Transcript Thyroid replacement hormone (levothyroxine sodium)

ATTITUDE
“The people who get on in this world are
the people who get up and look for the
circumstances they want, and if they
can’t find them, make them.”
-George Bernard Shaw
ENDOCRINE SYSTEM
DISEASES
‘CRINE’ – to secrete
Endocrine System Diseases
Main trigger: Hypothalamus
Review of the basics
• Endocrine ____________- basic units of the
endocrine system.
– Secrete hormones ___________ into the
bloodstream.
• Circulate throughout body and produce effects when
attach to receptors in or outside of cells.
– __________ glands.
• Exocrine glands- units that secrete their
products onto epithelial surfaces through tiny
tubes called _____________.
Hormones
• ___________ messengers produced by endocrine
glands and secreted directly into blood vessels.
• Produce effects when find their receptors in or on
cells.
– Each body cell has specific receptors to certain
hormones (___________).
– If body does not have receptor, hormone will pass by.
– Only certain hormones can _______ to receptors and
when it occurs, then it changes the activity of the cell.
Hormones
Control of Hormone Secretion
• “Negative Feedback System”
– Endocrine glands will be stimulated to produce more hormone
when it drops below a certain amount in the body.
– If hormone is of adequate levels, gland will either slow or stop
production of the hormone which is called negative feedback.
• Direct Stimulation of Nervous System
– Secretion of some hormones is stimulated by sympathetic nerve
impulses when an animal feels threatened.
• Fight or flight response from sympathetic nervous
system
DISEASES OF THE THYROID GLAND
HYPERTHYROIDISM
HYPOTHYROIDISM
Hypothyroidism
Thyroid Gland
• Gland not usually palpable
• Located at ventral cervical region along lateral margins of
trachea
• Hormones produced
– T3 (___________________) and T4 (_____________________),
iodine containing hormones.
• Produced by follicular cells
– ______________ – Causes Calcium deposition in bone which
decreases blood Calcium concentrations
• Produced by parafollicular cells
Hypothyroidism
• Definition: clinical state associated with
____________________ which causes low cell
metabolism in most tissues of the body
• Primary acquired – 90% of dogs
– Caused by ________________or
_________________________
– Also by iodine deficiency, neoplasia, infection
• Secondary acquired- RARE
– Anterior Pituitary dysfunction or destruction from neoplasia
– leads to ↓TSH
• Congenital Hypothyroidism-RARE
– Cretinism (newborns)
Hypothyroidism
• MOST COMMON ENDOCRINE DISEASE
IN____________; rare in cats
– Breeds: Golden Retriever, Doberman, Irish Setter,
Schnauzer, Cocker Spaniel, Dachshund, others
• 4-10 yrs of age
• Females
• Greyhounds and Scottish deerhounds
physiologically have lower T4 (thyroxine)
Hypothyroidism
• Clinical Signs - COMMON
– __________________________________
– Skin changes
• Bilaterally symmetric truncal alopecia (which
other disease has this clinical sign? )
• ______________________ neck, axillae, and
other areas of friction
• Seborrhea
• Superficial pyoderma
• Dry, lusterless haircoat
• Hyperpigmentation
– Cold intolerance (why?)
– Lethargy/sleeping
– Exercise intolerance
Hypothyroidism
Hypothyroidism
Hypothyroidism
Hypothyroidism
Hypothyroidism
• Clinical signs/Bloodwork – Less common
– ___________________– generalized weakness, ataxia, facial
paralysis/paresis, seizures (secondary to cerebral atherosclerosis)
– _______________– Constipation, Regurgitation caused by
megaesophagus
– Bloodwork abnormalities –_____________lipidemia is most
common, gross lipemia ( milky appearance to the serum),
____________________cholesterolemia (80%), anemia (mild nonregenrative)
– Eye – hyperlipidemia => corneal lipidosis and anterior uveitis
*Virtually all body systems are affected, clinical signs are
generally non-specific
Hypothyroidism: DIAGNOSIS
• Blood Tests
– Hypothyroid dogs have lowered level of T4
– Test total T4(TT4), +/- T3 levels
– Free T4: Free T4 is thyroxine that is not protein bound
(ED is most accurate test for fT4 measurement)
– Basal TSH concentration
• Measures TSH in blood, should be used in conjunction with
other tests and clinical signs
*ED = equilibrium dialysis
Hypothyroidism: Considerations
• Remember sick animals and animals on certain
medications (anti-epileptics, glucocorticoids)
may have depressed T4 levels.
(_________________)
– Wait and re-test after treatment of underlying cause
if clinical signs persist.
• Greyhounds have low T4 levels naturally
diagnose based on clinical signs as well as test
results; treat if clinically evident.
Hypothyroidism
• Treatment
– Thyroid supplement – _________________
• Oral, synthetic levothyroxine (0.02 mg/kg BID)
• Daily administration (after cs resolves consider
SID)
– Steady state levels – 4/8 wks (1st 6-8 months)
• Test levels and adjust dose until T4 normal
– Want to test 4-6 hours after dose is given (when serum
levels are highest)
Thyroid replacement hormone
(levothyroxine sodium)
Hypothyroidism
• Client Education
– Supplement for ________________
– Daily dosing required
– Overdose => hyperthyroidism
• Regular rechecks are recommended including
bloodwork.
• PU/PD; nervousness, weight loss, panting, weakness,
inc. appetite
– Vet may recommend a reduced fat diet until body
weight is satisfactory and T4 levels are normal.
Hyperthyroidism
Definition: Pathologic, sustained, high overall
metabolism caused by high circulating
concentrations of thyroid hormones
• Most common Endocrine disease in ____________
(one of the big 3 diseases of older cats)
– Very rare in dogs
• Pathophysiology
– Autonomously ___________________________, no
physiologic controls (functional thyroid adenoma)
– Secrete _______ and ____________
Hyperthyroidism in cats
Hyperthyroidism
• Clinical Signs
– Multi-systemic: reflects increase in metabolism
•
•
•
•
•
•
•
_________________
__________________
Vomiting/diarrhea
_____________________
Tachypnea/dyspnea
Hyperactivity
Aggression
Hyperthyroidism
• Clinical signs cont’d
– ____________________(thickening of LV
and heart muscle)
– Hypertension
– Poor body condition
– Thickened nails
– Unkempt appearance
– ______________________ gland 70% bilateral
Hyperthyroid cat
Middle age to older cats
Wt loss
Polyphagia
Tachycardia
Blindness with retinal detachment
Palpable enlarged Thyroid gland
Aggressive
unkempt haircoat
Hyperthyroid cat: Goiter
Hyperthyroidism
• Diagnosis
– Palpate enlarged thyroid gland
– Elevated T4, FT4
– X-rays for associated heart disease
Hyperthyroidism: Scintigraphy
Normal cat
Normal uptake in salivary glands
and thyroid glands
Hyperthyroid cat
Unilateral thyroid adenoma
Hyperthyroidism: Scintigraphy
Hyperthyroid cat
Bilateral thyroid adenoma
Hyperthyroid cat
Ectopic (intrathoracic)
thyroid adenoma
Hyperthyroid cat
Functional thyroid carcinoma
(represents regional metastasis)
Hyperthyroidism
• Treatment
– ______________________ (Tapazole) – anti-thyroid drug
– block incorporation of iodine into thyroglobulin.
– Monitor: q 2-3 weeks
• COMMON AND PRACTICAL FOR CLIENTS
– Radioiodine treatment – I131
• Effective
• Emitted radiation destroys functioning follicular cells
• ______________________________________________
– Surgical removal of gland
• May cause hypothyroidism
• May result in hypocalcemia due to hypoparathyroidism
Hyperthyroidism: Medical Rx
METHIMAZOLE
ORAL DRUG, BUT CAN BE FORMULATED INTO
A TRANSDERMAL OINTMENT
Hyperthyroidism
• Complications
– Renal disease/failure unveiled when thyroid levels controlled
• 2-3 months after medication started
– Occasionally tapazole will no longer be effective usually after 2-3
years of treatment
• Prognosis
– Excellent if uncomplicated
– If labs show ___________________ prior to treatment, prognosis
more guarded
Hyperthyroidism: Client Info
• Cause of disease is unknown
• Surgery or Radiation are only cures
• Cat may become hypothyroid following Rx –
usually not clinically significant and
supplementation can be initiated if necessary
• Following Tapazole, Blood pressure and
kidney values should be checked routinely
EDUCATION
Education is learning what you didn’t
even know you didn’t know.
-Daniel J. Boorstin
DISEASES OF THE PARATHYROID GLANDS
HYPERPARATHYROIDISM
HYPOPARATHYROIDISM
Thyroid/Parathyroid glands
1=normal thyroid gland
2 and 3=parathyroid gland
4=enlarged thyroid gland
Parathyroid gland
• Secretion: Parathyroid hormone (PTH,
Parathormone)
• Function: ↑ plasma Ca2+ concentration
– 1. ↑ osteoclast activity
– 2. ↑ Ca++ absorption from GI tract
– 3. ↑ Ca++ reabsorption from kidney tubules
• Hyperparathyroidism →hypercalcemia
• Hypoparathyroidism →hypocalcemia
Hyperparathyroidism
• Causes:
– 1º hyperparathyroidism—adenoma or carcinoma
– 2º hyperparathyroidism—poor diet; low Ca intake
• Clinical signs:
– Many animals show no clinical signs
– signs occur as organ dysfunction occurs
• urinary/renal calculi (high plasma Ca++)
• cardiac arrhythmias, tremors (Ca++ necessary
for normal muscle contraction
• Anorexia, vomiting, constipation
• weakness
Hyperparathyroidism
Dx:
• Routine chemistry panel
– ↑ blood Calcium (normal: ~8-10 mg/dl))
– +/- ↓ blood Phosphorus (normal: ~2-6 mg/dl)
• PTH assay
– normal PTH: dogs ~20 pg/ml, cats ~17 pg/ml
– In a normal animal: if blood Ca++ is high, PTH is low (neg feedback)
– 1º Hyperparathyroidism: Ca++ high, PTH elevated
• Ultrasound of neck – enlarged glands, abdomen uroliths
Hyperparathyroidism
Tx:
1. Surgical removal of diseased parathyroid (generally 4 lobes are
imbedded in thyroid gland)
Other options:
2. Ultrasound-guided chemical (ethanol)
3. Ultrasound-guided heat (laser) ablation
Post-Op Care:
1. Hospitalize for 1 wk; ↓PTH may predispose animal to
hypocalcemia
2. Calcium therapy (oral tabs, liquid)
3. Vit D supplements (promotes Ca intestinal absorption)
Hyperparathyroidism
Client Info
1. Most hyperparathyroid animals show no
signs when first diagnosed
2. Run yearly chem panels on all normal, older
animals
Hypercalcemia: Other causes
• Causes
– Neoplasia (lymphoma, perianal gland
tumors)
– Renal failure
– Hypoadenocorticism
– Vitamin D rodenticide
– Drugs or artifacts (ex lipemia)
• Clinical signs vary with cause
– PU/PD, anorexia, lethargy, vomiting,
weakness, stupor/coma (severe), uroliths
Hypercalcemia
• Tests
– Elevated serum calcium levels
– Low to low-normal phosphorus concentrations
Hypercalcemia
• Treatment
– Fluids: 0.9% NaCl
• No Ca2+ containing fluids
– Diuretics (furosemide)
– Steroids
• Complications
– Irreversible renal failure
– Soft tissue calcifications
Hypocalcemia
Causes:
1.
Parathyroid disease
a.
b.
2.
Chronic renal failure—
a.
b.
c.
3.
Inadvertent removal of parathyroid during thyroidectomy (most common cause
1º Hypoparathyroidism (uncommon in animals)
may cause ↑ serum P, which can result in ↓ serum Ca (Ca:P inverse relation)
Vit D normally activated in kidney
Protein-losing nephropathy results in loss of albumin-bound Ca
Puerperal Tetany (Eclampsia)—late gestation thru post-partum period
a.
b.
c.
Improper prenatal nutrition
Heavy lactation
Inappropriate Ca++ supplementation
http://www.thepetcenter.com/gen/eclampsia.html#The_video
Hypocalcemia
Clinical Signs:
1.
2.
3.
4.
Restlessness, muscle tremors, tonic-clonic contractions,
seizures
Tachycardia with excitement; bradycardia in severe cases
(Ca++ is necessary for proper muscle contractions)
Hyperthermia
Stiffness, ataxic
Hypocalcemia
Dx:
Total serum <6.5 mg/dl
Tx:
1.
2.
3.
4.
IV infusion of 10% Ca gluconate solution (monitor
HR and rhythm during infusion)
Diazepam (IV) to control seizures
Oral supplements of Ca (tabs, caps, syrup)
Improve nutrition
Hypocalcemia
Client info:
1. Well-balanced diet; increase volume as
pregnancy progresses
2. Signs in pregnant animal is emergency; call
vet immediately
3. May recur with subsequent pregnancies
4. Early weaning is recommended
LIFE
“Nobody can go back and start a new
beginning, but anyone can start today
and make a new ending.”
-Maria Robinson
DISEASES OF THE
PANCREAS
DIABETES MELLITUS
INSULINOMA
EXOCRINE PANCREATIC
INSUFFICIENCY
Review of pancreas functions
• Long flat organ near duodenum and
stomach
• Exocrine function (the majority of the
pancreas):
– Digestive enzymes
• Endocrine function – islets of
Langerhans
– Alpha cells => glucagon
– Beta cells => insulin
– Delta cells => somatostatin
Pancreas
Pancrea
s: beta
cells
Review
• Insulin
– Moves glucose into cells to be used for energy
– Decreases blood glucose
• Glucagon
– Raises blood glucose
• Stimulates liver to release glucose
• Stimulates gluconeogenesis
– Other hormones from other glands perform similar
functions (hyperglycemic effect)
• Growth hormone
• Glucocorticoids
Insulin/Glucagon Balance
Endocrine Pancreas
• Hyperglycemia
– Definition: Excessively high blood glucose
levels
• Normal in dogs: 60-120 mg/dl
• Normal in cats: 70 -150 mg/dl
Diabetes Mellitus
• Definition: Disorder of carbohydrate, fat
and protein metabolism caused by an
absolute or relative insulin deficiency
• Type I – Insulin Dependent DM – very
low or absent insulin secretory ability
• Type II – Non insulin dependent DM
(insulin insensitivity) – inadequate or
delayed insulin secretion relative to the
needs of the patient
Diabetes mellitus
Incidence:
Dogs: ~100% Type I (Insulin dependent)
Cats: ~ 50% Type I and 50% Type II
-non-insulin dependent cats
can sometimes be managed with
diet and drug therapy
Causes:
Chronic pancreatitis
Immune-mediated disease
-beta cell destruction
Predisposing/risk factors:
Cushing’s Disease
Acromegaly
Obesity
Genetic predisposition
Drugs (steroids)
Diabetes mellitus
• Age/sex:
– Dogs: 4-14 yrs, females 2x more likely to
be affected
– Cats: all ages, but 75% are 8-13yrs,
neutered males most affected
• Breeds: Poodles, Schnauzers, Keeshonds,
Cairn Terriers, Dachshunds, Cockers, Beagles
DM
• Pathophysiology
– Insulin deficiency => impaired ability to use glucose from
carbohydrates, fats and proteins
– Impaired glucose utilization + gluconeogenesis => hyperglycemia
– Clinical signs develop when:
• Exceeds capacity of renal tubular cells to reabsorb
• Dogs – BG > 180-220 mg/dl
• Cats - BG > 200-280 mg/dl
– Glycosuria develops
• Osmotic diuresis
• Polyuria/polydipsia
DM
• SYSTEMS AFFECTED:
– Endocrine/metabolic: electrolyte depletion
and metabolic acidosis
– Hepatic: liver failure 2° to hepatic lipidosis
(mobilization of free fatty acids to liver
leads to hepatic lipidosis and ketogenesis)
– Ophthalmic: cataracts (dogs) from
glaucoma
– Renal/urologic: UTI, osmotic diuresis
– Nervous: peripheral neuropathy in cats
– Musculoskeletal: Compensatory weight
loss
Diabetes Mellitus
• Clinical Signs:
– Polyuria
– Polydipsia
– Polyphagia
– Weight loss
– Dehydration
– Cataract formation-dogs
– Plantigrade stance-cats
Diabetes in Cats:
Plantigrade posture
Plantigrade posture
Diabetic neuropathy
Diabetes: Cataracts
Increase in sugar (sorbitol) in lens causes an influx
of water, which breaks down the lens fibers
Diabetic Ketoacidosis
2 metabolic crises:
↑ lipolysis in adipose tissue → fatty acids →ketone bodies →ketoacidosis →coma
(insulin normally inhibits lipolysis)
↑ hepatic gluconeogenesis (in spite of high plasma glucose levels)
(insulin normally inhibits gluconeogenesis)
Diabetic Ketoacidosis
• Definition: True medical emergency
secondary to absolute or relative insulin
deficiency causing hyperglycemia, ketonemia,
metabolic acidosis, dehydration and electrolyte
depletion
• DM causes increased lipolysis => ketone
production and acidosis
Diabetic Ketoacidosis
• Diagnosed with ketones in urine or ketones in blood
– Can use urine dip stick with serum.
• Clinical Signs
–
–
–
–
–
–
All of the DM signs
Depression
Weakness
Tachypnea
Vomiting
Odor of acetone on breath
Diabetic Ketoacidosis
• IV fluids to rehydrate 0.9% NaCl
– K (potassium) supplement
• Regular insulin to slowly decrease BG
• Monitor BG q 2-3 hrs
• When BG close to normal and patient
stable switch to longer acting insulin
DM
• DIAGNOSIS:
– CBC: normal
– Biochemistry panel:
• Glucose > 200 mg/dl (dogs), >250 (cats)
– UA
• Glycosuria!!!!
• Ketonuria
• USG – low
– Electrolytes may be low due to osmotic diuresis
– Blood gases (if ketoacidotic)
– Fructosamine levels – mean glucose level for last 2-3 weeks
(dogs)
• Ideal to test for regulation checks
DM Rx: INSULIN AND DIET!!!
Table 1. Traditional insulin outline.
Insulin types
Concentration
Rapid acting
Regular (Humulin R)
U-100 (100 units/ml)
Intermediate acting
NPH (Humulin N)
U-100
Lente (Vetsulin® by
Intervet) NO LONGER
AVAILABLE*
U-40 (40 units/ml)
PZI (Idexx)
U-40
Ultralente NO LONGER
AVAILABLE*
U-100
Glargine insulin analog
U-100
Duration/onset
category
Long acting
Diabetes: Insulin therapy
DM: Insulin therapy
• INSULIN
– Beef-origin insulin is biologically similar to
cat insulin
– Porcine-origin insulin is biologically similar
to dog insulin
– Dogs and cats have responded well to
human insulin products
• INSULIN ADMINISTRATION:
– ALWAYS USE THE APPROPRIATE
INSULIN SYRINGE! (U-40 vs. U-100)
• Insulin is given in units (insulin syringes are
DM: dietary management
• DIET
– DOGS: high fiber, complex carbohydrate diets
• Slows digestion, reduces the post-prandial glucose spike,
promotes weight loss, reduces risk of pancreatitis
• Hill’s R/D or W/D
– CATS: high protein, low carbohydrate diets
• Cats use protein as their primary source of energy – blood
glucose is maintained primarily through liver metabolism
of fats and proteins
• Purina DM, Hill’s M/D
• Often a diet change in cats can dramatically reduce or
eliminate the need for insulin
– This is particularly true for type II
DM
• Oral hypoglycemics
o Sulfonylureas – Glipizide
o Direct stimulation of insulin secretion from the pancreas
o Alpha-Glucosidase Inhibitors – Acarbose
o Delays digestion of complex carbohydrates and delays
absorption of glucose from the intestinal tract.
Diabetes Mellitus: Monitoring
Find an ear vein
Prick the ear to get
blood sample
Place drop of blood
on green tip; readout in
a few seconds
Diabetes Rx: Urine glucose
Diabetes monitoring: Urine
glucose
DM: monitoring
DM
• Client Education
–
–
–
–
–
–
–
–
Lifelong insulin replacement therapy
Insulin administered by injection
Refrigerate insulin, mix gently (no bubbles), single use syringes
Cataracts common, permanent
Consistent diet and exercise
Recheck BG or curve regularly or fructosamine levels
Progressive
If animal does not eat- NO INSULIN
Endocrine Pancreas
• Hypoglycemia
– Definition: Low blood glucose levels
– Causes
•
•
•
•
•
•
•
Neonatal and juvenile
Septicemia
Neoplasia
Starvation
Iatrogenic – insulin overdose
Portosystemic shunt
Many others
Insulin Shock
Causes:
1. Insulin overdose (misread syringe)
2. Too much exercise
3. Anorexia
Signs:
Weakness, incoordination, seizures, coma
Insulin Shock
Prevention
1. Consistent diet (type and amount)/consistent
exercise (less insulin with exercise)
2. Monitor urine/blood glucose at same time each
day
3. Feed 1/3 with insulin; the rest 8-10 h later (at
insulin peak)
4. Have sugar supply handy
Insulinoma
• CAUSE: tumor of beta cells, secreting an excess of insulin
• SIGNS: prolonged hypoglycemia→weakness, ataxia, muscle
fasciculations, posterior paresis, brain damage, seizures,
coma, death,
Insulinoma: Dx
• Chem Panel
– ↓blood glucose
– Simultaneous glucose and insulin tests
Low glucose, High insulin => insulinoma
• Observations
– Symptoms occur after fasting or exercise
– when symptomatic, blood glucose<50 mg/dl
– symptoms corrected with sugar administration
Insulinoma: Rx
Surgical Rx: removal of tumor
Medical Rx:
Acute, at home:
administer glucose (Karo); keep animal quiet, seek vet care
Acute, in Hosp
adm. glucose (50% Dextrose)
Chronic care
feed 3-6 small meals/day (high protein, low fat)
limited exercise
glucocorticooid therapy (antagonizes insulin effect at cellular
level)
Diazoxide (↓insulin secretion, tissue use of glucose, ↑blood
glucose)
Octreotide (Sandostatin) injections—inhibits synthesis and release
of insulin by both normal and neoplastic beta cells
Insulinoma: Client info
•
•
•
•
•
•
1. Usually, by the time insulinoma is diagnosed, metastasis has occurred
so prognosis is poor
2. With proper medical therapy, survival may be 12-24 mo
3. Always limit exercise and excitement
4. Feed multiple, small meals throughout day; keep sugar source close
during exercise
5. Karo syrup on mm provides for rapid absorption of glucose into
blood stream
6. Avoid placing hand into dog’s mouth during seizure to avoid being
bitten
Exocrine Pancreas Insufficiency (EPI)
• Inability to process nutrients efficiently due
to lack of production of enzymes from
pancreas.
– Pancreatic acinar atrophy
• Found most commonly in German
Shepherds and Rough Collies through a
recessive gene.
– In cats, EPI is primarily the result of chronic
pancreatitis
Diagnosis of EPI
• Not usually evident until 85-90% of pancreas
is unable to secrete enzymes.
– Weight loss although no change in diet or appetite
(appetite often increases)
– Persistent tarry diarrhea.
– Flatulence
– Poor haircoat
Testing and treatment for EPI
• TLI (trypsin-like immunoreactivity)
– Detects trypsin and trypsinogen
– Usually want below 2.5 in dogs to be diagnostic
• Canine 5.7-45.2
• Feline 12-82
• Treatment includes enzymatic supplement
– Viokase powder
– Raw ox or pig pancreas
Client considerations
•
•
•
•
Usually life long treatment.
Can be very expensive.
Can be well controlled.
Should not breed animal that has EPI.
LIFE
“Smooth seas do not make skillful
sailors.”
-African proverb
DISEASES OF THE ADRENAL GLANDS
CUSHING’S DISEASE
(Hyperadrenocorticism)
ADDISON’S DISEASE
(Hypoadrenocorticism)
Adrenal G
ADRENAL GLANDS
mineralocorticoids
Glucocorticoids
Androgens
epinephrine
Hyperadrenocorticism (Cushings Disease)
• Definition: Disorder caused by deleterious effects
of high circulating cortisol concentrations on
multiple organ systems
• Systems affected:
–
–
–
–
–
–
–
–
Renal
Skin
Cardiovascular
Respiratory
Endocrine/metabolic
Musculoskeletal
Nervous
Reproductive
Cushing’s Disease
Effects of excess glucocorticoids:
1.
2.
3.
suppress inflammation
suppress immune system
inhibit cartilage growth, development,
and repair
Causes:
1.
2.
3.
Anterior pituitary lesion (pituitary-dependent disease) – 85% of
cases
Adrenal tumor (excess cortisol secretion independent of pituitary
control) – 15-20% of cases
Overmedication with glucocorticoids - Iatrogenic
Cushing’s Disease
Cushing’s Disease
Bilaterally symmetrical alopecia, pot-belly, pyoderma
Cushing’s Disease
Pot bellied
PU/PD
Muscle wasting
Thin coat
Cushing’s Disease
•
signs are slow to develop and usually go unnoticed by owner
Clinical Signs:
1. Some are similar to hypothyroidism
2. Dog >6 yr old (most are female)
3. PU/PD/PP
4. Pot bellied; obese
5. Muscle atrophy and weakness, lethargy, excess
panting
6. Bilateral symmetric alopecia; pruritis; pyoderma (↓
immune response)
7. Calcinosis cutis (firm plaques of Ca++ under skin)
8. Abnormal gonadal function (lack of estrus; soft,
small testicles)
Cushing’s Disease: Calcinosis cutis
Commonly seen on the dorsal midline, ventral abdomen and inguinal region.
Skin is usually thin and atrophic
Cushing’s Disease: Dx
Chemistry Panel
1.
2.
3.
4.
↑ ALP, ALT, cholesterol, blood glucose
↓ BUN
Lipemia
Low USG < 1.015, proteinuria, hematuria, pyuria, bactiuria
Urine cortisol/creatinine ratios (sample collected at home)
1.
2.
Normal ratio=no Cushing’s
Elevated ratio=may be Cushing’s
ACTH Stimulation test
1.
2.
3.
Normal patients show an increase of plasma cortisol
Pituitary dependent disease (excess ACTH release) and Adrenal tumors: 60-85%
show EXAGGERATED cortisol response
Does not differentiate between Pit disease and Adrenal tumor
ACTH Stimulation for Hyperadrenocorticism
• Take a pre blood sample.
• Inject ACTH stimulation gel or liquid
– Verify amounts with lab as there is
difference between amount to be injected
with gel and liquid.
• Wait two hours and take a post sample
Cushing’s Disease: Dx
Low-Dose Dexamethasone Suppression Test
1.
2.
Inject low dose of steroid (should suppress ant. pit [ACTH])
Measure plasma cortisol at 0, 4, 8 h
Interpretation:
1.
2.
Normal dogs will show decrease in plasma cortisol
Pituitary tumor and adrenal tumor will not show any effect at 8 h
(cortisol will still be high)
Cushing’s Disease: Dx
High-Dose Dexamethasone Suppression Test (used to
differentiate between Pit Dis and Adrenal tumor)
1.
2.
Dosing: 0.1 mg/kg IV
Collect plasma cortisol at 0, 4, and 8 h
Interpretation:
1.
2.
Pituitary dependent disease—70-75% will show decrease at 4 or
8h
Adrenal tumor—no change in plasma cortisol level (tumor is
autonomous)
Cushing’s Disease: Rx
Surgical removal—
1.
2.
FAT - Specialized surgery; most vets would refer surgery
Pituitary tumors are not surgically removed
Medical treatment
1.
Lysodren (o,p,DDD)—necrosis of z fasiculata (middle), z reticularis
(deep)
-repeat ACTH stimulation q 7-10 d until cortisol normal
-like chemotherapy
-excess dose affects z glomerulus (Addison’s Dis)
Cushing’s Disease: Rx
2. trilostane (Vetoryl®)—less side-effects
than o,p,DDD
-interfers with cortisol production
(doesn’t kill cells)
-FDA approved
Cushing’s Disease: Client info
•
•
•
•
Serious disease; life-long treatment
Periodic monitoring required
Addison’s disease may result
Prognosis: average life expectancy is
20-30 mo on therapy with frequent
recurrence of clinical symptoms –
varies with cause (pit vs adrenal,
tumors)
HARD TIMES
“In the depths of winter, I finally
learned that within me there lay an
invincible summer.”
-Albert Camus
Addison’s Disease (Hypoadrenocorticism)
• Definition: Disorder caused by deficient
production of glucocorticoids (cortisol) or
mineralocorticoids (aldosterone) or both
• Secondary disease caused by chronic
administration of corticosteroids
Addison’s Disease (Hypoadrenocorticism)
•
•
•
Not as common as Cushing’s Disease; rarely seen in cats
Deficiency of Glucocorticoids and Mineralocordicoids
Clinical signs due to Mineralocorticoid (Aldosterone) deficiency
Clinical Signs:
1.
2.
3.
4.
lethargy, weakness, anorexia, wt loss
Vomiting/Diarrhea
PU/PD, dehydration
Bradycardia
Addison’s Disease
• Pathophysiology
– Decreased aldosterone => Increased K and
decreased Na
– => decreased volume => azotemia,
hypotension, dehydration, weakness,
depression
– Hyper K => heart (bradycardia)
– Glucocorticoid deficiency => vomiting,
diarrhea, melena, lethargy, wt loss,
hypoglycemia (less common than expected)
Addison’s Disease: Dx
Chem Panel
Na:K ratio <25:1 !!!(normal=27:1 to 40:1)
↑ BUN, Creatinine, Ca++
↓ blood glucose, albumin (less common
ACTH Stimulation test (definitive test)
normal dog= ↑ cortisol
hypoadrenocorticism dog= low, unchanged cortisol level
Endogenous ACTH will be increased (1º hypoadrenocorticism; lack of neg
feedback)
What is your Dx?
Chem Panel
Parameter
BUN
Creatinine
Sodium
Potassium
Na:K ratio
(What is not normal?)
Value
81 mg/dl
2.1 mg/dl
131 meq/L
6.5 meq/L
20
Normal value
7-27 mg/dl
0.4-1.8 mg/dl
141-156 meq/L
4.0-5.6 meq/L
27-40
What is your Dx?
ACTH Stimulation Test Results
Value
Plasma Cortisol
Pre-ACTH
Post-ACTH
Normal
0.2
0.3
2-6
6-18
Addison’s Disease: Rx
Acute Crisis (may be life-threatening situation)
Normal saline IV (low Na+ is hallmark finding of Addison’s)
Glucorticoid replacement(cortisol will also be low)
1.
2.
a.
3.
Dexamethasone or Prednisone (IV or IM)
Mineralocorcorticoid replacement
a.
b.
Florinef® (fludrocortisone acetate)—po
Percortin-V (desoxycorticosterone pivalate) injection
Chronic Management
1.
Glucocorticoid replacement
a.
b.
2.
Mineralocorcorticoid replacement
a.
b.
3.
Prednisone
Prenisolone
Florinef® (fludrocortisone acetate)—po daily (not cheap; 50¢/tab)
Percortin-V (desoxycorticosterone pivalate)—inj ~monthly (expensive)
Monitor electrolytes, BUN/Creatinine, clinical signs
Addison’s disease: Client info
1.
2.
3.
4.
5.
6.
Mineralocorticoid deficiency is life-threatening
Animal requires periodic blood tests
Glucocorticoids needed in times of stress
Always remind attending vet of pet’s condition
Hormone replacement therapy continued for life of
pet
Prognosis: Good to excellent after stabilization and
treatment