Prolactinoma

Introduction to prolactinoma Prolactinoma refers to a tumor in which the pituitary gland secretes PRL, and the incidence of pituitary functional (secreted) tumors is the highest. The clinical manifestations of typical prolactinoma are amenorrhea, galactorrhea, infertility (fertility), hyperprolactinemia, and pituitary changes. basic knowledge Probability ratio: 0.05% of female patients Susceptible people: good for women Mode of infection: non-infectious Complications: prolactinoma acromegaly

Prolactinoma etiology

(1) Causes of the disease

There are many reasons for high PRL. In addition to physiological high PRL, there are pathological and drug-induced causes. Unexplained patients are called idiopathic hyper-PRL.

1. Pathologically high PRL

Pathologically high PRL is more common in hypothalamic-pituitary diseases. PRL tumors are the most common. In addition to PRL tumors (or mixed tumors containing PRL tumors), other hypothalamic-pituitary tumors, invasive or inflammatory diseases, Disease, granuloma and trauma, radiation injury, etc. are due to hypothalamic dopamine production disorders or blocking pituitary portal blood flow caused by dopamine and other prolactin release inhibitors (PIF) can not reach the pituitary gland, due to prolactin release factor Increased (PRF) caused by high PRL is seen in primary hypothyroidism, stress stimulation and neurogenic stimulation. Patients with chronic renal failure have high PRL and cirrhosis due to glomerular filtration to clear PRL disorders. Patients with elevated PRL due to inactivation of estrogen and PRL in the liver, some rheumatic diseases such as systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis can also have high PRL, but with There is no correlation between disease activity and serological abnormalities. The cause of autoimmune disease with high PRL is unknown. Hyperprolactinemia may or may not be accompanied by galactorrhea.

2. Drug-induced high PRL

There are many drugs that can cause high PRL, including dopamine receptor antagonists, oral contraceptives containing estrogen, certain antihypertensives, opiates and H2 blockers (such as cimetidine). Among them, dopamine receptor antagonists are some drugs with stability, sedative or antiemetic effects, antidepressants and antipsychotic drugs. The blood PRL is generally not more than 100g/L at the usual dose, and high PRL is caused by oral domperidone for 5-7 days. The level is between 35 ~ 70g / L, even can be significantly increased, was misdiagnosed as PRL tumor, because chlorpromazine and metoclopramide (gastric ampoules) the strongest effect, 25mg chlorpromazine can make normal people Serum PRL levels increase by 5 to 7 times, so it is often used in the dynamic test of PRL to assist in the diagnosis of PRL tumors.

3.PRL tumor

There have been several hypotheses about the pathogenesis of PRL tumors. It has been thought that long-term administration of estrogen may be the cause of PRL tumor formation, but large-scale studies have shown that oral contraceptives, especially low-dose estrogens and PRL tumors are not associated with the formation of PRL tumors. It is believed that the pituitary autodefect is the starting cause of PRL tumor formation, and the hypothalamic regulatory disorder only plays a role of allowing and promoting. Some molecular genes are used to find candidate genes in human pituitary tumors, which are related to PRL tumors. The tumor activation genes include heparin binding secretory transforming gene (HST), pituitary tumor transforming gene (PTTG), tumor suppressor gene CDKN2A gene and MENI gene, and the latter in familial multiple In patients with endocrine adenoma syndrome-type I, it was found that due to the mutation of these genes, the growth inhibition state of pituitary stem cells was released, and it was transformed into one or several pituitary cells, and monoclonal proliferation occurred, and the hormone regulation disorder in the hypothalamus was observed. Localized tumor formation in the gland, leading to autonomy of one or several pituitary hormones Into and secretion.

The discovery of specific tumor molecular markers contributes to the early diagnosis and treatment of microadenomas, and provides a basis for selecting appropriate follow-up protocols. Family screening of familial MEN-I is also possible.

(two) pathogenesis

The pathogenesis of PRL tumors, since the progress of molecular biology technology research in the early 1990s, it is believed that the primary intrinsic defects of pituitary PRL secreting cells are the starting cause of PRL tumor formation, and the hypothalamic regulating pituitary PRL cell dysfunction only plays a role in allowing and promoting, both of which are involved in the development of pituitary PRL tumors.

Experiments have shown that estrogen can form PRL tumors in experimental rats. It is believed that the role of estrogen is to reduce the proliferation inhibitory factor (PIF) and weaken the regulation of PRL cells in the hypothalamus. Clinically, the incidence of PRL tumors in women of childbearing age is the highest. Pregnancy causes a significant increase in the original PRL tumor, about 10% of PRL tumors occur after pregnancy, and the use of dopamine agonist bromocriptine treatment reduces serum PRL levels in about 90% of patients with PRL tumors, and can make tumors Narrowing and other indicators suggest that there is a deficiency in the role of dopamine or PIF in the pathogenesis of PRL tumor.

On the other hand, both experimental and clinical studies have shown that PRL tumors have strong functional autonomy, and thus it is considered that PRL tumors regulate the hormone response to hypothalamic dysfunction. The dysfunction of tumor cells themselves is secondary to dysfunction. In recent years, through the use of X chromosome Inactivation analysis confirmed that most of the pituitary PRL tumors originated from abnormal clones from single PRL cells, indicating that the tumor originated from the primary defects of pituitary PRL cells. This finding, combined with the above clinical and experimental studies, can be based on phased theory. Explain the occurrence of PRL, the initial stage and the promotion stage of tumorigenesis. The former refers to spontaneous or acquired mutations in pituitary PRL cells, and the latter assumes that the mutated cells continue to clone and expand into tumors under the action of internal or external factors.

In recent years, molecular biology techniques have been used to find candidate genes in human pituitary tumors. Among them, the tumor activation genes associated with PRL tumors are heparin binding secretory transforming gene (HST), pituitary tumor transformation gene (pituitary). Tumor transforming germ, PTTC), tumor suppressor gene CDKNA gene has no diseases related to these drugs, such as hypertension, ulcer disease, mental disorders, insomnia, hormone therapy, menstrual birth history, breastfeeding history and the relationship between milk spill.

Prolactinoma prevention

1. Patients with clinical symptoms should be treated with drugs, correct hyperprolactinemia, inhibit lactation, restore menstruation, prevent possible adenoma or tumor enlargement, prevent or reduce osteoporosis, and should be followed up regularly.

2. Stop using various drugs that cause elevated levels of PRL.

Prolactinoma complications Complications prolactinoma acromegaly

Regardless of the male or female patient, prolactinoma may be associated with GH tumor or ACTH (mixed adenoma) with acromegaly or hypercortisol syndrome.

Prolactin symptoms Common symptoms Pituitary dysfunction Osteoporosis galactorrhea Hyperprolactinemia Amenorrhea Bone mineral density Increase Single eye blindness Nausea amenorrhea - Milk spill - No...

The clinical manifestations of high PRL caused by PRL tumors vary with age, gender, duration of high PRLemia, and tumor size. Although PRL and microadenomas found in autopsy have no gender differences in epidemiology. However, clinical PRL tumors are common in female patients, mostly occurring in 20 to 40 years old. Female PRL tumors often show galactorrhea-menopausal syndrome. The tumor size is positively correlated with serum PRL concentration. The larger the tumor, the higher the PRL level. The more obvious.

1. Female PRL tumor

Mostly microadenomas, seen in young people aged 20 to 30, the typical symptoms are amenorrhea-milk-infertility triad, secondary amenorrhea more common, accounting for about 90%, milk spill is the main manifestation of this disease, mostly for touch lactation , accounting for 50% to 90%, sexual dysfunction accounted for about 60%, complaining of decreased sexual desire or lack of sex, loss of sex, lack of orgasm, sputum pain, etc., other symptoms of hypogonadism have shortened menstrual period, the amount of blood is rare or excessive More, menstrual delay and infertility, in addition, due to serum reduction caused by breast atrophy, pubic hair loss, vulvar atrophy, vaginal secretions and other symptoms, female adolescent patients may have delayed puberty, growth retardation and primary amenorrhea, abortion 30%, there are accompanying metabolic disorders such as obesity, sodium and water retention syndrome, amenorrhea-infertility can be caused by hyperprolactinemia inhibition of sexual function, manifested in the hypothalamic level, because it interferes Normal estrogen has a positive feedback effect on gonadotropin releasing hormone (LRH) secretion leading to LH peak and ovulation.

Recently, it has been suggested that PRL increases the activity of endogenous opioid polypeptide (EOP) receptors, and EOP affects the changes of DA. PRL may increase DA release in the outer ridge of the median ridge, thereby inhibiting LRH release and reducing pituitary-gonadal axis function. Also acts on the ovarian level, PRL competition inhibits the effect of ovarian receptors on gonadotropins, which can cause luteal function deficiency, progesterone synthesis disorders and mild estrogen synthesis disorders, leading to menstrual disorders, amenorrhea, ovulation stop It can also cause low estrogenemia, which leads to decreased vaginal secretion, painful intercourse and loss of libido. Menstrual disorders are thought to be related to serum PRL levels and to tumor size, when they are in the stage of microadenomas (<10mm). There is still possibility of conception, but there are more chances of miscarriage than normal people. Some patients with long-term hyperprolactinemia may have reduced bone density due to low estrogenemia, such as excessive dehydroepiandrosterone produced by the adrenal gland. Mild hairy, hemorrhoids, in addition, female prolactin microadenomas in the amenorrhea-infertility treatment, due to the stimulation of exogenous estrogen, the tumor rapidly expands, so the value Get clinical attention.

2. Male PRL tumor

Male prolactinoma is generally diagnosed when it is large, often developing on the saddle, but relatively rare, mainly showing symptoms of sexual dysfunction, accounting for about 83%, may be complete or partial, such as varying degrees of libido, impotence Male infertility and the number of sperm decreased, because the symptoms progress slowly and have large fluctuations, it is not easy to cause the patient's attention. Most of the visits are late. At this time, the imaging examination confirmed that most of them were large adenomas, and the symptoms of nerve compression were more obvious. Physical examination revealed that the patient's whiskers were sparse, slow-growing, sparse pubic hair, and soft testicles. Male adolescents had puberty development and growth and development, abnormal posture and small testicles. In addition, about 69% of men were obese.

3. Tumor compression group

More common in large or advanced PRL tumors and other types of pituitary adenomas, hypothalamic and parasagittal tumors due to the huge expansion of the tumor to the saddle to block PIF caused by high PRL, the most common local compression symptoms are headache and vision Abnormal, headache is mostly due to increased intracranial pressure caused by large adenoma, may be associated with nausea and vomiting. The incidence of headache in male PRL tumor patients is higher than that of female patients, about 63%. Some PRL microadenomas do not occupy lesions. Obviously, headaches (50%) can also occur, the reasons for which are not known.

Pituitary tumors expand upward and compress the cross; visual anomalies, such as vision loss, blurred vision, visual field defects, extraocular muscle paralysis, etc., the most typical, common due to optic chiasm caused by bilateral hemianopia, oppression Different parts, different forms of visual field defects, ipsilateral hemianopia when oppression of optic tract, monocular blindness when oppression of optic nerve, early compression symptoms are not heavy, but due to blocked nutrient vessels, some nerve fibers are compressed and visual acuity declines and visual The object is blurred, and the fundus atrophy can be seen in the fundus examination. The pituitary tumor can cause the following five types of visual field defects and vision loss:

(1) sacral hemianopia: the most common type of visual field defect, accounting for 80%, because the pituitary tumor oppresses the leading edge of the chiasm, damages the nerve fibers from the lower side of the retina, and then the upper side of the nose, starting with The visual field of a wedge-shaped region of the outer upper quadrant is impeded, and then the visual field defect gradually expands to the entire outer quadrant, and then expands to the outer lower quadrant, forming a bilateral temporal hemianopia. In the early stage, the visual loss of red appears in red. It is easy to detect the presence of visual field defects early in the examination, and the patient's visual acuity is generally unaffected.

(2) Dark spots in the central side of the bilateral sacral side (dark-point visual field defect 3): This type of visual field defect accounts for about 10% to 15%. Because the pituitary tumor oppresses the posterior part of the chiasm, it damages the macular nerve fibers. In the case of the situation, the peripheral and central vision should be checked at the same time to avoid missed diagnosis. This type of visual field defect does not affect vision.

(3) isotropic hemianopia: less common (about 5%), due to tumor expansion to the upper rear or due to the patient's anterior optic chiasm (about 15%) caused by compression of one side of the beam, patient vision Normal, this type and the former type of visual field defect can also be seen in hypothalamic tumors such as craniopharyngioma, hypothalamic glioma and germ cell tumor.

(4) Monocular blindness: This condition is seen when the pituitary tumor expands forward or upward or the patient is a posterior type of optic chiasm (about 5%). The extended tumor oppresses one side of the optic nerve causing the central visual loss or even blindness of the side. Vision, normal vision.

(5) visual loss of one side of the contralateral side of the lateral side: this type and the former type are rare, because the upwardly expanding tumor compresses the side of the optic nerve near the end and the optic chiasm. From the contralateral nasal lower retinal nerve fibers, these nerve fibers form a hernia (anatomically called Wibrand knee) and enter the optic chiasm.

Clinically, the tumor is generally larger when there is a visual field defect, but a small number of microadenomas can cause bilateral hemianopia. This is because the optic chiasm and the pituitary are the same source of blood supply, and the blood supply in the middle of the optic chiasm is weak. The blood flow perfusion of the pituitary tumor is rich, resulting in "stealing blood" and causing bilateral hemianopia. The transsphenoidal surgery can remove the adenoma and correct the visual field defect.

The growth of the tumor to the sides of the sella can compress the cavernous sinus, compressing the first, III, IV, V, VI to the cerebral nerve, the olfactory nerve is compressed when there is olfactory loss; the third, IV, VI can be compressed by the cranial nerve Eye movement disorder, drooping eyelids, pupils disappearing from light reflection, etc.; V is secondary to trigeminal neuralgia and local numbness of the head and face.

A huge adenoma to the frontal lobe of the brain, the development of temporal lobe can cause seizures and mental symptoms. Tumor erosion on the saddle can cause cerebrospinal fluid rhinorrhea, and huge PRL tumors can cause unilateral ocular protrusion and bilateral pupils.

When the PRL large adenoma compresses the surrounding normal pituitary tissue, it can cause GH, ACTH, TSH, LH, FSH deficiency, and thyroid or adrenal insufficiency.

4. Osteoporosis

Long-term high PRL in patients with PRL tumors can cause osteoporosis. It was first reported by Kibanki et al in 1980. This disease can sometimes be the first symptom. The male patients have corrected the bone mineral density of the humerus after correcting high PRL and normal gland function. Increased bone density of vertebrae did not change significantly; bone mineral density did not increase in patients with normal PRL levels and failed to restore gland function. Schlechte et al. showed that after surgery, PRL levels remained low even after PRL levels returned to normal after surgery. In normal controls, it is suggested that elevated serum PRL levels play a role in promoting bone loss.

5. Acute pituitary apoplexy

Some fast-growing PRL tumors can also cause intratumoral hemorrhage, acute pituitary apoplexy, manifested as sudden headache, nausea, vomiting and sharp decline in visual acuity, and even coma and eyeballs, requiring emergency rescue. After successful rescue, patients often have pituitary dysfunction.

Prolactinoma examination

1. Basic PRL determination

The blood PRL basal concentration is generally less than 20g / L, the serum sample extraction time is not strictly limited, generally as long as the peak secretion time before waking up, there is no need to fast, in order to eliminate the impact of pulse secretion or venipuncture, should be repeated many times The best way to take a blood sample is to indwell the intravenous catheter. The patient takes blood after 2 hours of rest, and the specimen is taken several times. The interval is about 20 minutes, and the average value is taken about 6 times (eliminating the influence of pulse secretion).

The results of the analysis should be considered whether there is physiological or drug-induced factors. For example, blood PRL below 20 g/L can exclude hyperprolactinemia. When it is greater than 200 g/L, it can be confirmed as PRL tumor in combination with clinical and pituitary imaging. If it reaches 300-500g/L, after excluding physiological pregnancy and drug-related factors, even if there is no abnormality in imaging examination, it can be diagnosed as PRL tumor. If serum PRL is below 200g/L, various excitations or inhibitions are used (rare). The test to identify whether it is a PRL tumor, because these dynamic tests are not specific, and the stability is poor, so the clinical depends more on high-resolution CT and MRI, the general physiological increase of PRL is 20 ~ 60g / L Patients with basal serum PRL greater than 60 g/L and less than 200 g/L must be combined with hypothalamic-pituitary imaging findings to determine whether they are PRL tumors. A small number of patients with high PRL have no clinical symptoms despite elevated basal PRL, or Patients with PRL tumors have improved symptoms after drug treatment, but the PRL decline is not significant. It is necessary to pay attention to the heterogeneity of PRL components in circulating blood. Although the dimers and multimers of PRL are immunologically active, they are biologically active. Low, although most like normal PRL PRL tumor cells mainly as PRL secretion in monomeric form, but a few PRL tumors can produce more dimers and multimers PRL.

It must be noted that all patients with pathological hyperprolactinemia must have detailed medical history, physical examination and routine liver and renal function tests to rule out drug resistance and stress before MRI examination of hypothalamic-pituitary disease. , neurogenic and systemic diseases may be, in particular, to exclude primary hypothyroidism.

2.PRL dynamic test

(1) TRH stimulation test: in the basic state, static injection of TRH 200 ~ 400g (diluted with 2ml of normal saline), blood sampling before 30,0min before injection and 15,30,60,120 and 180min after injection Serum PRL, normal human and non-PRL tumors with high PRL patients peaked at 30 min after injection, peak/base value was greater than 2, PRL tumors were delayed, peak/base value <1.5.

(2) Chlorpromazine (or metoclopramide) stimulation test: intramuscular or oral chlorpromazine 30mg or metoclopramide (gastric ampoules) 10mg under basic conditions, 30 and 0 min before administration Blood samples were taken at 60, 90, 120 and 180 min after administration to measure PRL. The peak value of normal and non-PRL neoplastic patients with high PRL was 1 to 2 h, peak/base value was greater than 3, and PRL tumors had no obvious peaks or Peak delay, but peak/base value <1.5.

(3) L-dopa inhibition test: oral levodopa (L-dopa) 0.5g under basic conditions, 30 and 0 min before taking the drug, 60, 120, 180 min after taking the drug, 6 h blood sampling In PRL, the PRL level was inhibited below 4 g/L or the inhibition rate was greater than 50% 1 to 3 hours after the administration of the drug, and the PRL tumor was not inhibited.

(4) bromocriptine inhibition test: blood test for PRL level at 8:00 am (fasting) on the day of the drug, oral bromocriptine 2.5mg at 10-11 o'clock in the evening, 8 o'clock in the morning (fasting) and blood samples were taken to measure PRL level. The inhibition rate of more than 50% supports the diagnosis of non-neoplastic high PRL; the inhibition rate of less than 50% is consistent with pituitary neoplastic high PRL, and the inhibition rate of normal people is also greater than 50%. Nakasu et al reported a case of PRL tumor. In the bromocriptine inhibition test, shock occurred after 3.5 hours of the first dose (2.5 mg). Although this condition is extremely rare, it is necessary to check the cardiovascular function before taking bromocriptine.

(5) Determination of other hormones: In addition to measuring PRL, clinically suspected PRL tumors should also detect LH, FSH, TSH, -subunit, GH, ACTH, testosterone and estrogen. Long-term high PRL of PRL tumor leads to LH. FSH decreased, testosterone or estrogen levels decreased, some mixed adenomas (most common with increased GH secretion) in addition to increased PRL, there are other pituitary hormones increased, large PRL tumors can compress the surrounding pituitary tissue caused by one or Several secretions of pituitary hormones are reduced. In addition, the concentration of urinary 17-ketosteroids and various estrogen catabolic metabolites in patients with PRL tumors increases, which may be due to the high concentration of PRL reducing the activity of 5-reductase and 3-steroid dehydrogenase. Caused.

For all patients with pathologically high PRL, before X-ray, CT or MRI examination for suspected hypothalamic-pituitary disease, it is necessary to first inquire about the medical history, physical examination and routine liver and kidney function tests and rule out drug resistance one by one. Stress, neurogenic and systemic diseases are possible, especially in the diagnosis of primary hypothyroidism.

3. X-ray film in the saddle area

Because PRL tumor microadenomas are more common, conventional X-ray plain films can not find the saddle enlargement or erosion, and the pituitary tumors increase to a certain extent, which can cause X-ray manifestations of saddle bone destruction (such as saddle area enlargement, bone quality). Thinning or defect, etc.), which can be presumed to be the existence of pituitary tumors, but the tumor size cannot be determined, and pituitary microadenomas are not found. The normal saddle nodule angle is about 110°. With the increase of PRL tumor, this angle can be The gradual change is an acute angle. According to this, the existence of pituitary tumor can be inferred. Although the cerebral artery angiography or cerebral artery X-ray imaging examination can show the size of the pituitary tumor to some extent, it is an invasive examination with a certain risk. , has been replaced by the popular application of CT and MRI.

In addition, the positive sign of the saddle bottom in the thin layered (2 mm) multi-layer tomographic X-ray film showed a saddle bottom tilt in the positive position and a foamy expansion in the front lower wall of the saddle bottom with saddle nodule angle reduction. The point can be used as an important feature of X-ray of PRL tumor, and its diagnostic value is much higher than that of plain film. According to Guiot and Hardy's criteria, the radiological manifestations of pituitary microadenomas are divided into localized and erosive.

4. CT and MRI examination of the sellar area

Whether there are pituitary tumors, CT scan of the sella and MRI imaging are currently widely used imaging methods, especially MRI is better than CT and more applications.

(1) CT examination: CT scan overcomes the limitations of most conventional X-ray methods, requires only a small amount of X-ray radiation and can directly observe the image of pituitary tumors, using high-resolution direct coronal continuous thin layered dya Reconstructive scanning method, combined with intravenous X-ray contrast-enhanced contrast-enhanced scanning, can not only directly and clearly observe large pituitary adenomas, but also may find small adenomas of 3 ~ 4 mm, used for post-treatment review accuracy High, CT scan normal adult pituitary height, female <8mm, male <7mm, uniform density, slightly depressed upper edge, central pituitary stalk, bilateral symmetry, CT scan pituitary tumor positive see:

1 When there is no contrast agent (flat scan), there is a high-density area that is faintly visible.

2 After the contrast agent was injected, the image of the pituitary gland in the sellar region was enhanced, the height was higher than normal, and the pituitary stalk was displaced.

3 pituitary gland abnormalities, enlargement, upper margin bulging, bilateral asymmetry, large adenoma can be on the saddle, saddle expansion, occupying the upper saddle pool, the third ventricle, cavernous sinus and so on.

4 When the non-enhanced or enhanced scan, the density of the gland is uneven, there is a low-density area, and in the case of micro-adenoma, the diameter of the low-density area is 1/2 or more of the pituitary gland.

5 The bottom of the saddle is tilted and destroyed.

CT scan has its limitations, and the false positive and false negative of the saddle microadenomas are still high. Swartz et al reported that the upper edge of the pituitary gland can also have bulge, uneven density and local low density area. In the case of microadenomas, the CT detection rate was 85%.

When it is difficult to identify cystic masses and empty sella in the sellar region, water-soluble metrizamide can be used for cerebral angiography CT scan to obtain a clear diagnosis.

(2) MRI examination: MRI examination is more sensitive and specific than CT scan. MRI is superior to CT in the diagnosis of hypothalamic-pituitary diseases, especially pituitary tumors, although MRI and high-resolution CT (coronal multiple thin layer vector) Shape reconstruction scan can be found in small adenomas less than 3mm in diameter, but MRI can better observe the internal structure of pituitary tumors and its relationship with surrounding tissues, to understand whether the lesions invade the optic chiasm, jugular sinus, sphenoid sinus and degree of invasion, The observation of subtle changes in the slender pituitary stalk or the compression of the occupying lesion is also superior to CT.

The MRI T1-weighted images of pituitary microadenomas appear as circular low-density images, and the density of T2-weighted images is higher. The imaging images of large adenomas are similar to normal glandular tissues, but cystic changes and hemorrhagic lesions may occur within them. When it is suspected that the pituitary has PRL micro-gland, Gd-DPTA can be used as an enhancer for coronal MRI enhanced scan to increase the probability of micro-adenomas. MRI can also find some non-pituitary saddle-occupying lesions (such as meninges). Tumor and internal carotid aneurysm), the diagnosis of PRL microadenomas with MRI, the diagnostic value of pituitary bulge is not as high as the pituitary height, in addition, MRI can not show bone destruction and calcification.

5. Radionuclide examination

The use of 111In-pentertreotide for pituitary tumor imaging is satisfactory in growth hormone secretory tumors and non-functioning large adenomas. The value of PRL tumors, especially microadenomas and postoperative residual tumor imaging remains to be further studied.

Prolactinoma diagnosis and differentiation

Diagnostic criteria

1, related symptoms:

(1) Amenorrhea, there may be many menorrhagia or irregularity in the early stage.

(2) galactorrhea, accounting for about 50% of female patients.

(3) Both sexes may have infertility (education) and varying degrees of sexual dysfunction.

(4) Clinical symptoms and signs of pituitary tumor occupying oppression, such as headache, visual field defect and vision loss.

(5) Excluding certain drug factors.

2. Auxiliary inspection:

(1) Determination of blood PRL: normal human fasting serum PRL is less than 20g / L, prolactinoma patients serum PRL more than 100g / L, more than 300g / L almost certainly exist in prolactinoma.

(2) Sella positive, lateral radiograph of the pituitary CT or magnetic resonance examination: the presence of the tumor can be confirmed, and the visual field examination can assist in the diagnosis.

(3) Serum FSH, LH, and estradiol (E2) values can be reduced.

(4) The TRH stimulation test can be performed if necessary, and the metoclopramide test has certain reference value for the diagnosis of prolactinoma.

(5) for related examinations to exclude primary hypothyroidism and hypothalamic, pituitary and other endocrine diseases, except for brain and breast diseases.

Differential diagnosis

The patient has amenorrhea-lactation, male sexual dysfunction or infertility, serum PRL level is significantly elevated, CT or MRI imaging has pituitary tumors, PRL tumor diagnosis is mostly difficult, need to identify those with a slight increase in PRL levels With or without the saddle area occupying lesions, clinically, the diagnosis is based on the exclusion of other pituitary adenomas.

The differential diagnosis of PRL tumors is mainly focused on high PRL. When the serum PIL is mild to moderate (not reaching 200 nmol/L), it must be associated with idiopathic high PRL, pituitary non-PRL tumor, hypothalamic tumor or Identification of extracorporeal tumors in the sellar region.

Pituitary non-PPL tumor

The blood PRL is generally lower than 200nmol/L. MRI or CT examination can find a lesion in the pituitary gland. Expanding the compression of the pituitary stalk to the saddle can prevent the PIF from reaching the pituitary gland. The pituitary hormone test finds that in addition to the increase of PRL, there is another A hormone is increased (no function of adenoma), but other pituitary hormones are reduced. After treatment with bromocriptine, PRL is reduced to normal, but the size of pituitary tumors rarely changes. Consider pituitary non-PPL tumors, common with non-functional pituitary adenomas and GH tumors.

2. Hypothalamic tumor or sellar tumor in the sellar region

There are many types of tumors, the common point is that serum PRL is often less than 100nmol/L; MRI or CT examination shows no lesions in the pituitary; the mass is not associated with the pituitary gland, and is close to the pituitary stalk area and compresses the pituitary stalk to cause portal blood flow. Obstruction, or located in the hypothalamus interfere with the synthesis and secretion of dopamine, the general patients have more cranial nerve compression, increased intracranial pressure and diabetes insipidus, usually hypothalamic-pituitary MRI or high-resolution CT can be compared with PRL tumor Identification.

3. Primary hypothyroidism

In general, it is easy to distinguish it from PRL tumors. In a few cases, it not only causes high PRL blood, but also causes the pituitary gland to enlarge. MRI and other tests are mistaken for pituitary adenomas. In recent years, many cases of primary thyroid function have been reported. MRI examination of patients with hypotension revealed pituitary tumors, high PRL in laboratory tests, although clinical symptoms of hypothyroidism were not obvious, but thyroid function tests showed primary hypothyroidism, cured with thyroid hormone replacement therapy .

4. Idiopathic high PRL

The cause is unknown, may be caused by hypothalamic damage (undetected lesions), idiopathic high PRL must first rule out drug, pathological, physiological high PRL after the diagnosis can be established, CT or MRI no abnormalities It was found that the general serum PRL was only slightly elevated (more than 100nmol/L), and a few patients could later evolve into PRL tumors. Treatment with bromocriptine could prevent the formation of PRL tumors and should be followed up regularly.

5. Other

Other tumors and non-pituitary tumors with larger pituitary gland, such as craniopharyngioma, germ cell tumor, meningioma, and compression of the pituitary stalk can hinder the transmission of PIF (DA) in the hypothalamus, and can also produce high PRL. It is a "pseudoprolactinoma", but the latter serum PRL responds to MCP and TRH. The serum PRL decreases rapidly after the tumor is removed. It can be identified. The disease is accompanied by GH, ACTH, TSH and other pituitary hormones. In clinical manifestations, it can be diagnosed as a mixed PRL tumor containing other cells.

In conclusion, the diagnosis of patients with galactorrhea or amenorrhea should first consider the possibility of hyperprolactinemia. If the blood PRL is not elevated or the elevation is not obvious, further PRL stimulation test or necessary imaging examination should be performed.

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.