Upload
jeffrey-dyer
View
228
Download
0
Tags:
Embed Size (px)
DESCRIPTION
Hipotiroidisme Kuliah
Citation preview
HypothyroidismDiagnosis and Management
dr Pandji M,SpPD, KEMD ,FINASIM
Definition :
Hypothyroidism is a clinical syndrome resulting from a deficiency of thyroid hormone which in turn results in generalized slowing down of metabolic processes.
Etiology of HypothyroidismEtiology of HypothyroidismPrimary :1. Hashimoto’s thyroiditis :
a. With goiterb. “Idiopathic” thyroid atrophy, presumably end-stage auto-
immune thyroid disease, following either Hashimoto’s thyroiditis or Graves’ disease
c. Neonatal hypothyroidism due to placental transmision of TSH-R blocking antibodies.
2. Radioactive iodine therapy for Graves’ disease3. Subtotal thyroidectomy for Graves’ disease or nodular goiter4. Excessive iodide intake (kelp, radiocontrast dyes)5. Subacute thyroiditis6. Rare causes in the USA
a. Iodide deficiencyb. Other goitrogens
(Adapted : Greenspan FS, 2001)(Adapted : Greenspan FS, 2001)
Secondary: Hypopituitarism due to Pituitary Adenoma Hypopituitarism due to Pituitary Adenoma
Pituitary Ablative Therapy orPituitary Ablative Therapy or
Pituitary DestructionPituitary Destruction
Tertiary :Hypothalamic Dysfunction ( rare )Hypothalamic Dysfunction ( rare )
Peripheral resistance to the action of thyroid hormone
Pharmacologic Hypothyroidism
I. Thyroid Hormone Synthesis Inhibitor– Tionamide : MTU, PTU, Carbimazol– Perchlorat, Sulfonamid– Yodide (Expectoran, Amiodaron)– Lithium
II. Thyroid Hormone Destruction– Phenitoin & Phenobarbital– Enterohepatic pathway inhibitor of thyroid hormone
Colestipol, Colestyramin
The Hypothalamic-Hypophysial-Thyroid AxisThe Hypothalamic-Hypophysial-Thyroid AxisHypothalamusHypothalamus
TSHTSH
ThyroidThyroid
TT33
TT33
TT44
TT33TT44
TT44
AnteriorAnteriorpituitarypituitary
TissueTissue
““Free”Free”
++
++
TRHTRH
Portal systemPortal system
Grades of Grades of HypothyroidismHypothyroidism
Individual and median values of thyroid function tests in patients with various grades of hypothyroidism. Discontinuous horizontal lines represent upper limit (TSH) and lower limit (FT4, T3) of the normal reference ranges.
(Adapted : Greenspan FS, 2001)(Adapted : Greenspan FS, 2001)
200200
100100
4040
1010
4.04.0
TSH
mU
/LTS
H m
U/L
FTFT 44 p
mol
/L p
mol
/L 15151212
99663300
TT 33 nnm
ol/L
mol
/L
2.52.52.02.01.51.51.01.00.50.5
00Subclinical Subclinical
HypothyroldismHypothyroldismMild Mild
HypothyroldismHypothyroldismOvert Overt
HypothyroldismHypothyroldism
PathogenesisThyroid Hormones
Synthesis of hyaluronate fibronectin and collagen by fibroblast
Accumulation of glucosaminoglycans mostly hyaluronic acid in interstitial tissues
Hydrophilic substanceincrease capillary permeability to albumin
Interstitial edema
SkinSkin Many organsMany organs(heart muscle, s(heart muscle, strtriated muscle)iated muscle)
(Wiersinga, 2004: The thyroid and its disease)(Wiersinga, 2004: The thyroid and its disease)
Hypothyroidism in adult (myxedema)
Physiologic Effect of Thyroid HormonePhysiologic Effect of Thyroid Hormone
Tissue growthTissue growth
Brain maturityBrain maturity
Heat production &Heat production &Oxygen consumptionOxygen consumption
CardiovascularCardiovascular
SympatheticSympathetic
PulmonaryPulmonaryHematopoiticHematopoitic
GastrointestinalGastrointestinal
neuromuscularneuromuscular
SkeletalSkeletal
Lipid & carbohydrateLipid & carbohydratemetabolismmetabolism
EndocrineEndocrine
THYROIDTHYROID
DIAGNOSIS
HYPOTHYROIDISM
SubclinicalSubclinicalHypothyroidismHypothyroidism
SecondarySecondaryHypothyroidismHypothyroidism
Clinical HypothyroidismClinical Hypothyroidism
FT4FT4TSHTSH
FT4 NFT4 NTSH TSH
TRH TestTRH Test
PrimaryPrimaryHypothyroidismHypothyroidism
FT4 FT4 TSH TSH
FT4 NFT4 NTSH NTSH N
FT4 FT4 TSH N/TSH N/
PrimaryPrimaryHypothyroidismHypothyroidism NormalNormal
FT4 FT4 TSH TSH
FT4 FT4 TSH TSH
NoNoResponseResponse
TertiaryTertiaryHypothyroidismHypothyroidism
SecondarySecondaryHypothyroidismHypothyroidism
Management of Hypothyroidism
Pay attention to :1. Initial dosage of thyroxin2. The way to increase thyroxin dosage
The Purpose of Hypothyroidism Treatment
1. To relief symptom and sign2. To normalize metabolism3. To normalize TSH, level but not supressed4. To normalize T3 & T4 levels5. Avoid risk and complications
Principles to conduct thyroxine replacement therapy
1. The more severe the disease, the lower the initial and the slower the increase dosage of thyroxine
2. The older the patients should more pay attention especially in cases of angina pectoris, congestive heart failure, cardiac arythmia
Thyroid Hormone available on the market:
• L-Thyroxin (T4) EuthyroxL-Triiodothyronine (T3)Thyroid Extract
The best is L-Thyroxin
• Should be taken before meals
• Dosage Recommendation :– L-T4 : 112 ug/d or 1,6 ug/kgB.W– L-T3 : 25-50 ug
(RRJ : Djoko Moeljanto, 2002)(RRJ : Djoko Moeljanto, 2002)
Starting dose of thyroxin• There is no evidence base for determining how
thyroxine therapy should be initiated, but it is customary to prescribe 50 ug daily, increasing to 100 ug daily after 3-4 weeks.
• Measurement of serum T4 and TSH at two months after starting will dictate any further adjustment of dosage.
• In the elderly, symptomatic ischemic heart disease, starting dose of 25 ug/d is advisable with increments of 25 ug/3-4 weeks.
• A full replacement dose of 100-150 ug/d.
((Toff ADToff AD, 2001; Thyroid International), 2001; Thyroid International)
The TSH level can be used as a guideline to establish the substitution dosage of
thyroxin
TSH level Thyroxin
20 uU/ml 50-75 ug/d
44-75 uU/ml 100-150 ug/d
90% Hypothyroidism cases used LT4 100-200ug
(RRJ : Djoko Moeljanto, 2002)(RRJ : Djoko Moeljanto, 2002)
Variation in dosage of thyroxin
Once thyroxin therapy is established it is good practice to review patients annually and measure serum TSH not only to ensure compliance but also to determine whether and adjustment of dose is required.
Situation in which an adjustment of the dose of thyroxine may be necessary
Increased dose requiredUse of other medicationPhenobarbitonePhenytoinCarbamazepine increased thyroxine clearanceRifampicin
*Sertraline*Chloroquine
CholestyramineSucralfateAluminium hydroxide interference with intestinalFerrous sulphate absorptionDietary fibre supplements
Pregnancy increased concentration of serumOestrogen therapy thyroxine-binding globulin
After surgical or iodine-131 reduced thyroidal secretionablation of Graves’ disease with time
Malabsorption e.g. coelic disease
Decreased dose required
Aging decreased thyroxine clearance
Graves’ disease developing switch from production of blockingin patient with long-standing to stimulating TSH-receptor anti-primary hypothyroidish bodies
* mechanism not fully established (Adapted : (Adapted : Toff ADToff AD, 2001), 2001)
Suggested management of patients taking thyroxine replacement therapy, depending upon pattern of thyroid
function test results and clinical symptoms
TSH T4 T3 Symptoms Actionnormal normal or normal none none
raisednormal normal or normal present increase thyroxine by 25-50 g daily
raised until serum TSH is suppressed but ensure T3 unequivocally normal
< 0.05 mU/l normal or normal none noneraised
< 0.05 mU/l normal or normal yes* reduce thyroxine by 25-50 g dailyraised to restore normal TSH
< 0.05 mU/l normal or high normal yes* or no reduce thyroxine by 25-50 g dailyraised or raised to restore unequivocally normal T3
Symptoms of possible undertreatment might include tiredness and weight gain* Symptoms of possible overtreatment might include unexplained atrial fibrillation and reduced bone mineral density
(Adapted : (Adapted : Toff ADToff AD, 2001), 2001)
Summary
• Some basic principles to remember that active hormone is free hormone.
• Cells metabolism are based on FT3 not FT4• Diagnosis established by symptom, sign, FT4 and
TSH • Should be careful to start and increase the dosage
of thyroxine especially in case of angina pectoris,CHF,arythmia
• Drug of choice is L-thyroxine • Target of treatment is normal TSH level