Sie sind auf Seite 1von 123

Drh. M. Ar Raniri Putra (drh.

ArRan)

VETERINARY
ENDOCRINOLOGY
Hormones
Produksi dan Regulasi Hormon
• Pada hewan sehat perubahan
konsentrasi hormon ditentukan oleh
perubahan laju produksinya.
• Laju produksi dikontrol oleh sejumlah
“negative feedback loops”
• Respon terhadap feedbak system
akan berlangsung dalam hitungan
menit-jam hingga mencapai
HOMEOSTASIS
• Mekanisme regulasi hormon:
– Konsentrasi fluktuatif  insulin
– Konsentrasi konstan  thyroxine
Hormone Deficiency
(Hypofunction)
Decrease or
failure
production of
hormone Kegagalan
Acquired
dalam
disorders
beraksi

Congenital
Endocrine
defect of idiopathic
gland function
Hyperfunction

Functional
neoplasia

Endocrine Abnormalities
Hormon-like
of feedback
substance Hyperfunction regulation

Exogenous
hormone
administration
Polyuria and Polydipsia

PDHB’s In House CE- Drh. M. Ar Raniri Putra


Anti Diuretic Hormone (ADH)
• Neurohypophysis
Stimulasi:
Barbiturate,
nicotin, narcotic,
Inhibit: carbamazepine,
Ethanol vincristin,
Glucocorticoids cholinergic drugs,
Phenytoin β adrenergic drug,
chlorpropamide
dsb

• ADH Secretion
E. Coli endotoxin
Decrease sensitivity of renal
Hypokalemia
tubules to ADH
hypercalcemia
History
• PU n PD  biasanya terjadi bersamaan
• Polyuria vs Pollakiuria
• Estimasi water intake normal
– Anjing: 20-90 ml/kg/day
– Kucing: 0-45 ml/kg/day
• Estimasi produksi normal urine
– Anjing: 20-40 ml/kg/day
– Kucing: 20-45 ml/kg/day
Physical Exam
• Abd. Palpation (bladder, kidneys n Liver)
• Lymphnode palpation
• Rectal exam (urethra n Tumor)
– LUTD -> Tick of urethra
– Anal sack sarcoma -> hypercalcemic, polyuria,
large lymphnode
• Blood pressure (elevated: renal dz,
hyperthyroidism, cushing’s, diabetes in dog,
liver dz, CNS dz, hyperaldosteronism,
idiopathic hypertention)
• Banyak minum??
– >90 ml/kg/day (dog) >60ml/kg/day (cat)
• Water intake  variable
• Seberapa banyak owner yg mengukurnya?
• Banyak pipis??
– >50ml/kg/day
• Sulit diukur kalau tidak dilakukan observasi
di klinik
• When a Patient is
presented for PU/PD,
What’s the 1 test you
st

want to do?
URINALISIS
• SG  if USG >1.020 in a dog or >
1.030 in a cat  not consistent with
polyuria
• Full Urinalysis
– Casts, bacteria, cells, protein can suggest
renal disorder
– Glucose -> DM
– Mild proteinuria consistent with
hyperadrenocorticism
– Protein losing nephropathy
Other test
• Chemistry profile (BUN, Cr, SGPT,
ALP, Elektrolit (Ca, K, P, Na),
Glukosa)
• CBC (anemias, leukon)
• Imaging
– USG renal architecture, bladder, adrenal
gland, liver, Ln
– X-ray  abdomen: liver size, masses,
urolith, kidney
– Thorax  calcification, neoplasia
(hypercalcemia), effect of
hypertention
Most Common Causes - Dogs
• Renal Disease
• Diabetes Melitus
• Hypercortisolism
• Pyometra
• Subacute leptospirosis
• Hypercalcemia
• Hypoadrenocorticism
• Psychogenic
• Advanced Liver Disease
Most Common Causes - Cats

• Renal Disease
• Diabetes Melitus
• Hyperthyroidism
• Pyometra
• hypokalemia
Canine Hypothyroidism
Drh. M. Ar Raniri Putra
Principal cells (sel folicular): Thyroglobulin
Parafollicular cells : calsitonin
REGULATION
Canine Hypothyroidism
• Common endocrine disorders in dogs ??
• Over diagnosed
– Gejala klinis non spesifik
– Diganostic test yg tidak tepat
Thyroid Hormone Metabolism
• >99% dari T3 dan T4  protein bound
• Free hormones (Free T4)
– Enter cells
– Have metabolic effect
– Regulate pituitary feedback
• Total T4 = Free T4 + Bound T4
Canine Hypothyroidism
• Primary Hypothyroidism
– Destruksi thyroid gland
• Lymphocytic thyroiditis
• Idiopathic thyroid atrophy
• Central hypothyroidism
– Kegagalan sekresi TSH oleh pituitary
• Malformasi dari pituitary
• Supresi sekresi TSH dari pituitary  temporary dan
reversible
– Exogenous administration of glucocorticoid
– Spontaneous hyperadrenocorticism
• Congenital hypothyroidism
– Uncommon
– Thyroid hypoplasia, aplasia, dysgenesis atau
dyshormonogenesis
– “fading puppy” syndrome atau disproportionate
dwarfism
Clinical Features
• Metabolic features
– Lethargy
– Exercise intolerance
– Weight gain and obesity
Dermatological features
• Present in over 85% cases
• Alopecia
• Dryness
• Abnormal keratinitation (Scaling)  seborrhoea
• Hyperpigmentation
• Poor wound healing
• In extreme cases, mucopolysaccharides accumulate in
the skin causing it to thicken, especially in the face 
myxoedema
• Neuromuscular
– Myopathy
– LMN dz
– Laryngeal paralysis and megaoesophagus
– Mixoedema coma
• Cardiovascular
– DCM
• Reproductive
– Anestrus
– Infertilitas
– Penurunan libido jantan
Diagnosis
• Clinical pathology
– QBC: non regenerative anemia often presen
– Biochemistry
• Hypercholesterolaemia (>75% cases)
• Hyperlipidemia
• ↑ALP, ALT
• ↑ fructosamine (up to 80%)
Total T4
• Useful screening test
• Most of dogs with hypothyroidism have low value
• Many dogs with other diseases (ESS) have low value
too
• Further test should be performed if low, low normal
or unexpectedly high
The following may falsely decrease t4
• Glucocorticoid
• Sulphonamides
• Anticonvulsan
• Furosemide
• Euthyroid sick syndrome (ESS)
• Thyroid hormone autoantibodies
• Breed (sight hounds have lower T4 values)
Free T4
• Two assay methods
– Analogue techniques
• Confer no advantages over assay of total T4
– Equilibrium dialysis
• Increased sensitivity an spesificity over total T4
• Validated canine assay available
Advantages – free T4
• Free T4 is biologically active portion
– Diffuse into cells
– Exerts negative feedback on pituitary
• Changes in total T4 with illness and drugs may not
affect fT4
• Equilibrium dialysis assay is less affected by thyroid
hormone autoantibodies
Disadvantages-fT4
• Must be run with Equilibrium dialysis (human lab
used Analogue techniques)
• Expensive (ED)
T3 & rT3
• Poor indicator of thyroid function
– 80% is produced in extra-thyroidal tissues
• No difference in T3 in normal dogs, hypothyroid dogs
and ESS dogs.
• Anti-T3 autoantibodies are more common than anti-
T4
• rT3 partly increased in ESS dogs and after drug
application
TSH
• Lack of negative feedback on pituitary should lead to
elevation of TSH
• Combination with fT4 or T4 (High TSH & Low fT4 or
T4)
– Sensitivity 87%
– Specificity almost 100%
Feline Hyperthyroidism
Drh. M. Ar Raniri Putra
Etiology
• Adenomatous hyperplasia
• Histopatological similar to toxic nodular goiter
• Cause unknown
• No evidence of immunopathy
• Thyroid carcinoma in 1-2% of cats
Canned food and Hyperthyroidism
• Risk factors: Flea sprays, indoors, herbicides, canned food (scarlett et al,
1988)
• Increased risk in cats thet prefer fish or liver or giblets flavored canned
food (Martin et al, 2000)
• Cats fed pop-top canned food at any time had 2.5x to 5x risk of
hyperthyroidism VS cats fed dry food (Edinboro et al. 2004)
Breed
• Siamese
• Himalayan Decreased risk
• Purebred

Sex
• Male  increased risk

Age
• Middle-aged Older cat (>4yo)  increased risk
Historical Findings
• Weight loss 88%
• Hyperactivity 61%
• Polyphagia 49%
• PU/PD 36%
• Vomiting 44%
• Diarrhea 15%
• Decreased Appetite 16%
• Large fecal volume 8%
• Anorexia 7%
Physical Findings
• Goiter (enlargement of Thyroid Glnd) 83%
• Thin 65%
• Heart murmur 54%
• Tachycardia 42%
• Gallop 15%
• Aggression 15%
• Unkempt 9%
• Thick claws 6%
Diagnosis
• Urinalysis
• CBC
– Leukositosis, eosinopenia, increased PCV
• Chemistry profile
– Increased ALT (90%)
– Azotemia (25%)
• Blood pressure
• Serum total T4
Diagnostic test
Therapy Drug Dose Route Sampling Assay euthyroi HyperT
times dism
T3 Liothyron 20 mg Oral 0 and 2-4 Total T4 <20 >20nmol/
Suppressi ine q8h for 7 hours after nmol/l l ± <35%
on doses last dose with suppressi
>50% on
suppressi
on
TSH Bovine 0.5 IU/kg IV 0 and 6 Total T4 >100% Minimal
Stimulati TSH hours increase to no
on increase
rhTSH 25ug/cat IV 1 and 6-8 Total T4 >100% Minimal
hours increase to no
increase

TRH TRH 0.1 IV 0 and 4 Total T4 >60% <50%


Stimulati mg/kg hours increase increas
on
Treatment
• Antithyroid drugs
– Methimazole: 2.5mg/cat q12h
– Carbimazole : 5mg/cat q12h
• Radioactive Iodine
• Surgical
CANINE CUSHING’S SYNDROME:
AN OVERVIEW
Hypothalamus

CRF (+)

Pituitary pars
cortisol (-) distalis

ACTH (+) cortisol (-)

Adrenal cortex
CAUSES OF HYPERCORTISOLISM
 Pituitary-dependent hypercortisolism (PDH)
 Most common
 Persisten sekresi ACTH
 Micro or macroadenoma of pars distalis
 Bilateral adrenal hyperplasia
 ACTH merangsang sekresi cortisol tapi negative feed
back cortisol thd ACTH tidak terjadi  [cortisol] dan
[ACTH] ↑ ↑
 Adrenal Tumor
 Cortex secara autonom mensekresikan cortisol
 Negative feed back cortisol terhadap ACTH tetap
terjadi  [cortisol] ↑ sementara [ACTH]↓
 Iatrogenic = corticosteroid in long term
PREDISPOSITIONS
 Age Pred
 2-16 yo, adrenal tumor  rata2 11 tahun
 Breed Pred
 Dog : Poodle, boston terrier, boxer, dachshund
PDH;
 german shepherd and toy poodle  adrenal tumor
 Cat : none

 Sex pred
 Dog: none, but female make up 70% of adrenal tumor
 Cat: female
CLINICAL SIGN
 Pu.PD (90%)
 Due to ADH antagonism
 Decreased renal tubular water permeability
 Decreased vasopressin secretion
 Polyphagia
 Direct effect of glucocorticoid, or can be due to an anti
insulin effects (77-87% dogs)
CLINICAL SIGNS: SKIN
 Bilaterally symmetrical alopecia (55-90%)
 Thin skin
 Skin tears easily in cats
 Decubital ulcers in severe cases
 Pembuluh darah subcutis terlihat jelas

 Hyperpigmentation
 Comedones
CLINICAL SIGNS : MUSCLE
 Muscle atrophy and lethargy
 Direct effect of glucocortioids
 Abdominal enlargement (93-95%)
 Wasting Abd. Muscle
 Redistribution of fat to ventral abdomen
 Hepatomegaly induksi vakuolisasi sel hati dan
akumulasi glikogen
Muscle
Atrophi

Pot belly
CLINICAL SIGNS
 Respiratory system
 Panting is common abd. Fat n disposisi lemak yg
berlebih pada thorax, kelemahan otot respirasi
 Dyspnea due to pulmonary embolism

 Obesity
 Endocrine system
 Insulin resistance
 Diabetes is common in dogs and cats with hypercortisolism

 Infertility
 Malebilateral testis atrophy, penurunan libido
 Female (bitches) prolonged unestrus

 Nervous system
 Seizures, blindness, circling due to macroadenoma
DIAGNOSIS

History and PE are the most


important “tests” in diagnosis
of hyperadrenocotism.
DIAGNOSIS
 Urinalysis
 Isosthenuria, proteinuria
 CBC
 Lymphopenia, eosinopenia, neutrophilia, monocytosis
(stress leukogram)
 Serum chemistry
 Elevated ALP (90% dog), 5-40 times
 elevated ALT, hyperglycemia, hypernatremia,
hypercholesterolemia (90%), hypokalemia (50%)
 Blood pressure
 Mild elevation in 80% of dogs
DIAGNOSTIC IMAGING
 Radiography
 Hepatomegaly
 Mineralized adrenal tumors (35%)
 Pulmonary metastasis
 Ultrasound
 Adrenal hyperplasia vs atrophy vs tumor
 Liver and kidney imaging
PITUITARY ADRENAL FUNCTION TESTS
 Screening tests
 To establish a diagnosis of hyperadrenocortisism
 LDDS, ACTH stimulation tests
 Differentiation Tests
 To differentiate pituitary from adrenal tumor
 HDDS, endogenous ACTH
PITUITARY-ADRENAL FUNCTION TEST
 Basal cortisol
 Not useful
 ACTH stimulation Test
 Cortisol measured before and 60-90 min after 5ug/kg
synthetic ACTH IM
 Use normal value specific for your lab
 Cats may have cortisol peak 30 or 60 minutes
 Highly sensitive
 Tidak akurat pd kasus adrenal tumor
 Akurat dalam kasus iatrogenic hypercortisolism
TECHNIQUE
 Ambil darah 2ml untuk mengukur basal cortisol
 Inject 5 ug/kg synthetic ACTH IM

 Collect blood sample (2ml) in 30 min, 60 min and


90 min
 Ensure the tube are labelled correctly
PITUITARY-ADRENAL FUNCTION TEST
 Dexamethasone Supression Tests
 Low dose (0.01-0.015 mg/kg)
 High dose (0.1 – 1 mg/kg)
TECHNIQUE
 Ambil darah 2ml untuk dilakukan
pengecekan basal cortisol (0 Jam)
 Inject 0.01 mg/kg of dexamethasone
(LDDS) or 0.1 mg/kg (HDDS) into the
cephalic vein (it is preferable to place an
IV cath)
 Collect blood sample after 4 hrs and 8 hrs
THE GRAPHICS BELOW SHOWS POSSIBLE
LDDST RESULTS
16

14

12

?PDH/ADH
10

PDH
8

Normal
6

HypoAd or Iatrogenic
4 hyperAd

0
0 4 8
RATIO OF URINE CORTISOL AND
CREATININE

 First morning urine should be used


 Measure urine cortisol and creatinine in mmol/L

 Ratio of >35 is suggestive of Cushing’s

 High negative predictive value

 Very non specific


 Large breed
•have ratio >35 too
 dissect
TREATMENT
 Adrenocorticolytic Drugs
 Mitotane
 Steroidogenesis Inhibitors
 Several drugs
 Surgery
 Adrenalectomy
 For adrenal tumors or cats
 Hypophysectomy ??
MITOTANE (LYSODERM, OP-DDD)
 Induction phase  Medical
 50 mg/kg/day divided adrenalectomy can be
bid for 7-10 days done in cases with too
 Maintenance phase many relapses
 Begins when pre and  Prolonged induction
post ACTH are both phase
low-normal  Replacement
 50mg/kg/week hormones for life
(divided)  Also useful for adrenal
 Relapses are common tumors
 Re-induce and monitor  Higher doses
 Useful when surgery
is not indicated
SIDE EFFECTS
 Inappetance
 Anorexia

 Vomiting
Owner harus
 Collapse mempersiapkan
 Diare prednisone kalau side
 Ataxia
effect muncul
STEROIDOGENESIS INHIBITORS
 Ketoconazole
 Metyrapone

 Trilostane
Cholesterol

Pregnenolone 17OH-pregnenolone Dehydroepiandrosterone

Progesterone 17OH-progesterone Androststenedione

Deoxycortisol 11-deoxycortisol estrone testosterone

Corticosterone cortisol Estradiol

Aldosterone
Inhibited by ketoconazole
Inhibited by Trilostane
Inhibited by metyrapone
STEROIDOGENESIS INHIBITORS

 Side effects may be less common with Trilostane


than Lysodren
 Ketoconazole can be hepatotoxic
THERAPY FOR ADRENAL TUMORS
 Medical
 Mitotane at 50-75 mg/kg/day
 Administer prednisone at 0.2 mg/kg/day
 Some patients need mineralocorticoid
supplementation
 Maintenance doses of 200-300 mg/kg/week may be
needed
 Surgical
 Adrenalectomy
 The only viable therapy in cats regardless of etiology
Introduction to Diabetes
Mellitus in Dogs n Cats
Hyperglycemia
• Blood glucose > ref. Range
• Clinical signs occur when the renal
threshold is exceeded
– 180-220 mg/dl in dog
– ?-280 mg/dl in cat (not known)
– Results in glucosuria  osmotic diuresis 
PU/PD
Ruleouts for Hyperglycemia
• DM
– 1o Islet Destruction
• Immune mediated (type 1 or juvenile)
• Pancreatitis
– Insulin resistance
• Hypercortisolism
• Acromegaly  common in cat  high of growth
hormone
• Stressed cats  epinephrine release
• Hyperglycemia from glucocorticoids not
always accompanied by glycosuria
Pathophysiology
• Type 1
– Destruction/loss of beta cells
– May be partial  associated with pancreatitis
• Type 2
– Insulin resistance/dysfunctional beta cells
– Can be obesity-related
• Dogs are more like Type 1, cats more like
type 2, but all fall somewhere on
continuum between the two
Causes of DM in dogs
• Genetic predispositions
– Australian terrier, Schnauzer, Samoyed, mini
schnauzer, fox terrier, keeshond, bichon frise,
Poodle, Husky
• Age
– 8-15 yo (most over 10 yo)
• Obesity increases risk 3 – to 5 fold
• Female 2x more likely than male
• Dogs weighing less than 23 kg greater risk
(small – medium dog)
Cause of DM in Cats
• Islet-specific amyloid deposition
– Non diabetic cats have islet amyloidosis too
– Amyloid  co secreted with insulin, may induce inhibition
of insulin secretion, may cause insulin resistance
• Chronic pancreatitis
• Obesity
• Sex: neutered males more common
• Most are over 10 yo
• Infection and other illness (bacterial ginggivitis and
UTI)
• Drugs  glucocorticoid
Clinical Signs
• Polyuria
• Polydipsia
• Polyphagia  satety center has an
insulin mediated uptake of glucose
• Weigh loss
Diabetic cataracts
• Most occur in dogs
• The lens is freely permeable to glucose
• Normal anaerobic glycolytic pathways :
konversi glukosa mjd as. Lactad
• Hyperglycemia  saturated the pathway
• Glukosa akan dimetabolisme melalui sorbitol
pathway  sorbitol dan fruktosa (tdk freely
permeable)
• Menarik air ke dalam lensa  bengkak dan
menghancurkan fibers.
Diabetic cataracts
Diabetic neuropathy
• Seen in cats
• Plantigrade posture the hocks touching
the ground
• Cause is unknown
Initial diagnostics
• Urinalysis • Urinalysis
• CBC – Glycosuria
• Chemistry profile – Proteinuria
– Ketonuria
• Urine culture
– Bacteriuria
• +/- Fructosamine
• Chemistry
– Liver enzyme
abnormality
• Due to lipidosis n
pancreatitis
– Pre renal azotemia
– ↑ Cholesterol
Treatment
• Dietary • In cats
– High fiber – Obligate carnivores
– Avoid excessive – Amino acid signals
amounts of protein insulin release
– Avoid excessive – Maintain necessary
amounts of fat glucose levels from
amino acids and not
dietary carbohydrates
Feeding schedule Exercise

• If typically fed free choice, • Promote weight loss


continue • Glucose lowering effect
• Minimum of 2 meals daily
Insulin currently used
In cats In dogs
• Porcine lente • Porcine lente (most
• PZI common)
• Humulin N • Humulin N
• Lantus (most common) • Lantus
Insulin starting doses
Dogs cats
• 0.5-1 IU/kg bid  • 1-3 U/cat sid or bid 
BW<15kg long acting insulin
• 0.5 IU/kg bid  • 1-3 U/cat bid  NPH
BW>15Kg
Monitoring Insulin Therapy
• Clinical Signs
– Signs of hypoglycemia
– PU/PD
– Body condition
– Appetite
• Fruktosamine
• Spot BG
Oral Hypoglycemic Drugs
• Increasing Insulin secretion  glipizide
• Inhibit glucose release  metformin 
can be toxic in dog n cat
• Decrease glucose absorption  acarbose
• Increase sensitivity to insulin 
thiazolodine  very toxic in cats
• Kontraindikasi
– Hypoglycemia
– Development of ketonuria
– Lack of response
– hepatotoxic
Thank you..