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The Role of Thyroid Auto-antibodies

in the Management of
Thyroid Disorders
Dr. Charles Antonypillai

MBBS(Col), MD(Col), MRCP(UK)
MRCP(Endocrinology & Diabetes) UK

Consultant Endocrinologist
General Hospital (Teaching), Kandy

Thyroid Day
25-07-2012
Antibody
An antibody is a large Y-
shaped protein that is
used by the immune
system to identify and
neutralize foreign
objects.

Can cause auto-immune
diseases.
History
Hashimoto described dense lymphoid infiltration
causing goitre and hypothyroidism in 1912.

Auto antibodies (anti-thyroglobulin antibodies) were
detected in 1956.

Lead to the discovery of organ specific auto-immune
disorders.

Antithyroid peroxidase antibody was discovered in
1964.

Commercial assays are available for
Anti-thyroglobulin antibody (anti-Tg)

Anti-thyroid peroxidase antibody (anti-TPO)

Anti-TSH receptor antibody (anti TRAb)
Anti-thyroid antibodies and thyroid
disease
Condition Anti TPO Anti
thyroglobulin
Anti TSH
receptor
Graves Disease

70 80 % 30 50 % 70 100%
(stimulating)
Autoimmune
hypothyroidism
95% 60% 10 20%
(blocking)
Anti-TSH Receptor Antibodies
Graves Disease
Diagnosing the cause of Thyrotoxicosis
Grave's disease is an
organ-specific
autoimmune disease

Caused by stimulating
TRAb that stimulate the
thyroid function and
growth.

Resulting in
hyperthyroidism and
diffuse goitre.








Graves Disease
Diagnosing the cause of Thyrotoxicosis

TRAb assays are 85 100 % sensitive in
untreated Graves Disease (GD).

Thus, theoretically, the detection of TRAb in a
hyperthyroid patient is diagnostic of Grave's
disease.

Graves Disease
Is TRAb essential?

80% or more of patients with Grave's disease have a
diffuse goitre and homogeneous thyroid scan.

Most patients can be diagnosed by thyroid hormones
measurements without TRAb testing.

If radio iodine or thyroidectomy are used as treatment
separating GD from Nodular thyroid disease is not
essential.


Graves Disease


TRAb measurement has not been
recommended as a routine investigation in
recent guidelines.



Graves Disease
When is TRAb useful?

Mild hyperthyroidism and small or no goitre
In differentiating Graves disease from other
forms of thyrotoxicosis with other methods is
difficult
such as toxic nodular goitre, painless (autoimmune)
thyroiditis, or factitious thyrotoxicosis.
pregnant women or patients with recent iodine
load where radioiodine uptake or thyroid scan is
contraindicated.

Graves Disease
Predicting Remission after Thionamide
Therapy
The major problem with antithyroid drug(ATD) is
the high relapse rate (=> 50%) after 1-2 yr of
treatment.

Clinically important to identify patients who are
likely to achieve remission with ATD treatment.

Most reported studies suggest that initial TRAb
activity alone has not had satisfactory positive
and negative predictive values for remission or
relapse after ATD treatment.

Graves Disease
Predicting Remission after Thionamide
Therapy

Nevertheless, taking into account the initial titre of TRAb
and other clinical parameters give a better predictive value
for relapse.
age, gender, goitre size, the severity of hyperthyroidism, and the
presence of ophthalmopathy

The chance of remission during the 5 yr after completion of
12-24 months course of antithyroid drug treatment.
a small goitre (<40 mL) and low TBII level (<30 U/L) - 45%
a large goitre (>70 mL) and a higher TBII level -< 10%

Thyroid 1997; 7: 369-75
Graves Disease
Predicting Remission after Thionamide
Therapy

TRAb at the end of ATD treatment has > 90%
predictive value for relapse after treatment.

A positive value at the end of treatment will help
decide on continuation of treatment.

Especially useful in children and adolescents
where prolonged course of treatment is required.


Graves Disease
Monitoring fluctuating thyroid
function
Spontaneous evolution of hyperthyroid Grave's disease to hypothyroidism
has been well characterized.

Common cause - Thyroid destruction caused by concomitant autoimmune
thyroiditis .

But the presence of blocking TRAb along with stimulating TRAb is
considered to be another possible cause. (Cyclical GD)

TSBAbs may result from
a conversion of the bioactivity of TSAb
may coexist with TSAb at the time of hypothyroidism

Thus, the measurement of bioactivities of TRAb during the course of
Grave's disease is valuable in the case of fluctuating thyroid function.
Graves Disease
Guiding Management of Pregnancy
2 10% of GD has sufficient transplacental
transfer of TRAb to cause foetal or neonatal
hyperthyroididsm.
TRAb antibodies are universal in mothers of
neonates developing thyrotoxicosis.
Women previously treated with RI or Surgery
have a higher level of TRAb.
Graves Disease
Guiding Management of Pregnancy
European Thyroid association recommends

TRAb measurement in women previously treated
with RI or Surgery .

If high, need to monitor foetus for
hyperthyroidism and assess neonatal or cord
blood for thyroid hormone.

Graves Disease
Thyroid Eye Disease

Autoimmune inflammatory
disorder of the periorbital
connective tissue.
TSH receptors are expressed in the retrorbital
tissue.
TRAb is positive even in 10% of patients with
Graves ophthalmopathy with biochemical
euthyroidism.


Graves Disease
Thyroid Eye Disease

TRAb assay may be valuable in

In a patient who presents with Grave's
ophthalmopathy but is biochemically euthyroid.
Anti-TPO Antibodies
Anti-thyroid antibodies and thyroid
disease
Condition Anti TPO Anti
thyroglobulin
Anti TSH
receptor
Graves Disease

70 80 % 30 50 % 70 100%
(stimulating)
Autoimmune
hypothyroidism
95% 60% 10 20%
(blocking)
Recommendations for Anti-TPO-Ab testing
in Chronic Autoimmune Thyroiditis
In euthyroid goitre to identify Chronic Autoimmune Thyroiditis.

A rapidly enlarging goitre in the presence of thyroid antibodies
strongly suggests lymphoma.

In concomitant autoimmune diseases Anti-TPO antibody predates
hypothyroidism and increases the risk of significant thyroid
dysfunction.

In biochemical hypothyroidism to find the cause. Chronic
Autoimmune Thyroiditis is the commonest cause in iodine sufficient
areas.

Subclinical hypothyroidism to identify individuals who are most
likely to progress to overt hypothyroidism.

Postpartum Thyroiditis
5-9% of women experience postpartum
thyroiditis (PPT).
Rates are 3 times higher in women with type 1
DM
Risk of PPT
positive for thyroid auto Ab in T1 - 50%
Negative for thyroid auto Ab in T1 -2%


Postpartum Thyroiditis

Anti TPO Ab testing recommended in women
with Type 1 DM and with personal or F/H of
thyroid dysfunction to predict the likelihood of
PPT.

Anti-thyroglobulin Antibodies
Differentiated Thyroid Cancer
Serial measurements of serum Thyroglobulin
(Tg) levels are useful in identifying
recurrences.

When anti Tg antibodies are present Tg assays
become unreliable owing to immune
interference.

Differentiated Thyroid Cancer


Anti Tg antibody testing is mandatory in these
patients.

Summary
Anti- TSH Receptor Antibodies are useful in

Diagnosing Graves disease in patients with
ambiguous clinical features and investigation
results.
Diagnosing Graves ophthalmopathy in patients
without hyperthyroidism.
Predicting remission in patients with GD treated
with ATD.
Summary
Anti- TPO Antibodies are useful in

Diagnosing CAIT in patients with goitre,
hypothyroidism and subclinical hypothyroidism.

In predicting postpartum thyroiditis.
Summary
Anti-thyroglobulin Antibodies are useful in

Patients with differntiated thyoid cancer where
serial measurements of Tg is used to monitor
recurrence.