Thyroid Function and Disorders

8/6/2019 Thyroid Function and Disorders

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THYROIDFUNCTIONAND

DISORDERS

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Introduction

Largest endocrine gland

Secrets three hormonesThyroxineTri iodothyronineCalcitonin

Thyroid hormone affect each and every

cells in the body

In India at Sub-Himalayan regions thyroidhormone deficiency leads to mental

retardation and goiter 33


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Anatomy

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Second level Third level

Fourth level Fifth level

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Largest endocrine gland

15-25 gm in weight in adult

Bilobed structure joined by isthmus

Located on either side of trachea

Below larynx

Highly vascular structure

Blood flow 400-600ml/100gm/min

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HISTOLOGY

made up of an aggregation of severalfollicles

Functional unit of thyroid gland

Outer rim made up of a single layer offollicular epithelium

Rest on basement membrane

Surrounded by a rich capillary plexus.

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Click to edit Master text stylesSecond level

Third level Fourth level

Fifth level

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HISTOLOGYClick to edit Master text stylesSecond level


Fifth level

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COLLOID

Homogenous material

Fill in each cavity of follicle

Follicle stimulated- depleted colloidFollicle unstimulated- accumulate colloid

Constitute- thyroglobulin

Glycoprotin MW of 660,000

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PLASMA

T4T3

TISSUE

GUTIODIDE

THYROIDThyroglobulinIodine

T3 & T4

Foodiodine

T4 conjugateT3 sulphate

faeces

urinekidney

plasma

iodine

liver

IODINE CYCLE


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Biosynthesis thyroidhormones

1)Synthesis and secretion of thyroglobulin

2)Iodide trapping3)Oxidation of iodide

4)Organification of thyroglobulin

5)Couplig reaction

6)Storage

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STAGES IN FORMATION OF THYROIDHORMONES

1. IODIDE PUMP( iodide trapping)

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1. OXIDATION OF THE IODIDE ION promoted by enzymeperoxidase

2. IODINATION OF TYROSINEAND FORMATION OF

THYROID HORMONES ORGANIFICATION Iodinaseenzyme

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Monoiodotyrosine and diiodotyrosine 1616


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4. COUPLING

Monoiodotyrosine + diiodotyrosine = T3Diiodotyrosine + diiodotyrosine = T4

Release of T3 and T4 into circulating blood Proteinase enzyme

Transport of T3 and T4 combine with proteins

a.thyroxine binding globulunb.thyroxine binding pre-albuminc.albumin

T4 released to tissues every 6 days and T3 in one day

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storage

Stored in lumen of follicle in combinationwith TG

Each TG molecule contains 30 molecule of

thyroxine and few molecule oftriiodothyronine

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Hormone secretion

Endocytosis-TG retrived from the lumen of follicle byepithelial cell through endocytosis

-Colloid enters in cytoplasm in form ofcolloid droplets

-Moves from cytoplasm to basal

membraneProteolysis-colloid droplets fuses with the lysosomesvesicle-contains proteolytic enzymes 1919


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T4

T3

85% (peripheral conversion)

15%

Protein binding + 0.03% free T4

Protein binding + 0.3% free T3

(10-20x less than T4)

Normal Daily Thyroid Secretion Rate:T4 = 100 ug/dayT3 = 6 ug/day

( ratio T4:T3 = 14:1 )

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DISTRIBUTIONOF THYROID

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Metabolism and excretion ofthyroid hormone

Deiodination

Decarboxilation

Conjugation

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Regulation of thyroidhormone secretion

Hypothalamus-anterior pitutary thyroid axis

Autoregulation of thyroid gland

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1. TSH or Thyrotropin ( from the Anterior Pituitary Gland)

Increases Thyroid Secretion

Effects on the thyroid gland: a. Increased proteolysis of the thyroglobulin

b. Increased activity of the iodide pumpc. Increased iodination of tyrosined. Increased size and increased secretory activity of the

thyroid cellse. Increased number of thyroid cells


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TSH INCREASES ALL KNOWNSECRETORY ACTIVITIESOF THETHYROID GLAND CELLS

Cyclic Adenosine Monophosphate

Mediates the Stimulatory effect of TSH-cAMP act as second messengerin

many target tissues


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Th Th id F lli l


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The Thyroid Follicles

Figure 18.12b2828


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Autoregulation of

thyroid glandRegulated by food iodine contentDeficiency of iodine content in the dietiodine trapping mechanism become super

efficient

Excess of iodine in the food then iodinetrapping become less efficient

Organification of excess of amount ofiodine does not occur

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Wolff-Chaikoff Effect

Increasing doses of I- increasehormone synthesis initially

Higher doses cause cessation

of hormone formation.This effect is countered by theIodide leak from normal thyroidtissue.

Patients with autoimmunethyroiditis may fail to adapt andbecome hypothyroid.



Fifth level


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Jod-Basedow Effect

Opposite of the Wolff-Chaikoff effect

Excessive iodine loads induce hyperthyroidism

Observed in hyperthyroid disease processes

Graves diseaseToxic multinodular goiter

Toxic adenoma

This effect may lead to symptomatic thyrotoxicosis inpatients who receive large iodine doses from

Dietary changes

Contrast administration

Iodine containing medication (Amiodarone)


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MECHANISMS OF THYROID

HORMONE ACTION

Act by binding to Nuclear receptors, termed

Thyroid Hormone Receptors (TRs), Increasing

synthesis of proteins

At mitochondrial level increases number and

activity to increasing ATP production

At Cell membrane increases ions and

substrates transmembrane flux

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Thyroxine and its precursors:


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Thyroxine and its precursors:Activity

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FUNCTIONS OFTHYROID GLAND

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Effects on growth and tissuedevelopment

Body growth and skeletal maturation

- Direct : increases the protein synthesis

and enzymes

- Indirect : increases growth hormone andsomatomedins

Tissue differentiation and maturation

Development of nervous tissue-proper axonal and dendritic development 3535


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Effect on BMR

the basal rate of O2 consumption the heat production in most tissues except.

The brain, retina, gonads, lungs and spleen.

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Effect on metabolism

On carbohydrate metabolism

On fat

On protein

On vitamin metabolism

On water and electrolyte

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Carbohydrate metabolism

Two effects

1)hypoglycemia

Increases

Glucose consumption by peripheral tissues

Glucose uptake by the cells

Insulin secretion

2)hyperglycemia

Increses

Glucose absorption of the GI tract

Glycolysis

Gluconeogenesis

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Fat metabolism

Increase lipolysis and lipid mobilization with:

Cholesterol

Triglycerides

Free fatty acids

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Protein metabolism

Physiologically anabolic-increases protein synthesis

Hyper secretion causes protein catabolism

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Effect on vitaminmetabolism

Increases need for vitamins

- important part of enzymes and

coenzymes

Necessary for conversion of -carotene tovit A

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Respiratory effect

O2 consumption

CO2 and heat production

Rate and depth of respiration

O2 dissociation curve shift to right

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Effect on nervoussystem

cell membrane permeability to Na and K,for the action potential

neurotransmitter synthesis

receptors for neurotransmitters

enzymes that destroy neurotransmitters

Increase speed and amplitude ofperipheral nerve reflexes

Enhances wakefulness and alertness

Enhances memory and learning capacity 4343


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Effect on other endocrineglands

rate of secretion of most of otherendocrine gland

tissue demand for hormones

rate of inactivation of adrenoglucocorticoids so ACTHsecretion increase

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Effect on kidney

blood flow

GFR

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Effects ongastrointestinal tract

Thyroid hormone leads to increases in

- appetite

- food intake

- rate of secretion of digestive juices

- motility of gastrointestinal tract 4646


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Effects Of ThyroidHormones On TheCardiovascular System heart rate

force of cardiac muscle contractions

stroke volume

Cardiac output

U -re ulate catecholamine rece tors 4747


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Effects Of The ThyroidHormones On TheReproductive SystemRequired for normal follicular developmentand ovulation in the female

Required for the normal maintenance of

pregnancy

Required for normal spermatogenesis inthe male

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RELATION WITHCATECHOLAMINECatecholamine and thyroid hormone both- BMR- stimulate CNS

- heart rate and force of contractionCatecholamine can not increases theBMR in absence of thyroid hormone-it potentiates the catecholamine action

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Disorders OF

THYROID GLAND

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When the Thyroid

Doesnt Work

Hyperthyroidism

Too Much Thyroid Hormone

Metabolism Speeds Up

Hypothyroidism

Too Little Thyroid Hormone

Metabolism Slows Down

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Thyroid Evaluation


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Thyroid EvaluationClick to edit Master text stylesSecond level


Fifth level

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?Hyperthyroidism

O S


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HYPERTHYROIDISM

Hyperthyroidism is present when thethyroid gland is over secreting

hormones.

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Causes ofHyperthyroidism

Most common causes

Graves disease

Toxic multinodular goiter

Autonomously functioningnodule

Rarer causes

Thyroiditis or other causes ofdestruction

Thyrotoxicosis factitia

Iodine excess (Jod-Basedowphenomenon)

Struma ovarii

Secondary causes (TSH orHCG)

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H th idi


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HyperthyroidismSymptoms

Hyperactivity/ irritability/ dysphoria

Heat intolerance and sweating

Palpitations

Fatigue and weakness

Weight loss with increase of appetite

Diarrhoea

PolyuriaOligomenorrhoea, loss of libido

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H th idi Si


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Hyperthyroidism Signs



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Tachycardia (AF)

Tremor

Goiter

Warm moist skinProximal muscleweakness

Lid retraction or lag

Gynecomastia

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Complications ofHyperthyroidism

Thyroid Storm or Crisis

Acute aggravation of S & S

Heart failure

Shock

Hyperthermia

Tachycardia, Hypertension

Confusion

Seizures Coma

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Treatment ofhyperthyroidism

A n t i t

B e t a

M E D

S u b t o

S U R

R a d i o

L u g o

I O D

H Y P E

T y p e

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A ti th id d


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Anti thyroid drugs

Chemically block hormone synthesis

Enhance evolution to remission

Best indicated for children,adolescents,young

adults and pregnant women.Propylthiouracil-100-150mg every 6or 8 hrs

Carbimazole- 40-60mg daily initially for 3weeks,then reduce to 20-40mg for another 8

weeks and maintain at 5-20mg daily for 18-24months.

Methimazole-active metabolite of Carbimazole

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Duration of treatment

18-24 months

Side effects- Rash

Leukopenia

Agranulocytosis

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Control of adrenergicsymptomsAdrenergic antagonists:

Propranolol-40-120mg/day

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Surgical Treatment ofHyperthyroidism

Procedure: -thyroidectomysubtotal thyroidectomy

hemithyroidectomy

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Graves Disease

Autoimmune disorder

Abs directed against TSH receptor withintrinsic activity.

Responsible for 60-80% of Thyrotoxicosis

More common in women

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Eye Signs



Fifth level

N - no signs or symptoms

O only signs (lid retraction or lag)no symptoms

S soft tissue involvement (peri-orbital oedema)

P proptosis (>22 mm)(Hertls test)E extra ocular muscle involvement(diplopia)

C corneal involvement (keratitis)

S sight loss (compression of theoptic nerve)

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Other Manifestations


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Other Manifestations

Pretibial myxoedema

Thyroid acropathy

OnycholysisThyroid enlargement witha bruit frequently audibleover the thyroid

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Diagnosis

TSH , free T4 Thyroid auto antibodies

Nuclear thyroidscintigraphy (I123, Tc99)

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Treatment


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Treatment

Reduce thyroid hormone production or reducethe amount of thyroid tissue

Antithyroid drugs: propyl-thiouracil, carbimazole

RadioiodineSubtotal thyroidectomy relapse after antithyroidtherapy, pregnancy, young people?

Symptomatic treatment

Propranolol

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Hypothyroidism


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Hypothyroidism is present when the thyroidgland is producing little or no thyroidhormones. Thus slowing things down....

Hypothyroidism


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Causes of Hypothyroidism

Autoimmunehypothyroidism(Hashimotos, atrophicthyroiditis)

Iatrogenic(I123treatment,thyroidectomy, externalirradiation of the neck)

Drugs: iodine excess,lithium, antithyroiddrugs, etc

Iodine deficiency Infiltrative disorders of

the thyroid: amyloidosis,sarcoidosis,haemochromatosis, scleroderma

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Symptoms of Hypothyroidism


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Cold intoleranceSlow digestion

Weight gain

FatigueThin, coarse hair

Brittle fingernails

Muscle achesDizziness

Ringing in earsNumbness

Carpal tunnel

Poor memorySkin changes

Voice changes

Milky dischargefrom breasts

Symptoms of Hypothyroidism

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Hypothyroidism Signs

Dry skin, cool extremities

Puffy face, hands and feet

Delayed tendon reflex

relaxation Carpal tunnel syndrome

Bradycardia

Diffuse alopecia

Serous cavity effusions

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How to Rememberthe Signs and Symptoms of

HypothyroidismSleepiness, Fatigue, LethargyLoss of Memory, Trouble Concentrating

Unusually Dry, Coarse Skin

Goiter (Enlarged Thyroid)

Gradual Personality Change, Depression

Increase in Weight, Bloating or Puffiness (Edema)

Sensitivity to Cold

Hair Loss, Sparseness of Hair

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Lab Investigations of


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Lab Investigations ofHypothyroidism

TSH , free T4 Ultrasound of thyroid little value

Thyroid scintigraphy little value

Anti thyroid antibodies anti-TPO

S-CK , s-Chol , s-Triglyseride

Normochromic or macrocytic anemia

ECG: Bradycardia with small QRS complexes

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Myxedema


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Myxedema

Usually appears at the age of 40 yrs

Caused by1) thyroid deficiency due to

-thyroidectomy-neoplasm-chronic thyroiditis-radio-iodine therapy

2)Pitutary deficiency of TSH due to-tumours

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Sign and symptoms


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Sign and symptoms

Skin dry, rough, thick

Facial puffiness

Loss of hair

Husky voice

Intolerance to cold & hypothermia

Bradycardia, low voltage ECGFatigue, extreme somnolence

Poor memory, intellectual deterioration

Consti ation and anorexia 7575


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Fifth level

Treatment


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Treatment

Levothyroxine- altroxine tab given orally

Triiodothyronine for myxedema coma

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CRETINISM


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CRETINISMCaused by extreme hypothyroidism during fetal

life, infancy or childhood.

Characteristics:

a. Failure to growb. Mental retardationc. Skeletal growth characteristically moreinhibited than soft tissue growth

- child is obese, stocky and short appearance-tongue becomes large in relation to

skeletal growth

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CAUSES:

1. Congenital Cretinism results from congenitallack of a thyroid gland failure of thyroid glandto produce thyroid hormone

2.Endemic Cretinism iodine lack in the diet

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Goiter


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Enlargement of the thyroid gland is knownas the goiter-may be associated with the normalthyroid function, hypothyroid andhyperthyroidism.

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Endemic goiter


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Endemic goiter

also known as simple goiterdue to iodine deficiency in diet common

in region like Alps,Himalayan region

Lack of iodineDecreases thyroid homone in blood

Increases TSH secretion

Large amount of colloid formation

Increases size of thyroid

Common in female during puberty,8181

Idiopathic non-toxic


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Idiopathic non-toxiccolloid goiter

- iodine in the diet is normal-TSH secretion is depress which may bedue toa) mild thyroiditis

b) hereditary abnormal enzyme systemwhich are require for TSH synthesis

c) presence of goiterogenic substance indiet

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Hashimotos Thyroiditis


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Hashimoto s Thyroiditis

Common cause of goiter and hypothyroidism

Physical

Painless diffuse goiter

Lab studies

Hypothyroidism

Anti TPO antibodies (90%)

Anti Thyroglobulin antibodies (20-50%)

Acute Hyperthyroidism (5%)

Treatment

Levothyroxine if hypothyroid

Thyroid suppression (levothyroxine) to decrease goiter size

Contraindications

Stop therapy if no resolution noted

Surgery for compression or pain.

Subacute Thyroiditis


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Subacute ThyroiditisDeQuervains, Granulomatous

Most common cause of painfulthyroiditis

Often follows a URI

FNA may reveal multinuleatedgiant cells or granulomatous

change.Course

Pain and thyrotoxicosis (3-6 weeks)

Asymptomatic euthyroidism

Hypothyroid period (weeks to months)

Recovery (complete in 95% after 4-6months)



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Acute Thyroiditis


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Acute Thyroiditis

Causes68% Bacterial (S. aureus, S. pyogenes)

15% Fungal

9% Mycobacterial

May occur secondary to

Pyriform sinus fistulae

Pharyngeal space infections

Persistent Thyroglossal remnants

Thyroid surgery wound infections (rare)

More common in HIV

Acute Thyroiditis


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Acute Thyroiditis

DiagnosisWarm, tender, enlarged thyroid

FNA to drain abscess, obtain culture

RAIU normal (versus decreased in DeQuervains)

CT or US if infected TGDC suspected

Treatment

High mortality without prompt treatment

IV Antibiotics

Nafcillin / Gentamycin or Rocephin for empiric therapy

Search for pyriform fistulae (BA swallow, endoscopy)

Recovery is usually complete

Riedels Thyroiditis


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Riedel s Thyroiditis

Rare disease involving fibrosis of the thyroid gland

Diagnosis

Thyroid antibodies are present in 2/3

Painless goiter woodyOpen biopsy often needed to diagnose

Associated with focal sclerosis syndromes (retroperitoneal, mediastinal,retroorbital, and sclerosing cholangitis)

TreatmentResection for compressive symptoms

Chemotherapy with Tamoxifen, Methotrexate, or steroids may be effective

Thyroid hormone only for symptoms of hypothyroidism


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Thyroid Function and Disorders

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