Since there are many causes of short stature, a comprehensive examination (including detailed medical history, comprehensive physical examination and laboratory tests) must be conducted for children with short stature to clarify the causes for treatment.
1. Medical history
Medical history should include birth, birth weight and length, number of weeks of gestation, mode of delivery, ability to live during the neonatal period, physical development, motor and intellectual development of the child after birth, history of disease and treatment after birth. Maternal health status during pregnancy: delivery, number of births, number of deliveries, history of spontaneous abortions and stillbirths, etc. Family history of parents and all members height, history of pubertal development of parents. The status of the sick child in the family, the degree of parental concern for the sick child, and the presence of adverse factors in the family that affect the sick child’s spirit. The child’s annual height growth.
2.Physical examination
Physical measurements should include height, weight, sitting height, finger spacing, head circumference, etc. Observe whether the child’s physical development is proportional, head, trunk, limbs, finger spacing size pattern, etc. The distribution of the five senses and the facial features are special. The distribution of subcutaneous fat, muscle development, muscle tone, joint ligament activity, and sexual development. In addition, the following should be properly measured and recorded.
1) Current height and weight measurements and percentile.
2) Annual rate of height growth (at least 3 months of observation).
3) Target height as measured by the height of his parents.
4) BMI value.
5) Stages of sexual development.
3. Laboratory tests
1) X-ray examination: Children with short stature need to take left hand orthopantomographs to determine bone age. Under normal circumstances, the difference between bone age and actual age should be between ±1 year, and lagging behind or exceeding too much is considered abnormal.
If the patient’s physique is not homogeneous and skeletal lesions are suspected, further bone X-ray should be examined, including the spine, pelvis, thorax and, if necessary, the upper or (and) lower extremities, while observing the growth of bones and the density of bones can initially clarify the diagnosis of bone disease.
2) Routine examination: routine blood and urine examination, liver and kidney function and blood biochemistry, electrolytes, blood gas examination, blood calcium, phosphorus, zinc, alkaline phosphatase determination
3)Chromosome examination: If the girl is short or has mild deformity, cell chromosome examination should be done to clarify whether it is Turner syndrome.
4) Endocrine examination.
(1) Thyroid function: measurement of serum T3, T4 or TSH.
(2) Growth hormone an insulin-like growth factor I axis (GH-IGF-I) function measurement.
a) Measurement of growth hormone secretion function.
GH peak during the drug stimulation test <5 μg/L is considered complete growth hormone deficiency (GHD); between 5 and 10 μg/L is considered partial deficiency (pGHD); >10 μg/L is normal. Since there is a 15% false positive rate for either stimulation test (meaning low GH secretion), the diagnosis of GHD must be confirmed when both stimulation tests are abnormal. It can be performed over 2 d or given at the same time (combined stimulation). The insulin test is not only reliable, but also allows simultaneous measurement of hypothalamic-pituitary-adrenal axis function. Blood glucose is measured before and after insulin injection, and blood glucose <40 mg/dl or half of the basal value is considered effective stimulation. The pituitary function of children with GHD due to hypothalamic lesions is normal, and growth hormone-releasing hormone (GHRH) can promote normal secretion of GH by the pituitary gland. Therefore, the GHRH test is generally not used for diagnosis, but is often used to distinguish between hypothalamic or pituitary lesions. Colistin test may show symptoms such as fatigue and drowsiness, and a few have nausea and vomiting; pyridostigmine may cause abdominal pain, which is usually tolerated, and severe cases may be given atropine intramuscular injection, but it may affect the test results.
b) IGF1 and IGFBP3 measurement.
IGF1 and IGFBP3 levels are mainly regulated by GH, and their concentrations are consistent with GH concentrations in a wide range, which is an important indicator of GH-IGF function and an important indicator for the diagnosis of GH deficiency. Their serum concentrations increase with age and developmental process, and are related to nutrition and other factors.
In children with suspected GH resistance (Lamn syndrome), IGF1 production test can be performed to detect GH receptor function. Method 1: rhGH was injected subcutaneously at 0.075-0.15 U/(kg・d) every night for 1 week, and IGF1 was measured by taking blood samples before and on the 5th and 8th day after the injection; Method 2: rhGH was injected subcutaneously at 0.3 u/(kg・d) every night for 4 days, and IGF1 was measured by taking blood samples before and once after the last injection. After the injection, the serum IGF1 will increase more than 3 times the basal value, or reach the normal value corresponding to their age.
(3) Testing of other endocrine hormones: Based on the clinical manifestations of the child, the test will be selected as needed.
(5) Imaging of hypothalamus and pituitary gland: MRI of the skull should be performed in all children with short stature to exclude the possibility of congenital developmental abnormalities or tumors.