Corpus: Parathyroid hormone

Parathyroid hormone, or PTH for short, is a hormone produced by the main cells of the parathyroid glands (glandulae parathyreoidae).

Parathyroid hormone is a polypeptide consisting of 84 amino acids. The precursor of parathyroid hormone, pre-pro-parathyroid hormone, is initially synthesised as a 115 amino acid long protein in the ribosomes. The amino-terminal pre-sequence is cleaved cotranslationally. The resulting pro-parathyroid hormone, which is 90 amino acids long, then undergoes further cleavage post-translationally in the Golgi apparatus.

The N-terminal, 34 amino acid-long segment of the finished parathyroid hormone forms the biologically active part.

In order to exert its effect on effector cells, parathyroid hormone binds to special G-protein-coupled receptors known as parathyroid hormone receptor type 1 (PTH1R) and parathyroid hormone receptor type 2 (PTH2R).

The stimulus for the release of parathyroid hormone is a drop in the calcium level (hypocalcaemia). An increase in serum calcium above normal inhibits parathyroid hormone secretion in return - there is therefore a negative feedback loop.

Calcium levels are measured via calcium-sensitive receptors (CaSR) on the cell membrane of the main cells of the parathyroid gland. Like the parathyroid hormone receptors, they belong to the G-protein-coupled receptors.

The direct and indirect effects of parathyroid hormone cause an increase in the free (unbound) calcium concentration in the blood.

Mnemonic: "Parathyroid hormone makes calcium ready".

The antagonist of parathyroid hormone in the regulation of calcium levels is calcitonin.

Direct effects[Bearbeiten]

• Kidney: Promotes the reabsorption of calcium and inhibits the reabsorption of phosphate
• Bone: When administered intermittently, parathyroid hormone promotes periosteal and endosteal new bone formation by stimulating osteoblasts

Indirect effects[Bearbeiten]

• Bone: Parathyroid hormone leads to bone resorption through indirect stimulation of the osteoclasts, as osteoclasts themselves have no parathyroid hormone receptors. Parathyroid hormone binds to the PTH receptors of the osteoblasts, which then express more RANKL and secrete less osteoprotegerin (OPG). These two effects lead to the formation of new osteoclasts, which resorb the bone.
• Kidney: Stimulates the formation of calcitriol, which increases calcium absorption in the kidney
• Intestine: Stimulates the absorption of calcium in the small intestine.

Half-life[Bearbeiten]

The biological half-life of parathyroid hormone is very short. The polypeptide breaks down into fragments of different lengths after just 3-5 minutes.

Material[Bearbeiten]

1 ml of serum is required for the test.

Pre-analysis[Bearbeiten]

The blood sample is taken in the morning when the patient is fasting. Parathyroid hormone is not stable in whole blood as it is rapidly degraded by proteases in the blood. Blood samples for parathyroid hormone measurement must therefore be taken to the laboratory immediately. For longer transport times, the blood sample must be frozen (below -20 °C).

Method dependency[Bearbeiten]

The various reagents on the market have different specificities for parathyroid hormone fragments. The most common method is the detection of the entire protein with amino acids 1-84. These assays are referred to as "parathyroid hormone intact" and replaced earlier assays that were specific for the C-terminal or N-terminal region. However, older generation PTH intact assays still detect PTH 7-84. This accumulates in renal insufficiency, the measurement result can be higher due to this proportion.

The latest generation of PTH assays is specific for PTH 1-84; PTH 7-84 is no longer detected. This variant is referred to as "parathyroid hormone biointact". Measurement results from different laboratories can only be compared if the same test generation is used.

The differences are clinically significant, as PTH is often determined in patients with renal insufficiency or who require dialysis. In addition, fragments of PTH sometimes have a different, even opposite effect to the intact hormone (use as an osteoanabolic substance, see therapeutic relevance).

Reference range[Bearbeiten]

The normal value of parathyroid hormone in serum is 12 to 72 ng/l or 1.5 to 6.0 pmol/l.

Interpretation[Bearbeiten]

Note[Bearbeiten]

The diagnosis of hypo- or hyperparathyroidism is made by determining the serum concentrations of parathyroid hormone, calcium, phosphate, magnesium and alkaline phosphatase.

Hyperparathyroidism[Bearbeiten]

An increase in the parathyroid hormone level is referred to as hyperparathyroidism. A distinction is made between:

• primary hyperparathyroidism due to hyperfunction of the parathyroid gland (e.g. in the case of hormone-producing adenomas)
• secondary hyperparathyroidism as a result of hypocalcaemia and hyperphosphataemia (e.g. in the context of chronic renal insufficiency or liver cirrhosis)
• tertiary hyperparathyroidism due to autonomous overproduction of parathyroid hormone as a result of long-term secondary hyperparathyroidism

Hypoparathyroidism[Bearbeiten]

The reduction in parathyroid hormone levels is known as hypoparathyroidism. It occurs when the epithelial corpuscles are removed accidentally as part of a thyroidectomy or after targeted surgical removal of the epithelial corpuscles (parathyroidectomy).

Overview[Bearbeiten]

↑: increased; ↓: decreased

A recombinant fragment of parathyroid hormone (teriparatide) is used for osteoanabolic therapy of osteoporosis.

• Laborlexikon.de; retrieved on 19/04/2021