Transcript the molecular basis of apoptosis

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. Hashimoto’s thyroiditis :
a. With goiter
b. “Idiopathic” thyroid atrophy, presumably end-stage autoimmune 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’ 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
Grades of
Hypothyroidism
200
TSH mU/L
100
40
10
(Adapted : Greenspan FS, 2001)
FT4 pmol/L
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.
4.0
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
(RRJ : Djoko Moeljanto, 2002)
– L-T3 : 25-50 ug
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