Diabetes in Dogs - Australian Terrier Club of Americaaustralianterrier.org/PDF/Graves...
Transcript of Diabetes in Dogs - Australian Terrier Club of Americaaustralianterrier.org/PDF/Graves...
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Diabetes in Dogs
Thomas K. Graves, DVM, PhD, DACVIM
University of Illinois at Urbana-Champaign
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Outline
Pathophysiology
Can diabetes be prevented in dogs?
Initial diagnosis
Types of insulin available
Monitoring treatment
Insulin resistance
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The Endocrine Pancreas
The endocrine pancreas is comprised of the
islets of Langerhans & contains 4 cell
types
• Alpha cells secrete glucagon
• Beta cells secrete insulin
• Delta cells secrete somatostatin
• F cells secrete pancreatic polypeptide
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Hyperglycemia
• Definition: Blood glucose (BG) > ref range
• Clinical signs occur when the renal
threshold is exceeded
– 180-220 mg/dl in dog
– Results in glucosuria osmotic diuresis
– Polyuria-polydipsia
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Ruleouts for Hyperglycemia
• Diabetes Mellitus
– Primary Islet Destruction
• Immune-mediated
• Pancreatitis
– Insulin Resistance
• Hyperadrenocorticism
• Acromegaly
• Drugs (steroids most commonly)
– Hyperglycemia from glucocorticoids not always
accompanied by glycosuria
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Definition of Diabetes
• Fasting hyperglycemia
• Glucosuria
• Elevated fructosamine or glycosylated
hemoglobin
• This is a very conservative definition
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Pathophysiology
• Type 1 – Destruction/loss of beta cells
– May be partial
• Type 2 – Insulin resistance/dysfunctional beta cells
– Can be obesity-related
• Sometime classified as IDDM or NIDDM
• Dogs are more like Type 1, and cats more like Type 2, but all fall somewhere on a continuum between the two
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Causes of DM in dogs
• Genetic predispositions
• Immune-mediated
– Anti-islet antibodies
– Anti-insulin antibodies
• Pancreatitis
• Insulin-antagonistic drugs and diseases
• Obesity can cause insulin resistance but
not glucose intolerance in dogs
• Concurrent illnesses and infections
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DM in Dogs
• Incidence is approx. 70/10,000 cases
• Age
– 2.2% <1 year
– 0.67% 1–2 years
– 2.8% 3–4 years
– 15.4% 5–7 years
– 37.1% 8–10 years
– 39.2%11–15 years
– 1.8% >15 years
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DM in Dogs
• Female 2x more likely than male
• Dogs weighing less than 23 kg greater risk
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Australian Terrier 32.1 OR
St. Schnauzer 4.78
Samoyed 3.36
Mini Schnauzer* 3.13
Fox Terrier* 3.02
Keeshond* 2.45
Bichon Frise 2.40
Finnish Spitz* 2.32
Cairn Terrier* 2.07
Mini Poodle* 1.79
Siberian Husky 1.53
Toy Poodle* 1.29
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Breeds at lowest risk
• Boxer (OR = 0.07)
• German Shorthaired Pointer (0.14)
• Airedale Terrier (0.15)
• German Shepherd Dog (0.16)
• Pekingese (0.18)
• Collie (0.19)
• Shetland Sheepdog (0.23)
• Bulldog (0.23)
• Great Dane (0.24)
• Cocker Spaniel (0.25)
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Can Type I Diabetes be
Prevented? • First would have to know which animals
are at risk?
– Are there genetic markers?
– Studies of anti-insulin and anti-islet antibodies
are needed.
• Experimental evidence that cyclosporine
can prevent immune-mediated islet
destruction
• Diet cannot prevent diabetes
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Clinical Signs
• Increased thirst
(polydipsia)
• Increased urination
(polyuria)
• Increased appetite
(polyphagia)
• Weight loss
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DM- Clinical Features
• Peripheral tissues are not able to use
glucose breakdown of muscle & fat
leads to weight loss
• Increased appetitie b/c satiety center has
insulin-mediated uptake of glucose
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Diabetic cataracts
• The lens is freely
permeable to glucose
• In diabetics, there may be
saturation of the pathways
which metabolize glucose
• The sorbitol pathway will
then metabolize glucose
to sorbitol & fructose
• Sorbitol & fructose draw
H2O into the lens which
disrupts the fibers
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Diabetic neuropathy
• Seen in cats but not in dogs
• Plantigrade posture with the hocks
touching the ground
• Cause is not known
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Neuropathy does not always resolve or improve with treatment of diabetes
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Initial Diagnostics
• Urinalysis
• CBC
• Chemistry profile
• Urine culture
• +/- Fructosamine
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Urinalysis
• Glycosuria
• Proteinuria
• Ketonuria
– May find small amounts in otherwise healthy diabetic
• Bacteriuria
– Always culture given high prevalence of occult infections
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CBC
• HCT if dehydrated
• WBC w/ infection or inflammation
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Chemistry Panel
• Liver enzyme abnormalities
– Due to lipidosis and pancreatitis
– Changes in function tests may be noted
• Pre-renal azotemia may be seen
• Electrolyte abnormalities, esp. w/ DKA
• Cholesterol
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Treatment of Diabetes
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Therapy-Dietary
• Minimize post-prandial fluctuations in
blood glucose
– High fiber
• Promotes weight loss
• Slows glucose absorption from GI tract
– Complex carbohydrates
– Avoid excessive amounts of protein
– Avoid excessive amounts of fat
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Exercise
• Promotes weight loss
• Glucose lowering effect
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Insulin
• Different types of insulin are available
• Protamine and zinc are typically used to
prolong the duration of action
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Insulin
• Similarity of insulin structure
=
100% homology
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Insulin
• Similarity of insulin structure :
=
1 aa difference
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Insulin
Detemir*****
Glargine
PZI
Vetsulin
NPH
Regular
Potency
Duration
*****Detemir is very potent in dogs
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Point to Remember:
Every patient responds
differently to a given insulin
preparation. What works for
one dog might not work for
another.
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Regular Insulin
• Rapid onset
• Short acting
• Used at mealtime
• Used for
emergency
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NPH Insulin
• Similar to Vetsulin
in terms of kinetics
• May be shorter
acting
• Contains
protamine
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Vetsulin
• Porcine Insulin
• Contains zinc to
bind insulin
• U-40
• Moderate onset
and action
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PZI
• Moderately long-
acting
• Doesn’t work in all
dogs
• U-40
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Insulin Analogs
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Cys
Ile
Val
Glu Gln
Cys Thr Ser
Ile
Cys
Ser
Leu Tyr
Gln Leu
Glu
Asn Tyr
Cys
Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu
Gly Ser His Val
Glu Ala
Leu Tyr
Leu Val
Cys
A1
Gly Glu
Pro Lys
Gly
Phe
Phe Tyr Thr
Thr
S S
S S S
S
B1 A21
B29
Leu
Human Insulin
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Cys
Ile
Val
Glu Gln
Cys Thr Ser
Ile
Cys
Ser
Leu Tyr
Gln Leu
Glu
Asn Tyr
Cys
Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu
Gly Ser His Val
Glu Ala
Leu Tyr
Leu Val
Cys
A1
Gly Glu
Pro Lys
Gly
Phe
Phe Tyr Thr
Thr
S S
S S S
S
B1 A21
B29
Leu
Insulin Glargine
Gly
Asn D Gly
Arg Arg
Arg Arg Added
•Recombinant human insulin analog
•Long-acting, “peakless”
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Properties of Glargine
• AA mutations shift isoelectric point
• Completely soluble at pH4
• Acid is neutralized in subcutaneous tissue
• Insulin crystals precipitate (hexamers)
• Hexamers are slowly broken down
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Cys
Ile Val
Glu Gln Cys Thr Ser Ile
Cys
Ser Leu Tyr Gln Leu
Glu Asn Tyr
Cys Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu Gly Ser His Val
Glu Ala Leu
Tyr Leu
Val Cys
A1
Gly Glu
Pro Lys
Gly Phe
Phe Tyr Thr
Thr
S S
S S S S
B1 A21
B29
Leu
Gly
Arg Arg
Cys
Ile Val
Glu Gln Cys Thr Ser Ile
Cys
Ser Leu Tyr Gln Leu
Glu Asn Tyr
Cys Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu Gly Ser His Val
Glu Ala Leu
Tyr Leu
Val Cys
A1
Gly Glu
Pro Lys
Gly Phe
Phe Tyr Thr
Thr
S S
S S S S
B1 A21
B29
Leu
Gly
Arg Arg
Cys
Ile Val
Glu Gln Cys Thr Ser Ile
Cys
Ser Leu Tyr Gln Leu
Glu Asn Tyr
Cys Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu Gly Ser His Val
Glu Ala Leu
Tyr Leu
Val Cys
A1
Gly Glu
Pro Lys
Gly Phe
Phe Tyr Thr
Thr
S S
S S S S
B1 A21
B29
Leu
Gly
Arg Arg
Cys
Ile Val
Glu Gln Cys Thr Ser Ile
Cys
Ser Leu Tyr Gln Leu
Glu Asn Tyr
Cys Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu Gly Ser His Val
Glu Ala Leu
Tyr Leu
Val Cys
A1
Gly Glu
Pro Lys
Gly Phe
Phe Tyr Thr
Thr
S S
S S S S
B1 A21
B29
Leu
Gly
Arg Arg
Cys
Ile Val
Glu Gln Cys Thr Ser Ile
Cys
Ser Leu Tyr Gln Leu
Glu Asn Tyr
Cys Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu Gly Ser His Val
Glu Ala Leu
Tyr Leu
Val Cys
A1
Gly Glu
Pro Lys
Gly Phe
Phe Tyr Thr
Thr
S S
S S S S
B1 A21
B29
Leu
Gly
Arg Arg
Cys
Ile Val
Glu Gln Cys Thr Ser Ile
Cys
Ser Leu Tyr Gln Leu
Glu Asn Tyr
Cys Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu Gly Ser His Val
Glu Ala Leu
Tyr Leu
Val Cys
A1
Gly Glu
Pro Lys
Gly Phe
Phe Tyr Thr
Thr
S S
S S S S
B1 A21
B29
Leu
Gly
Arg Arg
Cys
Ile Val
Glu Gln Cys Thr Ser Ile
Cys
Ser Leu Tyr Gln Leu
Glu Asn Tyr
Cys Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu Gly Ser His Val
Glu Ala Leu
Tyr Leu
Val Cys
A1
Gly Glu
Pro Lys
Gly Phe
Phe Tyr Thr
Thr
S S
S S S S
B1 A21
B29
Leu
Gly
Arg Arg
In the bottle . . . In the body . . .
(monomer)
(hexamer)
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Cys
Ile
Val
Glu Gln
Cys Thr Ser
Ile
Cys
Ser
Leu Tyr
Gln Leu
Glu
Asn Tyr
Cys
Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu
Gly Ser His Val
Glu Ala
Leu Tyr
Leu Val
Cys
A1
Gly Glu
Pro Lys
Gly
Phe
Phe Tyr Thr
S S
S S S
S
B1 A21
B29
Leu
O
HO
Insulin Detemir
Thr
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Insulin detemir
• Liquid depot – detemir does not precipitate into
hexamers at the site of injection
• No mixing required
• Buffered by albumin
• Less weight gain in people
• In people detemir is more predictable than glargine
decreased frequency of hypoglycemic events
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In the bottle . . . In the body . . .
(unbound)
Cys
Ile
Val Glu Gln
Cys Thr Ser
Ile Cys
Ser
Leu Tyr
Gln Leu Glu
Asn Tyr Cys
Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu Gly
Ser His Val Glu Ala
Leu Tyr
Leu Val
Cys
A1
Gly Glu
Pro Lys
Gly
Phe Phe
Tyr Thr
S S
S S S S
B1 A21
B29
Leu
O
HO
Thr
Cys
Ile
Val Glu Gln
Cys Thr Ser
Ile Cys
Ser
Leu Tyr
Gln Leu Glu
Asn Tyr Cys
Gly Asn
Cys
Val
Asn
Gln
Phe
His Arg
Leu Gly
Ser His Val Glu Ala
Leu Tyr
Leu Val
Cys
A1
Gly Glu
Pro Lys
Gly
Phe Phe
Tyr Thr
S S
S S S S
B1 A21
B29
Leu
O
HO
Thr
Albumin (bound to albumin)
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Variability in insulin curves with NPH
Adapted from: Heise et al. Diabetes 2004;53(6):1614-20
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Variability in insulin curves with NPH vs. glargine
Adapted from: Heise et al. Diabetes 2004;53(6):1614-20
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Variability in insulin curves: NPH vs. glargine vs. detemir
Adapted from: Heise et al. Diabetes 2004;53(6):1614-20
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Oral Hypoglycemic Drugs
• Increase insulin secretion
– Sulfonylureas (glipizide)
• Inhibit glucose release
– biguanide drugs (metformin)
• Decrease glucose absorption
– acarbose
• Increase sensitivity to insulin
– thiazolodinediones
• Vanadium and Chromium
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Acarbose
• Mild glucose lowering effect if used as
single agent
• May be combined with sulfonylureas or
transition metals
• Give with meals
• Dose: 100-200 mg PO bid
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Glucose curves
• For a diabetic dog without cataracts,
glucose values should range between
100-250 mg/dL
• For diabetic dogs with cataracts, glucose
values should range between 100-300
mg/dL
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Glucose curve
• Interpretation:
• Was insulin effective in lowering BG?
– Establish highest BG
– Establish lowest BG
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Glucose curve
Was insulin effective in lowering BG? What is the lowest BG? How long does insulin last? How would you adjust insulin therapy?
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0
50
100
150
200
250
300
2 4 6 8 10 12
Insulin type or
dosing frequency
Insulin dose
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0 6 12 18 24
Blo
od G
lucose
Target
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0 6 12 18 24
Blo
od G
lucose
Target
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Somogyi Phenomenon
• Result of too much insulin
• Insulin-induced hyperglycemia
• Response to either hypoglycemia (BG<65)
or too rapid a decline in BG
• Secretion of diabetogenic hormones
– Catecholamines
– Glucagon
• hepatic glycogenolysis
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0 6 12 18 24
Blo
od G
lucose
Target
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0 6 12 18 24
Blo
od G
lucose
Target
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Bailey 9 yo FS yorkie 4.5 U Humulin N BID
0
100
200
300
400
500
600
0 2 4 6 8 10 12 14 16 18 20 22 24
Hours
Blo
od
Glu
co
se
= insulin and food
Bailey is PU/PD, eats canned Pedigree, serum fructoasamine is 640 mM
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Still PU/PD serum fructosamine = 545 uM
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Still PU/PD serum fructosamine = 560 mM
Bailey 9yo FS Yorkie 5.5 U Humulin U BID
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• Fleeman and Rand JAVMA 2003
– Paired BGC’s 2 weeks apart
– High CVs (68% - 100%) for mean, min, max,
pre-insulin glucose and glucose nadir
• Casella et al. JSAP 2003
– Compaired home vs. hospital
– Mean and max glucose sometimes highest at
home
– Treatment decision would have been different
42% of the time based on home vs. clinic
Are blood glucose curves useful?
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Monitoring
• Owners perceptions of pet’s quality of life
– Weight
– Water intake & urination frequency
– Food intake
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Monitoring
• Fructosamine
– Serum proteins that have undergone glycosylation
– Reflects glycemic control over 2-3 weeks
• Glycosylated hemoglobin
– Irreversible binding of glucose to hemoglobin in RBC
– Reflects glycemic control over 2-3 months
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Monitoring Insulin Therapy
• Clinical Signs
• Signs of Hypoglycemia
• PU/PD
• Spot BG can document hypoglycemia or
hyperglycemia
• Fructosamine
• Glucose curves?
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What if insulin is not
working?
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Insulin Resistance
• This term usually refers to the
pathogenesis of type 2 diabetes
mellitus in people, but is used
differently in clinical vet med. – Diet and obesity are associated with
ineffective action of insulin at the cellular
level.
– Leads to inappropriate insulin secretion and,
eventually, to exhaustion of beta cell function
and overt diabetes.
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Insulin Resistance
• Clinical definition used in veterinary
medicine: – Insulin dose > 1.5 U/kg in dog
– Insulin dose > 6-8 U/cat
– Apparent insulin resistance must be
differentiated from true insulin resistance.
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Apparent Insulin Resistance
• Is it really insulin resistance, or are owners not giving insulin properly? – Watch owners administer injection
– Type of syringe
– Site of injection?
– Check type and dose of insulin
– If using a diluted insulin, switch to non-diluted
– Handling of insulin & syringe
– Storage of insulin
– Expiration date of insulin
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Causes of Insulin Resistance • Problems with a Specific Insulin
• Problems with Endocrine Organs – Adipose
– Adrenal
– Pituitary
– Thyroid
– Pancreas
– Ovary
• Drugs
• Others
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Insulin Problems
• Rapid Metabolism of
Insulin
– Response to a given
insulin is unpredictable
• Somogyi
Phenomenon
Hyperinsulinemic euglycemic clamps: duration of action
0
100
200
300
400
500
600
700
800
900
1000
Jame JJ Shiraz Cabey Pinotcat
Min
ute
s
Regular
Glargine
Detemir
0 6 12 18 24
Blo
od G
lucose
Target
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Obesity
• Reversible insulin resistance
– Impaired insulin secretion
– Down-regulation of receptors
– Impaired receptor binding affinity
– Post-receptor defects
– Decreased adiponectin
– Increased resistin
– Pro-inflammatory cytokines
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Glucocorticoid Excess • Causes
– Stress
– Hypercortisolism
– Exogenous administration
• Effects of Glucocorticoids – Increased hepatic gluconeogenesis
– Decreased tissue utilization of glucose
– Decreased receptor affinity for insulin
– Decreased number and affinity of glucose
transporters
– Increased glucagon and free fatty acid
concentrations
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Clinical Signs -- Urinary System
• Polyuria/Polydipsia (90%) – Due to ADH antagonism
– Concurrent diabetes mellitus
– Decreased renal tubular water permeability
– Decreased vasopressin secretion
– Increased GFR?
• Urinary Tract Infection – Associated with steroids
– Dilute urine predisposes
– Can show signs of lower urinary tract disease
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Clinical Signs: Skin
• Bilaterally symmetrical alopecia (55 –
90%)
• Thin skin
• Hyperpigmentation
• Comedones
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Clinical Signs -- Muscle
Muscle atrophy direct effect of glucocorticoids
Pot Belly Abdominal muscle weakness
Redistribution of fat
Hepatomegaly
Myotonia Uncommon
Non-inflammatory degenerative myelopathy
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Clinical Signs
• Respiratory System
– Panting is common
– Dyspnea due to pulmonary embolism
• Endocrine System
– Insulin resistance
– Diabetes is common in dogs with hypercortisolism
• Nervous System
– Seizures, blindness, circling due to macroadenoma
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Growth Hormone Excess
• Acromegaly
• Only occurs in intact bitches
• Different from the disease in cats and
people
• Effects – Glucose transport inhibition
– Increased glucose production
– Decreased insulin receptor numbers
– Effects downstream of receptor
– Increased lipolysis
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Thyroid Hormone Excess
• Uncommon in dogs unless on thyroid
supplementation
• Feline hyperthyroidism and diabetes are
sometimes seen as co-morbid conditions
• Effects of thyroid hormone – Lower insulin production
– Insulin receptor binding defects
– Abnormal glucose transport?
• Clinical effects
– Hyperthyroid patients may need less insulin after treatment of thyroid
disease
– Human hyperthyroid patients commonly have glucosuria
– Hyperthyroidism associated with lower fructosamine
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Glucagon Excess
• Associated with… – Bacterial infection
– Pancreatitis
– Trauma
– Congestive heart failure
– Renal failure
– Glucagonoma
• Effects of Glucagon – Increased hepatic gluconeogenesis
– Increased hepatic glycogenolysis
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Progesterone Excess
• Cause of hyperprogesteronism – Diestrus/pregnancy
– Use of pregestagens (eg. megestrol acetate)
– Adrenal tumors?
• Effects of progesterone – Reduced insulin binding
– Reduced glucose transport in tissues
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Catecholamine Excess
• Causes – Stress
– Pheochromocytoma
– Hyperthyroidism?
• Effects of epinephrine – Stimulation hepatic and renal glucose production
– Decreased glucose utilization
– Decreased insulin secretion
– Stimulation glucagon secretion
– Gluconeogenesis
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Insulin Resistance
• Other things to consider:
– Administration of any drugs which antagonize
insulin (eye, ear Rx common culprits)
– Heat cycles?
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Common Causes of Insulin
Resistance
• Dogs
– Cushing’s disease
– Bacterial infections
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Anti-Insulin Antibodies
• Result of continued exposure to a foreign protein (insulin)
• Low levels may be beneficial in prolonging the duration of effect of insulin
• High levels may cause insulin resistance
• High levels may cause erratic fluctuations in blood glucose (D in binding affinity)
• Not a lot of evidence that these are important in veterinary patients
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Work-Up of Insulin Resistance
• Glucose curve?
• Full medical work-up
• Blood Pressure
• Urinalysis and culture
• Tests for Cushing’s disease?
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13-year-old Shih Tzu x Bichon
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June 09
• On Vetsulin for 3 years
• Presented for evaluation of neuro signs
• Owner reports dog is on 15 U BID
• Medical record says dog is on 5 U BID
• Diet of people food. Dog doesn’t always eat well.
• Exam: – 16 pounds
– Thin skin and bad hair
– BCS 3/9
– Severe dental disease
– Cataracts
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June 09
• Top ruleouts for neurological signs?
– Hypoglycemia
– Other metabolic disorders
– Neoplasia
– Vascular
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June 09
• Owner declines medical work-up other
than spot BG.
• BG = 49 mg/dl
• Plan: Decrease insulin dose to 4 U BID.
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August 09
• Owner reports dod is very PU/PD.
• Blood Glucose Curve
– 8 a.m. 204 mg/dl
– 10 a.m. 180 mg/dl
– Noon 166 mg/dl
– 2 p.m. 230 mg/dl
– 4 p.m. 291 mg/dl\
• Because of persistent PU/PD, Vetsulin dose was increased to 5 U BID
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October 09
• Owner reports dog is still very PU/PD.
• Blood Glucose Curve
– 8 a.m. 367 mg/dl
– 10 a.m. 280 mg/dl
– Noon 310 mg/dl
– 2 p.m. 297 mg/dl
– 4 p.m. 253 mg/dl\
• Vetsulin dose was increased to 5.5 U BID
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November 09
• Vetsulin alert issued by FDA
• Dog transitioned to Humulin-N
• Recommended dose of 3 U BID
• Owners ignored recommendation and
gave 5 U BID
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Later That November
• Owners report seizures.
• DVM recommends decreasing Humulin-N
to 4 U BID
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December 2009
• Owner reports dog is still very PU/PD.
• UA – glucose 1000, inactive sediment
• Blood Glucose Curve
– 8 a.m. 192 mg/dl
– 10 a.m. 297 mg/dl
– Noon 304 mg/dl
– 2 p.m. 297 mg/dl
– 4 p.m. 266 mg/dl
• Vetsulin dose was increased to 5 U BID
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January 2010
• Owner reports dog is still very PU/PD.
• UA – gluc 500, inactive sediment, SG = 1.030
• Blood Glucose Curve
– 8 a.m. 319 mg/dl
– 10 a.m. 265 mg/dl
– Noon 328 mg/dl
– 2 p.m. 242 mg/dl
– 4 p.m. 351 mg/dl
• Now what???
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Questions
• Why did the dog have seizures on 5 U BID in November, and persistent hyperglycemia in January?
• Why was the dog better controlled on 4 U of Vetsulin BID than on 5 U of Vetsulin BID?
• Should you trust BG curves?
• If the owners would agree to a more aggressive work-up, what should you do?
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Recommendations
• Measure blood pressure
• Start a diet that makes sense for a diabetic dog.
• Chemistry profile to look for causes of difficult regulation of insulin therapy
• Consider fructosamine rather than BG curves.
• Use 0.3-ml Lo-dose syringes for more consistent dosing of insulin
• Dental
• Urine Culture
• Are there other insulin options?
• Imaging studies (chronic pancreatitis, neoplasia, etc.)
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And a little about
hypothyroidism . . .
• Many veterinarians and breeders think that
hypothyroidism is common in dogs.
• From ATCA website—
– “..with a deficient endocrine system come
other related disorders such as Cushing’s
disease, Addison’s disease, thyroid
abnormalities . . . “
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“Hypothyroidism is the most frequently
diagnosed endocrinopathy found in the
dog. Whether these diagnoses
accurately reflect the true incidence of
hypothyroidism in dogs is clouded by
the controversy concerning the best
means of diagnosis, and by the pitfalls of
early recognition of the disease, which
are caused by the variety and subtleness
of hypothyroidism’s presenting signs.
Even so, there is little doubt that
hypothyroidism is a common endocrine
disease of the dog.”
Chastain and Ganjam,
Clinical Endocrinology of Companion Animals,
1986
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Kantrowitz et al. J Am Vet Med
Assoc 2001, 219(6):765-769
• Compared 233 dogs with non-thyroidal disease and 150 normal dogs
• Total T4, Free T4, and Total T3 were significantly lower in sick dogs
• TSH was significantly higher in sick dogs
• Conclusion TT4, FT4, and TT3 can be in the hypothyroid range in sick dogs
• TSH is more likely to be in the normal range for sick dogs, but can be high
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Peterson et al., J Am Vet Med
Assoc 1997;211(11)1396-1402
• 18% of healthy euthyroid dogs had low T4
• 24% of hypothyroid dogs had normal TSH
• TSH had a low sensitivity for
hypothyroidism
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Nelson et al., J Am Vet Med Assoc
1991;198(8):1401-1407.
• No difference in free T4 concentrations
comparing hypothyroid dogs and dogs
with diseases that look like hypothyroidism
(Cushings, peripheral neuropathy, etc.)
• Sick dogs with normal thyroid glands have
low free T4 (17%) and low T4 (20%)
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Many drugs affect thyroid
testing
• NSAIDS
• Glucocorticoids
• Anticonvulsants
• Sulfonamides
• Radiocontrast agents
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Breeds with lower T4
• Greyhound
• Scottish Deerhound
• Siberian Husky
• Others likely
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Diabetes and Hypothyroidism
• Dogs with diabetes usually have low T4
even with normal thyroid glands
• There is no known association between
diabetes and hypothyroidism
• Hypothyroidism is mistakenly diagnosed in
diabetic dogs
• Thyroid hormone supplementation could
make diabetes more difficult to control.
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Diabetes and Cushing’s
Disease
• These two disease can occur together
• Uncontrolled diabetes can result in false-
positive tests for Cushing’s disease
• Diabetes is extremely difficult to control
unless Cushing’s disease is controlled
first.
• The clinical signs of the two diseases are
similar.
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