Thyroid – Part 6 – Thyroxine T4, Free T4

Sample

1. This test is done in the serum.
2. Immediately refrigerate the serum.
3. The sample is stable at room temp. for 7 days but refrigeration is better.

Precaution

1. Avoid lipemic serum.
2. Neonates have a higher level than older children and adults.
3. Some of the drugs increase T4 levels like heparin, aspirin, propranolol, and danazol.
4. Some of the drugs decrease the T4 level like furosemide, rifampicin, phenytoin, and methadone.
5. If a patient taking exogenous thyroxine will have raised the free T4 level.

Indications

1. The FT4 level is used to evaluate thyroid function in a patient who has protein abnormality.
2. It is used to diagnose thyroid function.
3. This is done to monitor replacement and suppressive therapy.

Pathophysiology

1. Thyroid hormone is made of Triiodothyronine ( T3 ), and Thyroxine ( T4 ).
2. Over 90 % of thyroid hormone is made of Thyroxine T4.

3. As much as 99 % of T4 is bound to protein (Thyroid binding globulin TBG and albumin).
   1. Only 0.04% is free T4 and this is biologically active.

4. Only 1 to 5 % T4 is unbound or free T4 (source 2).
   1. Free thyroxine FT4 comprises a small fraction of total thyroxine.
   2. When measuring total T4 = unbound T4 + bound T4.
   3. The protein level influences the T4 level.
5. FT4 is unbound to protein and is available to the tissue.
   1. FT4 is a metabolically active hormone.
6. Pregnancy and hormone replacement therapy increase the TBG and lead to false increases at the T4 level.
   1. In that case, suggest hyperthyroidism when actually the patient is euthyroid.
   2. In such cases when you measure Free T4, it will be normal, indicating the measurement of the Free T4 is more accurate than the total T4.
   3. In the case of hypoproteinemia, TBG is low, so total T4 will be also low, suggesting hypothyroidism.
      1. Now if you measure Free T4, it will be the normal level, and negate the abnormal level of total T4 which is due to a low level of TBG and not as a result of hypothyroidism.
   4. Total T4 is a good indicator of thyroid function if the TBG is normal.

Normal

Source 1

T4 Free (FT4)

Age	ng/dL
Newborn 1 to 4 days	2.2 to 5.3
Child (2 weeks to 20 Years	0.8 to 2.0
Adult 21 to 87 years	0.8 to 2.7
Pregnancy
1st trimester	0.7 to 2.0
2nd and 3rd trimester	0.5 to 1.6

• To converts SI unit x 12.9 = nmol/L

T4 Total (T4)

Age	µg/dL
Cord blood	7.4 to 13.0
1 to 3 days	11.8 to 22.6
1 to 2 weeks	9.8 to 16.6
1 to 4 month	7.2 to 14.4
4 to 12 month	7.8 to 16.5
1 to 5 year	7.3 to 15.0
5 to 10 year	6.4 to 13.3
10 to 15 year	5.6 to 11.7
Adult	Male =  4.6 to 10.5           Female  =   5.5 to 11.0
>60 year	5.0 to 10.7
Maternal serum 15 to 40 weeks	9.1 to 14.0

Source 2

T4 Free

• Newborn (0 to 4 days) = 2 to 6 ng/dL  (26 to 77 pmol/L)
  • Child 2 weeks to 20 years = 0.8 to 2.0 ng//dL
• Adult  = 0.8 to 2.8 ng/dL (10 to 36 pmol/L)

Newborn FT4 index

• Newborn FT4 index = 9.9 to 7.5 ng/dL
• pubertal child and adult FT4 index = 4.2 to 13.0 ng/dL

T4 Total (T4)

Age	µg/dL
1 to 3 days	11.22
1 to 2 weeks	10 to 16
1 o 12 months	8 to 16
1 to 5 years	7 to 15
5 to 10 years	6 to 13
10 to 15 years	5 to 12
Adult	Male 4 to 12      Female 5 to 12
>60 years	5 to 11

The increased level is seen in:

1. Grave’s disease.
2. Hypothyroidism treated with thyroxine.
3. Euthyroid sick syndrome.
4. Hyperthyroidism.
5. Toxic thyroid adenoma.
6. Acute thyroiditis.
7. Struma ovarii.

The decreased level is seen in:

1. Primary hypothyroidism.
2. Secondary hypothyroidism (pituitary).
3. Congenital TBG deficiency.
4. Tertiary hypothyroidism (Hypothalamic).
5. Cushing’s disease.
6. Cirrhosis.
7. Renal failure.
8. Iodine insufficiency.
9. Myxedema.
10. Advanced cancer.

• Please see more details on the Thyroid function.

---