Abnormally elevated serum prolactin (PRL) greater than 1.14 nmol/L (25up/L) from various causes is called hyperprolactinemia.
Alias
hyperprolactinemia
Chinese medical name
Female hyperprolactinemia
Prevalent group
Women
Common symptoms
Overflowing breast, amenorrhea or infertility
Main complaints
Overflowing breast, amenorrhea or infertility are the main complaints of almost all patients, and very few patients present with decreased menstrual flow.
Etiology
(1) Pituitary gland or saddle area tumor;
(ii) Hypothyroidism;
③Drug-related, including dopamine receptor antagonists and estrogen, etc;
④Chronic renal failure;
⑤PRL is the largest stress hormone in the body, and any physical state of stress can cause a sharp increase in PRL.
Triggering factors
1, nerve stimulation: Experts say that skin stimulation in certain areas, especially the chest, including severe pain caused by damage to surrounding nerves, can cause increased prolactin through nerve transmission to the hypothalamus.
2, pituitary disorders: experts say that pituitary disorders mainly refer to a variety of tumors in the pituitary area, in addition, part of the vacuolus pterygoid saddle syndrome, hyperpituitary function, etc., can also cause overflow, amenorrhea.
3, drug factors: experts say that the secretion of high prolactin is affected by a variety of factors, for example, strenuous physical activity, some drugs, trauma and other acute situations can cause increased secretion of prolactin.
4, primary hypothyroidism: is also one of the causes of high prolactin, experts say, hypothyroidism, the thyroid gland does not secrete enough information feedback into the hypothalamus, so that the hypothalamus produces a large number of thyroid hormone release factor, this factor in stimulating the pituitary gland to secrete thyroid hormone, but also can stimulate the pituitary gland to secrete excess prolactin and cause overflow phenomenon.
5, hypothalamic disorders: what are the causes of high prolactin? Experts say that diseases of the hypothalamus and adjacent parts of the female brain can cause the hypothalamus to produce a decrease in prolactin inhibitory factor or an increase in prolactin releasing factor and thyroid stimulating hormone releasing factor.
Clinical features
Main symptoms
1. Menstrual disorders include a variety of menstrual disorders, ranging from oligomenorrhea and alenorrhea to amenorrhea, with amenorrhea being the most common. Primary amenorrhea is manifested before puberty or during adolescence, and sequential amenorrhea after the reproductive years.
2, Infertility abnormally elevated PRL inhibits ovulation, leading to infertility, and mildly elevated PRL causes luteal insufficiency, leading to miscarriage.
3, overflow usually manifests as bilateral breast outflow or can squeeze out non-bloody, milky or clear liquid, the amount does not vary.
Secondary in
1, headache, blurred vision and visual disturbance due to enlarged pituitary adenoma causing pressure on the surrounding brain tissue and visual cross, and cerebrospinal fluid reflux disorder leading to headache, blurred vision and visual disturbance.
2.Low estrogen status due to suppression of ovarian function, vasodilatory symptoms such as hot flashes and sweating, breast reduction, vaginal dryness, and low sexual function.
3.Other symptoms 20%-30% of hyperprolactinemia patients have hirsutism and acne, and a few patients may also have obesity.
Physical signs
1.Overflow of breast milk.
2, headache, blurred vision and visual impairment.
3.Hairiness and acne.
4. Obesity.
Misdiagnosis analysis
Since there are various causes of hyperprolactinemia, it is necessary to distinguish between hyperprolactinemia caused by function, pituitary tumors and other tumors. Hyperprolactinemia caused by lactation, stress, drugs, chest wall irritation, hypothyroidism, adrenal failure, ectopic secretory tumors, polycystic ovary syndrome, etc. should be excluded. If it is a pituitary tumor, it needs to be clarified whether it is a PRL-secreting tumor or another tumor.
1. 30% of PCOS with polycystic ovary syndrome are associated with elevated prolactin, which is caused by long-term sustained estrogen stimulation of the pituitary gland resulting in PRL secretion by the prolactin cells. some patients with PCOS will have scanty menstruation or even amenorrhea, but almost no lactation. Ultrasound of the pelvis shows polycystic ovarian changes. Endocrine tests show elevated LH, elevated estrogen, and no or mildly elevated PRL. In addition to the typical clinical manifestations of hyperprolactinemia, PRL is significantly elevated and FSH and LH are suppressed.
2, long-term use of the following drugs may cause lactation sedative drugs are chlorpromazine, phenothiazine, fenadine. The antiemetic metoclopramide. Gastric motility drug domperidone. Anti-hypertensive drugs rifampicin methyldopa, verapamil. In addition cocaine, monoamine oxidase inhibition, protease inhibitors can cause hyper-PRLemia.
3, renal disease 73%-90% of women with end-stage renal disease develop hyper-PRLemia, which is caused by decreased PRL clearance and increased autonomic production, bromocriptine can reduce PRL.
4, hepatic sclerosis some hepatic sclerosis PRL levels are increased, 50% of patients with hepatic encephalopathy have hyper-PRLemia, presumably related to insufficient hypothalamic dopamine production.
5, thyroid insufficiency TRH production increases in hypothyroidism, and lactating cells are sensitive to the stimulation of TRH, resulting in increased PRL levels. Take thyroxine tablets to bring PRL down to normal.
6. Adrenal insufficiency glucocorticoids have an inhibitory effect on PRL gene transcription and PRL release. Very few patients have hyper-PRLemia and PRL levels return to normal after glucocorticoid supplementation therapy.
7. Neurogenic stimulation of breast stimulation and sucking reflexively induced PRL release has been reported, and similar sustained elevation of PRL may occur with mastectomy, nipple puncture, thoracotomy, and chronic spinal cord injury.
Ectopic PRL secretion is extremely rare, however, PRL has been reported in one case of renal cell, one case of gonadotrophic tumor, and two cases of ovarian teratoma with ectopic pituitary tissue.
9. Hypothalamic-pituitary stalk disorders are caused by dysregulation of the neuroendocrine mechanisms that control PRL secretion and are associated with dopamine de-suppression. Craniopharyngioma is common.
10. Idiopathic hyper-PRLemia is defined as idiopathic hyper-PRLemia when no other specific cause is found for the hyper-PRLemia. In many of these cases, it may include small PRL tumors that are not detected by current imaging techniques. Other causes may include hypothalamic dysregulation. Long-term follow-up has found that PRL returns to normal in 1/3 of patients, with 10%-15% of patients with elevated PRL levels or more than 2-6 years of follow-up finding that 23 cases developed microadenomas.
When other tumors of pituitary gland are suspected, growth hormone, cortisol, FSH, LH, TSH, etc. should be measured to discharge tumors that secrete TSH and gonadotropins, acromegaly, and Cushing’s syndrome.
Ancillary tests
Primary examination
1. Physical examination of the whole body should pay attention to visual acuity, fingertip abnormalities, obesity, hypertension, hirsutism and chest wall lesions. The pelvic examination should pay attention to the development of genitalia and the presence of atrophy or pelvic mass. The breast examination paid attention to the presence of overflowing breast, whether the overflowing breast was on one side or both sides, the nature of the milk and the amount of lactation. The milk taken is visible as fat droplets for milk under low magnification.
2.Blood PRL level measurement is best done at 9-11 a.m. in a quiet state. if PRL is greater than 25up/L, it is considered hyper-PRL. If PRL value is greater than 50ug/L pituitary microadenoma incidence is about 25%, when PRL is greater than 250up/L, the possibility of pituitary macroadenoma is high.
3.Imaging blood test can detect pituitary microadenoma by enhanced magnetic resonance imaging and enhanced computerized body scan.
Secondary examinations
1.Visual field examination because pituitary tumor can invade or compress the visual cross and cause visual field defects. Visual field defects can range from classic, complete bilateral temporal hemianopsia to small partial quadrant defects or dark spots.
2. Gynecologic ultrasound to observe uterine morphology, size and ovaries for abnormalities.
Examination precautions
1, If mild elevation of PRL is found, a blood sample needs to be collected and redone to clarify the results.
2, MRL is indicated for patients with elevated PRL, even if it is slightly elevated.
3.Since MEL can help make an early diagnosis, visual field examination need not be a routine.
4.If the milk is bloody, you should be referred to the mammography department for consultation.
Treatment points
(A) Principles of masses
The principle of treatment is that hyperprolactinemia should be treated promptly after diagnosis, mainly by medication, supplemented by surgery and radiation therapy.
(B) Specific treatment methods
1.Drug treatment
(1) Bromocriptine: start with a small dose of 1.25mg/d, increase the dose in 3 days, gradually increase to 2.5mg each time in 7-10 days, twice a day, taken with meals, and measure PRL in 1-2 months. Bromocriptine treatment is well tolerated. Vaginal administration of bromocriptine can significantly reduce gastrointestinal reactions, and the dose is the same as the oral method.
(2) Thioproterenol mesylate: 50-150ug/d as a single dose, then gradually increase the dose as needed. This drug is similar to bromocriptine.
(3) Octahydrobenzylquinoline (Nogonin): Stronger than bromocriptine for PRL inhibition, relatively less adverse reactions, 25ug/d for the first 3 days, 50ug/d later, 75ug/d from the 7th day, then gradually increase the dosage according to the need, the maintenance amount is generally 75-150ug/d, a few patients can be increased to 1mg/d, given once a day, at bedtime. The duration of administration is similar to that of bromocriptine, but the drug is not approved by the FDA for the treatment of high PRL in the United States.
(4) Cabergoline: A dopamine (DA) agonist with a very long half-life that requires only 1-2 doses of 0.5-2 mg per week. It can also be given lightly vaginally.
(5) Vitamin B6: 300-600mg/d, divided into 3 oral doses, to inhibit PRL secretion through the center.
2.Surgical treatment is indicated for.
①When pituitary tumor produces obvious compression symptoms.
②When drug treatment is ineffective. The aim is to reduce the volume of very large tumor, not to cure it. Short-term administration of bromocriptine before surgery is to reduce the size of tumor and facilitate surgery.
3.Radiation therapy as a kind of complementary therapy is used with patients who are not satisfied with the effect of drug therapy or when PRL cannot be reduced to normal with residual in and tumor tissue after surgery, or when surgery is not appropriate or refused for other reasons. Normalization of PRL levels after radiotherapy mostly occurs 5-15 years after radiotherapy. The main adverse effect of radiotherapy is hypopituitarism, with an incidence of 93%; other complications include sequelae malignant transformation, cerebrovascular accident, and radioactive brain injury.
(C) Treatment precautions
1.The adverse reactions of bromocriptine include nausea, sometimes accompanied by vomiting; upright hypotension at the beginning of treatment; hallucinations, delusions and mood changes in a few patients.
2. Vaginal administration of bromocriptine in the same dosage form can significantly reduce gastrointestinal reactions, and the effect of lowering PRL level is the same as that of oral administration.
3.After pregnancy while taking bromocriptine, it is recommended to stop the drug with 3 months of pregnancy, and also to gradually reduce the dosage. If symptoms recur, consider re-dosing.
4, dopamine (DA) agonist a, discontinuation of the drug should be extra cautious, the usual practice is: according to the PRL level gradually reduce the dose, when the tumor shrinks to the maximum extent, or PRL level does not increase, then can completely stop the drug.
If the tumor shrinks and then increases during the treatment of dopamine agonists, it is usually due to the lack of compliance with the treatment. If the tendency is to resume the full dose immediately instead of gradually increasing the dose, it will worsen the disease and lead to the aggravation of adverse reactions and further reduce the compliance.
Preventive measures
1. Maintain a stable mood, avoid mental stimulation, and keep qi and blood flowing smoothly. During menstruation, you must pay attention to prevent cold and keep warm. Especially below the waist, make sure both feet will not be cold, do not touch cold water, and forbid eating cold food.
2, hyperprolactinemia in the diet should try to avoid dairy products, you can choose to eat more kelp, sardines, lettuce and so on, try not to drink alcohol and coffee.
3, pay attention to healthy exercise, enhance physical fitness, improve physical fitness, usually to strengthen physical exercise, to develop a daily health gymnastics or tai chi, etc., are very beneficial to the prevention of disease.
4, drink more juice, maintain a good regular sex life, because a good regular sex life is not easy to cause skin fever, and can indirectly stimulate the degenerated ovaries and ease the hormonal system.