Review of Pharmacology - 9E (2015)

Endocrinology
Important Points
Maximum glucocorticoid activity
Maximum mineralocorticoid activity
Glucocorticoid with Maximum mineralocorticoid activity
Least potent glucocorticoid
Most potent glucocorticoid
Selective mineralocorticoid action (with zero glucocorticoid
activity)
Selective glucocorticoid action (with zero mineralocorticoid
activity)
Steroid with maximum topical activity
Dexamethasone
Aldosterone
Hydrocortisone
Cortisone
Betamethasone
DOCA
Methylprednisolone, triamcinolone, paramethasone, dexamethasone,
betamethasone
Triamcinolone acetonide
Uses of Corticosteroids
1. Replacement Use
A) Acute adrenal insufficiency: It is an emergency condition and requires immediate
management with parenteral administration (i.v.) of hydrocortisone.
B) Chronic adrenal insufficiency (Addison’s disease): It is treated with oral doses of
hydrocortisone. Mineralocorticoids like fludrocortisone may also be required.
C) Congenital adrenal hyperplasia (CAH): This disorder is a result of congenital deficiency
of the enzymes involved in the synthesis of corticosteroids. Due to decreased
adrenal steroids, there is no feedback inhibition of pituitary and consequently
ACTH secretion increases. ACTH cannot release corticosteroids (because they
are not synthesized) but it results in overgrowth of adrenal glands leading to
symptoms. Thus, treatment of congenital adrenal hyperplasia (adrenogenital
syndrome) is aimed at reducing ACTH secretion. Exogenous glucocorticoids like
hydrocortisone cause feedback inhibition of HPA axis and lead to amelioration
of symptoms. To prevent CAH (in a pregnant female with history of baby with
CAH), steroids should be administered at 6 weeks period (i.e. as soon as the
pregnancy is diagnosed). The genotype and sex of the fetus is then determined. Steroid
therapy is stopped if sex is male. If genotyping reveals female sex, steroid therapy
is continued till delivery (to prevent virilization).
General Endocrinology Pharmacology
2. Diagnostic Use
Dexamethasone suppression test is used to test the intactness of HPA axis function and
diagnosis of Cushing’s syndrome. Dexamethasone in a normal person inhibits the release
of CRH (feedback inhibition) and it does not interfere with measurement of endogenous
corticosteroids in blood or urine. Dexamethasone (1 mg) is given orally at night (11 PM) and
plasma cortisol levels are measured in the morning (8 AM). If cortisol levels are less than
3 µg/dl (feedback inhibition is present), it signifies that HPA axis is functioning properly.
If cortisol in plasma is more than 5 µg/dl (no feedback inhibition), it indicates that there is
excessive secretion of cortisol due to adrenal or pituitary tumor (Cushing syndrome).
After confirmation of Cushing syndrome by dexamethasone suppression test, it is possible to
differentiate between Cushing’s disease (due to pituitary tumor) and other causes (adrenal
tumor or ectopic ACTH) by using large dose of dexamethasone. 8 mg of dexamethasone
is administered at night and plasma cortisol level is measured in the morning. If Cushing
disease is present, cortisol levels will be less than 50% of the previous value. If cortisol levels
are still high, ACTH levels are measured. Reduced ACTH levels suggest adrenal tumor
whereas elevated ACTH levels suggest ectopic ACTH production.
Dexamethasone suppres sion
test is used to test the intactness
of HPA axis function and diagnosis
of Cushing’s syndrome.
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