Fisiopatologia

Question 1

Adisson

Answer 1

T cells and cellular immunity also have important roles in the pathogenesis of autoimmune Addison’s disease, and the generation of autoantibodies can be secondary to tissue destruction

Question 2

The adrenal cortex has three distinct zones, which secrete

Answer 2

• Aldosterone is synthesised in the outermost zone, the zona glomerulosa. Its secretion is predominantly regulated by the renin– angiotensin system and extracellular potassium concentrations; therefore, it is not impaired in secondary and tertiary adrenal insuffi ciency
• Cortisol secretion from the zona fasciculata is primarily regulated by corticotropin, which is released from the anterior pituitary in response to the hypothalamic neuropeptides corticotropin-releasing hormone and arginine vasopressin.50,60,64 In healthy people, cortisol secretion is pulsatile, and circulating cortisol concentrations fl uctuate naturally in a circadian fashion, highest in the early morning (0600–0800 h) and lowest around midnight
• The adrenal androgens, androstenedione, dehydro-epiandrosterone, and the sulphate ester of dehydro-epiandrosterone, are synthesised in the innermost zona reticularis.50 Dehydroepiandrosterone and its sulphate show a characteristic, age-associated pattern, with very high concentrations in the neonatal period, a decline to very low concentrations during the fi rst few months of life, and a continuous increase starting between age 6 and 10 years, termed adrenarche. Peak concentrations of these two hormones are achieved during the third decade of life; they then decline steadily from the fi fth decade (adrenopause) with concentrations decreasing to 10–20% of the maximum at around age 70 years. The age-related decline in dehydro epiandrosterone sulphate does not refl ect a general loss of adrenocortical output because cortisol concentrations are maintained and even slightly rise with age

Question 3

In autoimmune adrenal insufficiency, the first zone affected by immune-mediated destruction is generally

Answer 3

the zona glomerulosa, possibly because it is thinner than the other two, or is more vulnerable to autoimmune attack. This feature might explain the fi rst step of adrenal failure, which is characterised by high plasma renin activity and low aldosterone concentrations, followed by a phase of progressive glucocorticoid defi ciency, initially with inadequate response to stressful stimuli and then by a phase of overt failure with low basal cortisol concentrations.