The Endocrine Genetic Metabolism Group of the Pediatrics Branch of the Chinese Medical Association (formulated at the Huangshan meeting in November 07) The Endocrine Genetic Metabolism Group of the Pediatrics Branch of the Chinese Medical Association proposed the clinical application of genetically recombinant human growth hormone in 1998 (Chinese Journal of Pediatrics, 1997, 37: 234), and on this basis, the diagnosis and treatment of children with short stature was discussed again in October 2006. On the basis of this, in October 2006, the diagnosis and treatment of children with short stature were discussed extensively and thoroughly, and a consensus was reached, which is now synthesized as follows for the reference of clinical workers. Definition of short stature
Short stature refers to individuals of the same race, sex and age whose height is lower than the average height of the normal population by 2 standard deviations (-2SD) or lower than the 3rd percentile (-1, 88SD) in a similar living environment, some of which are normal physiological variants.
Etiology
There are many factors leading to short stature, including many interactions, and the mechanism of short stature caused by many diseases has not been clarified so far (see Table 1) [Diagnosis].
Children with short stature must be examined comprehensively to clarify the cause for treatment.
A. Medical history should be taken carefully: pregnancy of the child’s mother; birth history of the child; birth length and weight; growth history; parents’ pubertal development and short stature in the family, etc.
In addition to the routine physical examination, the following items should be measured and recorded correctly: ① the measured value and percentile of current height and weight; ② the annual growth rate of height (at least 3 months of observation); ③ the target height measured according to the height of the parents; ④ the BMI value; ⑤ the sexual developmental stage.
Routine blood and urine tests and liver and kidney function tests should be performed routinely; blood gas and electrolyte analysis are recommended for suspected renal tubular toxicity; karyotype analysis is required for girls; thyroid hormone levels should be routinely tested to exclude subclinical hypothyroidism.
Bone Age (BA) is a good indicator for assessing the development of an organism. Bone age is the maturity of bone at each age, and is determined by observing the growth and development of each ossification center on orthogonal X-rays of the left wrist, palm and finger bones. The most used methods at home and abroad are the G-P method (Greulich & Pyle) and the TW3 method (Tanner-Whitehouse), and the G-P method is mostly used in our clinic. Under normal circumstances, the difference between bone age and actual age should be between ±1 year, lagging behind or exceeding too much is considered abnormal.
3.Special examination (1) Indications for special examination ① those whose height is lower than the normal reference value minus 2SD (or lower than the 3rd percentile); ② those whose bone age is lower than the actual age by more than 2 years; ③ those whose height growth rate is below the 25th percentile (according to bone age), i.e. <7CM/rh for children <2 years old; ④ those who have clinical symptoms of endocrine disorder or dysmorphic syndrome; ⑤ those who need to be examined for other reasons Pituitary gland function examination.
(2) Growth hormone-insulin-like growth factor-1 axis (GH-IGF-1) function determination The physiological screening tests such as exercise and sleep, which were used in the past, are rarely used nowadays, and most of them directly use drug stimulation tests (see Table 2).
(3) Measurement of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) Serum concentrations of both increase with age and development, and are related to nutrition and other factors, so each laboratory should establish its own reference data.
(4) IGF-1 production test For children suspected of GH resistance (Laron syndrome), this test can be used to detect GH receptor function. Method 1: 0,075-0,15 U/(kg?d) of rhGH is injected subcutaneously every night for 1 week, and blood samples are collected once before and once on the 5th and 8th day after the injection to determine IGF-1; Method 2: 0,3 U/(kg?d) of rhGH is injected subcutaneously every night for 4 days, and blood samples are collected once before and once after the last injection to determine IGF-1. The serum IGF-1 of normal individuals will increase more than 3 times its basal value after injection, or reach the normal value corresponding to their age.
(5) Testing of other endocrine hormones Depending on the clinical manifestations of the child, other hormonal options may be tested as needed (6) Imaging of hypothalamus and pituitary gland MRI of the skull should be performed in children with short stature to exclude the possibility of congenital developmental abnormalities or tumors.
(7) Karyotype analysis Karyotype analysis should be performed in all children suspected of having chromosomal aberrations.
Differential diagnosis
Based on medical history and physical examination, it is easy to identify short stature caused by malnutrition, psychosomatic family idiopathic short stature, small for gestational age, chronic systemic diseases, etc. The common causes of short stature should be identified, such as chondrodysplasia, hypothyroidism, and delayed somatic puberty. In addition, clinical attention should be paid to the possibility of certain syndromes, such as Prader-Willi syndrome, Silver-Russeli syndrome, Noonan syndrome, etc.
Treatment
1.Treatment measures for children with short stature depend on their etiology Psychosomatic, renal tubular acidosis and other children will see an increase in their height growth rate after the relevant factors have been eliminated, and daily nutrition and sleep protection are closely related to normal growth and development.
2.Growth hormone With the accumulation of experience in the clinical application of recombinant human growth hormone (rhGH), the number of diseases approved for treatment with rhGH has gradually increased. Prader-Willi syndrome (2000), small for gestational age (2001), and idiopathic short stature (2003).
Since most children younger than gestational age show catch-up growth in the first 2-3 years of life and can reach a growth curve proportional to their target height, they should be followed up regularly. In 2003, the FDA approved GH for idiopathic short stature, i.e.: (1) those with unknown causes of non-GH deficiency; (2) those whose height is lower than the normal reference value of 2,25 SD or more for children of the same sex and age; and (3) those who are expected to have a lifetime height of -2SDS or less in adulthood.
(1) Dosage form Domestic options include rhGH powder and water, with the latter having a slightly better growth effect.
(2) Dose The dose of growth hormone has a wide range and should be adjusted individually according to the need and the observed efficacy. At present, the commonly used doses in China are 0,1-0,15IU/kg?d, 0,23-0,35mg/kg per week; for children with pubertal development, Turner children, children younger than fetal age, children with idiopathic short stature and some children with partial growth hormone deficiency, the applied doses are 0,15-0,20IU/(K,d) 0,35-0,46(J,K) per week (Note. (Note: WHO labeled growth hormone 1J=30U) (3) Usage: Subcutaneous injection once a night before bedtime, the usual injection site is the outer and anterior side of the middle 1/2 of the thigh, and the injection site should be changed each time to avoid short-term repetition and degeneration of subcutaneous tissue.
(4) Course of treatment: The course of growth hormone treatment for short stature depends on the need, usually should not be shorter than 1-2 years, too short when the child’s benefit to its lifelong high effect is not great.
3, other drugs: ① the course of treatment should pay attention to calcium, trace elements and other supplements for bone growth; ② anabolic hormone: often used with growth hormone for the treatment of Turner syndrome, most domestic use stanozolol, Conilon), commonly used dose of 0, 025-0, 05J / (K, d) need to pay attention to the growth of bone age; ③ IGF-1 gonadal axis inhibition (GnRHa), aromatase inhibitors (Letrozole, Letrozole) have also been used to treat short stature, but there is not enough data to analyze in China, so it is not recommended for routine application.
Follow-up]
All children diagnosed with short stature should be followed up once every 3 months. Those who are treated with growth hormone should be followed up once every 3 months: height measurement (SSDS measurement is best) and IGF-1, IGFBP-3, T4, TSH, blood glucose and insulin tests should be performed here to adjust GH dose and thyroid hormone supplementation. Bone age should be checked once a year. Sexual development should be observed during the course of treatment and treated as needed. Regular repeat cranial MRI scans should be noted for suspected intracranial lesions.