HYPOTHYROIDISM :

ETIOLOGY,
PATHOPHYSIOLOGY AND
TREATMENT
Dr. I Gede palgunadi, SpPD
SMF Penyakit Dalam
Rumah Sakit Umum Mataram
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Introduction
The hypothalamic-hypohyseal-thyroid axis

INTRODUCTION
Hypothyroidism
Clinical syndrome ~ TH deficiency
metabolic process
Accumulation of glycosaminoglycans
Myxedema (adult), cretin (new born)
Myxedema coma (severe)
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INTRODUCTION
Hypothyroidism
Primary, secondary, tertiary and peripheral
resistance to TH
Most common : Primary Hypo
In iodine deficient areas : IDD
In iodine sufficient areas : Hashimoto
(Chronic Autoimmune Thyroiditis)
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ETIOLOGIC CLASSIFICATION
I. Primary Hypothyroidism
Destruction of thyroid tissue

A.
1.
2.
3.
4.

Thyroiditis (chronic autoimmune thyroiditis, subacute

thyroiditis, postpartum thyroiditis)
I131 therapy, external radiation (neck)
Thyroidectomy : subtotal, total
Infiltrative

Defect in TH biosynthesis

B.
1.
2.
3.
4.

Iodine deficiencies
Thyroid gland agenesis / dysgenesis
Hereditary defects in TH biosynthesis
Drugs with Antithyroid effect
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ETIOLOGIC CLASSIFICATION
II. Central Hypothyroidism
A.

B.

Thyrotropin deficiency pituitary diseases

(Secondary Hypo)
Thyrotropin Releasing Hormone Deficiency
Hypothalamic Disorders (Tertiary Hypo)

III. Generalized Resistance to

Thyroid Hormone (GRTH)
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PATHOPHYSIOLOGY
Normal :

T4 , T3 , T4 T3 (peripher)
T4 : 100 125 mcg/day

Sub Clinical : small in T4 (but still in N range) :

adequate source of T3 symptom (-)
stimulating TSH secretion
hyperplasia, hypertrophy
T4 & T3 still Normal, TSH , symptoms (-)
Overt Hypo : frank in T4 :
T3 symptom (+)
TSH
T4 & T3 , TSH , symptoms (+)
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PATOPHYSIOLOGY
T3

metabolic process
Hypothermic, hypercholesterolemia
Accumulation of glycosaminoglycans
Edema : skin, muscles
heart muscle contractility,
Cardiomegaly, pericardial effusion,
Stroke volume / COP
Reproduction :
Anovulation, irregular cycles,
infertility
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THYROID

rT3
T3

T4

T4

T4

T4

TR
T3

rT3
T3

T4

TR

MATERNAL
TISSUES

MOTHER

T3

TR

PLACENTA

T3

TR

FETUS

Possible sites of action of maternal thyroid hormone during early pregnancy.

(Pickard et al, 2002)

Iodine is the essential element for thyroid hormones, thyroid hormone is

indispensable for every living cells, thyroid hormone is a must for DNA
synthesis

Fatal circulation

Maternal circulation

THYROID
Pituitary/Chorionic TSH controlled
T4 synthesis and release

T4

FETUS

Chorionic
TSH

T4 deiodination
and metabolism

T4

free T4

free T4

TBG bound T4

TBG
LIVER
Estrogen/fT4 controlled
TBG synthesis
and release

Estrogen

Feedback control
of T4 delivery

PLACENTA
TBG/T4 controlled
T4 deiodination and transport,
and chorionic TSH secretion

Hypothetical control system governing fetal exposure to

maternal T4 during pregnancy
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DIAGNOSIS
Importance of Etiologic Diagnosis
1. The hypo may be transient
2. The hypo may be reversible by
alleviating responsible drugs
3. The hypo may be the first and the only
manifestation of hypothalamopituitary disorders
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DIAGNOSIS
I. CLINICAL SUSPICION
1. Symptoms, signs, Lab.
2. Deficiencies, exposures, diseases
3. Diseases ~ chronic autoim. thyroiditis

II. CONFIRMATIVE EXAM

1. T4 (FT4) , Normal FT4 : 0.8-2.8 ng/dl
2. TSH (Primary Hypo), Normal : 0.4-4 mu/l
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Severe primary hypothyroidism

A: A patient with unrecognised severe primary hypothyroidism who became severely obtunded after surgery
for fractured neck of femur. Marked myxoedema is evident. B: Several months later, after therapy including
thyroid hormone replacement.
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DIAGNOSIS
SUSPICION
SYMPTOMS

SIGNS

LAB, ETC

Weakness, fatique,
Cold intolerance,
Weight , constip.,
Hoarseness,
Menorraghia,
Depression

Dry skin
Bradycardia
Prolonged relaxation time of tendon
reflex

Hypercholest.
Hyponatremia
Pericard Effusion
Myocardial
contractility
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CLINICAL SUSPICION
T4 (FT4), TSH
T4 , TSH

T4 N, TSH

T4 , TSH

T4 N, TSH N

Primary hypo

Sub clinical
hypo

Central hypo

Normal

TRH Test
T4 , TSH

T4 , TSH

Resp. (-)

Primary hypo

Tertiary
hypo

Secondary
hypo

Figure 1. Algorithm Diagnosis of Hypothyroidism

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DIAGNOSIS
I. IODINE DEFICIENCY
1. Radioactive iodine uptake
2. Urinary iodine excretion
3. TSH

II. CHRONIC AUTOIMMUNE

THYROIDITIS
1. T4 , TSH
2. Autoantibody anti TPO
3. Autoantibody anti TG

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DIAGNOSIS

Increased TSH in some central Hypo ~

Immunoreactive (but bioinactive) TSH

Decreased TSH, T4, T3 in severe

non thyroidal illness

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TREATMENT
Lifelong levothyroxine (T4) except in :
transient Hypo
reversible Hypo
Goal : Clinical euthyroidism, Normal T4 and TSH
Levothyroxine :
- Half life 7 days once daily dosage
- dosage :
- Substitution (adult) : 1.6 mcg/BW/day
x 100 mcg/day (range 50-200 mcg/day)
Evaluation / Adjustment : T4 & TSH 3-6 wkly
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TREATMENT
DOSAGE VARIATION
Lower

: Hashimoto, post radioiodine

High

: Total thyroidectomi, central hypo,

severe hypo, BW, pregnancy,
estrogen therapy, malabsorption,
excretion (nephrotic syndrome),
metabolism

Small initial dose : increase gradually : elderly

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TREATMENT
PREGNANCY
Higher dose due to :
1.
2.
3.
4.
5.

maternal clearance of T4
T4 transfer to fetus
Placental degradation of T4 (deiodinase)
TBG ~ estrogen
absorption ~ Fe, Calcium
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TREATMENT
ELDERLY / CAD

- Initial dose :
- Elderly : 50 mcg/day orally
- CAD : 25 mcg/day orally
- Increase by 25 mcg/day every 3-6 weeks until
normal TSH or arrhytmia
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TREATMENT
SUBCLINICAL HYPO

- T4 to prevent conversion to overt hypo

- Especially :
- TSH > 10 mu/L
- anti TPO
- Goiter or non specific symptoms
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TREATMENT
CENTRAL HYPO

- Deficiency of other trophic hormone ?

- ACTH defic Adrenal insuff

- T4 : + Glucocorticoid to prevent adrenal crisis

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TREATMENT
POST TOTAL THYROIDECTOMY
- Higher dose T4 for :
1. Substitution
2. Erradicate metastasis / prevent relaps
- Target : TSH < 0,01 mU/L
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TREATMENT
MYXEDEMA COMA
- Aggressive, dose, IV T4
- After blood sample (T4, TSH, Cortisol)
- IV T4 : 200-300 mcg 50-100 mcg/day
(+ IV T3: 5-20 mcg 2,5-10 mcg/8 hours
- IV Hydrocortisone 100 mg/8 hr (2 days)
decreased
- Supportive :
- Mech. Ventilation, O2
- IVFD
- Correct : Hypo Na, Hypothermia
- Antibiotics
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.for the children..

Every child has the right to an adequate supply of iodine
to ensure his (or her) normal developments.

..for the unborn child..

Every mother has the right to an adequate iodine nutrition
to ensure her unborn child experiences normal mental
development

Declarations from:
Convention on the Rights of the Child, UN Assembly, New York 1989, World Summit for Children, UN New York
1990, The Survival, Protection and Development of Children , World Conference on Micronutrients: Eliminating
the Hidden Hunger, Montreal 1991 (Unicef, FAO,WHO, ICCIDD), World Conference on Nutrition, Rome 1992
WHO, FAO
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SUMMARY
Hypothyroidism ~ TH deficiency ~HypothalamoPituitary-Thyroid Axis Disorders
Most common etiology : Primary Hypo
Iodine deficiency, Hashimoto thyroiditis
Patophysiology : metabolic process and glycosaminoglycans accumulation
Diagnosis
Therapy
Prognosis

: Clinical + T4 + TSH
: Levothyroxine (T4)
: reversible (T4)
poor in myxedema coma
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