Modified-release hydrocortisone is associated with lower plasma renin activity in patients with salt-wasting congenital adrenal hyperplasia.

Objective: Poorly controlled salt-wasting (SW) congenital adrenal hyperplasia (CAH) patients often require high 9α-fluorocortisol doses as they show high levels of 17-hydroxyprogesterone (17OHP), which is a mineralocorticoid (MC)-receptor antagonist.

Design: We investigated the renin-angiotensin-aldosterone system in patients with SW-CAH receiving twice daily modified-release hydrocortisone (MR-HC, Efmody) compared with standard glucocorticoid (GC) therapy.

Methods: Data were analyzed from the 6-month, phase 3 study of MR-HC (n = 42) versus standard GC therapy (n = 41).

Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia.

Context: Standard glucocorticoid therapy in congenital adrenal hyperplasia (CAH) regularly fails to control androgen excess, causing glucocorticoid overexposure and poor health outcomes.

Objective: We investigated whether modified-release hydrocortisone (MR-HC), which mimics physiologic cortisol secretion, could improve disease control.

Methods: A 6-month, randomized, phase 3 study was conducted of MR-HC vs standard glucocorticoid, followed by a single-arm MR-HC extension study.

Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes , and .

Background: Germline pathogenic variants in / are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype-phenotype correlations in a large cohort of / mutation carriers.

Review of growth hormone therapy in adolescents and young adults with Prader-Willi syndrome.

Consensus guidelines from the Growth Hormone Research Society Workshop recommend growth hormone therapy in all children with genetically confirmed Prader-Willi syndrome (PWS) in combination with dietary, lifestyle and environmental interventions. As yet, however, there are limited published data regarding the use of growth hormone therapy in adolescents and young adults with PWS. This review focuses on the advantages and disadvantages of growth hormone therapy in this particular group.

Deficits in Trabecular Bone Microarchitecture in Young Women With Type 1 Diabetes Mellitus.

The pathophysiological mechanism of increased fractures in young adults with type 1 diabetes mellitus (T1DM) is unclear. We conducted a case-control study of trabecular bone microarchitecture and vertebral marrow adiposity in young women with T1DM. Thirty women with T1DM with a median age (range) age of 22.

Euglycemic clamp insulin sensitivity and longitudinal systolic blood pressure: role of sex.

Insulin resistance may be an independent risk factor for the development of hypertension, but change in blood pressure (BP) over time has not been adequately studied in healthy individuals fully characterized for insulin sensitivity. In the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study, we measured insulin sensitivity (M/I) using the euglycemic clamp technique in 1073 healthy European adults (587 women, 486 men) aged 30 to 60 years followed up 3 years later. Systolic BP (SBP) at baseline was higher in insulin-resistant women (ie, those in the low sex-specific M/I tertile) compared with those in the intermediate (P<0.

Urinary free (unconjugated) metadrenalines in different hereditary forms of catecholamine-secreting phaeochromocytoma/paraganglioma.

Background: Catecholamine-producing neuroendocrine tumours are found in chromaffin cells of the adrenal medulla (phaeochromocytoma) or extra-adrenal paraganglia (paraganglioma), known collectively as PPGLs. In approximately a quarter or more of cases of PPGL, these rare tumours arise as a result of germline mutations of several tumour susceptibility genes. At the Crosshouse laboratory, urine tests include free metadrenalines (fMAs) (also known as free metanephrines) which demonstrate superior sensitivity over that obtained by urinary vanillyl mandelic acid, catecholamines or plasma catecholamines in the diagnosis of PPGL.

Disorders of blood pressure regulation-role of catecholamine biosynthesis, release, and metabolism.

Catecholamines (epinephrine and norepinephrine) are synthesised and produced by the adrenal medulla and postganglionic nerve fibres of the sympathetic nervous system. It is known that essential hypertension has a significant neurogenic component, with the rise in blood pressure mediated at least in part by overactivity of the sympathetic nervous system. Moreover, novel therapeutic strategies aimed at reducing sympathetic activity show promise in the treatment of hypertension.

Molecular analysis of pheochromocytoma after maternal transmission of SDHD mutation elucidates mechanism of parent-of-origin effect.

Context: Pheochromocytoma/paraganglioma occurs almost exclusively after paternal transmission of succinate dehydrogenase D (SDHD) mutations. This parent-of-origin effect has not been fully explained but is accompanied by obligate loss of the maternal copy of chromosome 11. Loss of wild-type SDHD and an additional imprinted gene (hypothesized to be H19) appears necessary for tumor formation.

Comparison of diagnostic accuracy of urinary free metanephrines, vanillyl mandelic Acid, and catecholamines and plasma catecholamines for diagnosis of pheochromocytoma.

Context: Recent evidence suggests that plasma-free metanephrines provide a highly sensitive test in patients requiring exclusion of pheochromocytoma. The diagnostic efficacy of urinary free metanephrines, however, has not been evaluated. OBJECTIVE, DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: We compared retrospectively the diagnostic efficacy of 24-h urinary free metanephrines with our currently available measurements of 24-h urinary vanillyl mandelic acid (VMA), urinary catecholamines, and plasma catecholamines in 159 outpatients tested in a tertiary referral center for pheochromocytoma over a 4-yr period.

Effect of prior moderate exercise on postprandial metabolism in men with type 2 diabetes: heterogeneity of responses.

Unlabelled: Prior moderate exercise has been shown consistently to reduce postprandial triglyceride (TG) concentrations in non-diabetic adults, but its effects in men with type 2 diabetes are not known. This study aimed to determine the effect of moderate exercise on postprandial metabolism in men with type 2 diabetes. Ten middle-aged men with type 2 diabetes underwent two oral fat tolerance tests (blood taken fasting and for 8 h after a meal containing 80 g fat, 70 g carbohydrate) in random order.

Functioning paraganglioma and gastrointestinal stromal tumor of the jejunum in three women: syndrome or coincidence.

Functioning paraganglioma and gastrointestinal stromal tumor (GIST) are uncommon tumors that occur mostly in a sporadic and isolated form, occasionally as components of multiple neoplasia syndromes, either separately or together. Separately, they occur in several inherited syndromes including multiple endocrine neoplasia 2, and the GIST, lentigines, and mast cell tumor syndrome. Together, they are variably prominent components of three syndromes: the familial paraganglioma and gastric GIST syndrome, neurofibromatosis type 1, and the Carney triad.

Insulin-sensitising agents: beyond thiazolidinediones.

The global prevalence of Type 2 diabetes mellitus is increasing rapidly, at least in part as a function of obesity. The results of the United Kingdom Prospective Diabetes Study emphasise the importance of developing safe, efficacious new agents for the treatment of Type 2 diabetes. The pharmaceutical industry has recently focused on strategies to improve insulin resistance, particularly modulation of PPAR-gamma.

The role of insulin and the adipocytokines in regulation of vascular endothelial function.

Vascular integrity in the healthy endothelium is maintained through the release of a variety of paracrine factors such as NO (nitric oxide). Endothelial dysfunction, characterized by reduced NO bioavailability, is associated with obesity, insulin resistance and Type II diabetes. Insulin has been demonstrated to have direct effects on the endothelium to increase NO bioavailability.

Clinical impact of the new criteria for the diagnosis of diabetes mellitus.

In 1997 the American Diabetes Association lowered the threshold for diagnosis of diabetes from a fasting plasma glucose concentration of 7.8 mmol/l to 7.0 mmol/l and advised that the oral glucose tolerance test no longer be used in routine clinical practice.

Decreased insulin sensitivity during dietary sodium restriction is not mediated by effects of angiotensin II on insulin action.

We have previously reported that modest dietary sodium restriction, as advocated in management guidelines for diabetes, may reduce insulin sensitivity. It has since been suggested that this effect may be mediated via cross-talk between insulin and angiotensin II (AII)-stimulated intracellular second messengers. In order to assess the effect of 5 days of modest sodium restriction (to <80 mmol/day target sodium intake) on insulin sensitivity, 15 healthy males underwent a double-blind, placebo-controlled, randomized, cross-over euglycaemic hyperinsulinaemic clamp study.