A. Thyroids Hormones

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A. Thyroids Hormones

• Iodide actively transported into the thyroid
  follicular cell
• -gt 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

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• 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
• --gt facilitates endocytosis, digestion of
  thyroglobulin-containing 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

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• 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

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B. Evaluation

• 1. Thyroid Function.
• ?TBG conditions pregnancy, oral pill, ERT,
  hepatitis, genetic abnormality of TBG,
• --gt require measuring T3RU for clarification.
• FTI ( Free T4 Index ) free T4 ( T3RU ) T4
  total
• TSH measurement best single screen for thyroid
  dysfunction.

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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

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• -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
• --gt 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.

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C. Autoimmune Thyroid Disease

• -Hypothyroidism gt hyperthyroidism
• -FgtM
• -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...

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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

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• 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 (lt-- represent a variant of
  Graves' Dz.) - in 48
• -Diagnosis
• ? TSH level during routine screening
• ? serum antithyroglobulin antimicrosomal Ab
• ? ESR

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• 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

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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

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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

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• 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.

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

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2) Treatment

• Medication --gt 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) ß-blocker

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• Antithyroid Drugs
• PTU Methimazole
• Low doses block the secondary coupling Rx. that
  form T3 T4 from DIT MIT.
• Higher doses --gt block iodination of tyrosyl
  residues in thyroglobulin.
• 30 --gt 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.

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• Surgery
• Subtotal thyroidectomy
• Ix.
• Medical Tx failed
• Hypersensitive to medical Tx.
• Risk
• Hypoparathyroidism
• Recurrent laryngeal n. paralysis
• Hypothyroidism.

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4. Reproductive Effects of Hyperthyroidism

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

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5. Postpartum Thyroid Dysfunction

• Often difficult to diagnose,
• Sx. appear 1 8 months postpartum.
• Incidence 5 -gt 25 permanent hypothyroid
• Histo lymphocytic infiltration inflammation.
• Antimicrosomal Ab ()

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• 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 --gt permanent hypothyroidism)
• rarely hyperthyroid phase not routinely use
  of anti-thyroid medication, but
• propranolol for symptomatic relief.