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Adrenal Gland Disorders

Terms in this set (92)

How many adrenal glands are there and where are they located?
2 and upper part of each kidney
Where does the left adrenal gland drain?
Renal vein
Where does the right adrenal gland drain?
inferior vena cava
What is the center of the adrenal gland?
Adrenal medulla
What does the zona glomerulosa secrete?
mineralocorticoids (aldosterone)
What does the zona fasciculata secrete?
glucocorticoid reproduction
What does the zona reticularis secrete?
Adrenal androgen production (testosterone and estradiol)
Function of aldosterone
maintains electrolyte and volume homeostasis by altering K and Mg secretion and Na resorption
Function of Glucocorticoids
regulate fat, carbs, and protein metabolism
What hormone regulates glucocorticoid secretion?
ACTH
ACTH is a negative feedback loop, so what will inhibit its release?
increased cortisol levels
Hirsutism
increased androgen release
What regulates aldosterone?
RAAS system

Drop in BP-->Angiotensin 3 made--> Aldosterone secretion--> increased Na and water retention--> increased BP
What disease states are due to hyperfunction of the adrenal gland?
1. Cushing's
2. Hyperaldosteronism
What diease states are due to hypofunction of the adrenal gland?
1. Primary adrenal Insufficiency (Addisons disease)
2. Secondary adrenal insufficiency
3. Hypoaldosteronism
4. Congenital adrenal hyperplasia
5. Adrenal VIrilism
6. Hirsutism
What is Cushing's syndrome?
excess cortisol via either exogenous or endogenous
What pharmacological agents can cause iatrogenic cushing's syndrome?
-glucocorticoids
-medroxyprogesterone acetate
-megestrol acetate

**pts who take CYP3A4 inhibitors are at high risk
Clinical signs of cushing's syndrome?
-central obesity
-facial rounding (moon face)
-cutaneous red/purple striae along lower abdomen
-peripheral obestiry
-fat accumulation
-HTN
-Glucose intolerance
-Men: impotence
-Women-decreased menstrual cycle
-Mood changes

*risk of metabolic syndrome--> increased risk of CHD
How do you diagnose Cushing's?
-Rhythmic secretion of cortisol is lost

Measure by:
-x4 normal 24 hour urine free cortisol
-midnight plasma cortisol
-late night salivary cortisol
-low dose dexamethasone suppression test (only for screening)
What tests can determine the etiology of Cushings?
-high dose dexamethasone suppression test
-Metyrapone stimulation test
-plasma ACTH by radioimmunoassay
-Adrenal, chest, or abdominal CT
-Corticotropin releasing hormone stimulation test
-Pituitary MRI
-Inferior petrosal sinus sampling
What are the pharm txts for cushings?
1. Steroidogenic inhibitors
2. Adrenolytic agent
3. Neuromodulators of ACTH release
4. Mifepristone
What are the steroidogenic inhibitors?
-Metyrapone
-Aminoglutethimide
-Ketoconazole
-Etomidate
What is Mitotane?
Adrenolytic agent
When are Steroidogenic inhibitors NOT to be used?
after successful surgery
How do steroidogenic inhibitors work?
Inhibits cortisol production
AE of Metyrapone?
-CNS depression
-Hypotension
-GI
-Electrolyte abnormalites
Dosing for Metyrapone?
250mg PO QID
When is Aminoglutethimide indicated?
short term txt for cushing's if ectopic ACTH syndrome is etiology
What is Aminoglutethimide normally used in combination with?
MEtyrapone
AE of Aminoglutethimide?
-Hypothyroidism
-N/V
-HA
Dosing for Aminoglutethimide?
250mg PO Q6H
True or false: Txt for cushings using Ketoconazole is off label?
True
AE of Ketoconazole?
-Gynecomastia
-May lower plasma testosterone levels
-Hepatotoxicity
-GI

**measure LFTs
Dosing for Ketoconazole for Cushings?
800-1200mg PO daily divided doses
How is Etomidate administered?
IV only
When is Etomidate used?
Pts with acute hypercortisolemia who are waiting for surgery
What monitoring should be done for Etomidate?
Cardiac and BP
AE for Etomidate?
-pain at injection site
-N/V
-Transient skeletal movements
How does Mitotane work?
decreases cortisol secretion rate and urinary free cortisol
AE of Mitotane?
-Neurotoxicity with long term use
-CNS depression
-GI
-Dermatologic reaction
Dosing with Mitotane?
500mg PO TID, then titrate up

**should be initiated in the hospital
What is a special precaution with Mitotane?
cytotoxic-->wear gloves
How long may it take to see an effect from Mitotane?
2-3 months
True or false: Neuromodulators of ACTH release are first line txts for cushings
false
What is Mifepristone?
-Glucocorticoid receptor blocking agent (progesterone, androgen, and glucocorticoids receptor antagonist)
-inhibits dexamethasone suppression
-increases endogenous cortisol and ACTh levels
When is Mifepristone indicated?
To control hyperglycemia that occurs secondary to hypercortisolism in patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and who failed surgery or who are not surgical candidates
What is primary aldosteronism?
abnormality is within the adrenal cortex
What are common causes of primary aldosteronism?
-Bilateral adrenal hyperplasia
-Aldosterone producing adenoma
-Familial hyperaldosteronism
-Adrenal cortex adenoma
Clinical presentation of primary aldosteronism
-women 30-50
-HTN
-Muscle weakness, fatigue, HA
-some pts asymptomatic
Labs indicated primary aldosteronism?
-elevated aldosterone to plasma renin activity ratio or aldosterone to renin ratio
-suppressed renin activity
-elevated plasma aldosterone concentrations
-hypernatremia, elevated bicarb
-hypokalemia, hypomagnesemia
-Glucose intolerence
Testing for primary aldosteronism?
-Oral or IV saline loading
-Fludrocortisone suppression test
-Genetic testing
How do you treat primary aldosteronism due to bilateral adrenal hyperplasia?
Spironolactone (inhibits aldosterone synthesis)
When should a pt be assessed after starting spironolactone for primary aldosteronism?
4-8 weeks: check urinary electrolytes and BP control
How do you treat primary aldosteronism caused by a aldosterone producing adenoma?
1. Surgery
2. Spironolactone when surgery is CI
How do you treat glucocorticoid remediable aldosteronism?
low dose glucocorticoids
Causes of secondary aldosteronism?
-RASS system
-excessive K can increase aldosterone
-Oral contraceptives, pregnancy, menses
-CHF
-Cirrhosis
-Renal artery stenosis
How is secondary aldosteronism controlled?
spironolactone
What is Addison's disease?
-primary adrenal insufficiency
-autoimmune destruction of all regions of the adrenal cortex
-results in deficiencies in cortisol, aldosterone, and androgens
What medications can cause primary adrenal insufficiency?
-Ketoconazole (Inhibit cortisol synthesis)
-Phenytoin, Rifampin, Phenobarbital (accelerate cortisol metabolism)
What is secondary adrenal insufficiency?
-occurs after cessation of chronic exogenous steroid use
-hypothalamic pituitary adrenal axis is suppressed causing decreased release of ACTH which impairs androgen and cortisol production
Medications that cause secondary adrenal insufficiency?
Glucocorticoids, Mirtazapine, and Medroxyprogesterone acetate and megestrol acetate
Addison's clinical presentation?
-hyperpigmentation of skin
-hypotension
-weight loss
-dehydration, elevated BUN
-Hyponatremia
-Hyperkalemia
-Other endocrine deficiencies
What are the tests to diagnose Addison's diease?
-ACTH stimulation test/short cosyntropin stimulation test
-Insulin hypoglycemia test
-Metyrapone stimulation test
-Corticotropin releasing stimulation test
What is Cosyntropin?
Synthetic peptide that is similar to ACTH that is used to diagonse Addisons disease
Cortisol levels greater than or equal to ______ are not indicative of adrenal insufficiency
18
Treatment of Addison's disease?
-Hydrocortisone, Cortisone, or Prednisone

2/3 dose in morning and 1/3 dose in evening

*use lowest effective dose

-Fludrocortisone, Deoxycorticosterone trimethylacetate
When should assessments be done for txt of addison's diease?
every 6 to 8 weeks
How is secondary adrenal insufficiency treated?
Glucocorticoids following the same principles as txt for Addison's disease

*Mineralocorticoid supplementation is not usually necessary
What is acute adrenal insufficiency?
"Addisonian crisis"

-emergency
What can cause an acute adrenal insufficiency?
-stress
-surgery
-infection
-abrupt withdrawal of glucocorticoid theapry
Sxs of acute adrenal insufficiency?
First: myalgias, malasie, and anorexia
Then: vomiting, fever, hypotension
Ultimately: shock
How do you treat an acute adrenal insufficiency?
1. IV hydrocortisone
2. Fluid replacement with D5NS
3. If hyperkalemia: Fludrocortisone

**pts should have suppositories at home for use during an emergency
What are the causes of hypoaldosteronism?
-low renin status
-DM
-Complete heart block
-postural hypotension
-Post op following tumor removal
What is non selective hypoaldosteronism?
generalized adrenocorticcal insufficiency
What is selective hypoaldosteronism?
specific defect in the stimulation of adrenal aldosterone secretion or decreased aldosterone receptors
Clinical presentation of hypoaldosteronism?
-hyponatremia
-hyperkalemia
-hyperchloremic metabolic acidosis
How do you treat hypoaldosteronism?
Fludrocortisone
What should be monitored when treating someone for hypoaldosteronism
BP response and electrolyte status
What is congenital adrenal hyperplasia?
enzyme deficiency that disrupts the cholesterol to cortisol pathway resulting in chronic adrenal gland stimulation
Clinical presentation of congenital adrenal hyperplasia?
-enlarged female genitalia
-Pubertal irregularities
-BP abnormalities
Treatment of congenital adrenal hyperplasia?
-replace the hormone deficit
-psychological support
-surgical repair of female external genitalia
What is virilism?
Excessive secretion of androgens from the adrenal gland

**more in women
Treatment of virilism?
Suppression of pituitary adrenal axis
-exogenous glucocorticoids (dexamethasone, prednisone, hydrocortisone)
What is hirsutism?
Excessive male pattern terminal hair growth in women
What meds can cause Hypertrichosis?
-phenytoin
-minoxidil
-cyclosporine
-methyldopa
-danazol
-metoclopramide
-phenothiazines
Treatment for hirsutism
-Eflornithine topical
-Androgen antagonists (Spironolactone, Finasteride)
-Oral contraceptives (Norethindrone, Ethynodiol diacetate, Drospirenone)
-Glucocorticoids adrenal source
-Gonadotropin releasing hormone
What should be monitored for glucocorticoids?
-BP
-electrolytes
-opthalmic exams
What counseling should be done for glucocorticoids?
-Take with food to decrease GI upset
-Do not stop taking without talking with physician
-Wear medical ID bracelet
-Understand side effects
How is Glucocorticoid metabolized?
Renally excreted
What meds and diseases increase the clearance of steroids?
-phenytoin, phenobarbital, rifampin, and hyperthryoidism
What meds and diseases decrease clearance of steroids?
-estrogens, hypothryoidism, anorexia, liver disease, pregnancy
AE of Glucocorticoids?
Insomnia
Increased appetite, weight gain
Fluid retention
Hypertension
Diabetes mellitus
Peptic ulcer disease
Immunosuppression; may mask signs of infection
Impaired wound healing
Cushing's syndrome-like appearance
Adrenal suppression
Cataracts
Glaucoma
Osteoporosis
Psychosis
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