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