Cushing
decrease risk of morbidity and mortality, increase quality of life
Levoketoconazole MOA, BBW, monitoring?
inhibits CYP11B1 to decrease cortisol production
BBW: hepatotoxicity, QT prolongation
Monitor AST/ALT, bilirubin, ECG, potassium, magnesium
What are the 2 main causes for primary hyperaldosteronism? What is the treatment for each?
bilateral adrenal hyperplasia, aldosterone producing adenoma
BAH: aldosterone receptor antagonists
APA: adenoma resection, then aldosterone receptor antagonist if needed
What are the neuromodulatory agents? What are they not effective for?
cabergoline (dopamine agonist), pasireotide (somatostatin analog)
not effective for ACTH independent disease
What can cause adrenal crisis?
rapid GC withdrawal or failure to increase dose in times of increased physiologic stress
What does exogenous etiology refer to in regard to cushing syndrome? Endogenous?
exogenous: drug induced, correlated with dose and duration of steroids
endogenous: ACTH dependent (pituitary adenoma), ACTH independent (adrenal adenomas)
What are the steroidogenesis inhibitors?
ketoconazole, levoketoconazole, metyrapone, mitotane, etomidate, osilodrostat
Is GC and/or MC replacement therapy necessary for primary adrenal insufficiency (Addison disease)? Secondary adrenal insufficiency (drug induced)?
primary: both lifelong duration
secondary: GC, MC usually unnecessary, temporary until HPA axis recovers
Pasireotide MOA, monitoring, and AEs?
MOA: somatostatin analog, stimulation results in decrease ACTH release
monitoring: thyroid, gallbladder, IGF-1, FBG
AE:nausea, biliary tract disorders, hyperglycemia
How do we avoid drug induced cushing syndrome?
use lowest effective steroid dose for shortest duration possible
consider administration routes that minimize systemic exposure
avoid concurrent medications that inhibit steroid metabolism
How do we treat exogenous cushing syndrome?
gradual discontinuation of causative agent
Ketoconazole MOA, BBW, AEs? How long is onset of action?
inhibits 17 alpha hydroxylase, decrease in cortisol production
BBW: hepatotoxicity (contraindicated in patients with chronic liver disease), use with other meds can prolong QT interval
AE: hepatic dyscrasia (BBW), antiandrogen effects, GI
onset of action is weeks
Etomidate MOA, pearls?
reserved for emergency use, requires ICU monitoring (risk of sedation)
Cabergoline MOA and AEs?
MOA: long acting selective D2 receptor agonist, results in decreased ACTH release
AE: nausea, dizziness, orthostasis, nightmares, vivid dreams, psychosis
What is the treatment for acute adrenal crisis?
IV hydrocortisone 100mg bolus followed by continuous infusion
adequate IV fluid resuscitation
MC replacement therapy usually not necessary at first
Treatment options for endogenous cushing syndrome (in general)?
Surgical resection is first line
Second line: pharmacotherapy, radiation, bilanteral adrenalectomy (lifelong GC and mineralocorticoid replacement therapy necessary)
Metyrapone MOA, AEs, pearls?
Inhibits CYP11B1 to decrease cortisol production
AE: androgen related with chronic therapy, mineralocorticoid effects, GI
pearls: quicker onset, take with food to decrease GI upset
Osilodrostat MOA, warnings, monitoring, AEs?
Inhibits CYP11B1
warnings: adrenal insufficiency, androgenic effects, mineralocorticoid effects, QT prolongation
ECG at baseline, within one week after starting therapy and as indicated
AEs: HA, N/V, fatigue, edema
What needs to be monitored during treatment of cushing syndrome?
monitor for drug induced adrenal insufficiency (N/V, anorexia, fatigue)
24 hour UFC or morning serum cortisol (except mifepristone)
pts may feel unwell 6-9 months after starting treatment
ensure metabolic syndrome is treated (decrease CV morbidity)
may take 4-5 years for BMD to fully recover
What can be given to pediatric pts with adrenal insufficiency? How is it administered?
alkindi sprinkle (hydrocortisone) oral granules
DO NOT swallow the capsule, open capsule and poor granules onto tongue, do not add directly to liquid and do not chew or crush granules
consume fluid after dose to ensure all granules are swallowed
What are the drug classes used to treat cushing syndrome? Can they cure the disease?
cannot cure, just used to manage
steroidogenesis inhibitors, adrenolytic agent, neuromodulatory agents, GC receptor antagonist
Mitotane MOA, indication, pearls, AEs?
MOA: steroidogenesis inhibitor and adrenolytic agent
indication: adrenocortical carcinoma
pearls: slow onset of action, CYP3A4 interactions, teratogen, long half life and stored in adipose tissue
AEs: significant GI and CNS effects
What is the mainstay treatment for adrenal insufficiency? What is essential for patient counseling? goals of therapy?
corticosteroids
education on missed dose, stress dose, adherence, emergencies, AEs, expected outcomes
use lowest dose possible, prevent adrenal crisis, alleviate s/sx of adrenal insufficiency
MOA: glucocorticoid receptor antagonist
indication: control hyperglycemia occurring secondary to hypercortisolism
AEs: signs of cortisol insufficiency, mineralocorticoid effects, headache
BBW: termination of intrauterine pregnancy
What are some important corticosteroid therapy counseling points?
Take with food to decrease GI upset, do not take close to bedtime or may have trouble sleeping, do not stop taking steroid therapy on your own, dose may need increased when sick or stressed, do not take 2 doses at once