and testosterone metabolism. Waiting for new medical strategies on molecular targets, it will be mandatory to optimise the current knowledge by prospective trials and, in consideration of the rarity of the disease, collaborative studies between endocrinologists and oncologists are necessary.

In patients with type 2 diabetes (T2D), the excretion of glucose by the kidney with sodium-glucose cotransporter 2 (SGLT2) inhibitors lowers glycosylated haemoglobin (HbA1c) levels, decreases body weight and visceral adiposity, as well as improving cardio-renal haemodynamics. Currently, four SGLT2 inhibitors are approved in the US and Europe to improve glycaemic control - empagliflozin, dapagliflozin, canagliflozin, and ertuglifozin. Recently, the SGLT2 inhibitor empagliflozin was approved by the FDA for the reduction of cardiovascular (CV) death in adults with T2D and CV disease (CVD). This approval was based on the findings of the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) study, which was the first study to show a significant reduction of a primary CV endpoint with a glucose-lowering agent. In this study, the primary outcome (CV mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was reduced by empagliflozin (10.5%; 490/4,687) compared with placebo (12.1%; 282/2,333); hazard ratio (HR), 0.86 (95% confidence interval [CI]: 0.74, 0.99). The primary outcome was driven by a large reduction of CV mortality (relative risk reduction [RRR], 38%). Empagliflozin also reduced all-cause mortality (RRR, 32%). Furthermore, empagliflozin reduced the adjudicated outcome of heart failure (HF) hospitalisation by 35% (HR, 0.65; 95% CI: 0.50, 0.85). Other non-adjudicated measures of HF outcomes were similarly reduced including investigator reported HF, the introduction of loop diuretics and death from HF. In the analysis of renal outcomes, incident or worsening nephropathy was reduced for empagliflozin (12.7%) compared with placebo (18.8%); HR, 0.61 (95% CI: 0.53, 0.70). Empagliflozin significantly reduced the risk of progression to macroalbuminuria (38%) and doubling of creatinine (44%), as well as the need of starting renal-replacement therapy (55%). The benefits of empagliflozin for the reduction of CV death, all-cause death and hospitalisation for HF were observed across a range of baseline subgroups such as HbA1c level and renal function (down to estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m²). The rapid reduction of HF outcomes with empagliflozin is observed across the spectrum of CVD and HF risk and represents a therapeutic advance in the prevention and perhaps also in the treatment of HF, an often poorly recognised complication of T2D. This review discusses the EMPA-REG OUTCOME study and the implications for treating patients with T2D and CVD.

Acromegaly is a rare disease, caused largely by a growth hormone (GH) pituitary adenoma. Incidence is higher than previously thought. Due to increased morbidity and mortality, if not appropriately treated, early diagnosis efforts are essential. Screening is recommended for all patients with clinical features of GH excess. There is increased knowledge that classical diagnostic criteria no longer apply to all, and some patients can have GH excess with normal GH response to glucose. Treatment is multifactorial and personalised therapy is advised.

Insulin analogues play a key role in the effective management of type 2 diabetes. However, there are several behavioural barriers to appropriate early initiation of insulin therapy, despite compelling evidence supporting the benefits of this strategy in those patients for whom oral anti-diabetes agents provide insufficient control. The development of second-generation insulin analogues (insulin glargine 300 U/mL and insulin degludec) has provided physicians with agents that can provide comparable glycaemic control to first-generation insulin, but with a reduced risk of hypoglycaemia and modes of action suited to once-daily regimens. These characteristics may help overcome patient and physician concerns about early insulin use in disease management. To date, there have been no head-to-head comparisons of second-generation insulins: here we consider recent real-world evidence and the forthcoming direct comparison in the BRIGHT randomised controlled study, as presented at the recent 11^th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD) 2018.

The reliability of capillary blood glucose measurements is tremendously important for patients' care and follow-up. Some factors independent of glucose control could however affect readings during ambulatory monitoring of capillary glucose levels in patients with diabetes mellitus. We sought to evaluate the impact of three body lotions commonly used in Cameroon on different strata of glycaemia. We explored their influence over time on measured capillary glucose values. We enrolled 16 participants. Eligible individuals were adult patients with diabetes (n=12) stratified into three levels of capillary glucose values (100 ± 40 mg/dL [5.55 ± 2.22 mmol/L], 200 ± 40 mg/dL [11.1 ± 2.22 mmol/L] and 300 ± 40 mg/dL [16.65 ± 2.22 mmol/L]) and normoglycaemic individuals (n=4). We measured capillary blood glucose before application, immediately after, then 5, 30 and 60 minutes after application of sweet almond oil, corticosteroid cream and hydroquinone lotion. The measurements made on impregnated body lotion-permeated fingers were compared to that of a clean finger. We observed a significant increase (delta [95% confidence interval, CI]: 119.5% [77.4-222.1]) of capillary glucose level immediately after administration of hydroquinone-containing body lotion (p<0.001). Capillary glucose values after the use of corticoid cream and sweet almond oil was stable 5, 30 and 60 minutes after application (p=0.875 and p=0.883 respectively). In the case of the hydroquinone-containing body lotion, there was a significant difference between capillary glucose level at 5 minutes (delta [95%CI]: 81.6% [55.3-214.2]; p<0.001), 30 minutes (delta [95%CI]: 71.6% [21.8-134.6]; p<0.001) and 60 minutes (delta [95%CI]: 58.3% [2.8-133.3]; p=0.013) after application compared to the value obtained from the clean finger. We observed from our study that there were significant variations in capillary blood glucose measurements induced by the use of hydroquinone lotion.

Context: Managing diabetes efficiently demands a simple, safe, convenient and economical therapy. This study was done to understand the simplicity, safety, convenience and cost effectiveness of using pen versus syringe devices in patients on long-term insulin therapy. Design: This prospective observational study was conducted at the endocrine outpatient department of a universityaffiliated teaching hospital in North India. The investigator interviewed patients using a self-made questionnaire after obtaining consent; patients were scored based on their answers. A high score represented a poor response. A total of 90 completed questionnaires (45 from each group) were obtained. Results: Mean simplicity, safety and convenience score among the pen users was 5.31 ± 0.51, 5.4 ± 0.89 and 4.13 ± 1.04 respectively, as compared to 9.78 ± 1.43, 8.09 ± 2.02 and 8.67 ± 0.56 in syringe users respectively. The difference in these scores was statistically significant (p=0.0001). All patients felt that treatment using pen device was costlier when compared to using syringes, with pen users spending Rs1,756 per month on their insulin therapy, as compared to syringe users, who spent Rs590 per month. Among insulin pen users, 22.2% had optimal glycated haemoglobin levels (6-7.5%) as compared to 2.2% among syringe users, and this difference was statistically significant (p=0.007). Conclusions: An insulin pen is simple, safe and convenient to use, and may provide better glycaemic control. Treatment with a pen device is costlier, which may be due to the higher use of analogue insulin among pen users.

Cerebral oedema is the most common neurological complication of diabetic ketoacidosis (DKA). However, ischaemic and haemorrhagic brain injury has been reported infrequently. A 10-year old girl who was previously well presented with severe DKA. She was tachycardic with poor peripheral perfusion but normotensive. However, two fast boluses totalling 40 ml/kg normal saline were given. She was transferred to another hospital where she was intubated due to drowsiness. Rehydration fluid (maintenance and 48-hour correction for 7.5% dehydration) was started followed by insulin infusion. She was extubated within 24 hours of admission. Her ketosis resolved soon after and subcutaneous insulin was started. However, about 48 hours after admission, her Glasgow Coma Scale score dropped to 11/15 (E4M5V2) with expressive aphasia and upper motor neuron signs. One dose of mannitol was given. Her symptoms improved gradually and at 26-month follow-up she had a near-complete recovery with only minimal left lower limb weakness. Serial magnetic resonance imaging brain scans showed vascular ischaemic injury at the frontal-parietal watershed regions with haemorrhagic transformation. This case reiterates the importance of monitoring the neurological status of patient's with DKA closely for possible neurological complications including an ischaemic and haemorrhagic stroke.

The 2015 guidelines from the American Thyroid Association for adults with thyroid nodules and differentiated thyroid may be particularly important in minimising potential harm from overdiagnosis and overtreatment of thyroid tumours by providing more restrictive indications for biopsy of thyroid nodules, by considering active surveillance programs, as an alternative to surgery, for papillary microcarcinomas, and by recommending more conservative surgical approaches and a more judicious use of radioiodine.

Fatigue is a common symptom in clinical medicine. The complex and multifaceted etiopathogenesis of fatigue is a challenge for the differential diagnosis and management of fatigue. This brief communication shares two simple mnemonics - LEMON and ABCDE - which help in the evaluation of fatigue. These frameworks are as relevant to endocrinology and diabetes as to general practice. The mnemonic LEMON stands for lifestyle, endocrine, medical/metabolic, observer (physician) and nutrition-related factors which may cause fatigue; ABCDE lists the aetiology of fatigue in three columns related to physiological/nutritional, psychosocial and biomedical causes (each column includes one cause and how this relates to the ABCDE rubric).