Socrates-Erasmus

Vet. Clin. Path.

22-‹#›

Clinico-laboratory diagnosis:
Most common endocrinopathies

Kostas Papasouliotis
DVM PhD DipRCPath(Vet.Clin.Path.) DipECVCP MRCVS
Introduction
Clinical presentation extremely important

Concentrate of laboratory testing

 Hyperadrenocorticism (HyperA)
 Hypoadrenocorticism (HypoA)
 Hypothyroidism (HypoTh)
 Hyperthyroidism (HyperTh)
Canine Hyperadrenocorticism
Pathophysiology
Hypothalamus  CRH
Pituitary  ACTH
 Episodic & pulsatile secretion
CRH, ACTH, Cortisol
 secretion highest
 morning in Dog
 evening in Cat
Very stressed animals
 negative feedback not effective
Clinical signs: HyperA

PU/PD Panting
Polyphagia Obesity
Heat intolerant Muscle Weakness
Lethargy Recurrent urinary tract
Abdominal infection
enlargement Dermatological signs

Large breed dogs & recent/not chronic cases show less signs
Dermatological signs: HyperA
Alopecia (truncal) Secondary
Thin Skin demodecosis
Comedones Seborrhoea
Bruising Slow wound healing
Calcinosis cutis
Pyoderma
Dermal atrophy
+/-Hyperpigmentation
Clinico-pathological test results
Mild erythrocytosis
Stress leukogram
  neuts, monos,  lymphos, eosins

 ALP, ALT, CHOL,

GLUC (40-60% of cases; overt Diabetes 10% of cases)
 Urea, Phos

Urinalysis
 SG <1.015 can be <1.008
 glucosuria, proteinuria
 UTI in 50% cases
 lack of active sediment, +ve urine culture
 Diagnostic Tests for HyperA
Hypothalamus
Stress
CRH

Urinary Cortisol:Creatinine (UCCR) +

Pituitary
ACTH stimulation ACTH
Low Dose Dexamethasone -
Suppression (LDDS) +
Discriminatory Adrenal
 HDDS (High dose) glands
 endogenous ACTH Cortisol
 Imaging

Target cells
 Tests for canineHyperA
SENSITIVITY SPECIFICITY
(%) (%)
UCCR 75-100 24-77
ACTH stim test 80-95 86-91
LDDS test 85-100 44-73

• UCCR: good to “rule out” HyperA

• 15% of dogs without HyperA gave a “positive” ACTH stim test
(false positive)
• LDDS: Useful for the diagnosis of adrenal tumours
• ACTH stim: More difficult to diagnose adrenal tumours, useful
for baseline monitoring treatment
 Feline HyperA
Secondary infections
Common clinical signs  UTI, respiratory, skin, kidneys,
 PU/PD, Polyphagia, oral cavity
Weight loss, lethargy Clinicopathological test results
Physical findings Stress leukogram esp.
 Abdominal distension, lymphopenia
spontaneous alopecia Hyperglycaemia
& thin skin  82% diabetic in one report
 easily torn skin, dry
Increased liver enzymes
coat, seborrhoea,
cutaneous Increased cholesterol (50% cases)
hyperpigmentation,
folded pinnae,
failure to regrow
hair
Tests for felineHyperA
UCCR
 same limitations as in dogs

ACTH stim
 false +ve & -ve results

 useful

LDDS test
 positive in most cases -use as rule out

HDDS - more useful but for differentiation

Canine Hypoadrenocorticism

“Holly” before treatment “Holly” after treatment

Pathophysiology
Destruction of the cortex  adrenal
gland is unable to secrete aldosterone in
response to any stimuli
 Loss of prime mechanism for Na+ retention
 hyponatraemia and hypotension
Clinical signs: HypoA
Lethargy 95%
Anorexia 90% Collapse 35%
Vomiting 75% Response Tx 35%
Weakness 75% Hypothermia 35%
Weight loss 50% Slow CRT 30%
Dehydration 45% Shaking 27%
Diarrhoea 40% PU/PD 25%
Wax/waning 40% Weak pulse 20%
Bradycardia 18%
Melaena 15%
Painful abdomen 8%
Clinico-pathological test results (% of cases)

Hyperkalaemia 95% Anaemia 25%

Hyponatraemia 80% Eosinophilia 20%
Na:K < 27:1 95% Lymphocytosis 10%
Azotaemia 85%
Hypochloraemia 40%
Hypercalcaemia 30% USG < 1.030 75%
 AST / ALT 30%
 TBIL 20%
Hypoglycaemia 17%
 Diagnositic tests for HypoA
Low basal serum cortisol
 97% of cases have low cortisol concentrations
 Normal basal cortisol can rule out HypoA
Subnormal response to ACTH stimulation
Endogenous plasma ACTH
 ACTH is very labile – special transport to the lab
 results may be questionable
 Can differentiate primary from secondary HypoA
 Primary: ACTH 
 Secondary: ACTH 
 Chart of ACTH Stimulation
1200
1000
Cortisol nmol/l

800
Hyperadrenocorticism
600 Normal
400 Hypoadrenocorticism

200
0
0 30 60
Time
Hypothyroidism
Pathophysiology: Thyroid Control

Hypothyroidism Higher Centres Input

  T4 & T3 e.g. cold exposure
T4 & T3 highly protein bound Hypothalamus
 free part is active TRH
+
Primary
Pituitary
 >90% cases
TSH
 immune mediated destruction (50%) + -
 idiopathic atrophy (50%)
Thyroid
Secondary T4 & T3
 < 5% cases

 Failure TSH output

Target Cells
Historical & Clinical findings
Non specific & vague signs Dermatological
Lethargy Neurological
Exercise Intolerance Reproductive
Cold intolerance Myxoedema
Weight gain/obesity Ocular
Dwarfism
Myopathy
GI system
Dermatological findings
Alopecia
 limbs spared
 rat tail
Pyoderma
 Bacterial
 Malassezia
Seborrhoea sicca
Dry brittle, easily epilated coat
Ceruminous otitis externa
Clinicopathological test results

Mild non-regenerative CHOL 

 75% cases
normocytic,
normochromic anaemia   degradation > lipid

 30-50% cases synthesis

TRIGS 
 ALT / ALP
 < 2X upper normal

 CPK
 <20% cases

 due to myopathy or 

clearance
Diagnostic tests

Higher Centres Input

Serum total T4 (TT4) e.g. cold exposure
Serum free T4 (fT4)
Hypothalamus
Endogenous cTSH TRH
TT4 & cTSH +
TSH stimulation Pituitary
TSH
TRH response + -
Antibodies
Thyroid
T4 & T3

Target Cells
 Tests for hypothyroidism
SENSITIVITY SPECIFICITY
TT4 High Low
fT4 Slightly lower than TT4 Higher thanTT4
cTSH 63-87% 82-93%

• TT4: good to “rule out” disease if normal (except when T4

autoantibodies are present
• Low TT4 result is not definitive for disease
• fT4: Less affected by non-thyroid illness; HyperA &
glucocorticoids can lower fT4
• cTSH: Dogs with non-thyroid illness can have cTSH but TT4 is
normally within reference interval
• >80% of hypoTh dogs have TT4+ cTSH
 Diagnosis
To accurately diagnose hypothyroidism
 Measure TT4, fT4, and cTSH
 If 2 of the 3 tests indicate HypoTh
 >98% chance that the dog is hypothyroid
 Exceptions
 Tx with antiepileptic drugs (e.g. phenobarbital).
 Animals on these drugs can have thyroid tests that

indicate hypothyroidism even when they are

euthyroid
Hyperthyroidism
 Aetiology
Geographical variation
 within & between countries
Syndrome due to excessive circulating T4 & T3
 Functional thyroid adenoma (adenomatous hyperplasia) in
98-99% cases
 unilateral <30%
 bilateral >70%
 Functional thyroid carcinoma in 1-2% cases
 Clinical findings
Polyphagia 70-80% Palpable thyroid
Weight loss 90-100% nodule
 despite good appetite Tachycardia
PU/PD 70-80% Heart Murmur
GI signs 30-50% Gallop rhythm
Hyperactivity 70-80% Alopecia
Skin lesions 40% Tachypnoea,
Respiratory signs 40% Sneezing, Coughing
Physical Examination
Palpable thyroid nodule
Tachycardia
Heart Murmur
Gallop rhythm
Alopecia
Tachypnoea, Sneezing, Coughing
OCULAR examination
 Clinico-laboratory test results
Haematology
 Stress leukogram
 occasionally  lymphocytes &  eosinophils
 Mild erythrocytosis
 Microcytosis ( MCV)

Biochemistry
 90%  ALT, ALP, AST
 Concurrent renal disease?
 Hypokalaemia & hyperphosphataemia
Serum TT4 –Analytical aspects
HyperTh can be diagnosed by a single high TT4 result
 Almost 95% cases

Serum T4 can be measured in-practice lab

 ELISA test kit (SNAP/Idexx)1 or bench-top immunoassay
analyser (AIA-360/TOSOH)2
 Reliable results
 The generated results cannot be used interchangeably
 Specific Reference Intervals should always be used for each
method

1
Kempainen et al AJVR 2006
2
Higgs et al JSAP 2014
TT4 –Diagnostic aspects
Cat without clinical signs (especially without a palpable thyroid
nodule) and a high in-clinic TT4 value
 Repeat in an external laboratory

TT4 within or middle to top end of reference interval

 Almost 10% of all hyperthyroid cats

 Up to 40% of cats with early or mild hyperthyroidism

 fluctuations of TT4
 and/or concurrent severe non-thyroidal illness
 Next step

 repeat TT4 in 3-6 weeks or measure fT4 or cTSH

 Or perform thyroid function tests (less common)
 Tests for feline HyperTh
SENSITIVITY SPECIFICITY
(%) (%)

TT4 94 93
TT3 65 96
fT4 96 82
canineTSH 98 49
• TT4: the preferred screening test
• TT3: Not useful (not sensitive)
• fT4: should not be used as a single test for the diagnosis of
hyperthyroidism. Up to 20% of sick euthyroid cats, can have high fT4 (false
positive)
• cTSH: useful to rule out hyperthyroidism if result is within feline reference
interval. Over 75% of clinically healthy cats have undetectable TSH with this
canine assay (false positive).