Adrenal Disorders - Part 2 - Exam 3 Flashcards
What are the physiology effects of aldosterone?
aldosterone tells kidney to retain Na, water follows, blood volume and pressure increases and K is excreted
What is the physiological effects of cortisol?
decreases inflammation
increased gluconeogensis
decreases lymphatic tissue, decreases lymphocytes
dehydroepiandrosterone is ???
the precursor to sex steroids in the adrenal glands
______ autosomal recessive disorder involving a steroidogenic enzymatic block (defective or absent enzyme), leading to a deficiency in cortisol
Congenital Adrenal Hyperplasia (CAH)
Congenital Adrenal Hyperplasia (CAH) depending on the exact enzymatic block there will also be _______ and/or _____
either excessive or deficient aldosterone and/or androgen
What is the MC enzyme deficiency in Congenital Adrenal Hyperplasia (CAH)
21-hydroxylase (CYP21A)
What are the 3 pathophysiologcal presentations of CAH? What is the additional hormone in play?
salt wasting CAH : aldosterone deficiency
virilizing CAH: androgen excess
nonclassic CAH - less severe
CYP17A1, 3 beta-HSD (HSD3B2), CYP11B1, P450 oxidoreductase. What are these involved in?
other enzymes that could be the cause of Congenital Adrenal Hyperplasia (CAH)
What do you think happens to ACTH in Congenital Adrenal Hyperplasia?
ACTH will increase because no cortisol is being produced to shut off the negative feedback loop
What happens to androgens in Congenital Adrenal Hyperplasia?
increase in ACTH and increase in androgen
DHEA is a precursor for _____ and _____. DHEA produces ____ of estrogen before and ____ of estrogen after menopause.¹
estrogen and testosterone
75%
100%
genital atypia: clitoral enlargement, labial fusion, formation of a urogenital sinus, grossly normal appearing genitalia with hyperpigmented scrotum, enlarged phallus
vomiting, dehydration, hyponatremia, hyperkalemia, hypotensive shock
What am I?
Classic “salt-wasting” virilizing adrenal hyperplasia of CAH 21-hydroxylase deficiency
milder genital atypia presentations
precocious puberty (puberty before 9 years old), accelerated growth
early skeletal maturation
pubic hair, adult body odor
What am I?
Simple virilizing adrenal hyperplasia of CAH with 21-hydroxylase deficiency
_____ is noticed during adolescent/early adulthood - oligomenorrhea, hirsutism, and/or infertility
Nonclassic adrenal hyperplasia
ambiguous genitalia or female genitalia in Congenital Adrenal Hyperplasia results from ????
What three enzymes are involved?
results from an inadequate testosterone production in the 1st trimester of pregnancy due to complete androgenic enzymatic block
StAR protein
HSD3B2
CYP17A1
**In CAH _____ and _______ are elevated in 21-hydroxylase deficiency
serum 17-hydroxyprogesterone (CYP17) is elevated
What is the workup for CAH?
-newborn screening: 21-hydroxylase deficiency (CYP21A2)
-Ambiguous genitalia: immediate hormonal, genetic and chromosomal testing
-enzyme metabolites: serum 17-hydroxyprogesterone (CYP17) and serum DHEA
-CMP
-Consider imaging (NOT necessary for dx but can help further investigate)
In CAH _____ is used to rule out adrenal hemorrhage. When is it used?
_____ is used when assessing organic anomalies associated with ambiguous genitalia
CT abdomen
used only in patients without ambiguous genitalia
pelvic US
What is the treatment goal for CAH?
provide the smallest dose of gluco- and mineralocorticoid that will adequately suppress excess androgen precursors and produce normalization of growth velocity and skeletal maturation
What is likely to occur with high doses of glucocorticoids?
What is likely to occur with high doses of mineralocorticoids?
Cushings
HTN/hypernatremia/hypokalemia
What is the treatment for CAH? What do you need to monitor for? What are adjustments based on?
Hydrocortisone, dividing TID and Fludrocortisone 0.05 - 0.15 mg daily
monitor for normalization of serum 17-hydroxyprogesterone
adjust dose to maintain normal growth rate and skeletal maturation
When using Fludrocortisone 0.05 - 0.15 mg daily in CAH pts, what do you need to monitor?
monitor BP and plasma renin activity
Name some things that inadequate CAH control leads to?
precocious puberty (males)
masculinity (females)
rapid skeletal maturation resulting in tall children → short adults
adrenal crisis
psychosocial disturbances
______ A condition resulting from hypersecretion of aldosterone that doesn’t suppress with sodium loading
Primary hyperaldosteronism
What is Conn syndrome?
A benign growth in an adrenal gland (aldosterone-producing adenoma)
associated with primary hyperaldosteronism
What are the causes of primary hyperaldosteronism?
bilateral idiopathic adrenal hyperplasia - 60-70%
unilateral aldosterone-producing tumor (either benign or maligant)
refractory hypertension
headaches (HA)
muscle weakness
fatigue
polyuria
polydipsia
HA
paresthesias
tetany
What am I?
Primary Hyperaldosteronism
What will the BMP look like in a pt with primary hyperaldosteronism?
hypernatremia, (+/-)hypokalemia¹
increased CO2² (reflective of HCO3):metabolic alkalosis
May also be normal
____ is the initial diagnostic for primary hyperaldosteronism.
Plasma Renin Activity (PRA) and Aldosterone Concentration (PAC)
PRA: Low
PAC: Elevated
What is the Plasma aldosterone/renin ratio used in? What is normal?
primary hyperaldosteronism
normal is < 10
ratio > 20-25 ( 95% sensitivity and 75% specificity for primary aldosteronism)
PRA: Low
PAC: Elevated
What are the two pt education points for PAC/PRA Ratio test?
obtained in AM in a seated position
out of bed for 2 hours and seated for 15-60 minutes before blood draw (between 8-10 AM)
Avoid mineralocorticoid receptor antagonist (spironolactone and eplerenone), ACE inhibitors, ARBs, direct renin inhibitors because they can alter the lab results
____ is the confirmatory testing for primary hyperaldosteronism
Sodium loading either oral or IV
What is the method of oral sodium loading testing? What two things have to be adequate for sodium loading test to be accurate?
3 days of unrestricted salt (> 5g/d)
serum K+ must be assessed every day due to increased risk of low K+
if hypokalemia - replace with potassium chloride
on day 3 assess serum electrolytes and begin 24 hour urine collection for aldosterone, sodium and creatinine
urine Na > 250 mEq/L - ensures adequate sodium loading
normal urine creatinine - ensures adequate urine sample
urine aldosterone > 12 mcg/24h - confirms hyperaldosteronism
What is the method for IV sodium testing?
2L NS over 4 hours while seated
plasma aldosterone concentration > 10 ng/dL - consistent with dx
Why do you need a CT scan of the abdomen in primary hyperaldosteronism? What do you do if the CT scan is negative?
To check for masses and thickening of the adrenal gland
unilateral adrenal mass < 4 cm - “Conn syndrome”
> 4 cm adrenal mass - consider carcinoma
bilateral adrenal gland thickening or micronodular changes indicative of hyperplasia
consider adrenal vein sampling if surgery is considered
What is adrenal vein sampling assesses? What dz is it associated with? When is it indicated?
assessing aldosterone levels in blood from adrenal vein
Primary hyperaldosteronism
recommended only if severely uncontrolled HTN AND adrenalectomy is being considered for tx in order to determine which gland is hyperactive
What is the treatment for primary hyperaldosteronsim unilateral adrenal adenoma? bilateral adrenal hyperplasia? adrenal carcinoma?
Unilateral adrenal adenoma:
unilateral adrenalectomy
medical management while awaiting surgery
Bilateral adrenal hyperplasia:
medical management
Adrenal carcinoma:
refer to oncology for evaluation and management
What is the medical/lifestyle management for primary hyperaldosteronism?
low sodium diet
K+ sparing diuretics: spironolactone
alt: eplerenone
BP meds: ACEI, HCTZ, amiloride, triamterene (2nd line K+ sparing diuretics)
Want to refer a pt with primary hyperaldosteronism to ___ and ____. Why? What do you need to closely monitor?
endo and cardio (in the presence of long-standing HTN as cardiovascular complications are common)
closely monitor BP and K+
How are adrenal tumors categorized?
functional (hormone-secreting) or silent
benign or malignant
incidentaloma
______ a highly vascular tumor of the sympathetic paraganglia that arises most frequently from the adrenal medulla. What does it secrete?
Pheochromocytoma
epinephrine and norepinephrine (catecholamines)
How are pheochromocytomas categorized? When is the average age of onset?
by location either adrenal medulla (90%) or extra-adrenal sites (10%)
average is 40
What are the rules of 10s? What dz is it associated with?
10% are bilateral
10% are extra-adrenal
10% are malignant
Pheochromocytoma
What is the classic triad of Pheochromocytoma? What is it known as? What is one additional symptom that makes it highly suggestive for Pheochromocytoma?
Episodic palpitations, headache, profuse diaphoresis
“the great masquerader”
HTN
What is Pheochromocytoma commonly precipitated by? How long does it usually last?
emotions/physical stressors, change in position, urination (“bladder pheo”), various medications
less than 1 hour
HA
profuse sweating
palpitations/tachycardia
HTN
anxiety/panic attacks
pallor nausea
weakness
What am I?
Pheochromocytoma
______ is the most sensitive test to dx pheochromocytoma. What is important when drawing this lab? What is normal vs abnormal?
Plasma free metanephrines
sitting for 15 minutes before collection
normal results rule out pheochromocytoma
elevated - assess urine metanephrines
_____ is ordered if plasma free metanephrines is elevated. What is needed to make the dx?
Urine fractionated metanephrines and creatinine
BOTH plasma and urine metanephrine evaluation both need to be ** > 3x upper limit of normal to be diagnostic
_____ is utilized when metanephrines are indeterminate or concern for false elevation. What are the steps? How do you interpret it? What dz?
Clonidine suppression testing
Measure plasma metanephrines
Administer clonidine orally 0.3 mg
Wait 3 hours and reassess plasma metanephrines
If plasma metanephrines decrease into normal range or by 40% after clonidine, pheochromocytoma is unlikely
pheochromocytoma
What imaging do you want to order while working up a pt with pheochromocytoma? If negative what do you do
Non-contrast CT of adrenal gland
if negative: follow up with CT or MRI of chest, abdomen and pelvis to look for extra-adrenal disease
PET scan to rule out malignancy
What is the management for pheochromocytoma?
complete resection of the tumor
Post-sx asses ACTH level: risk of post-surgical adrenal insufficiency
What is the management for a pheochromocytoma pt who is awaiting sx?
alpha-adrenergic blockers at least 14 days prior to surgery
BP consistently needs to be less than 160/90 prior to surgery
high salt diet and increase water intake: start 3 days after alpha adrenergic blockage due to risk of orthostasis
Name some alpha-adrenergic blockers. Need to give them to _____ pts at least 14 days prior to sx
doxazosin (Cardura), prazosin (Minipress), terazosin (Hytrin)
Pheochromocytoma
_____ benign neoplasm of adrenocortical cells that does not secrete steroids
Nonfunctioning adrenal adenoma
_____ benign neoplasm >1 cm arising from the adrenal cortex that secrete steroids independently from ACTH or the RAA system
Functional adrenal adenoma
Functional Adrenal adenoma are related to ____. Name the dz associated with the layer
zona glomerulosa -_______
zona fasciculata - _______
zona reticularis - ______
adrenal medulla - ______
respective cellular involvement
hyperaldosteronism
Cushing’s Disease
hyperandrogenism
pheochromocytoma
What is the work up if you suspect adrenal adenoma?
Detailed H&P to determine presence hormone excess
Labs ordered based upon suspected adrenal zone affected by mass
Imaging - CT adrenal gland without contrast
refer to experienced surgeon
_____ a rare malignancy of the adrenal cortex. What are some risk factors?
Adrenal Carcinoma
children living in southern Brazil (environmental and genetic)
adrenal hyperplasia
How are adrenal carcinomas categorized? What age groups are at the highest risk?
functional (60%) vs nonfunctional (40%)
birth -10 years - functional tumors more common
30-40 y/o - nonfunctional tumors are more common
How do functional adrenal carcinomas present?
will present with symptoms respective of adrenocortical cells involved
gynecomastia in males
precocious sexual development in young females
How do nonfunctional adrenal carcinomas present?
presents with symptoms related to malignancy and/or metastasis, most pt present with advanced disease and multiple metastatic sites
Fever, weight loss, abdominal pain/tenderness, abdominal fullness, back pain
palpable, firm, adherent mass of the abdomen
What is the work-up for an adrenal carcinoma?
hormonal eval for all the following: pheochromocytoma
hyperaldosteronism
hypercortisolism
hyperandrogenism
imagining:
CT abdomen/pelvis with contrast
PET - increased uptake of radiotracer = higher suspicion
FSH, LH, DHEAS, prolactin, 17-OHP, and total and free testosterone are all labs associated with _______
hyperandrogenism
When do you use fine needle aspiration in adrenal carcinoma? what do you need to r/o first?
only to r/o metastasis in patients with known malignancy
must r/o pheochromocytoma prior to FNA
Why is it NOT recommended to use fine needle aspiration to differentiate between adenoma and carcinoma?
unreliable with risk of tumor seeding into the retroperitoneum
_____ is used to stage adrenal carcinoma. What is the management?
TNM staging
refer to surgeon for complete resection
______ and ______ are glucocorticoids available in a solution and syrup
prednisone: solution
prednisolone: syrup
____ is the short acting glucocorticoid
_____ is the long acting glucocorticoid
Hydrocortisone-> short
Dexamethasone -> long acting
What are the 3 intermediate glucocorticoids?
methylprednisolone
prednisone
prednisolone
What are the 5 important aspects of the MOA of glucocorticoids?
-Inhibit the inflammatory response
-Decrease chemotaxis of inflammatory cells
-Depress migration of polymorphonuclear (PMN) leukocytes
-Lympholysis (lysis of lymphocytes) → Decreased # of circulating lymphocytes
-Reduce phagocytic and killing ability of neutrophils & macrophages
What are the indications of glucocorticoids? Caution?
inflammatory conditions
caution:PUD, CVD or HTN with CHF, varicella, TB, acute psychosis, DM, osteoporosis, glaucoma
What are the CI of Glucocorticoids?
hypersensitivity, coadministration with live vaccines, systemic fungal infections
What is important about the dosing instructions for Glucocorticoids? What do you need to monitor?
Dosing titration indicated if >7-10 days of therapy
elevated glucose, Na retention, K+ loss
What are the Drug interactions with glucocorticoids? What is 1 important pt education point?
live vaccine, inactivated vaccine, other immunosuppressants (oral/topical)
take with meals to avoid GI upset
What are some important SE of Glucocorticoids?
-Suppression of hypothalamic-pituitary-adrenal (HPA) axis
-Gastric irritation, peptic ulcer
-Hypertension
-Congestive heart failure in predisposed patients
-Osteoporosis
-Elevated intraocular pressure/glaucoma
-Sleep disturbances
-Euphoria, depression, mania, psychosis
- Hypokalemia
