Veterinary Pathophysiology Lectures

5th semester

Pathoendocrinology II.

Thyroidal disorders and

other endocrine abnormalities

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

Hyperestrogenism in piglets

hormone-like substances (fusariotoxicosis)

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

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

From Rijnberk: Clinical Endocrinology of Dogs and Cats

Physiology of thyroid function

Normal thyroid tissue

Abnormalities of thyroidal function

Dotted arrows show inhibitory effects

sulphonamids

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

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

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

Myxoedema in different species

Alopecia in canine hypothyriodism

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

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

Thyroidal tumour in a dog

Graves-Basedow disease in humans

antibodies against TSH receptor

struma + exophtalmus

Feline hyperthyroidism

Source: Rijnberk: Clinical Endocrinology of Dogs and Cats

Enlarged thyroidal gland could be palpated.

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

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

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.

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

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

„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

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

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

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

Hypophyseal dwarfism

Decreased growth hormone production

BSAVA Endocrinology

Velasquez: Francisco Lezcano a törpe

(El Nino de Vallecas)

Museo del Prado, Madrid

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