Cushing's Disease Flashcards
Cushing’s is a disorder caused by…
Persistent exposure to excessive glucocorticoids
Cushing’s is primarily a result of…
Exogenous use of CS
Overproduction of endogenous cortisol can either be…
Endogenous hormones involved in HPA axis?
ACTH dependent (80%), or ACTH independent (20%)
ACTH dependent overproduction of cortisol is commonly caused by…
A benign pituitary tumour over-producing ACTH, or by an ectopic ACTH source
ACTH independent route of endogenous overproduction of cortisol can be caused by…
HPA-axis is not triggered
Adrenal gland tumours
Stimulate release of cortisol
Diagnosis of Cushing’s is often difficult and delayed, because…
It mimics other conditions; medical history and testing of HPA-axis is necessary
2 steps that are required when Cushing’s is suspected, is to…
Establish if hypercortisolism is present
Establish the cause
Clinical features of Cushing’s involves…
Think about CS adverse effects
Excess cortisol effects
ex: Centripetal obesity, skin changes,
acne, striae, fatigue, sexual dysfunction, irregular periods, HTN, osteopenia, growth suppression, bruising
Signs that may help to distinguish Cushing’s from obesity include…
Signs of protein wasting (thin skin, unusual bruising, muscle weakness), suddenly appearing red striae
Decreased linear growth evident in children
Treatment goals for Cushing’s involves:
Removing source of hypercortisolism, and restore cortisol secretion to normal
Reverse clinical features, and prevent dependency on medications
Treatment of Cushing’s is primarily aimed at removing the cause, which involves…
Surgical resection (of adrenal tumours, pituitary adenoma, etc.) or removal of the drug-induced cause
Surgical resection of ectopic ACTH syndrome is difficult, because…
Multiple tumour sites often exist; 10-30% are cured with surgical removal, and remaining 70-90% need post-op medication
When surgical removal of tumours cannot be done or is ineffective, what can be done?
Medications
Medication are used in Cushing’s to…
Lower cortisol levels pre-surgery
Adjunct tx after unsuccessful surgery/radiation, or for non-resectable tumours
Help treat severe symptoms
CS replacement therapy may be required after surgery because of…
HPA-axis suppression, due to excess cortisol present over long period of time
Steroidogenesis Inhibitors include the 3 following medications:
Ketoconazole, metyrapone, mitotane
A medication that inhibits ACTH secretion includes:
Pasireotide
Steroidogenesis inhibitors MOA is to…
Block the synthesis of cortisol
Typically, the drug of choice for Cushing’s treatment (if proceeding with pharmacotherapy) is…
And why? Dose?
Ketoconazole - effectiveness good, and adverse effect profile not as severe as others
Typical dose 200-400mg TID
Adverse effects with ketoconazole include…
GI upset, gynecomastia
Headache, sedation, impotence, decreased libido, increased LFT’s
Oral ketoconazole needs to be cautioned with other medications because…
Many DI’s are present - involved with CYP1A2, 2C9, 3A4
Ex: CCB’s, cyclosporin, benzo’s… etc.
Metyrapone is often used for the purpose of…
Adjunct therapy
Diagnostic agent
If experiencing dose-limiting adverse effects with ketoconazole
Adverse effect profile of metyrapone differs from ketoconazole, due to…
Significant androgenic adverse effects (hirsutism, acne)
Others: N/V, abdominal discomfort, headache, dizziness, allergic rash
Mitotane is unique as its indication is for…
Inoperable adrenal carcinoma
In combination with irradiation, or other steroidogenic inhibitors
