THE THYROID GLAND

Anatomical Structure

Gross Anatomy• Located in neck

– lobes– isthmus

• Relations– Larynx– Trachea– Recurrent laryngeal

nerves– Parathyroid glands– Carotid sheath

• Blood supply– Sup. thyroidal a.– Inf. thyroidal a.

Embryology

• Thyroglossal duct• Foramen caecum• Thyroid cysts

Histology

• Thyroid follicles– Simple cuboidal-

columnar

• Colloid– Thyroglobulin

• Rich vascularization

• Colloid– Thyroglobulin

• Rich vascularization

• Parafollicular cells• Parafollicular cells

Thyroid Hormone

• 3-Monoiodotyrosine (MIT)

• 3,5-Diiodotyrosine (DIT)• 3,5-Diiodotyrosine (DIT)

• 3,5,3’-Triiodothyronine (T3)• 3,5,3’-Triiodothyronine (T3)

• Tyrosine• Tyrosine

• 3,5,3’,5’-Tetraiodothyronine (T4)• 3,5,3’,5’-Tetraiodothyronine (T4)

• 3,3’,5’-Triiodothyronine (Reverse T3, rT3) • 3,3’,5’-Triiodothyronine (Reverse T3, rT3)

Thyroid Hormone Synthesis

• Tyrosine in Thyroglobulin

CH3CHCH3CH

NN

C=OC=O

RCRC

C=OC=O

RCRC

OH-OH-

Thyroid Hormone Synthesis

• Thyroperoxidase attaches Iodine to 3 position---MIT

CH3CHCH3CH

NN

C=OC=O

RCRC

C=OC=O

RCRC

II

OH-OH-

Thyroid Hormone Synthesis

• Thyroperoxidase attaches Iodine to 5 position---DIT

CH3CHCH3CH

NN

C=OC=O

RCRC

C=OC=O

RCRC

II

II

OH-OH-

Thyroid Hormone Synthesis

• Thyroperoxidase attaches ring from one DIT to adjacent DIT = Thyroxine (T4)

CH3CHCH3CH

NN

C=OC=O

RCRC

C=OC=O

RCRC

II

II

OO

II

II

OH-OH-

Thyroid Hormone Synthesis

• Thyroperoxidase attaches ring from one MIT to adjacent DIT = Triiodothyronine (T3)

CH3CHCH3CH

NN

C=OC=O

RCRC

C=OC=O

RCRC

II

II

OO

II

OH-OH-

Thyroid Hormone Synthesis

• Thyroperoxidase attaches ring from one DIT to adjacent MIT = Reverse T3

CH3CHCH3CH

NN

C=OC=O

RCRC

C=OC=O

RCRC

II

OO

II

II

OH-OH-

Thyroid Hormone Biosynthesis

• Iodine pump/trap• Thyroglobulin• Iodination• Thyronine• Thyroglobulin

pinocytosis• Hormone release

Thyroid hormone transport

• Thyroid binding globulin (TBG)– Highest affinity

• Thyroid binding prealbumin– Intermediate affinity

• Albumin– Low affinity, High capacity

Thyroid Hormone

• T3 is 3-8X more active than T4

• Thyroid Gland produces 10X T4 to T3

• 5’-deiodinase– Converts T4 to T3 in Target Tissues

– Primarily responsible for circulating levels of T3

• T4 probably a pro-hormone

• Thyroid hormone receptor– Nuclear

Physiological effects of thyroid hormone

• Increases oxygen consumption and heat production

• Positive chronotropic and inotropic effects on heart

• Increase sensitivity to adrenergic effectors– Up-regulates -adrenergic receptors

• Increase gut motility

• Increase bone turnover

Physiological effects of thyroid hormone

• Increases reflex response

• Increase hepatic glycogenolysis and gluconeogenesis

• Stimulates lipolysis

• Developmental effects– Growth– Brain development

REGULATION OF THE THYROID GLAND

THYROIDGLAND

THYROIDGLAND

ANTERIORPITUITARYANTERIORPITUITARY

HYPOTHALAMUSHYPOTHALAMUS

TRHTRH

TSHTSHT4T4

LONG-LOOPFEEDBACK

LONG-LOOPFEEDBACK

T3 & T4T3 & T4

TSHTSH

SHORT-LOOPFEEDBACK

SHORT-LOOPFEEDBACK

BODYTEMP.BODYTEMP.

EXPOSURETO COLD

EXPOSURETO COLD

STARVATIONSTARVATION

TSH-RECEPTOR

ANTIBODIES

TSH-RECEPTOR

ANTIBODIES

THYROID AUTOREGULATION

THYROID AUTOREGULATION

HIGHSERUM IODIDE

HIGHSERUM IODIDE

HIGHER BRAINCENTERS

HIGHER BRAINCENTERS

GOITROGENSGOITROGENS

Endocrinopathies

Hyperthyroidism

• Level of the defect (1, 2, 3)

• Thyrotoxicosis• Graves’ disease• Toxic Adenoma• Toxic Multinodular

Goiter• Chronic Thyroiditis

Hyperthyroidism Symptoms • Tachycardia/arrhythmia• Muscle tremors• Hyperreflexia• Increased core & skin

temp./ Heat Intolerant• Exophthalmos• Muscle wasting• Loose stool• Osteoporosis• Hair loss• Oligo-/amenorrhea• Irritability, Restlessness

Hypothyroidism

• 1, 2, 3 • Newborn

– Cretinism– Lack of myelination

• Children– Retarded Growth– Disproportionate

Hypothyroidism

• Adult– Muscle weakness– Mental slowness– Tired/fatigued– Cold– Slowed intestinal

peristalsis– Impaired renal

function– Anemia– Myxedema

Myxedema

Causes of Hypothyroidism

• Iodine deficiency

• Hashimoto’s Disease– Initially hyperthyroid

• Post-ablative

• 5’-Deiodinase Deficiency

Thyroid hormone resistance

• Mutation of the receptor.

• Characterized by high blood levels of both TSH and Thyroid hormones

Non-toxic goiter

• Iodine deficiency

Thyroiditis

• Subacute thyroiditis

• Chronic thyroiditis (Hashimoto’s Disease)– Autoimmune

Euthyroid Syndrome

• Patient presents and complains of hypothyroid type symptoms

• Levels of Thyroid hormones (free & total), & TSH in low normal range.

• May be due to a 5’-deiodinase deficiency

Allopathic treatments for thyroid disorders

• Hyperthyroidism– Goitrogens– Partial thyroidectomy– Radiothyroidectomy

• Hypothyroidism– Hormone Replacement