Thyroid Gland

Which microelement is essential for thyroid hormone synthesis?

Iodine – required for iodination of tyrosine residues in thyroglobulin to form T₃ and T₄.

How are thyroid hormones (TH) involved in cell function?

THs bind nuclear receptors, regulating transcription of genes that control metabolism, growth, and differentiation in nearly all cells.

Which factors regulate TH synthesis?

- TRH (from hypothalamus) → stimulates TSH release.

- TSH (from pituitary) → stimulates thyroid hormone production.

- Negative feedback from T₃/T₄ suppresses TRH and TSH.

- Additional modifiers: age, season, activity, diet, diseases, and drugs

Why are most THs in circulation bound to proteins?

- To prevent excessive hormone action.

- To reduce renal loss (prevent excretion in urine).

- To protect THs from metabolism.

- Only free THs are biologically active

What happens if TH concentrations are too low or too high?

- Low TH (hypothyroidism): ↓ metabolic rate, lethargy, weight gain, impaired growth/development.

- High TH (hyperthyroidism): ↑ metabolic rate, weight loss, tachycardia, hyperactivity.

During fetal development, why are THs essential?

They are crucial for tissue differentiation, especially in brain and skeletal development. Deficiency can cause irreversible developmental abnormalities

thyroid hormones

T3 and T4

Circulate mostly protein-bound (99%); only free fraction is active.

Contain iodine and are essential for growth, differentiation, and metabolism.

T3

T3 (triiodothyronine): active form.

T4

T4 (thyroxine): precursor/prohormone.

- Increase metabolic activity (↑ metabolic rate, O₂ consumption).

- Stimulate protein, fat, and carbohydrate catabolism.

- Essential for fetal development and growth.

- Regulate brain and skeletal differentiation, respiratory and cardiovascular function, reproductive function.

- Potentiate catecholamine effects.

List the biological targets of thyroid hormones.

Targets: virtually all cells (via nuclear receptors

List the factors that regulate thyroid hormones.

- HPT axis: TRH (hypothalamus) → TSH (pituitary) → T3/T4 (thyroid) with negative feedback.

- Physiological factors: age (higher in young), activity (higher with exercise), season (higher in cold), feeding (higher with high energy diet).

- Pathologic/Environmental factors: diseases (decrease TH), drugs (e.g., glucocorticoids, NSAIDs, sulfas → decrease TH), exogenous compounds (nitrates, thiocyanates → inhibit iodine uptake).

- Excess iodide: can cause hypo- or hyperthyroidism.

Thyroid Gland

Regulates tissue and energy metabolism as well as cell differentiation (and some calcium).

Free T3 and T4

Free (fT3, fT4) and bound to proteins (99% is bound).

Total T3 and T4

Important in growth, differentiation, and metabolism.

TRH

Thyrotropin-releasing hormone produced by hypothalamic neurons.

TSH

Thyroid-stimulating hormone produced by pituitary thyrotropes.

HPT Axis

Hypothalamus-Pituitary-Thyroid Axis, a regulatory system for thyroid hormones.

Thyroid Hormone Functions

Includes increasing metabolic activity, necessary for fetal development, and modulating other hormones.

Goiter

An enlargement of the thyroid gland that can affect respiratory and cardiovascular function.

Colloid

A substance in the thyroid follicles where thyroglobulin is iodinated.

Follicular cells

Cells in the thyroid that uptake iodine and synthesize thyroid hormones.

Parafollicular cells

Cells in the thyroid that produce calcitonin.

Sources of Iodine

Iodine is essential for the synthesis of thyroid hormones.

Deiodinases

Enzymes that convert T4 to T3 and regulate thyroid hormone activity.

Thyroglobulin

A protein secreted into the lumen of thyroid follicles for iodination.

NIS

Sodium/Iodine symporter that facilitates iodine uptake in follicular cells.

TH Transport

In blood, ~99% of thyroid hormones are bound to proteins like TBG and albumin.

TBG

Thyroid binding globulin, a protein that binds thyroid hormones in the blood.

TTR

Transthyretin, a protein that transports thyroid hormones in the blood.

Albumin

A protein in blood that also binds thyroid hormones.

Reverse T3

An inactive form of thyroid hormone that does not activate receptors.

Free THs

Thyroid hormones that are not bound to proteins and can activate receptors.

Proteolysis

The process of breaking down proteins, including thyroglobulin for hormone release.

TH Targets

Every cell in the body

Nuclear receptor

Use nuclear receptor

TH binding to receptor

↑↑ or ↓↓ transcription

Factors that affect thyroid function

Age, Season, Sex, Activity, Hormones, Breed, Exogenous compounds, Drugs, Feeding, Diseases

Age

The younger the higher THs

Season

The colder the higher - the hotter the lower THs

Sex

Depends on species, breed, size (e.g. higher in canine females)

Activity

Higher activity, higher THs

Hormones

Glucocorticoids decrease THs

Breed

Depends on species and size

Exogenous compounds

Most decrease THs (e.g. nitrates)

Drugs

Most decrease THs (e.g. NSAIDs, steroids, sulfas)

Feeding

High energy diets increase THs / fasting ↓↓

Diseases

Most diseases decrease THs

Hyperthyroidism

Too much TH → diseases or iatrogenic; increases metabolic activity

Hypothyroidism

Too little TH → diseases or iatrogenic; decreases metabolic activity

Consequences of ↓ TH

Diseases can decrease THs ≠ hypothyroidism

Thyroid hormones (TH)

Contain iodine

TH synthesis and secretion

Regulated by a negative feedback system (HPTA)

Importance of THs

Essential in development, differentiation, growth

Circulation of THs

Most in circulation is protein bound

Effects of THs

Mediated by intracellular/nuclear receptors

Disorders of THs

Common in veterinary practice