The document discusses the role of anti-thyroid antibodies in diagnosing autoimmune thyroid disorders, highlighting their prevalence in women and specific at-risk populations. It focuses on the significance of thyroglobulin (tg) as a tumor marker for differentiated thyroid cancer (DTC) and the clinical implications of measuring antibodies like anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg). Additionally, it outlines considerations for accurate serum tg assessment and the impact of these antibodies on disease management.

1. D R . T I T T U O O M M E N
Anti thyroid antibodies

2.  The diagnostic hallmark of the autoimmune thyroid
disorders is the presence, in most patients, of
circulating antibodies and reactive T cells against
one or another thyroid antigen.
 The most clinically relevant anti-thyroid
autoantibodies are:
 Anti-thyroid peroxidase antibodies (anti-TPO antibodies)
 Thyrotropin receptor antibodies (TRAbs)
 Thyroglobulin antibodies.

4.  At all ages, these antibodies are almost five times
more common in women than in men.
 Selected groups at risk include
 younger women and relatives of patients with an autoimmune
thyroid disorder, in whom the incidence is higher.
 The higher the concentration of autoantibody, the
greater the clinical specificity.
 Tg-Ab and TPO-Ab are more common in patients
with
 sporadic goiter, multinodular goiter, or isolated thyroid
nodules and cancer than in the general population.

5. Thyroglobulin (Tg) & Anti-Tg

6.  Thyroglobulin (Tg), the precursor protein for
thyroid hormone synthesis, is detectable in the
serum of most normal individuals when a sensitive
method is used.
 The serum Tg level integrates three major factors:
 (i) the mass of differentiated thyroid tissue present
 (ii) any inflammation or injury to the thyroid gland which
causes the release of Tg
 (iii) the amount of stimulation of the TSH receptor (by TSH,
hCG or TRAb).

7.  Tg is normally detected in the circulation in
concentrations between 3 and 40 ng/mL.
 When TSH is within the reference interval, each
gram of thyroid tissue provides approximately 1
ng/mL of Tg to the circulation.
 At TSH concentrations less than 0.1 mIU/L, each
gram of thyroid tissue releases only about 0.5 ng/dL
of Tg into the plasma.

8.  An elevated serum Tg concentration is a non-specific
indicator of thyroid dysfunction.
 Elevated Tg concentrations can be seen in
 Goiter or thyroid neoplasia
 Trauma to the thyroid gland
 Inflammation (such as subacute thyroiditis or amiodarone-induced
thyroiditis)
 Surgical removal, or irradiation.
 Tg is typically decreased in
 Acquired hypothyroidism
 Congenital hypothyroidism (from thyroid hypoplasia)
 Factitious hyperthyroidism (because of TSH suppression)
 Following thyroidectomy.

9. Uses of Tg
 The primary use of serum Tg measurements is as a tumor
marker for patients carrying a diagnosis of differentiated
thyroid cancer (DTC).
 After total thyroid ablation for papillary or follicular
thyroid carcinoma, Tg should not be detectable, and its
subsequent appearance signifies the presence of
persistent disease.
 The serum Tg level is related to the volume of neoplastic
tissue and may be undetectable in patients with small
lymph node metastases that can be detected on neck
ultrasonography.(current guidelines recommend
combination of Tg and anatomic imaging for post
operative monitoring of DTC.)

10.  Single rhTSH-stimulated serumTg<0.5 ng/mL in the
absence of anti-Tg antibody has an approximately
98–99.5% likelihood of identifying patients
completely free of tumor on follow-up*
 There is good evidence that a Tg cutoff level above 2
ng/mL following rhTSH stimulation is highly
sensitive in identifying patients with persistent
tumor*
* Revised American Thyroid Association Management Guidelines for
Patients with Thyroid Nodules and Differentiated Thyroid Cancer-2009

11.  Serum Tg should be measured every 6–12 months by
an immunometric assay .
 Ideally, serum Tg should be assessed in the same
laboratory and using the same assay.
 Thyroglobulin antibodies should be quantitatively
assessed with every measurement of serum Tg.
 The results can be artifactually altered by serum
anti-Tg antibodies (Tg-Ab), and serum should be
screened for Tg-Ab with a sensitive immunoassay.
 Interferences lead to underestimations of Tg or
false-negative values.

12. Differentiated Thyroid Cancer and Positive
Anti-Thyroglobulin Antibodies
 The frequency of antibodies is approximately 20–25%.
 Higher than the approximately 10% frequency reported
in the general population.
 The eventual disappearance of Tg antibodies takes
approximately 2–3 years on average.
 The difference in antibody prevalence in DTC
populations may in part be related to
 the use of different anti-Tg antibody assays or
 Differences in the frequency of lymphocytic thyroiditis.
 Anti-Tg antibodies tend to cause an underestimation of
Tg when IMA is used, whereas they can cause either an
under- or overestimation of RIA measurements.

13.  Discordant results between different assays may be
minimized by using:
 Lower limit of detection, rather than the lower part of the normal
range to define the presence of anti-Tg antibodies.
 To repeat the measurements using a different method(in case of
heterogenous epitopes)
 Studies suggest that neck ultrasound, perhaps in
combination with other imaging based on risk of
metastatic disease determined by risk features of
individual patients, should be performed in an effort to
identify disease in patients with persistent or rising
anti-Tg antibodies.

15. Serum Tg Measurement for Non-Neoplastic
Conditions
 For diagnosing thyrotoxicosis factitia which is
characterized by a non-elevated serum Tg.
 To investigate the etiology of congenital
hypothyroidism in infants detected by neonatal
screening.
 To assess the activity of inflammatory thyroiditis, eg
subacute thyroiditis, or amiodarone-induced
thyroiditis.
 Provides a good marker of iodine status in the
population.

16. Antithyroid peroxidase antibodies (Anti TPO)
 Anti-thyroid peroxidase (anti-TPO) antibodies are
specific for the autoantigen TPO, a 105kDa
glycoprotein that catalyses iodine oxidation and
thyroglobulin tyrosyl iodination reactions in the
thyroid gland
 Anti-TPO antibodies are the most common anti-
thyroid autoantibody.

17.  Appear to be a secondary response to thyroid injury
and are not thought to cause disease themselves,
although they may contribute to its development and
chronicity.
 TPO-Ab on the surface of B cells may be involved in
antigen presentation, thus activating thyroid-specific
T cells.

18.  The disease most widely associated with TPO-Ab is
autoimmune thyroiditis, or Hashimoto’s disease.
 Also detectable in 50% to 90% of patients with
Graves’ disease -Testing for TSHR antibodies
remains the test of choice in such patients.
 More common in patients with sporadic goiter,
multinodular goiter, or isolated thyroid nodules
and cancer than in the general population. This
finding usually represents an associated
thyroiditis on histologic examination.

19.  At all ages, these antibodies are almost five times
more common in women than in men.
 High levels remain a significant risk factor in
families with autoimmune thyroid disorders.

20. Thank you