1. HASHIMOTO’S
THYROIDITIS
Dr. Sangita

2. CASE
 48 yrs; Female
 Midline neck swelling,painless & diffuse,
gradually increasing in size x2mths
 Fatigue, depression, constipation, wt gain,
cold intolerance, dry &coarse hair and
skin.

3. PROPOSED INVESTIGATIONS
 Family history
 FNAC
 Thyroid Function tests- mainly TSH (early
stages-T3,T4normal)
 Thyroid antibody
 Thyroid scan
 Ultrasound

4.  Normal thyroid tissue
with follicles filled with
colloid .
 Thyroid cells form
follicles, spheres of
epithelial cells (always
single-layered in
health, usually more-or-
less cuboidal, variably
tall or short).
 The C-cells
(parafollicular cells) of
the thyroid are visible
between the follicles
NORMAL THYROID

5. Iodine transport
 Na+/I- symport
protein controls
serum I- uptake
 Based on Na+/K+
antiport potential
 Stimulated by
TSH
 Inhibited by
Perchlorate

6.  Thyroid Peroxidase (TPO)
◦ Apical membrane protein
◦ Catalyzes Iodine organification to tyrosine
residues of thyroglobulin
◦ Antagonized by methimazole, PTU
 Iodine coupled to Thyroglobulin
◦ Monoiodotyrosine (Tg + one I-)
◦ Diiodotyrosine (Tg + two I-)
 Pre-hormones secreted into follicular
space
Thyroid hormone formation

8. Thyroid Hormone Control

9.  Produced by Hypothalamus
 Release is pulsatile, circadian
 Downregulated by T3
 Travels through portal venous system to
adenohypophysis
 Stimulates TSH formation
TRH

10.  Produced by Adenohypophysis
Thyrotrophs
 Upregulated by TRH
 Downregulated by T4, T3
 Travels through portal venous system to
cavernous sinus, body.
 Stimulates several processes
◦ Iodine uptake
◦ Colloid endocytosis
◦ Growth of thyroid gland
TSH

11.  Majority of circulating hormone is T4
◦ 98.5% T4
◦ 1.5% T3
 Total Hormone load is influenced by serum
binding proteins
◦ Albumin 15%
◦ Thyroid Binding Globulin 70%
◦ Transthyretin 10%
 Regulation is based on the free component of
thyroid hormone
Thyroid Hormone

12.  TRH
 TSH
 Total T3, T4
 Free T3, T4
 RAIU
 Thyroglobulin
 Antibodies: Anti-TPO, Anti-TSHr
Thyroid Evaluation

13. Thyroid Evaluation

14.  Scintillation counter measures radioactivity after
I123 administration.
 Uptake varies greatly by iodine status
◦ Indigenous diet (normal uptake 10% vs. 90%)
◦ Amiodarone, Contrast study, Topical betadine
 Elevated RAIU with hyperthyroid symptoms
◦ Graves’
◦ Toxic goiter
 Low RAIU with hyperthyroid symptoms
◦ Thyroiditis (Subacute, Active Hashimoto’s)
◦ Hormone ingestion (Thyrotoxicosis factitia, Hamburger
Thyrotoxicosis)
◦ Excess I- intake in Graves’ (Jod-Basedow effect)
◦ Ectopic thyroid carcinoma (Struma ovarii)
RAIU

15. AUTOIMMUNE
HYPOTHYROIDISM

16.  SYMPTOMS- tiredness;weakness;dry skin;
feeling cold; hair loss; difficulty concentrating
and poor memory;constipation; wt gain with
poor apetite; dyspnea; hoarse voice;
menstrual irregularities;paraesthesia;
impaired healing.
 SIGNS- dry coarse skin, cool peripheral
extremities; puffy face,hands and feet;diffuse
alopecia; bradycardia; peripheral
edema;delayed tendon reflex
relaxation;carpal tunnel syndrome; serous
cavity effusions.

18.  Agenesis
 Thyroid destruction
◦ Hashimoto’s thyroiditis
◦ Surgery
◦ I131 ablation
◦ Infiltrative diseases
◦ Post-laryngectomy
 Inhibition of function
◦ Iodine deficiency
◦ Iodine administration
◦ Anti-thyroid medications (PTU, Methimazole, Lithium,
Interferon)
◦ Inherited defects
 Transient
◦ Postpartum
◦ Thyroiditis
Hypothyroidism

19. Hypothyroidism
 Cause is determined by geography
◦ Hashimoto’s in industrialized countries
◦ May be due to iodine excess in some costal
areas
 Diagnosis
◦ Low FT4, High TSH (Primary, check for
antibodies)
◦ Low FT4, Low TSH (Secondary or Tertiary, TRH
stimulation test, MRI)
 Treatment
◦ Levothyroxine (T4) due to longer half life
◦ Treatment prevents bone loss, cardiomyopathy,
myxedema

20. Hashimoto’s
(Chronic, Lymphocytic)
 Most common cause of hypothyroidism
 Result of antibodies to TPO, TBG
 Commonly presents in females 30-50 yrs.
 Usually non-tender and asymptomatic
 Lab values
◦ High TSH
◦ Low T4
◦ Anti-TPO Ab
◦ Anti-TBG Ab
 Treat with Levothyroxine

21.  Most common cause of goiter and hypothyroidism in the U.S.
 Physical
◦ Painless diffuse goiter
 Lab studies
◦ Hypothyroidism
◦ Anti TPO antibodies (90%)
◦ Anti Thyroglobulin antibodies (20-50%)
◦ Acute Hyperthyroidism (5%)
 Treatment
◦ Levothyroxine if hypothyroid
◦ Triiodothyronine (for myxedema coma)
◦ Thyroid suppression (levothyroxine) to decrease goiter size
 Contraindications
 Stop therapy if no resolution noted
◦ Surgery for compression or pain.
Hashimoto’s Thyroiditis

22.  Includes goitrous thyroiditis (hashimoto’s
thyroiditis & Atrophic thyroiditis)
 Symptoms range fm subclinical to overt
hypothyroidism.
AUTOIMMUNE
HYPOTHYROIDISM

23.  PREVALENCE - 4/1000 women; 1/1000
men.
 Japanese population, genetic factors,
chronic exposure to high iodine diet.
 Mean age at diagnosis 60yrs, prevalence
of hypothyroidism increases with age.

24.  A/ka Autoimmune thyroiditis & struma
lymphomatosa.
 Age & Gender: 45-65 years of age, more
common in women than in man, with a
female predominance of 10:1 to 20:1.
 Symptoms and signs: euthyroidism or
hypothyroidism.

25.  Sensitization of autoreactive CD4+ T-helper cells to thyroid
antigens appears to be the initiating event. The effector
mechanisms for thyrocyte death include the following:
◦ CD8+ cytotoxic T cell-mediated cell death: CD8+
cytotoxic T cells may cause thyrocyte destruction by one
of two pathways: exocytosis of perforin/granzyme
granules or engagement of death receptors, specifically
CD95 (also known as Fas) on the target cell
◦ Cytokine-mediated cell death: CD4+ T cells produce
inflammatory cytokines such as IFN-γ in the immediate
thyrocyte milieu, with resultant recruitment and
activation of macrophages and damage to follicles.
◦ Binding of antithyroid antibodies (anti-TSH receptor
antibodies, antithyroglobulin, and antithyroid peroxidase
antibodies) followed by antibody-dependent cell-
mediated cytotoxicity (ADCC)
PATHOGENESIS

26. Pathogenesis

27.  The goiter is generally symmetrical, often
with a conspicuous pyramidal lobe.
Grossly, the tissue involved by
Hashimoto's thyroiditis is pinkish-tan to
frankly yellowish and tends to have a
rubbery firmness. The capsular surface is
gently lobulated and non-adherent to
peri-thyroid structures.

28.  Symmetric enlargement with tan yellow
cut surface.
 Intact capsule.

29. Coexistent nodular hyperplasia

30.  Microscopically, there is a diffuse process
consisting of a combination of epithelial cell
destruction, lymphoid cellular infiltration, and
fibrosis.
 The thyroid cells tend to be slightly larger
and assume an acidophilic staining character;
they are then called Hurthle or Askanazy cells
and are packed with mitochondria.
 The follicular spaces shrink, and colloid is
absent or sparse. Fibrosis may be completely
absent or present in degrees ranging from
slight to moderate;
 In children, oxyphilia and fibrosis are less
prominent, and hyperplasia of epithelial cells
may be marked.

35. In 1912 ,Hashimoto
described four patients
with a chronic disorder
of the thyroid, which he
termed struma
lymphomatosa. The
thyroid glands of these
patients were
characterized by diffuse
lymphocytic infiltration,
fibrosis, parenchymal
atrophy, and an
Dr Hakaru Hashimoto eosinophilic change in
some of the acinar
cells.

36. EM- Deposits of dense material representing
IgG are found along the basement membrane
on electron microscopy

37. MANAGEMENT
 No cure or way to know the time duration
till how much the disease will last.
 Thyroid replacement medications.
 In patients with Hashimoto’s thyroiditis and
a large goiter, thyrotropin-suppressing
doses of levothyroxine sodium can be given
over the short term (i.e., six months) to
decrease the size of the goiter.
 In most patients with Hashimoto’s
thyroiditis (whether euthyroid or
hypothyroid), goiter size will decrease by
30% aftr 6 mths of therapy with
levothyroxine sodium

38.  Thank you for your attention.
The End