Growth Hormone (GH) is a protein synthesized and secreted by the anterior pituitary cells of the brain. It is a kind of peptide hormone. The main physiological role of GH is to promote the body’s anabolism and protein synthesis and stimulate bone growth. GH can directly act on pre-chondrocytes, differentiate them into chondrocytes, and stimulate the synthesis of liver and local insulin-like growth factor 1 (IGF-1), and also stimulate the expression of chondrocyte IGF-1 receptors. Grow. In addition, GH can directly stimulate osteoblast metabolism, increase osteocalcin levels and stimulate bone growth. After sexual maturity, the epiphyseal plate gradually merges, and the bone length no longer increases, but GH still plays an important role in bone metabolism and maintaining bone mineral content and bone density.
When the growth hormone deficiency is caused by the disease, the patient needs to be given growth hormone treatment. The currently available recombinant human growth hormone (rhGH) has brought the gospel to children with short stature and other diseases. However, the use of this drug in the clinic is not standardized. The situation, today will talk about how to regulate the application of the drug.
Where can rhGH be used
The diseases that can be treated with rhGH and lead to short stature include growth hormone deficiency (GHD), chronic renal insufficiency before kidney transplantation, Turner syndrome, Prader-Willi syndrome, infants less than gestational age, idiopathic short stature (ISS), Short bowel syndrome, SHOX gene deletion and Noonan syndrome.
At present, genetically recombinant human growth hormone is mainly used in pediatrics for the following endocrine genetic diseases, namely growth hormone deficiency, idiopathic short stature, infants less than gestational age, Turner syndrome, Prader-Willi syndrome and Noonan syndrome.
In addition, there are clinical data showing that children with central precocious puberty, congenital adrenal hyperplasia, and congenital hypothyroidism will continue to grow backward after treatment of the primary disease, and it is predicted that adult height will be significantly impaired (boy <160cm; girl 150cm) patients treated with rhGH can improve growth, but more evidence-based medicine is needed, and it is not recommended as a routine.
Types of rhGH
There are two types of rhGH biosynthesis technologies, one is bacterial (prokaryotic) recombination and the other is mammalian cell (eukaryotic) recombination. At home and abroad, rhGH is mostly synthesized using Escherichia coli secreted gene expression technology. Its amino acid content, sequence and protein structure are the same as natural growth hormone.
There are two domestic rhGH preparations: freeze-dried powder injection and liquid preparation.
Therapeutic dose of rhGH
Growth hormone helps promote bone growth, but its therapeutic effect has a dose effect, and there are individual differences at the same time, but it cannot be used arbitrarily. The initial dose of different diseases is different. rhGH treatment should be individualized treatment, should start from a small dose, the maximum does not exceed 0.2 U / (kg · d). Generally, in order to improve adult height, treatment should be at least 1 year.
Table 1 Therapeutic dose of rhGH
rhGH treatment is administered 6-6 days a week and is injected subcutaneously 30 minutes before bedtime. The commonly used injection site is the outer side of the middle part of the thigh, and the upper arm or abdominal wall can also be selected. Do not inject twice at the same site within 1 month, and the distance between the two needles is about 1.0cm, in order to prevent the short-term repeated injections causing degeneration of the subcutaneous tissue and affecting the efficacy.
How to monitor during rhGH treatment
Children treated with rhGH should regularly monitor the effectiveness and safety of treatment in the pediatric endocrine clinic.
Therapeutic effectiveness: Children who need to be treated with growth hormone should be treated as soon as possible. The sooner the treatment effect is better, the evaluation of treatment effect is divided into short-term effect and long-term effect.
For the short-term treatment effect evaluation, the change in height SDS is the best, and the growth rate, growth rate SDS or annual growth rate can be used for reference. The indicators of effective response in the first year of rhGH treatment are: (1) Height SDS increases by more than 0.3-0.5. (2) The growth rate increased by> 3cm / year compared with before treatment. (3) The growth rate SDS> 1.
Long-term treatment effect evaluation indicators are adult height SDS, adult height SDS and rhGH difference between height SDS at the beginning of treatment, adult height and predicted height, adult height and genetic target height.
In addition, IGF1 level is the main indicator to evaluate the safety and compliance of rhGH. The IGFI level should be maintained within the normal range during treatment. In the case of good compliance, if the growth is not ideal and the IGFl level is low, the rhGH dose can be increased within the approved dose range; after 2 years of initial treatment, if the serum IGFl level is higher than the normal range, especially continued Above 2.5SDS, reduction or withdrawal may be considered.
Treatment safety: The overall adverse reaction rate of rhGH treatment is less than 3%. The current adverse reactions reported by rhGH treatment are benign intracranial hypertension, the effect of glucose metabolism, hypothyroidism, spondylolisthesis, scoliosis, and tumor-induced Possibility, pigmented moles, enlarged hands and feet, etc. Local redness and rashes are not common injections, and there have been few reports of otitis media, pancreatitis, and male breast development. Some symptoms will appear in the early stage of treatment, and some adverse reactions (such as hypothyroidism) will appear within months of treatment or even after 1 year of treatment. Therefore, thyroid function tests need to be performed before growth hormone replacement therapy. If hypothyroidism is required Adjust the thyroid function to a normal level before starting treatment, and at the same time review the nail function every 3 months during treatment.