Hyper/Hypo Adrenocortistism Flashcards
Excessive production of glucocorticoids by the adrenal glands
Hyperadrenocortisim
What are the three forms of HAC
Pituitary dependent (PDH) Adrenocortical neoplasia (AT) Iatrogenic
What is the most common type of HAC?
Pituitary dependent
Accounts for 80-85% of cases
What type of HAC causes bilateral adrenocortical hyperplasia?
Pituitary dependent
What type of HAC causes bilateral adrenal atrophy?
Iatrogenic
What type of HAC has and enlarged adrenal gland with atrophy of the contralateral gland
Adrenocortical tumors (AT)
Species predisposed to HAC?
Poodles Boxer Dashunds Schnauzers Boston terriers German shepherds
At what age do you usually see HAC?
Middle aged to old dog, ave 12yrs
What is not a clinical finding associated with HAC?
PU/PD Bilaterally symmetrical alopecia Pendulous abdomen Seborrhea Calcinosis cutis
Seborrhea - associated with hypothyroidism
What would you expect to find on a CBC, chem panel and UA of a cushings patient
CBC- polycythemia, stress leukogram
Chem- increased ALP, hypercholesterolemia, mildly increase ALT and glucose
UA- decreased specific gravity, proteinuria
USG <1.025
What may you see on a radiograph of a HAC patient?
Hepatomegaly –corstiol makes the liver larger
Distended bladder- PU/PD
Mineralization
Osteopenia
Metastasis of adrenal tumors
Would you expect to see an increased BP in cushings patient?
50-80% of patients are hypertensive
Maybe du to PLN
T/F: baseline cortisol can be normal in cushings dogs
True
Secretion in episodic
Mean daily cortisol is increased but individual measurement can be normal
What would the urine cortisol: creatinine ratio be in a cushings patient?
Would be increased
Urine cortisol excretion increases with adrenal secretion of cortisol
T/F: a high urine cortisol: creatinine ratio can be diagnostic for cushings
False
Positive test makes cushings a possibility, but is not diagnostic
However, a negative test makes cushings unlikely
What is the low dose dexamethasone suppression test?
Dexamethasone inhibits release of ACTH from pituitary
Normal - cortisol suppressed
Cushings- no suppression
Low Dose Dex suppression test
50% suppression at 4 hrs with lack of suppression at 8hrs.
What is your interpretation?
Pituitary dependent hyperadrenocortisim
Low Dose Dex suppression test
No suppression at 8hrs or 4hrs.
What is your interpretation?
Cushings
Could be either AT or PDH
What is the test of choice for iatrogenic cushings?
ACTH stimulation test
What are the cons of the ACTH stimulation test?
Expensive
Compounded gels are not recommended.
What is the high dose Dex suppression text?
About 10x dose of LDDST
Cannot be used to diagnose cushings, test to differentiate between PDH and AT
Suppression =PDH
No suppression= inconclusive
Cannot definitely diagnose AT
What would you use an Endogenous corticotrophin to diagnose?
To differentate between PDH and AT
Cannot be used to diagnose cushings b/c of overlap in ACTH in normal animals and PDH animals
Normal 20-100pg/mL
PDH 40-500pg/mL
AT <20pg/mL
T/F: ultrasound can be used to differentiate malignant from benign adrenal tumors
False
Can usually only determine malignancy this way if there is invasion of the vena cava or liver metastases
What test would be the BEST to diagnose cushings in a case with only mild clinical signs or lab abnormalities only
ACTH stim
Also good for
- patients with concurrent nonadrenal illness
- patients with suspected iatrogenic cushings
- patients on phenobarbital
What test would be BEST to diagnose a cushings case in a patient with severe clinical signs and no evidence of non adrenal illness?
LDDS
What would be the BEST test to diagnose a suspected adrenal tumor?
LDDS
Which test is the BEST at differentiating PDH vs AT HAC, is this the most practical clinically?
Endogenous ACTH.
Not most clinically practical because test is expensive and sample required very careful handling. See more often in University setting.
Clinically, abdominal radiographs are used to visualize AT
You run LDDS, ACTH stim, Endogenous ACTH and they all come back negative, but the dog has classical cushingoid appearance.
What could be the problem with this dog?
Noncortisol hormones and cushings
-> derangement of steroid pathway and overproduction of precursors
If you think a dog has noncortisol cushings, how would you confirm your diagnosis?
Perform ACTH stimulation and assay noncortisol hormones (Eg progestin)
What are the medical therapy treatments for cushings?
Mitotane Selegiline Ketoconazole Trilostane Cyprohetadine Bromocriptine
What is the MOA of mitotane ?
Destroy zona fasciculata and reticularis of adrenal gland -> permanent atrophy
Inhibits cholesterol side chain cleavage.
What is the dosage of mitotane and how would you monitor this therapy?
Starting dose - 50mg/kg/day, divided BID with meals
Maintenance - 50mg/kg/week
Monitor - ACTH stim within 5-10days then 1 and 3 months after diagnosis
What is the MOA of selegiline
Irreversible inhibitor of monoamine oxidase type B -> restore central dopamine concentration
-> decrease the clinical signs of cushings, but does not have any effect on the tumor
Which therapy may be a good option for patients whose owners do not want to used Lysodren due to side effects or the high cost of Trilostane
Selegiline (Anipryl)
When is Anipryl use appropriate?
Patients with mild cushings signs but are negative on lab tests
May have a role in patients that test positive for cushings but have no clinical signs
Cognitive dysfunction
Behavior - pee in the right places
What is the MOA of trilostane?
Competitive inhibitor of 3B-hydroxysteroid dehydrogenase —> inhibit synthesis of steroids (cortisol and aldosterone)
T/F: Mitotane and Trilostane are reversible drug therapies
False
Only trilostane is reversible
What drug should you do periodic monitoring of electrolytes because it can cause a hyperkalemia ?
Trilostane
How does ketoconazole treat cushings?
Inhibit steroid biosynthesis
-> imidazole antifungal drug
EXPENSIVE
What are adverse effects of ketoconazole ?
Excessive glucocorticoids deficiency -> cessation of therapy
Vomiting, diarrhea, anorexia, and elevated liver enzymes
What is the MOA of cyprohetadine? How does this treat cushings?
Antiserotonin, anticholinergic, and antihistamine effects
Increased serotonin theroeticallly associated with excess pituitary ACTH
What are the non-drug therapies for cushings?
Surgical
- transsphenoidal hypophysectomy - very difficult and requried lifelong thyroid pred replacement
- bilateral adrenalectomy
Radiation therapy
What is the treatment of pituitary macroadenomas ?
Radiation therapy
-reduce tumor size and clinical signs.
Often still require medical therapy to control cushings disease
What is the treatment f choice for adrenal tumors?
Adrenalectomy
- are often vascular and invasive even if benign
50% malignant -> very poor prognosis
How can you reduce risk of thromboembolism post-adrenalectomy
Treatment with dexamethasone, heparin, plasma, and Hetastarch- over first 5 days
What are some complications associated with PDH?
Hypertension, PTE, CNS signs, infections, recurrence of disease, CHF
What are the 5P’s of HAC?
Panting PU PD PP Potbelly
What is the signalment of hypoadrenocorticism ?
Med to lg breed dogs
Younger
Release of aldosterone from the adrenal gland has what effect?
Increased Na and water reabsorption
Increased K secretion into urine
Increase blood volume
Aldosterone release from the adrenal gland is stimulated by?
Angiotensin II
Deficiency in aldosterone results in…?
HYPO natermia and chloremia
HYPER kalemia
What are the major regulators of aldosterone secretion?
Plasma K levels and RAAS
Where does aldosterone exert its effect?
DCT and collecting duct
-> increase Na reabsorption
What is the signalment of Addison’s disease?
Dog, young to middle aged
F>M
Clinical signs of Addisons?
“Ain’t doing right” Waxing and waning Anorexia Lethargy Dehydration Weakness Polyuria
What does an addisons crisis appear like?
Collapse, bradycardia, melena
What is “typical” hypoadrenocorticism ?
Deficient in both mineralalocortocoids and glucocorticoids
Due to primary lesions - usually immune mediated adrenal gland destruction
What is the normal function of glucocorticoids? What will you see in a deficiency?
Normal fx: increase blood glucose, gluconeogensis, glycogenolysis, muscle/fat catabolism
Deficiency: anorexia, lethargy, fasting hypoglycemia
What is atypical hypoadrenocorticism? What are the two causes?
Low glucocorticoids
- pituitary lesion so there is not enough ACTH
- early in a typical addisons, before it progresses to include mineralocorticoids
What is iatrogenic hypoadrenocorticism ?
Abrupt discontinuation of glucocorticoids without time for the atrophied adrenals to respond
Poodle 1.5yrs, history of lethargy and poor appetite
PE: recumbency and minimally responsive, positive skin tent, sunken eyes, tacky mm.
TPR: hypothermic and bradycardia
What’s you DDx, and what diagnostics would you run to confirm?
Hypoadrenocorticism
QATS - mild hypoglycemia, azotemia, USG 1.018
CBC, chem, UA
ECG
Poodle 1.5yrs, history of lethargy and poor appetite
PE: recumbency and minimally responsive, positive skin tent, sunken eyes, tacky mm.
TPR: hypothermic and bradycardia
What type of supportive care would you give this patient?
Heat
IV catch with fluids
Emerg hyperkalemia treatment
What type of fluids should be given to addisons patient?
Saline
Can have hyperkalemia, do NOT give fluids with K
What could you do to treat a hyperkalemia in an addisons patient?
Saline
Calcium gluconate: cardioprotective
Regular insulin with concurrent dextrose (draws potassium into cells and some diuretic effect)
Bicarb - patient are acidotic
What CBC, Chem and UA results would you expect in an Addisons patient?
CBC - NO stress leukogram
Chem- azotemia, hyponatremia, hyperkalemia
UA- isosthenuric
What test is diagnostic or hypoadrenocorticism
ACTH stimulation test
Endogenous ACTH levels
-can be used to differentiate type
Endogenous ACTH is high in ________________ hypoadrenocorticism and low in _________forms
Primary; secondary and tertiary
What is the treatment for an acute Addisonian crisis ??
Restore blood volume rapidly: 0.9% NaCl
Address life-threatening hyperkalemia: shock dose fluids then insulin/glucose, Ca gluconte, or Bicarb if nessessary
GIVE GLUCOCORTICOIDS ** dexamethasone **
Give mineralocorticoids - DOCP/Fludricortisone
Which therapy for mineralocorticoids, also has some glucocorticoid effect?
Fludrocortisone
T/F: glucocorticoids maintence therapy is needed by all addisons patients
False
More likely needed with DOCP
For maintenance therapy fo glucocorticoids, addisons patients should receive what type of dose?
Physiologic dose (0.25/kg/day)
All owners should have some to give under conditions of stress (0.5-1.5 mg/kg/day)
How do you treat atypical hypoadrenocorticism ?
Glucocorticoids supplementation
