Pituitary adenoma

Introduction to pituitary adenoma Pituitary adenoma is a common benign intracranial endocrine tumor. Marie first described acromegaly in 1886. In 1887, Minkowski talked about acromegaly caused by abnormal arrangement of pituitary gland. In 1900, Benda recognized the acromegaly. Eosinophilic adenomas and demonstrated that the tumor is a true tumor from the pituitary cells. basic knowledge The proportion of illness: 0.001% - 0.004% Susceptible people: no specific people Mode of infection: non-infectious Complications: subarachnoid hemorrhage nasal septum perforation diabetes insipidus fibrosarcoma

Cause of pituitary adenoma

(1) Causes of the disease

It is currently believed that pituitary adenomas are derived from pituitary cells, such as monohormone cell adenomas such as growth hormone, prolactin cell adenomas, etc., which are derived from glandular cells that secrete corresponding hormones, and are still controversial for some multi-hormone-derived adenomas. It is believed that a cell can only secrete a corresponding hormone. In the 1970s, Zimmemrman used PAP method to study 5 normal human pituitary tissues. It has particles in the same cell that can bind to both growth hormone and prolactin antibodies. , indicating that the two hormones can be produced in the same pituitary cells at the same time, Midyley believes that follicle stimulating hormone and luteinizing hormone can be secreted by the same cell, Horvath reported 9 cases of pituitary prolactin, growth hormone cell adenoma, Kovacs also pointed out that in non-tumor cases This double hormone-secreting cell is also scattered in the pituitary gland, but the number is small. The above research results show that a cell in the pituitary gland can not only secrete a corresponding hormone, such a multi-hormone cell adenoma, called "Heterologous pituitary adenoma", its mechanism of action is generally considered to be related to the gene expression of tumor cells, may involve Instability and advantages of the selection gene, may also be changes in cell phenotype, with no changes in gene potential.

In recent years, it is believed that chromophobe adenomas are derived from cells with low or no differentiation, and these cells can be transformed into other hormone-secreting cells, which may be accompanied by symptoms of increased secretion of hormones, and secretory granules can be seen under electron microscope. Leuis believes that such non-functional pituitary adenomas have secretory granules, but the tumor cells are less differentiated and fail to form biologically active hormones. Kovacs believes that the tumor cells can synthesize a small amount of hormones or produce inactive hormone precursors; Or for the hormones that have not yet been detected, Betzdorf determines the concentration of growth hormone in the tissue culture fluid of tumor cells, and found that some chromoblastic tumors are also elevated as eosinophils, which may explain some chromophoric glands. Why is the tumor associated with acromegaly?

(two) pathogenesis

The pathogenesis of pituitary adenomas can be classified into two universities: one is the abnormal theory in the pituitary, and the other is the hypothesis of the hypothalamic regulatory mechanism. After studying the molecular biology method, the long-standing controversial pituitary theory and the next The theory of thalamus tends to be unified. It is believed that the development of pituitary adenomas can be divided into two stages: the initial stage and the promotion stage, that is, the pituitary cells first undergo mutation, and then the cells proliferate under the promotion of internal and external factors, and develop into pituitary. Adenoma.

1. The pituitary is abnormal

(1) Gene mutation: The role of gene mutations in pituitary cells in the development of pituitary adenomas has been highly valued in recent years. At present, it is confirmed that some of the genes involved in cell signal transduction are point mutations, including G protein Gs. The subunit (Gs) gene, the ras proto-oncogene, the alpha subtype (PKC) gene of protein kinase C, and the like.

Gs is the first gene to be associated with pituitary adenomas. This study began in the mid-1980s when about 1/3 of GH adenoma cyclase (AC) activity was observed. The level of cAMP is elevated and is not regulated by GHRH and cholera toxin (which can activate AC by stimulating Gs). Later studies confirmed that activation of AC in GH tumor cells is caused by mutation of Gs, and Gs has two mutation hotspots. One makes the arginine at position 201 to cysteine or histidine; the other makes 227 glutamine to arginine or leucine, which is extremely important for the GTPase activity of Gs. Mutations cause a decrease in the GTPase activity of Gs, resulting in a continuous activation of the Gs signaling system, and thus an increase in cAMP production. In pituitary cells, cAMP is not only involved in the synthesis and release of hormones, but also involved in cell proliferation. It has been found that cholera toxin transgenic The proliferation of the pituitary of mice indicates that the activation of the Gs signaling system can indeed cause the proliferation of pituitary cells. It is known that about 40% of GH tumors and about 10% of non-functioning pituitary adenomas are associated with mutations in Gs, and the Gs gene is now Proto-oncogene , called gsp, Gi is also a G protein, its function is opposite to Gs, Gi mutation is also related to pituitary adenoma, 2 cases were found in 32 cases of ACTH tumor, and 3 cases were found in 22 cases of nonfunctioning pituitary adenoma There is a mutation in the Gi subunit, and Gi has also been regarded as a proto-oncogene called gip. The relationship between other G proteins and pituitary adenomas is unclear.

The product of ras proto-oncogene, P21ras, plays an important role in cell signal transduction. It has been found that the activation of ras protooncogene is an important cause of many human tumors. The mutation of Ras gene also has certain in human pituitary adenoma. The significance of this study, 11 cases of non-functional pituitary adenoma, 6 cases of GH tumor and 2 cases of PRL tumor, only found in a case of PRL tumor ras mutation, suggesting that ras gene mutation in human pituitary adenoma Rarely, some subsequent studies have reached similar conclusions. It is currently believed that although the mutation of the ras proto-oncogene has an important position in human non-endocrine tumors, it is not a common cause of human endocrine tumors.

PKC is a kind of protein kinase that plays an important role in cell signal transduction. Alvaro et al found that PKC expression in pituitary adenomas was higher than that in normal pituitary tissues; PKC expression in invasive pituitary adenomas was higher, and they also found some Invasive pituitary adenoma has a mutation in PKC, which causes its 294 aspartate to become glycine. This mutation site is located in the V3 region of the PKC molecule, which contains a Ca2 binding site. The above mutation leads to excessive activation of PKC. PKC can regulate the activity of various proteases and collagenases outside the cell. The increase of PKC activity can promote the infiltration of tumors into normal tissues. Therefore, it is believed that the mutation of PKC is related to the invasiveness of pituitary adenomas.

Studies have shown that the expression of PTTG in pituitary tumor tissues is significantly increased, suggesting that PTTG has a certain role in the formation and development of pituitary tumors. At present, the mechanism of action on PTTG is still unclear, but relevant research has provided some information, The PTTG protein contains a SH3 docking motif, suggesting that it is involved in cell signaling. Human PTTG protein also induces expression of fibroblast growth factor (FGF), which promotes cell growth and angiogenesis, thus PTTG protein may play a tumorigenic role by affecting cell signal transduction and promoting the expression of FGF.

Some studies have shown that the expression of cmyc and c-fos in some pituitary adenoma cells is increased, suggesting that these proto-oncogenes may also be involved in the development of pituitary adenomas. Pituitary adenoma cells can produce many biologically active substances, including hypothalamic pituitary. Release hormones (TRH, CRH, GHRH), growth factors, etc. These biologically active substances may also play a role in the development of pituitary adenomas.

(2) Abnormalities of hormone receptors: hypothalamic hormones or factors can act on receptors on the surface of pituitary cells, and the number and/or affinity of these receptors are altered, expression abnormalities, receptor-G protein-effect Coupling abnormalities play an important role in the development of pituitary adenomas.

1 dopamine receptor: dopamine receptors have DL, D2, D3, D4, D5 five subtypes, they are G-protein coupled receptors, pituitary cells express D2 subtype, it has D2A and D2B 2 aliens Body, these two isoforms are formed due to different splicing of mRNA, D2B is slightly shorter than D2A, and its signal transduction ability is lower than D2A.

2 Somatostatin (SS) receptors: SS receptors (SSTR) have five subtypes: SSTR1, SSTR2, SSTR3, SSTR4 and SSTR5, which bind with high affinity to SS-14 and SS-28, SS is similar Octopidine has higher affinity with SSTR2 and SSTR5, moderate affinity with SSTR3, and lower affinity with SSTR1 and SSTR4. The inhibition of GH release by SS and its analogues is mainly mediated by SSTR2: SSTR2 can be activated. Inhibition of AC activity, opening K channel, cell hyperpolarization, and voltage-dependent Ca2 channel closure on the cell membrane, causing [Ca2]i decline, thereby inhibiting the release of GH, SS and its analogues inhibiting GH cell proliferation It is mainly achieved by activation of phosphotyrosine phosphatase, which is mediated by SSTR2 and SSTR5.

GH tumor cells express a variety of SSTR subtypes, of which SSTR2 and SSTR5 are more important. When these two subtypes are activated, the levels of [Ca2]i and cAMP can be reduced, so that both GH release and GH cell proliferation can be inhibited. In vitro binding experiments showed that the number of SS binding sites is related to the reactivity of tumors to SS analogs. The more binding sites, the better the therapeutic effect of SS analogs. The SS binding sites of gsp mutant GH tumors are generally better. More, this tumor responds better to octreotide.

The nucleic acid hybridization technique was also used to detect the mRNA of various subtypes of SSTR in PRL tumors, ACTH tumors, TSH tumors and non-functioning pituitary adenomas, indicating that these tumor cells also have SSTR expression, which can also be caused by activation of these receptors. Decreased levels of Ca2]i and cAMP suggest that they also function, but the SSTR on some tumor cells excites [Ca2]i, which may be due to abnormal coupling of the SSTR-G protein-effector.

3TRH receptor: TRH receptor also belongs to GPCR, which is coupled with Gq. After excitation, it activates phospholipase C (PLC), which increases [Ca2]i, and most PRL tumor cells have high affinity TRH receptors, but these Tumors do not respond to TRH, the cause is unknown, speculation may be related to post-receptor defects, TSH tumors are rare, it is not clear whether TRH receptors are included, some scholars believe that TSH tumors are not based on the fact that most TSH tumors do not respond to TRH Expression of TRH receptor or expression but no expression of product, contrary to PRL tumor and TSH tumor, many GH tumors (40% to 50%), non-functioning pituitary adenoma (30% to 50%), ACTH tumor (20 30%), gonadotropin tumors (70% to 80%) respond to TRH, indicating that these tumors express TRH receptors, which has no therapeutic significance but has certain diagnostic value.

4GnRH receptor: GnRH receptor also belongs to GPCR. After excitatory activation, phospholipase C can be activated to increase [Ca2]i, resulting in a series of effects. Most gonadotrophomas express GnRH receptor and respond to GnRH. Some gonadotropinomas do not respond to GnRH, probably because of the defective GnRH receptor signaling system in these tumors. The GnRH receptor of gonadotrophinoma cells is significantly different from the normal GnRH receptor: the latter It is desensitized when stimulated by persistent GnRH, ie no longer responds to GnRH; the former has no desensitization, ie it still responds to the continuous stimulation of GnRH, due to the absence of desensitization of the GnRH receptor of gonadotrophinoma Phenomenon, long-acting GnRH analogues are not effective against these tumors.

15% to 20% of GH tumors and ACTH tumors also express GnRH receptors. These patients have significantly elevated blood GH or ACTH levels after GnRH administration, indicating that these receptors are functional, most patients with nonfunctioning pituitary adenomas Increased levels of blood gonadotropin and/or subunits after receiving GnRH indicate that GnRH receptors are also present in non-functional pituitary adenomas.

5GHRH receptor: Most GH tumors express GHRH receptors. These tumors respond to GHRH. Nucleic acid hybridization studies show that there is no correlation between GH tumor response to GHRH and GHRH receptor mRNA levels. Other pituitary adenomas such as PRL tumors, ACTH tumors and non-functional pituitary adenomas also contain GHRH receptors, but the expression levels are low, these tumors also have poor response to GHRH, and GHRH receptors have no desensitization.

6CRH receptor: CRH receptor is also a GPCR. AC activation activates AC, ACTH tumor expresses CRH receptor, which is the basis of their response to CRH. The CRH receptor of ACTH tumor is neither regulated by cortisol. Also, it is not regulated by CRH, and non-ACTH tumors rarely express CRH receptors.

2. The abnormality of the adjustment mechanism

It has long been suggested that the abnormality of the hormone regulation mechanism is an important cause of pituitary adenoma. The evidence supporting this theory is that hypothalamic GHRH tumor and CRH tumor can cause pituitary GH tumor and ACTH tumor, respectively; ectopic GHRH can also Causes GH tumor, but the effect is weaker than that of hypothalamic GHRH tumor (the reason may be that the GHRH produced by the latter directly enters the pituitary portal system, so the GHRH concentration in the pituitary is higher). In recent years, animal experiments have proved that GHRH transgenic mice are extremely easy. The occurrence of GH tumors, these indicate that the hypothalamic pituitary hormone release hormone plays an important role in the occurrence of pituitary adenomas. Then, can the hypothalamic pituitary hormone (factor) deficiency also cause pituitary adenomas? Persuasive evidence, some studies have shown that there is no decrease in hypothalamic dopamine levels in patients with PRL tumors, suggesting that hypothalamic inhibitory factors may not play an important role in the pathogenesis of pituitary adenomas.

A decrease in peripheral target gland hormone levels may attenuate its inhibition of the pituitary gland, thereby promoting the proliferation of the corresponding pituitary cells. For example, in patients with Cushing disease, the resection of the bilateral adrenal glands may transform the existing ACTH microadenomas into large adenomas ( Nelson syndrome), studies have shown that the incidence of pituitary adenoma in primary hypogonadism is not higher than the general population; primary hypothyroidism, although TSH cell proliferation but rare TSH tumor, these tips peripheral The lack of target gland hormones is not the initiating factor in the development of pituitary adenomas.

In recent years, some scholars have used molecular biology techniques to study the clonality of pituitary adenoma cells, which has led to a new understanding of the mechanism of pituitary adenomas. According to the theory of hypothalamic dysregulation, pituitary adenomas should be more The origin of cloning; according to the theory of pituitary origin, pituitary adenomas should be of monoclonal origin. Studies by Alexander et al. have shown that almost all pituitary adenomas are of monoclonal origin, a result that strongly supports the theory of pituitary origin, however, Does not mean that hypothalamic regulatory mechanisms do not play a role in the development of pituitary adenomas. In fact, the occurrence of pituitary adenomas may be multistage, which begins with the internal abnormalities of pituitary cells (such as genetic mutations). On the basis of this, the following disorder of the regulation of the thalamus further stimulates the proliferation of pituitary cells, and finally forms a tumor. The abnormal regulation mechanism of the hypothalamus may be a promoting factor for the formation of pituitary adenoma, but long-term excessive hypothalamic promoting pituitary hormone release stimulation May induce mutations in the corresponding pituitary cells, which may explain why hypothalamic pituitary hormone tumors can cause It should pituitary adenoma.

Randomized autopsy and population census results with high-resolution MRI showed that small asymptomatic pituitary adenomas are quite common (about 10%), but the prevalence of clinically dominant pituitary adenomas is very low (1/500). ~1/1000), which indicates that the abnormality of the pituitary gland in the pituitary adenoma is quite common, but it must be combined with other factors that promote pituitary cell proliferation to further form a dominant pituitary adenoma, affecting the pituitary gland. The factors of cell proliferation may not be limited to hypothalamic hormones or factors. Local autocrine/paracrine factors and certain gonadal peptides of pituitary gland also play an important role. They may also participate in the development of pituitary adenomas.

Some studies have suggested that pituitary adenomas are associated with viral infections. It has been reported that mice infected with murine polyomavirus are prone to pituitary adenomas; polyomamiddle T antigen transgenic mice are also susceptible to pituitary adenomas. However, these studies have not been confirmed by human epidemiological data, indicating that viral infection has little to do with human pituitary adenomas.

The normal pituitary gland seen during operation is orange-red and tough, while the adenoma is often purplish red and soft, and some are muddy. When there is degeneration, the tumor tissue can be grayish white; some with tumor necrosis, bleeding Or cystic changes, combined with autopsy material under light microscopy, pituitary adenoma has a boundary outside, but no capsule, large adenoma part can be the capsule of the pituitary gland, the tumor tissue is different from the pituitary tissue, in general, Tumor cells are more consistent in morphology, but round, cuboidal or polygonal. The size of the tumor cells varies greatly: small is similar to lymphocytes, only a small amount of cytoplasm outside the nucleus, these are mostly undifferentiated stem cells; The cytoplasm is more, which can be filled with some particles or foamy. The size of the tumor cells is relatively uniform, and the large nucleus and the dinucleus are also common. Occasionally, the annular nucleus is the nucleus concave, and a part of the cytoplasm is encapsulated into the nucleus. See nuclear division.

Pituitary adenoma prevention

There is no effective preventive measure for this disease. Early detection and early diagnosis are the key to the prevention and treatment of this disease.

Pituitary adenoma complications Complications brain subarachnoid hemorrhage nasal septum perforation diabetes insipidus fibrosarcoma

1. Complications of surgical treatment

(1) Intra-saddle complications: including internal carotid artery injury (0.4% to 1.4%), can cause pseudoaneurysm, internal carotid artery-cavernous fistula, postoperative large vasospasm, occlusion, and cranial nerve injury ( It accounts for 0.4% to 1.9% of the total, especially for nerve damage.

(2) Complications caused by operation on the saddle: including hypothalamus, pituitary stalk, pituitary injury; optic nerve, optic chiasm and peripheral blood vessel damage leading to vision loss or blindness (0.4% to 2.4%), the latter can also be residual tumor Bleeding, swelling, excessive packing in the saddle, etc.; cerebrospinal fluid leakage (1.5% to 4.2%, very high 9% to 15%) caused by rupture of saddle and arachnoid damage, can cause cranial and meningitis 0% to 2%); other subarachnoid hemorrhage, double epidural hematoma, epilepsy and so on.

(3) transsphenoidal approach and sphenoid sinus complications: may have nasal septal perforation (3.3% ~ 7.6%), upper lip and teeth numbness, nasal deformity, maxilla, humerus, ethmoid fractures, sphenoid sinusitis (1 %~4%) or abscess, as well as damage to the internal carotid artery stenosis in the sphenoid sinus cavity on both sides of the inferior wall of the sella (the arterial surface covers the bone defect, only about 4% of the mucosa) and on the sphenoid sinus cavity The lateral side (the lower middle wall bone defect with optic nerve hole) damages the optic nerve.

(4) Endocrine symptoms: 10% to 60% of patients may develop diabetes insipidus, most of which are transient, 0.5% to 15% of persistent, and 1% to 10% of postoperative pituitary dysfunction. It is a large adenoma, and there are patients with hypopituitarism before surgery.

2. Complications after radiotherapy

(1) Radioactive necrosis: the peak period of general incidence is 1 to 3 years after radiotherapy. If the radiation dose is 45Gy, the incidence rate is only 0.4%. The site may involve the inner side of the bilateral frontal lobe, and the anterior medial aspect of the temporal lobe is hooked back. Hypothalamus and optic chiasm, the anterior wall of the third ventricle, etc., clinical manifestations of vision, increased visual field symptoms, hypothalamic symptoms and headache, nausea, etc., often mistaken for tumor recurrence, treatment with supportive therapy, giving a lot of vitamins, energy Mixture and alternative hormone therapy.

(2) New organism formation: the most common glioma, meningioma, fibrosarcoma, the risk of occurrence is 9 to 16 times that of the normal population, often occurring after several years or even 10 years.

(3) hypopituitarism: after 8 to 10 years of follow-up, the incidence rate is 13% to 30%, or even higher, manifested as gonads, thyroid and adrenal axis dysfunction, requiring hormone replacement therapy.

(4) Other complications: such as intratumoral hemorrhage or cystic change, empty sella syndrome, optic nerve damage, etc., are characterized by re-reduction of visual acuity, and may also be mistaken for tumor recurrence.

Pituitary adenoma symptoms Common symptoms Amenorrhea do not ovulate pituitary dysfunction nasal congestion diffuse headache oculomotor nerve paralysis saddle deformation

The doubling time of pituitary adenoma cells is 100-700 days, so the tumor grows slowly. This biological characteristic determines that the pituitary adenoma is generally insidious, early can be asymptomatic, and some tumors even have no symptoms from beginning to end. The autopsy was discovered. Pituitary adenomas mainly have intracranial nerve dysfunction and endocrine dysfunction:

Neurological dysfunction

The neurological symptoms caused by pituitary adenomas are directly related to the size of the tumor and its growth direction. Generally, the adenomas without secretory function often have a large tumor volume at the time of diagnosis, and the growth of multiple saddles and saddles is more obvious. Because of the early endocrine hyperthyroidism, the adenomas are mostly small in size. The tumors are mostly located in the sella or slightly on the saddle. There is no clinical or only mild neurological symptoms.

(1) Headache: About 2/3 of patients without secretory pituitary adenoma may have headache, but it is not too serious. Early headache is caused by the saddle of the third branch of the trigeminal nerve when the tumor grows upward. Located in the sacral region, forehead, nasal roots or posterior part of the eyeball, intermittent attacks. The headache can be alleviated or disappeared after the tumor penetrates the saddle. Late headache may affect the skull base, arterial ring, large blood vessels due to tumor enlargement. Caused by pain-sensitive tissues such as the large sinus, such as the dura mater supplied by the trigeminal or posterior cranial nerves, the headache is located in the anterior or posterior occipital region, the tumor grows to the third ventricle, and the interventricular pores are blocked to cause intracranial Increased pressure can cause diffuse headache. Sometimes intratumoral hemorrhage or tumor cyst rupture can cause acute severe headache. The headache caused by GH adenoma is obvious and stubborn. Most of them are full headaches. The reason is that in addition to tumor growth, pulling the saddle, mainly It is because the entire skull and dural hyperplasia, caused by stimulation of the sensory nerve.

(2) symptoms of optic nerve compression: pituitary adenomas grow upwards can be placed at the top of the saddle or break the saddle to oppress the optic nerve to produce vision, visual field changes.

1 visual field change: the position of the optic chiasm and the pituitary varies greatly, so the visual field changes are quite inconsistent. Because the retinal fibers and the macular fibers have a certain position in the optic chiasm, there is a certain order of visual field defects, and the tumor is from the saddle. Upward growth can oppress the lower and the rear of the optic chiasm, pushing the cross-over to the upper and upper, and even erecting the optic chiasm. At this time, the first oppression is the fiber in the lower quadrant of the retina below the cross, causing the upper quadrant of the temporal field. Defect, the tumor continues to grow, which may involve the upper quadrant of the retinal nucleus in the nucleus of the optic chiasm, thus producing a defect in the temporal side of the temporal quadrant. At this time, the sacral side is blunt, and sometimes the fiber in the upper quadrant of the retina is mixed and not crossed. In the fiber, it is located on the side of the optic chiasm, so the small field of view can be preserved in the temporal hemianopia, called the "small side island", the compression and the outer retinal outer quadrant of the outer fiber (not intersecting), can produce the view of the nasal lower quadrant In the defect, the fiber in the outer quadrant of the outermost retina of the optic chiasm is the least susceptible to oppression, so the field of view of the upper quadrant of the nose Preserved until the final pressure after the loss.

If the tumor is located behind the optic chiasm, it may involve the macular fiber located at the posterior part of the optic chiasm, and the dark spot of the central visual field appears, which is called the dark-point visual field defect. The development sequence is also the same as the peripheral visual field, and gradually with the peripheral visual field defect. When the early disease, such as the peripheral visual field, is less affected, the dark spot of the central visual field should be examined at the same time, so that the misdiagnosis is not caused. If the tumor grows to one side and oppresses the optic tract, the same direction hemianopia may occur. This is rare. A small number of anterior-posterior patients, the tumor grows to the top of the saddle, and there is no visual field disorder.

It must be noted that the change of visual field is firstly the defect of colored visual field, and the red visual field defect is the earliest. Therefore, for early cases, the application of small test or colored visual mark is the most easy to find the problem, and the early diagnosis is obtained. In general, the visual field changes and Tumor size is parallel, but if the tumor develops very slowly, even if the tumor is large, because the optic nerve can be avoided, there is no visual field change; if the tumor grows quickly, the dark spot often appears first.

2 vision changes: vision loss and visual field defects are not parallel, both sides are also asymmetrical, often appear in the late stage, and can develop blindness, which is mainly the result of primary atrophy of the optic nerve.

3 optic disc changes: due to optic nerve compression and blood circulation disorders, most patients have primary atrophy of the optic disc, and most of the two sides start at the same time, but the degree is not equal, a few can start on one side, the atrophy starts from the nasal side first, In a small number of cases, due to obstructive hydrocephalus, increased intracranial pressure, retinal venous return disorder, optic disc edema may occur, but if the primary optic disc atrophy has occurred, even if there is a cranial hypertension, it will not cause optic disc edema, because At this time, the arachnoid sheath around the optic nerve has been closed, preventing the appearance of optic disc edema. In a few cases, the tumor is biased to one side, which can cause primary atrophy of the optic nerve and contralateral disc edema (Foster-Kennedy syndrome).

(3) Adjacent symptoms: The tumor is caused by the growth of the adjacent structure outside the saddle.

1 to the lateral development: compression or invasion of the cavernous sinus, can produce the third, IV, VI on the cranial nerve and the first branch of the trigeminal nerve, which is most often involved in the oculomotor nerve, causing one side of the eyelid drooping, eye movement disorders, Tumor grows around the internal carotid artery, which can gradually narrow or occlude the lumen of the artery, resulting in hemiplegia, aphasia, etc. The tumor grows into the trigeminal semilunar sac, which can produce secondary trigeminal neuralgia and grow into the skull. The litter can affect the temporal lobe, and there are hook-back episodes, such as magical smell, illusion, hemiparesis, aphasia and other symptoms.

2 development forward: can oppress the frontal lobe and produce mental symptoms, such as apathy, euphoria, sharp decline in intelligence, forgetfulness, inability to take care of themselves, epilepsy, unilateral or bilateral olfactory disorders.

3 development to the rear: can grow into the inter-foot fossa, oppress the cerebral and oculomotor nerves, causing one side of the oculomotor nerve paralysis, contralateral hemiparesis, that is, Weber syndrome.

4 to grow upwards: affect the third ventricle, can produce hypothalamic symptoms, such as polydipsia, polyuria, lethargy and mental symptoms, such as recent forgotten, fiction, hallucinations, poor orientation, dullness, as well as optic disc edema, coma and so on.

5 to grow below: can destroy the saddle bottom into the sphenoid sinus, nasopharyngeal, resulting in repeated small nose bleeding, nasal congestion and cerebrospinal fluid rhinorrhea.

6 outward growth: can grow into the internal capsule, basal ganglia, etc., resulting in hemiplegia, sensory disturbances and so on.

2. Endocrine dysfunction

Various types of secretory adenomas can secrete too many hormones, which can produce different symptoms of endocrine hyperactivity in the early stage. Non-secretory adenomas can compress and destroy pituitary cells, causing hormone reduction and corresponding target cell dysfunction, and clinical endocrine function. Reduced symptoms, a small number of endocrine adenoma cases can also produce hypopituitarism in the late stages of the disease.

(1) PRL adenoma: more common in young women (20 to 30 years old), male cases account for about 15%, due to increased PRL inhibition of hypothalamic gonadotropin-releasing hormone secretion, estrogen decreased, LH, FSH secretion is normal or Lowering, there is also a belief that high PRL blood affects the negative feedback of normal estrogen and the synthesis of progesterone. The clinical manifestation is amenorrhea-galactorrious-infertility triad (called Forbes-Albright syndrome), and a few are not fully equipped. In the above three joints, when the PRL is increased to 60g/L, menstrual disorders may occur, such as less menstruation, delay, or menstruation but no ovulation, progesterone deficiency, luteal phase is not significant, etc., with the further increase of PRL, amenorrhea may occur. Amenorrhea cases are accompanied by galactorrhea, but most of them squeeze a small amount of milk when they are squeezed; some patients are not accompanied by galactorrhea, others may have loss of libido, miscarriage, obesity, facial flushing, etc., in adolescents There may be a delay in development, primary amenorrhea, because estrogen can promote the proliferation of PRL cells, so clinically, PRL tumors occur after pregnancy, oral contraceptives (especially those with low estrogen activity) and PRL tumors occur. turn off.

Men with high PRL can cause blood testosterone production and metabolic disorders, blood testosterone reduction, spermatogenesis disorders, decreased number, decreased vitality, abnormal morphology, clinical impotence, sexual dysfunction, infertility, testicular shrinkage, a small number of hair Rare, obese, breast development and galactorrhea (about 20%).

Female patients can be diagnosed early, and 2/3 cases are saddle microadenomas (tumor diameter <10mm). Neurological symptoms are rare. Male patients often do not pay attention to early symptoms of libido, so most of the tumors are larger and salvage at the time of diagnosis. Growing up, causing headaches and visual symptoms, etc., there are many reasons for high PRL, and other causes must be excluded before the diagnosis of this disease.

(2) GH adenoma: GH promotes growth mainly through the action of the liver on various cells containing GH receptors. GH adenomas occur as a "giant disease" before puberty closure. In adults, it is characterized by "acromegaly", which was first described by Marie (1886). The course of the disease develops slowly, often only 6 to 9 years before it is diagnosed.

1 giant disease: patients (most before the age of 15) early height abnormalities, even up to 2 meters, and the growth is extremely rapid, the weight is far more than the same age, the external genitalia develops like an adult, but no sexual desire, increased hair, great strength After adulthood, about 40% of patients may have acromegaly changes. In the advanced stage, there may be general weakness, mental decline, hair loss, dry skin shrinkage, lethargy, headache, and urine collapse. The patient died early and the average life expectancy is 20 Years old.

2 acromegaly: the patient's hands, feet, thoracic and thoracic limbs are progressively enlarged, the hands and feet are thick, the fingers are thickened, the distal end is spherical, the forehead is raised, the ankle, the tibia and the lower jaw are prominently prominent, forming the so-called "Jaw deformity", widening of the teeth, the jaw of the jaw is farther, the lips are thicker, the bridge of the nose is wide and flat, the auricle is enlarged, the hat, shoes and socks are often replaced with large size, rough skin, pigmentation, hair Increased, scalp sagging, more oily, sweaty, female patients look like men, some patients with kyphosis due to excessive spine growth, clavicle, sternum overgrown and lordosis, can also be barrel chest due to enlarged chest, due to Tongue, pharynx, soft palate, uvula are hypertrophy, hoarse voice when speaking, easy to snoring during sleep, tuber wall hypertrophy can cause stenosis, lung function is affected, heart hypertrophy, a few can develop heart failure, blood vessel wall thickening, Increased blood pressure, sometimes stroke can occur, other such as gastrointestinal, liver and spleen, thyroid, thymus, etc. can be hypertrophy, due to tissue hyperplasia can cause multiple pain, in addition to headache, patients often early due to body pain Misdiagnosed as "rheumatoid arthritis", due to thickening of the transverse ligament of the wrist can compress the median nerve to produce carpal tunnel syndrome, spinal hyperplasia makes the intervertebral foramen narrow and oppress the spinal nerve root, causing back pain or paresthesia, due to bones, joints, cartilage Hyperplasia can cause limb pain, joint pain, limited mobility, etc., due to spinal canal hyperplasia, can produce spinal cord compression, a few women have menstrual disorders, amenorrhea (with galactorrhea may be GH-PRL mixed adenoma), early men Sexual stagnation, decreased in the late stage, resulting in no desire, impotence, sometimes genital atrophy, both sexes can be infertile, about 20% of patients may have mucinous edema or hyperthyroidism, such as sweating, sweat odor and exophthalmia, About 35% of patients have diabetes, the patient gains weight in the early stage due to polyphagia, late weight loss, polyuria, polydipsia, genital itching, foot gangrene, diabetic retinitis, and even diabetes coma, blood sugar may rise High, half of patients with urine glucose positive, impaired glucose tolerance, elevated blood lipids, increased blood phosphorus, a small number of blood calcium, blood alkaline phosphatase can also increase, patients early Energetic and irritating; late in exhaustion, lack of concentration, lack of interest in the outside world, poor memory, GH adenoma if not treated, often due to metabolic complications, diabetes, secondary infection, heart, cerebrovascular and respiratory diseases And die.

Acromegaly caused by GH adenoma should be differentiated from ectopic growth hormone releasing factor syndrome, which secretly secretes GHRF, which causes GH cells to proliferate and secrete excessive GH. This condition is rare: A. Hypothalamic nerve Gangliomas, can be combined with acromegaly, more common in 40 to 60 years old, in addition to changes in acromegaly, there are headaches, visual field impairment, diabetes, amenorrhea, galactorrhea, gonads and adrenal insufficiency and other symptoms, B. Heterotopic tumors such as lung, thymus, pancreas, gastrointestinal, etc., may also have changes in acromegaly and corresponding clinical symptoms. Blood GH, interleukin-C and immunoreactive growth hormone releasing factor (IR-GRF) are increased. GH is not inhibited by glucose, and systemic CT or MRI can sometimes detect ectopic tumors.

There are a few patients with GH adenoma whose tumor size, GH value and clinical manifestations are not consistent. For example, if the tumor is large or the GH is significantly increased, the clinical manifestation is slight, or the blood GH value is not significant, but the symptoms are obvious. The reasons are as follows: A. It is related to the length of the disease. In about 20% of cases, the GH value is <5~10g/L, but the clinical symptoms are obvious. Otherwise, there may be a significant increase in GH, but the duration is not long. The symptoms are not as obvious as the GH is slightly elevated and lasted for a long time. B.GH has two kinds of immunological activity (large GH) and biological activity (small GH). Most of GH adenomas secrete highly biologically active GH, and a few secretory secretions have immunological activity. GH, clinical symptoms are more obvious with biologically active GH, C. GH promotes growth in vivo through the growth of liver cells, estrogen can reduce the activity and concentration of interleukin in plasma, thereby reducing Systemic effect of GH, when estrogen is reduced in patients with GH tumors (such as menopausal patients or tumors affecting the release of estrogen from pituitary gonadotropin), the clinical symptoms are significant, and stroke occurs in D. GH tumor, causing degeneration necrosis Cystic Who can relieve symptoms go even larger tumor volume, which value can be increased GH vain, symptoms may remain stable long time.

(3) ACTH adenoma (Cushing's disease): more common in young adults, mainly female, most of the tumors are small, do not produce neurological symptoms, and even difficult to be detected by radiological examination, this disease is characterized by excessive secretion of ACTH by tumor cells and Related to the polypeptide, leading to adrenal hyperplasia, producing high cortisolemia, which can cause a variety of metabolic disorders in the body, showing typical Cushing's syndrome, which was first described by Cushing in 1932. Named after the patient of the syndrome, and suggested that pituitary basophil adenoma may be the cause, the clinical symptoms of the disease are as follows:

1 fat metabolism disorder, can produce typical "central obesity", the patient's head, face, neck and trunk increased fat, the face is round (called full moon face), the spine is protruding backwards, there is fat in the neck and back junction The layer forms a "buffalo back", but the limbs are relatively small and have atherosclerotic changes in the late stage.

2 protein metabolism disorders, can lead to excessive protein consumption in the skin, bones, muscles, etc., collagen fibers break in the skin, dermis, subcutaneous blood vessels are exposed and appear "purple" (see in the lower limbs, thighs, buttocks and upper arms) And facial plethora, due to osteoporosis of the spine and skull, about 50% of patients have low back pain, vitamin D deficiency, rickets and pathological compression fractures, children can affect bone growth, due to vascular fragility Increased and easy to produce skin ecchymosis, wounds are not easy to heal, easy to infect.

3 disorders of glucose metabolism, can cause steroid-induced diabetes (20% to 25%), manifested as polydipsia, polyuria, increased fasting blood glucose, decreased glucose tolerance, generally more lightweight and reversible.

4 electrolyte metabolism disorder, seen in a small number of patients, late in the blood potassium and blood chlorine, blood sodium increased, causing low potassium, low chloride alkalosis.

5 gonad dysfunction, hypercortisolemia can inhibit pituitary gonadotropin secretion, female patients with blood testosterone increased significantly, 70% to 80% of amenorrhea, infertility and varying degrees of masculinity, such as breast atrophy, increased hair, Hemorrhoids, increased laryngeal nodes and low sonication, male patients with decreased blood testosterone caused by loss of libido, impotence, testicular atrophy, etc., children with growth and development disorders.

6 hypertension, about 85% of cases have high blood pressure, long-term high blood pressure can be complicated by left ventricular hypertrophy, heart failure, arrhythmia, stroke and renal failure.

7 psychiatric symptoms, about 2 / 3 patients have psychiatric symptoms, mild insomnia, emotional instability, susceptibility to stimulation, memory loss; severe psychosis.

8 anti-viral resistance, increased cortisol can reduce antibody immune function, so that the lysosomal membrane remains stable, is not conducive to the elimination of antigen, resulting in significant decline in anti-infective function, such as skin susceptible to fungal infection, bacterial infection is difficult to control, and often long Not healed.

Nelson's syndrome was proposed by Nelson in 1958. After suffering from Cushing's syndrome for bilateral adrenalectomy, 10% to 30% of patients may have pituitary tumors 1 to 16 years after surgery. Most of the tumors are considered to be original. Cortisol is caused by ACTH microadenomas, but the tumor is very small, the examination was not found, or was ignored without further examination. After bilateral adrenalectomy, negative feedback of CRH in the hypothalamus due to lack of cortisol The role of CRH can cause long-term stimulation of the pituitary gland to cause adenoma, or the original ACTH microadenomas rapidly grow up, secrete a large amount of ACTH and MSH to produce whole body skin, mucosal hyperpigmentation, clinically known as Nelson syndrome, Some researchers believe that this syndrome is easy to occur in young women (under 30 years old), pregnancy is more likely to occur after resection of the adrenal gland, 10% to 25% of the disease is aggressive, easy to grow into the saddle dura, bone And cavernous sinus, etc., produce cranial nerve palsy, and can be transferred to other parts of the brain and extracranial, a small number of patients may have increased PRL and galactorrhea, may be hypothalamic dysfunction or pituitary adenoma compression of the hypothalamus, resulting in Attenuating PIF inhibition results in increased PRL secretion.

Among the causes of hypercortisolemia, 60% to 80% are ACTH and its related polypeptide adenomas, and 15% to 25% are adrenal tumors (including adrenal adenomas and carcinomas), 5% to 15%.ACTH()

(4)(GnHFSHLH)()3

FSHFSH-LHLHFSH

LHLHFSHFSHFSH(E2)FSH

FSH/LHFSHLH

(5)TSHTSHTSHTSHTSH

(6)

(7)PRLGHPRL

(8)GHPRL

(9)305040%PRL35%FSHLH10%-TSHFSH(LH)PRLGH

Laboratory inspection

1.(GH)

GHGHGH12hGH24g/L90%GHGH10g/LGH510g/LGH100g2hGH34hGH1(IGF-1)24h GHCHGHTRHGHGHGHGHGHGH

2.ACTH

ACTH(80%)<5mm60%70%CT30%1.5TMRI50%60%CTMRI

ACTHACTH--ACTHACTH(81022pg/ml10119.6pg/ml)ACTH;(2030g);(UFC2080g/24h)>100µg(ACTHACTH)ACTH24h(UFC/24h)(50%)ACTH()ACTH()17-OHCS80%UFC/24h92.5%ACTHACTHCRH

3.

TSHTSHTSH510U/mlTSHTSHTSH(TRHRH)TSH 510

4.

FSHLHFSHLHFSH120g/LLH40g/LFSH/LHFSH/LHFSHLH

5.

MSH20110pg/mlMSHMSH

6.

1717;

Film degree exam

1.CTMRI

(1)()(1)()3mm1/3()-()()()()()()()

(2)

()8mm>8mmCT91%

2mmCT

CT;MRI

CT

()()()

2.CTMRI

CTMRI(2)

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3.X

;;;;

CTMRI

4.PET

PET2080PET

PRL11C18F(18F-fluorodeoxyglucose18F-FDG)11C-18F-FDG11CD2(methylspiperone)(raclopride)PRL11C

diagnosis

Differential diagnosis

1.70%CTMRI

2.CTMRIT1WT2W

3.CT;MRI

4.MRI

5.XCT

6.XCT

7.

8.CTMRI

9.Rathke

10.CT

11.

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