Thyroid D isease Facts

Dr. SUHAEMI, SpPD,

FINASIM

Sejarah Penyakit Tiroid

1800: pembesaran tiroid dianggap sebagai

suatu pembengkakan dari saluran nafas di

leher.
Tumit guttur ( latin ) : swollen throat
Goitre ( Prancis )( Inggeris )
Goiter ( Amerika )
Goiter ( Indonesia ), Struma (Pembengkakan )
Wharton , 1656 : Thyroid gland
Kendall, 1915 : hormon tiroksin,T4
Harrinton dan Barger : Rumus kimia T4

Sejarah Penyakit Tiroid

Parry 1825, Graves 1835, Von

Basedow 1840: Hipertiroid.

Parrys diseases, Graves Diseases,
Von Basedow Diseases
. Tiroiditis : Riedel 1896, Hashimoto
1912, De Quervain 1936.
Akhir abad 19 : Kanker tiroid
1909, Theodor Kocher : Operasi tiroid I
( NOBEL di Kedokteran)

Thyroid

Apical
Membran
e

Basal Membrane

Colloid

B A SIC TH YR O ID FU N C TIO N
Maintains Basal Metabolic Rate

(BMR)
Oxygen requirements

Regulates heat production

Influences body & tissue growth
Development of the nervous

system in the fetus and young

child

FEEDBACK REGULATION
THE HYPOTHALAMIC-PITUITARY-THYROID AXIS
Hormones derived from the pituitary that regulate
the synthesis and/or secretion of other hormones are
known as trophic hormones.

Key players for the thyroid include:

TRH - Thyrophin Releasing Hormone
TSH - Thyroid Stimulating Hormone
T4/T3 - Thyroid hormones

Kontrolkelenjar tiroid
Hormon tirotropin (TRH) yang dikeluarkan oleh

hipotalamus.
Menstimulasi pituitari anterior untuk
memproduksi tiroid stimulating hormon (TSH).
TSH akan memacu tiroid untuk memproduksi
tiroksin atau T4 (karena mengandung 4 atom
yodium).
Tiroksin akan menuju sel-sel sasaran.
Bila sel-sel sasaran kebutuhannya telah
mencukupi maka tiroksin akan memiliki efek
umpan balik negatif, artinya tiroksin akan
menghambat hipotalamus untuk memproduksi
TRH dan menghambat pituitari anterior untuk
memproduksi TSH.

Hypothalamus
TRH
+

Pituitary
TSH
+
TSHR-Ab
Thyroid
Iodine

T3 / T4
+
Ginjal, hati,
Otot, Otak, dsb

Pengatura
n Faal
Kelenjar
Tiroid

Thyroid H orm ones (T3 and T4)

H ow does thyroid horm one increase

m etabolism ?

1. Increase synthesis of Na/K

pump
2. Increase synthesis of
uncoupling protein UCP3
3. Increase protein synthesis and
degradation
4. Increase lipid synthesis and
degradation

ATP

ADP

Thyroid Function
1. Follicle cells make thyroglobulin protein
2.
3.
4.
5.

and secrete into apical space for storage

Follicle cells take up iodide from blood
Thyroid peroxidase adds iodide moieties
to make T3 and T4
TSH stimulates follicle cell to REUPTAKE
thyroglobulin
Follicle cells secrete T3 and T4 into blood.

M etabolism e H orm on Tiroksin

Waktu paruh di Plasma T4 : 6 hari dan T3 :

24 30 jam.
Dilakukan proses deiodinasi guna
mempertahankan hormon aktif sesuai dengan
kebutuhan.
3 macam deiodinasi
Deiodinasi tipe I (DI) :
Konversi T4 @ T3 di perifer. Tidak berubah waktu hamil
Deiodinasi tipe II (DII)
:
Konversi T4 @ T3 secara Lokal (di Placenta, Otak, SSP).
Penting untuk mempertahankan kadar T3 lokal
Deiodinasi tipe III (DIII) :
Mengubah T4 menjadi rT3 dan T3 @ T2. Khususnya di
Plasenta untuk mengurangi masuknya hormon ibu yang
berlebihan ke fetus.

rT3 ( reversed T3) secara metabolik tidak

aktif.

Form ation ofThyroid

H orm ones:
MIT (Monoiodotyrosine)
DIT (Diiodotyrosine)
Thyroxine (DIT x 2 = T4)
Triiodothyronine (2 DIT + 1 MIT = T3)

THYROID HORMONES
OH

OH

O
NH2

I
O

Thyroxine (T4)

OH

NH2

I
O

OH

3,5,3-Triiodothyronine (T3)

Only T3 is active at tissues

T4 is converted in tissues to T3

BASICS OF THYROID HORMONE

ACTION IN THE CELL

Thyroid Stim ulating H orm one (TSH )

TSH stimulates the

synthesis & secretion

of T3 and T4
Iodide uptake
Thyroid peroxidase
activity
Thyroglobulin
synthesis
Metabolic rate

Overview of Thyroid Function

Tests
TSH
FT4
Clinical Status
HIGH

LOW

LOW

Primary Hypothyroidism, Thyroiditis (stage 3)

NORMAL

Subclinical Hypothyroidism

HIGH

Pituitary Hyperthyroidism

HIGH

Thyrotoxicosis, Thyroiditis (stage 1)

NORMAL

Subclinical Hyperthyroidism, Autonomous nodules

LOW

Pituitary Hypothyroidism

Thyroid Tests
1. Thyroid Function
2. Iodine Kinetics
3. Thyroid Structure
4. FNA
5. Thyroid Antibodies
6. Thyroglobulin

Thyroid Testing
Radioactive Iodine Uptake and Scan

(RAIU/Scan)
123-RAIU/Scan or 131-RAIU/Scan
Indications:

biochemically hyperthyroid pt
No role in euthyroid or hypothyroid pts
RAIU produces a number.

4-hr (normal 10-15%)

24-hr (normal 20-30%)
The scan produces a picture
Tc99m-Pertechnetate Scan
Picture only, no number

Thyroid Function Tests

TSH
0.4 5.0 mU/L
Free T4 (thyroxine)
9.1 23.8 pM
Free T3 (triiodothyronine) 2.23-5.3 pM

T4

Protein* binding

+ 0.03% free T4

80% (peripheral)
20%

T3

Protein* binding
freeless
T3 than T4)
(10-20x

Total T460-155 nM
Total T30.7-2.1 nM
T3RU/THBI 0.77-1.23

+ 0.3%

*
TBG
75%
TBPA 15%
Albumin
10%

RAIU /Scan
Increased RAIU
Graves Disease
Toxic Nodules
MNG
Adenoma

hCG secreting tumors

Hydatidiform mole
Choriocarcinoma

RAIU produces a number.

4-hr (normal 10-15%)
24-hr (normal 20-30%)
The scan produces a
picture.

TSH mediated thyrotoxicosis

Pituitary tumor
Pituitary resistance to thyroid
hormone

Iodine Deficiency

RAIU /Scan
Decreased RAIU
Thyroiditis
Chronic painless
Postpartum
Subacute
Amiodarone-induced

Thyroiditis Factitia
Iodine Excess
Contrast dye
Diet
Amiodarone

RAIU produces a number.

4-hr (normal 10-15%)
24-hr (normal 20-30%)
The scan produces a
picture.

Struma ovarii:
(ectopic thyroid hormone production
from thyroid tissue in an ovarian
teratoma)

Thyroid Scan
Thyroid nodule: risk of malignancy 6.5%
only 5-10% of nodules

Cold nodule

16-20% malignant

Warm Nodule

(indeterminant)
5% malignant

Hot Nodule

Tc-99m < 5% malignan

I123 < 1% malignant

Thyroid N odules
Structural disorders of the thyroid

(i.e. nodules- simple or multiple)

are more common than functional
disorders.
Prevalence
Palpable: 5%
Non-Palpable: 40-50%
Cancer in nodules: 5%
Risks
Women > Men
Smoking
h/o XRT to head/neck (esp
children)
Iodine deficiency
Most are Euthyroid and
Asymptomatic
Less than 1% with thyrotoxicosis

Fine N eedle A spiration (FN A )

25G Needle, 10cc syringe
Done in Office
+/- Local
3-5 passes
SEN 95-99% (False Negative rate 1-

5%)
SPEC > 95%

FN A R esults
Nondiagnostic: repeat FNA
Benign: macrofollicular or "colloid"

adenomas, chronic autoimmune

(Hashimoto's) thyroiditis
Suspicious or Indeterminant:
microfollicular or cellular adenomas
(follicular neoplasm)
Malignant

B enign Lesions

Papillary Carcinoma
Surgical Specimen

FNA

Follicular Lesions on FNA: Cant Distinguish!

Thyroid nodules
U/S more sensitive than P.E., particularly for

nodules that are < 1 cm or located posteriorly

in the gland.
U/S also more SEN than thyroid scan
U/S too Sensitive?
Thyroid Incidentaloma (Carotid duplex, etc.)

TSH-R ab block
Thyroglobulin ab
Microsomal ab

Autoimmune
Thyroid Disease

TSH-R ab stim

Hashimotos

Graves Dx

(hypothyroid)

(hyperthyroid)

Thyroid Antibodies
Hashimotos
Thyroglobulin AB (<40 KIU/L)
Thyroid peroxidase AB (< 35 KIU/L)

Graves

TSI or TSH Receptor Ab (Stim): IgG antibody

SEN 60% SPEC 90%
2-3 month turn-around time
Indications:
Pregnant & present or past hx Graves: check 2 nd trimester
(if hi-titre > 5X normal needs PTU as TSI crosses placenta)
? Euthyroid Graves ophthalmopathy
Alternating hyper/hypo function due to alternating
Stim/Block TSI

Palpasi
Tiroid

Kelenjar

52

Goiter

G O ITER

54

Cretinsm

Mental Deficiency
Deafness
Motor Disorder
Short Stature

Cretinsm

Endemic Goiter

Three women of the Himalayas with typical endemic goiters.

Normal
deficient

Iodine-

Hypothyroidism

EXAMPLES OF THYROID DISEASES

1 Hypothyroidism

Hyperthyroidism

www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

EXAMPLES OF THYROID DISEASES

Juvenile Hypothyroidism

Congenital Hypothyroidism

www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

Graves Disease

exophthalmos

due to
edema
in the orbits

H yperthyroid Eye D isease

Hyperthyroidism (any cause)
Lid lag, lid retraction and stare
Due to increased adrenergic

tone stimulating the levator

palpebral muscles.

True Graves Ophthalmopathy

Proptosis
Diplopia
Inflammatory changes

Conjunctival injection
Periorbital edema
Chemosis
Due to thyroid autoAbs that
cross-react w/ Ags in
fibroblasts, adipo-cytes, +
myocytes behind the eyes.

Endem ic G oiter

71

www.drsarma.in

Urine Iodine Conc. < 50

g/L

72

www.drsarma.in

M yxedem a

www.drsarma.in

73

M yxedem a

74

www.drsarma.in

Thyroid Cancer

Thyroid Cancer
Papillary Thyroid Ca (PTC): 75%
Follicular Thyroid Ca (FTC): 15

20%
Medullary Thyroid Ca (MTC): <
5%
Anaplastic: < 5 %
Lymphoma: rare
Hashimotos is a risk factor
Metastatic to thyroid: rare
Breast, Renal cell, melanoma
and lung Ca

MTC
FMTC
MEN2A
MTC, HyperPTH, Pheo
MEN2B
MTC, Pheo, Mucosal neuromas

Thyroid D isease in Pregnancy

Four factors alter thyroid function in pregnancy
1) Transient in hCG, during the 1st trimester can stimulate the
TSH-R
- Gestational Transient Thyrotoxicosis (GTT)
- Hyperemesis gravidarum

2) E2-induced in TBG during the 1st trimester, which is

sustained during pregnancy.
3) Alterations in immune function leading to onset, exacerbation,
or
amelioration of an underlying autoimmune thyroid
disease.
4) urinary iodide excretion, which can cause impaired thyroid
hormone production in areas of marginal iodine deficiency
(<50 g/d).
- risk of goiter and hypothyroidism

Thyroid D isease in Pregnancy

Stage 1

Stage 2
Stage 4
Stage 3

Frequency of various clinical presentations of postpartum

thyroid dysfunction
Hypothyroid (postpartum exacerbation of Hashimotos):
40%
Hyper-/Hypothyroid (postpartum thyroiditis): 25%
Hyperthyroid Thyroiditis (postpartum thyroiditis): 24%
Hyperthyroid Graves: 20%

Thyroid D isease in Pregnancy

Graves (Treatment)
PTU, Tapazole and -blockers all cross the placenta.
ATDs still mainstay of tx
PTU preferred (crosses placenta < Tapazole)
Tapazole may be assoc w/ aplasia cutis
The lowest possible dose should be given

Goal of tx w/ ATD: maintain the mothers FT4 or FT3 in the

high-normal range.
TSH levels often remain suppressed w/ FT4 or FT3 in
these ranges + cant be accurately used for titrating
ATD.
If unable to use ATD- surgery (subtotal thyroidectomy) can
be done during 2nd trimester.
1st trimester: risk of miscarriage
3rd trimester: risk of preterm labor

D rugs Aff
ecting Thyroid Function

Somatostatin,
Glucocorticoids

Dopamine

Amiodarone Effect on Thyroid Function

T

T = Tyrosyl ring
(aka Inner ring)
P = Phenolic ring
(aka Outer ring)

TSH

Thyroid & D rug Interactions

1) Warfarin
T4 increases catabolism of vitamin K dependent clotting

factors.
Increase LT4/hyperthyroidism will increase sensitivity to

warfarin (decrease dose).

Decrease LT4/hypothyroidism will decrease sensitivity

to warfarin (increase dose).

2) Cholestyramine
Binds T4 & T3
4-5h between resin & LT4 or T3.

3) Iron or Calcium
Also binds T4 & T3

Thyroid & D rug Interactions

4) Estrogens
Increase TBG, decrease FT4 level
Need to increase LT4 in some patients

5) Androgens/corticosteroids
Decrease TBG, increase FT4 level
Need to decrease LT4 in some patients

5) Diabetes
Increase LT4/hyperthyroidism will increase insulin/OHA

requirements.
Decrease LT4/hypothyroidism will decrease insulin/OHA

requirements.

The End!