Adrenal Disorders Flashcards
How much steroid or cortisol does an adult produce in one day?
Normal adult produces 10-30mg cortisol daily
what’s the conversion of methlyprednisolone to prednisone?
Addisonian Crisis
Methylprednisone 4 mg = prednisone 5mg
How is Acute Adrenal Insufficiency treated?
hypo function of adrenals
Hydrocortisone 100 mg intravenously through rapid infusion (IV) and followed by 100 mg of hydrocortisone administered by intravenous
What are the agents of choice for Adrenal Insufficiency
prednisone and hydrocortisone
-morning dose of prednisone 5 mg or hydrocortisone 20 mg
how to we prevent hyperkalmia in Adrenal Insufficiency?
To replace mineralocorticoid loss and to prevent hyperkalemia, the administration of fludrocortisone acetate (Florinef ® ).- Increase K+ secreation prevent hyperalemia
what is the brand name of Fludrocorisone?
Florinef
Describe primary Primary (Addison’s)?
Hyperpigmentation
Weight loss
Dehydration and electrolyte abnormalities are more severe
Describe primary secondary (Addison’s)?
Dehydration and electrolyte abnormalities are less severe
What are the symptoms of Symptoms of Primary and Secondary Adrenal Insufficiency?
Weakness Weight loss Increased pigmentation Hypotension Vitiligo MUST TAKE STERIODS and must be aware of Cortisone Crisis****
Life Threatening – Potentially Fatal
Adrenal hemorrhage
Septicemia
How does Primary Insufficiency (Addison’s Disease)
occur?
90% of the cortex must be destroyed before deficiency occurs.—JFK had Addison’s Disease
How does How does secondary Insufficiency (Addison’s Disease) occur?
hypothalamic-pituitary deficiency of ACTH, producing low concentrations of androgen and cortisol.
Common cause: overuse of exogenous glucocorticoids
which of the three zones have Glucocorticoids: cortisol ?
Zona fasciculata
which of the three zones have Androgens: testosterone and estradiol ?
Zona reticularis
which of the three zones have Mineralocorticoids: aldosterone ?
Zona glomerulosa
ACTH stimulates ?
release cortisol and to a lesser extent aldosterone and androgens
CRH stimulates
anterior pituitary to secrete Adrenocorticotropic Hormone (ACTH)
response to decreased cortisol
Corticotropin Releasing Hormone (CRH) is secreted by the median eminence of the hypothalamus
Aldosterone secretion is increased by:
Decreased blood pressure
Salt depletion
Beta adrenergic stimulation
CNS excitation
Aldosterone secretion is inhibited by:
Salt loading Vasopressin Potassium Calcium Increased blood pressure
Circadian Rhythm: Dawn Phenomenon
Maximal secretion: before and in the initial hours of wakefulness
Cause of hyper function of adrnal gland?
Cushing’s Syndrome
Supraphysiologic levels of endogenous cortisol
Pituitary-dependent disease accounts for 60-70% of all Cushing’s cases
Adrenal adenomas, adrenal carcinomas and ectopic ACTH-secreting tumors make-up the remaining 30-40%
Cushing’s Syndrome: Presentation?
Central obesity Facial rounding Buffalo hump Facial plethora Hirsutism Hypertension Gonadal dysfunction Amenorrhea Osteoporosis Psychiatric changes Glucose intolerance Muscle weakness
HTN in 80% of people
Name the diagnostic test for hyperfution adrenal (Cushings??
Midnight Plasma Cortisol-** LOW**
Late-Night Salivary Cortisol- if elvated suggest Cushing’s
24-hour Urine Free Cortisol: when elevated this is highly suggestive of Cushing’s.
1mg Overnight Dexamethasone Suppression Test: 1 mg of dexamethasone is given at 11PM and an 8AM plasma cortisol is measured
If treatment of choice is SURGERY for cushings who gets the drug therapy?
Drug therapy is reserved for:
Preoperative patients
Adjunct in postoperative patients awaiting response—POST OP
Rarely, palliative therapy when surgery is not indicated
Drug therapy for cushsings?
Steroidogenesis Inhibitors: Block cortisol production
- Metyrapone
- Ketoconazole
- Etomidate
- Aminoglutethimide
Adrenolytic Agent
-Mitotane
Neuromodulatory Agent
-Cyproheptadine
Glucocorticoid-Receptor Blocker
Mifepristone—BABY KILLER
Whats the brand name of Etomidate?
Amidate
Whats the brand name of Aminoglutethimide ?
Cytadren
Whats the brand name of Metyrapone?
Metopirone
whats the brand name of Ketoconazole
Nizoral
Whats the details of Metyrapone?
Steroidogenesis Inhibitors
Only available by Compassionate Use – Not over the counter commonly
DOC- Ectopic ACTH syndrome
Works quickly
Significant androgenic effects
Hirsutism, acne
Whats the details of Ketoconazole?
Steroidogenesis Inhibitors
Works slowly, several weeks
Ectopic ACTH syndrome
Antiandrogenic effects
Whats the details Etomidate?
Steroidogenesis Inhibitors
Only available intravenously
Works quickly
Used for acute, emergent treatment. –ER or OR
General anesthetics
Whats the details of Aminoglutethimide?
Steroidogenesis Inhibitors
Inhibits cortisol, aldosterone and androgens
Second line agent–sedation is common
Ectopic ACTH syndrome
whats the brand name of Mitotane?
Lysodren
Whats the brand name of Mifepristone?
(Korlym®) (RU-486)
Whats the brand name of Pasireotide?
Signifor
Whats the brand name of Eplerenone?
Inspra
What agents are used to treat Hyperaldosteronism?
Aldosterone Receptor Antagonists
- Spironolactone
- ->Avoid salicylates
- ->Wait 4-8 weeks for full effect
-Eplerenone (Inspra)-(Less sex-steroid adverse effects)
Potassium –Sparing Diuretic
Amiloride to manage HTN
Whats the presentation of Hyperaldosteronism?
Serum potassium of less than 3.5 mEq/L with concurrent urinary potassium of greater than 30 mEq (one way to detect aldosterone***
Hypertension Tetany/paralysis Polydipsia Nocturnal polyuria Fatigue Suppressed renin Hypokalemia Hypomagnesemia Increased plasma aldosterone
Whats the details of Mitotane?
Adrenolytic Agent
Cytotoxic
Adrenal Carcinoma
(Destroys adrenal cortex)
Significant neurologic and GI adverse effects
–Avoid pregnancy for 5 years after use, stored in adipose tissue.
Adrenolytic Agent
Whats the brand name of Cyproheptadine?
Periactin
Whats the details of Cyproheptadine?
Neuromodulatory Agent
Sedation and weight gain limit its use.
Anticholinergic side effects also limit use
Nonselective serotonin receptor antagonist and anticholinergic agent*** What to minimized ACTH secretion.
Pituitary dependent Cushings
whats the details of Mifepristone?
Glucocorticoid-Receptor Blocker
Potent progesterone and glucocorticoid receptor antagonist
Effective at reversing hyperglycemia, HTN and weight gain due to hypercortisolism
Reduced serum potassium-Change in K
—K supplement needed or spironolactone
Abortifacient, R/O pregnancy prior to use
whats the details of Pasireotide?
Somatostatin analogue
Binds to somatostatin receptors (sst1-5).
Activates sst5 –>and inhibits ACTH secretion.
Indicated for pituitary Cushing’s.
Hyperglycemia/DM on initiation (avoid with DM pts)
Bradycardia/QT prolongation
Pituitary-Dependent Cushing Disease
Why shouldn’t we used systemic therapy for Cushings?
Systemic steroid administration can cause iatrogenic
Cushing’s syndrome and can lead to: Susceptibility to infection Sodium retention Hypokalemia Cataracts Osteoporosis Edema Hypomagnesemia Peptic Ulcer Disease Generalized suppression of the HPA axis
