FK
Hyperfunction:
Cushing’s Syndrome
Hyperaldosteronism
Hypofunction:
Acute Adrenal Insufficiency
Possible Treatment Options Based on Etiology
Etiology
Nondrug
Treatment
Drug Name
Ectopic ACTH Surgery, Metyrapone
syndrome chemotherapy,
irradiation
Pituitary-dependent Surgery, irradiation Mitotane
Metyrapone
Mifepristone
Cyproheptadine
Adrenal adenoma Surgery, Ketokonazole
postoperative
replacement
Agent: mitotane
A cytotoxic drug, structurally resembles DDT
Inhibits the 11-hydroxylation of 11-desoxycortisol &
11-desoxycortocosterone inhibition of cortisol &
corticosterone
Therapeutical effects after weeks to months
Exerts cytotoxic effects: atrophy of the adrenal cortex
Significant neurologic & GI side effects
Neuromodulators of ACTH release
Pituitary secretion of ACTH mediated by various
neurotransmitters: serotonin, GABA, acetylcholine,
catecholamines
Agents: cyproheptadine, ritanserin, ketanserin,
bromocriptine, cabergoline, valproic acid,
octreotide, lanreotide, rosiglitazone, tretinoin
Cyproheptadine: a non-selective serotonin receptor
antagonist & anticolinergic drug
Significant side effect: sedation, weight gain
limitid use
Glucocorticoid-receptor blocking
agents
Mifepristone (RU-486): a potent progesterone &
glucocorticoid-receptor antagonist
Inhibits dexamethasone supression, endogenous
cortisol & ACTH level
Highly effective in reversing the manifestation of
hypercortisolism (hyperglicemia, hypertension,
weight gain)
Induces a compensatory rise in ACTH & cortisol
level efficacy & toxicity monitoring rely on clinical
sign rather than laboratory assessment
Drug Monitoring