I. Medical history
Careful questions should be asked about: the pregnancy of the child’s mother; the child’s birth history; birth length and weight; growth history; and the parents’ pubertal development and short stature in the family.
Physical examination
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 from the height of the parents; ④ the BMI value; ⑤ the sexual development stage.
III. Laboratory tests
Blood and urine tests and liver and kidney function tests should be routinely performed; blood gas and electrolyte analysis should be performed for suspected renal tubular toxicity; karyotype analysis should be performed 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, and being too far behind or too far ahead is considered abnormal.
3.Special examination
(1) Indications for special examination ① those whose height is lower than the normal reference value minus 2 SD (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. <7 CM/rh for children <2 years old; ④ those with clinical symptoms of endocrine disorders or malformation syndrome; ⑤ those who need pituitary function examination for other reasons (2) Growth hormone - insulin
(2) Growth hormone-insulin-like growth factor-1 axis (GH-IGF-1) function measurement 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. As shown in Table 2.
(3) Measurement of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) The 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 the injection 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 the injection 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 hormone options may be tested as needed
(6) Imaging of hypothalamus and pituitary gland MRI 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 Psycho-psychological and renal tubular acidosis, etc. After the relevant factors are eliminated, their height growth rate will be increased, and the daily nutrition and sleep guarantee 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 dose in China is 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, idiopathic short stature and some children with partial growth hormone deficiency, the applied dose is 0.15-0.20IU/(K.d) 0.35-0.46(J.K) per week (Note: The WHO labeled growth hormone 1J=3). WHO labeled growth hormone 1J=3IU)
(3) Usage: Subcutaneous injection is given once a night before bedtime, and the usual injection site is the outer and anterior side of the middle 1/2 of the thigh.
(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.
(5) Side effects: The common side effects are: (1) hypothyroidism: it occurs every 2-3 months after the start of injection and can be corrected by giving L-thyroxine tablets as needed; (2) altered glucose metabolism: the long-term use of large amounts of growth hormone may cause insulin resistance in children. Fasting blood glucose and insulin levels may rise, but rarely exceed the normal high limit, which can be recovered after several months of growth hormone discontinuation, and should be monitored during the course of treatment, especially in children with a family history of diabetes and obese children. The growth disorders caused by chronic renal failure, Turner syndrome and GH deficiency may lead to suspension of GH therapy and addition of small doses (e.g., hydrochlorothiazide) to reduce intracranial pressure. (6) Local redness or rash of injection: usually disappears within a few days and can continue to be used, which is now rare (7) The possibility of tumor induction: international organizations have conducted relevant research studies, according to the National Cooperative Growth Group and Drug Therapy Research Center. The results show that GH treatment does not increase the risk of leukemia and tumor recurrence in children without potential tumor risk factors, but caution should be exercised in the application of long-term supraphysiological doses of GH in children with previous tumors, genetic predisposition to tumor development in families, and malformation syndromes, and the treatment process should be closely monitored. In the course of treatment, the serum IGF-1 level should be closely monitored and should be temporarily discontinued if it exceeds the normal reference value +2SD.
3, other drugs: ① during the course of treatment should pay attention to the supplementation of calcium, trace elements, etc., for bone growth; ② anabolic hormone: often used with growth hormone to treat Turner syndrome, most of the domestic use of stanozolol, Conilon), the common 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 for the treatment of short stature, but there is not enough information 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.