Hyperprolactinemia

Hyperprolactinemia
Summary:



Hyperprolactinemia (Hyperpro-lactinemia, HPRL), the means by the internal and external environment factors, increased to PRL (≥ 25 ng / ml), amenorrhea, Yiru, no ovulation and infertility for the characteristics of the syndrome. Nearly 20 years ago, on the physiological and biochemical research PRL made tremendous progress, and PRL RIA determination of brain CT and MRI diagnosis of advances in technology, improve the diagnosis of the HPRL, also increased the incidence trends. At the same time anti-drug bromocriptine prolactin (Bromocriptine, Parlodel) and the advent of the transsphenoidal microsurgery in the diagnosis and treatment appear to HPRL a new situation.



[Diagnosis]




First, history

Focus on understanding menstrual history, the history of marriage and child rearing, and Yiru amenorrhea due to the beginning, incentives and systemic diseases caused HPRL related medication history.

Second, the investigation of

Body search of. Pay attention to whether Acromegaly, myxedema等症like. Xingqi gynaecological examinations understanding of the levy and whether atrophy and organic diseases. Breast examination attention to the size, shape, whether mass inflammation Yiru (light squeeze hands breast). Overflow of characters and quantity.

3, endocrine function tests

(1) of pituitary function: FSH, LH lower LH / FSH ratio increased. PRL increased ≥ 25 ng / ml, respectively. Generally believed that <100 ng / ml for more than functional. ≥ 100 mg / ml, the attention should be excluded PRL adenoma. PRL greater tumor higher. If tumor diameter d ≤ 5 mm, 171 ± 38ng/ml for PRL; d = 5 ~ 10mm 206 ± 29ng/ml; ≥ 10 mm485 ± 158ng/ml. Great adenoma hemorrhage and necrosis, PRL may increase.

Be pointed out: PRL currently used by clinical radiology Shuoxiang only of small molecule PRL (MW25000), but not Determination / greatly molecules (MW5 ~ 100000) PRL, the clear and certain clinical symptoms PRL normal, we can not rule out the so-called occult high hyperprolactinemia (occult hyperprolactinemia), which is big / significant elements hyperprolactinemia.

(B) ovarian function: E2, lower P, T increased.

(C) thyroid function test: A low HPRL merger elevated TSH, T3, T4, PBI lower.

(D) adrenal function test: HPEL merger Cushing's disease symptoms and masculine, T, △ 4 dione, DHT, DHEA, 17KS increased plasma cortisol increased.

(5) pancreas function: HPRL with diabetes, Acromegaly, should be of insulin, glucose, glucagon and oral glucose tolerance test.

4, prolactin function tests

(1) prolactin stimulation test

1. Thyrotropin-releasing hormone test (TRHtest): normal women 1 intravenous TRH100 ~ 400 μ g, 15 to 30 minutes before the injection PRL than 5 to 10 times higher, TSH increased 2-fold. Pituitary tumor, not escalating.

2. Chlorpromazine test (Chlorpromazine test): Chlorpromazine the receptor mechanism, inhibit norepinephrine dopamine uptake and transformation functions, the promotion of PRL secretion. Intramuscular injection of 25 normal women ~ 60 ~ 50 mg blood PRL than 90 minutes before the injection increased 1 ~ 2 times, lasted three hours. Pituitary tumor, not escalating.

3. Eliminate vomit Ling test (Metoclopramide test): The dopamine receptor antagonist drug to promote the synthesis and release of PRL. 10 mg intravenous normal women 30 to 60 minutes before the injection than PRL increased more than three times. Pituitary tumor, not escalating.

(B) prolactin inhibition test

1. Test levodopa (L-Dopa test): the drug for the dopamine precursor, the delinking of hydroxyl inhibit the formation DA PRL secretion. 500 mg oral normal women after 2 to 3 hours PRL decreased significantly. Pituitary tumors are not lowered.

2. Bromocriptine test (Bromocriptine test): the drug for the dopamine receptor agonist, strongly inhibited PRL synthesis and release. Normal women oral 2.5 ~ 5.0 mm 2 to 4 hours after the PRL lower ≥ 50% for 20 to 30 hours. HPRL functional and PRL significantly decreased adenoma, and GH and ACTH decreased less than the former two.


[Treatment]




First, the original due to the incidence and treatment

If wipe out bad mental stimulation, out of HPRL drugs, aggressive treatment of primary diseases, such as pituitary tumor, hypothyroidism, Cushing's症等.

Second, anti-PRL - bromocriptine therapy

Bromocriptine is a semi-synthetic ergot derivatives, dopamine receptor agonists, the receptor mechanism, and promote PRL-IH synthesis and secretion, and the inhibition of PRL release, and direct role in the pituitary tumor cells and PRL Inhibition of tumor growth and curb PRL, GH, TSH and ACTH secretion.

Bromocriptine treatment applicable to all types HPRL is pituitary adenoma (Micro / Giant adenoma) preferred treatment, especially in younger infertility expectations fertile area. Dose of 2.5 to 7.5 mg / d oral. Other drugs, including anti-PRL: levodopa (Levo-Dopa), benzo eight hydrogen quinoline (CV205-502), such as vitamin B6. See Chapter endocrine therapy section of prolactin.

Third, ovulation induction treatment

Apply to HPRL, anovulatory infertility, Bromocriptine treatment alone can not succeed ovulation and pregnancy. Bromocriptine is mainly used to, compatibility other ovulation drug combination therapy: ① bromocriptine - CC-hCG; ② bromocriptine - hMG-hCG; ③ GnRH. Pulse therapy - such as bromocriptine. Comprehensive Treatment of prolactin can be saved, shorten treatment cycles and improved ovulation rate and pregnancy rate.

4, surgical therapy

Giant adenoma in a suitable compression symptoms, as well as tumor resistance, and suspicion Bromocriptine treatment void with a variety of tumor cells, secretion of pituitary hormones.

Existing Transsphenoidal Microsurgery (trans-sphenoidal microsurgery), safe, convenient and easy, similar to the effect of bromocriptine therapy. Compatibility with bromocriptine before and after surgery can improve efficacy. Surgery weaknesses are: no pituitary tumor capsule, border unclear, difficult to completely or surgical injury to the nasal cavity into cerebrospinal fluid fistula secondary pituitary dysfunction.

5, radiotherapy

HP system applicable to non-functional tumor, as well as drug and surgical treatment were ineffective. Irradiation methods include: Deep X-ray, 60 Co, α-ray particles and protons. Isotope Yttrium-90, 198, such as the pituitary implantation.


[Etiology:




Normal pulse of PRL release and circadian rhythm on breast development, milk and ovarian function plays an important regulatory role. PRL secretion by the hypothalamus PRL and PRL-RH-IH double-conditioning while in the normal menstrual cycle, ovulation PRL always be in the hypothalamus CNS dopamine neurons media and PRL-IH tension inhibitory regulation, once this regulation imbalance that is caused by HPPL. HPRL living can be rational and disease caused by irrational factors.

1, physiological hyperprolactinemia

(1) night and sleep (2-6 Am).

(2) egg stage and late luteal phase.

(C) Pregnancy: ≥ higher than that of non-pregnant 10 times.

(D) lactation period: by massage, nipple sucking cause acute, short-term or continuous increase in secretion.

(5) puerperium: 3 to 4 weeks.

(6) low blood sugar.

(7) Movement and the stress stimulation.

(8) sexual intercourse: the height of increased significantly.

(9) fetal and neonatal (≥ 28 gestational weeks postpartum 2 ~ ~ 3 weeks).

Second, pathologic hyperprolactinemia

(1) the hypothalamus - pituitary lesion

1. Tumor:

Non-functional - craniopharyngioma, sarcomatoid disease (sarcoid) glial cell tumors.

Functional - PRL adenoma 46%; GH adenoma 22 ~ 31%. PRL-GH adenoma 5 ~ 7%; ACTH adenoma & Nelson's syndrome4 ~ 15%. - 10% of adenoma; undifferentiated of 19 ~ 27%.

2. Inflammation: the skull base meningitis, tuberculosis, syphilis, actinomycosis.

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

4. Vacuoles sella syndrome.

5. Pituitary stalk lesion, injury or tumor suppression.

6. Mental trauma and stress.

7. Parkinson's disease.

(B) primary and / or secondary hypothyroidism.

1. False hypoparathyroidism (Pseudo-parathyroidism).

2. Hashimoto's thyroiditis (Hashimoto's thyroiditis).

(C) ectopic PRL secretion syndrome: undifferentiated bronchial lung, adrenal carcinoma, embryonic carcinoma.

(D) adrenal and kidney: Adisen's disease, chronic renal failure.

(5) polycystic ovary syndrome.

(6) cirrhosis.

(7) gynecologic surgery: abortion, induced abortion, stillbirth, hysterectomy, tubal ligation, ovariectomy.

(8) The local irritation: Nipple-yim, Chapped Nipple, chest trauma, herpes zoster, tuberculosis, surgery.

(9) medical source - Drug factors:

1. Insulin hypoglycemia.

2. Sex hormones (estrogen - progesterone contraceptives).

3. Synthesis TSH-RH.

4. Anesthetics: morphine, methadone, methionine enkephalin.

5. Dopamine receptor antagonist: Phenothiazones, Haloperidol, Metoclprimide, Domperidone, Pimozide, Sulpiride.

6. Reabsorption of dopamine antagonist: Nomifensine.

7.CNS degradation of dopamine: Reserpine, amethyl-Dopa.

8. Into dopamine inhibitors: A peptide.

9. Monoamine oxidase inhibitor.

10. Diphenyl nitrogen derivatives: diphenyl oxazolidine Nitrogen, carbamoyl nitrogen, because suddenly Dayton, imipramine (Imipramine) amitriptyline (Amitriptyline) phenytoin (phenytoin) stability and clonazepam for methamphetamine (Clonazepam).

11. Histamine and histamine H1, H2 receptor antagonists: 5 serotonin, Amphetamines, Hallucinogens, H1 receptor antagonist (chlorobenzene a triazine meclizine, topiramate benzyl that Pyribenzamine), H2 receptor antagonist ( A microphone Chat Cimitidine cyanide).

(10) of idiopathic.


[Pathological changes:




1, tumor type Hyperprolactinemia

2, and after-Hyperprolactinemia

Third, special hairstyle Hyperprolactinemia

4, iatrogenic Hyperprolactinemia


[Clinical]




First, menstrual disorder

4% of primary amenorrhea, 89 per cent of secondary amenorrhea, menstruation scarce, and too few 7%. Reactive blood-luteal function, 23 ~ 77%.

Second, Yiru

HPRL typical performance for the amenorrhea - Yiru syndrome, in the non-tumor-for 20.84%, 70.58% in the tumor-alone Yiru 63 ~ 83.55%. Yiru is dominant or breast compression occurs when the water samples, slurry, or milk. Breast more than normal, or with lobular hyperplasia or Big (macromastia).

Third, infertility

70.71% of primary or secondary. Department of anovulation, the corpus luteum or not-do not rupture luteinized follicular syndrome (LUFS) caused.


[Complications]




(1) low estrogen response: long-term amenorrhea were found, such as flushing, palpitation, spontaneous perspiration, vaginal dryness, painful intercourse, such as loss of libido.

(B) changes in visual acuity and vision: pituitary tumor found in cross-optic involved, there will be the vision loss, headache, dizziness, Pianmang and blindness, as well as cranial nerves Ⅱ, Ⅲ, Ⅳ dysfunction. Retinal edema, exudative.

(C) Kaohsiung hormone response: moderate obesity, excess fat, acne and more hair.

(D) Acromegaly: PRL-GH adenoma seen, the increased GH.

(5) myxedema: A merger is seen at low.

(6) diabetes and abnormal glucose tolerance test.


[Auxiliary]




(1) Sella fault: normal women Sella diameter <17 mm and depth of <13 mm area of <130 mm2, volume <1100 mm3. If there are scenes should be CT: ① boat-shaped expansion of the wind (ballooning); ② pair of saddle-edge or end (double floors); ③ intrasellar high / low density areas or not homogeneous; ④ Bingmin deformation (saucer, like pattern ); ⑤ saddle on the calcification foci (hyperostosis); ⑥ bed after osteoporosis or sudden intrasellar vacuolar change; ⑦ bone destruction (erosion).

(Ii) E-computed tomography (CT) and magnetic resonance (MRI): intracranial lesions with precise positioning and radiation measurement.

(C) performed: including: sponge sinus angiography (intercavernous sinus venography), gas cerebral angiography (pneumoencephalography) and cerebral angiography (vasoencephalography).

Eye checks including eye, vision, IOP, fundus examination to determine whether compression as intracranial tumors.