Thyroxine Free T4 (FT4)

What sample is needed for Thyroxine Free T4?

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

What are the precautions for Thyroxine Free T4?

1. Avoid lipemic serum.
2. Neonates have a higher level than older children and adults.
3. Some 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 has raised the free T4 level.

What are the indications for Thyroxine Free T4?

1. The thyroxine-free T4 level evaluates thyroid function in a protein abnormality patient.
2. It is used to diagnose thyroid function.
3. This is done to monitor replacement and suppressive therapy like levothyroxine. TSH takes 6 to 8 weeks to show changes.
4. Free T4 gives corrected values in patients where the total T4 is changed on account of changes in serum proteins or in binding sites like:
   1. Drugs such as androgens, birth control pills, estrogens, and phenytoin.
   2. In pregnancy.
   3. In the case of nephrosis, where serum proteins are altered.
5. Usually, it is not helpful unless hypothalamus/pituitary disease is suspected.

How will you discuss the Pathophysiology of thyroid hormones?

1. The thyroid hormone comprises 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 and albumin).
   1. Only 0.04% is Thyroxine free T4, and this is biologically active.

4. Only 1 to 5% of 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.
5. The protein level influences the T4 level.
6. FT4 is unbound to protein and is available to the tissue.
   1. FT4 is a metabolically active hormone.
7. 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.
8. In the case of hypoproteinemia, TBG is low, so total T4 will also be 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 a result of hypothyroidism.
   2. Total T4 is a good indicator of thyroid function if the TBG is normal.

What is Normal Thyroxine T4 Free (FT4)?

Source 1

T4 Free (FT4)

• To converts SI unit x 12.9 = nmol/L

T4 Total (T4)

Another 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)

What are the causes of increased Thyroxine-Free T4 (FT4)?

1. Hyperthyroidism.
2. Grave’s disease.
3. Hypothyroidism is treated with thyroxine.
4. Euthyroid sick syndrome.
5. Toxic thyroid adenoma.
6. Acute thyroiditis.
7. Struma ovarii.
8. Patients with hydatidiform mole or choriocarcinoma where the HCG level is raised will show:
   1. Increased Free T4.
   2. Suppressed TSH.
   3. Blunted response of TSH response to TRH stimulation.

What are the causes of decreased Thyroxine-Free T4?

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

How will you differentiate different thyroid diseases?

Questions and answers:

• Please see more details on Thyroid function.