1. Compression symptoms
Headache (1): seen in 1/3 ~ 2/3 patients, it is not very severe at the initial stage, mainly pain, which can be aggravated intermittently. Headaches are mostly located in temples, foreheads, behind eyeballs or nasal roots. The main cause of headache is that the sellar diaphragm and the surrounding dura mater are pulled by the upward growth of tumors. When the tumor pierces the sellar diaphragm, the pain can be alleviated or disappeared. If the diaphragm of sellar foramen is large, the resistance to tumor growth is small and the headache is not obvious.
Tumors compress adjacent pain-sensitive tissues, such as dura mater and the wall of great vessels, which can cause severe headache, diffuse and often accompanied by vomiting. Tumors invade the hypothalamus and the third ventricle, blocking the interventricular foramen, which can increase intracranial pressure and aggravate headache.
(2) Compression of optic nerve pathway: pituitary adenoma spread to sella turcica and compressed optic chiasma. Can lead to different types of visual field defects, with or without visual loss. This is due to the different growth directions of tumors and/or the variation of anatomical relationship between optic chiasma and pituitary gland. Pituitary tumors can cause the following five kinds of visual field defects and vision loss (see figure 1): ① Bilateral temporal hemianopia. It is the most common type of visual field defect, accounting for about 80%. It is caused by pituitary adenoma compressing the anterior edge of chiasma, damaging nerve fibers from the lower nasal side of retina and then from the upper nasal side. At first, a wedge-shaped area of the outer upper quadrant was blocked, and then the visual field defect gradually expanded to the whole outer upper quadrant and then to the outer lower quadrant, forming bilateral temporal hemianopia. In the early stage, red vision loss occurs first, and it is easy to find the existence of visual field defect in the early stage by taking the red visual target as an examination. Patients' vision is generally unaffected; ② Bilateral scotoma of temporal central visual field (scotoma visual field defect). This kind of visual field defect accounts for 10% ~ 15%. Pituitary tumor compresses the posterior part of optic chiasm and damages macular nerve fibers. In this case, we should check the peripheral and central visual fields at the same time to avoid missed diagnosis. This visual field defect does not affect vision; ③ Homosexual hemianopia. It is rare (about 5%), because the tumor spreads backward and upward or because the patient has anterior chiasma (about 15%), resulting in lateral bundle compression. The patient's vision is normal. This type and the former type of visual field defect can also be seen in hypothalamic tumors, such as craniopharyngioma, hypothalamic neuroma and germ cell tumor; ④ Blindness in one eye. This situation can be seen in patients (about 5%) with pituitary adenoma spreading forwards or backwards. The enlarged tumor compresses one side of the optic nerve, which leads to the decrease or even blindness of the central vision of this side, and the contralateral visual field and vision are normal. ⑤ One side has decreased vision, and the other side has supratemporal visual field defect. This type is rare compared with the former type, because the upward expanding tumor compresses the position where the proximal optic nerve meets the chiasma. There are nerve fibers from the contralateral inferior nasal retina, which form a ring here (anatomically called Wilbrand knee) and then enter the optic chiasma.
Due to the compression of the optic nerve and blood circulation disorder, the optic nerve gradually shrinks, resulting in decreased vision. The occurrence time and severity of vision loss and visual field defect are not necessarily parallel. Obstructive hydrocephalus and optic disc edema in a few patients are caused by increased intracranial pressure and retinal vein reflux disorder.
(3) Other symptoms: When the tumor spreads to both sides of the sella turcica and compresses the cavernous sinus, it can cause the so-called cavernous sinus syndrome (third, fourth, fifth and sixth cranial nerve damage). When the oculomotor nerve located in it is damaged, diplopia may occur. Generally, unilateral oculomotor nerve paralysis is relatively rare. If it appears, it suggests that there may be an invasive tumor invading the cavernous sinus. The sixth cranial nerve is protected by the internal carotid artery, and the damage probability is less than that of the third and fourth cranial nerves. The loss of skin sensation in the area dominated by the ophthalmic branch and maxillary branch of trigeminal nerve is also caused by the invasion of cavernous sinus. Some patients can still lose their sense of smell due to olfactory nerve damage. Giant adenomas can invade the hypothalamus. The tumor pressed the hypothalamus without invasion, and there was no obvious hypothalamic dysfunction. If you invade it, you may have a series of symptoms such as diabetes insipidus, lethargy, and disorder of body temperature regulation. If the tumor compresses the third ventricle and blocks the interventricular foramen, it will cause hydrocephalus, increased intracranial pressure and aggravated headache. Tumors can occasionally spread to the frontal and temporal lobes, causing epileptic seizures, hemiplegia, pyramidal signs and mental symptoms. When the tumor erodes the sellar floor and sphenoid sinus, it can cause cerebrospinal fluid rhinorrhea. Some patients with pituitary adenoma found that cerebrospinal fluid pressure increased and protein increased, but the number of cells did not increase, and the sugar content in cerebrospinal fluid increased.
2. Abnormal hormone secretion syndrome
(1) Decreased pituitary hormone secretion: Generally, the decrease of pituitary hormone secretion in patients with pituitary adenoma is light and the progress is slow. It was not until 3/4 glands were destroyed that obvious symptoms of pituitary hypofunction appeared in clinic. Even if the tumor is large, the symptoms of hormone deficiency rarely reach the severity after pituitary resection. Therefore, generally speaking, pituitary adenomas are less prone to symptoms of decreased pituitary hormone secretion, especially functional adenomas. However, sometimes the decrease of pituitary hormone secretion can also become a prominent manifestation of this disease, especially in childhood, which is characterized by short stature and sexual hypoplasia. Sometimes tumors can also affect hypothalamus and neurohypophysis, and the synthesis and secretion of vasopressin are blocked, causing diabetes insipidus.
Among pituitary adenoma patients with hypopituitarism, 3/4 patients have hypogonadism. Hypothyroidism is not as common as gonadism, but subclinical hypothyroidism (only laboratory evidence of hypothyroidism, no clinical symptoms) is still common. Adrenal cortical function can usually be maintained normally without severe stress, but acute adrenal cortical dysfunction (adrenal crisis) can occur due to insufficient ACTH reserve in pituitary during stress. The patients with pituitary adenoma and hypopituitarism have pale face and pale skin pigment, which may be related to the decrease of melanocyte stimulating hormone secretion. Male patients are slightly obese, and their fat distribution is similar to that of women. Axillary hair and pubic hair are scarce, and the hair is sparse and soft. The pubic hair of male patients is distributed in women. Weight can be reduced, and sometimes weight does not decrease or even increase, which is related to hypothalamic dysfunction. Female patients with amenorrhea or less menstrual flow have decreased sexual desire; In addition to decreased sexual desire and sexual dysfunction, men may also have genital atrophy and soft and small testicles. Patients' intelligence is generally unaffected. In case of stress (such as infection and operation), the patient's resistance is very low, and it is easy to have a crisis or even coma.
Pituitary adenoma can sometimes cause acute pituitary hemorrhage syndrome (pituitary apoplexy) due to hemorrhage and infarction, and its incidence rate is 5% ~ 10%. The onset of pituitary apoplexy is sudden, which is characterized by severe pain on the forehead or the posterior side of the orbit, which can radiate to the face, and rapidly appear different degrees of vision decline. In severe cases, both eyes can be blind within a few hours, often accompanied by extraocular muscle paralysis, especially the third pair of cranial nerves, which can also involve the fourth and sixth pairs of cranial nerves. In severe cases, there will be confusion, disorientation, stiff neck and even coma. Some patients have acute adrenocortical failure. The cerebrospinal fluid of most patients is clear, and some may be bloody. CT showed enlarged sella turcica. Pituitary adenoma is prone to intra-tumor bleeding, especially when the tumor is large. Most of the inducing factors are trauma and radiotherapy. And there may be no obvious inducing factors. Patients with acute visual impairment should be operated as soon as possible under the protection of glucocorticoid. There is no consensus on whether patients with pituitary apoplexy can receive radiotherapy.
(2) Increased secretion of pituitary hormones: Because different functional adenomas secrete different pituitary hormones, their clinical manifestations are also different.
The main points of diagnosis of nonfunctional pituitary adenoma are as follows:
1. Imaging evidence of pituitary adenoma.
2. There are symptoms of pituitary occupying such as headache and visual field defect.
3. No clinical manifestations and laboratory evidence of pituitary hormone excess (except PRL).
4. There is pituitary hypofunction.
5. Because the blood PRL level of most patients with nonfunctional adenoma is elevated, the determination of PRL is of great significance. The blood gonadotropin level in most patients is decreased or within the normal range, but the blood gonadotropin and/or its subunit may be increased in a few patients. Sex hormone levels generally decreased. The levels of TSH, GH and ACTH in blood are generally normal or slightly decreased, and their reserve function and target hormone levels also decreased, but the significant decrease is rare. Occasionally, when the nonfunctional adenoma is subclinical GH tumor or ACTH tumor, the 24-hour urinary cortisol or blood IGF- 1 level may be slightly increased. The response of nonfunctional pituitary adenoma to hypothalamic hormones has certain characteristics, which is of great significance for diagnosis. Common diagnostic tests using hypothalamic hormones are:
(1)TRH test: There is no TRH receptor in normal gonadotropin cells, so injecting TRH into normal people will not cause the increase of blood LH and FSH levels. Most nonfunctional adenomas originate from gonadotropin cells, and about 1/3 of tumor gonadotropin cells contain TRH receptors and respond to TRH. About 40% patients with nonfunctional adenoma have increased gonadotropin and/or its subunit levels after TRH injection.
(2)GnRH test: Most nonfunctional pituitary adenomas originate from gonadotropin cells, and these neoplastic gonadotropin cells contain GnRH receptors, so they all respond to endogenous GnRH, GnRH agonist analogues and GnRH antagonists. Under normal circumstances, the stimulating effect of GnRH on gonadotropin cells depends on its characteristic pulse secretion. If GnRH or long-acting GnRH analogues are given continuously, desensitization will occur, but gonadotropin secretion will decrease. Non-functional adenoma does not have this desensitization phenomenon, which is one of its characteristics. According to Klibanski et al. (1989), a long-acting GnRH analogue DTrp6-Pro9-NEt- is continuously given to patients with nonfunctional adenoma.
After LHRH, the levels of LH, FSH and α subunit in blood all increased.
6. Because of the lack of specific serum hormone markers, the diagnosis of nonfunctional pituitary adenoma is often difficult, and sometimes it depends on pathological examination and immunocytochemical examination of surgical specimens.
Differential diagnosis of intermittent headache;
1, Recurrent Headache Recurrent Headache: Headache is one of the common clinical symptoms, which usually refers to the pain confined to the upper part of the skull, including the eyebrow arch, the upper edge of the helix and the connecting line above the occipital protuberance. Recurrent head diseases.
2, intractable headache: intractable headache: symptoms of persistent headache for many years.
3. Chronic headache: Chronic daily headache (CHD for short) refers to frequent headache attacks 15 days or more every month, and the headache lasts for more than 4 hours every day. There are two types: primary and secondary. Primary coronary heart disease refers to headache 15 days per month, without organic or systemic diseases. A survey shows that 4-5% of the total population in the United States, Europe and Asia suffer from primary coronary heart disease, and chronic tension headache (that is, nervous headache) accounts for the first place in coronary heart disease, and chronic vascular migraine is the main reason for coming to clinic.
Prevention: In some extremely huge pituitary nonfunctional tumors, angiography is sometimes needed before operation to determine the relationship between tumor and blood vessels, so as to avoid damaging blood vessels and accidents during operation.
treat cordially
Like other pituitary adenomas, the treatment of nonfunctional adenomas includes surgical treatment, radiotherapy and drug treatment. At present, surgical treatment is still the first choice. Radiotherapy can be added to patients with poor surgical effect or postoperative recurrence. Drug therapy can be tried for those who have no symptoms of tumor compression. If drug treatment is ineffective, surgery should still be taken.
1. Whether to adopt surgical treatment often depends on the size and clinical manifestations of the tumor. Surgical treatment is generally recommended for patients with obvious compression symptoms and large tumors. Successful operation can effectively alleviate a series of symptoms caused by tumor occupying effect, and immunocytochemical examination can be carried out on surgical specimens, which is of great significance for definite diagnosis. Surgical treatment of asymptomatic microadenomas is not recommended. It is generally believed that patients with visual field defect and nervous system symptoms should be operated as soon as possible to prevent irreversible damage to optic chiasma and cranial nerves. At present, transsphenoidal surgery is mostly used, and about 90% of cases have improved visual field defect, and about 60% cases have completely recovered their vision. The main complication of transsphenoidal surgery is pituitary dysfunction. According to Arafah, the incidence of postoperative GH deficiency, hypothyroidism, adrenocortical hypofunction and gonadal hypofunction were 85%, 35%, 46% and 65% respectively. Obviously, the incidence of postoperative pituitary dysfunction is significantly lower than that before operation, which shows that transsphenoidal surgery is effective in restoring pituitary function. However, transsphenoidal surgery has no good effect on improving GH deficiency, which may be because GH cells are difficult to recover once they are damaged.
2. Postoperative radiotherapy can be used for patients with incomplete surgical resection or postoperative recurrence. The research shows that the recurrence rate of postoperative radiotherapy patients is not lower than that of postoperative radiotherapy patients, and the reason for this result may be the different case selection. At present, most scholars believe that postoperative radiotherapy is of certain significance to improve the prognosis of nonfunctional adenoma. Katznelson et al. suggested to follow up 1 time every six months within 1 year after transsphenoidal surgery, and 1 time every five years, and then every two years. MRI and visual field examination should be done every follow-up. If there are signs of tumor growth, radiotherapy should be started immediately (or transsphenoidal surgery should be considered again). The total dose of conventional radiotherapy is about 45Gy, and the daily dose is1.8Gy. The main side effect of radiotherapy is pituitary dysfunction. According to statistics of Snyder et al. (1986), the incidence of secondary adrenal, thyroid and gonadal hypofunction in 4-5 years after radiotherapy was 62%, 39% and 62% respectively. Therefore, the levels of pituitary hormones and target gland hormones should be determined regularly after radiotherapy.
3. In recent years, great progress has been made in drug treatment of nonfunctional pituitary adenoma, but it is still unsatisfactory. At present, somatostatin analogues and dopamine enhancers are the main drugs used for treatment. GnRH agonists and GnRH antagonists have also been tried in clinic, but they have not been widely used because of their poor effects.