delayed puberty in males
Introduction
Introduction to male puberty development delay Male puberty development delay (maledelayedpuberty) refers to the phenomenon that boys have reached normal puberty developmental age and still have no sexual development. There are many reasons for this. There are many puberty developmental dysplasia caused by delayed puberty development, systemic diseases or malnutrition. Dysplasia. Most of the patients with hypogonadism have a sexual development in the prepubertal stage. A few patients have started puberty, and the testicle size has reached the level of puberty II to III. 80% to 90% of patients have small larynx, lack of pubic hair, and pubic hair stays in Tanne I or II, 20% of patients have mild mammary gland development, can be associated with cryptorchidism, 80% of bone age is behind the actual age, about 40% of patients with olfactory loss or decline (IHH with olfactory abnormality, also known as Kallmann synthesis Other signs of physical malformation or abnormalities include obesity, short stature, cleft lip, cleft palate, high zygomatic arch, short lingual cord, neurological deafness, red-green blindness, osteoporosis, short fourth metacarpal, phalanx Long and congenital heart disease and kidney deformity, most of the intelligence is normal. The main clinical manifestations of intrinsic are muscle tension and mental retardation, poor academic performance, IQ level of about 60, hypogonadism with no developmental or hypoplasia of the external genitalia, small penis, may be associated with cryptorchidism, the main cause of obesity may have been eaten More related to the reduction of activities, some patients with diabetes, its pathogenesis is unknown, but at least related to obesity, patients with short stature, short limbs, uneven face, small amount, small eye cracks, strabismus or with the face, head And other deformities of the limbs. basic knowledge The proportion of illness: the incidence rate is about 0.01%-0.02%, mostly delayed puberty Susceptible people: male Mode of infection: non-infectious Complications: anemia, adult hypopituitarism
Cause
Delayed etiology of male puberty
(1) Causes of the disease
The cause of most patients with delayed puberty development is unknown, but the etiology of some low-gonadotropin hypogonadism has been elucidated, such as a part of patients due to KAL, GnRH receptor, PROP1 or DAX1 gene mutation.
Some hereditary diseases have their own special clinical manifestations, and general diagnosis is not difficult, such as Kallmann syndrome, gonadotropin deficiency hypogonadism, Fröhlich syndrome and Laurence-MoonBiedl syndrome, etc., such as the inability to determine the genes involved in the etiology Mutation identification.
The etiology of male and female puberty development delays.
1. Severe chronic systemic disease According to the history and severity of the disease, it can be concluded that genetic defects lead to abnormal secretion of gonadotropin, which is manifested by the ability of the hypothalamus to lose synthesis and secrete GnRH (may be complete or Incompleteness, can occur at any age, most of the disease from childhood, using frequent blood collection (every 5 to 10 minutes) to collect peripheral blood to measure LH, indirect reflection of GnRH secretion pulse by LH pulse analysis has been applied to IHH patients The diagnosis found that there are five types of abnormalities: 1 no pulsed GnRH secretion, accounting for about 3/4. 2 GnRH pulse secretion occurs during nighttime sleep. These patients have larger testicles or have a history of early puberty, similar to early puberty. 3 GnRH pulse secretion, but the pulse amplitude is lower than normal, this small LH pulse is not enough to stimulate Leydig cells to secrete testosterone. The pulse amplitude of 4GnRH is as high as normal, but the pulse frequency is only about half of that of normal people (normally, 12.0±1.1 pulses/24h). In these patients, testosterone secretion is highly fluctuated, and testosterone levels are decreased during no pulse. 5GnRH-induced LH pulse secretion is normal, but LH has no biological activity and cannot excite Leydig cells.
Most of the patients with hypogonadism have a sexual development in the prepubertal stage. A few patients have started puberty, and the testicle size has reached the level of puberty II to III. 80% to 90% of patients have small larynx, lack of pubic hair, and pubic hair stays in Tanne I or II, 20% of patients have mild mammary gland development, can be associated with cryptorchidism, 80% of bone age is behind the actual age, about 40% of patients with olfactory loss or decline (IHH with olfactory abnormality, also known as Kallmann synthesis Other signs of physical malformation or abnormalities include obesity, short stature, cleft lip, cleft palate, high zygomatic arch, short lingual cord, neurological deafness, red-green blindness, osteoporosis, short fourth metacarpal, phalanx Long and congenital heart disease and kidney deformity, most of the intelligence is normal.
2. Prader-Willi syndrome Prader-Willi syndrome, also known as Prader-Labhart-Willi-Fanconi syndrome, Prader-Labhart-Willi syndrome or hypotonia - mental retardation - hypogonadism - obesity syndrome.
In 1956, Prader first reported that China reported 7 cases by Wang Defen in 1985. The etiology of the intrinsic is unknown. It is often found that the patient has a translocation of the chromosome 15 centromere. In recent years, a microdeletion of 15q11-12 was found. But often accompanied by other abnormalities on the 14th and 15th chromosomes.
The main clinical manifestations of intrinsic are muscle tension and mental retardation, poor academic performance, IQ level of about 60, hypogonadism with no developmental or hypoplasia of the external genitalia, small penis, may be associated with cryptorchidism, the main cause of obesity may have been eaten More related to the reduction of activities, some patients with diabetes, its pathogenesis is unknown, but at least related to obesity, patients with short stature, short limbs, uneven face, small amount, small eye cracks, strabismus or with the face, head And other deformities of the limbs.
The diagnosis of this disease is mainly based on muscle tension and mental retardation, hypogonadism (or no puberty development) and obesity to make a clinical diagnosis, but must pay attention to congenital muscular dystrophy, myasthenia gravis, obesity-reproductive incompetence syndrome ( Fröhlich syndrome) and Laurence Moon-Biedl syndrome.
3. Thalassemia thalassemia boys are often accompanied by low gonadotropin hypogonadism, with reduced GnRH secretion and no pulse. Severe cases (with severe ironosis) are often irreversible damage, while light Degree cases are often reversible. One of the methods to identify reversible and irreversible lesions is to accurately measure the pulse characteristics of GnRH. MRI shows that some patients have vacuolar sella syndrome, pituitary volume is reduced, pituitary gland is atrophy, pituitary stalk is thin, There is iron deposit in the pituitary and midbrain. Therefore, patients should be treated with HCG and/or androgen as early as possible, and prevent iron deposition caused by excessive blood transfusion.
4. Congenital adrenal dysplasia with hypogonadism DAX1 (AHC) gene mutation leads to X-linked chain hereditary adrenal dysplasia and low gonadotropin hypogonadism, male infants show after birth Primary adrenal insufficiency, can be improved to some extent in childhood, but no puberty development, some mild cases are incomplete, the symptoms are very light, can only be manifested as delayed puberty and mild adrenal insufficiency Sometimes misdiagnosed as "physical puberty development delay", for example, Achermann et al reported 106 cases of sporadic low gonadotropin hypogonadism and "physical puberty development delay" in the screening of DAX1 gene mutation, did not find There are positive cases of mutations, so the puberty development delay caused by mutation of DAX1 gene is rare.
(two) pathogenesis
Many pathological conditions can cause delayed development of puberty. Clinically, it is more common: 1 central nervous system tumors, such as craniopharyngioma and germ cell tumors. 2 hypothalamic-glandular pituitary dysfunction, such as idiopathic hypogonadotropin hypogonadism and pituitary dwarf. 3 primary testicular dysfunction, such as Klinefelter syndrome and gonadal dysplasia. 4 severe chronic systemic diseases, such as malnutrition, malabsorption syndrome, bronchial asthma, nephropathy and congenital heart disease, etc., the pathological puberty delay patients do not have the above pathological conditions, the pathogenesis of which is unknown.
The delayed development of constitutional puberty is due to the delay of reactivation of the LHRH pulse generator, resulting in a lack of LHRH secretion in children at the age of puberty, accompanied by a decrease in gonadotropic response to gonadotropin, a functional hypogonadism Is a variant of normal puberty development. Gonadal dysplasia is delayed or undeveloped due to abnormal pubertal development due to organic lesions of the hypothalamic-pituitary-gonadal axis.
Prevention
Delayed prevention of male puberty
1. There are many reasons for this disease. One of the reasons can be inherited by autosomal dominant, recessive, X-linked, and can be familial or sporadic. It can be used for pre-pregnancy and pre-pregnancy genetic tests.
2. If there is a high degree of suspicion of puberty development delay, you can do the necessary checks, such as poor development of individual items, do not make random diagnosis, generally can be observed for 1 to 2 years.
Complication
Male puberty development delay complications Complications, anemia, adult hypopituitarism
Pituitary dysfunction, anemia.
Symptom
Delayed symptoms of male puberty, common symptoms, hypopituitarism, asphyxia
Although the reasons are different, the common features of clinical manifestations are: delayed or undeveloped puberty, physical examination shows that the external genitalia is naive, in the stage of puberty development, pubic hair, mane growth is not obvious, testicular volume is less than 4ml, sound Still childish, because of the childish appearance, parents, teachers and classmates often treat patients as children, which impairs the patient's self-esteem, and even inferiority, and is reluctant to participate in group activities, thus affecting the interpersonal relationship processing ability after adulthood.
Examine
Delayed development of male puberty
The relevant examinations were selected according to the condition, and the levels of thalamic-pituitary-gonadal hormones (blood LH, FSH, T) and other endocrine hormones (such as T3, T4, TSH and GH) were determined as follows, and GH excitation test was performed if necessary.
Chromosome examination is used to exclude gonadal developmental disorders caused by chromosomal abnormalities, such as Turmer syndrome and Kline-Felter syndrome.
MRI or CT imaging examination in order to timely detect saddle area lesions or other diseases, X-ray determination of bone age, to understand the presence or absence of pituitary dysfunction.
Diagnosis
Delayed diagnosis and identification of male puberty
Diagnostic criteria
1. A comprehensive understanding of the relevant situation, in order to facilitate the correct judgment, including understanding the patient's condition at birth, pay attention to the history of dystocia, birth injury and asphyxia, height and weight at birth and at the time of the visit, growth and development after birth, pay attention to Whether there are chronic medical diseases such as anemia, bronchial asthma, heart, kidney, liver disease, etc., calculate the annual growth rate and the proportion of upper body/lower body length, pay attention to the presence or absence of olfactory abnormalities and midline developmental disorders, and understand the developmental history of the parents' puberty. Such as father's voice change, shaving and body length, age of mother's menarche, etc., detailed physical examination, to understand the patient's mane, pubic hair growth, accurately record testicular volume, check blood, urine, liver, kidney function , blood electrolyte levels, etc., to exclude some of the acute and chronic diseases affecting growth and development, X-ray determination of bone age of 12 to 13 years old still no signs of puberty development, it is necessary to identify physical and organic gonadal dysplasia; such as bone age just reached adolescence Developmental age can be observed for half a year or IHRH stimulation test, such as bone age has not reached puberty development Age can be followed up once every six months until the age of skeletal age should be pubertal development. If the bone age is still significantly behind the actual age, the function of the pituitary gland should be evaluated to see if there is hypopituitarism.
2. The level of hypothalamic-pituitary-gonadal hormone (blood LH, FSH, T) and other endocrine hormones (such as blood T3, T4, TSH and GH) should be determined according to the condition, and GH excitation test should be performed if necessary. Chromosome examination is used to exclude gonadal developmental disorders caused by chromosomal abnormalities, such as Tumer syndrome and Kline-Felter syndrome, MRI or CT imaging to detect saddle-occupying lesions or other disorders in time.
Differential diagnosis
1. If you are young, you can continue to observe, and follow up once every six months to observe secondary sexual characteristics, external genital development, LH, FSH, sex hormone levels, bone age, height, secondary sexual characteristics, etc. Some patients are in a few months. Adolescent development can be initiated automatically.
2. In the identification of gonadotropin deficiency and constitutional puberty, it can be treated with testosterone for 4 months. Physique patients such as simple obesity respond well to testosterone, and the longitudinal growth rate can be increased from 4.3cm/year to 11.2cm / year, testicular enlargement is obvious, but the response of the organic gonadotropin deficiency is poor.
