Faculty of Medicine Epidemiology of thyroid diseases - PowerPoint Presentation

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Faculty of Medicine Epidemiology of thyroid diseases

By Hatim JaberMD MPH JBCM PhD19 -12- 2018

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Presentation outlineTime

Introduction : Epidemiology and Overview of Thyroid Dysfunction11:00– 11:10Risk factors of Thyroid Dysfunction

11:10– 11:20

Iodine and thyroid

11:20– 11:30

Phenylketonuria

11:30– 11:50

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79 million newborns protected from losses in learning ability in the developing world

Source: SOWC 2004

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Overview of Thyroid DysfunctionHypothyroidismHyperthyroidism

Disorders of the thyroid are common and consist of 2 general presentations: changes in the size or shape of the gland or changes in secretion

of hormones from the gland.

Hypothyroidism refers to the inadequate production of thyroid hormone or

diminished stimulation of the thyroid by TSH;

hyperthyroidism

refers to those conditions in which thyroid hormones are excessively released due to gland hyperfunction.4

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Epidemiology of Thyroid Dysfunction Hypothyroidism and HyperthyroidismThyroid disorders are amongst the most prevalent of medical conditionsTheir manifestations vary considerably from area to area and are determined

principally by the availability of iodine in the diet.Almost one-third of the world's population lives in areas of iodine deficiencyIn areas where the daily iodine intake is below 50

μg, goitre

is usually endemic, and when the daily intake falls below 25

μg

,

hypothyroidism is seen

The prevalence of goitre in areas of severe iodine deficiency can be as high as 80 %.5

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Epidemiology of Thyroid Dysfunction Hypothyroidism and HyperthyroidismThe most common cause of thyroid disorders worldwide is iodine deficiency, leading to goitre

formation and hypothyroidism. In iodine-replete areas, most persons with thyroid disorders have autoimmune disease. The prevalence of thyroid dysfunction increases with age and diagnosis may be complicated in the older age group due to concomitant disease or therapy 6

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Epidemiology of Thyroid Dysfunction Hypothyroidism and HyperthyroidismThyroid Disorder and Diseases (Graves and Hashimotos) are growing worldwide.

200 million worldwide have a Thyroid Disorder…80% of all cases of Graves’ Disease are diagnosed in females20% of Thyroid Storm cases end in death80% of all Thyroid Disease cases are diagnosed as Hypothyroidism and 20% HyperthyroidismFemales are 5 times more likely to develop a hypothyroid disease condition over males20% of people with Diabetes will experience an onset of a thyroid disorder

50% of children with parents having a thyroid disorder may develop a thyroid disorder themselves by age 40

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Prevalence of Elevated Serum TSH by Decade of Age and Gender

At <40 years of age, prevalence is relatively low and similar between males and femalesAt ≥40 years of age, a higher percentage of female patients have elevated TSH levels

Males

Females

NHANES III Study (N=17 353)

Hollowell JG, et al.

J Clin Endocrinol Metab

. 2002;87:489-499.

Participants With Elevated TSH, %

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DisordersHypothyrodismHyperthyroidismCongenitalAcquired

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Typical Thyroid Hormone Levels in Thyroid Disease TSH T4 T

3Hypothyroidism High Low Low Hyperthyroidism Low High HighMeasurement of the total plasma hormone concentration may not provide an accurate assessment

of thyroid gland activity because total hormone concentration is affected by changes in either the amount of thyroxine

-binding globulin (TBG) or the affinity of hormones to TBG in plasma.

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Hypothyroidism Hypothyroidism is a disorder with multiple causes in which the thyroid fails to secrete an adequate amount of thyroid hormone

The most common thyroid disorder Usually caused by primary thyroid gland failureAlso may result from diminished stimulation of the thyroid gland by TSH

known as myxedema when severe

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Causes of hypothyroidismCongenitalAutoimmune (Hashimoto)Iodine deficiencySubacute

thyroiditisDrugs (amiodarone)IrradiationThyroid surgeryCentral hypothyroidism (radiotherapy, surgery, tumor)

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Clinical features of Acquired hypothyroidismWeight gainGoitreShort satureFatigueConstipation

Dry skinCold IntoleranceHoarsenessSinus Bradycardia13

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Hashimoto’s DiseaseMost common cause of hypothyroidism Autoimmune lymphocytic

thyroiditisAntithyroid antibodies:Thyroglobulin AbMicrosomal AbTSH-R Ab

(block)Females > Males

Runs in Families!

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Subacute (de Quervain’s) ThyroiditisPreceding viral infectionInfiltration of the gland with

granulomasPainful goitreHyperthyroid phase  Hypothyroid phase15

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16Congenital Hypothyroidism- CH

Clinical condition associated with decreased function of the thyroid gland and a decrease in the circulating level of thyroid hormones1:3500 to 1:4000 newbornsOne of most common preventable causes of mental retardationFemale : Male is

2 : 1Almost all affected ---

have no S/S

at birth

The most treatable cause of mental retardation

Biochemical (screening)

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Causes of Congenital Hypothyroidism1. Dysgenesis (85%)2. Ectopic 3. Enzyme defect (10%)

4. Pituitary, Hypothalamic5. Iodine deficiencyThe most common cause of congenital hypothyroidism is iodine deficiency.

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suspectClinical

ConfirmRx & FU

Biochemical (screening)

Lab ( TSH & FT4 )

T scan

B age

Optional

Thyroxine

Congenital Hypothyroidism

X

Growth & D

TSH & FT4

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Populations at Risk for Hypothyroidism WomenPrior history of Graves disease or postpartum thyroid dysfunctionElderly

Other autoimmune diseaseFamily history of Thyroid diseasePernicious anemiaType 1 Diabetes mellitusCaraccio N, et al.

J Clin Endocrinol Metab. 2002;87:1533-1538.Carmel R, et al.

Arch Intern Med. 1982;142:1465-1469.Perros P, et al.

Diabetes Med

. 1995;12:622-627.

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HypothyroidismCauses Primary: chronic autoimmune thyroiditis, prior radiation therapy (either 131I or radiation to head and neck);

subtotal / total thyroidectomy; defective TH production (due to iodine deficiency, use of drugs such as lithium, iodine, some contrast agents); infiltrative diseases of thyroid (amyloidosis, scleroderma); post-viral / postpartum thyroiditis. Secondary (central): pituitary or hypothalamic disease.

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Iodine – deficiency is one cause of hypothyroidism. However, studies are also showing that in the case of chronic autoimmune thyroiditis, the highest prevalence occurs in countries with the highest intake of iodine, such as the US and Japan.  So, although iodine supplementation should be implemented to prevent and treat iodine-deficiency disorders, supplementation should be maintained at a safe level. 

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Soy - high soy consumers and users of isoflavone supplements can be at risk of thyroid disorders since soy isoflavones can damage thyroid function. This is actually a rare occurance.Smoking – has a negative impact on thyroid function and can cause a 3 to 5 fold increase in the risk of all types of thyroid disease.

Tap water - Standard water-treatment plants cannot remove the chemical perchlorate from the water supply. According to one researcher, "There is a statistical association between low-level contamination with ammonium perchlorate and elevated or abnormal thyroid function." Also, chlorine content in the water can displace the much-needed iodine.22

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Fluoride – is an enzyme poison which accumulates in the body. Since the body can only eliminate 50% of its total fluoride intake, this build-up can cause harm to the thyroid by blocking the use of iodine.Pesticides - such as sumithrin (Anvil) and resmethrin (Scourge), are coming under considerable criticism for their adverse chronic effects on the thyroid.

Family history – of thyroid disease is a warning signal. Also a family history of depression, autoimmune disease, chronic fatigue or weight issues can signify thyroid problems.Radiation and X-Rays – are known to cause damage to the thyroid and technicians should always cover the patient’s throat.Stress – is a factor in almost every kind of disease and can affect the thyroid.Pregnancy – It is estimated that between 5-10% of all pregnancies will result in PPT (Postpartum Thyroiditis).Menopause – hormonal changes during this period of a woman’s life can wreak havoc on her thyroid.

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Prevalence of hypothyroidismIn iodine-replete communities, the prevalence of spontaneous hypothyroidism is between 1 % and 2 %, and it is more common in older women and ten times

more common in women than in men.24

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Definition of Subclinical Hypothyroidism Patients with mild thyroid failure have mildly elevated TSH levels and normal T3 and T4 levels

An isolated elevated TSH level in the setting of normal T3 and T4 levels Symptoms may be present or absent

Cooper DS. N Engl J Med. 2001;345:260-265.

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Subclinical Hypothyroidism PrevalenceWorldwide prevalence between 1% and 10% of the population worldwide.

Highest rates are in women older than 60 years of ageOver the age of 74, 16% of men and 21% of women have the disorderCooper DS. N Engl J Med. 2001;345:260-264.

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Impact of Maternal Hypothyroidism on Subsequent Neuropsychological Development of Offspring

Undiagnosed hypothyroidism in pregnant women may adversely affect fetusesMaternal hypothyroidism is associated with decreased IQ in newbornsScreening for hypothyroidism before or very early in pregnancy may be warranted

Haddow JE, et al. N Engl J Med. 1999;341:549-555.

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Thyrotoxicosis and HyperthyroidismDefinitions

ThyrotoxicosisThe clinical syndrome of hypermetabolism that results when the serum concentrations of free T4, T3, or both are increasedHyperthyroidism

Sustained increases in thyroid hormone biosynthesis and secretion by the thyroid glandThe 2 terms are

not synonymous

2% of women and 0.2% of men

Many patients

with

thyrotoxicosis have hyperthyroidism, others do not, such as those who have thyrotoxicosis from excess intake of exogenous thyroid hormone.

Braverman LE, et al.

Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text

. 8th ed. 2000.

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Hyperthyroidism Underlying Causes

Signs and symptoms can be caused by any disorder that results in an increase in circulation of thyroid hormone Toxic diffuse goiter (Graves disease)Toxic uninodular or multinodular goiter

Painful subacute thyroiditis

Silent

thyroiditis

Toxic adenoma

Iodine and iodine-containing drugs and radiographic contrast agents

Trophoblastic disease, including hydatidiform moleExogenous thyroid hormone ingestion29

The

most common cause of hyperthyroidism

Accounts

for 60% to 90% of cases

Incidence in the United States estimated at 0.02% to 0.4% of the population

Affects more females than males, especially in the reproductive age range

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Hyperthyroidism S&SHeat intoleranceHyperactivity, irritabilityWeight loss (normal to increased appetite)diarrheaTremor, Palpitations

Diaphoresis (sweating)Lid retraction & Lid Lag (thyroid stare)proptosis menstrual irregularityGoitreTachcardia30

1.

Eyes

2.Tachycardia

3. Tremor

4. Brisk tendon reflexes

5. Increased growth and bone age

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32Iodine Deficiency Disorders (IDD)Endemic goiter

Endemic cretinismIntellectual disabilityGrowth retardationNeonatal hypothyroidismIncreased early and late pregnancy loss

Increased perinatal

and infant mortality

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33Iodine Deficiency DisorderIDD severe to cause goiter in

30% or more of populationCorrection of iodine deficiency before pregnancySevere hypothyroidism in infancy termed cretinismMaternal hypothyroidism is a factor contributing to cretinismMost common preventable cause of mental deficits in the worldThe WHO estimated that 20 million people in the world

had varying degrees of preventable brain damage due to effects of iodine deficiency on fetal brain developmentPopulation at risk for IDD caused by low levels of iodine in the soil was estimated to

be 1 billion, approximately 20% of whom have goiter

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The spectrum of iodine deficiency disorders (IDD)The most critical period is from the second trimester of pregnancy to the third year after birth

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Neonatal HyperthyroidismTransient Mother high TSIPersistent Family History of Graves35

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Thyroid Diseases risk factorsGenderAgePersonal History 

- Autoimmune DiseasePersonal History - PregnancyFamily HistoryThyroid SurgeryCigarette SmokingGoitrogenic FoodsIodine Exposure/IntakeIodine Deficiency

Medications and TreatmentsMedical Radiation ExposureEnvironmental Radiation ExposureMedical Tests Involving Radiographic Contrast Agents/Contrast Dye

Neck Surgery/TraumaSurgical Antiseptic ExposureOther Factors: Stress, left handed, ambidextrous or prematurely gray

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Thyroid Diseases risk factors cont…..Gender Women face a greater risk of developing thyroid disease than men. 6 to 8 times more likely than men to develop a thyroid condition.Age

Being 50 and above increases the risk of thyroid disease for both men and women. By age 60, as many as 17 % of women and 9 % of men have an underactive thyroid.Personal History - Autoimmune Disease A personal history of thyroid disease increases your current risk for developing thyroid disease. For example, A personal history of

any autoimmune disease slightly increases your risk of developing an autoimmune thyroid disease such as Hashimoto's disease or Graves' disease.

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Thyroid Diseases risk factors cont…..Personal History - Pregnancy Nearly one out of 50 women is diagnosed with

hypothyroidism during pregnancy. Six out of every 100 miscarriages are associated with thyroid hormone deficiencies during pregnancy.Family History A family history of thyroid disease increases your risk for developing thyroid disease. The risk is slightly greater if you have a first-degree female relative (mother, sister, daughter) with thyroid disease. 39

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Thyroid Diseases risk factors cont…..Thyroid SurgerySurgical removal of all or part of the thyroid usually results in hypothyroidism -- an underactive thyroid.Radioactive Iodine Treatment (RAI) to the thyroid –- which is used to treat Graves' disease/hyperthyroidism and is often used as part of thyroid cancer treatment after surgery –- typically results in hypothyroidism.

Cigarette SmokingSmoking increases the risk of developing autoimmune thyroid disease.. Researchers have found that smoking may increase the risk, severity and side effects of hypothyroidism40

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Thyroid Diseases risk factors cont…..Goitrogenic FoodsSome foods –- when eaten raw and in large quantities -- naturally contain chemicals that can promote goiter

(enlarged thyroid) and cause hypothyroidism in some people. brussel sproutsbroccolicabbagecauliflowerkalekohlrabimilletradishesrutabagas

soyturnips

بروسل براعمبروكليالكرنب

قرنبيط

كرنب

الكرنب السلقي

الدخنفجلاللفتالصويافجل41

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Thyroid Diseases risk factors cont…..Iodine Exposure/IntakeUse of iodine or herbal supplements containing iodine, in pill or liquid form, by people who are iodine sufficient increases the risk of autoimmune thyroid disease and

hypothyroidism, and, less commonly, hyperthyroidism or thyrotoxicosis.Iodine DeficiencyLack of sufficient iodine  increases the risk of hypothyroidism and goiter. 42

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Thyroid Diseases risk factors cont…..Medications and TreatmentsCertain medical treatments and drugs such as  Interferon Beta-1b, Interleukin-4, immunosuppressants, antiretrovirals

, monoclonal antibody (Campath-1H), bone marrow transplant, Lithium, and amiodarone (Cordarone), among others increase the risk of developing an underactive thyroid.Medical Radiation ExposureExposure of the neck area to radiation, such as in medical treatments for head or neck cancer, increases the risk of autoimmune thyroid disease, and thyroid cancer.

Environmental Radiation ExposureAccidental radiation exposure in the environment, like that experienced by people who were exposed to radiation-contaminated air, food, milk and water after the 1986

Chernobyl nuclear accident, also increases the risk of autoimmune thyroid disease and thyroid cancer

.

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Thyroid Diseases risk factors cont…..Other FactorsOther research points to, but does not definitely establish, an increased risk of autoimmune disease -- including autoimmune thyroid disease -- in people who are left-handed, ambidextrous or prematurely gray. It's thought that these traits may be found on a particular gene that is also shared by certain autoimmune tendencies.

StressMajor stress –- emotional or physical (like a car accident) is considered an environmental factor for autoimmune thyroid disease.45

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Thyroid Diseases risk factors cont…..While almost anyone can develop thyroid disease, individuals fitting one or more of the following descriptions are at an increased risk: Women over the age of 60Individuals with a

preexisting autoimmune disorderIndividuals with close family member that has been diagnosed with an autoimmune diseaseYou have been recently treated with radioactive iodine or received radiation treatmentPatients who have undergone a previous thyroid procedure or partial thyroidectomyHave been pregnant or given

birth with in the last 6 – 8 months

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Thyroid Diseases risk factors cont….. Risk Factors for Thyroid Disease• personal history of autoimmune disease (i.e. Type I Diabetes)•

family history of thyroid disease• personal history of neck irradiation• drug therapies (lithium, amiodarone)• women > 50 years of age• women in the period of up to 6 months post-partum

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Thyroid Function: blood testsTSH 0.4 –5.0 mU/LFree T4 (thyroxine

) 9.1 – 23.8 pMFree T3 (triiodothyronine) 2.23-5.3 pM48

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Principal of newborn screeningAim is to identify affected infants before development of clinical signs

Objective : Eradication of MR secondary to CHThe earlier dx the better IQ

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DefinitionsScreening: search for a disease in a large unselected population

PKUCongenital hypothyroidismcord blood TSH

blood spot in a filter paper obtained by heel brick for TSH /T4

Screening Technique

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> screening< screening52

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Congenital Hypothyroidism

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Neonatal hyperthyroidism born to mother with Graves’ disease

A Color Atlas of Endocrinology p5154

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Hyperthyroid Eye Disease

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58PhenylketonuriaWhat is PKU?

it is an Autosomal recessive inborn error of metabolism found on the 12th chromosomeCausing an inherited metabolic disease that passes through familiesIt is rare condition characterized by the

deficiency in the enzyme (Phenylalanine Hydroxylase).

Normally: phenylalanine  tyrosine by liver enzyme phenylalanine

hydroxylase

(PAH)

The baby is born

lacking the ability to break down phenylalanine into tyrosine.

PKU

Genogram

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59Incidence of PKU1 out of 50 people are carriers

of this defective gene; causing incidence of 1 in 10,000 to 1 in 15,000 births.Mostly those of northern European background. Asians, and Africans are less commonly affected.

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60Diagnosis of PKUNearly all

cases of PKU are found in newborns screening tests after birthA small sample of blood to test if the trait is present on the 12th chromosome.A “

heel stick” is done and then collected on special blotter paper

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61Diagnostic findingsNormal: 120 – 360 umol/L or 1.6mg/dl

PAH Deficient: Mild: 600 – 1200 umol/LClassical: > 1200 umol/L

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62Symptoms of PKUVomiting

Skin RashesHyperactivity Small head sizeMental Retardation

Behavioral and social problemsSeizures tremors or jerking movements

A musty odor in the skin, breath or urine caused by too much Phenylketonuria

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63Prevention of PKUPatients are highly recommend to have strong relationship with physician - Genetic counseling is important especially to newly married and diagnosed couples

An Enzyme Assay can determine if parents carry defective geneChorionic villus Sampling - screen unborn baby for possibility of PKU

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Newborn ScreeningA state mandated public health program that begins with a “heel poke” for every baby before hospital discharge

First screen must be taken 24-48 hours of life regardless of feeding status or weight

Blood Sample on Guthrie Filter Paper Card64

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Why Salt?Possible: technologically easy to add iodine to saltCheap: 0.02 US$ per person per yearSafe: salt consumption 5-15 gr/day; iodine added does not exceed maximum limit and is still enough to meet daily requirement

Available to all: salt is everywhereAffordable for all: salt is cheapIdeal: Table + Food + Animal65

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Recommended Screening for Disorders of Thyroid Function

Population

Testing Frequency

Men

Every 5 years beginning at 35 years of age

Women

Every 5 years beginning at 35 years of age

Pregnant women

As soon as possible after conception; up to 3 months after giving birth

Patients >60 years of age

Once a year

The Endocrine Society Web site. Available at: http://www.endo-society.org/pubrelations/pressReleases/archives/1999/hypothyroid.cfm. Accessed April 17, 2003.

Loyola University New Orleans Web site. Available at: http://www.loyno.edu/~msthomas/hypo.html. Accessed April 17, 2003.

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PRACTICE POINTSThyroid disorders are among the most prevalent of medical disorders, especially in women; therefore the possibility of thyroid disease should be included in the differential diagnosis of a patient especially in the presence of non-specific symptoms.• Assessment of TSH and T4 should provide definitive evidence of overt / subclinical thyroid dysfunction.

• In subclinical hypothyroidism, the higher the level of TSH, the more likely the patient is to develop overt hypothyroidism over time.• Patients with evidence of subclinical hyperthyroidism require regular clinical and laboratory follow-up.67