Monitoring thyroid function during amiodarone use.

Amiodarone is an antiarrhythmic drug used to treat cardiac tachyarrhythmias. It has many adverse effects, with thyroid dysfunction one of the most notable. Through various mechanisms, both thyrotoxicosis and hypothyroidism can occur secondary to amiodarone therapy. There are two types of amiodarone-induced thyrotoxicosis: type 1 occurs in those with pre-existing thyroid disease and is treated with thionamide, whereas type 2 occurs in those without and is treated with glucocorticoids. Patients with amiodarone-induced hypothyroidism may be given levothyroxine to replace thyroid hormone, but in some cases, the appropriate management may be cessation of amiodarone.

Pharmacotherapy of type 2 diabetes mellitus in frail elderly patients.

The prevalence of type 2 diabetes mellitus is expected to rise in the frail elderly population, which will have significant consequences for the health economy. Symptoms of hypoglycaemia can be subtle in the elderly. Hypoglycaemia accounts for more hospital admissions than hyperglycaemia. Treatment targets are set based on the risk of adverse events resulting from treatment and the benefits expected from tighter glycaemic control. The different medications available are discussed including the different types of insulin, in particular relation to usage in older adults. The choice of therapy is based on the targets, comorbidities and the characteristics of each antidiabetic agent. Deintensification of therapy should be considered in patients who experience adverse effects. Treatment guidelines should be formulated based on the above principles, as many current guidelines do not incorporate deintensification of therapy.

Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse.

Testosterone deficiency is commonly associated with obesity, metabolic syndrome, type 2 diabetes and their clinical consequences-hepatic steatosis and atherosclerosis. The testicular feminised mouse (non-functional androgen receptor and low testosterone) develops fatty liver and aortic lipid streaks on a high-fat diet, whereas androgen-replete XY littermate controls do not. Testosterone treatment ameliorates these effects, although the underlying mechanisms remain unknown. We compared the influence of testosterone on the expression of regulatory targets of glucose, cholesterol and lipid metabolism in muscle, liver, abdominal subcutaneous and visceral adipose tissue. Testicular feminised mice displayed significantly reduced GLUT4 in muscle and glycolytic enzymes in muscle, liver and abdominal subcutaneous but not visceral adipose tissue. Lipoprotein lipase required for fatty acid uptake was only reduced in subcutaneous adipose tissue; enzymes of fatty acid synthesis were increased in liver and subcutaneous tissue. Stearoyl-CoA desaturase-1 that catalyses oleic acid synthesis and is associated with insulin resistance was increased in visceral adipose tissue and cholesterol efflux components (ABCA1, apoE) were decreased in subcutaneous and liver tissue. Master regulator nuclear receptors involved in metabolism-Liver X receptor expression was suppressed in all tissues except visceral adipose tissue, whereas PPARγ was lower in abdominal subcutaneous and visceral adipose tissue and PPARα only in abdominal subcutaneous. Testosterone treatment improved the expression (androgen receptor independent) of some targets but not all. These exploratory data suggest that androgen deficiency may reduce the buffering capability for glucose uptake and utilisation in abdominal subcutaneous and muscle and fatty acids in abdominal subcutaneous. This would lead to an overspill and uptake of excess glucose and triglycerides into visceral adipose tissue, liver and arterial walls.

Testosterone and mortality.

Epidemiological studies have found that men with low or low normal endogenous testosterone are at an increased risk of mortality than those with higher levels. Cardiovascular disease accounts for the greater proportion of deaths in those with low testosterone. Cancer and respiratory deaths in some of the studies are also significantly more prevalent. Disease-specific studies have identified that there are higher mortality rates in men with cardiovascular, respiratory and renal diseases, type 2 diabetes and cancer with low testosterone. Obesity, metabolic syndrome, type 2 diabetes, cardiovascular disease and inflammatory disorders are all associated with an increased prevalence of testosterone deficiency. Two major questions that arise from these findings are (1) is testosterone deficiency directly involved in the pathogenesis of these conditions and/or a contributory factor impairing the body's natural defences or is it merely a biomarker of ill health and the severity of underlying disease process? (2) Does testosterone replacement therapy retard disease progression and ultimately enhance the clinical prognosis and survival? This review will discuss the current state of knowledge and discuss whether or not there are any answers to either of these questions. There is convincing evidence that low testosterone is a biomarker for disease severity and mortality. Testosterone deficiency is associated with adverse effects on certain cardiovascular risk factors that when combined could potentially promote atherosclerosis. The issue of whether or not testosterone replacement therapy improves outcomes is controversial. Two retrospective studies in men with diagnosed hypogonadism with or without type 2 diabetes have reported significantly improved survival.

Testosterone suppresses the expression of regulatory enzymes of fatty acid synthesis and protects against hepatic steatosis in cholesterol-fed androgen deficient mice.

AIMS: Non-alcoholic fatty liver disease and its precursor hepatic steatosis is common in obesity and type-2 diabetes and is associated with cardiovascular disease (CVD). Men with type-2 diabetes and/or CVD have a high prevalence of testosterone deficiency. Testosterone replacement improves key cardiovascular risk factors. The effects of testosterone on hepatic steatosis are not fully understood. MAIN METHODS: Testicular feminised (Tfm) mice, which have a non-functional androgen receptor (AR) and very low serum testosterone levels, were used to investigate testosterone effects on high-cholesterol diet-induced hepatic steatosis. KEY FINDINGS: Hepatic lipid deposition was increased in Tfm mice and orchidectomised wild-type littermates versus intact wild-type littermate controls with normal androgen physiology. Lipid deposition was reduced in Tfm mice receiving testosterone treatment compared to placebo. Oestrogen receptor blockade significantly, but only partially, reduced the beneficial effects of testosterone treatment on hepatic lipid accumulation. Expression of key regulatory enzymes of fatty acid synthesis, acetyl-CoA carboxylase alpha (ACACA) and fatty acid synthase (FASN) were elevated in placebo-treated Tfm mice versus placebo-treated littermates and Tfm mice receiving testosterone treatment. Tfm mice on normal diet had increased lipid accumulation compared to littermates but significantly less than cholesterol-fed Tfm mice and demonstrated increased gene expression of hormone sensitive lipase, stearyl-CoA desaturase-1 and peroxisome proliferator-activated receptor-gamma but FASN and ACACA were not altered. SIGNIFICANCE: An action of testosterone on hepatic lipid deposition which is independent of the classic AR is implicated. Testosterone may act in part via an effect on the key regulatory lipogenic enzymes to protect against hepatic steatosis.

Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes.

OBJECTIVE: Men with type 2 diabetes are known to have a high prevalence of testosterone deficiency. No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy (TRT). We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone. RESEARCH DESIGN AND METHODS: A total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.81.3 S.D. years. mortality rates were compared between total testosterone 10.4nmol/l (300ng/dl; n=343) and testosterone 10.4nmol/l (n=238). the effect of TRT (as per normal clinical practise: 85.9% testosterone gel and 14.1% intramuscular testosterone undecanoate) was assessed retrospectively within the low testosterone group. RESULTS: Mortality was increased in the low testosterone group (17.2%) compared with the normal testosterone group (9%; P=0.003) when controlled for covariates. In the Cox regression model, multivariate-adjusted hazard ratio (HR) for decreased survival was 2.02 (P=0.009, 95% CI 1.2-3.4). TRT (mean duration 41.6±20.7 months; n=64) was associated with a reduced mortality of 8.4% compared with 19.2% (P=0.002) in the untreated group (n=174). The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 (95% CI 1.3-3.9, P=0.004). CONCLUSIONS: Low testosterone levels predict an increase in all-cause mortality during long-term follow-up. Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes.

Comparison of endoscopic and microscopic trans-sphenoidal pituitary surgery: early results in a single centre.

INTRODUCTION: Pituitary surgery has seen a recent shift from a microscopic to an endoscopic trans-sphenoidal approach. We present our early experience with endoscopic surgery and compare the outcome with our recent microscopic experience. METHODS: From January 2008 until present time, 80 consecutive patients underwent trans-sphenoidal pituitary surgery in our institution. Until September 2009, all patients had a microscopic trans-septal approach. After this time, the patients underwent endoscopic trans-sphenoidal surgery. All patients underwent pre- and post-operative MRI and full endocrinological evaluation. Data was collected prospectively including tumour volume, endocrine function, visual function, length of stay and complications. RESULTS: There were 40 patients in each group. In the microscopic group, there were 26 non-functioning tumours and 14 functioning tumours. In the endoscopic group, there were 24 non-functioning and 16 functioning tumours. There were significantly better results in terms of tumour resection (p = 0.002) and remission (p = 0.018) in the endoscopic group. In this group there was also a lower incidence of CSF leaks and a shorter length of stay for secreting tumours (p = 0.005). 1 patient in the endoscopic group died at day 43 post-operatively, having initially presented in a poor clinical state with pituitary apoplexy. CONCLUSION: Microscopic trans-sphenoidal surgery remains the benchmark for future surgical techniques. Our early results suggest that endoscopic trans-sphenoidal surgery provides favourable results in both tumour resection and control of secreting tumours in comparison with microscopic surgery. Further longer-term evaluation is required to ensure the outcome of endoscopic surgery.

Testosterone and the metabolic syndrome.

Metabolic syndrome and testosterone deficiency in men are closely Linked. Epidemiological studies have shown that Low testosterone Levels are associated with obesity, insulin resistance and an adverse Lipid profile in men. Conversely in men with metabolic syndrome and type 2 diabetes have a high prevalence of hypogonadism. Metabolic syndrome and Low testosterone status are both independently associated with increased all-cause and cardiovascular mortality. Observational and experimental data suggest that physiological replacement of testosterone produces improvement in insulin resistance, obesity, dyslipidae-mia and sexual dysfunction along with improved quality of Life. However, there are no Long-term interventional studies to assess the effect of testosterone replacement on mortality in men with Low testosterone Levels. This article reviews the observational and interventional clinical data in relation to testosterone and metabolic syndrome.