Defense & Barriers 2: (3) Endocrine Diseases of the Adrenal Gland

Question 1

trilostane vs. mitotane?

Answer 1

both had SIMILAR SURVIVAL TIMES but TRILOSTANE HAD MUCH LESS DRAMATIC SIDE EFFECTS

Question 2

DOSAGE for trilostane…
how OFTEN is it given?
what dose USUALLY works?
what dose CAN WE GO UP TO? who is this usually reserved for?
in what 2 ways can the dose be adjusted?

Answer 2

how OFTEN? = TWICE daily

what dose USUALLY works? = 0.5 –> 1 mg/kg BID PO

what dose CAN WE GO UP TO? = 40-50 mg/kg/day, usually reserved for ALOPECIA X PATIENTS

what 2 ways can the dose be adjusted?
1. some dogs need a GRADUAL INCREASE in dose within first few months of treatment or throughout life

2. other dogs may require discontinuation because they develop hypoadrenocorticism/Addisonian crisis

Question 3

ACTH stim as a MONITOR for TRILOSTANE…
at WHAT DAYS should we perform an ACTH STIM for TRILOSTANE MONITORING? (3 parameters, 3 subs for second one)
AFTER this, how often should we test?
what 2 things can we also measure at time of ACTH stim?

Answer 3

1. DAYS 10-14
2. DAY 30
   –> The RISK OF ADRENAL NECROSIS IS HIGHEST DURING THE FIRST 30 DAYS
   –> Owners should LOOK FOR CLINICAL SIGNS as the most important monitoring tool!
   –> Can be difficult to monitor, but look for DECREASED APPETITE as a sign of this!
3. DAY 90

AFTER this…
–> THEN, ACTH STIM every 3-4 MONTHS

can also measure Na and K

Question 4

HOW to perform ACTH stim to MONITOR for TRILOSTANE…
how much LATER after giving trilostane should we perform it? why?
VHUP vs. literature parameters? but at the end of the day it’s ___ ____ ____!
WHAT should we base our DOSE ADJUSTMENTS on?

Answer 4

how much LATER?
–> measurement should be 4-6 HOURS AFTER giving trilostane because it has PEAK ACTIVITY
–> want to make sure NO ADDISONIAN CRISIS AT TRILOSTANE’S PEAK

parameters?
–> VHUP = cortisol should be LESS THAN 2 ug/dL
–> LITERATURE = cortisol should be LESS THAN 5 ug/dL
but at the end of the day, it’s UP TO YOU!

BASE DOSE ADJUSTMENTS ON CLINICAL SIGNS!!! cortisol can change and be imperfect for many reasons

Question 5

LYSODREN…
also called what?
causes… (2)
dosing?
indication?

Answer 5

also called MITOTANE

causes…
1. SEVERE NECROSIS of ZONA FASCICULATA and RETICULARIS
2. SOME NECROSIS of ZONA GLOMERULOSA

dosing?
–> usually has INDUCTION and MAINTENANCE dosing at LARGE DOSES

indication?
–> recommended when SURGERY NOT RECOMMENDED DUE TO METASTASIS

Question 6

L-DEPRENYL…
2 alternative names?
= what is it?
what does it cause?
what is it indicated for? (2)

Answer 6

alternative names?
1. selegiline
2. Anipryl

= IRREVERSIBLE INHIBITOR of MONOAMINE OXIDASE TYPE B

causes INCREASED DOPAMINE CONCENTRATION which then INHIBITS ACTH FROM INTERMEDIATE PITUITARY

indications?
1. even though most dogs have pituitary tumors in ANTERIOR lobe, helps with INTERMEDIATE PITUITARY MASSES causing Cushing’s
2. good for ELDERLY DOGS WITH CUSHING’S with COGNITIVE DYSFUNCTION

Question 7

HYPOPHYSECTOMY
= what is it?
indication?
for the HIGHEST CHANCE OF SUCCESS, when should it be done?
post-op care? (4)
most common complication?

Answer 7

= surgical REMOVAL of the PITUITARY gland

indication?
–> If a dog with a LARGE TUMOR developed CENTRAL DIABETES INSIPIDUS

when?
–> EARLY intervention BEFORE ONSET OF NEUROLOGIC SIGNS

post-op care?
1. LIFELONG SUPPLEMENTATION NECESSARY
2. GCCs
3. thyroid hormones
4. DDABP if concurrent diabetes insipidus

most common complication?
–> DECREASED TEAR PRODUCTION

Question 8

treatment for ADRENAL TUMORS…
what is usually NECESSARY?
when can this treatment be CURATIVE?
post-op treatment? (2)

Answer 8

usually…
–> NEED TO COME OUT VIA SURGERY unless METASTASIZED TO ABDOMEN or CAUDAL VENA CAVA

can be CURATIVE for ADRENAL ADENOMAS

post-op treatment?
1. AT LEAST 4 MONTHS of GCC and MINERALOCORTICOID SUPPLEMENTATION
2. then, GRADUALLY wean off!

Question 9

STEREOTACTIC RADIATION THERAPY…
= what is it?
what is it good for? (lesion & what organ)

Answer 9

= a highly FOCUSED dose of radiation on the TUMOR so that we can give HIGH DOSES VERY FEW TIMES

good for MACROADENOMAS on PITUITARY GLAND

Question 10

what 2 treatments are NOT recommended for Cushing’s/why?

Answer 10

1. KETOCONAZOLE = a cytochrome P450 inhibitor, TOO MANY SIDE EFFECTS
2. PHOTON IRRADIATION = causes too much damage to SURROUNDING TISSUE

Question 11

ATYPICAL hyperadrenocorticism…
= what is it?
what causes it?

Answer 11

= when a dog appears to have hyperadrenocorticism clinically, but ADRENAL AXIS TESTING IS NORMAL  NO EXCESS CORTISOL

cause?
–> usually because ANOTHER hormone is binding CORTISOL RECEPTORS and causing SAME CLINICAL SIGNS AS EXCESS CORTISOL

Question 12

ID disease

Answer 12

FELINE HYPERADRENOCORTICISM

** SKIN TEARS COMMON

Question 13

FELINE hyperadrenocorticism…
commonality?
concurrent disease? (2)
hematology? (2)
treatment? (3, 2 points for 2/3)

Answer 13

commonality?
–> RARE

concurrent dz?
1. MOST cats with Cushing’s ALSO HAVE DIABETES MELLITUS!
2. If you don’t also see diabetes, take Cushing’s OFF OF DDXs!

hematology?
–> NO STEROID-INDUCED ALKP INCREASE because NO STEROID-INDUCED ISOENZYME
diagnosis?
–> Can perform ACTH STIM & LDDS test, but PROTOCOLS ARE DIFFERENT!

Treatment?
1. METYRAPONE (11-beta-hydroxylase enzyme-inhibitor)
2. TRILOSTANE
–> It works but NOT SUPER WELL
–> Requires MUCH HIGHER DOSES THAN DOGS
3. SURGERY
–> **Need to make sure skin has good integrity first
–> But THIS IS A GOOD TREATMENT OPTION –> if we CAN take cats with Cushing’s to surgery, WE DO!

Question 14

true/false

1. Skin tears are much more common in cats with hyperadrenocorticism than in dogs with hyperadrenocorticism
2. Trilostane can cause adrenal necrosis as an undesired side effect, however, with Lysodren, adrenal necrosis is the actual mechanism of action.
3. With trilostane treatment, hyperkalemia does not necessarily mean that the dog is experiencing an Addisonian crisis

Answer 14

1. Skin tears are much more common in cats with hyperadrenocorticism than in dogs with hyperadrenocorticism = TRUE
2. Trilostane can cause adrenal necrosis as an undesired side effect, however, with Lysodren, adrenal necrosis is the actual mechanism of action. = TRUE
3. With trilostane treatment, hyperkalemia does not necessarily mean that the dog is experiencing an Addisonian crisis = TRUE

Question 15

PRIMARY HYPERALDOSTERONISM…
commonality? (2)
etiology? (2)
3 electrolyte/bloodwork findings?
clinical sign?

Answer 15

commonality?
1. RARE
2. Diagnosed mostly in CATS

etiology?
1. UNILATERAL ADRENAL ADENOMA or CARCINOMA
2. OR BILATERAL ADRENAL HYPERPLASIA

4 findings?
1. EXCESS SODIUM RETENTION = increased EXTRACELLULAR & PLASMA VOLUMES, HYPERTENSION
2. HYPOKALEMIA
3. Elevated SERUM ALDOSTERONE

clinical sign?
–> WEAKNESS & VENTROFLEXION of the neck due to HYPOKALEMIA

Question 16

PHEOCHROMOCYTOMA…
= what is it?
commonality?
signalment? (2, second is a LACK of signalment)
history/clinical signs are generally ____ & list some examples
what SPECIFIC hematologic finding causes 3 specific clinical signs?
diagnosis? (5, including why it’s DIFFICULT/how it’s usually diagnosed, and HOW TO DEFINITIVELY DIAGNOSE)
CBC/chem findings?
urinalysis findings?
behavior of disease?
treatment? (4)

Answer 16

= MASS in the adrenal MEDULLA

commonality?
–> UNCOMMON in DOGS & CATS
signalment?
1. OLDER dogs (~11 years)
2. No specific sex or breed predilection

history/clinical signs are GENERALLY VAGUE
–> D+, weight loss, abdominal distention, edema, lethargy, anorexia, V+, PU/PD

SPECIFIC finding?
–> HYPERTENSION, which can cause…
1. Epistaxis
2. Acute blindness (+ from RETINAL DETACHMENT)
3. Cardiac arrhythmias

diagnosis?
1. DIFFICULT to diagnose ANTEMORTEM (before death), more often an INCIDENTAL finding on necropsy
2. Arterial BP, SOMETIMES dogs with pheochromocytomas CAN HAVE HYPERTENSION
3. Hormonal testing
4. EXCLUSION of other diseases that could cause same clinical signs
5. SURGICAL EXPLORATION AND HISTOPATHOLOGY/BIOPSY is the ONLY WAY TO DEFINITIVELY DIAGNOSE!!

CBC/chem?
–> USUALLY NORMAL, so not super helpful but helps RULE OUT CUSHING’S

urinalysis?
–> PROTEINURIA from HYPERTENSION possible

behavior?
–> Usually MALIGNANT, often metastasize to caudal vena cava and liver

treatment?
1. CAN be taken out, but because they’ve often spread don’t usually do surgery
2. Can use PHENOXYBENZAMINE (alpha/beta adrenergic blocker) PO to HELP WITH HYPERTENSION; give for 2 weeks prior to Sx to DECREASE BP
3. PHENTOLAMINE or LOBETALOL = bring down BP during SX in DOGS
4. HYDRALAZINE = bring down BP during SX in CATS

Question 17

measurement of NORMETANEPHRINE represents a true determinant of ____ levels in dogs & can be used to help increase suspicion for diagnosis of ____

Answer 17

CATECHOLAMINE, PHEOCHROMOCYTOMA

Question 18

HYPERTENSION parameters?
if an animal is HYPERTENSIVE, what disease can be associated?

Answer 18

Hypertension parameters?
Systolic = >160 mmHg, Diastolic = >95 mmHg

can be associated with PHEOCHROMOCYTOMA

Question 19

toceranib phosphate
brand name?
= what is it?
indication?

Answer 19

brand name? –> PALLADIA

= a TYROSINE KINASE INHIBITOR that BLOCKS RECEPTORS ASSOCIATED WITH ANGIOGENESIS and CELL PROLIFERATION to achieve ANTI-NEOPLASTIC EFFECTS

indication?
–> Good for DOGS WITH INOPERABLE/METASTATIC PHEOCHROMOCYTOMAS