Growth Failure
Growth deficiency (growth hormone deficiency) occurs with a large number of diseases and syndromes. According to etiology, congenital and acquired as well as organic and idiopathic growth hormone deficiency are distinguished.
In the most common form, somatotropic deficiency is manifested as nanism syndrome. Nanism is a clinical syndrome characterized by a sharp lag in growth and physical development associated with an absolute or relative deficiency of growth hormone.
In most patients, pathology of regulation and secretion of other pituitary hormones occurs, as a rule, there are impaired secretion of FSH, LH, and TSH, which is accompanied by various combinations of endocrine and metabolic disorders (panhypopituitary nanism).
Men of dwarf growth include men with a height below 130 cm and women below 120 cm. The smallest described growth of a dwarf was 38 cm.
Most forms of somatotropic insufficiency are genetic, more often there is a primary pathology of a hypothalamic nature, and insufficiency of hormones of the anterior pituitary is a secondary phenomenon.
Genetic forms of nanism with isolated growth hormone deficiency were identified during the deletion of the growth hormone gene and with the biological inactivity of growth hormone due to the mutation of this gene. Nanism due to peripheral tissue insensitivity to growth hormone is associated with a deficiency of somatomedes or a defect in growth hormone receptors.
Causes of pituitary nanism can be underdevelopment or aplasia of the pituitary, its dystopia, cystic degeneration, atrophy or compression by a tumor (craniopharyngioma, chromo-
phobic adenoma, meningioma, glioma), trauma of the central nervous system of the prenatal, generic or postnatal period.
Tumors of the adenohypophysis, hypothalamus, intracellular cysts and craniopharyngiomas lead to insufficiency of growth hormone production.
When this occurs, compression of the pituitary tissue occurs with wrinkling, degeneration and involution of glandular cells, including somatotrophs, with a decrease in the level of hormone secretion of growth.
Infectious and toxic damage to the central nervous system in early childhood is important. Intrauterine lesions of the fetus can lead to “nanizmu since birth,” the so-called cerebral primordial nanizmu.
This term unites a group of diseases, which include Silver’s nanizm with hemiasymmetry of the body and a high level of gonadotropins, Russell’s inborn nanizm.
Severe chronic somatic diseases are often accompanied by severe short stature, for example, glomerulone-frit, in which azotemia directly affects liver cells, reducing the synthesis of somatomedins; cirrhosis of the liver.
Changes in the internal organs during dwarfism are reduced to thinning of the bones, delayed differentiation and ossification of the skeleton.
Internal organs are hypoplastic, muscles and subcutaneous fat are poorly developed. With isolated growth hormone deficiency, morphological changes in the pituitary gland are rarely detected.
Over a long period of time, the absolute or relative deficiency of growth hormone was regarded as a problem of exceptionally pediatric endocrinology, and the main purpose of the appointment of replacement therapy was to achieve socially acceptable growth.
Growth hormone deficiency, which first arose in adulthood, occurs with a frequency of 1: 10,000. Its most frequent causes are pituitary adenomas or other tumors of the circulatory area, the consequences of therapeutic measures for these tumors (operations, radiation therapy). .
Clinic
The main signs of nanism are a sharp lag in growth and physical development. Prenatal growth retardation is typical for children with intrauterine growth retardation with genetic syndromes, chromosomal abnormalities, hereditary growth hormone deficiency due to deletion of the growth hormone gene.
Children with classical somatotropic insufficiency are born with a normal mass and body length and begin to lag behind in age from 2-4 years of age. To explain this phenomenon, it is assumed that up to 2-4 years of age, prolactin can produce an effect similar to a growth hormone in children.
A number of works refutes these ideas, pointing out that some lag in growth is noted after birth.
Children with organic genesis of growth hormone deficiency (with craniopharyngioma, craniocerebral injury) are characterized by later periods of growth deficiency after 5-6 years of age.
In case of idiopathic growth hormone deficiency, a high frequency of perinatal pathology is detected: asphyxia, respiratory distress syndrome, hypoglycemic states.
In the family history of children with constitutional growth retardation and puberty, with which it is necessary to differentiate somatotropic insufficiency, in most cases it is possible to identify similar cases of short stature in children one of the parents.
In case of idiopathic pituitary nanism, against the background of stunted growth, normal proportions of the child’s body are observed.
Untreated adults show children’s body proportions. The facial features are small (“puppet face”), the bridge of nose sinks. The skin is pale, with a yellowish tinge, dry, sometimes cyanosis is observed, marbling of the skin.
In untreated patients, the “old form”, thinning and wrinkling of the skin (geroderma) appear early, which is due to the insufficiency of the anabolic effect of growth hormone and the slow change of cell generations.
The distribution of subcutaneous fat varies from depletion to obesity. Secondary hair distribution is more often absent. The muscular system is underdeveloped. Boys, as a rule, have micropenis.
Sexual development is delayed and occurs when the bone age of the child reaches pubertal level. A significant proportion of children with growth hormone deficiency has a concomitant gonadotropin deficiency.
Diagnostics
The main methods of clinical diagnosis of growth retardation are anthropometry and comparison of its results with percentile tables.
On the basis of dynamic observation, growth curves are plotted. In children with growth hormone deficiency, the growth rate does not exceed 4 cm per year. To exclude various skeletal dysplasias (achondroplasia, hypochondroplasia), it is advisable to estimate body proportions.
In evaluating the radiographs of the hands and wrist joints, the so-called bone age is determined, and in this case, the hypohyseal nanism is characterized by a significant delay in ossification. In addition, in some patients, destruction of areas of the skeleton, heads of the femoral bones with the development of aseptic osteochondrosis, is observed as the most injured under static load of the skeleton.
When radiography of the skull with pituitary nanism, as a rule, they reveal the unchanged size of the Turkish saddle, but it often retains the children’s form of a “standing oval”, has a wide (“juvenile”) back.
An MRI scan of the brain is shown for any effect on intracranial pathology. The study of somatotropic function is leading for the diagnosis of hypophysical anisle.
A single determination of the level of growth hormone in the blood for the diagnosis of somatotropic insufficiency does not matter because of the episodic nature of the secretion of growth hormone and the possibility of obtaining low, and in some cases zero, baseline values of growth hormone even in healthy children. For screening studies, it is acceptable to determine urine growth hormone excretion.
In clinical practice, stimulation tests with insulin, clonidine, arginine and a number of others are most widely used.
Growth hormone deficiency in adults is accompanied by a violation of all types of metabolism and extensive clinical symptoms. An increase in the content of triglycerides, total cholesterol and low density lipoproteins, a decrease in lipolysis is noted.
Obesity develops predominantly in visceral type. Violation of protein synthesis leads to a decrease in the mass and strength of skeletal muscles, marked myocardial dystrophy with a decrease in the cardiac output fraction. There is a violation of glucose tolerance, insulin resistance. Hypoglycemic states are not uncommon. Psychological changes are one of the most prominent manifestations of the disease. There are tendencies to depression, anxiety, fatigue, poor general well-being, impaired emotional reactions, a tendency to social exclusion.
Reduced blood fibrinolytic activity, lipid spectrum disorders leading to the development of atherosclerosis, as well as changes in the structure and function of the heart muscle are the causes of a twofold increase in the death rate from cardiovascular diseases among patients with panhypopituitarism who receive replacement therapy that does not precede the appointment of growth hormone.
Against the background of somatotropin deficiency, a decrease in bone mass due to the acceleration of bone resorption develops, which leads to an increase in the frequency of fractures. One of the most valuable studies in the diagnosis of somatotropic insufficiency is the determination of the level of IGF-1 and IGF-2, as well as somatome dinosaur protein.
These studies underlie the diagnosis of dwarfism and other conditions belonging to the group of peripheral resistance to the action of growth hormone. The most informative and simple study is the determination of the plasma level of IGF-1. With its decrease, stimulating tests are carried out with insulin, clonidine, arginine, somatoliberin.
Treatment
The basis of pathogenetic therapy of pituitary nanism is replacement therapy with growth hormone preparations. The drug of choice is the genetic engineering human growth hormone. The recommended standard dose of growth hormone in the treatment of classical growth hormone deficiency is 0.07–0.1 U / kg of body weight per injection daily subcutaneously at 20: 00–22:00 h
A promising area of treatment for peripheral growth hormone resistance is treatment with recombinant IGF-1.
If growth hormone deficiency has developed within the framework of panhypopituitism, moreover, replacement therapy for hypothyroidism, hypocorticism, hypogonadism, and diabetes insipidus is prescribed.
For the treatment of somatotropic insufficiency in adults, recommended doses of genetic engineering human growth hormone range from 0.125 U / kg (initial dose) to 0.25 U / kg (maximum dose).
The optimal maintenance dose is selected individually based on the study of the dynamics of IGF1. The question of the total duration of growth hormone therapy currently remains open.