Too little growth hormone
Introduction
Introduction Because of the low secretion of growth hormone secreted by the anterior pituitary, children's growth and development disorders, short stature is called growth hormone deficiency. Primary growth hormone deficiency is more common in boys. The child's height and weight are normal at birth, and growth retardation occurs several weeks later. It gradually becomes obvious after 2-3 years old. Its appearance is obviously smaller than the actual age, but the proportion of various parts of the body is still well-balanced. Intelligent development is also normal. The height is lower than 30% of normal children of the same age. A decrease in secondary sexual characteristics and sexual organ dysplasia can occur with age. Secondary growth hormone deficiency can occur at any age. In addition to the above symptoms, there are various symptoms and signs of the primary disease. Once the disease is diagnosed, growth hormone replacement therapy should be used as soon as possible. The younger the treatment, the better the effect. Domestically produced recombinant human growth hormone has been widely used.
Cause
Cause
Growth hormone deficiency is due to insufficient secretion of human growth hormone (hGH) as follows:
1, idiopathic (primary)
There is no obvious lesion in the hypothalamus and pituitary in this type of child, but the cause of GH secretion is insufficient. Among them, due to defects in the neurotransmitter-neurohormonal function pathway, the short stature caused by insufficient secretion of GHRG is called growth hormone neurosecretory dysfunction (GHND). The GHD caused by hypothalamic dysfunction is far less than that of pituitary function. More.
About 5% of children with GHD are caused by genetic factors, called hereditary growth hormone deficiency (HGHD). The human growth hormone gene cluster is encoded by genes such as GH1 (GH-N) and CSHP1, CSH1, GH2, and CSH2. The DNA chain of about 55Kbp long, which is caused by the deficiency of pituitary Pit-1 transcription factor due to the lack of GH1 gene called simple growth hormone deficiency (IGHD), is clinically characterized by a variety of pituitary hormone deficiency. Combined with pituitary hormone deficiency (CPHD), IGHD is genetically classified into three types: I (AR), II (AD), and III (X-linked). In addition, a small number of short stature children are due to abnormal GH molecular structure, GH Caused by body defect (Laron syndrome) or IGF receptor deficiency (Pygmy human), the clinical symptoms are similar to GHD, but it shows GH no resistance or IGF-1 resistance, serum GH level does not decrease or increase, it is rare Hereditary disease.
2, organic (acquired)
Secondary to hypothalamic, pituitary or other intracranial tumors, infection, cell infiltration, radiation damage and head trauma, etc., of which birth injury is the most important cause of domestic GHD, in addition, pituitary developmental abnormalities, such as non-development, dysplasia Or empty sella, some of them related to the development of septal hypoplasia, cleft lip, cleft palate and other malformations, can cause growth hormone synthesis and secretion disorders.
3. Temporary
Physical puberty growth delay, psychosocial growth inhibition, primary hypothyroidism, etc. can cause temporary GH secretion dysfunction, and can be restored after the elimination of external adverse factors or treatment of primary disease.
Examine
an examination
Related inspection
Insulin growth hormone blood glucose sleep test insulin hypoglycemia excitatory GH, ACTH test
First, laboratory inspection
1. Growth hormone stimulation experiment
The diagnosis of growth hormone deficiency depends on GH. The normal human serum GH value is very low, and it is pulsed secretion. It is affected by various factors. Therefore, blood sampling and blood GH are not meaningful for diagnosis, but if the blood GH level is significantly higher. At normal (>10 g/L), GHD can be excluded. Therefore, children with GHD are suspected of having to undergo a GH stimulation test to determine the function of the pituitary to secrete GH.
The physiological test is a screening test and a drug test is a confirmed test. It is generally believed that during the test, the peak value of GH is <10 g/L, which means that the secretion function is abnormal. The peak of GH is <5 g/L, which is no complete deficiency of GH. The peak of GH is 5-10 g/L, which is a lack of GH. Because of the limitations of various GH stimulation tests, GHD must be diagnosed if the results of two or more drug stimulation tests are not normal. In general, insulin is added to the clonidine or levodopa test. For younger children, especially those with hypoglycemia on an empty stomach, special care should be taken for insulin, which can cause serious reactions such as hypoglycemia and convulsions. In addition, if it is necessary to distinguish whether the lesion is in the hypothalamus or in the pituitary, a GHRH stimulation test is required.
2. Determination of 24H secretion spectrum of blood GH
The peak value of growth hormone in normal people is very different from the base value. The secretion of H in 24 hours can correctly reflect the secretion of GH in the body. Especially for children with GHND, the GH secretion can be normal, but the secretion of 24h is normal. Insufficient, the peak of GH at night is also low, but the program is cumbersome and has a lot of blood draws, which is not intended for patients.
3. Determination of pancreatic nucleus growth factor (IGF-1)
IGF-1 is mainly present in the blood circulation in the form of protein binding (IGF-BPs), of which IGF-BP3 is predominant (more than 95%). IGF-BP3 has co-cooling for transporting and regulating IGF-1, and its synthesis is also affected. The regulation of GH-IGF axis, therefore, both IGF-1 and IGF-BP3 are indicators for detecting the function of the axis. The secretion mode of the two is different from GH, and it is non-pulsed, so it is stable, and its concentration is below 5 years old. Very low, and with age and development performance, puberty peak, girls reach the peak two years earlier than boys, currently can be used as a GHD screening test for children from 5 years old to puberty, this indicator has certain limitations It is also affected by factors such as nutritional status, sexual development and thyroid function, and should be noted when judging the results.
4. Other auxiliary inspections
(1) X-ray examination: bone age is usually assessed by right wrist and metacarpal bone. The bone age of children with GHD lags behind the actual age of 2 years or older.
(2) CT or MRI examination: children who have been diagnosed with GHD, choose head CT or MRI as needed to understand the hypothalamic-pituitary organic lesions, especially for tumors.
5, other endocrine examination
Once GHD is established, other functions of the hypothalamic-pituitary axis must be examined. TSH, T4 or thyrotropin-releasing hormone (TRI) stimulation test and luteinizing hormone-releasing hormone (LHRH) can be selected according to clinical manifestations. The function of the thalamus-pituitary, thyroid axis and gonadal axis.
Second, the main diagnosis basis
1 short stature, height behind the third percentile of normal children of the same age and same sex,
2 slow growth, growth rate <4cm / year,
3 bone age is behind the actual age of more than 2 years,
The 4GH stimulation test showed partial or complete deficiency of GH,
5 intelligence is normal, commensurate with age,
6 Exclude other disease effects.
Diagnosis
Differential diagnosis
Differential diagnosis of too little growth hormone secretion:
1. Short stature caused by non-endocrine factors
(1) Constitutional short stature: not a disease, a positive family history, height at birth, normal weight, slow growth in childhood, delayed development of puberty, accelerated growth during puberty, some people are not obvious, adult height is normal or The normal low limit. During the growth retardation period, the child had no facial manifestations of pituitary pygmy, normal body shape, normal or slightly delayed bone age, and other laboratory tests were normal.
(2) genetic hereditary dwarfism: related to family, ethnicity, no endocrine dysfunction, normal bone age.
(3) Prenatal dysplasia: After birth, some low-weight children and premature babies have been growing with low percentiles and still very short after adults. The child's face may have naive, round face, and even fine wrinkles, normal body shape, normal or slightly delayed bone age, and normal endocrine function.
A variety of serious chronic diseases of the whole body or organs can cause growth disorders in children and adolescents. More serious are malnutrition, malabsorption, chronic liver disease, congenital heart disease, chronic kidney disease, chronic lung disease. Before the endocrine examination of dwarfism, these aspects should be noted or checked.
(4) various short syndromes: congenital or hereditary diseases such as Turner syndrome, Noonan syndrome (pseudo Turner syndrome), Prader-Willi-Lalhert syndrome, Laurence-Moon-Biedle syndrome, and autosomes All kinds of abnormalities can be manifested as short stature in childhood and even in adults; in addition to short stature, they also have their own unique clinical manifestations, which are easier to distinguish from growth hormone deficiency.
(5) bone and cartilage hypoplasia: children with many limb malformations, easy to distinguish.
2. Other shortcomings caused by endocrine factors
(1) Laron gnome: increased blood GH, but defective in liver receptors or receptors, resulting in a decrease in insulin-like growth factor-I (IGF-I); the latter is the main growth factor for growth after birth. The disease is autosomal recessive, its clinical manifestations are consistent with growth hormone deficiency, and the diagnosis depends on the increase in blood GH in children to make a judgment; the determination of blood IGF-I deficiency or significant reduction, plus GH rise High, you can confirm the diagnosis.
(2) Pygmies pygmy: found in the Pygmy ethnic group in Central Africa, Central South Asia and the Atlantic Ocean, is autosomal recessive. Serum GH is normal or elevated, but IGF-I is decreased, IGF-II is normal, and exogenous GH cannot improve growth.
(3) Abnormal GH secretion of molecular structure: Rarely, the concentration of immunologically active GH in blood is increased, but its biological activity is decreased or absent.
(4) Hypothyroidism: In children, cretinism, mental retardation, and abnormal body shape. However, some children have atypical performance, with obvious growth and development disorders, and other symptoms are mild, which should be noticed.
(5) Hypercorticosteroids: including Cushing's disease, excessive secretion of cortisol from adrenal tumors, and long-term treatment with glucocorticoids. The reasons are manifold, mainly because a large number of glucocorticoids inhibit GH secretion, inhibit the stimulation of growth hormone on the growth of cartilage, and cause negative nitrogen balance, protein synthesis disorders and bone decalcification, such bone matrix formation Slowly, calcium salts cannot be deposited and growth is inhibited.
(6) Diabetes: The control of childhood diabetes is not good, and some children have growth and development disorders. The reason may be that there are too many endogenous glucocorticoids in this part of the child, and the lack of insulin, the protein synthesis is seriously affected. Effective treatment of diabetes can restore growth. If the child has diabetes, short stature and hepatosplenomegaly, it is called Mauric syndrome.
(7) Diabetes insipidus: Uncontrolled children have growth disorders due to reduced food intake and internal environment and metabolic disorders. After correction, most can resume growth.
