Az endokrin szervek funkciózavarai II. (hypo-, és hyperthyreosis ... · Classification of...
Transcript of Az endokrin szervek funkciózavarai II. (hypo-, és hyperthyreosis ... · Classification of...
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Veterinary Pathophysiology Lectures
5th semester
Pathoendocrinology II.
Thyroidal disorders and
other endocrine abnormalities
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Endocrine disorders could be:
primary - secondary - tertiary
Dysfunction may lead to:
increased function: production or hormonal effect
decreased function: production or hormonal effect
HYPERFUNCTION:
hyperplastic or neoplastic cells
iatrogenous factors
abnormalities of feed back mechanism
hormone-like substances
decreased or altered hormone metabolism
HYPOFUNCTION:
inflammation, atrophy, fibrosis, neoplastic alteration of the hormone-producing tissue, congenital hypoplasia, atrophy, diminished hormone synthesis, absence of substrates
structural or funtional alteration of target cells (receptor)
Classification of endocrine disorders
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Hyperestrogenism in piglets
hormone-like substances (fusariotoxicosis)
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Physiology of thyroid function
Source: Rijnberk-Kooistra: Clinical Endocrinology of Dogs and Cats
hypothalamus
adenohypophyis
thyroidal
glands Peripherial
tissues
3,5,3’-triiodo-
thyronin
Type I. 5’-deiodinase
Type II. 5’-deiodinase
rT3
3,3’,5’-triiodo-
thyronin
carrier
molecules:
TBG, TBPA,
albumine
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Healthy individuals:
diurnal rythm
age
body weight/body size
gender, phase of oestrus cycle
breed-specific reference interval
Systemic disorders* which not affect the thyroidal gland:
* Non-thyroidal illness (NTI)
inflammatory disorders, organ dysfunction
several drugs (corticosteroids, NSAID’s, sulphonamids, phenobarbital, …)
Factors which affect
the hypothalamic-pituitary-thyroidal gland axis
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From Rijnberk: Clinical Endocrinology of Dogs and Cats
Physiology of thyroid function
Normal thyroid tissue
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Abnormalities of thyroidal function
Dotted arrows show inhibitory effects
sulphonamids
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Hypothyroidism decreased function
congenital
acquired (primary-thyroids, secondary-Hf, tertiary-Ht)
iatrogenous
Ethiology:
• iodine deficiency: ho & Ru, Su, Eq
• goitrogenous substances: Ru, Su, Eq
• nutritiants (protein), vitamins (ACE) és minerals (Se) deficiency
• enzimopathy (pl. sulphonamids)
• immune-mediated process: lymphocytic thyroiditis (TgAB, anti-colloidal or anti-microsomal antibodies, autoT4/T3 ab) ca
• idiopathic follicular atrophy: ca
• iatrogenous: by treatment of hyperthyreosis fe
Hyperthyroidism increased function
• thyroidal hyperplasia or neoplasia (fe: adenoma; ca: carcinoma)
Disorders of thyroid function
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Source: Rijnberk: Clinical Endocrinology of Dogs and Cats
Ethiology of canine hypothyroidism
normal thyroid tissue lymphocytic infiltration
Primary hypothyroidism is the most common alteration in dogs.
decreased totalT4 & elevated TSH
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systemic effect → variable & individual clinical signs
inherited or congenital:
stillbirth, retarded growth, disproportional dwarfism, mental retardation (cretenism)
acquired:
decreased metabolic rate
weakness, excersice intolerance, cold intolerance, gain weight (without marked polyphagia), constipation
bradycardia, weak pulse, arrythmia
skin: myxedema, alopecia, seborrhea, hyperpigmentation, „therapy-resistant ” pyoderma
reproduction disorders (decreased fertility, abortus)
neuromuscular dx, haemorrhagic diathesis, ocular signs
…
Hypofunction of thyroidal gland
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Myxoedema in different species
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Alopecia in canine hypothyriodism
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see practical lectures
routine laboratory tests
• normocytic normochromic anaemia
• elevated ALT, TG, TChol, fructosamine (with euglykaemia)
endocrine tests
• total thyroxin (tT4)
• free thyroxin (fT4) measured by equilibrium dialysis
• endogenous TSH
• TSH-/TRH-stimulation test
• tT3, fT3, TgAB, autoT4/T3 antibodies,…
thyroidal scintigraphy
Laboratory diagnosis of hypothyroidism
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most common endocrinopathy in elderly cats
ethiology:
hyperplasia (fe), adenoma (fe), adenocarcinoma (ca, 1% fe)
iatrogenous thyrotoxicosis
consequences: increased metabolic rate (systemic effect)
• heat intolerance
• restlessness, aggressive behaviour
• reduced stress tolerance
• weight loss inspite of increased appetite
• polyuria polydypsia
• diarrhea, vomitus
• tachycardia, tachyarrythmia, hypertonia
• dyspnoe
Hyperfunction of thyroidal gland
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Thyroidal tumour in a dog
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Graves-Basedow disease in humans
antibodies against TSH receptor
struma + exophtalmus
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Feline hyperthyroidism
Source: Rijnberk: Clinical Endocrinology of Dogs and Cats
Enlarged thyroidal gland could be palpated.
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see practical lectures
routine laboratroy tests
• polycythaemia
• elevated AST, ALT, ALKP
• persistant hyperglycemia & normal fructosamine level
endocrine tests
• total thyroxin (tT4) • free thyroxin (fT4) measured by equilibrium dialysis
• endogenous TSH (?) • T3-supression test
thyroidal scintigraphy
Laboratory diagnosis of hyperthyroidism
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Laboratory diagnosis of hyperthyroidism
high tT4 → hyperthyroidism
BUT! might be normal tT4
diurnal rythm
effect of NTI
E-217971
10 y castrated tomcat
totalT4: 182 nmol/l
(ref. range.: 10-50 nmol/l)
histopath: follicular carcinoma
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parathormon
hypofunction, hyperfunction (rare disorders)
Disturbances of Ca-homeostasis calcitonin, vitamine D
Dysfunction of parathyroidal glands
From: BSAVA Clinical Pathology
Ca2+ reabsorp.
PO42- excret.
incr.
Ca-mobiliz.
C-cells:
calcitonin
decr.
Ca-mobiliz.
Ca-absorp
Incr.
Ca-mobiliz.
Ca2+ reabsorp.
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primary hypoparathyroidism
• immune-mediated process
• iatrogenously
primary hyperparathyroidism
• parathyroidal hyperplasia or adenoma (adenocarcinoma)
• dog >> cat
secondary hyperparathyroidism
• renal
• alimentary
pseudohyperparathyroidism
Dysfunction of parathyroidal glands
PTH-level increased → HYPERCALCAEMIA
PTH-level decreased → HYPOCALCAEMIA
compensatory process
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secondary alimentary hyperparathyroidism
• malnutrition
• „all meat diet” syndrome (low Ca:PO4 ratio in diet)
• malabsorption
• low – normal Ca-level & high PTH
secondary renal hyperparathyroidism
• increased phosphate retention
• decreased calcium absorption
• decreased vitamine D production
• malabsorption
• low – normal Ca-level & high PTH
Dysfunction of parathyroidal glands
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„relative” hypoparathyroidism
• milk fever, puerperal tetany, eclampsia
• nutritional failure
• calcium loss due to lactation
pseudohyperparathyroidism
• neoplastic cells producing parathormone-related peptids (PTHrP)
• hypercalcaemia
• perianal adenocarcinoma, lymphosarcoma
• PTHrP-detection
Dysfunction of parathyroidal glands
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Dysfunction of parathyroidal glands
HYPOCALCAEMIA
muscle weakness, tremor,
muscle fasciculation,
generalized tetany
hyperthermia
osteomalacia
pathologic bone fracture
rubbing of the head
HYPERCALCAEMIA
soft tissue mineralisation
tubulopathy
urolithiasis
PU/PD
anorexia, vomitus
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see practical lectures
parathormon detection
• peptid hormone → special sample handling!
• expensive!
• PTH-level should be correlated to calcium concentration
• (vitamine D-level determination)
• do not forget to measure PO42--, urea-, and creatinine
concentration
• PTHrP-detection does not belong to the routine clinical work
Laboratory diagnostic of parathyroidal dysfunctions
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malignant insulin-producing pancreas tumour
• ferret, dog, (>>>> cat)
Anamnesis, symptoms
dog: middle aged - older, middle-sized – large breed, but WHWT
increased appetite, weight gain
neurological signs
Laboratory diagnostics:
persistant hypoglycaemia
fructosamine level: low-normal/low
diagnostic imaging US/CT/MRI/scintigraphy
Endocrine tests:
insulin-level measurement, spec. sample handling, insulin/glucose ratio
Insulinoma
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Hypophyseal dwarfism
Decreased growth hormone production
BSAVA Endocrinology
Velasquez: Francisco Lezcano a törpe
(El Nino de Vallecas)
Museo del Prado, Madrid
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Gigantism: GH excess before closure of epiphyses
Acromegaly: GH excess after closure of epiphyses
cat: tumor in adenohypophysis (insulin resistant DM)
dog: GH-production in mammary gland during luteal phase
Growth hormone (GH) excess
BSAVA Endocrinology