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Thyroid:- Part 1 – Thyroid Function Test (Thyroid Hormones) T4, T3, TSH

March 27, 2023Chemical pathologyLab Tests

Table of Contents

  • Thyroid Function Test
      • Sample for Thyroid Function Test
      • Precautions for Thyroid Function Test
      • Thyroid functions tests advised are:
      • Indications for Thyroid Function Test
      • Pathophysiology of thyroid hormones
      • Functions of the thyroid:
      • TSH induces:
      • The cycle of thyroid hormone formation:
      • Thyroid hormones regulatory control:
      • Metabolism of T3 and T4:
      • Normal Values of thyroid hormones
      • T3 Total
          • Source 1
      • Free T3
      • T3 total
        • T4 Total (T4)
      • Another source 1
        • T4 Free (FT4)
        • T4 Total (T4)
      • Another source 2
      • T4 Free
      • TSH
      • Another source
    • Hypothyroidism
      • Myxedema:
      • Thyroid function in Hypothyroidism:
    • Hyperthyroidism (Thyrotoxicosis)
    • Graves disease
      • Thyroid functions in Hyperthyroidism:
  • Goiter
      • Euthyroid sick syndrome:
      • Thyroid function tests Summary:                       

Thyroid Function Test

Sample for Thyroid Function Test

  1. The serum of a patient is needed.
  2. TSH sample is stable for 5 to 7 days at 4 °C.
  3. T4 and T3 samples are stable for 7 to 14 days at room temperature (37 °C) or 2 to 8 °C.

Precautions for Thyroid Function Test

  1. Sample with hemolysis or lipemia is rejected.
  2. Centrifuge the turbid sample before performing the test.

Thyroid functions tests advised are:

  1. T3 uptake.
  2. Free T3.
  3. Total T3.
  4. Total T4.
  5. Free T4.
  6. Free thyroxine index.
  7. TSH.
  8. Thyroglobulin (Tg)

Indications for Thyroid Function Test

  1. These tests are done to evaluate thyroid dysfunction.
  2. T3 is advised to diagnose hyperthyroidism.
  3. T3 and T4 are advised to monitor replacement and suppressive therapy.
  4. Free T4 is advised to evaluate the thyroid function in a patient with protein abnormality, which will affect total T4.
  5. The thyroid function test differentiates between :
    1. Euthyroid (thyroid function is normal).
    2. Hyperthyroidism (Increased thyroid function).
    3. Hypothyroidism (decreased thyroid function).

Pathophysiology of thyroid hormones

  1. Thyroid follicles are the basic secretory unit of the thyroid gland.
  2. The follicle has an outer epithelial cell layer surrounding the amorphous colloid material.
  3. Colloid mainly consists of thyroglobulin and a small amount of thyroalbumin.
Thyroglobulin role in the synthesis of T3 and T4

Thyroglobulin’s role in the synthesis of T3 and T4

Thyroglobulin role in T3 T4 synthesis

Thyroglobulin role in T3 T4 synthesis

Thyroid hormone carrier protein

Thyroid hormone carrier protein

Thyroxine binding protein

Thyroxine binding protein

  1. The thyroid gland has another cell, the parafollicular cell or C cell, present within the follicular basement or interfollicular spaces. These cells produce a hormone known as Calcitonin.
    1. The thyroid gland produces thyroxine (T4) and Triiodothyronine (T3).
    2. Diiodothyronine is the precursor of T3 and T4.
TSH role on thyroid gland

TSH’s role on the thyroid gland

  1. T4 changes into T3 and reverse T3 (rT3) by deiodination.
T4 free T3 free function

T4 free T3 free function

Functions of the thyroid:

  1. Control energy expenditure of the body.
  2. Stimulate heart contraction and heart rate.
  3. Stimulate carbohydrate and protein metabolism.
  4. Increase in the synthesis and degradation of cholesterol and triglycerides.
  5. It increases the sensitivity of the beta-adrenergic receptor to catecholamine.
Thyroid functions

Thyroid functions

Increased Thyroid hormones

Increased Thyroid hormones

  1. Pituitary thyroid-stimulating hormone (TSH) regulates the synthesis of thyroid hormone.

TSH induces:

  1. Increase in the size and number of thyroid follicles.
  2. Prolonged TSH stimulation leads to increased vascularity and may form a goiter.
  3. The thyroid hormone maintains the rate at which your body uses fats and carbohydrates.
  4. Control your body temperature.
  5. Regulate the production of protein.
  6. The thyroid gland also produces calcitonin, a hormone that helps regulate the amount of calcium in your blood.

The cycle of thyroid hormone formation:

  1. The rate at which T3 and T4  are released is controlled by the pituitary gland and hypothalamus (which acts as a thermostat).
    1. The hypothalamus signals the pituitary gland it makes Thyroid-stimulating hormone (TSH).
    2. The pituitary gland is a source of TSH.
    3. TSH amounts depend on the amount of T3 and T4 in the blood.
    4. There is a feedback mechanism. If there is a decreased level of T3 and T4, the TSH level will increase.
  2. If T3 and T4 are increased, the TSH level will fall below normal.
  3. The thyroid gland regulates its production of T3 and T4 based on the amount of TSH it receives.

Thyroid hormones regulatory control:

  1. Hypothalamus produces TRH + Somatotropin, which stimulates the Pituitary gland to produce TSH.
  2. TSH  acts on the thyroid gland to stimulate secretion of T4 + iodine trapping + new hormone synthesis + stimulate thyroid cell hypertrophy (Goiter).
  3. T4 + T3 = negative feedback mechanism on pituitary gland + hypothalamus.
TSH role in thyroid gland secretion

TSH’s role in thyroid gland secretion

  1. Hypothyroidism occurs when the thyroid does not produce enough T3 and T4.
  2. Hyperthyroidism occurs when thyroid glands produce an excess of T3 and T4.
TSH role for the diagnosis of Hyperthyroidism and Hypothyroidism

TSH’s role in the diagnosis of Hyperthyroidism and Hypothyroidism

Metabolism of T3 and T4:

  1. T3 and T4 conjugate in the liver to form Sulphate and glucuronide.
  2. These conjugates enter the bile and the intestine.
  3. Thyroid hormone conjugates are hydrolyzed and reabsorbed from the intestine (Enterohepatic circulation), and some are excreted in the stool.
  4. The T3 rise may be the first and only abnormality in the case of Hyperthyroidism.
T4 and T3 metabolism

T4 and T3 metabolism

  • The thyroid function tests are depended upon various factors.
Thyroid functions are dependent upon various factors

Thyroid functions are dependent upon various factors

Normal Values of thyroid hormones

Source 1

T3 Total

  • Cord blood  (>37 weeks) = 5 to 141 ng/dL
  • 1 to 3 days = 100 to 740 ng/dL
  • 1 to 11 months = 105 to 245
  • Children
    1. 1 -5 years = 105  to 269 ng/dL
    2. 6 to 10 years = 94 to 241 ng/dL
    3. 16 to 20 years = 80 to 210 ng/dL
  • Adult
    1. 20 to 50 years = 70 to 204 ng/dL
    2. 50 to 90 years = 40 to 181 ng/dL
  • Pregnancy
    1. Last 5 months = 116 to 247 ng/dL
      1. To convert into SI unit x 0.0154 = nmol/L
Source 1

Free T3

  • Cord blood (>37 weeks ) = 15 to 391 pg/dL
  • Child and adult = 260 to 480 pg/dL  (4.0 to 7.4 pmol/L)
  • Pregnancy
    • First trimester = 211 to 383 pg/dL
    • Second and third trimesters = 196 to 338 pg/dL

Another source 2

T3 total

  • 1 to 3 days = 100 to 740 ng/dL
  • 1 to 11 months = 105 to 245 ng/dL
  • 1 to 5 years = 105 to  270 ng/dL
  • 6 to 10 years = 95 to 240 ng/dL
  • 11 to 15 years = 80 to 215 ng/dL
  • 16 to 20 years = 80 to 210 ng/dL
  • 20 to 50 years = 75 to 220 ng/dL
  • >50 years = 40 to 180 ng/dL

Another 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

Another 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

Source 2

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
5to 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

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)
T4 free T3 free function

T4 free T3 free function

TSH

Source 1

Age µU/mL

Premature infants

28 to 36 weeks gestation

0.7 to 27
1 to 4 days 1.0 to 39
2 to 20 weeks 1.7 to 9.1
5 months to 20 years 0.7 to 6.4
Adults
21 to 54 years 0.4 to 4.2
55 to 87 years 0.5 to 8.9
Pregnancy
First trimester 0.3 to 4.5
Second trimester 0.5 to 4.6
Third trimester 0.8 to 5.2
  • To converts into SI unit x 1.0 = mU/L

Source 2

  • Adult = 0.4 to 5.6 mIU/L
  • Newborn = 3 to 20 mIU/L
  • Cord blood = 3 to 12 µU/mL
    • Values vary between laboratories.

Another source

  • Adult
  • 21 to 54 years = 0.4 to 4.2 mU/L
  • 55 to 87 years = 0.5 to 8.9 mU/L
  • Newborn = 1.7  to 9.1 mU/L
    • 0.3 to 3.04 mIU/L  (another reference)
  • Pregnancy
    • First trimester = 0.3 to 4.5 mU/L
    • Second trimester = 0.5 to 4.6 mU/L
    • Third trimester = 0.8 to 5.2 mU/L

(Normal values varies from lab to lab and different methodology)

Thyroid disease T4 total T4 free T3 total T3 free TSH
Normal N N N N N
Hypothyroidism Low Low Low low Low High
Hyperthyroidism High High High High low or absent

Hypothyroidism

  1. There is inadequate production of thyroid hormones:
  2. It is characterized by decreased T4.
  3. Ther is an increased level of TSH.
  4. Signs and Symptoms of Hypothyroidism:
    1. The signs and symptoms of hypothyroidism vary widely, depending on the severity of the hormone deficiency.
    2. At first, you may barely notice symptoms such as fatigue and sluggishness.
    3. Increased sensitivity to cold
    4. Constipation.
    5. Skin is pale and dry skin.
    6. There is puffiness of the face due to edema.
    7. The patient develops Hoarseness of voice.
    8. There is an increased level of cholesterol.
    9. The patient also gains weight.
    10. There are Muscle aches, tenderness, and stiffness.
    11. There is Muscle weakness
    12. There may be pain, stiffness, or swelling of joints.
    13. Female patients develop heavier menstrual periods.
    14. The patient may develop signs of Depression.
    15. Usually, these patients become obese.
    16. There may be joint pain.
    17. This patient may suffer from infertility.
    18. These patients may develop heart problems.
    19. In untreated cases, signs and symptoms become worse.
    20. Constant stimulation of the thyroid gives rise to enlargement of the gland, which is called Goiter.
    21. Advanced hypothyroidism is known as Myxedema.

Myxedema:

  1. It includes more signs and symptoms like :
    1. Low blood pressure.
    2. Decreased breathing.
    3. Decreased body temperature.
    4. Unresponsiveness and even the patient may go into a coma.
    5. Myxedema may be fatal in some patients.
  2. Causes of hypothyroidism
    1. Autoimmune thyroid disease.
    2. Iodine deficiency.
    3. Iodine-induced.
    4. Goitrogen exposure.
    5. A defect in hormone synthesis.
    6. Thyroid ablation by surgery or radiation.
    7. Thyroid agenesis or dysgenesis.
    8. Hypothalamic-pituitary disease.

Thyroid function in Hypothyroidism:

Causes  TSH T3 T4
Pituitary abnormality High Low Low
Hashimoto’s disease  in an early stage High Low Low
Hashimoto’s disease in late-stage High Low or normal Low or normal

Hyperthyroidism (Thyrotoxicosis)

  1. , There is excessive production of thyroid hormones:
  2. It is characterized by elevated T4.
  3. There is a decreased or even absent level of  TSH.
  4. Signs and Symptoms of Hyperthyroidism
  5. Hyperthyroidism can significantly accelerate your body’s metabolism, causing :
  6. Sudden weight loss, even appetite, and food intake remain normal or increase.
  7. Rapid or irregular heartbeat ( Tachycardia, Palpitation may be more than 100 beats/minutes.).
  8. The patient may even develop Arrhythmias.
  9. The patient develops sweating.
  10. Nervousness or irritability.

Graves disease

  1. This is an autoimmune disorder.
  2. Grave’s Disease is due to Hyperthyroidism.
  3. Symptoms of hyperthyroidism:
    1. Tremors are usually fine, trembling with hands and fingers.
    2. Patients have increased sensitivity to heat.
    3. Changes in bowel patterns, especially more frequent bowel movements.
    4. An enlarged thyroid gland (goiter).
    5. The patient will have Fatigue and muscle weakness.
    6. The patient will have sleep difficulty.
  4. Beta-blockers can mask many of the symptoms of hyperthyroidism.
  5. Causes of hyperthyroidism
    1. Multinodular goiter.
    2. Single toxic goiter.
    3. Subacute thyroiditis.
    4. Autoimmune thyroid disease.
    5. Pituitary adenoma (thyrotropin-producing tumor).
    6. Gestational trophoblastic tumor.
    7. Postpartum Thyroid disease.
    8. Hyperemesis gravidarum.
    9. Exogenous thyroid hormones.
    10. Metastatic thyroid cancer.
    11. Iodine-induced.
TSH role in thyroid diseases

TSH’s role in thyroid diseases

Thyroid functions in Hyperthyroidism:

Causes   TSH T3 T4
Grave’s Disease Low Raised Raised
Thyroiditis with hyperthyroidism Low Raised Raised
Thyroid nodule (hot or toxic ) Low Raised Raised

Table showing lab. Test in Thyroid diseases:

Disease TSH T4
Multinodular goiter low high
Single toxic nodule low normal or high
Subacute thyroiditis low high
Autoimmune thyroid disease low high
TRH pituitary adenoma normal or high high
Gestational neoplasm low high
Postpartum hyperthyroidism low high
Hyperemesis gravidarum low or normal high
Metastatic thyroid cancer low high
Iodine-induced variable high
Exogenous thyroxine low high

Goiter

  1. Definition This is an enlarged thyroid gland because of any cause.
  2. Causes are :
    1. Inflammatory.
    2. A function that may be normally increased or decreased.
    3. Neoplastic.
  3. Most of the goiter has normal function seen in 90 % of the multinodular goiter; almost all are colloid goiter.

Euthyroid sick syndrome:

  1. This is also known as low T3 syndrome
  2. There is biochemical hypothyroidism as T4 is shifted away to form T3.
  3. Total T4 and TSH usually remain within normal limits.

Thyroid function tests Summary:                       

Disease T3 T4 (total) T4 free TSH Cholesterol
Hypothyroidism decreased decreased low increased increased
Hyperthyroidism increased increased increased decreased or absent decreased
Excess Thyroid binding globulin (TBG) increased increased Normal decreased
Decreased thyroglobulin (TBG) Low Low Normal
  • Please see more details in T3 and T4.

Possible References Used
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