Sodium-glucose co-transporter 2 inhibitors and heart failure-the present and the future.

Type 2 diabetes mellitus is associated with an increased risk of heart failure. The prevalence of type 2 diabetes mellitus is on an upward trend. Heart failure represents one of the major causes for hospitalisation and mortality despite advances in management. Recent cardiovascular outcome trials have demonstrated that sodium-glucose co-transporter 2 inhibitors, which were introduced to the market in 2013, can incur a clinically significant risk reduction in heart failure outcomes in such patients. In this review, we discuss the epidemiology and pathophysiology of heart failure in diabetes and explore the landmark trials, the potential mechanisms of benefit of SGLT-2 inhibitors in heart failure, how the trials have led to major changes in treatment guidelines, and future potential directions for use of these drugs, including in those without diabetes.

Flash glucose monitoring: Impact on markers of glycaemic control and patient-reported outcomes in individuals with type 1 diabetes mellitus in the real-world setting.

AIMS: We aimed to evaluate both glycaemic parameters and patient-reported outcomes in patients prescribed FGM based on the local criteria at our institution. METHODS: This retrospective observational study included patients aged > 18 years with a diagnosis of type 1 diabetes mellitus (T1DM) who were prescribed FreeStyle Libre FGM (n = 90). Quantitative data on glycaemic parameters was collected pre- and post-initiation of FGM in addition to patient-reported outcome measures (PROMs). The primary outcome was change in pre- and post-FGM levels of glycosylated haemoglobin (HbA1C). RESULTS: There was a mean reduction in HbA1c of -7.29 ±â€¯10.76 mmol/mol (p < 0.001, CI95% 4.94-9.64) sustained to the latest reading. There was also a mean reduction in the number of hypoglycaemic episodes per week of 3.20 (percentage reduction 51.86%, p < 0.001, CI95% 1.64-4.77). A significant improvement in quality of life scores was noted in all five domains of the abbreviated DDS between before and after starting FGM (p < 0.001). Key themes highlighted in inductive content analysis include 'life-changing', 'positive experience', and 'convenient'. CONCLUSION: Flash glucose monitoring is associated with significant improvement in HbA1c to a mean follow-up of 4.6 months. Additionally, patients reported positive experiences of FGM with significant improvement in all aspects of a focussed Diabetes Distress Scale.

Just another case of bacterial meningitis or is it?

Non-traumatic cerebrospinal fluid (CSF) rhinorrhoea is a rare condition. We describe a case of a 62-year-old woman with pneumococcal bacterial meningitis who later was found to have CSF rhinorrhoea secondary to an eroding skull base tumour, which was proven to be pituitary macroadenoma on biopsy. She recovered well from meningitis without any neurological sequelae and underwent trans-sphenoidal surgery for tumour removal as well as dural repair.

Inhaled corticosteroids and HPA axis suppression: how important is it and how should it be managed?

Inhaled corticosteroids (ICS) are established as a cornerstone of management for patients with bronchoconstrictive lung disease. However, systemic absorption may lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis in a significant minority of patients. This is more likely in 'higher risk' patients exposed to high cumulative ICS doses, and in those treated with frequent oral corticosteroids or drugs which inhibit cytochrome p450 3A4. Hypothalamic-pituitary-adrenal axis suppression is frequently unrecognized, such that some patients, notably children, only come to light when an adrenal crisis is precipitated by physical stress. To minimize this risk, 'higher risk' patients and those with previously identified suppressed cortisol responses to Synacthen testing should undergo an education programme to inform them about sick day rules. A review of ICS therapy should also be undertaken to ensure that the dose administered is the minimum required to control symptoms.

Use of day 1 early morning cortisol to predict the need for glucocorticoid replacement after pituitary surgery.

BACKGROUND: Assessment of adrenal reserve in patients who have undergone pituitary surgery is crucial. However, there is no clear consensus with regards to the type and timing of the test that should be used in the immediate post-operative period. Recently, there has been increased interest in measuring post-operative cortisol levels. We present our data utilising day 1 post-operative early morning cortisol as a tool to assess adrenal reserve in steroid-naive patients. METHODS: A retrospective analysis of endoscopic pituitary surgery undertaken over a 2-year period. 82 patients underwent 84 surgeries in total. Patients who were already on glucocorticoids pre-operatively and patients with Cushing's disease, pituitary apoplexy and those without follow-up data were excluded, leaving a study group of 44 patients with 45 operations. A 9am day 1 post-operative cortisol value of > 400 nmol/L was taken as an indicator of adequate adrenal reserve. All the patients were reassessed at 6 weeks with a standard short synacthen test (SST) using 250 micrograms of intravenous synacthen. RESULTS: 22 out of 45 patients had a cortisol value of > 400 nmol/L on day 1 post-operatively and were discharged without glucocorticoid supplementation. Of these, only 2 patients subsequently failed the SST when reassessed at 6-8 weeks. The remaining 23 patients had a cortisol value of < 400 nmol/L on day 1 post-operatively and were discharged on hydrocortisone 10 mg twice daily. At 6-8 weeks, nine continued to show suboptimal stimulated cortisol levels whereas the remaining fourteen patients showed adequate adrenal reserve. The 9 am cortisol value had high specificity (81.8%) and positive predictive value (90.9%) for integrity of the HPA axis. Sensitivity was 58.8% and negative predictive value was 39.1%. CONCLUSION: A day 1 post-operative early morning cortisol is a useful tool to predict adrenal reserve post-pituitary surgery, enabling clinicians to avoid unnecessary blanket glucocorticoid replacement.

Resistant hypertension with adrenal nodule: are we removing the right gland?

UNLABELLED: Resistant hypertension is often difficult to treat and may be associated with underlying primary aldosteronism (PA). We describe the case of an elderly gentleman who presented with severe and resistant hypertension and was found to have a left adrenal incidentaloma during evaluation but had aldosterone excess secondary to unilateral adrenal hyperplasia (UAH) of the contralateral gland, which needed surgical intervention. A 65-year-old gentleman was evaluated for uncontrolled high blood pressure (BP) in spite of taking four antihypertensive medications. The high BP was confirmed on a 24-h ambulatory reading, and further biochemical evaluation showed an elevated serum aldosterone renin ratio (ARR) (1577 pmol/l per ng per ml per h). Radiological evaluation showed an adrenal nodule (15 mm) in the left adrenal gland but an adrenal vein sampling demonstrated a lateralization towards the opposite site favouring the right adrenal to be the source of excess aldosterone. A laparoscopic right adrenalectomy was performed and the histology of the gland confirmed nodular hyperplasia. Following surgery, the patient's BP improved remarkably although he remained on antihypertensives and under regular endocrine follow-up. PA remains the most common form of secondary and difficult-to-treat hypertension. Investigations may reveal incidental adrenal lesions, which may not be the actual source of excess aldosterone, but UAH may be a contributor and may coexist and amenable to surgical treatment. An adrenal vein sampling should be undertaken for correct lateralization of the source, otherwise a correctable diagnosis may be missed and the incorrect adrenal gland may be removed. LEARNING POINTS: Severe and resistant hypertension can often be associated with underlying PA.ARR is an excellent screening tool in patients with suspected PA.Lateralization with adrenal venous sampling is essential to isolate the source and differentiate between unilateral and bilateral causes of hyperaldosteronism.Adrenal incidentalomas and UAH may coexist and the latter may often be the sole cause of excess aldosterone secretion.Decisions about adrenalectomy should be made only after integrating and interpreting radiological and biochemical test findings properly.

Impact of vitamin D replacement in patients with normocalcaemic and hypercalcaemic primary hyperparathyroidism and coexisting vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is increasingly recognized in patients with primary hyperparathyroidism but some clinicians are reluctant to replace vitamin D due to concerns with aggravating hypercalcaemia. We investigated the impact of vitamin D repletion in asymptomatic patients with normocalcaemic and hypercalcaemic primary hyperparathyroidism. METHODS: This is a retrospective analysis of 111 patients with elevated parathyroid hormone concentrations (>6.4 pmol/L) referred to our endocrine clinic between January and December 2012; we identified 39 patients with primary hyperparathyroidism and vitamin D deficiency, i.e. 25 hydroxy vitamin D <20 µg/L. Patients were categorized into normocalcaemic (n = 23) and hypercalcaemic (n = 16) groups and the impact on biochemical parameters was recorded after at least six months treatment with either 1600 or 3200 units daily of cholecalciferol. RESULTS: Both normocalcaemic and hypercalcaemic groups showed a rise in 25 hydroxy vitamin D concentrations after replacement (p <0.0001). Parathyroid hormone concentrations fell in the normocalcaemic group (p = 0.08) but individually, five patients showed a rise (8-38% of baseline). In the hypercalcaemic group, parathyroid hormone remained static but the adjusted calcium concentration fell significantly (p = 0.006) except in two patients who showed mild rises (3 and 6%, respectively). There was no deterioration in renal function or calcium-related adverse events in any of the groups. CONCLUSIONS: Our study supports the safety of vitamin D replacement in patients with mild asymptomatic primary hyperparathyroidism and coexistent vitamin D deficiency. Repletion does not aggravate hypercalcaemia and may limit disease progression. Patients with normocalcaemic primary hyperparathyroidism need further characterization from longitudinal studies.

Targeted thyroid testing in acute illness: achieving success through audit.

Thyroid tests are done in acutely ill patients who often have confusing transient thyroid abnormalities, despite a lack of clarity about intervention and cost benefit. A retrospective analysis of patients admitted to the Medical Assessment Unit (MAU) was undertaken in 2004 to assess the frequency and utility, pattern of abnormalities and cost of thyroid testing. Guidelines were issued and the audit was repeated in 2008. 53.8% of 1593 subjects were offered thyroid tests in 2004 with a significant reduction to 21.7% of 1176 in 2008 (p<0.001). Free T4 or TSH was outside the reference range in 11.2% (2004) and 7.5% (2008) (p=0.10) and low TSH (52.7% in 2004 and 64.3% in 2008) was commonly combined with normal free T4. Appropriate indications for testing were documented in 43.9 vs 73.7% of patients with abnormal thyroid results (p=0.004) and in 14.3 vs 16% (2004 vs 2008) of a random sample of subjects with normal thyroid results, respectively (p=0.77). Documentation of intervention (25.5. vs 92.9%; p=0.001) and follow-up (45.5 vs 85.7%; p=0.001) had also improved significantly in 2008. We have demonstrated a significant reduction in thyroid testing in acutely ill patients after audit and the issue of guidelines. We currently recommend thyroid tests only in those with previous thyroid disease, the presence of clinical features and risk factors for thyroid disease, the use of relevant drugs, and unexplained tachydysrhythmias. The difficulties in interpreting results, the lack of clarity about intervention and follow up and possible cost savings would argue against an unrestricted policy.

Glucose intolerance and diabetes mellitus in endocrine disorders - two case reports and a review.

Impaired glucose tolerance and diabetes mellitus are a manifestation of several well recognised endocrine disorders. Hyperglycaemia subsides upon removal of the underlying cause in these conditions - usually a hormone secreting tumour. We describe two subjects who were cured of their poorly controlled diabetes mellitus following surgical removal of a phaeochromocytoma and a cortisol secreting adrenal adenoma and review the mechanisms underlying glucose intolerance in endocrine disorders. The reported incidence of diabetes is variable in these conditions and may range between 2-95%. The severity is also variable as some affected individuals have only minor glucose intolerance while others have frank symptomatic diabetes mellitus which forms a major manifestation of their illness. The mechanisms causing hyperglycaemia are (a) insulin resistance, (b) increased hepatic glucose production and output, (c) decreased insulin production and release and (d) increased intestinal glucose absorption. Multiple intermediate mechanisms which include electrolyte perturbations and hormone receptor and post receptor mediated effects are responsible for these abnormalities. An understanding of these mechanisms and diagnostic strategies is important as these may be used to advantage in managing these patients. We describe some of these in greater detail below.