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Thyroid:- Part 5 – Thyroxine Total, T4

December 17, 2024Chemical pathologyLab Tests

Table of Contents

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  • Thyroxine Total,T4
        • What sample is needed for T4 Total?
        • What are the precautions for Thyroxine Total (T4 Total)?
        • What are the indications for Thyroxine Total (T4 Total)?
        • How will you define Thyroxine Total (T4 Total)?
        • How will you discuss the pathophysiology of thyroid hormones?
        • How will you interpret Thyroxine (T4)?
        • What are Thyroxine (T4) and triiodothyronine (T3) functions?
        • What are the normal values of thyroxine (T4)?  
      • T4 Total (T4)
        • Source 1
      • T4 Free (FT4)
      • T4 Total (T4)
        • Another Source 2
      • T4 Free
        • What are the causes of increased T4 levels?
        • What are the causes of decreased T4 levels?

Thyroxine Total,T4

What sample is needed for T4 Total?

  1. This test is done on the patient’s serum.
  2. The sample is stable for 7 days at room temperature, but refrigeration at 4 °C is preferred.

What are the precautions for Thyroxine Total (T4 Total)?

  • Avoid lipemic serum.

What are the indications for Thyroxine Total (T4 Total)?

  1. This is done to assess thyroid function.
  2. It is advised to diagnose thyroid diseases like hypo or hyperthyroidism.
  3. This is also done to monitor the therapy.

How will you define Thyroxine Total (T4 Total)?

  1. Thyroxine, also known as T4, is the major secretion of the thyroid gland, bound to thyroid-binding globulin, prealbumin, and albumin.
  2. Thyroxine is produced in the thyroid gland and is stimulated by the TSH hormone.
  3. In tissue, thyroxine (T4) is deiodinated into T3, which causes hormonal action.
  4. Thyroxine is needed for the body’s growth, body metabolism, and energy.
  5. Thyroxine (T4) is synthesized in the thyroid gland by the amino acid tyrosine and iodine.

How will you discuss the pathophysiology of thyroid hormones?

  1. Thyroid hormone formation is basically intrathyroidal iodine metabolism.
  2. This process consists of the following stages:
    1. Iodine trapping is an uptake of iodine by the follicular cells.
    2. Oganification or iodination is the process where iodine is incorporated into thyroid hormones.
      1. Normally thyroid organifies about 75 µg of iodine per day.
    3. Coupling.
    4. Storage.
    5. Secretion.
  3. Thyroxine T4 forms by the combination of:
    1. diiodotyrosine + diiodotyrosine = Tetra-Iodo-Tyrosine (Thyroxine or T4).
Thyroglobulin role in the synthesis of T3 and T4

Thyroglobulin’s role in the synthesis of T3 and T4

How will you interpret Thyroxine (T4)?

  1. T4 makes most of the thyroid hormone because T3 is only 10%.
    1. 80% of the T4 is metabolized into:
      1. T3 = 35%
      2. rT3 (reverse T3)  = 45%
      3. rT3 is a biologically inactive isomer.
  2. Most of the T4 is bound to thyroglobulin, prealbumin, and albumin.
    1. T4  is pro-hormone with thyroglobulin binding (TBG).
Thyroxine carrier proteins

Thyroxine (T4) carrier proteins

  1. There is a very small fraction of free T4.
    1. Serum Total T4 = Bound T4 + Free T4
  2. When T4 converts into T3, then hormonal action starts.
Thyroxine formation

Thyroxine (T4)  formation

What are Thyroxine (T4) and triiodothyronine (T3) functions?

  1. Thyroid glands play a major role in body function. T4 and T3 are involved in the growth and maturation of bone and skeletal systems.
  2. T3 is 3 to 8 times more metabolically active than T4 and is considered the active form of the thyroid hormone.
    1. It regulates body temperature.
    2. It plays a role in the body’s metabolism of fats, carbohydrates, and proteins.
Thyroid T4 and T3 functions

Thyroid T4 and T3 functions

What is the effect of raised thyroid hormones, T4 and T3?

Increased Thyroid hormones

Increased Thyroid hormones

What are the normal values of thyroxine (T4)?  

Source 1

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 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
 Adults 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

Another source 2

T4 Total (T4)

Age µg/dL
1 to 3 days 11.22
1 to 2 weeks 10 to 16
One o 12 months 8 to 16
1 to 5 years 7 to 15
5 to ten 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

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)
  • Infants 1 to 3 days = 11 to 22  µg/dL.
    • Infants 1 to 4 months = 8 to 16 .µg/dL
  • Child 1 to 5 years = 7 to 15 .µg/dL
    • Child 10 to 15 years = 5 to 12 µg/dL.
  • Adult Male = 4 to 12  µg/dL.
    • Adult female = 5 to 12 µg/dL.
    • Adult > 60 years = 5 to 11 µg/dL.

What are the causes of increased T4 levels?

  1. Grave’s disease.
  2. Toxic thyroid adenoma.
  3. Struma ovarii.
  4. Acute thyroiditis.

What are the causes of decreased T4 levels?

  1. Hypothyroidism like:
    1. Cretinism.
    2. Myxedema.
    3. Surgical ablation.
  2. Failure of the hypothalamus.
  3. Protein-losing conditions like :
    1. Nephrotic syndrome.
    2. Renal failure.
  4. Iodine insufficiency.
  5. Cirrhosis.
  6. Cushing’s syndrome.
  7. Advanced cancers.
  8. Pituitary insufficiency.

The critical value of T4 Total:

  • Newborn = <7 µg/dL
  • Adult = <2 µg/dL

How will you differentiate different thyroid diseases?

Clinical disease Free T4 Total T4 T3 TSH Thyroglobulin
Hyperthyroidism primary clinical Increased Increased Increased Decreased Normal
Hyperthyroidism subclinical Normal Normal Normal Decreased Normal
Hypothyroidism primary clinical Decreased Decreased Decreased Increased Normal/Increased
Hypothyroidism primary subclinical Normal Normal Normal Increased Normal
Hypothyroidism Secondary Decreased Decreased Decreased Normal/Decreased
T3 thyrotoxicosis Normal Normal Increased Decreased Normal
TSH-secreting tumors Increased Increased Increased Increased Normal
Pregnancy with hyperthyroidism Increased Increased Increased Normal Increased
Pregnancy with hypothyroidism Decreased Increased Increased Increased Increased
Goiter Normal Normal Normal Normal Normal
Thyroid carcinoma Normal Normal Normal Normal Increased
Hashimoto’s thyroiditis Variable Variable Variable Variable
Nephrosis Decreased Decreased Normal Decreased

Questions and answers:

Question 1: What is thyroxine?
Show answer
Thyroxine is also called as T4. It includes free and bound T4.
Question 2: Which thyroid hormone is biologically active?
Show answer
T4 is converted to T3 and free T3 is biologically active.

Please see more details on Free T4 and thyroid function.


Possible References Used
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