Adrenal cortex

Regarding hormone production in the adrenal cortex, the following statements are true

EXCEPT which one? (CRH: corticotropin releasing hormone; ACTH: adrenocorticotrophin

hormone)

a) Secretion of cortisol is under the exclusive control of the hypothalamopituitary

CRH–ACTH axis

b) ACTH stimulates aldosterone secretion

c) Hyperkalaemia is a major stimulus to aldosterone secretion

d) Etomidate inhibits 17α-hydroxylase in the zona glomerulosa

e) Urinary cortisol metabolites give a reliable representation of cortisol secretion

Answer: d

Explanation

The adrenal cortex consists anatomically and functionally of three distinct zones, from

superficial to deep, the zona glomerulosa, zona fasciculata and zona reticularis, which

are responsible for the production of mineralocorticoids, glucocorticoids and androgens

respectively. The precursor of all steroids produced here is cholesterol and

subsequently pregnenolone, but then the synthetic pathways diverge and the steroid

molecule ultimately produced depends on the enzymes to which it is exposed. The

enzymes are of the cytochrome P450 superfamily and in each cortical zone are found

those isoforms necessary for the production of the target steroid. The zona glomerulosa

is deficient in 17α-hydroxylase hence it produces aldosterone whose biosynthesis does

not require that enzyme. Etomidate inhibits 11β-hydroxylase and 17α-hydroxylase,

both required for the production of cortisol in the zona fasciculata. Consequently,

etomidate produces adrenal suppression, which after a single induction dose is of

debated significance but if infused is associated with poor outcome. For this reason

etomidate has been withdrawn for administration by intravenous infusion and in some

countries it has been withdrawn altogether. Whereas cortisol secretion is responsive

only to changes in ACTH level, aldosterone secretion can be influenced by angiotensin

II, hyperkalaemia and ACTH. Cortisol secreted by the zona fasciculata and to a lesser

extent the zona reticularis is 80% protein-bound in the plasma to a specific α2-globulin.

It undergoes hepatic reduction in phase I then conjugation with glucuronides during

phase II. The glucuronides of cortisol are excreted renally. In the presence of normal

hepatic and renal functions, measurement of urinary cortisol metabolites does give a

true impression of glucocorticoid secretion.