Self-assessment questions: Targeting endogenous glucocorticoids in degenerative disease
Obesity is associated with:
Type 2 diabetes, dyslipidaemia and hypertension in people with Cushing's syndrome
Increased levels of cortisol in serum
Enhanced clearance of cortisol
Impaired suppression of cortisol in the dexamethasone suppression test
Normal negative feedback control of cortisol, as assessed by the combined receptor antagonist stimulation of the hypothalamic-pituitary-adrenal (HPA) axis (CRASH) test
With regard to 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1):
It is responsible for extra-adrenal production of cortisol
It regenerates cortisol from metabolically inert cortisone in the kidney
It is upregulated in the adipose tissue in obese people
Its activity results in inhibition of angiogenesis after myocardial infarction
It increases insulin sensitivity in skeletal muscle
Cognitive function:
Is often impaired in people with Cushing's syndrome
Declines more rapidly with age in mice with brain-specific overexpression of 11β-HSD1
Is reduced by intracerebroventricular infusion of glucocorticoid antagonists
Is enhanced in young 11β-HSD1 knockout mice relative to wildtype counterparts
Can be improved with 11β-HSD1 inhibition in humans
Inhibition of 11β-HSD1:
Has not been demonstrated to affect glycaemic control in patients with type 2 diabetes
Causes significant weight gain
Results in worsening of dyslipidaemia in patients with type 2 diabetes
Reduces levels of cortisol in serum
Results in increased adrenal production of androgens
Answers to these self-assessment questions can be found on page s92.
- © 2012 Royal College of Physicians
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