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Thyroid:- Part 2 – Thyroid-Stimulating Hormone (TSH), Thyrotropin, and Graves’ Disease

December 17, 2024Chemical pathologyLab Tests

Table of Contents

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  • Thyroid-stimulating hormone (TSH)
        • What sample is needed for Thyroid-stimulating hormone (TSH)?
        • What are the indications for Thyroid-Stimulating Hormone (TSH)?
        • How will you define thyroid-stimulating hormone (TSH)?
        • What is the structure of Thyroid-Stimulating Hormone (TSH)?
        • What is the role of TSH?
        • What are the functions of TSH and the thyroid gland?
        • What are the interpretations of TSH?
        • What is the normal TSH level?
      • What are the causes of increased TSH levels?
      • What are the causes of decreased TSH levels?
  • Graves disease
        • How will you define Graves disease?
        • What is the mechanism of Graves’ disease?
        • What will be the clinical presentation?
        • How will you diagnose Graves’ disease?
      • Questions and answers:

Thyroid-stimulating hormone (TSH)

What sample is needed for Thyroid-stimulating hormone (TSH)?

  • Venous blood is taken, and the test is done on the patient’s serum.

What are the indications for Thyroid-Stimulating Hormone (TSH)?

  1. TSH differentiates Hypothyroidism from hyperthyroidism.
  2. TSH is used to diagnose primary hypothyroidism.
  3. TSH is used to differentiate primary from secondary hypothyroidism.
  4. TSH also differentiates hypothyroidism due to the hypothalamus (Tertiary hypothyroidism).
  5. TSH level is also done for suppressive or replacement therapy.
  6. TSH has also been done in a newborn with primary hypothyroidism with a low T4 level.

How will you define thyroid-stimulating hormone (TSH)?

  1. The anterior pituitary gland produces TSH.
  2. TSH plays an important role in regulating the thyroid glands’ activity, which produces important hormones for the body.
  3. TSH controls the metabolism, growth, and development of the body.

What is the structure of Thyroid-Stimulating Hormone (TSH)?

  1. TSH is a glycoprotein hormone composed of two polypeptide chains, alpha and beta.
    1. Alpha (α) subunit consists of 92 amino acids.
    2. The beta (β) subunit consists of 118 amino acids, and the biological activity is because of the Beta subunit.
    3. TSH molecular weight is 28,000 Da.
TSH structure

TSH structure

  1. It arises from the prehormone and prohormone.
  2. It has a short half-life of minutes to a few hours compared to other hormones like steroids.
  3. TSH binds with the specific receptors for TSH found in the cytoplasmic membrane of the thyroid cells.
  4. It releases the second messenger that activates cAMP and protein kinase and stimulates further biochemical reactions.
  5. TSH is transported free and not bound to protein carriers in the body fluids.
  6. With other adrenergic neuropeptides, TSH binds to the cytoplasm membrane receptors, and the thyroid gland secretes the T4 and T3.
  7. The thyroid gland has large hormone stores and a slow normal turnover rate.

What is the role of TSH?

  1. The pituitary gland produces TSH, which stimulates the thyroid gland to distribute stored hormones.
  2. TSH stimulates the secretion of T4 and T3.
    1. TSH secretion is regulated by T4 and T3 feedback inhibition.
    2. Low levels of T3 and T4  are stimuli for TSH and TRH.
TSH role in T3 and T4 formation

TSH role in T3 and T4 formation

  1. TSH influences our bodies in different ways.
TSH role on thyroid gland

TSH’s role in the thyroid gland

TSH role in thyroid gland secretion

TSH’s role in thyroid gland secretion

What are the functions of TSH and the thyroid gland?

  1. TSH stimulates the thyroid gland and leads to the secretion of T3 and T4.
  2. T3 and T4 have specific functions.
Thyroid functions

Thyroid functions

Thyroglobulin role in the synthesis of T3 and T4

Thyroglobulin’s role in the synthesis of T3 and T4

What are the interpretations of TSH?

  1. Thyrotropin-releasing hormone (TRH) from the hypothalamus regulates TSH stimulation.
    1. TSH is the single most common test for primary hypothyroidism.
  2. In the damaged Pituitary and hypothalamus, TSH and TRH are low or zero in spite of low T3 and T4.
  3. If there is clear evidence of hypothyroidism and TSH is normal, then think about the possibility of hypopituitarism.
    1. TSH level is high in primary hypothyroidism.
    2. TSH levels are low in hyperthyroidism.
TSH role for the diagnosis of Hyperthyroidism and Hypothyroidism

TSH’s role in the diagnosis of Hyperthyroidism and Hypothyroidism

  1. Thyroid disorder = T4 decreased + TSH normal or raised
  2. Pituitary disorder = T4 decreased + TSH decreased
TSH role in thyroid diseases

TSH’s role in thyroid diseases

What is the normal TSH level?

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 vary from lab to lab and different methodologies)

  • Adult = 0.4 to 4.2  µIU/L ( SI units are the same )
  • Neonates = 3 to 20  µIU/L

What are the causes of increased TSH levels?

  1. Adults and neonates with primary hypothyroidism.
    1. Congenital Cretinism.
  2. Hashimoto’s thyroiditis.
  3. The hypothyroid patient received inadequate treatment.
  4. Thyrotoxicosis due to pituitary tumors.
  5. Thyrotropin-producing tumors, e.g., ectopic TSH produced by lung and breast cancers
  6. TSH antibodies.
  7. Large doses of iodine.
  8. Chronic and severe illness.

What are the causes of decreased TSH levels?

  1. Primary Hyperthyroidism.
  2. Secondary and tertiary hypothyroidism.
  3. Overtreatment in a hypothyroid patient.
  4. Treated Grave’s disease patient.

What is the picture of thyroid hormones in various diseases?

Clinical disease TSH T3 T4 Free T4
Primary Hypothyroidism increased decreased deceased deceased
Secondary Hypothyroidism decreased decreased decreased decreased
Primary Hyperthyroidism decreased increased increased increased
Secondary hyperthyroidism increased increased increased increased

Graves disease

How will you define Graves disease?

  1. Graves’ disease is an autoimmune disorder that primarily affects the thyroid glands, leading to hyperthyroidism.
  2. There is an overproduction of thyroid hormones.

What is the mechanism of Graves’ disease?

  1. It is one of the most common causes of hyperthyroidism.
  2. The immune system produces antibodies that stimulate the thyroid gland.
  3. These antibodies are called thyroid-stimulating immunoglobulins.
  4. What are the risk factors:
    1. If there is a family history of autoimmune diseases.
    2. It is more common in females.
    3. Smoking is a risk factor and leads to ophthalmopathy.
    4. If there is stress or emotional trauma.
  5. It causes the increased size of the thyroid gland.
  6. It increases the amount of hormones.

What will be the clinical presentation?

  1. There is an increase in the size of the thyroid gland (Goiter).
  2. There is weight loss even with increased appetite.
  3. Heartbeats are irregular, leading to tachycardia or arrhythmias.
  4. There is nervousness, irritability, and anxiety.
  5. There is heat intolerance and sweating.
  6. There are tremors of hands or fingers.
  7. The patient may have weakness or fatigue.
  8. These patients typically have exophthalmos.
    1. The eyes are dry and irritable.
    2. These patients’ eyes may be red.
    3. These patients have sensitivity to light.
  9. These patients may have overall vision problems.
  10. These patients’ skin is red or swollen, called graves’ dermopathy.

How will you diagnose Graves’ disease?

  1. There is a high level of T4 and T3.
  2. There is a decreased level of TSH.
  3. There is the presence of antibodies (thyroid-stimulating antibodies).
  4. Check the eyes for the Graves’ ophthalmopathy.
  5. Advise Ultrasonography for goiter.
  6. Advise radio-iodine uptake to assess the thyroid function.
    1.  TSH is decreased.
    2.  Free T4 is increased.

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 will be the value of TSH in hypothyroidism?
Show answer
TSH value is increased in hypothyroidism.
Question 2: What will be the value of TSH in hyperthyroidism?
Show answer
TSH value will be very low in hyperthyroidism.
  • Note, please see more details on the thyroid function test.

Possible References Used
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