Parathyroid hormone (PTH)

Sample

1. The serum of the patient is required.
   1. A fasting sample is preferred.
   2. Place on ice.
2. The serum should be separated immediately because the PTH is unstable at room temperature and even on refrigeration.
   1. Refrigerate during centrifugation.
   2. Immediately freeze the sample.
   3. Can store at -20 °C to -70 ° C.
3. A lower level has seen if the sample left at room temperature even for 4 hours.
4. Also, a lower level has seen if the sample is kept at 4 °C for one day.
5. If the chemical method allows then the EDTA plasma is the best choice.
6. Simultaneous estimation of total calcium, ionized calcium, and phosphorus is recommended

Purpose of the test (Indications)

1. This is done to evaluate hypercalcemia or hypocalcemia.
2. This is also done to establish the diagnosis of hyperparathyroidism.
3. PTH differentiates hyperparathyroidism from Nonparathyroid causes leading to hypercalcemia.

Precaution

1. lipemic serum and hemolysis interfere with the method.
2. Some drugs may affect the result and increase PTH value like:
   1. Anticonvulsants.
   2. Isoniazid.
   3. Lithium.
   4. Rifampicin.
   5. Steroids.
3. Drugs which decrease PTH are:
   1. Cimetidine.
   2. Propranolol.

Pathophysiology

1. This is a polypeptide hormone produced in the parathyroid gland.
   1. These 4 in number and present close to or on the posterior surface of the thyroid gland.
   2. Additional parathyroid glands may be found in the mediastinum (in thymus gland) or neck.

2. Formation of PTH:
   1. Preparathyroid (115 AA) is synthesized in the ribosomes of Cheif cells.
   2. By proteolysis converted into Pro-PTH (90 AA).
   3. By the second proteolysis converted into Intact-PTH (1- 84 AA).
   4. PTH-1-84 is metabolized in the peripheral tissue mainly the liver and kidney.
   5. This is stored in the gland and some of it goes into blood circulation.
   6. The biological activity of the PTH resides in the first 30 AA of the N-terminal.
   7. The concentration of the biologically active form of PTH is very low in the blood circulation (10 pmol/L or 0.1 ng/mL).
   8. PTH secretion is directly controlled by plasma calcium.

3. This is the main hormone to regulate the concentration of Calcium in the extracellular fluid.
   1. A decrease in the ionized calcium is the stimulus for the PTH secretion.
   2. PTH + 1,25- hydroxy D3 rais the calcium level by the following mechanisms:
      1. It promotes dissolving of the bone.
      2. Increases renal tubular reabsorption of calcium in the kidney.
      3. Increase intestinal absorption of the calcium.
   3. A rise in Calcium inhibits PTH secretion.

4. Magnesium also influences the PTH level.
   1. Hypermagnesemia suppresses the PTH secretion, although not like Calcium.

Clinical condition	PTH	PTH
Ionized hypocalcemia	Stimulate
Ionized hypercalcemia		Suppress
Hyperphosphatemia	stimulate
Hypermagnesemia		Suppress

5. Primary hyperparathyroidism is caused by parathyroid adenoma or rarely by cancer.
   1. The patient will have high PTH.
   2. and high Calcium level.
6. Secondary hyperparathyroidism is due to chronic renal failure where the patient has low calcium and high phosphate.
   1. Now parathyroid glands persistently produce PTH to maintain Calcium level.
   2. These patients have high PTH and low calcium.
7. Tertiary hyperparathyroidism In this case patients bypasses the compensatory mechanism.
   1. Develops a high PTH level.
   2. This PTH leads to hypercalcemia.
   3. These patients have high PTH and High calcium levels.
8. Intact PTH molecule metabolized to three different molecules:
   1. N-terminal.
   2. Mid-Region.
   3. C- terminal.
9. PTH level has diurnal variation. it is the highest at around 2 AM and lowest at around 2 PM.

Normal

Source 1

C- terminal and midmolecule

• Serm (by RIA)
  • 1 to 16 years = 51 to 217 pg/mL
  • Adult = 50 to 300 pg/mL

N- Terminal

• Serum (by RIA)
  • 2 to 13 year = 14 to 21 pg/mL
  • Adult = 8 to 24 pg/mL

Intact molecule

• Serum (by ICMA))
  • Cord blood = ≤ 3 pg/mL
  • 2 to 20 year = 9 to 52 pg/mL
  • Adult = 10 to 65 pg/mL

Source 2

• Intact PTH molecule = 10 to 65 pg/mL (10 to 65 ng/mL)
• N-terminal intact PTH = 8 to 24 pg/L (8 to 24 ng/L)
• C-terminal  intact PTH = 50 to 330 pg/L (50 to 330 ng/L)
  • Mostly the intact PTH molecule is recommended.

Increased PTH level is seen in:

1. Primary hyperparathyroidism.
2. Pseudohypoparathyroidism ( Secondary hyperparathyroidism ).
3. Vit. D deficiency ( hereditary ) and rickets.
4. Zollinger Ellison syndrome.
5. Non-PTH producing tumors give rise to the paraneoplastic syndrome, They produce PTH like protein which acts like PTH.
6. Chronic renal failure.
7. Hypocalcemia.
8. Malabsorption.

Decreased PTH level is seen in:

1. Grave’s disease ( Hypoparathyroidism ).
2. Non-Parathyroid hypercalcemia.
3. Surgical, secondary hypoparathyroidism.
4. Sarcoidosis.
5. Metastatic bone tumors.
6. Vit.D intoxication.
7. Milk-alkali syndrome.
8. DiGeorge syndrome.

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