Endocrine Abstracts

The Metabolic Syndrome (insulin resistance, hyperglycaemia, dyslipidaemia, hypertension) amplified by visceral obesity resembles Cushing's but plasma cortisol levels are not usually elevated. To explain this paradox altered tissue sensitivity to glucocorticoids has been invoked. 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) reactivates cortisone to cortisol, thus amplifying local glucocorticoid action. An adipose-selective increase in 11b-HSD1 may underlie the Metabolic S...

The contribution of conventional hormone replacement to the clinical features attributed to adult growth hormone deficiency (GHD) is poorly defined. We measured baseline bone mineral density (BMD/DXA) at the lumbar spine and femoral neck in patients with isolated GHD (IGHD, 16 patients, 14 female, 4 childhood onset, mean age 39, range 19- 63 years) and patients with multiple pituitary hormone deficiencies (MPD, 135 patients, 94 female, 14 childhood onset, mean age 44, range 19...

Glucocorticoids are an important adipogenic factor. In man, circulating cortisol excess causes visceral obesity, but in simple obesity glucocorticoid levels are usually normal. However, in adipose tissue cortisol availability to bind to the glucocorticoid receptor (GR) is modulated by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). Human preadipocytes display both dehydrogenase (cortisol to cortisone) and oxo-reductase (cortisone to cortisol) activity. Recent genet...

Maternal nutrient restriction (NR) during late-gestation can influence liver growth by altering maturation of the hypothalamus. Maternal NR during late-gestation increases fetal plasma GH levels whilst circulating IGF-I and IGF-II levels decrease. This study aimed to determine whether maternal NR during late-gestation altered the hepatic IGF system in resultant offspring.Fourteen primiparous twin pregnant Border Leicester cross Swaledale ewes were fed <i...

11HSD1 regenerates cortisol from cortisone and maintains glucocorticoid receptor (GR) activation. Adipose-specific transgenic 11HSD1 overexpression in mice causes obesity, insulin resistance, and hypertension (reflecting increased adipose angiotensinogen); however, the effect depended upon local GR expression. In human obesity, 11HSD1 activity is increased similarly in biopsied adipose, but the impact remains uncertain. We tested whether increased adipose 11HSD1 activity in ob...

Inhibiting 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) has been proposed to prevent local regeneration of cortisol from cortisone, and thus enhance hepatic and adipose insulin sensitivity. In healthy men and patients with type 2 diabetes, the non-selective 11HSD inhibitor carbenoxolone enhances hepatic insulin sensitivity but, paradoxically, does not increase peripheral glucose disposal. In obesity, 11HSD1 activity and mRNA are increased in adipose biopsies. We tested ...

The contribution to adult growth hormone deficiency (GHD) of hormone replacement and other aspects of hypopituitarism are poorly defined. We compared baseline characteristics and response to GH treatment of patients with isolated GHD (IGHD, 16 patients) to patients with multiple pituitary hormone deficiencies (MPD, 135 patients). At baseline, MPD patients showed significantly greater waist-hip ratios (0.87 plus/minus 0.007 vs. 0.82 plus/minus 0.02, mean plus/minus SD; P < 0...

Background: Sotos syndrome is an uncommon condition characterised by rapid growth, large body size and acromegaloid facies.There is limited data on metabolic abnormalities in Sotos syndrome.Aims: We investigated insulin sensitivity and secretion rates in a 22 year old girl with Sotos syndrome, prompted by the observation of a flat glucose response after an oral glucose challenge.Methods: Glucose tolerance was assessed with a 75g 2-h oral glucose tolerance test (OGTT), ...

Alstrom syndrome is an autosomal recessive disorder characterised by obesity, sensorineural deafness, cone-rod dystrophy and hypergonadotrophic hypogonadism. Diabetes in these patients is characterised by severe insulin resistance.We describe the management of diabetes in a 28 year old male patient with Alstrom syndrome and severe insulin resistance. Obesity developed early in childhood and at 3 years weight was 22.2 kg. Genetic studies revealed that the patient is a compo...

The route of oestrogen replacement has an important influence on growth hormone (GH) sensitivity, but it remains unclear whether the route of testosterone treatment in hypopituitarism influences the response to GH replacement. We have compared IGF-I levels, body composition and BMD in hypopituitary male patients with severe GH-deficiency receiving either oral testosterone undecanoate (T.U.)(80-160 milligrams per day) or intramuscular testosterone (I.M.) (250-500 milligrams per...