Dwarfism is defined as a child whose height is less than two standard deviations (-2SD, the standard line is called SD) from the average height of children of the same sex, age, and race, and whose growth rate is less than 5 cm per year.
The following conditions suggest that the child is growing slowly.
① the growth rate of the child is less than 7 cm/year until the age of 3 years.
(ii) Less than 5 cm/year from age 3 to puberty.
(iii) less than 6 cm/year at puberty.
Etiology
1. Growth hormone deficiency or insufficient secretion, resulting in height failure to grow normally (i.e., commonly referred to as dwarfism, GHD), and without growth hormone replacement therapy, the final height can only reach about 130 cm.
Causes of growth hormone deficiency.
① Idiopathic (primary): These children have no obvious foci in the hypothalamus or pituitary gland, but the GH secretion function is insufficient and its cause is unknown.
(2) Organic (acquired): secondary to hypothalamic, pituitary or other intracranial tumors, infection, cellular infiltration, radiation injury and cranial trauma, among which birth injury is the most important cause of domestic GHD. In addition, developmental abnormalities of the pituitary gland, such as dysplasia, hypoplasia or empty pterygoid saddle, some of which are accompanied by malformations such as optic septal hypoplasia, cleft lip and cleft palate, can cause impaired synthesis and secretion of growth hormone, as well as a variety of anterior pituitary hormone deficiency.
Temporary physical puberty growth delay, psychosocial growth inhibition, primary hypothyroidism, etc. can cause temporary GH secretion hypofunction, which can return to normal after the elimination of external adverse factors or treatment of primary diseases.
2.Familial short stature.
3.Growth hormone insensitivity or resistance syndrome, mostly caused by mutation of growth hormone receptor gene, mostly autosomal recessive inheritance.
4, Congenital ovarian hypoplasia (Turner syndrome), karyotype analysis should be performed to identify.
5. About 1/3 of children with intrauterine growth retardation are short in stature in adulthood.
6.Disorders of skeletal development: various bone and cartilage dysplasia, etc., all have special facial and physical appearance.
7, other endocrine metabolic diseases caused by growth lag: congenital hypothyroidism, congenital adrenocortical hyperplasia, precocious puberty, cortisolism, mucopolysaccharidosis, glycogen accumulation disease, renal tubular acidosis, etc. each have their own clinical manifestations, easy to distinguish. Certain chronic diseases and malnutrition, etc.
Clinical manifestations
1. Short stature, slowed growth rate, delayed bone maturation and metabolic abnormalities.
Classification of short stature
① Slow growth dwarfism: uniform dwarfism in appearance, but slow growth, most commonly due to growth hormone deficiency, others are dwarfism caused by environmental and psychiatric factors, Turner syndrome caused by chromosomal lesions, dwarfism caused by chronic diseases (such as malnutrition, chronic kidney disease, congenital heart disease, chronic asthma, etc.).
② Disproportionate dwarfism: disproportionate dwarfism in appearance, i.e., children with disproportionate length of trunk and limbs, is commonly seen in chondrodysplasia, osteogenesis imperfecta and hypothyroidism.
(3) Dwarfism with normal body shape and normal growth rate: The appearance is proportional dwarfism and the annual growth rate is normal, which is common in familial dwarfism.
2.Primary illness or accompanying symptoms
In addition to stunted growth, low basal metabolic rate, and significantly lower bone age, there is also low intelligence in thyroid hormone (TSH) deficiency; gonadal hypoplasia in gonadotropin deficiency, small penis (i.e., the length of straightened penis is less than 2.5 cm), and no development of sexual organs and secondary sexual characteristics at puberty. In the case of intracranial tumors, there are mostly symptoms and signs of increased intracranial pressure and compression of the optic nerve, such as headache, vomiting and visual field defects.
Examination
1.Growth hormone stimulation test
GH stimulation test must be done in children suspected of GHD to determine the function of GH secretion by pituitary gland.
The physiological test is a screening test and the drug test is a confirmatory test. It is generally considered that a peak GH value <10ug/L during the test is an abnormal secretion function, a peak GH value <5ug/L is a complete GH deficiency, and a peak GH value 5-10ug/L is a partial GH deficiency. The diagnosis of GHD can only be confirmed when the results of two or more drug stimulation tests are abnormal because of the limitations of various GH stimulation tests, and generally insulin plus colistin or levodopa tests are chosen. For younger children, especially those with hypoglycemic symptoms during fasting, insulin should be given with special care, as it is likely to cause serious reactions such as hypoglycemic convulsions. In addition, if we need to distinguish whether the lesion is in hypothalamus or pituitary gland, GHRH stimulation test should be done.
2.Measurement of 24h secretion profile of blood GH
The 24h GH secretion can reflect the GH secretion in the body more correctly, especially for children with GHND, whose GH secretion function can be normal in the drug stimulation test, but their 24h secretion is insufficient, and the peak GH secretion during sleep at night is also low. However, this method is tedious and the number of blood draws is high, so it is not easy for patients to accept.
3. Measurement of insulin-like growth factor (1GF-1)
IGF-1 mainly exists in the blood circulation in the form of protein-bound (1GF-BPs), among which IGF-BP3 is predominant (more than 95%), IGF-1 and IGF-BP3 rarely fluctuate day and night and are very stable. This index has certain limitations and is also affected by factors such as nutritional status, degree of sexual development and thyroid function, so care should be taken when judging the results.
4.Other auxiliary examinations
①X-ray examination: the left wrist metacarpal bone film is often used to assess the bone age, and the bone age of children with GHD is 2 years or more behind the actual age. ②CT or MRI examination: Children diagnosed with GHD should choose cranial CT or MRI examination as needed to understand whether there are organic lesions in the hypothalamus-pituitary gland, especially for tumors.
5.Other endocrine examinations
Once GHD is established, other functions of hypothalamic-pituitary axis must be checked. According to the clinical manifestations, TSH, butyl-4 or thyrotropin-releasing hormone stimulation test and luteinizing hormone-releasing hormone stimulation test can be chosen to determine the function of hypothalamic-pituitary-thyroid axis and gonadal axis.
Diagnosis
The main diagnostic bases are.
① short stature, with height lagging behind 2 standard deviations from the average height of normal children of the same age and sex.
② Slow growth, growth rate <5cm/year.
③ bone age lagging behind the actual age by more than 2 years.
④Select the corresponding auxiliary examination according to the clinical manifestations.
Treatment
Corresponding treatment should be taken according to different etiologies.
1.Etiology treatment.
2.Nutrition, exercise and psychotherapy.
3.Replacement therapy, according to the deficient hormone to give the corresponding replacement therapy.
(1) Growth hormone growth hormone is suitable for people with growth hormone deficiency, intrauterine growth retardation, idiopathic dwarfism, congenital chondrodysplasia, and familial dwarfism who actively request treatment.
Genetically recombinant human growth hormone (rhGH) replacement therapy has been widely used, and most of them currently use a regimen of 0,1-0,2/(kg?day) subcutaneous injections once before bedtime, 6-7 times a week. The treatment should be continued until the epiphysis heals. The younger the age at the time of treatment, the better the effect, with the best effect in the first year, annual growth can reach more than 10cm, and later the growth rate gradually decreases. Thyroxine deficiency can occur during rhGH treatment, so thyroid function should be monitored and thyroxine should be added to the treatment if there is a deficiency.
The side effects of rhGH treatment are few, mainly include.
① local redness and swelling of the injection, which is related to the lack of purity of rhGH preparation and individual reaction, and can disappear after stopping the drug.
(ii) A few injections produce antibodies for several months after injection, but they have no significant effect on growth promotion efficacy.
(iii) Less common side effects include temporary optic papilloedema and intracranial hypertension.
④In addition, studies have found an increased incidence of femoral epiphyseal slippage and necrosis, but the risk is quite low. It is prohibited to use rhGH in patients with malignant tumor or potential tumor malignancy, or in patients with severe diabetes.
(2) Growth hormone-releasing hormone (GHRH) is known to be hypothalamic in nature, so GHRH can be effective in GHND, but it is not effective in pituitary GH deficiency. Generally, the daily dosage is 8-30ug/kg, and it is injected subcutaneously once a day in the morning and evening or continuously by 24h subcutaneous micro-pump.
(3) IGF-1 treatment for growth hormone insensitivity or resistance syndrome.
(4) Oral sex hormone anabolic steroid hormones are
(1) Fluoxymesterone 2,5mg/m2 per day.
②Oxymetholone 0,1~0,25mg/kg per day.
All of them are androgen derivatives with strong anabolic effects and weak androgenic effects, which have the side effects of accelerating skeletal maturation and masculinization, so the skeletal development should be closely observed. Nandrolone phenylpropionate has been used less frequently.
For males, testosterone enanthate 25mg can be injected once a month and increased by 25mg every 3 months until l00mg per month; for females, ethinyl estradiol 1~2ug/day or premarin can be used to gradually increase from 0,3mg per day, while bone age should be monitored.