Hypothyroidism

Diagnosis 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 Hypothyroidism
Primary :
1. Hashimotos thyroiditis :
a. With goiter
b. Idiopathic thyroid atrophy, presumably end-stage autoimmune thyroid disease, following either Hashimotos
thyroiditis or Graves disease
c. Neonatal hypothyroidism due to placental transmision of
TSH-R blocking antibodies.
2. Radioactive iodine therapy for Graves disease
3. Subtotal thyroidectomy for Graves disease or nodular goiter
4. Excessive iodide intake (kelp, radiocontrast dyes)
5. Subacute thyroiditis
6. Rare causes in the USA
a. Iodide deficiency
b. Other goitrogens
(Adapted : Greenspan FS, 2001)

Secondary:

Hypopituitarism due to Pituitary Adenoma

Pituitary Ablative Therapy or
Pituitary Destruction

Tertiary :
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 Axis

Hypothalamus
TRH
T3
Portal system
Anterior
pituitary
T4
Free

T4

T3

T3

+
TSH

Tissue

+
T4

Thyroid

200

100

TSH mU/L

Grades of
Hypothyroidism

40

10

(Adapted : Greenspan FS, 2001)

FT4 pmol/L

4.0

T3 nmol/L

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.

15
12
9
6
3
0
2.5
2.0
1.5
1.0
0.5
0

Subclinical
Hypothyroldism

Mild
Overt
Hypothyroldism Hypothyroldism

Pathogenesis
Thyroid Hormones
Synthesis of hyaluronate fibronectin and
collagen by fibroblast
Accumulation of glucosaminoglycans
mostly hyaluronic acid in interstitial tissues
Hydrophilic substance
increase capillary permeability to albumin
Interstitial edema
Skin
(Wiersinga, 2004: The thyroid and its disease)

Many organs
(heart muscle, striated muscle)

Hypothyroidism in adult (myxedema)

Physiologic Effect of Thyroid Hormone

Endocrine

Tissue growth

Lipid & carbohydrate

metabolism

Brain maturity

Heat production &

Oxygen consumption

Skeletal
neuromuscular

THYROID

Gastrointestinal

Cardiovascular

Sympathetic
Hematopoitic

Pulmonary

DIAGNOSIS
HYPOTHYROIDISM

Clinical Hypothyroidism
FT4
TSH
FT4
TSH

FT4 N
TSH

FT4

TSH N/

FT4 N
TSH N

Primary
Hypothyroidism

Subclinical
Hypothyroidism

Secondary
Hypothyroidism

Normal

TRH Test
FT4
TSH

FT4
TSH

No
Response

Primary
Hypothyroidism

Tertiary
Hypothyroidism

Secondary
Hypothyroidism

Management of
Hypothyroidism
Pay attention to :
1. Initial dosage of thyroxin
2. The way to increase thyroxin dosage

The Purpose of Hypothyroidism

Treatment
1. To relief symptom and sign
2. To normalize metabolism
3. To normalize TSH, level but not supressed
4. To normalize T3 & T4 levels
5. 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) Euthyrox
L-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)

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 AD, 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)

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 required
Use of other medication
Phenobarbitone
Phenytoin
Carbamazepine
Rifampicin
*Sertraline
*Chloroquine
Cholestyramine
Sucralfate
Aluminium hydroxide
Ferrous sulphate
Dietary fibre supplements

increased thyroxine clearance

interference with intestinal

absorption

Pregnancy
Oestrogen therapy

increased concentration of serum

thyroxine-binding globulin

After surgical or iodine-131

ablation of Graves disease

reduced thyroidal secretion

with time

Malabsorption e.g. coelic disease

Decreased dose required
Aging

decreased thyroxine clearance

Graves disease developing

in patient with long-standing
primary hypothyroidish

switch from production of blocking

to stimulating TSH-receptor antibodies

* mechanism not fully established

(Adapted : Toff AD, 2001)

Suggested management of patients taking thyroxine

replacement therapy, depending upon pattern of thyroid
function test results and clinical symptoms
TSH

T4

T3

Symptoms

Action

normal

normal or
raised
normal or
raised

normal

none

none

normal

present

normal or
raised
normal or
raised
normal or
raised

normal

none

increase thyroxine by 25-50 g daily

until serum TSH is suppressed but
ensure T3 unequivocally normal
none

normal

yes*

normal
< 0.05 mU/l
< 0.05 mU/l
< 0.05 mU/l

high normal yes* or no

or raised

reduce thyroxine by 25-50 g daily

to restore normal TSH
reduce thyroxine by 25-50 g daily
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 : Toff AD, 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