HYPERTHYROIDISM AND

HYPOTHYROIDISM
Introduction

The terms of hyper- and hypothyroidism are

related to the function of thyroid gland
Thyrotoxicosis is clinical syndrome that results
when tissues are exposed to high levels of
circulating thyroid hormones
The function of thyroid gland is synthesis of
thyroid hormones: T4 (tetraiodothyronine/
thyroxine) and T3 (triiodothyronine)
Laboratory examination of thyroid function

The function of the thyroid gland may be

evaluated in many different ways: 1. test of
thyroid hormones in blood, 2. evaluation of the
hypothalamic-pituitary-thyroid axis, 3.
assessment of iodine metabolism, 4. estimation
of gland size, 5. thyroid biopsy 6. observation
on peripheral tissue, and 7. measurement of
thyroid autoantibodies (Greenspan, 2004)

TSH (thyroid stimulating hormone), T4

(thyroxine), T3 (triiodothyronine)
Physiologic effects of thyroid hormones
Effects on fetal development (brain development, skeletal
maturation)
Effects on oxygen consumption, heat production, and free radical
formation
Cardiovascular effects (positive inotropic and chronotropic effects)
Sympathetic effects (sensitivity to cathecolamine is markedly
increased)
Pulmonary effects
Hematopoietic effects (increased production of erythropoietin)
Gastrointestinal effects (stimulated gut motility)
Skeletal effects (stimulated bone turnover, bone resorption
Neuromuscular effects
Effects on lipid and carbohydrate metabolism
Endocrine effects
 Draft: Not Approved for Use

TRH
 High
Primary Subclinical Secondary

THYROTROPIN (TSH) LEVEL

Hypofuncti Hypofunction Hyperfuncti
on on

Normal

Normal
range

Pituitary Subclinical Primary

Low

Failure Hyperfunction Hyperfuncti

on

Low Normal High

THYROID HORMONE LEVEL
HYPERTHYROIDISM
THYROTOXICOSIS:
a condition caused by excessive thyroid
hormon whether the excess result from
overproduction by thyroid gland, originates
outside the thyroid or is due to loss/leakage of
storage from thyroid gland.

HYPERTHYROIDISM:
a condition caused by excessive thyroid
hormon whether the excess result from
overproduction by thyroid hyperfunction
Hyperthyroidism: clinical signs and symptoms

Skin: warm, smooth, sweating increases,

hyperpigmentation, pruritus
Eyes: lid lag (sclera can be seen above the iris as the
patient looks downward)
Cardiovascular system: increased cardiac output,
tachycardia, atrial fibrillation (10-20%)
Serum lipid: low total cholesterol, low HDL-C
Respiratory system: dyspnea (increased oxygen
consumption and CO2 production, respiratory muscle
weakness)
Gastrointestinal system: weight loss, increased gut
motility, hyperphagia, malabsorption, vomiting,
abnormality in liver function test
 Hyperthyroidism: clinical signs and symptoms

Hematologic system: normochromic-normocytic anemia

Genitourinary system: frequency, nocturia, in women high
serum estrogen concentrations, oligomenorrhea, anovulatory
infertility. In men high serum total testosterone
concentrations, gynecomastia, reduced libido, erectile
dysfunction
Skeletal system: stimulation of bone resorption, osteoporosis
Neuromuscular system: tremor, deep tendon reflexes are
hyperactive, hyperactivity, emotional lability, anxiety,
inability to concentrate, insomnia, hypokalemic periodic
paralysis
Hyperglycemia: antagonism to peripheral action of insulin
(increased gluconeogenesis, -glycogenolysis, - intestinal
glucose absorption)
Hyperthyroidism: clinical signs and symptoms

Primary hyperthyroidism: TSH decreases, FT4 or FT3

increases (low TSH concentration with normal FT4
concentration is named subclinical hyperthyroidism)
Secondary hyperthyroidism: TSH increases, FT4 or FT3
increases, TRH decreases
Tertiary hyperthyroidism: TSH increases, TRH
increases, and FT4 or FT3 increases
The clinical manifestations of hyperthyroidism are
largely independent of it cause
 Graves' Disease
(Diffuse Toxic Goiter)

Parrysdisease or Basedows disease

The most common form of
hyperthyroidism accounting for 60-
70% of all cases.
It occurs in up to 3% of the
population.
 A disorder with 3 major manifestations :

1. Hyperthyroidis
m with diffuse
goiter
2. Opthalmopath
y
3. Dermopathy
Stress, infection, trauma, drugs
OCULAR SIGNS & SYMPTOMS
GRAVES DISEASE
- Wide palpebral aperture
(Dalrymples sign)
- Lid lag (von Graefes sign)
- Staring or frigthened
expressions
- Infrequent blinking
(Stellwags sign)
- Absence of farehead
wringkling on upward
(Joffroys sign)
- Inability to keep converged
(Mobius sign)
- Diplopia
- Swelling of orbital contents
and puffiness of the lids
- Chemosis, corneal
injection/ulceration
- Exophthalmus
- Decreased visual acuity,
retinal edema/hemorrhages,
optic nerve damage
 21 months post Graves Disease
diagnosis and treatment with MMI.
DIAGNOSIS

Signs and
symptoms
Laboratory :
Increased value of
FT3, FT4
Decreased value of
TSH
Increased value of
RAIU (hyperfunction)
 TREATMENT

Anti Thyroid Drug

Radioactive Iodine
Surgical Therapy
 Anti Thyroid Drug
1. Thionamides :
Propylthiouracil (PTU)
Methimazole (MMI) &
Carbimazole
2. Inorganic Iodide
3. Potassium Perchlorate
4. Lithium Carbonate
-adrenergic Antagonist Drugs
PTU & MMI
Action
1. Intrathyroidal
Inhibition of iodine oxidation & organification
a.
Inhibition of iodotyrosine coupling
b.
Possible alteration of structure of
c.
thyroglobulin
d. Possible inhibition of thyroglobulin
biosynthesis
2. Extrathyroidal : inhibition of conversion of T4
to T3 (only by PTU)
3. On the immune system
 XX
X

X PTU
 PTU & MMI

Long-term treatment of Graves'

disease (preferred 1st-line
treatment in Europe, Japan, &
Australia)
PTU is treatment of choice in
patients who are pregnant and
those with severe Graves' disease.
Both medications considered safe
for use while breastfeeding
 PTU
300 mg daily in 3 divided
doses.
Severe hyperthyroidism or
very large goiters, initial
dosage may be increased to
400 mg/day, up to 600 to 900
mg/day.
The maintenance dosage is
100 to 150 mg/day every 8 h.
duration of action from 12 to
24 h
PO peak serum concentrations
occurring in one hour
MMI
15 to 30 mg/day as a single dose.
15 mg/day for mild
hyperthyroidism
30-40 mg/day for moderately
hyperthyroidism.
60 mg/day for severe
hyperthyroidism.
The daily dose is divided into 3
doses administered every 8
hours.
The maintenance dose is 5-15
mg/day
duration of action even longer
 antithyroid drugs have immunosuppressive effects, a
higher dose or longer treatment duration might
enhance the chances of remission.
300-900mg
PTU
15-60mg MMI
Follow-up testing
of thyroid
function
4 to 6 weeksAfter the first 3 to 6 months,
follow-up intervals can be increased
to every 2 to 3 months
and then every 4 to 6 months.
100-150mg PTU
5-15mg MMI Duration of
treatment
4-12 weeks patients will improve 12 to 18
months
Antithyroid drugs are usually stopped or tapered after 12 to 18
months.
P T U & M M I

- Relapse more likely in smokers,

patients with large goiters, and
patients with positive thyroid-
stimulating antibody levels at end of
therapy.
therapy
Relapse usually occurs within the first
three to six months after medication is
stopped.
Methimazole, with its once daily
schedule, has decided advantages over
propylthiouracil, including better
adherence

Finally, differences in the side-effect

profiles of the two drugs favor
methimazole.
Thyroid Crisis
 Life threatening clinical extreme of
hyperthyroidism

Female > Male

Mortality 10-20% with treatment
FT3 and FT4 correlate poorly with
severity of condition: condition is
essentially an inability of end-organs
to modulate their response to excess
thyroid hormone
 Aetiology
Usually occurs in patients with poorly
controlled-unrecognized
hyperthyroidism
Precipitated by intercurrent illness : infection,
trauma, surgery, uncontrolled DM, labour,
eclampsia
Other precipitants include excessive palpation
of thyroid, incomplete pre-op preparation,
inadequate peri-operative dose of beta
blockers, use of radio-iodine in unprepared
patients, drugs such as iodides in patients
with impaired autoregulation, haloperidol,
massive overdose of thyroid hormone
The classic clinical presentation: fever, tachycardia,
tremor, nausea+vomiting, diarrhea, dehydration,
delirium, coma

Hyperpyrexia. May be extreme (>41oC) and is

generally considered essential to diagnosis.
Confusion, coma, muscle weakness.
Arrhythmias, cardiac failure. Decreasing pulse
rate and BP with the development of shock are
associated with poor prognosis
Vomiting, diarrhoea. Occasionally jaundice:
associated with poor prognosis
Apathetic hyperthyroidism (elderly patients)
may present in crisis with features of profound
exhaustion, tachycardia, hyporeflexia, severe
myopathy, marked weight loss and
hypotension
 Treatment
1. Treat underlying cause
2. Decrease thyroid hormone
concentrations
3. Reduce peripheral action of
thyroid hormones
4. Supportive therapy
Treatment to reduce thyroid hormone
concentrations
1. Iodine:in large doses inhibits release of
thyroid hormones. Generally given > 1 h
after PTU/carbimazole/methimazole, - it
may lead to an increase in thyroid hormone
synthesis.
Use Lugol's iodine (16 mg bd PO),
potassium iodide (50 mg bd PO) or sodium
iodide (0.5 mg bd IV).
Lithium carbonate (300 mg qds titrated to a
serum lithium level of 0.7-1.4 mmol/l) is an
alternative in patients who are allergic to
iodine.
Treatment to reduce thyroid hormone
concentrations

2. Propylthiouracil (inhibits conversion of T4

to T3 as well as blocking iodination of
tyrosine and hence secretion of T4).
PO/NG 1 g loading followed by 200-300
mg 4-6 hrly.
Rapid onset of action.
Alternatives are methimazole and
carbimazole Methimazole may be
absorbed more slowly than PTU but is
longer acting. Does not affect peripheral
conversion of T4.
Treatment to reduce peripheral action of thyroid
hormones

Beta blockade: IV propranolol 0,5 mg to a

total of 10 mg. Give further doses 4-6 hrly.
Drug of choice: inhibits peripheral
conversion of T4 to T3.
Beta1 selective agents do not inhibit T4 to
T3 conversion as effectively but may be
preferred in patients with reactive airways or
heart failure.
Diltiazem, reserpine and guanethidine
should be considered in patients in whom
beta blockade is contraindicated
 Supportive therapy
1. Nutrition.
2. Steroids: hydrocortisone 300 mg loading
followed by 100 mg tds. Relative
hypoadrenalism occurs as a result of
increased metabolism of corticosteroids
3. Sedation
4. NGT
5. Vitamins
6. Active cooling. Chlorpromazine 25-50 mg 4-6
hrly to prevent shivering
7. Fluid replacement. Patients tend to be fluid
depleted because of increased insensible
loss, diarrhoea and vomiting
40
 Introduction
Hypothyroidism is common
endocrine disorders
1%-2% of the population
Incidence in Women (2%) > Men
(0,2%)
Women: postpartum, elderly & with
autoimmune disorders

41
 Causes of Hypothyroidism

Primary hypothyroidism
Destruction of thyroid tissue
Chronic autoimmune thyroiditis (Hashimotos),
radiation, thyroidectomy, infiltrative disease
Defective thyroid hormone synthesis
iodine deficiency, drugs with antithyroid actions

Central hypothyroidism: pituitary, hypothalamic

Transient hypothyroidism
Silent thyroiditis, subacute thyroiditis, after
withdrawal of thyroid hormone therapy in euthyroid
patients
 Tabel 1. Penyebab Hipotiroidisme

PENYEBAB HIPOTIROIDISME
Primer Sentral

Tiroiditis Autoimun Kronik Tumor

Tiroiditis autoimun reversibel Trauma

(subakut,postpartum)

Ablasi RadioIodin Vaskuler

Pembedahan Infeksi
Radiasi Infiltrasi
Penyakit infeksi dan infiltrative Kongenital
Disgenesis Tiroid congenital Obat-obatan
Defisiensi yodium
Obat-obatan
43
44
 Tabel 2. Obat yang berhubungan dengan Hipotiroidisme
Diambil dari Woolever dan Beutler, 2007 (1)

OBAT-OBAT yang berhubungan

dengan Hipotiroidisme
FUNGSI JENIS OBAT

Menurunkan sekresi TSH Dopamine

Glukokortikoids
Octeotride
Menurunkan sekresi hormon
Tiroid Lithium
Iodide
Amiodarone
Menurunkan absorpsi T4
Colestipol
Cholestyramine
Aluminium hydroxide
Ferrous sulfate
Sucralfate
Calcium
Meningkatkan metabolisme Phenobarbital
hormon Tiroid Rifampin
Phenytoin
Carbamazepine 45
46
 Tabel 3. Manifestasi Klinis Utama Hipotiroidisme

Manifestasi klinis utama Hipotiroidisme

Sistem Efek Hipotiroidisme Sensitifitas Spesifisitas
(%) (%)
Kulit Kering, Kasar ( aktiftas kel. Keringat) 76 64
Penyembuhan lambat, mudah memar (kapiler rapuh) - -
Kulit dingin 50 80
Mlksedema - -
Rambut Kering, mudah patah, kusam, mudah rontok - -

Kardiovaskular Denyut jantung , isi sekuncup 58 42

GastroIntestinal Kenaikan BB ringan karena retensi cairan 54 78
Nafsu makan menurun - -
Konstipasi 48 85
Efek kompleks dari absorpsi usus - -
Saraf Pusat Inisiatif hilang, letargi, somno - -
Lambat berbicara 36 99
Reflek melambat 77 94
Geriatri: Dementia (mirip dementia senilis), dapat
sebabkan Gangguan psikiatrik (paranoid & depresi)

Muskuloskeletal Nyeri otot dan kaku - -

Hematologi Anemia, mudah berdarah (trmbosit , pembekuan ) - -
Reproduksi Wanita: libido menurun, anovulasi - -
Pria: libido menurun, impoten, oligospermi
Metabolisme sintesis protein menurun - -
Penurunan degradasi lipid dan LDL meningkat

47
48
 Hypothyroidism: laboratory findings

Primary hypothyroidism: high serum TSH concentration and low

serum FT4 concentration (high serum TSH concentration with
normal serum FT4 concentration is named subclinical
hypothyroidism)
Secondary hypothyroidism: low serum FT4 concentation with low
serum TSH concentration, and high serum TRH concentration
Tertiary (central) hypothyroidism: low serum FT4 concentration
with low serum TSH concentration and low serum TRH
concentration
 Tabel 4. Nilai Laboratorium pada Hipotiroidisme

Nilai Laboratorium
Kadar TSH
Hipotiroidisme
FT4 FT3 Kemungkinan Diagnosis
Tinggi Rendah Rendah Hipotiroidisme Primer

Tinggi Normal Normal Hipotiroidisme subklinis dg risiko tinggi menjadi

(>10mlU/L) Hipotiroidisme klinis
Tinggi Normal Normal Hipotiroidisme subklinis dg risiko rendah menjadi

(4,5-10mlU/L) Hipotiroidisme klinis

Tinggi Tinggi//rendah Tanpa Enzim yg konversi T4-T3 secara congenital;
Efek Amiodaron pada konversi T4-T3
Tinggi Tinggi Tinggi Resisten hormon Tiroid di Perifer
Rendah Rendah Rendah Defisiensi Hipofise-Tiroid/Hipotiroidisme sentral;
Withdrawl Tiroxin sesudah Tx hormon berlebihan

50
Algoritma Penyakit Kel.
Tiroid

51
 Treating Hypothyroidism

The goals for managing

hypothyroidism are to increase the
serum concentration of thyroid
hormone, provide the patient
symptomatic relief and reverse any
biochemical abnormalities that could
cause serious clinical consequences
Levothyroxine sodium is the synthetic
treatment of choice because it is well
tolerated, and efficacious
52
53
 Dosing and Monitoring

Levothyroxine dosing is individualized and

depends on patient age and cardiac disease
history.
Gastrointestinal disorders and pregnancy
can increase levothyroxine dose
requirements to achieve normal thyroid
function.
The therapeutic dose for most patients is
100 to 125 mcg once daily.
The levothyroxine dose for patients older
than 50 years or younger patients with
cardiac disease should be 25 to 50 mcg daily
6 to 8 weeks after levothyroxine therapy
begins, assess the clinical response and 54
 Monitoring
If the TSH level remains elevated, the daily levothyroxine
dose should be increased by 12.5-25 mcg.

Conversely, if the TSH level is below normal, then the

levothyroxine dose should be decreased by 12.5-25 mcg

After any dose adjustment, the patients TSH should be

checked every 8 to 12 weeks and the dose should be
refined as necessary.

If the TSH concentration normalizes, retain the

levothyroxine dose and monitor the patient less
frequently 6 to 12-month intervals are usually sufficient

55
 Thyroid stimulating hormone Thyroid stimulating hormone Thyroid stimulating hormone
level >10 mU/l with or without level 5-10 mU/l with level 5-10 mU/l with
low free serum thyroxine low free serum thyroxine normal free serum thyroxine

Symptoms of hypothyroidism

Yes
No

3-6 months trial of thyroxine

Check status of thyroid
peroxidase antibody
Symptom resolved?
Positive result Negative
result
Yes No
Recheck Recheck
thyroid thyroid
Treat with Consider stimulating stimulating
thyroxine life long alternative hormone hormone level
diagnosis level annually every three
years

Vaidya B and Peacrce SHS. BMJ 2008; 337: 284-289

IODINE DEFICIENCY DISORDERS
(IDD)

Iodine has major role in the development of

physical and mental of children during pregnancy
The consequence of iodine deficiency beyond
endemic goiter and endemic cretinsim
 Spektrum GAKI

Fetus abortus, lahir mati

anomali kongenital
peningkatan kematian perinatal
peningkatan kematian anak
kretin endemi -gangguan mental
-bisu tuli
-diplegia spastik
-mata juling
kretin miksedematosa -cebol
-gangguan mental
defek psikomotor
Neonatus gondok neonatal, hipotiroid neonatal
Anak & gondok, hipotiroid juvenile, gangguan mental
remaja gangguan perkembangan fisik
Dewasa gondok dengan segala akibatnya, hipotiroid,
Djokomoeljanto, 1974
Pembesaran kelenjar gondok (goiter)

Grade 0 tidak teraba

Grade 1a tidak teraba atau bila teraba
tidak lebih besar dari normal
Grade 1b jelas teraba dan membesar,
tetapi tidak terlihat meskipun
kepala ditengadahkan
Grade II mudah dilihat, kepala posisi
biasa
Grademasyarakat
Survei III terlihat
dilakukandari
bila jarak tertentu
ditemukan 30% pada
anak sekolah (termasuk grade I)k
Bila gondok endemik >5% perlu perhatian
Bila gondok endemik >10% perlu pengobatan pencegahan
 Derajat endemi

Endemi grade I (ringan)

bila nilai median ekskresi yodium urin
>50 ug I/g kreatinin atau median urin 5-9,9 ug/dl,
prevalensi gondok anak sekolah 5-20%
Endemi grade II (sedang)
bila nilai median ekskresi yodium urin
25-50 ug I/g kreatinin atau median 2-4,9
ug/dl, prevelensi gondok anak sekolah sampai 30%
Endemi grade III (berat)
bila median <25 ug I/g kreatinin atau <2 ug/dl,
prevalensi gondok anak sekolah >30%, prevalensi
kretin endemik 1-10%
 Diagnosis kretin endemik secara individu
Seorang yang lahir di daerah defisiensi yodium
berat dengan 2 atau lebih kombinasi gejala
ireversibel berikut: retardasi mental, kelainan
neuromotorik (gangguan bicara, cara berjalan
khas, refleks patologis dan refleks fisiologias
meninggi, mata juling, gangguan akibat kerusakan
batang otak, serta late walker), dan gangguan
pendengaran (bilateral, tipe preseptif dan pada
nada tinggi)
Dengan atau tanpa hipotiroid