[Endocrine and metabolic consequences of massive obesity]

Massive obesity is always accompanied by insulin resistance with hyperinsulinaemia in proportion to the amount of visceral fat, which has repercussions on oxidative and non-oxidative glucose metabolism. The increase of free fatty acids in direct relation to the adipocytic mass reduces the hepatic insulin uptake; it increases the suprahepatic glucose flow and the production of very low density lipoproteins. The adipose tissue exerts a feminizing effect in men and a masculinizing effect in women. Women have disorders of ovulation and hirsutism, with increase of free testosterone and elevation of luteotropic hormone levels. Men have hypoandrism due to excessive aromatization of androgens and oestrogens. The adipose tissue accelerates the turnover of cortisol and facilitates cortisone production, which stimulates ACTH secretion and maintains stimulation of the adrenal cortex. Hyperinsulinism and resistance to insulin also intervene in hormonal regulation. They elevate the insulin-like growth factor 1 (IGF-1) which inhibits the production of growth hormone and reduces its plasma half-life; hyperinsulinism and IGF-1 facilitate ovarian androgen production; hypothalamic disturbances occur by diminution of sensitivity to hypoglycaemia, and there are abnormalities in monoaminergic and serotoninergic control. Bone tissue density is preserved for a long time, as it is in proportion to the fatty mass and to the oestrogen and IGF-1 levels, but it may be gradually reduced by secondary hyperparathyroidism. Thyroid function and thyrotropic regulations are unaffected.