Lecture 7 Adrenal disorders Flashcards
Where is the adrenal glands located?
2in x 1inch triangle gland sitting atop each kidney
What are the layers of adrenal glands? (out to in)
Capsule
Cortex
Medulla
What are the zones of the cortex? (out to in)
Zona glomerules
Zona Fasciculata
Zona Reticularis
What is the purpose for the glomerulosa?
Secrete mineralcorticoids/aldosterone
What is the function of mineralcorticoids?
Regulate BP and electrolyte balance through RAAS
Na/water retention
K excretion
Increase BP and blood volume
What is the function of aldosterone?
Na/water retention
How does renin relate to aldosterone?
Renin is released from kidneys to help produce aldosterone
Its a negative feedback loop so…
Excess aldosterone causes a decrease of renin and vice versa
What is the function of the fasciculate?
Secretes glucocorticoids/cortisol
What is the function of glucocorticoids?
Gluconeogensis in liver(use/decrease protein stores)
Immune system suppression(decrease eosinophil, lymphocytes, and lymph tissue)
Decrease inflammation
When are glucocorticoids release?
Circadian rhythm
After meals
Response to endogenous/exogenous stressors
What kind of feedback is cortisol?
Negative feedback
What is the function of reticularis?
Secretes gonadocorticoids/DHEA
What is the goal of gonadocorticoids?
Converts sex steroids in gonads (development of sex characteristics)
What is the function of the medulla?
Secretes Epi/NoEpi
What is the medulla composed of?
Chromaffin cells
What is needed for steroid synthesis?
ACTH stimulation and cholesterol
What are the types of adrenal insufficiency?
Primary
Secondary
Tertiary
What is primal adrenal insufficiency?
Adrenal gland dysfunction
Decrease in cortisol/aldosterone
Addisons disease
What is 2ndary adrenal insufficiency?
Pituitary gland dysfunction
Decrease in ACTH, and cortisol
What is tertiary adrenal insufficiency?
Hypothalamic dysfunction
Decrease in CRH, ACTH, cortisol
What is Addison’s disease?
Destruction/dysfunction of adrenal cortex causing not enough glucocorticoids and mineralocorticoids being made
Usually an autoimmune dysfunction (80% of cases)
What specific enzymes does Addisons disease affect?
CYP21A2 (MC)
CYP11A1
CYP17
What are possible causes of Addisons decrease?
Autoimmune
Adrenoleukodystropy
Congenital adrenal insufficiency/hyperplasia(mutation or absence of cortex)
Infection (rare but usually from TB)
What is adrenaleukodystropy?
Genetic disorder
Accumulates long-chain FA in adrenal cortex inhibiting the effects of ACTH on adrenocortical cells
What drugs can cause chronic Addisons disease?
Ketoconazole (inhibits cortisol synthesis)
Phenytoin, barbiturates, rifampin(Increase metabolism of cortisol)
Mitotane(adrenocorticolytic drug, blocks steroid synthesis)
Glucocorticoids(suppress CRH/ACTH production)
What is used to treat adrenocortical carcinoma?
Mitotane
What can cause acute Addisons disease?
Adrenal hemorrhage
What can cause adrenal hemorrhage?
Sepsis
HIT
Anticoagulation
Antiphospholipid antibody syndrome
Trauma
Surgery
What is an adrenal “addisonian” crisis?
Emergent condition from insufficient cortisol
Caused by physical or emotional stressor in an Addison’s disease pt
Ex: infection, trauma, surgery, emotional turmoil
What are S/S of Chronic Addisons present?
S/S of glucocorticoid and mineralocorticoid deficiency
Onset is insidious and nonspecific
Skin and mucosal hyperpigmentation
Chronic: Vitiligo (from autoimmune destruction of dermal melanocytes, 10% of pts)
Anorexia, weight loss, fatigue, decrease stamina (first symptoms)
Why do pts with Addisons have hyperpigmentation?
ACTH binds to melanotic receptors
What are other general symptoms/presentations of chronic addisons?
Hypotension, dehydration, orthostatic lightheadedness
Hypoglycemia, weakness
Fevers, lymphoid tissue hyperplasia
Abdominal pain, N/V/D
Generalized pain
Change in axillary, public, body hair
Psychiatric
Neurologic
Amenorrhea
Which enzyme affect women body hair?
Loss of 11A1, 17 or Excess 21A2
How does acute addisons present?
Adrenal crisis…
Fever 105+
N/V abdominal pain
Confusion
Hypotensive shock(weakness, tachycardia)
How would an adrenal hemorrhage present?
Just like an adrenal crisis without the fever
What labs would you order for Addisons?
CBC (eosinophilia, lymphocytosis)
CMP (HypoN, HyperK, vomiting can mask; Increase BUN/Cr from dehydration, hypoglycemia)
Cultures(blood, sputum, urine)
Plasma Cortisol(8AM <3 r/I if elevated ACTH, random cortisol >25 r/o Addisons)
Plasma ACTH(>200)
What other labs would you order for Addisons?
Rapid ACTH stimulation test (normal rise >20, Addisons rise of cortisol <20)
Plasma renin(increased, multifactorial)
CXR
CT abdomen
What do you need to consider in a rapid ACTH stimulation test?
A rise in serum cortisol can indicate secondary/tertiary etiology
Hold hydrocortisones for 24hours before test
Long acting(dexamathasone) needs to go to short acting(hydrocortisone) before testing
Has to be performed in hospital
Only used when serum cortisol or ACTH are non-diagnostic
What is the drug and SE for Rapid ACTH stimulation test?
Cosyntropin(synthetic ACTH) measure after 45min
SE…
N, HA, dizziness, dyspnea
Palpitations
Flushing edema
Local site reaction
What could plasma renin tell us?
When increased from Addisons from reduced aldosterone(cause low intravascular volume)
Indicate need for mineralocorticoid replacement
What CT abdomen findings can help determine that is causing Addisons?
Small w/o calcifications: autoimmune
Enlarged: TB, fungal, adrenal hemorrhage, metastatic
Calcifications: TB, fungal, adrenal hemorrhage, pheochromocytoma, melanoma
How do you treat chronic Addisons?
Hydrocortisone 15-30mg daily
2/3 in morning 1/3 in afternoon/evening
OR
Prednisone or methylprednisone
3-6mg divided the same 2/3morning 1/3 evening
Glucocorticoid stress therapy(increase 30mg to 45mg, 50% increase)
Mineralocorticoid therapy(>100mg, for mineralocorticoid activity)
How does dosing change in glucocorticoid stress therapy?
Depends on severity of stress and symptoms
Return dose to baseline when stressor is resolved
What mineral corticoid supplement is needed in low maintenance glucocorticoid doses in mineralocorticoid therapy? How do you monitor?
Fludrocortisone 0.05-0.3mg daily or every other day
Increased dosage for orthostatic hypotension, hypoN, Hyperk
PRA(panel reactive antibody): if high, dose increases
How do you treat acute adrenal crisis?
- Loading lose of IV hydrocortisone 100-300mg in NS
- IV hydrocortisone 50-100mg q6h for 1 day then taper
- Switch to oral when pt can tolerate 10-20mg q6h and then reduce to maintenance
You still order serum cortisol and ACTH but you don’t need to wait to start treatment
What are other treatments for acute adrenal crisis?
Broad spectrum ABX
Treat electrolyte/glucose/volume abnormalities
Who do you refer Addison pts to for management?
Endocrinologist
What should you monitor for Addisons disease: management?
Symptom resolution w/o Cushing syndrome development
WBC Diff, electrolytes, and renal function should return to normal
DEXA scan: to check osteroporsis
What can increase risk of osteoporosis?
Chronic steroid use
What are some pt education for Addisons?
Medical alert bracelet
Infections treated immediately
How to use injectable hydrocortisone
What is Cushings syndrome/disease?
Results from excessive systemic cortisol
Syndrome are due to excess cortisol
Disease is due to hyper-secretion of ACTH causing excess cortisol
Syndrome is AKA ACTH independent
Disease is AKA ACTH dependent
What is the main cause of Cushing syndrome? disease?
Syndrome: 99% iatrogenic(high oral glucocorticoids>1 month)
Disease: Benign anterior pituitary adenoma
(MC in females)
What are other causes of Cushing syndrome?
Adrenocorticol adenomas/carcinomas
What are other causes of Cushing disease?
Ectopic secretion of ACTH (lungs, thymus, pancreas)
Ectopic secretion of CRH(Non-hypothalamic tumors, <1%)
Iatrogenic(exogenous ACTH administration, <1%)
How does cushings present?
Fatigue, reduced physical endurance
Weight gain(central obesity)
Moon face, buffalo hump, supraclavicular fat pads)
Skin atrophy with purple striae
Easy bruising
Muscle weakness
Immune system suppression
Menstrual irregularities
What s/s in Cushing is associated with ACTH?
Hyperpigementation
Hypertension
Hirsutism
What labs would you order for Cushings?
CBC: leukocytosis, neutrophilia, lymphocytopenia, decrease eosinophils
CMP: Hyperglycemia, hyperN, hypoK
What are the diagnostic goals for cushings?
Exogenous or endogenous etiology
Presence of hypercortisolism
Cause of hypercortisolism
When do we need a workup for cushings?
Endogenous needs a workup
What tests do we use to establish hypercortisolism?
Dexamethasone suppression test (dexamethasone 11PM, serum cortisol 8AM)
24hour urine free cortisol
Late night salivary cortisol
Need two highly positive test to diagnose
What results do you need on the low-dose dexamethasone suppression test to diagnose? What are reasons for inaccuracy?
<5mcg/dL r/o cushings
3% false-negative rate (8% of curshings have normal suppression)
antiseizure drugs, rifampin, estrogens lower supressibility
20-30% false-positive rate(psychiatric disorders, stress)
How would a 24hour urine free cortisol test to diagnose? How is collected?
3x upper limit of normal urine cortisol on both occasions(depends on age/sex)
Collected AFTER first morning void, then collect for 24hours including the first morning void of the next day
How do you collect late night salivary cortisol?
Collect between 11pm to midnight
Stored in room temp for days
Perform on 2 separate occasions
Both must be elevated to be considered positive
What should you do before collecting night salivary cortisol?
No steroids before 24hours(cream, lotion, inhalers)
No drinking/eating before 30mins
Avoid brushing and floss before collecting, if bleeding in mouth DO NOT collect
What can cause increased salivary cortisol?
Irregular sleep
Pregnancy
Steroid/estrogen use, anticonvulsant
Mental illness
Alcohol use
Acute stress
How do we interpret the diagnostic tests?
2 tests negative and low suspicion: no workup
2 tests negative and high suspicion: refer to endo
1 out of 2 positive: repeat saliva or 24UFC at random if not confirmatory or refer to endo
Consider cyclic Cushing disease as dx
2 positive: refer to endo to evaluate etiology
How do we determine the cause for hypercortisolism?
Serum ACTH(differentiates ACTH-dependent/independent)
<20pg/dL order adrenal CT
>20pg/dL order pituitary MRI
How do we collect serum ACTH?
6-9am in an EDTA tube on ice
Spun after collection and stored a -20C until assay
How would we interpret a CT of the adrenal gland?
Determine if its benign or malignant
Malignant if…
<4cm
Growth of nodule(need previous CT)
Density of lesion is >10 HU(hounsfield, radio density, air -1000, water 0)
How would we interpret a MRI w/ contrast of the pituitary gland?
No lesion or lesion <5mm then take inferior petrosal sinus sampling
If elevated ACTH lvls, then pituitary cushings disease
If normal ACTH lvls: ectopic source of ACTH
If lesion >5mm begin treatment
How would we find the ectopic source for cushings?
CT scan of chest/abdomen
Whole body PET scan if CT is negative
How do we treat exogenous Cushing syndrome?
Titrate down exogenous glucocorticoids/ACTH therapy
Recovered within 6-12months
Short acting glucocorticoids helps recovery(hydrocortisone)
Why do we titrate slowly for treatment of exogenous Cushing syndrome?
Rapid withdrawal can result in acute adrenal insufficiency
Prolonged therapy can suppress HPA axis
How do we treat tumors causing cushings?
Surgical removal
Pituitary radiation
What does a pt need after surgical removal?
They may have post surgical adrenal insufficiency so…
Lifelong glucocorticoid replacement
When is medical management indicated and what are they?
When they can’t do surgery
Hypercortisolism: 11B-hydroylase inhibitors, ketoconazole
Pituitary ACTH tumor: pasireotide
What does 11B-hydrolyase inhibitors do?
Block cortisol steroid-genesis
RX: metyrapone osilodrostat
What does pasireotide do?
Somatostatin analog
Inhibits ACTH secretion
How do we manage mineralocorticoid HTN?
1st line: Spironalactone, eplerenoen
Mineralocorticoid receptor antagonist(K sparing diuretic)
2nd line: ACEI
How do we manage hyperandrogegism in women? MOA?
Flutamide: antiandrogen agent
Inhibits androgen uptake
Inhibits binding of androgen in tissues
What complications should we monitor and treat in cushings?
Osteoporosis
CVD
Psychiatric(memory loss, insomnia)
DM
HypoK
Muscle Weakness
Infections
Sleep apnea
If no treatment for cushings is given what would result?
High morbidity/mortality
HTN, DM, Infection
Complications from osteroprosis
Nephrolithiasis(kidney stones)
Psychosis
