EXAM 3 Adrenal Gland disorders Dr. Hess Flashcards
Why do Cushings cause diabetes?
too much cortisol -> glucose production ->
-> increase in insulin resistnace
What are the 3 adrenal gland produced corticosteroids?
-Cortisol (glucocorticoid)
-Aldosterone (mineralcorticoid)
-DHEA (androgen)
Which part of the adrenal gland secretes the corticosteroids?
adrenal cortex
(the adrenal medulla secrets catecholamines: NE and epinephrine)
What is the cause of adrenal insufficiency?
Addison’s disease
-auto-immune disease
-Effects all regions of the adrenal gland
secondary cause:
-abrupt d/c of exogenous glucocorticoids (meds)
What are the secondary causes of adrenal insufficiency?
-abrupt d/c of exogenous glucocorticoids (meds)
-most common cause
-> shuts down the HPA axis
patients may stop due to a stressful event (infection, couldn’t afford the meds, quit due to side effects)
-> risk for adrenal crisis
Which drug may cause adrenal insufficiency?
Ketoconazole
Functions of Cortisol
Cortisol:
-Regulates metabolism of fat, carbohydrates and
protein
Functions of Aldosterone and its effect in Addison’s disease
Maintains electrolyte balance and volume Aldosterone homeostasis (Na+ and fluid retention)
in Addisons’ disease:
-hypotension
-hyperkalemia, hyponatremia
Functions of DHEA and its effect in Addison’s disease
converted to testosterone or estradiol – expression
of primary and secondary sex characteristics
-women are more affected bc 25% of their testosterone comes from the adrenal gland vs in men only 5%
-in Addison’s disease: decreased libido and secondary sex characteritiscs
Clinical Presentation in Addison Disease - Symptoms
-fatigue, malaise, anorexia, weakness
-postural dizziness, syncope
-GI: N/V, diarrhea, constipation, abdominal pain
-myaglia, arthlagia
-decreased libido, amenorrhea
-> all related to low levels of cortisol, aldosterone, DHEA
Patient presentation
Look great feel awful
-thin and tanned
Signs of Addison’s disease
-Weight loss
-Hyperpigmentation
-Hypotension
-thinning of axillary and pubic hair
-vitiligo (loss in skin color in patches - no melanocytes due to autoimmune)
What causes hyperpigmentation in Addison’s disease?
due to increased ACTH release from the anterior pituitary gland that is upregulated in low cortisol
-> with ACTH the myelocyte-stimulating hormone is expressed
In what pattern is cortisol physiologically released?
pulsatile pattern in a circardian rythm
-naturally it is high in the morning
-patients should take it as the first thing in the morning to mimic physiologic release
-highest dose in the morning
What is the drug of choice and the starting dose in Addison’s disease?
Hydrocortisone
-starting dose: 15-20 mg per day
may also use: 5mg of prednisone (or equivalent) per day
-using a long-acting steroid (dexamethasone, highly cortical activity) may lead to overtreatment of the cortical compartment
-> leads to diabetes, cataracts, obesity, heart disease???
Which of the glucocorticoids have mineralocorticoid activity?
-Cortisone (the inactive form of cortisol) - 2
-Hydrocortisone (binds MR and GR) - 2
-Prednisone (prodrug) - 1
-Prednisolone - 1
1=less MR activity
2= more MR activity
-when dosing, we have to take the MR properties (Na and water retention) and the patient’s BP goal into account !!! (EXAM Q???)
Hypotension and corticostroid dosing
-when we dose to get their BP up we might overtreat the cortisol component (GR receptor)
Which of the corticosteroids are short and long-acting?
short-acting:
-Cortisone
-Hydrocrtisone
long-acting:
Dexamethasone
Which of the corticosteroids are intermediate acting?
-Prednisone (prodrug)
-Prednisolone
-Methylprednisolone
Advantages of the short-acting glucocorticoid steroids
-more flexible in making adjustments, since the effect is short
-more mineralocorticoid activity -> BP regulation
BUT effects wears off quickly, so it has to be dose multiple times a day
Advantage of intermediae-acting steroids
Prednisone, Prednisolone
-longer-acting -> once daily dosing
-smoother blood levels
BUT it is less adjustable and it may have too much glucocorticoid activity
What do dose adjustments for glucocorticoids depend on?
Dose adjustments q 6- 8 weeks based on improvement of patient signs and symptoms
What are the short-term ADRs?
may happen due to overtreatment
-Insomnia/excitability
-Elevated glucose
-GI upset
-Increased appetite/Weight gain
What are the long-term ADRs?
may happen due to overtreatment
-Diabetes
-HTN
-Osteoporosis
-Cataracts
-Slow wound healing
How would the dose of steroids change in stressful events?
Exercise (small stress)
- Extra 5mg hydrocortisone?
Sickness or injury (e.g., flu) (moderate stress)
-2-3x the usual GC replacement dose until recovery
Critically ill, Major surgery, Major trauma (High stress)
-Up to 10x usual GC replacement doses
-Refer to ER if vomitin, consider IV
Which drug may be used to treat orthostatic hypotension?
Fludrocortisone
-> also used for Addison’s disease when we have reached the ideal glucocorticosteroid supplement but not enough mineralcorticoid supplementation
-used in combination with glucocorticoids
-it only has mineralocorticoid activity!!!
What are the signs of overtreatment with Fludrocortisone?
too much mineralcorticoid activity
-increased BP
-edema
-Hypokalemia
When is Androgen replacement therapy considered?
after 6 months of cortisol corticosteroid treatment
-fix the cortisol first
-make sure the BP is fine
-treat with DHEA if the patient is still complaining about androgen-related symptoms (decreased libido)
What is the drug of choice for Androgen replacement therapy?
Dehydroepiandrosterone (DHEA)
-25 – 50mg daily (OTC)
-only for women (since men only produce 5% of androgens from their adrenal gland)
Which labs should be monitored for Addison’s disease?
-Patient symptoms
-Vitals
-Electrolytes
-Signs/Symptoms of overdosin
-we dont check for ACTH bc
-remember we dose adjust based on patients’ symptoms
What is an Acute Adrenal Insufficiency
-Addisonian Crisis after abruplty stopping steroid supplement -> HPA axis is not active
-5 S’s
-Steroids IV
-Salt (2-3L of NS or D5NS bolus, bc they are hypotensive)
-Sugar (they may have low blood sugar)
-Support and Search (find the cause)
-> to prevent this we use stress-dosing
What is the treatment dose in Addisonian Crisis?
-Hydrocortisone 100mg IV bolus q 8 hrs x 24 hrs then 50mg q 6-8 hrs after hemodynamic stability.
-Taper to a maintenance dose after 4 -5 days
-Monitor symptoms, BP, Weight and Electrolytes
When should we consider tapering when d/c steroids?
Supraphysiologic doses (> 7.5mg/day prednisone or equivalent) in long-term steroid therapy (> 3 weeks)
-there may be different ways (regimen) to taper down
-Taper by 5 – 20% every 1 – 2 weeks
-Increase dose and slow taper for disease
flare
Clinical presentation of Cushing’s disease - Head
-thinning hair
-moon face
-cereblra atrophy
-fat deposition on the back
Clinical presentation of Cushing’s disease - Inner
-diabetes
-osteoporosis (catabloic effect)
-HTN (too much mineralcorticoid activitiy)
-immunosuppression
-adrenal hyperplasia
-poor wound healing
-muscle weakness (catabolic effect)
-obese (trunk area - too much cortisol and altered fat deposition)
-thin arms and legs (catabolic effects)
-moon face
-fat deposition on the neck
-strae on the skin
What is the treatment of choice in Cushing’s Syndrome?
-Surgery (80-90% cure rate)
Pharmacotherapy for patients:
-Tumor can’t be localized
-Not surgical candidates
-Failed surgery
-relapse after surgery
-adjunctive therapy is needed for remission
Pharmacotherapy targets
Hypothalamus: suppress the release of CSH
Anterior pituitary: suppress the release of ACTH
-Dopamine agonists
-Somatostatin analogs
-PPAR-gamma ligands
Adrenal gland: suppress the release of the steroids
-Ketoconazole
-Metyrapone
-Mitotane
-Etomidate
block cortisol receptor
-Mifepristone
Which levels are monitored in Cushing’s disease
Urinary Free Cortisol (UFC)
-hypercortisolemia -> leads to increased cortisol in the urine
-a marker on how well a patient is responding to therapy
(reference ranges are provided on the EXAM)
What is the drug of choice and the starting dose in Cushings disease?
Ketoconazole
400mg - 1.6g per day
What is the BBW for Ketocanozole
hepatotoxicity
-> monitor liver function
monitor urinary free cortisol in Cushing’s treatment
What is required for proper absorption of Ketoconazole and what are potential DDIs?
it needs an acidic environment (stomach pH)
DDIs:
-PPIs and H2R antagonist
-warfarin and many more
-Ketoconazole is a potent CYP3A4 inhibitor
Which of the drugs is a adrenolytic agent?
Mitotane
tetragenic, avoid pregnancy for 5 years
Which drug is indicated for Cushing’s and diabetes or glucose intolerance?
Mifepristone (Korlym)
Hyperaldosteronism Quote
When BP can not be controlled with 3+ medications
(including a diuretic), think hyperaldosteronism
What are the effects of Hyperaldosteronism on the cardiovascular system?
too much aldosterone -> Na+/K+ transporter synthesis
-Salt retention-> HTN
-detection of HTN leads to downregulation of Renin
-Hypokalemia
Clinical Presentation in Hyperaldosteronism
Symptoms
-mood disturbance
-headache, tiredness
-Polyuria
-Nocturia
-Muscle weakness, Paraesthesia
Signs
-HTN
What is the drug of choice in Hyperaldosteronism?
Spironolactone
-> overtreatment: hyperkalemia, impotence, gynecomastia, menstrual irregularities
-monitor potassium
How is Spironolactone different from the other aldosterone antagonists?
it is not specific to aldosterone
it also has antitestosterone effects binding to androgen receptors
-useds for anti-testosterone effects: POCS, acne, hirsutism
-other uses: HTN, HF, ascites (fluid collection in the stomach)
Which drugs to use if spironolactone has too many antitestosterone effects during therapy?
Eplerenone (Inspara)
-selective to MR -> fewer antitestosterone related side effects
3rd line option for Hyperaldosteronism
Finerenone (Kerendia) - non-steroidal
-actually indicated for CKD in patients with diabetes
Which patients should not be treated with Aldosterone antagonists?
patients with renal impairment
-risk for hyperkalemia
