Thyroid Hormones

location of the thyroid gland

below the larynx and on either side of and anterior to the trachea

structures of the thyroid gland

thyroid hormones

1. thyroxine

2. triiodothyronine

3. calcitonin or thyrocalcitonin

T₄ is known as

Thyroxine

T₃ is known as

Triiodothyronine

secretory cell of th

secretory cell of calcitonin or thyrocalcitonin

thyroid parafollicular cells

stimulator for T₃ and T₄

exposure of animal to low environmental temperature (cold)

inhibitor for T₃ and T₄ secretion

conditions that stimulate the sympathetic nervous system

• excitement

• anxiety

Regulation of Thyroid Hormone Secretion

TSH Signaling Pathway of Thyroid Follicular Cells

Synthesis of T₃ and T₄ by Thyroid Follicular Cells

1. Iodide Trapping

2. Formation & Secretion of Thyroglobulin

3. Oxidation of Iodide Ions

4. Iodination of Tyrosine & Formation of Thyroid Hormones or Organification of Thyroglobulin

5. Coupling Reaction

6. Storage of T₃ and T₄

7. Release of T₃ and T₄ from Thyroid Gland

Iodide Trapping Mechanism

Formation & Secretion of Thyroglobulin

Oxidation of Iodide Ions

Iodination of Tyrosine & Formation of Thyroid Hormones

or

Organification of Thyroglobulin

chemical name of T₃

3,5,3-triiodothyronine

Coupling Reaction (T₃)

chemical name of T₄

3,5,3,5-tetraiodothyronine

Coupling Reaction (T₄)

Storage of T₃ and T₄ Hormones

how many molecules of T₃ and T₄ in a thyroglobulin molecule

T₃ - 1 molecule

T₄ - 1-3 molecules

Release of T₃ and T₄ from Thyroid Gland

plasma proteins which bind to T₃ and T₄

1. thyroxine binding globulin (TBG)

2. thyroxine binding prealbumin

3. albumin

binding affinity of thyroxine binding globulin

high affinity for thyroxine

binding affinity of thyroxine binding prealbumin

binds T₃ and T₄

binding affinity of albumin

binds T₃ and T₄

percentage of T₃ and T₄ in free form

<0.05% of T₃ and <0.05% of T₄

features of T₃ and T₄ in bound form (in dogs)

• TBG - high affinity for T₄

• prealbumin & albumin - low affinity T₃ and T₄

features of T₃ and T₄ in bound form (in cats)

• prealbumin - high affinity T₃ and T₄

Features of T₃ and T₄

• blood level

• potency

• duration of action

• binding with plasma proteins

• how much is released in x days

T₃

• blood level 7%

• potency 4x higher

• duration short

• binding with plasma proteins

  • weakly bound

• ½ released in 1 day

T₄

• blood level 93%

• potency 4x lesser

• duration long

• binding with plasma proteins

  • strongly bound

• ½ released in 6 days

monodeiodination of T₄

site of monodeiodination

liver & kidney

Thyroid Hormone Receptors in Target Cells

1. TRa

   1. TRa1

   2. TRa2

   3. TRa3

2. TRb

   1. TRb1

   2. TRb2

   3. TRb3

distribution of TRa1

all tissues, abundant in heart, skeletal muscle, brown adipose tissue, brain

distribution of TRb1

liver & kidneys

distribution of TRb2

• anterior pituitary gland

• hypothalamus

• inner ear

• developing brain

distribution of TRb3

• kidney

• liver

• lungs

Effect of Thyroid Hormones on Different Body Systems

1. maintains normal basal metabolic rate (BMR)

2. effect on metabolism

3. maintains normal blood lipid levels

4. maintains normal body weight

5. increases formation of enzymes or co-enzymes essential for vitamin formation

6. promotes growth of animals

7. effect on circulatory system

8. increases respiratory function

9. increases food intake, appetite, digestion

10. increases brain cerebration

11. promotes muscle to react with vigor

12. promotes good sleep

13. maintains normal body temperature

14. needed for normal reproduction

1. maintains normal basal metabolic rate (BMR)

hyperthyroidism vs hypothyroidism

• increases metabolism in almost all cells

hyperthyroidism - increases BMR by 60-100%

hypothyroidism - decreases BMR by 30-50%

2. effect on metabolism

• carbohydrates (CHO)

  • promotes glucose absorption in GIT

  • promotes glucose uptake by cell through stimulation of insulin secretion

  • deficit in glucose

    • glycogenolysis

    • gluconeogenesis

• fats

  • mobilize fats in adipose

  • lipolysis

  • promotes utilization of cholesterol for bile acid formation

  • activates lipoprotein lipase

    • catalyze hydrolysis of chylomicrons (TG) into glycerol + FA

• protein

  • protein anabolism

  • formation of enzymes

  • formation of structural proteins

3. maintains normal blood lipid levels

hyperthyroidism vs hypothyroidism

hyperthyroidism

• low plasma cholesterol, phospholipids, TAG

hypothyroidism

• high plasma cholesterol, phospholipids, TAG

• fatty liver

• development of atherosclerosis

  • due to high blood cholesterol level

4. maintains normal body weight

hyperthyroidism vs hypothyroidism

hyperthyroidism

• decrease in body weight

• weight loss

hypothyroidism

• increase in body weight

• develops obesity

5. increases formation of enzymes/co-enzymes essential for vitamin formation

hyperthyroidism vs hypothyroidism

chronic hyperthyroidism

• initially increases vitamin formation then deficiency in vitamins occur

chronic hypothyroidism

• vitamin deficiency

6. promotes growth of animals

hyperthyroidism vs hypothyroidism

• bone, brain, muscles, etc.

chronic hyperthyroidism

• early closure of epiphyseal plate

• rapid bone maturation

chronic hypothyroidism

• stunted growth

• retarded brain development

6. effects on circulatory system

• increases blood flow to tissues

  • increased BMR

  • increases O₂ utilization by tissues

• increases cardiac output

  • increased O₂ demand

• increases heart rate

  • increased O₂ demand

• arterial vasodilation

  • increase transport of blood to the tissues

• development of hypertrophic cardiomyopathy

heart function abnormality

hyperthyroidism vs hypothyroidism

chronic hyperthyroidism

• tachycardia

• cardiac murmurs

chronic hypothyroidism

• bradycardia

• slow heart sound

• arrythmia

7. increases respiratory function

hyperthyroidism vs hypothyroidism

• increases RR due to increased O₂ consumption and CO₂ formation by cells (due to increased BMR)

chronic hyperthyroidism

• high RR

• fast shallow breathing

chronic hypothyroidism

• low RR

• slow, deep breathing

8. increases food intake, appetite, digestion

hyperthyroidism vs hypothyroidism

• increases appetite and feed intake

• increases GIT motility & digestive juice secretions

chronic hyperthyroidism

• diarrhea

chronic hypothyroidism

• constipation

9. increases brain cerebration

hyperthyroidism vs. hypothyroidism

chronic hyperthyroidism

• extreme nervousness

• anxiety

chronic hypothyroidism

• lame

• inactive disposition

10. promotes muscle to react with vigor

hyperthyroidism vs. hypothyroidism

chronic hyperthyroidism

• fine muscle tremors

*more muscle proteins catabolized - leads to muscle weakness

chronic hypothyroidism

• muscle sluggish

• muscle relax slowly

11. promotes good sleep

hyperthyroidism vs. hypothyroidism

chronic hyperthyroidism

• difficulty in sleeping

• short sleep hours

• exhaustion of brain and skeletal muscles

chronic hypothyroidism

• extreme somnolence

• 12-14 hours sleep per day

12. maintains normal body temperature

hyperthyroidism vs. hypothyroidism

chronic hyperthyroidism

• high body temp

• heat production

• sweating, panting

chronic hypothyroidism

• difficulty to maintain normal body temp

• cold intolerance - skin feels cold

• heat seekers - blankets, TV, fridge

13. needed for normal reproduction

hyperthyroidism vs. hypothyroidism

chronic hyperthyroidism

• male

  • impotence

• female

  • irregular estrous cycle

  • infertility

chronic hypothyroidism

• male

  • loss of libido

  • poor sperm quality

  • testicular atrophy

• female

  • loss of libido

  • irregular estrous cycle

  • prolonged anestrus

  • low fertility & conception rates

  • high abortion rate

thyroid hormone abnormalities

• hyperthyroidism

• hypothyroidism

etiology of hypothyroidism

deficiency in thyroid hormone secretion

types of hypothyroidism

congenital and acquired

hypothyroidism is common in what age of dogs

young to middle aged dogs

hypothyroidism can be observed in what species

• dogs

• cats

• cattle

• sheep

• goat

• poultry

• horse

hypothyroidism

dog breeds

• high risk

• moderately at risk

• low risk

high risk

• edit

moderately at risk

• shetland sheepdog

• miniature schnauzer

• beagle

• dachshund

• pomeranian

• cocker spaniel

• airedale terrier

low risk

• German shepherd

• mixed breed

types of congenital hypothyroidism in dogs

• primary congenital hypothyroidism

• secondary congenital hypothyroidism

etiology of primary congenital hypothyroidism

• thyroid dysgenesis

  • thyroid hypoplasia, athyreosis

• dyhormonogenesis

  • inherent inability to synthesize T₃ and T₄

• thyroid not responding to TSH

clinical signs of primary congenital hypothyroidism

• goiter

• underdeveloped long bones

  • epiphyseal dysgenesis

• short vertebral bodies

etiology of secondary congenital hypothyroidism

• cystic rathke’s pocket

  • congenital deficiency in TSH

breed predilection of secondary congenital hypothyroidism

• giant schnauzers

• german shepherd

clinical signs of secondary congenital hypothyroidism

• pituitary dwarfism

• disproportionate dwarfism

• lethargy

• constipation

• gait abnormalities

types of acquired hypothyroidism in dogs

• primary acquired hypothyroidism

• secondary acquired hypothyroidism

• tertiary acquired hypothyroidism

• lymphocytic thyroiditis

• idiopathic thyroid follicular atrophy

• autoimmune thyroiditis

type of hypothyroidism of thyroid origin

primary acquired hypothyroidism

95% of clinical cases in animals

type of hypothyroidism of pituitary origin

secondary acquired hypothyroidism

rare in animals

type of hypothyroidism of hypothalamic origin

tertiary acquired hypothyroidism

rare in animals

etiology of primary acquired hypothyroidism

1. lymphocytic thyroiditis

2. idopathic thyroid follicular atrophy

3. autoimmune thyroiditis

4. neoplasm of thyroid

5. iodine deficiency

6. iatrogenic (drugs)

7. radioactive iodine treatment Tx

signs of primary acquired hypothyroidism

• insensitive to TSH

• high TSH; low

etiology of secondary acquired hypothyroidism

1. pituitary gland tumor

2. infection of the pituitary gland

3. inflammation of the pituitary gland

4. iatrogenic (drugs, hormones)

signs of secondary acquired hypothyroidism

• low TSH levels

• low T₃ and T₄

etiology of tertiary acquired hypothyroidism

• tumors of the hypothalamus

• trauma of the hypothalamus

• inflammation of the hypothalamus

signs of tertiary acquired hypothyroidism

• low TRH levels

• low TSH levels

• low T₃ and T₄

immune mediated thyroid atrophy

lymphocytic thyroiditis

similar to human hashimoto’s disease

lymphocytic thyroiditis

non-inflammatory destruction of the thyroid

idiopathic thyroid follicular atrophy

autoimmune destruction of the thyroid

autoimmune thyroiditis

production of autoantibodies against the thyroglobulin

lymphocytic thyroiditis

humoral & cell-mediated destruction of the thyroid

idiopathic thyroid follicular atrophy

lymphocytic thyroiditis (mechanism)

• diffused infiltration of lymphocytes, plasma cells and macrophages

• destruction of thyroid follicles and secondary fibrosis

idiopathic thyroid follicular atrophy

loss of thyroid parenchyma and replacement by adipose tissue

autoimmune thyroiditis is prevalent in what dog breeds

• doberman

• pinscher

• beagle

• akita

• golden retriever

types of hypothyroidism in cats

• primary congenital hypothyroidism

• primary acquired hypothyroidism

*secondary and tertiary congenital & acquired hypothyroidism not documented

etiology of primary congenital hypothyroidism (cats)

• thyroid dysgenesis

• dyshormonogenesis

• thyroid not responding to TSH

etiology of primary acquired hypothyroidism (cats)

• after radioactive iodine treatment Tx for hyperthyroidism

• surgical thyroidectomy

• use anti-thyroid drugs

common cause of cases in cats

primary acquired hypothyroidism

signs of primary congenital hypothyroidism (cats)

• insensitive to TSH

• high TSH

• low T₃

signs of primary acquired hypothyroidism (cats)

• insensitive to TSH

• high TSH

• low T₃ and T₄

goitrogenic substances mechanism of action

inhibits iodide trapping

goitrogenic substances

• thiocyanates

• complex anions

examples of thiocyanates

• cabbage

• lentils

• peanuts

• soybeans

• turnips

examples of complex anions

• perchlorate

• pernechnetate

• perhennate

• tetrafluoroborate

anti-thyroid drugs

• thiocarbamids

• propylthiouracil

• sulfonamides

thiocarbamids mechanism of action

inhibits peroxidase