Transcript A. Thyroids Hormones

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
 Can’t regress the size but prevent further
growth of size
Pregnant women with↑ TSH level
L-thyroxine.
:Can’t 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) β-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.