Endocrine Abstracts

Insulin resistance and androgen excess are the cardinal features of polycystic ovary syndrome (PCOS). The severity of hyperandrogenism and metabolic dysfunction in PCOS are closely correlated but the underlying mechanisms are poorly understood. Aldoketoreductase type 1C3 (AKR1C3) is an important source of adipose androgen generation (converting androstenedione to testosterone) and we have postulated that it may have a critical role linking androgen metabolism and meta...

Background: Insulin resistance is the reduced responsiveness of the body to the glucose-lowering activity of insulin. It is usually associated with obesity, but in a minority of patients, this is not the case. Single gene mutations can often be found in such patients, some of which affect the insulin receptor (INSR). There is a spectrum of genetic insulin receptoropathies. These can be considered as two groups. One group comprises rare, severe, autosomal recessive disorders: D...

Background: Infrared thermography (IRT) can assess human brown adipose tissue (BAT) activity non-invasively. However, it remains unclear if skin temperature is altered in obesity. We compared skin temperatures of lean and obese individuals following cold exposure and studied its relationship with energy expenditure (EE).Methods: 10 lean (age 28.3±2.1y, BMI 21.5±0.4kg/m2) and 10 obese (age 28.2±2.1y, BMI 36.2±1.3kg/m2</...

Background: Alström Syndrome (AS) is a rare autosomal recessive disease featuring highly accelerated insulin resistance, fatty liver, diabetes and heart failure among other syndromic features. Heart failure leads to significant early mortality, but is complex and likely multifactorial, with developmental defects, accelerated atherosclerosis, and fibrosis all implicated. These cardiometabolic complications occur in the face of only moderate obesity in many patients. AS is ...

Autoimmune immunoglobulins directed against peptide hormones are well-described. These are often clinically benign, but may cause a deleterious effect on the accuracy of clinical immunoassays. A notable exception is Insulin Autoimmune Syndrome (IAS, also known as Hirata disease), where antibody-binding has a direct effect on insulin kinetics resulting in aberrant glucose control. Current methods to diagnose IAS rely on crude immune-subtraction techniques such as polyethylene g...

Case history: A 38-year-old man was referred with a 12-month history of recurrent bouts of transient hyponatraemia (serum sodium ranging from 115 to 125 mmol/l). Citalopram, which he was taking for depression, was discontinued, but the episodes continued.Initial investigations: Whilst symptomatic, and clinically euvolaemic, his biochemical profile was consistent with a syndrome of inappropriate antidiuresis (SIAD): sodium 124 mmol/l, potassium 4.5 mmol/l...

Introduction: We have reported a syndrome of hypoketotic hypoglycaemia due to the de novo p.Glu17Lys mutation in AKT2, a serine threonine kinase central to insulin signalling. We aimed to evaluate further the physiological and cellular consequences of the p.Glu17Lys mutation.Results: Two previously reported 17-year-old men heterozygous for the AKT2 p.Glu17Lys mutation, each of whom had experienced severe fasting hypoglycaemia in early life, were...

AKT serine-threonine kinases are critical mediators of both growth and metabolic actions of insulin. AKT2 is believed to exert predominantly metabolic effects, while AKT1 has been more strongly implicated in growth. We have recently reported that the de novo AKT2 p.Glu17Lys mutation produces a sporadic syndrome of severe persistent hypoinsulinaemic hypoglycaemia associated with left-sided hemihypertrophy. Glucose requirements in affected patients are far lower than seen in hyp...

Genetic defects in PCNT, encoding the centrosomal protein pericentrin, cause a rare syndrome of primordial dwarfism, skeletal dysplasia and facial dysmorphism, known as Majewski Osteodysplastic Primordial Dwarfism Type II (MOPDII). We now report that 11 out of 15 patients with PCNT defects had clinical and/or biochemical evidence of severe insulin resistance (IR), many also with severe dyslipidaemia; the remaining four were under 4 years-old. The metabolic profil...

Introduction: Generalised lipodystrophy is clinically characterised by lipoatrophy, hepatomegaly, hypertriglyceridemia, insulin resistance and acromegaloid features. It is recognised that diencephalic syndrome is a rare presentation of hypothalamic tumours in infants and young children. Children with this disorder have profound emaciation and generalised loss of subcutaneous fat, growth acceleration, hyperkinesia and euphoria. Hypothalamic tumours, particularly pilocytic astro...