A. Thyroids Hormones <ul><li>Iodide : actively transported into the thyroid follicular cell  </li></ul><ul><li>-> Thyroid ...
<ul><li>TPO : membrane-bound,  </li></ul><ul><li>heme-containing oligomer,  </li></ul><ul><li>localized in rourg ER, Golgi...
<ul><li>1. Iodide Metabolism   </li></ul><ul><li>- Daily allowance : 150 ~ 300 g/day  </li></ul><ul><li>- Sufficiency of i...
B. Evaluation <ul><li>1. Thyroid Function .  </li></ul><ul><li>↑ TBG conditions : pregnancy, oral pill, ERT, hepatitis, ge...
2. Immunologic Abnormalities <ul><li>- Antithyroglobuliin Ab .  </li></ul><ul><li>: noncomplement-fixing IgG polyclonal an...
<ul><li>-Atibody to T3 & T4.  </li></ul><ul><li>: (+) in Hashimoto's thyroiditis & Graves' Dz. who have antithyroglobulin ...
 
C. Autoimmune Thyroid Disease <ul><li>-Hypothyroidism > hyperthyroidism  </li></ul><ul><li>-F>M  </li></ul><ul><li>-Other ...
1. Hashimoto's thyroiditis <ul><li>- Chronic lymphocytic thyroiditis  </li></ul><ul><li>- Present as hyperthyroidism, hypo...
<ul><li>1) Clinical Characteristics & Dx.   </li></ul><ul><li>- Mostly, relatively asymptomatic with painless goiter & hyp...
<ul><li>2) Treatment  </li></ul><ul><ul><li>Symptomatic hypothyroidism  </li></ul></ul><ul><ul><ul><li>   T4 replacement ...
2. Reproductive effects of Hypothyroidism <ul><li>.  </li></ul><ul><li>- Hypothyroidism : a/w↓ fertility resulting from ov...
3. Graves' Disease <ul><li>Heritable specific defect by suppressor T cell  </li></ul><ul><li>   development of helper T c...
<ul><li>1) Clinical Characteristics & Dx .  </li></ul><ul><li>Classical triad : Exophthalmos, goiter, & hyperthyroidism  <...
<ul><li>Diagnosis   </li></ul><ul><li>T3 ↑, but T4 levels - mostly normal  </li></ul><ul><li>TSH↓  </li></ul><ul><li>Antim...
2) Treatment <ul><li>Medication --> potentially harmful effects on the fetus, special attention must be given to the case ...
<ul><li>* Antithyroid Drugs </li></ul><ul><li>PTU & Methimazole  </li></ul><ul><ul><li>Low doses : block the secondary cou...
<ul><li>* Surgery </li></ul><ul><li>Subtotal thyroidectomy  </li></ul><ul><li>Ix.  </li></ul><ul><ul><li>Medical Tx failed...
4. Reproductive Effects of Hyperthyroidism <ul><li>Most women. : ovulatory & fertile  </li></ul><ul><li>Severe thyrotoxico...
5. Postpartum Thyroid Dysfunction <ul><li>Often difficult to diagnose,  </li></ul><ul><li>Sx. appear 1 ~ 8 months postpart...
<ul><li>1) Clinical Characteristics & Dx.   </li></ul><ul><ul><li>Symptom : Depression, fatigue, palpitation, at 6 ~ 12 wk...
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  1. 1. A. Thyroids Hormones <ul><li>Iodide : actively transported into the thyroid follicular cell </li></ul><ul><li>-> Thyroid peroxide (TPO) oxidizes iodide near the cell-colloid surface & </li></ul><ul><li>Incorporates it into tyrosyl residues within the thyroglobulin molecule </li></ul><ul><li>result in the formation of monoiodotyrosine (MIT) & diiodotyrosine (DIT) </li></ul><ul><li>Triiodothyronine (T3) & Thyroxine (T4) formed by secondary coupling of MIT & DIT catalyzed by TPO </li></ul>
  2. 2. <ul><li>TPO : membrane-bound, </li></ul><ul><li>heme-containing oligomer, </li></ul><ul><li>localized in rourg ER, Golgi vesicle & follicular cell surface </li></ul><ul><li>Thyroid antimicrosomal antibodies found in patients with autoimmune thyroid disease are directed against the TPO enzyme </li></ul><ul><li>Thyroid-stimulating hormone (TSH) </li></ul><ul><li>: regulates thyroidal iodine metabolism by activation of adenylate cyclase </li></ul><ul><li>--> facilitates endocytosis, digestion of thyroglobulin-containing colloid & </li></ul><ul><li>release of thyroid hormones T4, T3, rT3 </li></ul><ul><li>Thyroid hormones - effects on cells include increased oxygen consumption, heat production, increased metabolism of fat, proteins & carbohydrate </li></ul>
  3. 3. <ul><li>1. Iodide Metabolism </li></ul><ul><li>- Daily allowance : 150 ~ 300 g/day </li></ul><ul><li>- Sufficiency of iodine : associated with development of autoimmune thyroid disorder. </li></ul><ul><li>2. Factors affecting Thyroid function </li></ul><ul><li>- Iodide </li></ul><ul><li>- Pollutants (plasticizers, polychlorinated bipheols & coal processing pollutants) </li></ul><ul><li>- Ab to Yersinia enterocolitica. </li></ul><ul><li>Female hormonal milieu & its potential effects on immune surveillance </li></ul>
  4. 4. B. Evaluation <ul><li>1. Thyroid Function . </li></ul><ul><li>↑ TBG conditions : pregnancy, oral pill, ERT, hepatitis, genetic abnormality of TBG, </li></ul><ul><li>--> require measuring T3RU for clarification. </li></ul><ul><li>FTI ( Free T4 Index ) : % free T4 ( T3RU ) × T4 total </li></ul><ul><li>TSH measurement : best single screen for thyroid dysfunction. </li></ul>
  5. 5. 2. Immunologic Abnormalities <ul><li>- Antithyroglobuliin Ab . </li></ul><ul><li>: noncomplement-fixing IgG polyclonal antibodies, </li></ul><ul><li>(+) in Hashimoto's thyroiditis, Graves' Dz, acute thyroiditis, nontoxic goiter, thyroid cancer, normal women. </li></ul><ul><li>-Antimicrosomal antibody-direct against TPO </li></ul><ul><li>: cytotoxic, complement fixing Ig G Ab (+) in Hashimoto's thyroiditis, Graves' disease & postpartum thyroiditis </li></ul>
  6. 6. <ul><li>-Atibody to T3 & T4. </li></ul><ul><li>: (+) in Hashimoto's thyroiditis & Graves' Dz. who have antithyroglobulin Antibody </li></ul><ul><li>-Antibody to TSH receptor </li></ul><ul><ul><li>-TSAb. (Thyroid-stimulating Ab) or TSI (Thyroid stimulating Ig) </li></ul></ul><ul><li>: monoclonal or limited polyclonal </li></ul><ul><li>--> mimic TSH action </li></ul><ul><ul><li>-TBII (TSH-binding Inhibitor Ig) </li></ul></ul><ul><ul><ul><li>-block TSH binding </li></ul></ul></ul><ul><ul><ul><li>-block both pre-& postreceptor process </li></ul></ul></ul><ul><ul><li>-TGI (Thyroid Growth-promoting Ig) </li></ul></ul><ul><li>- stimulate growth, but not hormone release . </li></ul>
  7. 8. C. Autoimmune Thyroid Disease <ul><li>-Hypothyroidism > hyperthyroidism </li></ul><ul><li>-F>M </li></ul><ul><li>-Other autoimmune conditions associated with Graves' Dz. </li></ul><ul><li>: Hashimoto's thyroiditis, Addison's Dz, ovarian failure, RA, Sjoren's SD, IDDM, vitiligo, pernicious anemia, MG, ITP... </li></ul>
  8. 9. 1. Hashimoto's thyroiditis <ul><li>- Chronic lymphocytic thyroiditis </li></ul><ul><li>- Present as hyperthyroidism, hypothyroidism, euthyroid goiter, or diffuse goiter. </li></ul><ul><li>- High levels of anti-microsomal & antithyroglobulin Ab (+) </li></ul><ul><li>- The composition of various Ab (TBII, TGI etc.) result in varied physical finding </li></ul><ul><li>- Autoantibody </li></ul><ul><ul><li>TBII : causing the atophic form & congenital hypothyroidism in some neonates. </li></ul></ul><ul><ul><li>TGI : causing the goitrous variety </li></ul></ul><ul><li>- 3 Classic types of autoimmune injury </li></ul><ul><ul><li>complement-mediated cytotoxicity </li></ul></ul><ul><ul><li>Ab dependant cell mediated cytotoxicity </li></ul></ul><ul><ul><li>stimulation or blockade of hormone receptor </li></ul></ul>
  9. 10. <ul><li>1) Clinical Characteristics & Dx. </li></ul><ul><li>- Mostly, relatively asymptomatic with painless goiter & hypothyroidism </li></ul><ul><li>- Symptom : Cold intolerance, constipation, carotene deposition in the periorbital region, carpal tunnel syndrome, dry skin, fatigue, hair loss, lethargy, wt.gain. </li></ul><ul><li>c.f Hashitoxicosis (<-- represent a variant of Graves' Dz.) - in 4~8% </li></ul><ul><li>-Diagnosis </li></ul><ul><li>↑ TSH level during routine screening </li></ul><ul><li>↑ serum antithyroglobulin & antimicrosomal Ab </li></ul><ul><li>↑ ESR </li></ul>
  10. 11. <ul><li>2) Treatment </li></ul><ul><ul><li>Symptomatic hypothyroidism </li></ul></ul><ul><ul><ul><li> T4 replacement </li></ul></ul></ul><ul><ul><li>Goiter </li></ul></ul><ul><ul><ul><li> Can’t regress the size but prevent further growth of size </li></ul></ul></ul><ul><ul><li>Pregnant women with↑ TSH level </li></ul></ul><ul><ul><ul><li>L-thyroxine. </li></ul></ul></ul><ul><ul><ul><ul><li>:Can’t slow progression of the disease </li></ul></ul></ul></ul><ul><ul><ul><ul><li>6wks of Tx are necessary before the effect of the dose change </li></ul></ul></ul></ul>
  11. 12. 2. Reproductive effects of Hypothyroidism <ul><li>. </li></ul><ul><li>- Hypothyroidism : a/w↓ fertility resulting from ovulatory difficulties and not spontaneous abortion. </li></ul><ul><li>- Menorrhagia, amenorrhea, anovulation, luteal phase defect </li></ul><ul><li>TSH increase </li></ul><ul><li>defective in Dopamine turnover </li></ul><ul><li>Enhanced sensitivity of prolactin secreting cell </li></ul><ul><li> hyperprolactinemia </li></ul><ul><li>- Replacement therapy - reverse the hyperprolactinemia & correct ovulatory defect </li></ul>
  12. 13. 3. Graves' Disease <ul><li>Heritable specific defect by suppressor T cell </li></ul><ul><li> development of helper T cell </li></ul><ul><li> react to thyroid antigen </li></ul><ul><li>induce B-cell mediated response </li></ul><ul><li>Result in the clinical feature of Graves’ dz </li></ul><ul><li>HLA class II antigen DR, DP, DQ, DS can present antigen to T cell </li></ul>
  13. 14. <ul><li>1) Clinical Characteristics & Dx . </li></ul><ul><li>Classical triad : Exophthalmos, goiter, & hyperthyroidism </li></ul><ul><li> symptom :↑bowel movement, heat intolerance, irritability, nervousness, palpitation, tachycardia, tremor, wt.loss, lower external swelling. </li></ul><ul><li>P/E : lidlag, nontender thyroid enlargement, onycholysis, palmar erythema, proptosis, staring gaze, thick skin... </li></ul><ul><li>if. severe cases : acropachy, chemosis, clubbing, dermopathy, exophalmus with ophthalmoplegia, follicular conjunctivitis, pretibial myxedema, vision loss. </li></ul>
  14. 15. <ul><li>Diagnosis </li></ul><ul><li>T3 ↑, but T4 levels - mostly normal </li></ul><ul><li>TSH↓ </li></ul><ul><li>Antimicrosomal Ab (+) </li></ul><ul><li>TSAb : useful in evaluating medical treatment, prognosis & potential fetal complication.. </li></ul>
  15. 16. 2) Treatment <ul><li>Medication --> potentially harmful effects on the fetus, special attention must be given to the case of contraception & the potential for pregnancy. </li></ul><ul><li>(1) 131I Ablation </li></ul><ul><ul><li>Effective care in about 80% of cases </li></ul></ul><ul><ul><li>Most commonly utilized definitive Tx. in nonpregnant women </li></ul></ul><ul><ul><li>Postablative hypothyroidism : 50% within 1st year. </li></ul></ul><ul><li>(2) Antithyroid Drugs </li></ul><ul><li>(3) Surgery </li></ul><ul><li>(4) β-blocker </li></ul>
  16. 17. <ul><li>* Antithyroid Drugs </li></ul><ul><li>PTU & Methimazole </li></ul><ul><ul><li>Low doses : block the secondary coupling Rx. that form T3 & T4 from DIT & MIT. </li></ul></ul><ul><ul><li>Higher doses --> block iodination of tyrosyl residues in thyroglobulin. </li></ul></ul><ul><ul><li>30% --> remission. </li></ul></ul><ul><li>2. PTU (100mg, every 8 ~ 24hr) </li></ul><ul><ul><li>- block the intrathyroid synthesis of T3 & the pph conversion of T4 to T3. </li></ul></ul><ul><ul><li>- not cross placenta. </li></ul></ul><ul><ul><li>drug of choice in pregnancy. </li></ul></ul><ul><li>3. Methimazole (10mg, every 8 ~ 24hr) </li></ul><ul><ul><li>- not drug of choice in pregnancy , d/t not block pph conversion & cross </li></ul></ul><ul><ul><li>placenta. </li></ul></ul><ul><li>4. Iodide & Lithium. </li></ul><ul><ul><li>reduce thyroid hormone release & inhibit the organification of iodine. </li></ul></ul>
  17. 18. <ul><li>* Surgery </li></ul><ul><li>Subtotal thyroidectomy </li></ul><ul><li>Ix. </li></ul><ul><ul><li>Medical Tx failed </li></ul></ul><ul><ul><li>Hypersensitive to medical Tx. </li></ul></ul><ul><li>Risk </li></ul><ul><ul><li>Hypoparathyroidism </li></ul></ul><ul><ul><li>Recurrent laryngeal n. paralysis </li></ul></ul><ul><ul><li>Hypothyroidism. </li></ul></ul>
  18. 19. 4. Reproductive Effects of Hyperthyroidism <ul><li>Most women. : ovulatory & fertile </li></ul><ul><li>Severe thyrotoxicosis : </li></ul><ul><ul><li>wt. loss, irregular mens, amenorrhea, ↑spontaneous abortion, </li></ul></ul><ul><ul><li>↑ congenital anomalies. </li></ul></ul>
  19. 20. 5. Postpartum Thyroid Dysfunction <ul><li>Often difficult to diagnose, </li></ul><ul><li>Sx. appear 1 ~ 8 months postpartum. </li></ul><ul><li>Incidence : 5 % -> 25% permanent hypothyroid </li></ul><ul><li>Histo : lymphocytic infiltration & inflammation. </li></ul><ul><li>Antimicrosomal Ab (+) </li></ul>
  20. 21. <ul><li>1) Clinical Characteristics & Dx. </li></ul><ul><ul><li>Symptom : Depression, fatigue, palpitation, at 6 ~ 12 wks. postpartum. </li></ul></ul><ul><ul><li>c.f. postpartum thyroid dysfunction should be considered in all women with postpartum psychosis. </li></ul></ul><ul><ul><li>Diagnosis </li></ul></ul><ul><ul><li>: (-) of thyroid tenderness, pain, fever, ↑ESR, leucocytosis </li></ul></ul><ul><ul><li>TSH, T4, T, T3RU, antimicrosomal Ab titer. </li></ul></ul><ul><li>2) Treatment </li></ul><ul><ul><li>: mostly hypothyroid phase and require 6 ~ 12 months of T4 replacement if they are </li></ul></ul><ul><ul><li>symptomatic. </li></ul></ul><ul><li> (c.f.. 10 ~ 30% --> permanent hypothyroidism) </li></ul><ul><ul><li>: rarely hyperthyroid phase : not routinely use of anti-thyroid medication, but </li></ul></ul><ul><ul><li>propranolol for symptomatic relief. </li></ul></ul>
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