ThyroidThyroid diseasesdiseases HypothyroidismHypothyroidism

MildMild HypothyroidismHypothyroidism ThyroiditisThyroiditis

Dr hab. Jacek Daroszewski Department of Endocrinology, Diabetes and Isotope Treatment

PrevalencePrevalence of of thyroidthyroid diseasesdiseases (USA)(USA)

1. Canaris GJ, et al. Arch Intern Med. 2000;160:526-534. 2. National Center for Health Statistics. Fast stats A-Z. Available at: http://www.cdc.gov/nchs/ fastats/default.htm.

Accessed February 16, 2006. 3. U.S. Census Bureau Web site. 1997 Population Profile of the United States, p23-194. Available at: http:// www.census.gov/prod/3/98pubs/p23-

194.pdf. Accessed February 16, 2006. 4. AACE Thyroid Task Force. Guidelines. Endocr Pract. 2002;8:458-469.

33.0

Asthma 17.6

Diabetes 10.0

POCD 9.6

Thyroid diseases Hypothyroidism Nodules 21.3

CVSa 15.0

0 5 10 15 20

Patients (million)1,2,3,4

25 35 30

J.Daroszewski

Arthritis

Hypothyroidism & Hypothyroidism & ThyrotoxicosisThyrotoxicosis –– DefinitionsDefinitions areare basedbased on TSH on TSH concentrationconcentration

TSHTSH

FTFT44

Euthyroidism

Overt

Hypothyroidism

Mild Overt

Thyrotoxicosis

Mild

Progression from mild hypo- to overt ca. 4%/year

Causes of hypothyroidism (1)Causes of hypothyroidism (1) ((without without goitgoiteerr) )

Congenital failureCongenital failure ––agenesiaagenesia, , hypoplasiahypoplasia

ThyroidectomyThyroidectomy

131131--II therapytherapy

External irradiation External irradiation

((xx--rayray for lymphoma, breast cafor lymphoma, breast ca.) .)

Causes of hypothyroidism (Causes of hypothyroidism (22)) sometimessometimes with with goitgoiteerr

ChronicChronic autoimmuneautoimmune thyroiditisthyroiditis

(Hashimoto)(Hashimoto)

Congenital defects in TH synthesisCongenital defects in TH synthesis

((familialfamilial, , rarerare))

IIodineodine deficiencydeficiency

I I containigcontainig drugs: lithium, drugs: lithium, amiodaronamiodaronee, , iodine, contrast agents iodine, contrast agents

IFIF--alphaalpha, , ILIL--22

Causes of hypothyroidismCauses of hypothyroidism (3)(3) secondarysecondary (central)(central)

Hypopituitarism Hypopituitarism

Congenital malformation of Congenital malformation of hypothalamhypothalamuuss

Inflammation or neoplasm of Inflammation or neoplasm of hypothalmhypothalmuuss

Tumor, Tumor, postpost--surgerysurgery, , postpost--xx--rayray

REGULACJA WYDZIELANIA HORMONÓW TARCZYCY Hypothalamus

Pituitary

Thyroid

ThyroidThyroid hormonehormone transport and actiontransport and action

T3 T3

TR

TRE

TRANS

PORTER

T3

resp. gen

mRNA protein

effect

biol. T3

T3 T4 fT4

Deiodinase t. I

T4

Propranolol

GCS

Thyroid Binding Globulin

Prealbumin

Albumins

Affected by:

Pregnancy

Starvation

Concomitant diseases

(-)

Thyroid hormone actionThyroid hormone action

brain

nervous system

muscles (myocaridum)

gastrointestinal tract

kidney

skin

bones

endocrine system

T3

HypothyroidismHypothyroidism symptomssymptoms and and signssigns

Fatigue

Increased sensitivity to cold

Constipation

Dry skin

Unexplained weight gain

Puffy face

Hoarseness

Muscle weakness

Elevated blood cholesterol level

Muscle aches, tenderness and

stiffness

Pain, stiffness or swelling in

joints

Heavier than normal or

irregular menstrual periods

Thinning hair

Slowed heart rate

Depression

Impaired memory

Hypothyroidism and DepressionHypothyroidism and Depression Have Many Common FeaturesHave Many Common Features

Depression Hypothyroidism

• Sleep decrease

• Suicidal ideation

• Weight loss

• Appetite increase/

decrease

Nemeroff CB, J Clin Psychiatry. 1989;50(suppl):13-20.

• Bradycardia

• Cardiac and lipid

abnormalities

• Cold intolerance

• Delayed reflexes

• Goiter

• Hair and skin

changes

• Constipation

• Appetite decrease

• Decreased concentration

• Decreased libido

• Delusions

• Depressed mood

• Diminished interest

• Sleep increase

• Weight increase

• Fatigue

Diagnosis of hypothyroidism on Diagnosis of hypothyroidism on tthe basishe basis oof clinical symptoms is difficultf clinical symptoms is difficult

982 estimations of TSH with suspicion of 982 estimations of TSH with suspicion of hypothyroidism hypothyroidism -- GP)GP)

TSH in 42 subjects (4.3%)TSH in 42 subjects (4.3%)

SchectmanSchectman, 1989, 1989

Risk Factors for DevelopingRisk Factors for Developing Thyroid FailureThyroid Failure (1)(1)

Medical history of Surgical or 131I treatment

Neck irradiation

Postpartum thyroiditis

Certain autoimmune disorders: type 1 diabetes, RA, Addison

Treatment with lithium, immune-response modulators (eg, interferon alfa), amiodarone,

x-ray contrast agents

Most patients have no obvious risk factorsMost patients have no obvious risk factors

Cooper DS. N Engl J Med. 2001;345:260-264.

HypercholestrolemiaHypercholestrolemia

AtaxiaAtaxia syndromssyndroms

KlinefelterKlinefelter--, Down, Down--, Turner, Turner--, , syndromessyndromes

Risk Factors for Developing Thyroid FailureRisk Factors for Developing Thyroid Failure (2)(2)

DiagnosDiagnosttiicc Algorithm for Algorithm for HypothyroidismHypothyroidism

TSH

0.4 to 4.0 IU/mL

Patient

Euthyroid

TSH

<0.4 IU/mL

Patient Hyperthyroid?

Consult Hyperthyroidism

Diagnosis

Algorithms

TSH

>4.0 IU/mL

Measure FT4

Singer PA, et al. JAMA. 1995;273:808-812.

Demers LM, Spencer CA, eds. The National Academy of Clinical

Biochemistry Web site. Available at:

http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed July 1, 2003.

Suspect

Hypothyroid? Test TSH

Hypothyroidism Treatment GoalHypothyroidism Treatment Goal EuthyroidismEuthyroidism

The goal of hypothyroidism therapy is The goal of hypothyroidism therapy is to replace thyroxine to mimic normal, to replace thyroxine to mimic normal, physiologic levels and alleviate signs, physiologic levels and alleviate signs, symptoms, and biochemical symptoms, and biochemical abnormalitiesabnormalities

Braverman LE, et al. Werner & Ingbar’s The Thyroid. A

Fundamental and Clinical Text. 8th ed. 2000.

Hypothyroidism Hypothyroidism -- TreatmentTreatment Levothyroxine sodium is the treatment of choice for the

routine management of hypothyroidism Adults: about 1.7 g/kg of body weight/d (50-200 g/d) Elderly <1.0 g/kg of body weight/d

Shoul be taken at least 30 min. before breakfast

Clinical and biochemical evaluations at 6- to 8-week

intervals until the serum TSH concentration is normalized (lower half part of the range)

Given the narrow and precise treatment range for levothyroxine therapy, it is preferable to maintain the patient on the same brand throughout treatment

Singer PA, et al. JAMA. 1995;273:808-812.

Endocr Pract. 2002;8:457-469.

Primary Hypothyroidism Treatment AlgorithmPrimary Hypothyroidism Treatment Algorithm

TSH >4 IU/mL TSH <0.5 IU/mL

Initial Levothyroxine Dose

Increase

Levothyroxine

Dose by

12.5 to 25 g/d

Repeat TSH Test

6-8 Weeks

TSH 0.5- 2.0 IU/mL

Symptoms Resolved

Measure TSH at 6 Months,

Then Annually or

When Symptomatic

Continue Dose Decrease

Levothyroxine

Dose by

12.5 to 25 g/d

Singer PA, et al. JAMA. 1995;273:808-812.

Demers LM, Spencer CA, eds. The National Academy of

Clinical Biochemistry Web site. Available at:

http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed.

Mild Thyroid FailureMild Thyroid Failure ((subclinicalsubclinical))

Progression of Thyroid Disease Progression of Thyroid Disease

Ayala AR, et al. Endocrinologist. 1997;7:44-50.

Years

Normal Range

TSH

Overt Hypothyroidism

Mild Thyroid Failure Euthyroid

T3

T4

Definition of Mild Thyroid FailureDefinition of Mild Thyroid Failure

An isolated elevated TSH level in the An isolated elevated TSH level in the setting of normal Tsetting of normal T33 and Tand T44 levels levels

Symptoms may be present or absentSymptoms may be present or absent

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

Mild Thyroid FailureMild Thyroid Failure PrevalencePrevalence

Worldwide prevalence between 1% and 10%Worldwide prevalence between 1% and 10%

Highest rates are in women older than 60 Highest rates are in women older than 60 years of ageyears of age

Over the age of 74, 16% of men and 21% of Over the age of 74, 16% of men and 21% of women have the disorderwomen have the disorder

Cooper DS. N Engl J Med. 2001;345:260-264.

Prevalence of Elevated Serum TSH Prevalence of Elevated Serum TSH by Decade of Age and Genderby Decade of Age and Gender

• At <40 years of

age, prevalence is

relatively low and

similar between

males and

females

• At ≥40 years of

age, a higher

percentage of

female patients

have elevated

TSH levels

Males

FemalesFemales

NHANES III Study (N=17 353)

Hollowell JG, et al. J Clin Endocrinol Metab. 2002;87:489-499.

Part

icip

ants

With

Ele

vate

d T

SH

, %

Potential benefits from treatmentPotential benefits from treatment

Prevent progression to overt Prevent progression to overt hypothyroidismhypothyroidism

Improve serum lipid profile, which may Improve serum lipid profile, which may reduce the risk of death from reduce the risk of death from cardiovascular causescardiovascular causes

Reduce symptoms, including psychiatric Reduce symptoms, including psychiatric and cognitive abnormalitiesand cognitive abnormalities

Cooper DS. N Engl J Med. 2001;345:260-264.

Rationale for Treating Rationale for Treating Mild Thyroid FailureMild Thyroid Failure

ThyroiditisThyroiditis

AcuteAcute –– suppurativesuppurative ((bacterialbacterial infectioninfection))

SubacuteSubacute painfulpainful (de (de Quervain’sQuervain’s) )

viralviral, , unknownunknown

ChronicChronic ((lymphocyticlymphocytic, , HashimotoHashimoto))

SubacuteSubacute autoimmuneautoimmune

SilentSilent

PostPost--partumpartum

ChronicChronic fibroticfibrotic ((Riedel’sRiedel’s thyroiditisthyroiditis))

Chronic Chronic ThyroiditisThyroiditis

Also known as Hashimoto’s diseaseAlso known as Hashimoto’s disease

TThe most common cause of he most common cause of spontaneousspontaneous hypothyroidismhypothyroidism

AutoantibodiesAutoantibodies::

TPO TPO antibody antibody

thyroglobulinthyroglobulin antibodyantibody

Gross and Microscopic Pathology Gross and Microscopic Pathology of Chronic of Chronic ThyroiditisThyroiditis

UltrasoundUltrasound imagingimaging of HTof HT

Presentation and CoursePresentation and Course

Painless goiter in a patient who is either Painless goiter in a patient who is either euthyroideuthyroid or hypothyroidor hypothyroid

MajorityMajority of of patientspatients withoutwithout goitergoiter

May have periods of May have periods of thyrotoxicosisthyrotoxicosis

Treat with Treat with levothyroxinelevothyroxine

No No immunosuppressionimmunosuppression

SubacuteSubacute PainfulPainful ThyroiditisThyroiditis

Also known as De Quervain's thyroiditisAlso known as De Quervain's thyroiditis

Most common cause of thyroid pain and Most common cause of thyroid pain and tendernesstenderness

Pain may radiate to ear, teeth, jawPain may radiate to ear, teeth, jaw

Acute inflammatory disease most likely due to Acute inflammatory disease most likely due to viral infectionviral infection

Transient hyperthyroidism followed by Transient hyperthyroidism followed by transient hypothyroidism; permanent transient hypothyroidism; permanent hypothyroidism or relapses are uncommonhypothyroidism or relapses are uncommon

44--phase phase coursecourse of of subacutesubacute thyroiditisthyroiditis ((painfulpainful and and autoimmunologicalautoimmunological))

FunctionFunction 131131I I uptakeuptake

1. 1. HyperHyper--

2. 2. EuEu--

3. 3. HypoHypo--

4. 4. EuEu-- NN 1 2 3 4

Treatment of Treatment of SubacuteSubacute ThyroiditisThyroiditis

Symptomatic: NSAIDS or a Symptomatic: NSAIDS or a glucocorticoidglucocorticoid ((prednisonprednison 3030--40 mg/40 mg/dayday))

BetaBeta--blockers indicated if there are signs of blockers indicated if there are signs of thyrotoxicosisthyrotoxicosis

LevothyroxineLevothyroxine may be given during may be given during hypothyroid phasehypothyroid phase

SummarySummary

Thyroid disease is a prevalent conditionThyroid disease is a prevalent condition

Effective screening requires biochemical Effective screening requires biochemical confirmation to avoid misdiagnosis confirmation to avoid misdiagnosis

Levothyroxine therapy is recommended Levothyroxine therapy is recommended for for majoritymajority of of patientspatients

Effective in different types of thyroid disordersEffective in different types of thyroid disorders

Provides benefit for many organ systemsProvides benefit for many organ systems

Reduces CAD risk factorsReduces CAD risk factors

ImprovesImproves mentalmental disordersdisorders