pituitary amenorrhea
Introduction
Introduction Pituitary amenorrhea: amenorrhea caused by pituitary tumors may be accompanied by headache, unclear vision, or lactation; amenorrhea in the anterior pituitary, occurs in postpartum hemorrhage, manifested as loss of libido, genital atrophy, fatigue, cold, hair loss. Primary pituitary gonads are hypofunction, this disease is rare, the patient's ovary has primordial follicles, but because the pituitary GnH secretion is low, follicles can not grow and develop, so the primary amenorrhea, the internal and external reproductive organs are naive, the second sexual characteristics are not Development, intracellular chromatin is positive, karyotype is 46XX, effective with gonadotropin treatment.
Cause
Cause
Pituitary closure through the pituitary organic lesions or dysfunction, affecting the secretion of GnH, thereby affecting ovarian function caused by amenorrhea.
1. Pituitary damage, pituitary tumor enlargement can compress cells with GnH function; after pituitary radiotherapy or surgery, brain trauma, intracranial inflammation can destroy pituitary tissue; postpartum hemorrhage can cause pituitary blood supply disorder and ischemic necrosis . All of the above can reduce the secretion of pituitary GnH and cause amenorrhea.
2. Primary pituitary gonads are hypofunction, this disease is rare, the patient's ovary has primordial follicles, but because the pituitary GnH secretion is low, follicles can not grow and develop, so the primary amenorrhea, its internal and external reproductive organs naive, second sex The sign is not developed, the intracellular chromatin is positive, the karyotype is 46XX, and it is effective with gonadotropin treatment.
Examine
an examination
1. Vaginal exfoliation cell examination: It is a commonly used method to understand estrogen levels. After immersing the saline in a cotton stick, the exfoliated cells on the side wall of the upper part of the vagina were taken and coated on a glass slide. After fixation and staining, the percentage of cells in the middle, bottom and bottom layers was observed. The higher the percentage of superficial cells, the higher the estrogen level.
2. Cervical mucus: If the cervical mucus of the amenorrhea is found to be transparent, the thin mucus with good pulling force, after drying on the glass piece, the fern-like crystal can be seen under the microscope, indicating that the patient's ovary has the function of secreting estrogen.
3. Drug-testing: This is a commonly used clinical diagnostic test for amenorrhea, especially in experimental equipment lacking hormone determination. Drug testing is important for assessing ovarian function and endometrial function.
(1) Progesterone test: application of progesterone to amenorrhea patients, intramuscular injection of 20mg / d, for 3 to 5 days, 3 to 7 days after withdrawal (usually no longer than 2 weeks), withdrawal of drug withdrawal is positive , Tip: the endometrium has function, can exclude uterine amenorrhea; ovary has the function of secreting estrogen, the endometrium is affected by a certain level of estrogen before it can react to progesterone and fall off bleeding. It indicates that amenorrhea is not a lack of estrogen, but a lack of progesterone due to various anovulations. If the progesterone test is negative, there is no bleeding after stopping the drug, suggesting the following possibilities: First, the ovarian function is low, there is no proper estrogen to act on the endometrium; Second, the ovary function is normal, but the endometrial defect or damage Can not respond to estrogen, that is, does not rule out uterine amenorrhea; third is not to exclude pregnancy.
(2) Estrogen test: amenorrhea patients with negative progesterone test were given oral diethylstilbestrol 1 mg/d, or ethinyl estradiol 10 g/d, or other estrogens with considerable biological effects for 20 consecutive days. The last 3 to 5 days plus progesterone 20mg / d, intramuscular injection. 3 to 7 days after stopping the drug, observe whether there is withdrawal of blood. If there is still no bleeding, the lesion may be in the uterus, ie uterine amenorrhea. Those who have withdrawn from the blood by the above test indicate that the endometrium responds to the effects of estrogen and progesterone, and can cause normal growth and shedding changes. The cause of amenorrhea should be in the ovary or higher. Sex hormone levels should be further tested to confirm the diagnosis.
4. Determination of sex hormone levels: Determination of pituitary hormones is particularly important for the diagnosis of amenorrhea. Patients with amenorrhea and low estrogen should further measure the levels of blood FSH, LH and prolactin (PRL). If FSH and LH increase, suggesting ovarian amenorrhea, if FSH, LH is low, the cause may be in the pituitary or hypothalamus; FSH, LH is equivalent to normal follicular phase, amenorrhea is due to hypothalamic secretion dysfunction; if LH Increased and relatively insufficient FSH, the diagnosis of polycystic ovary syndrome should be considered; if abnormal PRL is elevated, amenorrhea is caused by hyperprolactinemia, the cause of hyperprolactinemia should be further examined, especially the pituitary The possibility of a tumor.
When the FSH and LH levels are low, the pituitary stimulation test can further distinguish whether the lesion is in the pituitary or in the hypothalamus. In the pituitary stimulation test, 100 g of luteinizing hormone releasing hormone (LHRH) was dissolved in 5 ml of physiological saline, intravenously injected, and injected within 30 seconds. Blood LH was taken before injection and at 15, 30, 60, and 120 minutes after injection. If the LH value rises to more than 3 times before injection 30~60min after injection, it suggests that the pituitary function is good, the response to hypothalamic hormone LHRH is normal, and the cause of amenorrhea is in the lower part of the thalamus or higher. If the LH does not increase or increase after injection, it is not obvious, indicating that the pituitary is lack of response, and the cause of amenorrhea may be in the pituitary.
5. Determination of basal body temperature: Indirect understanding of ovulation function. The corpus luteum after ovulation secretes progesterone, and progesterone has the effect of increasing body temperature. During the normal menstrual cycle, the body temperature during the follicular phase is relatively stable, generally fluctuating below 36.5 °C. After ovulation, the body temperature rose by O.3 ~ 0.5 °C, maintained for 12 to 16 days, and decreased to the follicular phase on the day before menstruation or on the day of menstrual cramps. The basal body temperature, which is low in the first half cycle and elevated in the second half cycle, is called biphasic body temperature, and generally indicates ovulation or corpus luteum formation. The body temperature without this change is called single-phase body temperature, indicating no ovulation. The basal body temperature of amenorrhea patients is mostly single-phase, but uterine amenorrhea is normal because of its ovarian function, so it can show biphasic basal body temperature.
6. Other examinations: pelvic B-ultrasound can help diagnose whether there is a congenital uterus deficiency or deformity. Imaging studies in the sellar area can diagnose the presence of pituitary tumors. Diagnostic curettage, uterine lipiodol angiography and endoscopy can be used to understand the uterine cavity and endometrium. In addition, if other endocrine abnormalities or developmental abnormalities are to be excluded, other hormone levels such as thyroid gland and adrenal gland, biochemical, pathophysiological examination and chromosome examination should be examined.
Diagnosis
Differential diagnosis
First, primary amenorrhea
(a) uterine vaginal hypoplasia
Mainly due to dysplasia of the renal tube in both sides. The middle and the tail segments of the bilateral middle and middle kidney tubes were not developed, that is, the secondary renal tube was stopped before it reached the midline, and thus the uterus was not synthesized. Clinical manifestations of congenital absence of uterus, no vagina. If the development of the renal tube on both sides stops shortly after the union, the primordial uterus is formed. This uterus is small and has no endometrium, so there is no menstruation. If the bilateral renal tube meets to form the uterus, but does not penetrate, it forms a solid uterus, no endometrium; or stops shortly after the development, forming a naive uterus. It manifests as primary amenorrhea. If there is part of the endometrium, amenorrhea may be associated with periodic abdominal pain. Intelligence, posture and secondary sexual characteristics develop normally. The hypothalamic-pituitary-ovarian axis has normal function and the karyotype is 46, XX.
(2) Androgen insensitivity syndrome
Also known as testicular feminization or male pseudohermaphroditism, the patient's gonads are male, there are testes in the body. In the early embryonic rate, the testosterone secretes testosterone, but due to the lack of androgen receptor in the target organ cells, it does not react to testosterone, which hinders the development of secondary genitalia and male secondary sexual characteristics. After puberty, testicular development, while secreting estrogen to produce feminization, causing breast development and appearance of women like a woman, it is called male pseudohermaphroditism. Clinically, it is divided into two types, which are completely insensitive to androgen and partially insensitive.
1. It is completely insensitive to androgen: the patient develops normally, the body is tall, the arm is long, the foot is huge, the breast is developing, but the nipple is small, the areola is weak, and the pubic hair and the mane are scarce. The external genitalia is female, the labia minora is poorly developed, the vagina is short, the upper segment is blind, there is no uterus, and the testicles may be in the abdominal cavity or in the groin.
2. Insensitivity to androgen: The external genitalia can be expressed as a clitoris or a short penis, often accompanied by hypospadias. Therefore, for patients with primary amenorrhea with vaginal blind end and no uterus, the presence of testicular feminization syndrome should be considered. The karyotype is XY, blood FSH (follicle stimulating hormone) and LH (luteinizing hormone) are increased, and testosterone is increased or increased in normal males, which is the basis for diagnosis of this disease.
(3) Deportation syndrome
Also known as gonadal dysplasia with short stature and other body deformities. The normal female karyotype is 46, XX. The normal development of the ovary must have all the genes of two chromosomes, in which the genes preventing the short stature and the residual neck are located on the short arm of the X chromosome. When a sex cell divides, the sex chromosome may not be separated due to a certain factor, and the zygote formed may have only one chromosome; or during the division process, the short arm of the X chromosome is broken or lost, resulting in abnormal chromosome number and structure, and the ovary may appear. The hypoplasia syndrome is clinically referred to as congenital ovarian hypoplasia or degenerative syndrome. The ovary has a cord-like fibrous tissue, no oocytes or follicles, and therefore does not secrete estrogen. Therefore, the manifestations of primary amenorrhea, short stature, warm neck, barrel chest, elbow valgus, posterior hairline, secondary sexual characteristics are not developed; genital maturation is often accompanied by aortic stenosis and urinary system abnormalities.
Low levels of blood estrogen, with high levels of blood gonadotropin. The karyotype is 45, XO, the most common chimeric type is 45, XO/46, XY.
(four) simple gonadal dysplasia
Simple gonadal dysplasia, no chromosomal abnormalities, karyotype can be divided into 46, XX or 46, XY, the patient's appearance is female.
1.XX simple gonadal dysplasia: also known as true ovarian hypoplasia, because the ovary is not developed, it is manifested as dysplastic female genitalia, but no deformity. The second sexuality was poorly developed, but it was not characterized by short stature and other disjunction syndromes, and the karyotype was 46, XX. Blood estrogen levels are low and blood gonadotropins are elevated. No reproductive function.
2. XY simple gonadal dysplasia: under normal circumstances, the early testicular secretion of the male embryos of the testosterone and the secondary renal tubular inhibitor, testosterone promotes the development of the middle kidney tube into the male reproductive system, including the attached star, vas deferens, seminal vesicle, prostate and The penis and scrotum, and the secondary renal tube inhibitory factor promote the degeneration of the renal tube. In patients with XY simple gonadal dysgenesis, due to genetic mutations in the chromosome, the testis in the embryonic stage is not developed, and the ketone and the secondary renal tubular inhibitor are not secreted. Therefore, the renal tube is degenerated and no longer develops into the male genitalia. The middle kidney tube develops into the female reproductive system; the patient's appearance is female, often taking women's life. Often due to primary amenorrhea, the body is tall, the hands and feet are thick and the room is not developed, and the pubic hair is less. The internal and external genitalia are female, but they are poorly developed. Lack of characteristics of the degenerative syndrome. The karyotype is 46, XY, the estrogen level is low, the blood gonadotropin is increased, and the blood testosterone is low, which can be distinguished from the star pill feminization syndrome.
(5) Congenital adrenal hyperplasia
Also known as adrenal reproductive syndrome, or female pseudohermaphroditism.
The patient has a gonadal female. Due to the lack of 21-hydroxylase or 11-hydroxylase in the congenital adrenal cortex, it is not possible to synthesize adrenocortical hormone, which causes excessive secretion of adrenocorticotropic hormone in the anterior pituitary gland, which causes compensatory hyperplasia of the adrenal cortex. After adrenal hyperplasia, a large amount of 17-hydroxypregnenolone and 17-hydroxyprogesterone are secreted and converted into androgens, so male signs appear. Patients often have a family history and are inherited by autosomal recession. Because of the excessive androgenic effects in the fetal period, at birth, it can be manifested as an enlarged clitoris, a fusion of the labia on both sides, and incomplete differentiation of the urethra and vagina. Abnormalities of the external genitalia are caused by the attention of their parents and are often seen in childhood. After puberty, hairy, muscular, larynx and beard, hair is distributed in males, breasts are not developed, uterus is small, no menstruation. The patient has male habits.
The karyotype is 46, XX, the estrogen level is low, the blood LH may be elevated, the blood androgen is high, and the urinary 17-ketone and 17-hydroxysteroid are high.
Second, secondary amenorrhea
(1) Cervical intrauterine adhesions (IUA)
Injury curettage, infection, cauterization and specific inflammation (tuberculosis, schistosomiasis, amebiasis and actinomycosis) damage the endometrium, causing adhesion of the uterine wall tissue, adhesion of the epilepsy to the cervical canal or intrauterine adhesions . Cervical intrauterine adhesions account for about 1.7% of secondary amenorrhea. Such as simple cervical atresia can cause uterine bleeding, and the complete adhesion of the uterine cavity can cause amenorrhea. This type of secondary amenorrhea has curettage, gynecological surgery and infertility history; hypothalamic-pituitary-ovarian axis secretion function is normal; female-progesterone test is negative; hysteroscopy and hysterosalpingography can be diagnosed.
(two) premature ovarian failure (POF)
Refers to premature menopause after puberty to 40 years old, caused by delayed ovarian hypoplasia or acquired ovarian injury. More than half of the secondary amenorrhea caused by premature ovarian failure has karyotype abnormalities and follicular dysplasia. Or autoimmune ovarian failure, that is, the presence of anti-ovarian antibodies, multi-organ specific liquid antibodies in the patient's blood. Oocytes in the ovary are reduced or disappeared. These patients also often have a variety of autoimmune diseases, such as hyperthyroidism, hypothyroidism, myasthenia gravis, insulin resistance, diabetes, etc., and other congenital egg cell reserves are too small or depleted. Too much, X chromosome number and structural abnormalities and acquired physical, chemical, radiological, and adenoviral infections also accelerate egg cell degradation.
It can be divided into two types: no follicle type and follicular type: 1 no follicular type, abnormal karyotype, no follicle in ovarian cortex; 2 follicular type, normal karyotype, a small number of primordial follicles in ovary but no follicular development series; Secondary amenorrhea is mostly follicular type, premature menopause before the age of 40, that is, after menarche, menstrual thinning, menorrhagia, amenorrhea and infertility and ovarian function decline symptoms such as hot flashes, spontaneous sweating, Heart vaginal dryness, sexual organs and breast atrophy, upper arteries and portal vein plexus, 10%-20% from the internal carotid artery, so once the cerebral circulation blood perfusion is insufficient to measure ischemia; hypoxia first starts from the level of the pituitary stalk The anterior pituitary gland extends, the longer the ischemic time, the more severe the pituitary necrosis and functional damage.
The anterior pituitary has a strong functional compensatory ability. According to its tissue necrosis and functional damage degree, it is divided into: 1 severe pituitary tissue loss 95%, severe symptoms; 2 moderate pituitary tissue loss 75%, obvious symptoms; 3 light 60% of pituitary tissue loss, mild symptoms; 4 pituitary tissue loss of 550%, generally no obvious symptoms. Extreme physical exhaustion occurred 3-5 weeks after postpartum hemorrhage. No milk, anemia combined with infection. Progressive degeneration, hair loss, amenorrhea, reproductive organs and breast atrophy.
Insulin deficiency is characterized by hypoglycemia; thyroid stimulating hormone (TSH) deficiency manifests as new fluid edema; adrenocorticotropic hormone (ACTH) deficiency presents signs of Addison disease: hypoglycemia, hypothermia, bradycardia, and susceptibility Infection and concurrent shock.
Estrogen levels were low, and gonadotropins, thyroid stimulating hormones, and adrenocorticotropic hormones were significantly lower than normal. According to the above characteristics can be diagnosed.
(6) pituitary tumors
The most common anterior pituitary tumor, which is most common with chromophobe adenoma, after the onset of puberty, manifested as secondary amenorrhea and other accompanying symptoms, local symptoms caused by tumor compression, visual impairment, diplopia, headache Cerebrospinal fluid rhinorrhea, nasal regulation and hypothalamic syndrome can produce diabetes insipidus, lethargy, temperature regulation disorder, obesity, polyphagia, anorexia and so on. Symptoms of the tumor causing the pituitary itself to be stressed, the earliest and most serious are gonadotropins, the symptoms of anterior pituitary dysfunction, followed by thyroid-stimulating hormone, adrenocorticotropic hormone decline, corresponding symptoms of hypofunction, sometimes tumor Pressurization of the posterior pituitary or hypothalamus can produce diabetes insipidus.
Through the positive side of the skull and the positive lateral fault phase, the damage of the saddle is known. CT scan, plus intravenous infusion of iodine-containing contrast agent, can increase the detection rate of tumors.
(VII) The hypothalamic and hypothalamic hypothalamic-pituitary-ovarian axis dysfunction caused by hypothalamic and central neuropathy is a secondary cause of secondary amenorrhea. Common causes cause dysfunction: 1 mental and neurological factors, mental stress, fear and anxiety, Changes in the living environment can cause central nervous system and hypothalamic dysfunction, especially in young women, ovarian function is still healthy, more likely to appear amenorrhea. It is not uncommon to strongly expect menopausal and pseudopregnancy in pregnant women.
This type of amenorrhea does not require treatment to naturally recover. 2 wasting disease or malnutrition, systemic wasting diseases such as gastrointestinal disorders, severe tuberculosis and severe anemia can affect the synthesis and secretion of hypothalamic and pituitary hormones, leading to amenorrhea. Anorexia nervosa is a hypothalamic dysfunction caused by mental factors, resulting in severe malnutrition, sudden weight loss, and hypopituitarism; 3 drug-induced amenorrhea, a few women after taking oral contraceptives or long-acting injectables Amenorrhea occurs because of the persistent inhibition of the contraceptive on the pituitary axis in the lower thalamus, causing excessive inhibition syndrome. Women who have had menstrual disorders or spawning diarrhea, or who take contraceptives too early after abortion or full-term delivery, are prone to amenorrhea.
In addition, certain drugs, such as sedatives, can also affect the function of the hypothalamus in the normal dose range and cause amenorrhea, which can naturally restore menstruation after stopping the drug. This kind of closure often happens suddenly. Most patients have a certain level of estrogen, so the second sexual characteristics are normal. The FSH and LH values in the blood can be within the normal range, but if the condition is serious, both can be low, especially the LH value is lower than hH. The blood PRL (prolactin) value is normal, and estrogen shows the early level of follicles in the normal menstrual cycle. The skull X-ray was normal.
(8) Amenorrhea caused by adrenal gland and thyroid disease
The ovary is an important link and component of the neuroendocrine system, and the ovarian function is bound to be restricted by the functional status of other endocrine glands. When the adrenal function is hyperactive, such as Cushing's syndrome, there is amenorrhea in the early stage of the disease, accompanied by masculinization. Adrenal insufficiency, such as Addison's disease, often occurs in the late stage of amenorrhea. Hyperthyroidism or hypothyroidism can cause amenorrhea through the hypothalamus that affects pituitary function.
