Adrenal Disorders - Part 1 - Exam 3 Flashcards
What are the 2 types of tissues in the adrenal glands? They are both enclosed by _____
Cortex and Medulla
enclosed by a capsule
The ____ of the adrenal glands has 3 zones. Name them
Cortex
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
____ is secreted from the Zona Glomerulosa (outer). What is the function?
mineralocorticoids primarily aldosterone
sodium retention
water retention
potassium excretion
increases blood pressure and blood volume
aka: kidneys retain Na, gets ride of K, when aldosterone is present, pee out K and keep Na and water follows so blood volume and pressure will increase
What is the function of aldosterone? **What is the effect on Renin when aldosterone is in excess and deficient?
-Na retention and water follows
-K+ excretion
**Aldosterone excess
Renin ↓
Aldosterone deficiency
Renin ↑ **
____ is secreted from the Zona Fasciculata (middle). What is the function?
glucocorticoids -> think cortisol
-gluconeogenesis in liver: utilizes (decreases) protein stores
-immune system suppression: ↓ eosinophil, lymphocytes and lymph tissue
-decreases inflammation
What is gluconeogenesis?
Gluconeogenesis refers to synthesis of new glucose from noncarbohydrate precursors, and provides glucose when dietary intake is insufficient or absent.
How much cortisol is released on a normal day? What happens when the body is stressed?
10-20 mg daily (basal level - w/o stress)
increased cortisol release during stress via ACTH stimulation (from the pituitary)
Describe the HPA axis and its function.
hypothalamus releases corticotropin-releasing hormone (CRH) -> CRH goes to Anterior Pituitary Gland and adrenocorticotropic hormone (ACTH) is released -> ACTH goes to adrenal cortex and cortisol is released -> cortisol exerts a negative feedback in the hypothalamus and shuts off the release of CRH and ACTH
controls glucocorticoid release
Describe the circadian rhythm of cortisol
highest in the morning around 8am and lowest around 8pm
____ is secreted from the Zona Reticularis (inner). What is the function?
secretes gonadocorticoids
primarily dehydroepiandrosterone (DHEA)
converts to sex steroids in gonads
The adrenal medulla is composed of ___ cells. What do they secrete?
chromaffin cells
secrete epinephrine and norepinephrine, which control the fight-or-flight response
_____ can result in a chronic increase in a patient’s ACTH and CRH levels.
Destruction of the adrenal glands
______ stimulates adrenal cells to begin steroid synthesis.
Adrenal cells require _____ to synthesize steroid hormones.
ACTH
cholesterol
All steroidogenic pathways require _____ import into the mitochondrion, a process initiated by the action of the ______, which shuttles _____ from the outer to the inner mitochondrial membrane.
cholesterol
steroidogenic acute regulatory (StAR) protein
cholesterol
______ are very important in the process that forms aldosterone, cortisone, androgens and DHEAS. What happens if they mess up?
Enzymes
major effects on adrenal gland disfunction, could result in excessive amounts of sex hormones
??Consider memorizing this picture if times allows??
What is primary adrenal insufficiency?
adrenal gland dysfunction
↓ cortisol/aldosterone
What is secondary adrenal insufficiency?
pituitary gland dysfunction
↓ ACTH
↓ cortisol
What is tertiary adrenal insufficiency?
hypothalamic dysfunction
↓ CRH
↓ ACTH
↓ cortisol
Why is aldosterone not affected in secondary or tertiary adrenal insufficiency?
aldosterone is controlled by the RAA system and not the HPA axis
____ is a destruction/dysfunction of the adrenal cortex resulting in insufficient production of glucocorticoids and mineralocorticoids
Addison’s disease aka primary adrenal insuffiency
What is the MC cause of Addison’s disease? What are the autoantigen’s involved? What age range?
autoimmune destruction of adrenal enzymes (80% of cases in US) slow decrease over several years
**CYP21A2 (21-hydroxylase) - MC autoantigen
CYP11A1 (side-chain cleavage enzyme)
CYP17 (17-alpha-hydroxylase)
10-40 years old
What will a reduction/malfunction of CYP17A1 lead to?
excessive aldosterone and reduction in all hormones created by the adrenal gland
_______ genetic disorder resulting in accumulation of very long-chain fatty acids in the adrenal cortex. What does it inhibit?
Adrenoleukodystrophy
inhibiting the effects of ACTH on the adrenocortical cells
______ genetic mutation or absence of adrenal cortex
Congenital adrenal insufficiency/hyperplasia
What is the MC cause of infectious Addison’s disease?
TB but rare
Chronic Addison’s dz can be caused by ORAL ketoconazole. Why?
inhibits the production of cortisol by blocking the CYP450 enzyme
phenytoin, barbiturates, rifampin all can ???? causing ????
accelerate the metabolism of cortisol
causing Addison’s disease
aka the drugs break cortisol down faster before it can do its job
_____ is an adrenocorticolytic drug that diminishes cortisol synthesis by blocking steroid biosynthesis - used to treat adrenocortical carcinoma
mitotane
**_______ suppress the CRH or ACTH production.
glucocorticoids
stopping steroid’s abruptly can cause addison’s dz
What are 2 causes of acute addison’s dz?
Adrenal hemorrhage
Adrenal “addisonian” Crisis
What can cause an adrenal hemorrhage?
results from sepsis, heparin-induced thrombocytopenia, anticoagulation, antiphospholipid antibody syndrome, trauma, surgery
**What is an adrenal crisis usually caused by?
insufficient cortisol caused by physical or emotional stress in an Addison’s pt
Bronze pigmentation of skin (extensor surfaces, palmar creases, nail beds, mucosal membranes)
changes in distribution of body hair
GI disturbances: abdominal pain, N/V/D
weakness, fatigue, decrease in stamina
hypoglycemia
postural hypotension
weight loss, dehydration
anorexia
slow onset and nonspecific s/s
vitiligo in 10% of pts
generalized pain
anxiety, irritability, depression
gait disturbances, cognitive dysfunction
amenorrhea (25% of female pts)
What am I?
**What are the first symptoms?
Chronic addison’s dz presentation
anorexia, weight loss, fatigue, ↓ stamina
profound fatigue
dehydration
vascular collapse decrease BP
renal shut down
decrease serum Na
increase serum K
What am I?
acute addison’s dz
What is the function of mineralcorticoids?
increase Na retention
increase water in the blood vessel
increase blood volume and pressure
K is eliminated into the urine
What is the function of glucocorticoids?
gluconeogensis in the liver
decreases the immune response
decreases protein stores aka muscle break down
decreased inflammation
Why do patients with Addison’s disease present with hyperpigmentation?
ACTH attaches to melanotic receptors
What is vitiligo? When will you see it? What is it a result from?
patchy hypopigmentation
result of autoimmune destruction of dermal melanocytes
occurs in 10% of chronic addison’s dz patients
sudden onset
severe fever - 105℉ or higher
severe abdominal pain, nausea, vomiting
similar to an “acute abdomen¹”
confusion
hypotensive shock
weakness, dizziness, syncope, hypotension, tachycardia
Addison’s dz Adrenal crisis
**What is the key difference between an adrenal hemorrhage and an adrenal crisis?
adrenal hemorrhage will present like adrenal crisis without the fever
What will each lab value show of pt with addison’s dz? CBC and CMP
CBC:eosinophilia, lymphocytosis
CMP: hyponatremia, hyperkalemia (unless the pt has been vomiting/diarrhea may mask hyperkalemia)
↑ BUN/Cr - results from dehydration
hypoglycemia if fasting or may occur spontaneously
**What additional tests would you want to order if you suspect Addison’s dz? What results would you expect?
Plasma Cortisol at 8am! low cortisol (less than 3mcg) AND elevated ACTH
low cortisol AND high ACTH
______
Plasma ACTH should be high in Addison’s dz
greater than > 200 pg/mL (7-63 pg/mL - normal value 7-10 AM)
How would you rule OUT addison’s disease in am emergency setting?
Random cortisol > 25 mcg/dL usually rules out Addison’s
Describe the rapid ACTH stimulation test. When is it indicated? When is it used? What results would you expect with a pt with Addison’s dz?
when serum cortisol and serum ACTH are non-diagnostic
Pre-test: hold steroids 24 hours before test
Hospital setting
Step 1: Measure serum cortisol
Step 2: Administer Cosyntropin (synthetic ACTH) 0.25 mg given IM
Step 3: Measure serum cortisol 45 minutes post injection
————
Normal - rise in serum cortisol ≥ 20 mcg/dL
a rise could also indicated a
Addison’s Disease - rise in serum cortisol less < 20 mcg/dL
normal should rise more than 20mcg, Addison’s there is a minor to no increase
When in the plasma renin test used? What would you expect to see? What is the drawback?
on a pt with Addison’s dz to determine if they need mineralcorticoid replacement
increased in Addison’s disease due to diminished aldosterone resulting in depleted intravascular volume
has MANY interfering factors!!
What imaging would you order for a pt with Addison’s dz? Why?
CXR: if you suspect TB or pneu
CT of the abdomen to scan the adrenal gland
What are some common finds on a CT of the abdomen on a Addison’s pt? What does it mean?
small without calcifications - autoimmune
enlarged - TB, fungal, adrenal hemorrhage, metastatic
calcifications - TB, fungal, adrenal hemorrhage, pheochromocytoma, melanoma
What is the treatment for chronic addison’s dz? What is the dosing? What is the alt?
Hydrocortisone 15-30 mg daily: ⅔ dose in morning and ⅓ dose in late afternoon/early evening
Prednisone or methylprednisolone alternative glucocorticoids
AND
Fludrocortisone 0.05–0.3 mg daily or every other day
What is the treatment for Addison’s dz if the pt is stressed?
increase dose of glucocorticoid by up to 50%
at higher stress doses of glucocorticoids (> 100 mg/d of hydrocortisone) Fludrocortisone is not needed
How do you monitor fludrocortisone? When do you need to increase the dose?
monitor with PRA - if increased, fludrocortisone dose needs increased
orthostatic hypotension, hyponatremia, hyperkalemia
What is the treatment for an acute addison’s dz?
1st: order serum cortisol and ACTH but DO NOT WAIT on results to start treatment
1st: IV hydrocortisone then switch to oral hydrocortisone once the pt can tolerate oral intake
2nd: broad spectrum abx and treat all electrolyte abnormalities
What is the addison’s dz management and monitoring?
monitor for Cushing Syndrome
WBC w/ diff to monitor for electrolytes and renal function
DEXA scan: screen for osteoporosis
What are some pt education points to know about Addison’s dz?
medical alert bracelet
all infections must be treated immediately: aka the abx threshold is much lower
educate the pts on how to do injectable hydrocortisone
______ a condition that results from an excessive amount of systemic cortisol. What is the MC cause? Is it ACTH dependent or independent?
Cushing’s SYNDROME
aka too many prescribed steroids
Independent
_____ manifestations of excessive corticosteroids due to hypersecretion of ACTH. What is the MC cause? What gender?
Is it ACTH dependent or independent?
Cushing DISEASE
benign anterior pituitary adenoma
females > male
dependent
What are 4 causes of Cushing DISEASE?
pituitary hypersecretion of ACTH
Ectopic secretion of ACTH
Ectopic secretion of CRH
factitious Cushing’s syndrome: due to administration of exogenous ACTH – rare < 1 %
Ectopic secretion of ACTH is caused by ??? Name some common locations
non-pituitary tumor - MC locations lungs, thymus, pancreas
Ectopic secretion of CRH are caused by ???
non-hypothalamic tumors causing pituitary hypersecretion of ACTH - rare < 1 %
What are the effects of cortisol?
gluconeogensis
decreased protein stores
suppresses the immune system
decreased inflammation
How does ACTH affect aldosterone?
ACTH can stimulate the adrenal cells of the zona glomerulosa to release aldosterone outside of the RAAS
Fatigue
reduced physical endurance
weight gain: central obesity with protuberant abdomen with thin extremities
mood face
supraclavicular fat pads
buffalo hump
skin atrophy with large purple striae
easy bruisability
proximal muscle weakness: especially shoulders and hips
immune system suppression: frequent infections
menstrual irregularities
hyperpigmentation
elevated BP
hirsutism, male pattern hair loss
What am I?
Cushing disease
What would a CBC and CMP look like on a pt with Cushing’s syndrome?
CBC: leukocytosis with neutrophilia¹, lymphocytopenia, ↓ eosinophils
CMP: elevated glucose
+/- hypernatremia, hypokalemia
When would you expect to find abnormal Na and K levels?
Cushing’s disease increase in ACTH stimulates aldosterone
Zona glomerulosa is secreting too much aldosterone
What is the workup goals for Cushing disease?
Is it due to excessive steroid use?
Is there hypercortisolism? then determine the cause
What are the 3 first line tests for Cushings? When can you dx Cushings?
Dexamethasone Suppression Test
24 Urine Free Cortisol (2 separate measurements)
Late night salivary cortisol (2 separate measurements)
**need TWO positive tests for diagnosis
What are the guidelines when performing a Low-dose Dexamethasone Suppression Test? What can cause the test to be “off’?
give dexamethasone 1 mg PO at 11 PM then serum cortisol next morning at 8 AM
Results - < 5 mcg/dL likely excludes Cushing’s syndrome
3% false-negative rate: antiseizure drugs, rifampin and estrogens diminish suppressibility
20-30% false-positive rate: psychiatric disorders, emotional/physical stress
What are the guidelines for 24 hour urine free cortisol test? What is considered a positive test?
day 1: first morning void in the toilet, collect all urine throughout the day
day 2: first morning void in the jug
test complete
3x upper limit of normal on both occasions (around 150mcg)
What are the guidelines for the late night salivary cortisol test?
Place swab in mouth and leave for 90 seconds. Allow saliva to saturate. Do not chew swab
collected by patient between 11 pm and midnight. Normal: less than 100
lots of interfering factors!: steroid use, brushed teeth, oral intake, inadequate collection
must be performed on 2 separate occasions!! and both must be elevated to be positive
What are some conditions in which a late night salivary test might be falsely elevated.
erratic sleep schedules or shift work
pregnancy
exogenous steroid/estrogen use, anticonvulsants
mental illness, chronic alcohol use
acute stress (hospitalization/surgery)
what are the guidelines for Cushing dz test interpretation.
2 first line test with negative results
if low index of suspicion - no further workup - monitor pt
if high index of suspicion - refer to endocrinologist
1 out of 2 are positive:
repeat test at random intervals
consider: cyclic Cushing Disease as dx
refer to endo
2/2 are positive
refer to endo
What is the MC cause of cyclic Cushing Disease?
ACTH-secreting pituitary adenoma
_____ is a good test to order when determining the cause for hypercortisolism. Why? **How do you interpret the results?
Serum ACTH
will differentiate ACTH-dependent vs. ACTH-independent etiology
**interpretation
< 20 pg/dL order adrenal CT; > 20 pg/dL order pituitary MRI
**What are the three red flags for malignant adrenal gland CT?
greater than > 4 cm
growth of nodule (requires previous CT for comparison)
density of lesion is > 10 Hounsfield units (HU)
What is the best way to view the pituitary gland? What is the parameter for treatment if you find a lesion?
MRI with contrast
lesion greater than 5mm begin treatment
no lesion or lesion less than 5mm do an inferior petrosal sinus sampling
the inferior petrosal sinus sampling comes back elevated, what does this mean? normal?
elevated ACTH levels - pituitary Cushing’s disease
normal ACTH level - look for ectopic source of ACTH, order CT scan of chest/abdomen. If negative, perform whole body PET scan
When stopping glucocorticoid/ACTH therapy, what is the protocol?
prolonged therapy can suppress the HPA axis; rapid withdrawal can result in acute adrenal insufficiency
HPA axis is usually fully recovered within 6-12 months
What is the management for Cushing dz caused by a adenoma/ACTH-secreting tumor?
surgery: post surgical adrenal insufficiency will require lifelong glucocorticoid replacement
radiation
While waiting for sx or sx not an option, how do you treat Cushings Dz?
**11β-hydroxylase inhibitors - blocking cortisol steroidogenesis
What is the medical management for a pituitary ACTH tumor?
pasireotide (Signifor) - somatostatin analog - inhibits ACTH secretion
What is the medical management for an adrenocortical carcinoma?
mitotane - blocks cortisol secretion
What is the medical management of mineralcorticoid HTN?
1st: K+ sparing diuretic: spironolactone, eplerenone
2nd: ACEI
_____ is given to women for hyperandrogenism. Its MOA inhibits androgen uptake and/or inhibits binding of androgen in target tissues
flutamide
What are some other conditions that commonly arise along side of Cushings dz?
HTN, DM, increased risk of infection, complications from osteoporosis, nephrolithiasis, psychosis
