Hyperprolactinemia

Introduction to hyperprolactinemia Hyperprolactimia is the most common pituitary disease, which is characterized by galactorrhea and hypogonadism. If the patient has both galactorrhea and amenorrhea, it is called galactorrhea-abated syndrome, such as Chiari-Fromeel syndrome, which occurs in postpartum; Forbes-Albright syndrome with pituitary tumors; non-postpartum without pituitary tumors It is called delCastillo syndrome. The most important difference between the above syndromes is that there are two kinds of pituitary tumors and no pituitary tumors. Other differences are only in the time of illness. Therefore, the names of these syndromes have recently been mentioned less frequently. basic knowledge The proportion of illness: 0.001% Susceptible people: good for postpartum women Mode of infection: non-infectious Complications: Osteoporosis

Cause of hyperprolactinemia

Physiological factors (35%):

Normal healthy women during the night and sleep (2 ~ 6am), elevated plasma prolactin in the late follicular and luteal phase, plasma prolactin increased by 5 to 10 times during pregnancy, the prolactin concentration in amniotic fluid after the second trimester is higher than plasma, lactation Women, plasma prolactin concentration is higher than non-pregnant period, fetal and neonatal ( 28 weeks gestation ~ 2 to 3 weeks postpartum) plasma prolactin equivalent to maternal level, massage the breast and sucking nipple reflective promotion of prolactin secretion, During the puerperium (within 4 weeks), plasma prolactin remained at a high level. Prolactin in non-lactating women decreased to non-pregnant levels within 3 months, fasting, insulin-induced hypoglycemia, exercise, stress, and prolactin increased significantly during sexual intercourse. .

Disease factors (65%):

(1) Hypothalamic-pituitary lesions

(2) thyroid and adrenal diseases: including primary and secondary hypothyroidism, pseudohypoparathyroidism, Hashimoto's thyroiditis, adrenal diseases, including chronic kidney disease, Addison's disease and chronic renal failure may occur Hyperprolactinemia.

(3) ectopic prolactin secretion syndrome: including undifferentiated bronchogenic lung cancer, adrenal cancer and embryonal cancer.

(4) Polycystic ovary syndrome.

(5) Obstetrics and gynecology surgery and local stimulation: including induced abortion, invasive hydatidiform mole or stillbirth, after hysterectomy, tubal ligation, oophorectomy, local breast stimulation, including papillitis, cleft palate, chest wall trauma, belt Herpes zoster, tuberculosis and chest wall surgery can also cause hyperprolactinemia.

(6) Drugs that promote prolactin secretion:

1 anesthetic drugs: including morphine, methadone, methionine enkephalin.

2 psychiatric drugs: including phenothiazines, including haloperidol, fluphenazine, chlorpromazine, tricyclic antidepressants, alpha peptides, chlordiazepines, amphetamine and diazepam.

3 hormone drugs: including estrogen, oral contraceptives, thyroid stimulating hormone releasing hormone (TSH-RH).

4 antihypertensive drugs: including methyldopa, reserpine, verapamil (icopidine).

5 affecting dopamine metabolism and functional drugs: including: A. dopamine receptor antagonists, including phenothiazine, haloperidol, metoclopramide, morphine, piperazine (pimozide); B. Dopamine reuptake blocker: nomifensine (phenylisoquineamine); C. dopamine degrading agent, including reserpine, methyldopa; D. dopamine conversion inhibitor: apeptide.

6 monoamine oxidase inhibitor.

7 benzodiazepine derivatives: including dibenzoxazole nitrogen leather, carbamoyl chloride, due to stunned, imipramine, amitriptyline, phenytoin, diazepam, clonazepam.

8 histamine and histamine H1, H2 receptor antagonists: including serotonin, amphetamine, etc., H1 receptor antagonists, including meclizine, pyridoxamine, H2 receptor antagonist cyanoguanidine.

9 antiemetic drugs: including sulpiride, promethazine (purazine), perphenazine.

10 other: cyproheptadine.

Pathogenesis

The secretion of pituitary prolactin (PRL) is strongly controlled by dopaminergic neurons in the hypothalamic nodules-funnel, so any damage to the hypothalamic lesions such as tumors, radiation damage and inflammation may increase the secretion of pituitary PRL, resulting in High PRL, some pituitary diseases (such as inflammation), if the pituitary stalk is damaged, can reduce the dopamine of the hypothalamus to the pituitary PRL cells and cause high PRL, some non-PRL pituitary tumors such as GH tumor, ACTH tumor Such as the compression of the pituitary stalk can cause high PRL, TRH has a strong stimulation of PRL secretion, and thyroid hormone can slightly inhibit the reaction of PRL cells to TRH, so high PRL can occur in primary hypothyroidism Hypertension, 30% to 80% of patients with end-stage renal failure have mild to moderate high PRL, which may be due to the accelerated dopamine metabolism in these patients, and high PRL due to abnormal metabolism of neurotransmitters in cirrhosis. Hypertension, some chest and breast diseases such as thoracic surgery, chest herpes zoster, mastitis, etc. can also cause high PRL, some non-endocrine gland tumors such as bronchial carcinoma can also secrete PRL, resulting in high PRL, but extremely See.

Hyperprolactinemia prevention

Treatment of primary diseases (pituitary tumors, hypothyroidism and Cushing's syndrome); try to avoid bad mental stimulation; reduce or avoid the use of elevated prolactin drugs. Dairy products should be avoided in the diet: yogurt and dairy products can easily cause skin fever, so dairy products should be avoided in the diet. Try to avoid bad mental stimulation.

Hyperprolactinemia complications Complications Osteoporosis

High PRL can also cause significant osteoporosis, which may be due to a decrease in estrogen levels, but it is also believed that PRL itself has a negative effect on bone density, and some patients are associated with lobular hyperplasia or large breasts.

Hyperprolactinemia symptoms Common symptoms galactorrhea libido libido hemian hypertestosteroneemia dizziness osteoporosis palpitations

1. General performance

(1) Menstrual disorders: primary amenorrhea accounted for 4%, secondary amenorrhea accounted for 89%, menstrual thinning, menstruation less 7%, dysfunctional bleeding and luteal insufficiency accounted for 23% to 77%.

(2) The typical amenorrhea-galactorrhea syndrome of galactorrhea is 20.84% in non-tumor hyperprolactinemia, 70.6% in tumor type, 63%-83.5% in simple galactorrhea, or galactorrhea is dominant or squeezed breast When it appears, it is watery, serous, or milky, and the breasts are normal.

(3) The incidence of infertility is 70.7%, which may be primary or secondary infertility, and is associated with anovulatory, luteal insufficiency or luteinized non-ruptured follicular syndrome (LUFS).

(4) low estrogenemia and hyperandrogenism: decreased estrogen causes flushing, palpitations, spontaneous sweating, vaginal dryness, dyspareunia, loss of libido, etc., androgen elevation causes moderate obesity, seborrheic, acne and hairy .

(5) Visual acuity and visual field changes: Pituitary tumors can cause vision loss, headache, dizziness, hemianopia and blindness, as well as brain nerve II, III, IV dysfunction, fundus edema and exudation.

(6) Acromegaly: When seen in PRL-GH adenoma, mucinous edema is seen in patients with hypothyroidism, and some patients have type 2 diabetes and osteoporosis.

2. Clinical classification

(1) Tumor-type hyperprolactinemia: 71.61% of hyperprolactinemia, of which prolactin adenomas account for 46%, microadenomas account for 66%, giant adenomas account for 34%, and a few are prolactin-growth Hormone adenomas and suspected cell tumors, most pituitary adenomas PRL200ng/ml, some pituitary adenomas can naturally resolve.

(2) Postpartum hyperprolactinemia: 30% of hyperprolactinemia occurs in pregnancy, childbirth, abortion, plasma prolactin is mildly elevated within 3 years after induction of labor, patients have menstrual thinning, menstrual disorders, The galactorrhea has a good prognosis.

(3) special hyperprolactinemia: rare, mostly traumatic, stress-related, and some are very small adenomas.

(4) iatrogenic hyperprolactinemia is caused by iatrogenic factors or drugs, mostly caused by other diseases (such as hypothyroidism), which can be naturally recovered after the cause is removed.

(5) Potential hyperprolactinemia (OHP) is also known as occult hyperprolactinemia.

Hyperprolactinemia test

1. Hypothalamic-pituitary-ovarian axis reproductive hormone determination: FSH, LH decreased, LH / FSH ratio increased, such as PRL 100ng / ml is more functional, PRL 100ng / ml is more tumoric, The larger the tumor, the higher the PRL, such as tumor diameter 5mm, PRL is (171 ± 38) ng / ml; tumor diameter 5 ~ 10mm, PRL is (206 ± 29) ng / ml; tumor diameter 10mm, PRL is mostly (485±158) ng/ml, plasma PRL may not increase when hemorrhagic necrosis of giant adenoma.

2. Thyroid, adrenal and pancreatic function tests: high prolactinemia with elevated TSH, lower T3, T4, PBI, high prolactinemia combined with Cushing's disease and masculinization, testosterone (T), Androstenedione (4dione), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), 17 ketosteroid (17KS) and elevated plasma cortisol, hyperprolactinemia with diabetes and acromegaly Plasma insulin, blood glucose, glucagon, and glucose tolerance tests should be performed.

3. Prolactin stimulation test

(1) Thyroid stimulating hormone releasing hormone (TRH) test: normal women with intravenous injection of TRH 100 ~ 400pg, 15 ~ 30min PRL increased 5 to 10 times before injection, TSH increased 2 times, pituitary tumor does not rise high.

(2) Chlorpromazine test: Chlorpromazine inhibits norepinephrine reabsorption and dopamine function through the receptor mechanism, promotes PRL secretion, normal women, intramuscular injection of chlorpromazine 25 ~ 50mg, 60 ~ 90min blood PRL It is 1 to 2 times higher than that before injection, and lasts for 3 hours, and it does not increase in pituitary tumors.

(3) Metoclopramide test: Metoclopramide promotes the production and release of PRL. In normal women, 30 to 60 minutes after intravenous injection of 10 mg, PRL is more than 3 times higher than that before injection, and the pituitary tumor does not increase.

4. Prolactin inhibition test

(1) Levodopa test: Levodopa is a dopamine precursor substance, which is converted to dopamine by decarboxylase to inhibit the production and secretion of PRL. After normal oral administration of 500 mg for 2 to 3 hours, PRL is significantly decreased, and pituitary tumors are not decreased.

(2) bromocriptine test: levodopa is a dopamine receptor agonist, inhibiting PRL production and release, normal women after oral administration of 2.5 ~ 5mg 2 ~ 4h, PRL decreased by more than 50%, lasting 20 ~ 30h, functional high lactation Prolactin was significantly reduced after administration of nephroemia and prolactin adenoma, while GH and ACTH were decreased, while GH and ACTH were not significantly reduced.

1. Sella substomach (CT) examination of normal women's saddle anteroposterior diameter <17mm, depth <13mm, area <130mm2, volume <1100mm3, if the following image should be CT:

1 The sailboat is expanded;

2 double saddle bottom or heavy edge;

3 high/low density areas in the saddle or inhomogeneity;

4 plate deformation;

5 saddle calcification;

6 front and rear bed osteoporosis;

7 inside the saddle vacuole;

8 bone destruction.

2. Magnetic resonance imaging (MRI), cavernous sinus angiography, gas angiography and cerebral angiography can determine the location and size of the tumor, and help to identify other intracranial lesions, due to CT diagnosis of false positive and false negative rate of 20%, The accuracy rate is only 61%, so MRI is recommended for diagnosis.

3. Ophthalmic examination: including vision, visual field, intraocular pressure, fundus examination to determine the presence or absence of intracranial tumor compression signs (bilateral side ocular hemianopia, vision loss, blindness, nausea, vomiting and headache).

Diagnosis and identification of hyperprolactinemia

1. Prolactin normal galactorrhea

Some women have galactorrhea but normal blood PRL levels, called prolactin normal lactorrhea (normoprolactinaemic lactorrhea), prolactin normal galactorrhea is not uncommon, according to foreign data: 28% to 55% of female galactorrhea blood PRL level Normal, prolactin normal galactorrhea occurs in women of childbearing age, less menstrual disorders (about 1/3), some patients with galactorrhea is associated with normal pregnancy, breastfeeding, these women stop breastfeeding after normal breastfeeding, And for a long time, others are related to oral contraceptives, and some are unknown. The current mechanism of prolactin normal galactorrhea is not well understood. Some people think that there is a variant PRL in the patient, it It has normal biological activity but cannot be measured by the usual radioimmunoassay method. Therefore, the patient has galactorrhea but the blood PRL level is normal. Some people think that it may be caused by elevated levels of other prolactin-producing hormones (such as hGH) in the body. The viewpoint has not been confirmed so far. At present, most scholars believe that the sensitivity of patients to PRL is increased, and the reason for the increased sensitivity of the body to PRL. It is unclear that it may be related to an increase in the level of PRL receptors. Johnston et al. believe that normal women have a physiological increase in PRL receptor levels during pregnancy and lactation, and blood PRL and breast PRL receptor levels return to normal after stopping breastfeeding. However, a small number of patients have maintained a high level of PRL receptors after stopping breastfeeding due to certain defects. Therefore, although the blood PRL level is normal, there is still galactorrhea (the formation mechanism of oral contraceptives is similar), and some people use small doses. The bromocriptine (although the blood PRL level is normal), the blood PRL level is reduced to the normal low limit, and the symptoms of galactorrhea can be improved, which also supports this view.

Prolactin normal galactorrhea is characterized by normal secretion of PRL. Patients not only have normal basal PRL levels, but also normal hypoglycemia and TRH responses, which can be differentiated from galactorrhea caused by high PRL.

2. Identification of the cause of high PRLemia

After determining the presence of high PRL, the cause should be further diagnosed. First, the history should be asked in detail to determine whether high PRL is caused by drugs. Secondly, liver and kidney function should be measured to determine whether high PRL is due to cirrhosis. Or renal failure, TSH, T3, T4 determination is necessary, such as TSH, T3, T4 are significantly increased, may be high PRL caused by pituitary TSH tumor; such as increased TSH and T3, T4 decreased, possible For high PRL caused by primary hypothyroidism, blood GH, ACTH and cortisol levels should be measured to determine the presence of GH tumors and ACTH tumors, as they all cause high PRL, FSH/LH and alpha. The determination of subunits contributes to the diagnosis of gonadotropinoma and non-functioning pituitary adenomas, which is also valuable in identifying the causes of high PRL.

Pituitary CT, MRI and blood PRL are important for etiological diagnosis. Generally speaking, if CT and MRI are positive, and blood PRL level exceeds 9.1 nmol/L (200 ng/ml), the diagnosis of PRL tumor can be established. The level of blood PRL is closely related to tumor size. The PRL level of large adenoma is more than 11.38nmol/L (250ng/ml), while the microadenomas are more than 9.1nmol/L (200ng/ml), such as blood PRL level. Only mild to moderate elevation (less than 9.1nmol / L) and CT, MRI showed large adenoma, this tumor is often not a true PRL tumor, belonging to the so-called pseudo PRL tumor.

In recent years, 11C-labeled dopamine D2 receptor antagonists methyl spiperone and rallopride for PET imaging are not only diagnostic, but also predict the efficacy of dopamine agonists. The responder responded well to dopamine receptor agonists.

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