Hyperprolactinemia

　　Normal PRL pulsatile release and its circadian rhythm play an important regulatory role in breast development, lactation, and ovarian function. PRL secretion is regulated by the hypothalamic PRL-RH and PRL-IH, and in the normal ovulatory menstrual cycle, PRL is always under the inhibitory regulation of CNS hypothalamic dopaminergic neurotransmitters and PRL-IH. Once this regulatory imbalance occurs, it leads to hyperprolactinemia. HPRL can be caused by both physiological and pathological factors.

　　I. Physiological hyperprolactinemia

　　1. Night and sleep (2-6 AM).

　　2. Late ovulatory and luteal phase.

　　3. Pregnancy: increased ≥10 times compared to non-pregnancy.

　　4. Lactation period: acute, short-term or persistent secretion increase caused by massage, nipple suckling.

　　5. Postpartum period: 3-4 weeks.

　　6. Hypoglycemia.

　　7. Exercise and stress stimuli.

　　8. Sexual intercourse: marked increase at the climax of orgasm.

　　9. Fetus and newborn (≥28 weeks gestation to 2-3 weeks postpartum).

　　II. Pathological hyperprolactinemia

　　1. Hypothalamic-pituitary lesions

　　(1) Tumor:

　　Non-functional - craniopharyngioma, sarcoidosis-like disease (sarcoid) glioma.

　　Functionality - PRL adenoma 46%; GH adenoma 22-31%. PRL-GH adenoma 5-7%; ACTH adenoma & Nelson's syndrome 4-15%. Multifunctional adenoma 10%; undifferentiated tumor 19-27%.

　　(2) Inflammation: cranial base meningitis, tuberculosis, syphilis, actinomycosis.

　　(3) Destruction: injury, surgery, arteriovenous malformation, granulomatous disease (Hand-Schüller-Christian's syndrome).

　　(4) Empty sella syndrome.

　　(5) Pituitary stalk lesions, injuries, or tumor compression.

　　(6) Psychological trauma and stress.

　　(7) Parkinson's disease.

　　2, Primary and/or secondary hypothyroidism.

　　(1) Pseudo-hypoparathyroidism.

　　(2) Hashimoto's thyroiditis.

　　3, Ectopic PRL secretion syndrome: Undifferentiated bronchial lung cancer, adrenal cancer, embryonal cancer.

　　4, Adrenal and renal disease: Addison's disease, chronic renal insufficiency.

　　5, Polycystic ovary syndrome.

　　6, Liver cirrhosis.

　　7, Gynecological and obstetric surgery: induced abortion, cesarean section, stillbirth, hysterectomy, tubal ligation, oophorectomy.

　　8, Local irritation: mastitis, fissures, chest wall injury, herpes zoster, tuberculosis, surgery.

　　Three, Iatrogenic-drug factors

　　1, Hypoglycemia due to insulin.

　　2, Sex hormones (estrogen-progesterone contraceptives).

　　3, Synthetic TSH-RH.

　　4, Anesthetics: Morphine, methadone, methionine enkephalin.

　　5, Dopamine receptor blockers: Phenothiazines, Haloperidol, Metoclprimide, Domperidone, Pimozide, Sulpiride.

　　6, Dopamine reuptake blockers: Nomifensine.

　　7, CNS dopamine degradants: Reserpine, amethyl-Dopa.

　　8, Dopamine conversion inhibitors: Apomorphine.

　　9, Monoamine oxidase inhibitors.

　　10, Derivatives of diphenylhydrazine: diphenylhydrazine, carbamylhydrazine, phenylhydrazine, imipramine, amitriptyline, phenytoin, tranquilizers, and clonazepam.

　　11, Antihistamines and H1, H2 receptor antagonists: Serotonin, Amphetamines, Hallucinogens, H1 receptor antagonists (meclizine, pyribenzamine, chlorphenamine), H2 receptor antagonists (cimetidine).

　　12, Idiopathic.

　　1, Low estrogen response: Seen in long-term amenorrheic patients, such as flushing, palpitations, spontaneous sweating, vaginal dryness, sexual intercourse pain, and decreased libido.

　　2, Changes in vision and field of vision: Vision loss, headache, dizziness, hemianopia, and blindness, as well as cranial nerve II, III, IV dysfunction, may occur when pituitary tumors involve the optic nerve chiasm. Fundus edema and exudation.

　　3. Hyperandrogenic response: moderate obesity, seborrhea, acne, and hirsutism.

　　4. Acromegaly: seen in PRL-GH adenoma, with increased GH.

　　5. Mucinous edema: seen in combination with hypothyroidism.

　　6. Diabetes and abnormal glucose tolerance test.

　　1. Menstrual disorders

　　Primary amenorrhea 4%, secondary amenorrhea 89%, oligomenorrhea, less than 7%, dysfunctional uterine bleeding, poor luteal function 23-77%.

　　2. Galactorrhea

　　The typical manifestation of HPRL is amenorrheic-galactorrhea syndrome, accounting for 20.84% in non-tumor types and 70.58% in tumor types, galactorrhea accounting for 63-83.55%, galactorrhea appearing as watery, serous, or milk, most breasts are normal, or accompanied by lobular hyperplasia or macromastia.

　　3. Infertility

　　70.71% primary or secondary, due to anovulation, poor corpus luteum, or luteinized unruptured follicle syndrome (LUFS).

　　1. In the diet of hyperprolactinemia, it is advisable to avoid dairy products and eat more green vegetables, kelp, salmon (with bones), sardines, etc., and reduce caffeine and alcohol.

　　2. Drink more water or fruit juice, maintain regular sexual life, because regular sexual life is not easy to cause skin heat, and can indirectly stimulate degenerated ovaries to mitigate the hormone system and prevent a sharp decrease in estrogen.

　　3. How to prevent hyperprolactinemia? Strengthen physical fitness, improve health level, strengthen physical exercise in daily life, and often do health exercises or Tai Chi.

　　4. Avoid mental stimulation, stabilize emotions, and keep the Qi and blood unobstructed. Pay attention to keeping warm during the menstrual period, especially below the waist, keep the feet warm, avoid cold water, and avoid eating raw and cold fruits and vegetables.

　　One, sellar tomography

　　For normal women, the anteroposterior diameter of the sella turcica is less than 17mm, the depth is less than 13mm, the area is less than 130mm2, the volume is less than 1100mm3. If the following situations occur, CT should be performed: ①ballooning; ②double floors or double edges; ③high/low density areas or heterogeneity within the sella; ④saucer-like deformation; ⑤calcification foci above the sella; ⑥osteoporosis of the anterior and posterior pterygoid processes or vacuolization within the sella; ⑦bone erosion.

　　Two, Electronic Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI)

　　Precise localization of intracranial lesions and radiation measurement.

　　Three,造影检查造影 examination

　　Including: cavernous sinus angiography (intercavernous sinus venography), pneumoencephalography, and cerebrovascular angiography.

　　Four, Endocrine function examination

　　1. Pituitary function:FSH, LH decrease, LH/FSH ratio increases, PRL increases ≥25ng/ml. It is generally considered that <100ng/ml is mostly functional, and ≥100ng/ml should be cautious to exclude PRL adenoma. The larger the tumor, the higher the PRL, such as when the tumor diameter d≤5mm, PRL is 171±38ng/ml; d=5～10mm 206±29ng/ml; ≥10mm 485±158ng/ml. In the case of hemorrhage and necrosis of large adenomas, PRL may not increase. It should be pointed out that: the PRL radioligand currently used in clinical practice only measures small molecular PRL (MW25000) and cannot measure large/mega-molecular (MW5～100000) PRL. Therefore, some patients with obvious clinical symptoms but normal PRL cannot be excluded for so-called occult hyperprolactinemia, that is, large/mega-molecular hyperprolactinemia.

　　2. Ovarian function examination:E2, P decrease, T increase.

　　3. Thyroid function examination:When HPRL is complicated with hypothyroidism, TSH increases, and T3, T4, PBI decrease.

　　4. Adrenal function examination:When HPEL is complicated with Cushing's syndrome and virilization symptoms, T, △4dione, DHT, DHEA, 17KS increase, and plasma cortisol increases.

　　5. Pancreatic function examination:When HPRL is complicated with diabetes and acromegaly, insulin, blood glucose, glucagon, and glucose tolerance test should be measured.

　　Five, Prolactin function test

　　1. Prolactin stimulation test:

　　(1) Thyrotropin-releasing hormone (TRH) test: Normal women show a PRL increase of 5 to 10 times above the pre-injection level and TSH increase by 2 times after a single intravenous injection of 100 to 400μg of TRH, 15 to 30 minutes later, but this does not occur in pituitary tumors.

　　(2) Chlorpromazine test: Chlorpromazine, through receptor mechanisms, inhibits the absorption of norepinephrine and the conversion of dopamine function, promoting PRL secretion. Normal women show a blood PRL increase of 1 to 2 times above the pre-injection level 60 to 90 minutes after intramuscular injection of 25 to 50mg, lasting for 3 hours, but this does not occur in pituitary tumors.

　　(3) Metoclopramide test: This drug is a dopamine receptor antagonist that promotes PRL synthesis and release. Normal women show a PRL increase of more than 3 times above the pre-injection level 30 to 60 minutes after intravenous injection of 10mg, but this does not occur in pituitary tumors.

　　2. Prolactin suppression test:

　　(1) L-Dopa test: This drug is a dopamine precursor that, after being acted upon by decarboxylase, generates DA and inhibits PRL secretion. Normal women show a significant decrease in PRL 2 to 3 hours after taking 500mg orally, but this does not occur in pituitary tumors.

　　(2) Bromocriptine test (Bromocriptine test): This drug is a dopamine receptor agonist that strongly inhibits PRL synthesis and release. Normal women have a decrease in PRL of ≥50% within 2 to 4 hours after oral administration of 2.5 to 5.0 mg, and it lasts for 20 to 30 hours. The decrease is significant in functional HPRL and PRL adenomas, while the decrease in GH and ACTH is less than the previous two.

　　6. Ophthalmological Examination

　　Including vision, field of vision, intraocular pressure, and fundus examination to determine if there are symptoms of intracranial tumor compression.

　　Dietary recipe for hyperprolactinemia:

　　Hawthorn and Barley Tea:50 grams of Fructus Crataegi, 30 grams of germinated barley; or 60 grams of single germinated barley. Boil the herbs in water as a tea, 1 dose per day. It has the function of stopping lactation. It is used to treat various galactorrhea, including hyperprolactinemia, postpartum lactation cessation, and lactation after abortion.

　　1. Traditional Chinese Medicine Treatment

　　It is believed that the etiology and pathogenesis of this disease are relatively complex, but in principle, they can be divided into two categories: deficiency and excess. Deficiency refers to liver and kidney deficiencies, insufficient essence and blood, an empty blood sea, with no blood to descend causing amenorrhea; Qi and blood deficiency, kidney Qi not being stable leading to spontaneous milk leakage. Excess refers to liver Qi stagnation, blood stasis, phlegm obstruction, and the unblocking of meridians, causing menstrual blood to descend; or liver channel stagnation and heat, abnormal drainage, and milk leakage. Due to insufficient endowment, insufficient kidney Qi, insufficient essence, insufficient liver blood, the Chong and Ren channels not being nourished, and being unable to transform into menstrual blood; or due to sexual overexertion, chronic illness, leading to kidney essence depletion, liver blood deficiency, insufficient essence and blood, the source being cut off, the Chong and Ren channels being deficient, the uterus having no blood to descend, and causing amenorrhea.

　　As stated in 'The Correct Transmission of Medicine': 'Menstruation relies entirely on the transformation of kidney water, and once the kidney water is depleted, the menstrual water will gradually dry up.' Or if there is inherent kidney Yang deficiency, the Yang Qi does not reach its destination, leading to cold due to Yang deficiency, and blood stasis due to cold; or kidney Yang deficiency cannot warm and transport the spleen to solidify, causing loss of control over intake and excretion, and milk leakage due to continuous transformation. If the spleen and stomach are inherently weak, or due to improper diet, overexertion, taking medicine incorrectly, or excessive worry and thought, the heart and spleen are damaged, leading to insufficient nourishing Qi and blood; or due to chronic illness, miscarriage, or abortion, several losses of blood, or prolonged breastfeeding that injures Qi and consumes blood, leading to great deficiency of the Chong and Ren channels and an empty blood sea, with no blood to descend and causing amenorrhea.

　　As mentioned in 'The Secret Storage of the Orchid Room': 'If a woman's spleen is weakened for a long time, or her body is emaciated and her Qi and blood are depleted, it can lead to the cessation of menstrual flow.' If there is internal injury from the seven emotions, the liver Qi is stagnant and cannot reach its destination, causing Qi stagnation and blood stasis, obstruction of the Chong and Ren channels, and blockage of the uterine vessels, leading to the obstruction of menstrual flow and amenorrhea; or anger can injure the liver, causing hyperactivity of liver fire, excessive drainage, and milk leakage. 'The Heart Method of Fetal and Maternal Medicine' says: 'The liver channel's anger fire rises, causing breast swelling and leakage.' There are also obese individuals with excessive phlegm and dampness, which block the meridians; or the spleen Yang is not transported, dampness accumulates into phlegm, and fat-phlegm dampness blocks the Chong and Ren channels, causing the uterine vessels to close and menstrual flow to stop.

　　The 'Female Medicine Essentials' states: 'Obese and fair individuals who experience amenorrhea without menstruation are definitely due to the blockage of damp phlegm and fat membrane.' In summary, the occurrence of this disease involves liver, spleen, and kidney deficiencies, leading to deficiencies in essence, Qi, and blood, or due to the blockage of Qi, blood, and phlegm, causing the obstruction.

　　II. Treatment for the Cause and Primary Disease

　　If removing adverse mental stimulation, stopping the use of drugs that cause HPRL, actively treating primary diseases such as pituitary tumors, hypothyroidism, Cushing's syndrome, etc. Antiprolactin - bromocriptine therapy

　　Bromocriptine is a semi-synthetic ergot alkaloid derivative, a dopamine receptor agonist, which can promote the synthesis and secretion of PRL-IH through receptor mechanisms, inhibit the synthesis and release of PRL, and directly act on pituitary tumors and PRL cells to inhibit tumor growth and suppress the secretion of PRL, GH, TSH, and ACTH.

　　Bromocriptine therapy is suitable for all types of HPRL and is the first-line therapy for pituitary adenomas (micro/giant adenomas), especially for young infertile couples who wish to have children. The dose is 2.5-7.5mg/d, taken orally. Other antiprolactin drugs include: levodopa (LevoDopa), octahydrobenzodiazepine (CV205-502), vitamin B6, etc. For details, see the section on antiprolactin in the endocrine treatment chapter.

　　III. Ovulation Induction Therapy

　　Applicable to HPRL, infertility due to anovulation, and those who cannot achieve ovulation and pregnancy with simple bromocriptine treatment. That is, a comprehensive therapy using bromocriptine as the main treatment, combined with other ovulation-inducing drugs: ① Bromocriptine-CC-hCG; ② Bromocriptine-hMG-hCG; ③ GnRH. Pulse therapy - bromocriptine, etc. Comprehensive therapy can save antiprolactin, shorten the treatment cycle, and improve the ovulation rate and pregnancy rate.

　　IV. Surgical Therapy

　　Suitable for patients with giant adenomas with compression symptoms, as well as those with tumor resistance, ineffective bromocriptine treatment, and嫌染细胞瘤 with multiple pituitary hormone secretions.

　　The current trans-sphenoidal microsurgery (trans-sphenoidal microsurgery) is safe, convenient, and easy to perform, and its efficacy is similar to that of bromocriptine therapy. The use of bromocriptine before and after surgery can improve the efficacy. The disadvantages of the operation are: in cases where the pituitary tumor has no obvious capsule and unclear boundaries, the operation is not easy to be thorough or may cause injury, leading to cerebrospinal fluid nasal fistula and secondary hypopituitarism.

　　V. Radiotherapy

　　Applicable to non-functional tumors in HP system, as well as those who are ineffective for drug and surgical treatment. The irradiation methods include: deep X-rays, 60Co, alpha particles and proton beams. Isotopes such as 90Y and 198Au pituitary implantation, etc.