What Is Pituitary Dwarfism?

The disease can be divided into two categories based on the cause.

Pituitary dwarfism

Pituitary dwarfism (pituitarydwarfism) refers to anterior pituitary dysfunction or hypothalamic lesions that cause growth hormone (GH) to be secreted insufficiently, resulting in slow growth and development. The etiology is divided into three categories: idiopathic pituitary dwarfism, which can be GH deficiency alone, or multiple anterior pituitary hormone deficiency. Secondary pituitary dwarfism, due to organic lesions of the pituitary or hypothalamus, such as birth injury, tumors, infections, bleeding, X-ray radiation, etc., cause GH secretion disorders. Hereditary dwarfism, pituitary dysplasia, and some GH are not lacking, but are caused by disorders of somatomedin (SM) synthesis or abnormal receptors.

Pathogenesis of pituitary dwarfism

The disease can be divided into two categories based on the cause.

I. Primary: Most patients have unknown causes and no family history. Only a small part of them have a family history of onset, and they are autosomal recessive.

Second, secondary: relatively rare, any lesions can cause growth and development arrest when the anterior pituitary or hypothalamus is damaged, and common tumors (such as craniopharyngioma, interstitial or hypothalamic glioma, pituitary xanthomas, etc.) ), Infections (such as encephalitis, tuberculosis, schistosomiasis, toxoplasmosis, etc.), trauma, vascular necrosis and X-ray damage.

Pathological changes of pituitary dwarfism

Pituitary atrophy is the main cause, growth hormone secretion from the anterior pituitary gland is insufficient to cause developmental delay, and it may also be due to hypothalamus growth hormone release factor deficiency. Growth hormone directly affects tissue cells throughout the body, which can increase the volume and number of cells, and promote body growth. Growth hormone is mainly a protein synthesis hormone, which can accelerate the transport of amino acids from outside the cell into the cell and stimulate the recovery of DNA.

Pituitary dwarfism Growth control can reduce the use of glucose in peripheral tissues, and thus increase blood glucose. It can inhibit the transfer of glucose into cells, which is exactly the opposite of insulin's role in promoting glucose to move into cells. Therefore, it is in contrast to insulin. There are antagonistic effects in the regulation of glucose metabolism; in addition, it can promote the mobilization and utilization of fat to supply energy. When growth hormone is deficient, it causes slow growth or even stagnation.

Most patients also have insufficient secretion of pituitary gonadotropin, and some cases also have insufficient secretion of thyroid stimulating hormone and adrenocorticotropic hormone, which cause dysfunction of endocrine glands.

Diagnosis of pituitary dwarfism

Growth and developmental disorders. May have familial inheritance. Secondary patients often have intracranial tumors (such as craniopharyngioma, chromocytoma), infection, trauma, or a history of high-dose glucocorticoids.

The height is lower than normal people of the same age and gender, and the average height is mostly below 130cm (usually the average height of normal people-3 times the standard deviation). The growth rate is less than 4cm / year, and intellectual development is generally normal.

Metatarsal age is slow, more than 4 years below the actual age, and epiphyseal fusion is delayed. No special saddle size

Pituitary dwarfism However, those with lesions in the saddle area may have calcification on the saddle, enlargement of the saddle, and bone destruction.

Infant sexual organs are not developed, secondary sexual characteristics are lacking, and other infantile manifestations, thyroid and adrenal cortex function may be slightly reduced and highly sensitive to insulin.

The serum growth hormone level is low, and it does not respond to insulin-induced hyperglycemia and excitatory tests such as arginine, levodopa, and pirostamine (less than 5 g / L). Serum gonadotropin levels are low after puberty.

Exclude the following diseases: constitutional delay of puberty, primorrhea dwarfism, hypothyroidism in children, skeletal diseases (chondrogenesis disorders, osteogenesis imperfecta), nutritional metabolic diseases, congenital heart disease, gonadal development disorders (such as Turner syndrome ) And other dwarfism.

Clinical manifestations of pituitary dwarfism

Primary pituitary dwarfism is more common in boys. Length and weight are usually normal at birth. Initially, there is no significant difference from normal children in one or two years. The growth rate has slowed down since 1 to 2 years old, and has stopped stagnation in early childhood. Age The greater the backwardness, the more obvious it will be, and the adult will not grow more than 130 cm in length, but the intellectual development is normal, the appearance of the child is smaller than the actual age, but the amount of upper body

Pituitary dwarfism The proportion to the lower part is often similar to its actual age, so the proportion of development of each part is still proportional. The patient's head is slightly larger and rounder, with less hair and softer texture, and the skin is thin and creamy. His face is often younger than his actual age, his chest is narrow, and his hands and feet are smaller. Teething was delayed, ossification centers were stunted, bone age was similar to children of the same height and age, and the crotch fusion was late.

Most children have hypogonadism and lack of secondary sexual characteristics. By puberty, the male genitalia are still as small as young children, cryptorchidism is quite common, and the tone is like childish sounds. Women often have primary amenorrhea, with undeveloped breasts and buttocks. They do not have the characteristics of a female adult. They have a small uterus and a vulva like a girl. Thyroid and adrenal cortex functions are often low, but clinical symptoms are often not obvious.

Secondary pituitary dwarfism can occur at any age. After the illness, growth and development begin to slow down with the symptoms of primary disease. Patients with intracranial tumors can see symptoms and signs of increased intracranial pressure and optic nerve compression, such as headache. , Vomiting, visual field defect or shrinkage, etc., even because the posterior pituitary or hypothalamus is also damaged and concurrent diabetes insipidus.

Diagnosis of pituitary dwarfism

Diagnosis is mainly based on medical history and physical examination. After 1 to 2 years of age, it grows slowly, and its length is lower than three standard deviations (S.D.) of normal children of the same age. Attention should also be paid to check for primary disease.

In recent years, the concentration of growth hormone in serum has been measured, and patients often decrease significantly. The growth hormone concentration in the fasting (before breakfast) serum of a normal person is 3 ng / ml, the child is 5 ng / ml, and the child is usually less than 5 ng / ml. Due to its small amount, the measurement is not easy to be accurate. Normal people increase their serum growth hormone levels when they fall asleep or after meals and exercise. Therefore, blood can be taken 60 to 90 minutes after falling asleep or 10 minutes after exercise for 2 hours after eating. Patients often do not increase or <5 Nanograms per milliliter, some people use insulin or L-arginine intravenously to produce hypoglycemia, in normal people can promote a temporary rise in serum growth hormone, but patients do not respond.

Patients with pituitary dwarfism often have insufficient secretion of pituitary thyroid stimulating hormone and adrenocorticotropic hormone, their serum cholesterol can increase, and serum T3 and T4 often decrease or are at the marginal level. Both 17-hydroxysteroids and 17-ketosteroids were reduced in urine.

Differential diagnosis of pituitary dwarfism

Dwarf caused by non-endocrine factors of pituitary dwarfism

Physique dwarf: Not a disease, a positive family history, normal height and weight at birth, childhood growth has been retarded, delayed puberty, delayed growth in adolescence, some people are not obvious, adult normal height or normal low growth retardation Within, the child had no pituitary dwarf facial manifestations, normal body shape, normal bone age, or a slight delay in other laboratory tests.

Genetic dwarfism: related to family and race, no endocrine disorders

Pituitary dwarfism often.

(3) Fetal dysplasia: Premature babies with low birth weight are born in some patients after birth and have grown at low percentiles. Children with short babies may have childish faces on their faces, and may also have fine wrinkles. Delayed, normal endocrine function

A variety of severe systemic or organ chronic diseases can cause growth disorders in children and adolescents. The more serious ones are malnutrition, malabsorption, chronic liver disease, congenital heart disease, chronic kidney disease, and chronic lung disease. Before endocrine examination of dwarfism, these issues should be noted or checked.

Various dwarf syndromes: Congenital or hereditary diseases such as Turner, Syndrome Noonan, Syndrome, (False Turner Syndrome) Prader-Willi-Lalhert syndrome, Laurence-Moon-Biedle syndrome, and autosomal abnormalities A variety of conditions caused by them can be manifested as short stature in childhood and even adults; in addition to short stature, their unique clinical manifestations are easier to distinguish from pituitary dwarfism.

Metatarsal and cartilage hypoplasia: Children often have limb deformities that are easy to distinguish.

Pituitary dwarfism caused by other endocrine factors

Laron dwarf: GH in blood increases but liver receptors or receptors are defective, and insulin-like growth factor-I (IGF-) production is reduced; the latter is the main growth mediator that promotes growth after birth. The disease is an autosomal recessive inheritance, and its clinical manifestations are consistent with pituitary dwarfism. The diagnosis depends on the increase of blood GH in the child to make a judgment; the determination of IGF- in the blood is deficient or significantly reduced, followed by an increase in GH. , You can confirm the diagnosis. Pygmies pygmy: found in the Pygmies of Central Africa, Central and South Asia, and the Atlantic Ocean. It is autosomal recessive. Serum GH is normal or increased but IGF- decreases. IGF- is normal. Exogenous GH does not improve growth.

(3) GH secretion with abnormal molecular structure: Rarely, the concentration of immunologically active GH in blood is increased but its biological activity is reduced or lacking.

Hypothyroidism: Cretinism in children, mental retardation, abnormal body shape but

Pituitary dwarfism Some children have atypical manifestations, with obvious growth and development disorders and other mild symptoms, which should be paid attention to.

Glucocorticoid hyperthyroidism: Including excessive cortisol secretion from adrenal tumors of Cushing's disease and long-term treatment with glucocorticoids. There are many reasons. The main reason is that a large number of glucocorticoids inhibit the secretion of GH and inhibit the growth mediator's stimulating effect on cartilage growth, and cause negative nitrogen balance to impede protein synthesis and decalcify the bone, so that the formation of bone matrix is delayed. Salt cannot be deposited and growth is inhibited.

Diabetes: Diabetes in early childhood is not well controlled, and some children have growth and development disorders. The reason may be that these children have too many endogenous glucocorticoids and insufficient insulin, and their protein synthesis has been seriously affected. Effective treatment of diabetes can restore growth. Children with diabetic dwarf and hepatosplenomegaly are called Mauric syndrome.

Diabetes insipidus: Uncontrolled children suffer from growth disorders due to reduced food intake and internal environment and metabolic disorders. Most of them can resume growth after correction.

Treatment of pituitary dwarfism

Secondary pituitary dwarfism requires etiological treatment, such as craniopharyngioma surgery as soon as possible. Idiopathic

Pituitary dwarfism In patients with somatic dwarfism, pituitary growth hormone deficiency is best replaced with growth hormone replacement therapy. These patients can grow taller when treated with growth hormone. Several drug treatment methods are described below. They can be used alone or in combination, the key is to use according to the specific situation of the patient.

Pituitary dwarfism growth hormone

Since its application in 1958, it has been clinically proven effective, but its sources are limited and expensive, and it has not been widely used. Usage is: Generally, the dosage is 1-2 mg each time, intramuscular injection, 3 times a week. 20 to 45 mg per month. Because human growth hormone is mostly secreted daily at night, injection of the drug is generally best performed 1 hour before bedtime. The effect was most significant at the beginning of 6-12 weeks of treatment, and it could be increased by 5-10 cm in the first year. After long-term application, the growth rate slows down, increasing by 3 to 5 cm per year. The earlier you start this treatment, the better. Those who have the conditions should be treated for a long time, although the growth has basically stopped. If androgen drugs that promote protein synthesis are added, the effect may increase. Growth hormones and androgens have a synergistic effect on growth.

Pituitary dwarfism ) androgen

Synthetic anabolic hormone Nandrolone phenylpropionate, also known as l9-desmethyl-testosterone propionate, with a total monthly dose of 1.1 mg per kilogram of body weight, divided into intramuscular injections, usually weekly Times. The age at which treatment is started is generally considered to be better at the age of 10-14. Nandrolone phenylpropionate promotes bone growth at the same time as promoting growth and development, so the effect is often significant when starting the drug, and the effect is worse in the future. During treatment, avoid excessive dosage and premature fusion of epiphysis. It is best to observe the bone age when it is applied. When the bone age is less than 3 years old, it should not be used again. The rabbit will affect the final height. With this drug a course of 3 to 6 months, treatment can be repeated after 3 to 6 months.

(3) chorionic gonadotropin; generally women can take medicine after 16 years old, men can take medicine after 19 years old. The age of medication should not be too early, because it can promote epiphyseal fusion and eventually hinder bone growth. Usage: intramuscular injection, 2 times 3 times a week, 3 to 6 months as a course of treatment.

Prevention of pituitary dwarfism

Prognosis of pituitary dwarfism

If the disease is not diagnosed and treated in a timely manner, it will lead to significantly shorter stature in adults and an increased incidence of cardiovascular disease. There are also many cases with gonadal dysplasia, central hypothyroidism, and adrenocorticotropic hormone ( Growth hormone deficiency dwarfism (GHD), which cannot be treated with ACTH) deficiency, will seriously affect future work, study of marriage psychology and quality of life, etc. If early treatment can be obtained, body height can reach as high as normal, . In addition, it also plays an important role in maintaining muscle vitality, improving heart function, delaying aging, preventing osteoporosis, and treating obesity.

Hypothalamic-pituitary tumors may cause vision loss, visual field defects, and later manifestations of increased intracranial pressure, as well as salivation and convulsions.

Prevention of pituitary dwarfism

GH deficiency has obvious family genetic characteristics and can be examined by chromosomes.

Periodic health care should be done regularly to avoid the history of perinatal lesions, such as dystocia and intrauterine asphyxia, so as not to cause brain damage.

Diagnosis of pituitary dwarfism

1. Growth and developmental disorders. May have familial inheritance. Secondary patients often have intracranial tumors (such as craniopharyngioma, chromocytoma), infection, trauma, or a history of high-dose glucocorticoids.

2. The height is lower than normal people of the same age and gender, and the average height is mostly below 130cm (generally the average height of normal people-3 times the standard deviation). The growth rate is less than 4cm / year, and intellectual development is generally normal.

3. The bone age is delayed, more than 4 years below the actual age, and the epiphysis fusion is delayed. There is no special pituitary dwarfism in the size of the saddle, but those with lesions in the saddle area may have calcification on the saddle, enlarge the saddle, and bone destruction.

4. Sexual organs are not developed, secondary sexual characteristics are lacking, and other infantile manifestations, thyroid and adrenal cortex function may be slightly reduced, and highly sensitive to insulin.

5. Serum growth hormone levels are low, and there is no response to insulin-induced hyperglycemia and excitatory tests such as arginine, levodopa, and pirostamine (less than 5 g / L). Serum gonadotropin levels are low after puberty.

6.Exclude the following diseases: constitutional delayed puberty, primorrhea dwarfism, hypothyroidism in children, skeletal disease (chondrogenesis disorder, osteogenesis imperfecta), nutritional metabolic disease, congenital heart disease, gonadal development disorder (such as Turner syndrome Sign) and other dwarfism. ^[1]