autoimmune thyroid disorders_medimail_march 2012
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Autoimmune Thyroid Disorders
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What is AITD?Autoimmune thyroid disease (AITD) is a common
organ specific autoimmune disorder seen mostly inwomen between 30-50 yrs of age.
Forms of AITD Hyperthyroid Graves disease (GD)
Hashimotos (goitrous) thyroiditis
Atrophic autoimmune hypothyroidism
Postpartum thyroiditis (PPT)
Thyroid associated orbitopathy (TAO)
Hashimotos thyroiditis (HT) and Graves disease (GD) are thecommonest type and share many features immunologically
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Prevalence of AITD
Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html
About 2 to 4 percent of women and up to 1% of menare affected worldwide, and the prevalence rateincreases with advancing age.
Prevalence rate of autoimmune mediatedhypothyroidism is about 0.8 per 100 and 95% amongthem are women.
Graves disease is about one tenth as common as
hypothyroidism and tends to occur more in youngerindividuals.
Scenario in India The true prevalence and incidence in India of thyroid
disorders is difficult to estimate.
7.5% prevalence of autoimmune thyroiditis wasdemonstrable by fine needle aspiration biopsyamong female goitrous students.
As India is now predominantly iodine sufficient weare nearing the peak prevalence of the autoimmuneepidemic.
Thyroid Autoantibody Prevalence andAssociation with Hypothyroidism
(NHANES III. 2002;J Clin Endocrinol Metab2002,87:489-99)
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Etiology Multifactorial
Genetic
HLA complex (HLA DR-3) [HLA-A10, B8 and DQw2 is seen inIndia]
T cell regulatory gene (CTLA 4)
Environmental
Etiology Multifactorial
Source: Thyroid 2003 Mary Ann Liebert, Inc
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Pathogenesis of AITD
The development ofantibodies to thyroid
peroxidase (TPO),thyroglobulin (TG) and
thyroid stimulating hormone
receptor (TSHR) is the mainhallmark of AITD
Source: Clin Endocrinol 2004 Blackwell Publishing
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Diagnosis of AITD: Indian Thyroid
Guidelines 2011
Tests for antibodies against:
Thyroid peroxidase (TPOAb),Thyroglobulin (TgAb) and
TSH receptors (TRAb)
are used in the diagnosis of autoimmune thyroiddisorders.
Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html
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Characterization of Thyroid DisordersAccording to Results of Thyroid Function Tests
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Clinical Use of TPOAb Tests
Recommendations Detectable level of TPOAb typically precedes the
development of an elevated TSH and is thereforea risk factor for hypothyroidism.
Although the appearance of TPOAb usually
precedes the development of thyroid dysfunction,recent studies suggest that a hypoechoicultrasound pattern may precede a biochemicalTPOAb abnormality.
Although changes in autoantibody concentrationsoften reflect a change in disease activity, serial
thyroid autoantibody measurements are notrecommended for monitoring treatment for AITD.
TPOAb Found in1. 70-80 % of patients with
Graves disease2. Virtually all patients with
Hashimotos, atrophic
thyroiditis or post-partumthyroiditis3. Reproductive complications
(such as miscarriage,infertility, IVF failure, fetaldeath, pre-eclampsia,preterm delivery and post-
partum thyroiditis anddepression)
Futuristic PerspectiveMay be used as a prognostic indicator for
thyroid dysfunction.Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html
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Clinical Use of TgAb
Recommendations
Auto antibodies against Tg are encountered in autoimmune thyroidconditions, usually in association with TPOAb.
However, the recent NHANES III study found that 3 % of subjects with norisk factors for thyroid disease had detectable TgAb without TPOAb. Inthese subjects with only TgAb detected, no association with TSHabnormalities was found so that the clinical significance of an isolated TgAbabnormality remains to be established. This suggests that it is unnecessaryto measure both TPOAb and TgAb for a routine evaluation of thyroidautoimmunity.
According to the current guidelines, all sera should be pre-screened forTgAb by a sensitive immunoassay method prior to Tg testing. Therefore,TgAb is primarily used as an adjunct test for serum Tg estimation.
Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html
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TRAb & Its Classes
(a) thyroid stimulating autoantibodies(TSAb) cause Graveshyperthyroidism
(a) thyroid stimulation-blockingantibodies (TBAb) block receptorbinding of TSH
Each class of TRAb (TSAb andTBAb) may be detected alone orin combination. The relativeconcentrations of the two classesof TRAb may modulate the
severity of Graveshyperthyroidism and may changein response to therapy orpregnancy.
Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html
TBII (Thyrotrophin Binding InhibitingImmunoglobulin) assays have comparablediagnostic sensitivity to TSAb bioassays(70-95%) for diagnosing Graveshyperthyroidism or detecting a relapse orresponse to therapy.
TBII tests are important for evaluatingpregnant patients with a history ofautoimmune thyroid disease, in whomthere is a risk of transplacental passage ofTRAb to the infant .
Since TRAb and other thyroid antibodieslevels increase acutely significantly afterradioiodine therapy, a TRAb measurementprior to radioiodine therapy may be usefulto predict risk of TAO (Thyroid-AssociatedOrbitopathy).
Clinical Use of TRAb Tests
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Postpartum thyroiditis (PPT)
PPT is destructive thyroiditis during the first 12 month postpartum. Itoccurs in 5-9% of unselected postpartum women, with 3 fold
increase risk of PPT in women with type 1 diabetes. It may alsooccur after loss of pregnancy at 520 wk gestation.
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Guidelines for PPT
TSH estimation at 3 and 6 months inwomen known to be TPOAb positive & forwomen with type 1 diabetes mellitus (PPT3-fold greater).
Women with a history of PPT have amarkedly heightened risk of developingpermanent primary hypothyroidism within5 to 10 years, should undergo annual TSH
assessments.
Asymptomatic women with PPT who havea TSH above the reference range but lessthan 10mU/ml and who are not planning asubsequent pregnancy do not necessarilyrequire intervention but should, ifuntreated, be re-monitored in 48 weeks.
Symptomatic women and women with aTSH above normal and who areattempting pregnancy should be treatedwith levothyroxine.
Women with postpartum depressionshould be screened for hypothyroidismand appropriately treated.
Source: http://www.japi.org/thyroid_special_jan_issue_2011/index.html
Clinical Decision Tree
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Guidelines of the American Thyroid Association (2011) forthe Diagnosis and Management of Thyroid Disease During
Pregnancy and Postpartum
Source: ATA Guidelines 2011
Euthyroid women (not receiving LT4) who areTAb+ require monitoring for hypothyroidismduring pregnancy. Serum TSH should beevaluated every 4 weeks during the first half ofpregnancy and at least once between 26 and 32weeks gestation.
Selenium supplementation is not recommendedfor TPOAb+ women during pregnancy.
In the presence of a suppressed serum TSH inthe first trimester (TSH
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Interpretation
1.Hashimotos thyroiditis is a probable diagnosis,because the microsomal auto-antibodies havecaused atrophy of the thyroid andhypothyroidism (myxoedema). A high TSH leveland a low total or fT4 in plasma confirms thediagnosis primary hypothyroidism.Hypercholesterolaemia is typical as is increasedconcentrations of liver and muscle enzymes
(aspartate transferase, creatine kinase) in theplasma.
2.Thyroid hormone in the form of levo-thyroxine isthe treatment of choice. The initial dose to oldpatients has to be cautiously low such as 50 mgorally once or twice a week, since any overdoseelicits cardiac arrhythmia or failure.
3. A patient with one organ-specific autoimmunedisorder (here pernicious anaemia) is prone toget another (Hashimotos thyroiditis with atrophyand myxoedema).
Case Study
A female, 62 years of age, suffers frompernicious anaemia for which she has received1 (one) mg cyanocobalamine intramuscularlyevery 3 month for the last 10 years. At a routinevisit the patient is found with a puffy swollenface due to a non-pitting oedema. Her skin is
dry and cold, the heart rate is 55 beats per min,her hair is sparse, and she complains ofconstipation and fatigue. A series of blood testsreveals the following: High levels of microsomalautoantibodies against the thyroid gland andautoantibodies against her parietal cells. TheTSH concentration in the plasma is high,whereas the T4 is low. The haematological
variables are satisfying.1. What is the probable diagnosis?2. What are the treatment?3. Is there any connection between perniciousanaemia and the other condition?
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Tests Done in SRL
3238ChemiluminescenceTBG
3254IRIATSH Receptor Ab
TSPChemiluminescenceThyroid Screening Panel (FT4,
TSH3G UL & TPO)
TPCChemiluminescenceThyroid Panel IV (T3, T4, TSH)
1499ChemiluminescenceThyroid Panel II (FT3,
FT4, TSH3G UL)
1016ChemiluminescenceThyroid Autoantibodies Panel(Thyroid Peroxidase (alsoknown as Anti Microsomal Ab) &
Thyroglobulin Ab)
1499RTPChemiluminescenceRational Thyroid Panel (TSH3GUL If abnormal then FT3 & FT4)
CodeMethodTest
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