A.

Thyroids Hormones
Iodide : actively transported into the thyroid follicular cell -> Thyroid peroxide (TPO) oxidizes iodide near the cell-colloid surface & Incorporates it into tyrosyl residues within the thyroglobulin molecule result in the formation of monoiodotyrosine (MIT) & diiodotyrosine (DIT) Triiodothyronine (T3) & Thyroxine (T4) formed by secondary coupling of MIT & DIT catalyzed by TPO

 TPO : membrane-bound, heme-containing oligomer, localized in rourg ER, Golgi vesicle & follicular cell surface Thyroid antimicrosomal antibodies found in patients with autoimmune thyroid disease are directed against the TPO enzyme
Thyroid-stimulating hormone (TSH) : regulates thyroidal iodine metabolism by activation of adenylate cyclase --> facilitates endocytosis, digestion of thyroglobulincontaining colloid & release of thyroid hormones T4, T3, rT3 Thyroid hormones - effects on cells include increased oxygen consumption, heat production, increased metabolism of fat, proteins & carbohydrate

1. Iodide Metabolism
- Daily allowance : 150 ~ 300 g/day - Sufficiency of iodine : associated with development of autoimmune thyroid disorder.

2. Factors affecting Thyroid function

- Iodide - Pollutants (plasticizers, polychlorinated bipheols & coal processing pollutants) - Ab to Yersinia enterocolitica. - Female hormonal milieu & its potential effects on immune surveillance

B. Evaluation
1. Thyroid Function.
TBG conditions : pregnancy, oral pill, ERT, hepatitis, genetic abnormality of TBG, --> require measuring T3RU for clarification. FTI ( Free T4 Index ) : % free T4 ( T3RU ) T4 total

TSH measurement : best single screen for thyroid dysfunction.

2. Immunologic Abnormalities
-Antithyroglobuliin Ab. : noncomplement-fixing IgG polyclonal antibodies, (+) in Hashimoto's thyroiditis, Graves' Dz, acute thyroiditis, nontoxic goiter, thyroid cancer, normal women.

-Antimicrosomal antibody-direct against TPO

: cytotoxic, complement fixing Ig G Ab (+) in Hashimoto's thyroiditis, Graves' disease & postpartum thyroiditis

-Atibody to T3 & T4.

: (+) in Hashimoto's thyroiditis & Graves' Dz. who have antithyroglobulin Antibody

-Antibody to TSH receptor

-TSAb. (Thyroid-stimulating Ab) or TSI (Thyroid stimulating Ig)
: monoclonal or limited polyclonal --> mimic TSH action

-TBII (TSH-binding Inhibitor Ig)

-block TSH binding -block both pre-& postreceptor process

-TGI (Thyroid Growth-promoting Ig)

-

stimulate growth, but not hormone release.

C. Autoimmune Thyroid Disease

-Hypothyroidism > hyperthyroidism
-F>M

-Other autoimmune conditions associated with Graves' Dz. : Hashimoto's thyroiditis, Addison's Dz, ovarian failure, RA, Sjoren's SD, IDDM, vitiligo, pernicious anemia, MG, ITP...

1. Hashimoto's thyroiditis
- Chronic lymphocytic thyroiditis - Present as hyperthyroidism, hypothyroidism, euthyroid goiter, or diffuse goiter. - High levels of anti-microsomal & antithyroglobulin Ab (+) - The composition of various Ab (TBII, TGI etc.) result in varied physical finding - Autoantibody
TBII : causing the atophic form & congenital hypothyroidism in some neonates. TGI : causing the goitrous variety

- 3 Classic types of autoimmune injury

complement-mediated cytotoxicity Ab dependant cell mediated cytotoxicity stimulation or blockade of hormone receptor

1) Clinical Characteristics & Dx.

- Mostly, relatively asymptomatic with painless goiter & hypothyroidism - Symptom : Cold intolerance, constipation, carotene deposition in the periorbital region, carpal tunnel syndrome, dry skin, fatigue, hair loss, lethargy, wt.gain. c.f Hashitoxicosis (<-- represent a variant of Graves' Dz.) - in 4~8%

-Diagnosis
TSH level during routine screening serum antithyroglobulin & antimicrosomal Ab ESR

2) Treatment
Symptomatic hypothyroidism
T4 replacement

Goiter
Cant regress the size but prevent further growth of size

Pregnant women with TSH level

L-thyroxine.
:Cant slow progression of the disease 6wks of Tx are necessary before the effect of the dose change

2. Reproductive effects of Hypothyroidism

. - Hypothyroidism : a/w fertility resulting from ovulatory difficulties and not spontaneous abortion. - Menorrhagia, amenorrhea, anovulation, luteal phase defect - TSH increase defective in Dopamine turnover Enhanced sensitivity of prolactin secreting cell hyperprolactinemia

- Replacement therapy - reverse the hyperprolactinemia & correct ovulatory defect

3. Graves' Disease
Heritable specific defect by suppressor T cell development of helper T cell react to thyroid antigen induce B-cell mediated response Result in the clinical feature of Graves dz HLA class II antigen DR, DP, DQ, DS can present antigen to T cell

1) Clinical Characteristics & Dx.

Classical triad : Exophthalmos, goiter, & hyperthyroidism symptom :bowel movement, heat intolerance, irritability, nervousness, palpitation, tachycardia, tremor, wt.loss, lower external swelling.

P/E : lidlag, nontender thyroid enlargement, onycholysis, palmar erythema, proptosis, staring gaze, thick skin...
if. severe cases : acropachy, chemosis, clubbing, dermopathy, exophalmus with ophthalmoplegia, follicular conjunctivitis, pretibial myxedema, vision loss.

Diagnosis
T3 , but T4 levels - mostly normal TSH Antimicrosomal Ab (+) TSAb : useful in evaluating medical treatment, prognosis & potential fetal complication..

2) Treatment
Medication --> potentially harmful effects on the fetus, special attention must be given to the case of contraception & the potential for pregnancy. (1) 131I Ablation
Effective care in about 80% of cases Most commonly utilized definitive Tx. in nonpregnant women Postablative hypothyroidism : 50% within 1st year.

(2) Antithyroid Drugs (3) Surgery (4) -blocker

* Antithyroid Drugs
1. PTU & Methimazole
Low doses : block the secondary coupling Rx. that form T3 & T4 from DIT & MIT. Higher doses --> block iodination of tyrosyl residues in thyroglobulin. 30% --> remission.

2. PTU (100mg, every 8 ~ 24hr)

- block the intrathyroid synthesis of T3 & the pph conversion of T4 to T3. - not cross placenta. - drug of choice in pregnancy.

3. Methimazole (10mg, every 8 ~ 24hr)

- not drug of choice in pregnancy , d/t not block pph conversion & cross placenta.

4. Iodide & Lithium.

- reduce thyroid hormone release & inhibit the organification of iodine.

* Surgery Subtotal thyroidectomy Ix.

Medical Tx failed Hypersensitive to medical Tx.

Risk
Hypoparathyroidism Recurrent laryngeal n. paralysis Hypothyroidism.

4. Reproductive Effects of Hyperthyroidism

Most women. : ovulatory & fertile Severe thyrotoxicosis :
wt. loss, irregular mens, amenorrhea, spontaneous abortion, congenital anomalies.

5. Postpartum Thyroid Dysfunction

Often difficult to diagnose, Sx. appear 1 ~ 8 months postpartum. Incidence : 5 % -> 25% permanent hypothyroid

Histo : lymphocytic infiltration & inflammation.

Antimicrosomal Ab (+)

1) Clinical Characteristics & Dx.

Symptom : Depression, fatigue, palpitation, at 6 ~ 12 wks. postpartum. c.f. postpartum thyroid dysfunction should be considered in all women with postpartum psychosis.

Diagnosis : (-) of thyroid tenderness, pain, fever, ESR, leucocytosis TSH, T4, T, T3RU, antimicrosomal Ab titer.

2) Treatment
: mostly hypothyroid phase and require 6 ~ 12 months of T4 replacement if they are symptomatic.

(c.f.. 10 ~ 30% --> permanent hypothyroidism)

: rarely hyperthyroid phase : not routinely use of anti-thyroid medication, but propranolol for symptomatic relief.