Delayed puberty and sexual immaturity

Introduction to puberty development and sexual naivety Delayed puberty and sexual naivety are called puberty when puberty develops 2.5 standard deviations later than the average age at which the normal population begins to appear. It usually means that the girl still has no breast development after the age of 13 or no menarche at the age of 15 or no menarche after 5 years of breast development. Delay in youth can be idiopathic or due to various pathological factors. Children who have reached this age and still have no sexual development should distinguish between delayed youth and permanent sexual naiveness. Strictly speaking, youth delay refers to the delay of puberty, so it is mostly idiopathic and sexually naive. Accompanied by congenital anomalies. basic knowledge The proportion of sickness: 0.00002% Susceptible people: no specific population Mode of infection: non-infectious Complications: short stature

Delayed puberty and sexual naive causes

(1) Causes of the disease

Delayed puberty and sexual naiveness may be caused by various diseases that affect the pulse secretion of gonadotropin-releasing hormone (GnRH), or may be caused by hypofunction of the pituitary gland or gonads. Therefore, it may be divided into physical puberty according to its etiology. Delayed, low gonadotropin hypogonadism (hypothalamic-pituitary abnormalities) and high gonadotropin hypogonadism (gonadal abnormalities).

1. Physical puberty development delay (CDGM) Also known as idiopathic puberty development delay: refers to normal healthy girls still not into puberty after 13 years of age, no pathological causes have been found through various examinations, delayed development of sexual characteristics is Due to the delayed activation of the pulsed secretion function of the hypothalamic GnRH.

2. Low gonadotropin hypogonadism refers to the girl's sexual development is not due to lack of GnRH pulse secretion caused by insufficient secretion of FSFI and LH. The cause of GnRH deficiency may be congenital or postnatal developmental defects, or Tumor, inflammatory process or injury.

(1) Central nervous system diseases: mainly tumors of the central nervous system, infection, injury or congenital defects, and some patients have not found pituitary tumors but elevated prolactin, called idiopathic hyperprolactinemia, patients have lactation It may also be related to youth delay.

(2) Isolated gonadotropin deficiency: These patients only have gonadotropin deficiency, due to low levels of sex hormones, and slower closure of the epiphysis, allowing long bones to grow.

(3) idiopathic pituitary hypoxia: shortly due to the lack of hypothalamic release factors.

(4) Functional gonadotropin hypoxia: severe systemic and chronic wasting diseases and malnutrition cause youth delay.

Anorexia nervosa is a low-grade functional gonadotropin caused by mental and endocrine abnormalities. It is common in girls who insist on losing weight or mental stress. Patients have abnormal eating habits or anorexia or appetite.

Some high-intensity athletes or ballerinas have a large amount of exercise, too little body fat, and pre-puberty hyperprolactinemia can cause youth delay.

Recent studies have also suggested that drug abuse among adolescents can also lead to delays in youth.

3. High gonadotropin hypogonadism is not developed due to primary ovarian hypoplasia or dysfunction.

(two) pathogenesis

1. Delayed development of constitutional puberty delayed development is due to delayed activation of the pulsed secretion function of the hypothalamic GnRH, which activates the hypothalamic-pituitary-gonadal axis function late. Some stimulation studies have shown that these patients have growth hormone (GH). The baseline value is low, and the response after stimulation is also insufficient, indicating that these patients have a deficiency of GH, and growth hormone releasing hormone (GHRH) and IGF-I are also lacking. This condition is also called combined pituitary hormone deficiency (CPHD). However, this deficiency is temporary. Once puberty begins, its growth rate and GH secretion will become normal. The influence of family genetic factors on the final height is very important. The parents or sisters of the child may develop late.

2. Low gonadotropin hypogonadism The lack of GnRH secretion may be a relative or absolute deficiency; it may also be an abnormal form of secretion, such as the magnitude and frequency of GnRH secretion, which is especially important for women.

(1) Central nervous system diseases: Tumors located in the sellar region may interfere with the synthesis and secretion of GnRH, often accompanied by the deficiency and abnormalities of several pituitary hormones.

Other central nervous system disorders such as central nervous system infections, injuries, congenital malformations or head radiotherapy may have gonadotropin secretion disorders and delayed youth.

(2) Isolated gonadotropin deficiency: The disease is not accompanied by abnormal growth hormone or other pituitary hormones. Kallmann syndrome is a relatively common isolated gonadotropin deficiency, which is a heterogeneous inheritance. Disease, a mutation in the KAL1 gene encoding extracellular adhesion molecules, studies in rodents indicate that the cause of Kallmann syndrome is due to the lack of GnRH neurons from the olfactory plate to the hypothalamus, which can be autosomal dominant, autosomal Recessive or X-linked inheritance can be expressed in multiple types due to different genetic patterns. The MRI of these patients shows lack of olfactory sulcus and olfactory bulb.

(3) Idiopathic pituitary dysplasia: breech birth and perinatal injury may be associated with this isolated pituitary dysfunction.

(4) Functional gonadotropin hypoxia: hypothyroidism and Cushing's sign are often associated with delayed youth.

The pathophysiological changes of anorexia nervosa include abnormal neuroendocrine metabolism, mental and psychological abnormalities and malnutrition. The patient loses normal self-feeling and judgment on the body fat and thin, and the level of estrogen in the anorexia nervosa is very low. Testosterone levels were maintained in the normal female range, and the metabolism of estradiol and testosterone was abnormal. The production of estriol was caused by the transfer of 16-hydroxylase to 2-hydroxylase in the metabolism of estradiol. Decreased and 2-hydroxyestrone is inappropriately increased; because the latter can bind to the receptor of estrogen without the biological activity of estrogen, leading to further deficiency of estrogen, this metabolic change and body weight, body composition Related to nutritional status, the abnormality of androgen metabolism is mainly the decrease of 5-reductase activity, which hinders the conversion of testosterone to dihydrotestosterone. The regulation of hypothalamic-pituitary-adrenal axis also changes in patients with anorexia nervosa. Cortisone increases the activity of the hypothalamus-GRF-ACTH-adrenal gland, but the secretion of adrenal androgen is inhibited, and the peripheral metabolism of cortisone Less likely to be caused by T3 deficiency, T3 can make the above changes back to normal, the hypothalamic-pituitary-thyroid axis changes are low levels of T3 and T4, T3 is especially reduced, forming low T3 syndrome, anorexia nervosa The patient's growth hormone may be elevated, partly due to the decrease in IGF-I negative feedback. The level of IGF-I in the blood of the patient is reduced. There is a significant negative correlation between this level and body weight. Studies have shown that IGF-I Decrease and increase in GH are caused by hunger.

Some high-intensity athletes or ballerinas are prone to youth delay due to their large amount of exercise and too little body fat.

3. High gonadotropin hypogonadism due to low ovarian function, can not synthesize and secrete enough sex hormones, E2 levels are low, interfere with the negative feedback regulation of the pituitary and hypothalamus, so that FSH and LH levels rise, so it is called "High gonadotropin-induced hypogonadism", gonads are cord-like, 46, XX simple gonadal dysplasia is autosomal recessive inheritance, 46, XY simple gonad insufficiency is X-linked inheritance, there are also a few It is autosomal recessive inheritance, premature ovarian premature aging, ovarian resection at an early age or ovarian function due to radiotherapy or chemotherapy at the ovary site, can affect puberty.

Delayed puberty and prevention of childishness

Early diagnosis, early treatment, and follow-up. Need to pay attention to regular testing, early detection, in order to symptomatic treatment.

Delayed puberty and sexual complications Complications short stature

Short stature, deformity, visceral deformity, etc.

Delayed puberty and idiopathic symptoms Common symptoms No menstrual cramps Hypotension Precocious puberty Polyuria Anorexia Neonatal hypothermia Barrel thoracic visual impairment Thyroid hypofunction Visual field defect

1. The constitutional puberty development delay is 13 years old and there is no secondary sexual development. The height may be 2 standard deviations shorter than the same age children. The bone age is less than the actual age. The height and growth rate are consistent with the bone age. The blood FSH, LH and E2 concentrations And the response of LH to GnRH was prepubertal.

Children with delayed constitutional youth are shorter in their childhood and adolescence than their peers. Once the bone age reaches the age of puberty (12-13 years old), sexual maturity also occurs, and normal development progresses to sexual maturity. And normal adult height, patients with delayed constitutional puberty, their height growth is slow before puberty.

2. Low gonadotropin hypogonadism

(1) Central nervous system diseases: The more common tumors associated with delayed puberty are craniopharyngioma, clinical manifestations of headache, visual field defects (mostly bilateral ankle defects), short stature, limb weakness, sexual development is not developed , diabetes and hypothyroidism, small tumors can be removed by microsurgery, the tumor volume should be craniotomy, postoperative radiotherapy.

Other central nervous system tumors associated with youth delay are pineal tumors, ectopic pineal tumors, germ cell tumors and prolactinomas, some of which may have polydipsia, polyuria, visual impairment and growth disorders, growth hormone and A variety of pituitary hormone levels are low, prolactin can sometimes be elevated, chromoblastoma and prolactinoma are rare in children, and occasionally in the teens can lead to delayed youth, primary amenorrhea.

(2) Isolated gonadotropin deficiency: patients with long limbs, large finger distance, reduced proportion of upper body and lower body, Kallmann syndrome is a more common isolated gonadotropin deficiency, reaching adolescent age and still no sex Development, often accompanied by olfactory disorders and other deformities.

(3) idiopathic pituitary dysfunction: shortness of expression: only patients with isolated growth hormone deficiency, when the bone age reaches the age of puberty, it will automatically show the characteristics of puberty, and the lack of gonadotropin In the treatment of GH, although the bone age has exceeded the age of puberty, there is still no automatic puberty.

(4) Functional gonadotropin hypoxia: clinical manifestations of delayed youth may occur.

Anorexia nervosa patients have abnormal eating habits, or anorexia or appetite, and have severe low body weight, hypothermia, hypotension, chills, hyperkinesia, emotional stress, etc. These girls are generally introverted and behaviorally compulsive. Also showing sexual signs are not developed, primary amenorrhea or secondary amenorrhea, anorexia nervosa can cause youth delay if it occurs before youth.

The frequency and amplitude of GnRH pulse secretion in the hypothalamus reduces the secretion of gonadotropins, resulting in a low gonadotropin state.

High-intensity training athletes or ballerinas have puberty development, menarche is more late than girls of the same age, and youth drug use can lead to delayed performance in youth.

3. High gonadotropin hypogonadism due to low ovarian function, can not synthesize and secrete enough sex hormones, E2 levels are low, interfere with the negative feedback regulation of the pituitary and hypothalamus, so that FSH and LH levels increase, so called "high gonadotropin-induced hypogonadism", this situation is more common in congenital dysplasia, often manifested as sexual naive, such as Turner syndrome, is a congenital disease of X chromosome number or structural abnormalities, The typical karyotype is 45, X or other variants. The ovary of the child is not developed and is in the form of a cord. Due to the lack of sex hormones, the sexual characteristics are not developed, and it is sexually naive. In addition, there is often a set of physical abnormalities. Such as short stature, neck sputum, faceted sputum, barrel chest, elbow valgus and other visceral multiple deformities, high gonadotropin hypogonadism is also seen in 46, XX and 46, XY simple gonadal dysplasia, patient appearance The internal and external genitals are female, but the sexual characteristics are not developed and the primary amenorrhea, the gonads are strip-like, 46, XX simple gonadal dysplasia is autosomal recessive inheritance, 46, XY simple gonads are not X-sexual linkage inheritance, and a few are autosomal recessive inheritance. Due to the presence of Y, the risk of developing gonads is greatly increased, premature ovarian premature aging, ovariectomy or ovarian parts at an early age. Radiotherapy or chemotherapy damages ovarian function and can affect puberty.

The diarrhea and sexual naive diagnosis steps and examinations are similar to those of precocious puberty. History, physical examination, imaging examination, and bone age assessment are equally important in the diagnosis of puberty delay and sexual naivety. In addition, pituitary gonadotropins, Prolactin, estradiol is determined to identify whether the cause is indispensable in the gonad or in the pituitary and hypothalamus.

High gonadotropin hypogonadism can be easily diagnosed by measuring the levels of blood FSH and LH. Girls are 13 years old and have no sexual development or sexual characteristics. There is no menstrual cramps for 5 years. FSH should be performed. LH and E2 measurements, if the FSH and LH levels are elevated, it indicates that the cause is in the gonads, and the karyotype examination is also necessary for girls with low gonadotropin hypogonadism.

Delayed puberty and sexual naive examination

1. Hormone levels are detected when one or more pituitary hormone levels (such as gonadotropins, thyroid stimulating hormone, and adrenocorticotropic hormone) are low, and sometimes prolactin is elevated.

2. Chromosome examination.

1. Bone age, head imaging CT or MRI examination, etc. About 70% of the sphenoid enlargement or calcification, CT or MRI can make a more detailed diagnosis of the tumor.

2. Pelvic ultrasound examination of pelvic ultrasound is not a necessary examination for patients with low gonadotropin hypogonadism, but it is helpful to understand the development of uterus and ovaries.

Delay in puberty development and differential diagnosis of naive

Other central nervous system tumors associated with delayed youth are pineal tumors, ectopic pineal tumors, germ cell tumors, and prolactinomas, most of which can be diagnosed earlier.

The differential diagnosis of low gonadotropin hypogonadism and constitutional puberty is sometimes difficult, detailed history, growth history, birth history, head trauma history, etc. to determine whether youth delay and congenital abnormalities, perinatal events and Malnutrition, etc., physical examination should first measure the height and weight and calculate the standard deviation of their mean and peers, check the development of sexual characteristics and determine the stage of their development, physical examination should also pay attention to exclude heart, lung, kidney and stomach Intestinal disorders, when the above examination is still not diagnosed, sometimes a follow-up observation is necessary to determine whether there is a secondary sexual manifestation or development, and the first feature of sexual maturity after 18 years of age is still not present. And the levels of gonadotropins and sex hormones have not increased, and blood DHAS levels have reached the corresponding age, often suggesting the diagnosis of isolated gonadotropin deficiency.

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