Transcript 1-Adrenals

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The cortex consists of 3 layers
1st is zona granulosa mineralocorticoids, for example
aldosterone.
The inner 2 layers are zona fasiculata
and zona reticularis - glucocorticoids
(e.g. cortisol) and androgens (e.g.
dehydroepiandrosterone—DHEA).
Excess or deficiency in serum level of
any of these layers results in diseases.
• Steroid hormones, bile salts and vitamin D all
are derived from cholesterol that's why the
steroid-producing tissues are all rich in
cholesterol.
• Cholesterol is a 27C molecule; its derivative
steroids contain either of 18, 19 or 21C
molecules according to its type:
• 21C- progesterone, glucocorticoids and
mineralocorticoids, 19C-androgens 18Coestrogens
• The rate-limiting step is the first step which is the
conversion of cholesterol to pregnenolone, the final
products are cortisol, aldosterone and androgens—
DHEA, and oestrogen (oestrone).
• The pituitary hormone ACTH is stimulator of the
inner two layers but not on the outer layer; therefore
it stimulates production of cortisol and androgen.
• The outer layer of this gland is controlled by another
system in the body called renin-angiotensin system
which stimulates production of aldosterone
(mineralocorticoid derivative).
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Glucocorticoids: include cortisone and cortisol.
Cortisol stimulates gluconeogenesis, lipolysis
and protein breakdown (catabolic hormone) and
antagonizes the action of insulin.
That's why they are called diabetogenic agents.
• Cortisol is normally involved in retention of water
and electrolytes from renal tubules to ECF.
This explains why deficiency of this enzyme results
in hypotension, while excess amounts results in
hypertension.
Cortisol also suppresses the immune and
inflammatory responses (antiinflammatory), because it decreases the
number of leucocytes and also their
migration and inhibits phospholipase A2,
which is important for production of
inflammatory molecules
(prostaglandins and leucotrienes).
For this reason, this hormone is used as a
drug in the treatment of inflammatory
conditions such as allergy and
rheumatic diseases in form of cortisone
(Hydrocortisone™) which converts
inside the body to cortisol—the active
form.
• In blood, 95 per cent of cortisol is bound to cortisolbinding protein (CBP). The other 5 per cent of hormone
is unbound to protein (free).
• In CBG↑ due to genetic causes or pregnancy, or if the
patient is on contraceptive pills so the total cortisol in
serum is high due to high level of bound form only.
• In contrast, loss of CBG, like nephrotic syndrome,
androgen therapy, leading to decrease in total level of
hormones, due to a decrease in the bound form only,
while the free form is normal in both cases (no
symptoms).
• The hormone is inactivated by liver cells through
conjugation with sulphate or glucoronate to sulphated
or glucoronated hormone can be excreted in urine.
• cortisol is the only steroid involved in HPA axis.
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Increased serum cortisol level is due to
several causes, such as:
ACTH↑ (common): (1) as part of a
syndrome due to pituitary adenoma
(Cushing's disease) (2) caused by nonpituitary carcinoma or (3) by ACTH therapy
as a drug.
Cortisol↑: (1) due to tumor in adrenal
cortex, or (2) by cortisol therapy as a drug¹
in both there is ACTH↓.
1. high cortisol results in hyperglycaemia and
glucosuria, because cortisol antagonises the
activity of insulin and increases protein
breakdown and lipolysis, therefore increases the
activity of gluconeogenesis. [Diabetogenic]
2. Protein breakdown also causes negative
nitrogen balance (increased loss of nitrogen in
urine) loss of bone matrix is due to defect in
collagen and this result in osteoporosis. Also,
protein breakdown results in muscle wasting and
thin skin with bruising. (striae atrophicae).
3. High cortisol acts like aldosterone, therefore it
enhances sodium reabsorption in exchange to
hydrogen and potassium ions in the renal
tubules. This means it causes hypernatraemia
(Na⁺↑) and increased loss of potassium and
hydrogen in urine, therefore results in
hypokalaemia (K⁺↓) and alkalosis (pH＞7.45),
respectively.
4. If the cause of Cushing's syndrome is increased
ACTH, this hormone will stimulate androgen
production as well as cortisol. This explains
hirsutism and virilism in female subjects with
menstrual disturbances.
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Serum cortisol: we should measure this hormone in the
morning and evening to see if there is any defect in
circadian rhythm, which is a diagnostic feature of
Cushing's syndrome. However, the presence of
significantly high serum cortisol levels in the evening
sample is also diagnostic.
Urine cortisol: in 24hr urine samples is diagnostic when it
is at very high levels.
Tests for HPA axis: by checking both serum cortisol and
serum ACTH, in order to differentiate the cause of
disease (primary or secondary).
If both are increased, this indicates secondary (explain
how). If one of them (only cortisol) is high and ACTH is
undetectable, this indicates primary endocrine disease. If
both are low, it indicates drug therapy.