HASHIMOTO’S THYROIDITIS

Dr. Sangita

CASE48 yrs; FemaleMidline neck swelling,painless & diffuse,

gradually increasing in size x2mthsFatigue, depression, constipation, wt gain,

cold intolerance, dry &coarse hair and skin.

PROPOSED INVESTIGATIONS

Family historyFNACThyroid Function tests- mainly TSH (early stages-

T3,T4normal)Thyroid antibodyThyroid scanUltrasound

NORMAL THYROID

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

Iodine transport Na+/I- symport

protein controls serum I- uptake

Based on Na+/K+ antiport potential

Stimulated by TSH

Inhibited by Perchlorate

Thyroid hormone formation

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 Control

TRH

Produced by Hypothalamus Release is pulsatile, circadian Downregulated by T3

Travels through portal venous system to adenohypophysis

Stimulates TSH formation

TSH

Produced by Adenohypophysis ThyrotrophsUpregulated 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

Thyroid Hormone

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 Evaluation

TRH TSH Total T3, T4

Free T3, T4

RAIU Thyroglobulin Antibodies: Anti-TPO, Anti-TSHr

Thyroid Evaluation

RAIU

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)

AUTOIMMUNE HYPOTHYROIDISM

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.

Hypothyroidism

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 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

Hashimoto’s(Chronic, Lymphocytic)

Most common cause of hypothyroidismResult of antibodies to TPO, TBGCommonly presents in females 30-50 yrs.Usually non-tender and asymptomaticLab values

◦ High TSH

◦ Low T4

◦ Anti-TPO Ab◦ Anti-TBG Ab

Treat with Levothyroxine

Hashimoto’s Thyroiditis

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.

AUTOIMMUNE HYPOTHYROIDISM

Includes goitrous thyroiditis (hashimoto’s thyroiditis & Atrophic thyroiditis)

Symptoms range fm subclinical to overt hypothyroidism.

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.

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.

PATHOGENESIS

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

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.

Symmetric enlargement with tan yellow cut surface.

Intact capsule.

Coexistent nodular hyperplasia

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.

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 eosinophilic change in some of the acinar cells.

Dr Hakaru Hashimoto

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

MANAGEMENTNo 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

The End

Thank you for your attention.