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 folliclesNORMAL 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 spaceThyroid hormone formation
7. Thyroid Hormone Control
8. Produced by Hypothalamus Release is pulsatile, circadian Downregulated by T3 Travels through portal venous system to adenohypophysis Stimulates TSH formationTRH
9. 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 glandTSH
10. 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 hormoneThyroid Hormone
17. 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
18. 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
19. 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
20. Includes goitrous thyroiditis (hashimoto’s thyroiditis & Atrophic thyroiditis) Symptoms range fm subclinical to overt hypothyroidism.AUTOIMMUNEHYPOTHYROIDISM
21. 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.
22. 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.
23. 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
25. The goiter is generally symmetrical, often with a conspicuous pyramidal lobe. Grossly, the tissue involved by Hashimotos 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.
26. Symmetric enlargement with tan yellow cut surface. Intact capsule.
27. Coexistent nodular hyperplasia
28. 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.
29. 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 anDr Hakaru Hashimoto eosinophilic change in some of the acinar cells.
30. EM- Deposits of dense material representingIgG are found along the basement membraneon electron microscopy
31. 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