Done By:Ahmed Mohammed Sayed Gad (235)khaled Abd Ul-Karim Daif (432)

THYROID GLAND

Head of department : Dr. Maha Gamal Supervised By: Dr. Maged Haron

Table of ContentIntroduction of thyroid Gland.

Historical background

Development of thyroid Gland .

Relations of Thyroid gland.

Histology of the Thyroid Gland

Thyroid Hormones.

Actions of thyroid Hormones.

Pituitary Gland.

Diseases found in Pituitary Gland.

Diagrams.

Functions of Pituitary Gland.

Introduction

Unique endocrine glandLocated superficially

Uses raw material – supplied

externally ( Iodine )

Stores the product (2

months)

Rich blood supply 5 ml/g/min

5 l/hr.

0.4% of body weight - 2% of

total blood flow

Historical background

Goiters were known long before the thyroid gland itself.

Hippocrates (460-337 BC) “...when glands of the neck become diseased

themselves, they become tubercular and produce struma....” (struma –

goiter).Hippocrates failed to differentiate between the thyroid and the

cervical glands

Gallen (130-200 AD) described operations on two boys by ignorant

physicians who removed tubercular nodes with their fingernails,

rendering one boy mute and the other semi-mute.

Leonardo Da Vinci is generally credited as the first to draw the thyroid

gland as an anatomical organ in 1508 AD

Andreas Vesalius (1514-1564) correctly described the anatomy of thyroid

gland.

Thomas Warton (1614- 1673) gave the gland its modern name of thyroid

Development

Starts from 3rd week of IUL -1st

endocrine gland to develop

Proliferation of cells from

caudal end of Thyroglossal

duct - endoderm

PF or C cells – Ultimibranchial

body – 4th/5th pharyngeal

pouch – neural crest cells

Applied Anatomy

Congenital thyroid disorders Aberrant thyroid tissue

Lingual thyroid

Thyroglossal cyst 50% close to or just inferior to body of

hyoid bone

Thyroglossal fistula – secondary to

rupture of cyst

Relations

Lobes: Δr in cross section – 3

surfaces: ant-lat, med & post.

Only posteromedial border is

prominent.

Med surface – 2 each; cartilage,

muscle, tubes & nerves.

Para thyroids lie in post. Surface

b/w 2 capsules.

Gland enlargement – extends

posteriorly & inferiorly.

Microscopic Structure

Stroma:

– Fibroelastic true

capsule -> septae ->

ill defined lobules ->

Pseudolobulated

– Septae: blood vs,

nerves lymphatics

– Intralobular loose CT

Follicles: arrangement of

cells in hollow spherical or

short cylindrical masses 0.2-

0.9 mm - Structural &

functional units

Filled with gel like substance

- colloid- Thyroglobulin

Simple Principal/Follicular

cells

Parafollicular or ‘C’ cells

Parenchyma

Principal/Follicular cells

Nuclei- Spherical, 1-2

nucleoli

Golgi, rER - prominent

Cytoplasm –

basophilic

Apical vacuoles

Microvilli

Thyroglobulin - Stored follicle – iodine

trapping and iodination - reuptake

(Scalloped margins) – lysosmes - broken

into T3 & T4 – secreted.

Parafollicular or Clear cells or ‘C’ cells

Lie beside follicle

Enclosed in same BM but not reaching

lumen

Larger, rounded & paler

Nucleus round /oval, eccentric

Secretory granules – Calcitonin (PTH

Antagonist

Thyroid hormones

Primary function of the thyroid -

production of T3, T4, and calcitonin

T3 & T4 – essential for normal growth,

development & metabolism

T4 -> T3 by peripheral organs like liver,

kidney, spleen

T3 is 4 - 10 X more active than T4

Hypothalamo – pitutary – thyroid axis

• T3 is 5 times more potent > T4

• Half life of T4 is 6-7 days and T3 is 1-2 days – hyper and hypothyroidism

• T4 is the major circulating hormone – bound more to plasma proteins

• T4 is less active and a precursor of T3 - the major mediator of physiological effects

• The term thyroid hormone is used to comprise both T4 plus T3

• T4 deiodination to T3 or reverse T3

• T3 & reverse T3 deiodination to three di-iodothyronines, deiodinated to two monoiodothyronines - (inactive)

Thyrocytes (follicular cells)

have four functions:

– collect and transport iodine

– they synthesize thyroglobulin

and secrete it into the colloid

– fix iodine to the thyroglobulin

to generate thyroid hormones

– remove the thyroid

hormones from thyroglobulin

and secrete them into the

circulation.

Synthesis of thyroid hormones

Thyroglobulin is synthesized in the rough endoplasmic reticulum and follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle by exocytosis.

Meanwhile, a sodium-iodide (Na/I) symporter pumps iodide (I-) actively into the cell, which previously has crossed the endothelium by largely unknown mechanisms.

This iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a purportedly passive manner

In the colloid, iodide (I-) is oxidized to iodine (I0) by an enzyme called thyroid peroxidase.

Iodine (I0) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain (in total containing approximately 120 tyrosyl residues).

In conjugation, adjacent tyrosyl residues are paired together. The entire complex re-enters the follicular cell by endocytosis. Proteolysis by various proteases liberates thyroxine and

triiodothyronine molecules, which enters the blood by largely unknown mechanisms.

T3 Vs T4

• Highly bound to plasma protein but only 0.04% of T3 and 0.2% T4 are in free form

• All Protein Bound Iodine (PBI) in plasma is thyroid hormone – 95% is T4

• Main Plasma proteins for T4 are – TGB, TBP and albumin• Only free form of hormone is available for action and metabolism• Metabolism occurs by deiodination and conjugation, mainly in

liver and kidneys• T4 is deiodinated to T3 (active) or rT3 (inactive) by deiodination• Conjugated products are excreted in bile – enterohepatic

circulation• Finally excreted in urine

Calcitonin • 32 - aa linear polypeptide - C cells

• Not under control of hypothalamus or pitutary

• Secretion -> Ca2+, gastrin and pentagastrin

• not essential for life – no replacement required

following thyroidectomy unlike parathyroids.

• antagonist to PTH - reduces Ca2+ level

• Inhibits: Ca2+ absorption by intestine, osteoclast

activity in bone & renal tubular cell reabsorption

of Ca2+

• Agonist to PTH -> Inhibits phosphate reabsorption

by the kidney

• Used clinically for Tt of hypercalcemia &

osteoporosis

Action of thyroid hormones

On Growth and development• Normal growth and development of organism• DNA transcription, critical control of protein synthesis and translation

of genetic code• T3 – Tadpole to frog transformation• Brain development• Irreversible mental retardation (cretinism) in absence of thyroid

hormones during active neurogenesis (upto 6 month postpartum)• Severe morphological alteration in brain• Supplementation during first 2 weeks of life prevent development of

brain changes

Action of thyroid hormones

On Metabolism:• Lipid: Induce lipolysis (catecholamines), ↑ free plasma fatty

acid and all phases of cholesterol metabolism enhanced (bile acid more)– Hyperthyroidism – hypercholesterolemia

• Carbohydrate:Stimulation of carbohydrate metbolism, glycogenolysis, gluconeogenesis– Hyperthyroidism – diabetes-like state

• Protein: Certain protein synthesis increased but overall catabolic action – negative nitrogen balance– Hyperthyroidism – Weight loss and wasting

Action of thyroid hormones

Calorigenic & CVS Effects• T3 and T4 increases BMR by stimulation of cellular metabolism –

maintenance of body temperature• Brain, gonads and spleen unresponsive to calorigenic effects• Hyperdynamic state of circulation - due to direct CVS action and ↑

peripheral demand• Hyperthyroidism: tachycardia, ↑ SV, ↑ TPR• Hypothyrodism: bradycardia, ↓ cardic index, pericardial effusion , ↓ TPR,

↓ PP

Others: Nervous system – mental retardation, GIT – Increased gut motility, Haematopoiesis – anaemia

thyroid disturbance

Blood tests

• Thyroid Function Test• mesure serum TSH• free T4 & free T3

• Thyroid Autoantibody estimation .• Antithyroid Abthyroid microsomal Ab (TMAb) 95% of patients

with Hashimoto.D

• Thyroglobulin Ab (TGAb) 60% of patients with Hashimoto.D

• Ab against thyroid TSH receptors (TRAbs) seen in patients with Graves . D

• Serum thyrogloublin …used in follow up of metastatic thyroid carcinoma after tyhyroidectomy

X- rays

• Plain radiograph chest & thoracic inlet ….to detect retrosternal thyroid extension ,thyroid

calcification ,bony or mediastinal LN & lung metastases

• CT scan……For detecting regional &distant metasasis from thyroid

cancr

• MRI….diagnosis of cervical LN metastasis

Ultrasound• Used to establish the size & shape of the gland .• May indicate if nodules are single or multiple.• It will distinguish between cystic & solid lesions.

(intrathyroid lesion)

Radioisotpe scan

• Single or multiple nodules .• Over functioning (hot nodules) or non-

functioning (cold nodules) • 20% of cold nodules are malignant• Hot nodules ….rarely malignant

Hot nCold n

Hyperthyroidism Vs. thyrotoxicosis

Graves’ disease—an autoimmune disease

involving autoantibody stimulation of TSH

receptors.

Toxic multinodular goiter — nodular

enlargement of the thyroid in the elderly.

Toxic nodule—autonomously functioning

thyroid nodule; most are adenomas

Lymphocytic thyroiditis /Hashimoto’s

thyroiditis—inflammation causes release of

stored hormones (followed by hypothyroid

phase).

Subacute (de Quervain’s) thyroiditis —

thyroiditis associated with a painful goiter.

• Hyperthyroidism is the overproduction of thyroid hormones by an overactive thyroid

• Thyrotoxicosis is a syndrome of excess of thyroid hormones in the blood, causing a variety of symptoms that include rapid heart beat, sweating, anxiety, and tremor

• Causes of thyrotoxicosis:1. Most common cause (70%) is Grave`s disease: overproduction

of thyroid hormone by the entire gland (autoimune and IgG to TSH receptors)

2. Toxic nodular or multinodular goiter: lumps in the thyroid gland and overproduction (independent of TSH)

3. Thyroiditis: Temporary symptoms of hyperthyroidism (leakage)4. Tablet intake (thyroid hormone) in excess – exogenous

• Laboratory: High T3 and T4 + low TSH

Hyperthyroidism - definition

• Skin flushed, warm, moist• Tremor• Heat intolerance (Preference to cold)• Exphthalmous (grave`s disease)• Muscles weak• Heart rate rapid, heart beat forceful, bounding arterial pulses• ↑ energy expenditure & appetite, loss of weight• Insomnia, anxiety, apprehension• Diarrhoea• Angina, arrhythmia and heart failure• Muscular wasting, thyroid myopathy• Untreated thyrotoxicosis – osteoporosis

Hyperthyroidism – symptoms

Antithyroid drugs:1. Propyl thiouracil (PTU) = 100-300mg TID2. Methimazole (Tapazole) = 10-20 TID then OD3. Carbimazole = 40mg OD

• Inhibits the organic binding of iodine and coupling of iodotyrosine• PTU can also lower conversion of T4 to T3; it can also decrease thyroid

autoantibody levels

• Radioiodine: Diffuse, Nodular goiter– Decrease size

• Surgery: Young pt. with relapsing thyrotoxiocsis, obstruction of neck vein or trachea

Choice of treatment forhyperthyroidism

Multinodular

Endemic

Hypothyroidism

Myxedema Cretinism

Endemic or sporadic• Endemic - extreme iodine deficiency• Sporadic – failure of thyroid to develop normally or defective

hormone synthesis• Detectable at birth, may not be recognized until 3-5 mths of

age• Dwarfism ,mental retardation, short extremities, inactive,

listless, puffy & expressionless face, enlarged tongue, skin yellow, dry & cool, bradycardia, low body temp., late teeth eruption, delayed closure of fontanelle

• Poor appetite, feeding slow, constipation, umbilical hernia• Iodine replacement institution prior to pregnancy till end of

2nd trimester

Cretinism

• T4 10-15 μg/kg daily• T4 levels normalize within 1-2 weeks• Adjust dosage at 4-6 weeks in first 6 months

and then at 2 month during 6 to 18 month.• Thereafter, 3 - 6 month to maintain T4 10 -16

μg/dL and TSH normal range

Cretinism - treatment

• Causes: – thyroiditis or thyroidectomy– Drugs: I131, iodides, lithium and amiodarone– May be simple goitre or idiopathic

• Face: expressionless, puffy, pallid• Skin: cold, dry, scaly scalp• Hair: coarse, brittle, sparse• Fingernails: thickened, brittle• Voice: husky, low pitched, slow speech• Poor appetite, constipation• Voluntary muscles weak and relaxation of deep tendon reflexes delayed• Dilated heart, pericardial effusion, ascites, Hyperlipidemia, anaemia• Cold intolerance(Subclinical hypothyroidism)

Adult Hypothyroidism

• Severe, long-standing hypothyroidism• Serious medical emergency, mortality rate high (60%) despite

early diagnosis and treatment• Elderly patient during winter months• Pulmonary infections, CVA, CHF precipitate coma.• Sedative, narcotics, antidepressants and tranquillizers• Profound hypothermia, respiratory depression, unconscious,

bradycardia, delayed reflexes, dry skin• Estimate Serum free thyroxine index & TSH • LP – High proteins

Myxoedema Coma

• Ventilatory support• Rewarming• Correct hyponatremia• IV steroid• IV T4 (200 – 300 μg) bolus• IV T4 (100 μg ) after 24 hrs• Oral T4 (500 μg) < 50 yrs plus inj.T3 IV 10 μg 8 hrly. till

patient is conscious• Do not exceed T4 > 500 μg / day or T3 > 75 μg / day

Myxoedema Coma - treatment

GOITER

• Enlargement of the thyroid gland in a euthyroid pt not associated with neoplasm or inflammation:

1. Familial:• Inherited enzymatic defect (dyshormonogenesis)• Autosomal recessive• Hypothyroidism / euthyroid

2. Endemic:• Iodine deficiency

3. Sporadic:• No definite cause, excludes goiter caused by

thyroiditis and neoplasm as well as endemic goiter

GOITERPathology:

• May be diffusely enlarged and smooth, or enlarged markedly nodular

• Nodules are filled w/ gelatinous, colloid rich material and scattered between areas of normal thyroid tissues

• With areas of degeneration, hemorrhage and calcification.

GOITERS/Sx:• Asymptomatic usually• Pressure symptoms usually

1. Dysphagia2. Dyspnea3. Paralysis of recurrent laryngeal

nerve4. Sudden pain associated with

rapid enlargement of the gland ---> hemorrhage into a colloid nodule or cyst

5. Superior venacaval syndrome due retro-sternal extension causing facial flushing that is accentuated by raising his arm above the head (Pemberton’s sign).

Thyroid lumps

Thyroid cysts.

Nodule of multinodular

goiter.

Follicular adenoma.

Malignancy – 20%

• Papillary

• Follicular

• Medullary – C cells -> PNPS

• Malignant lymphoma

• Anaplastic

Applied anatomy

Thyroidectomy

lobe, subtotal, total

Transverse skin incision 2.5 cm

above jugular notch

Gap b/w ST & SH opened up –

trachea & isthmus exposed

Muscles retracted laterally or

divided at upper ends –

preserve nerve supply from

ansa cervicalis

Later lobes displayed

Plane of cleavage: b/w 2 capsules

Vessels ligated and divided – STA

right at the lower pole; ITA at

some distance from lower pole

During removal of gland

Ligament of berry released – RLN

injury

Wedge shaped areas on post-

medial surface is left behind- PT

Complications

ELN injury – CT paralysis,

hoarseness of voice,

temporary until the

other side takes over

RLN injury – all intrinsic

muscles except CT

paralyzed, no recovery