Nonfunctioning pituitary adenoma
Introduction
Introduction to nonfunctioning pituitary adenoma Most pituitary adenomas have a high secretion function, which raises blood hormone levels and produces corresponding clinical symptoms. However, some pituitary adenomas do not increase blood hormone levels, and there are no symptoms of excessive hormones. They are called clinical nonfunctioning pituitary adenomas. They are called nonfunctioning pituitary adenomas. They are also called clinically inactive pituitary adenomas. (clinically inactivepituitaryadenoma, CIPA), endocrine inactiveadenoma or nonsecretory pituitary adenoma, non-functioning adenomas account for 25% to 30% of all pituitary adenomas. Non-functional pituitary adenomas are actually a group of heterogeneous tumors, most of which have a dividing function (mostly gonadotropins), but their secretion function is low, does not cause an increase in blood levels, such tumors Known as silentadenoma, some non-functioning adenomas may indeed have no secretory function, and their cell origin is unclear, called nude cell tumor or uncharacterized cell adenoma (nullcelladenoma). basic knowledge Sickness ratio: 0.0012% Susceptible people: no special people Mode of infection: non-infectious Complications: dehydration, hypernatremia, irregular menstruation, amenorrhea
Cause
Non-functioning pituitary adenoma
(1) Causes of the disease
Non-functional pituitary adenomas are actually a group of heterogeneous tumors, most of which have a dividing function (mostly gonadotropins), but their secretion function is low, does not cause an increase in blood levels, such tumors Known as silent adenoma, some non-functional adenomas may indeed have no secretory function, and their cell sources are unclear, called nude cell adenoma or null cell adenoma.
(two) pathogenesis
There have been two theories in the pathogenesis of pituitary tumors, namely, the pituitary cell self-defect theory and the hypothalamic regulation disorder theory, which are basically unified. It is believed that the development of pituitary tumors can be divided into two stages: the initial stage and the promotion stage. In the initial stage, pituitary cell self-deficiency is the main cause of onset, and factors such as hypothalamic dysregulation in the promotion phase play a major role, that is, mutation of a certain pituitary cell leads to loss of oncogene activation and/or tumor suppressor gene Live, and then promoted by the internal and external factors, the monoclonal mutant cells continue to proliferate and gradually develop into pituitary tumors.
1. Intrinsic Defects of Pituitary Tumor Cells: It is now clear that most functional and non-functional adenomas are monoclonal-derived using molecular biology techniques, resulting from the unrestricted proliferation of a single mutant cell, which is mutated. The reason is the activation of oncogenes and/or the inactivation of tumor suppressor genes. The main oncogenes identified are gsp, gip, ras, hst and PTTG. The tumor suppressor genes include MEN-1, p53, Nm23 and CDKN2A. Among them, gsp gene is found in 40% of GH tumors, 10% of non-functioning adenomas, and 6% of ACTH tumors. Activation of gsp gene and gip2 gene inhibits endogenous GTPase activity, so Gs protein and Gi2 protein The -subunit is continuously activated, and the latter two can be regarded as the products of the gsp oncogene and the gip2 oncogene, respectively. These two oncogene products can directly activate the activation of nuclear transcription factors such as AP-1, CREB and Pit-1. Increases hormone secretion and initiates tumor growth. In addition, oncogene activation leads to increased intracellular cAMP levels. cAMP stimulates cyclin (cyclin) DL and 3 to produce cdk2 and cdk4, which promote cell entry from G1 phase. In stage S, increased cAMP levels can also induce ras cancer gene stimulation , RAS oncogene and synergy cmyc gene prevents binding of pRb F 2F, since the latter will bind the cell cycle is blocked, the combination of the two to prevent accelerated into the cells from G1 to S phase.
The reason for the inactivation of tumor suppressor gene such as MEN-1 is the deletion of the allele at the 13th locus of the long arm of chromosome 11 (11q13). The pathogenesis of various pituitary tumors involves the loss of the tumor suppressor gene P16/CDKN 2A. Live, the frequent methylation of the CpG island of this gene is the cause of inactivation. Therefore, it is possible to develop a therapeutic method to demethylate the CpG island of the tumor suppressor gene and restore its anticancer effect for therapeutic purposes. .
2. Paracrine and autocrine dysfunction: hypothalamic pituitary hormones and paracrine or autocrine hormones in the pituitary may play a role in the promotion of pituitary tumor formation. GHRH promotes GH secretion and mitosis of GH cells. Ectopic tumors secreting GHRH can cause pituitary GH tumors. Animals implanted with GHRH gene can cause GH cell proliferation and induce pituitary tumors. All of the above indicate that increased GHRH can induce pituitary tumor formation, and some growth factors such as FTH-related peptides ( PTHrP), platelet-derived growth factor (PDGF), transforming growth factor alpha and beta (TGF- and TGF-), IL, IGF-1, etc. have higher levels of expression in different pituitary tumors, they may be next to Secretion or autocrine promotes the growth and differentiation of pituitary tumor cells. The lack of nerve growth factor (NGF) promotes the development and progression of PRL tumors. In the developmental stage of normal pituitary gland, NGF promotes the differentiation of prolactin cells. And the role of proliferation, in the treatment of PRL tumors, in patients with insensitivity to dopamine agonists, after the administration of exogenous NGF, NGF promotes further differentiation of tumor cells into Expression D2 receptor protein more similar to the normal prolactin cells, so that the degree of drug resistance can be improved.
3. Hypothalamic regulatory dysfunction: weakened hypothalamic inhibitory factor may also promote tumorigenesis. In patients with adrenal Cushing syndrome, negative feedback inhibition of CRH secretion from hypothalamus is weakened after adrenalectomy. Increased CRH secretion, patients with ACTH adenoma soon, chronic pituitary TSH tumors often occur in patients with chronic hypothyroidism, which is sufficient to demonstrate the lack of normal target glandular hormone negative feedback mechanism and subsequent hypothalamic dysfunction It can play a role in the development of pituitary adenomas.
Prevention
Non-functional pituitary adenoma prevention
In some small-sized pituitary non-functional tumors, angiography is sometimes required before surgery to determine the relationship between the tumor and the blood vessels, to avoid damage to the blood vessels during surgery, and accidents.
Complication
Nonfunctioning pituitary adenoma complications Complications dehydration hypernatremia menstrual irregular amenorrhea
1. Diabetes insipidus: 1 a large number of low specific gravity urine, urine volume more than 3L / d; 2 because the saddle area tumor is too large or outward expansion, often there is compression of the surrounding nerve tissue of the sella, such as vision loss, visual field loss; 3 people with thirst disorders, dehydration, hypernatremia, hypertonic state, fever, convulsions, and even cerebrovascular accidents.
(1) Laboratory inspection:
1 Urine osmotic pressure: 50 ~ 200mOsm / kg H2O, significantly lower than plasma osmotic pressure, plasma osmotic pressure can be higher than 300mmol / L (normal reference value is 280 ~ 295mmol / L).
2 plasma vasopressin value: decreased (normal basal value of 1 ~ 1.5pg / ml), especially when the water is banned and instilled high-osmotic saline can not rise, suggesting that the pituitary vasopressin reserve capacity is reduced.
3 water-free test: it is the most commonly used functional test to help diagnose pituitary diabetes insipidus. Methods: Before the test, the body weight, blood pressure, urine volume, urine specific gravity, urine osmotic pressure, urine urination every hour, urine volume measurement, Urine specific gravity, urine osmotic pressure, body weight, blood pressure, etc., no change in urine volume, urine specific gravity and urine osmotic pressure continue to rise twice, blood osmotic pressure, and subcutaneous injection of vasopressin (aqueous agent) 5U Collect urine volume every hour, measure urine specific gravity, urine osmotic pressure 1 or 2 times, generally need to ban water for 8 ~ 12h or more, if blood pressure drops, weight loss is more than 3kg, the test should be terminated, normal people or mental annoyance Thirsty, the amount of urine after the water is reduced, urine specific gravity, urine osmotic pressure is increased, so blood pressure, body weight often does not change significantly, plasma osmotic pressure will not exceed 300mmol / L, urine volume will not continue to decrease after injection of vasopressin Urine specific gravity, urine osmotic pressure no longer continue to increase, urine volume reduction after pituitary diabetes insipidus is not obvious, urine specific gravity, urine osmotic pressure is not significantly increased, especially complete pituitary diabetes insipidus, weight can occur And blood pressure is significantly reduced, plasma Increased osmotic pressure (greater than 300mmol / L), urine volume decreased significantly after injection of vasopressin, urine specific gravity, urine osmotic pressure doubled, partial pituitary diabetes insipidus changes not as significant as pituitary diabetes insipidus, sometimes It is difficult to distinguish from mental polydipsia. The water-free and intramuscular anti-diuretic hormones in patients with renal diabetes insipidus can not reduce urine output and urine concentration.
4 Cranial and sellar CT, magnetic resonance examination: to help the diagnosis and differentiation of organic lesions in this area.
(2) treatment: partial pituitary diabetes insipidus can be given hydrochlorothiazide (hydrochlorothiazide) 25 ~ 50mg, oral, 3 times / d, while avoiding coffee, etc., clofibrate (clofibrate) 0.25 ~ 0.5g, oral, 3 times / d, carbamazepine 0.1g, oral, 3 times / d, may have white blood cell reduction, liver damage, lethargy, dizziness, rash and other adverse reactions, complete pituitary diabetes insipidus should be supplemented with vasopressin, commonly used Oil citrate vasopressin (long-acting urine collapse) (5U / ml), starting from 0.1ml, deep intramuscular injection, generally 0.3 ~ 0.5ml, to maintain about 5 days is appropriate, adverse reactions have headache, blood pressure Elevation, abdominal pain, etc., powder after the pituitary powder (50U / ml) 5 ~ 10U, nasal suction, every 4 ~ 6 hours, can cause chronic rhinitis and affect the efficacy, 1-cysteine-8 - right-handed Arginine vasopressin increases antidiuretic activity and reduces adverse reactions. Starting from 0.1mg/d, the dosage is gradually increased according to the amount of urine, and the dose adjusted to a urine volume of about 2000ml/d is maintained, generally 0.1-0.2mg. Oral, 2 ~ 3 times / d, or 4mg / ml, intramuscular injection, 2 ~ 3 times / d, alert to excessive water poisoning, such as pale, abdominal pain, blood pressure, Caused by tumors, surgery or radiation therapy should, nephrogenic diabetes insipidus can also be tested hydrochlorothiazide, the same dosage of the former.
2. Pituitary hypofunction:
The clinical manifestations of hypopituitarism are diverse, and sometimes there are multiple hormone deficiency manifestations, and some have only one or two hormone deficiency. Therefore, the following problems should be noted in diagnosis and treatment:
(1) Diagnostic aspects:
1 Identification of pituitary hypofunction: clinical manifestations are diverse, symptoms gradually appear, usually pre-prolactin, gonadotropin, symptoms of growth hormone deficiency, then thyroid stimulating hormone, finally adrenocorticotropic hormone, sometimes adrenal insufficiency Appears earlier than hypothyroidism, may have the following clinical manifestations, should be noted in the diagnosis:
A. Mainly manifested in the central nervous system: such as headache, vision loss, signs of visual field defects, pale optic disc, optic disc edema, extraocular muscle paralysis, lack of smell and so on.
B. Mainly characterized by gonad: female patients showed irregular menstruation or amenorrhea, loss of libido or disappearance, breast and genital atrophy; male showed short penis, testicular development or atrophy, infertility or less refined, loss of libido, impotence The second sexual characteristics are degraded, such as the body hair is sparse, the sound becomes soft, and the muscles are underdeveloped.
C. To lose weight, loss of appetite: can be accompanied by weakness, dizziness, fatigue, anemia, palpitations, nausea, occasional vomiting, poor body resistance.
D. Mainly coma: may be hypoglycemia, low blood sodium, water poisoning, low temperature coma or infection, sedatives, anesthetic-induced coma, may be caused by the above factors, or a factor.
E. Mainly due to mental symptoms: due to thyroid hormone deficiency, it can also be caused by excessive stimulation caused by high-dose glucocorticoids during crisis rescue. Some patients are misdiagnosed as schizophrenia.
F. Unexplained hypoglycemia: Considering the lack of growth hormone, because growth hormone has the effect of raising blood sugar, the measured value of IGF-I is more meaningful than GH.
G. Other manifestations: edema, lighter skin tone, anemia, hypotension, chills, hypothermia, lethargy, convulsions, cholestasis, etc.
H. Children's growth retardation should consider the possibility of this disease.
I. Infection-induced pituitary dysfunction crisis often causes clinicians to pay attention only to infection, while neglecting pituitary dysfunction itself, due to severe infection can also occur high fever, lower blood pressure, disturbance of consciousness, so it is easy to miss diagnosis or misdiagnosis, the key should Pay attention to the characteristics of his medical history and physical signs, and the infection itself is not too heavy, and there is a shock or disturbance of consciousness that is not well explained. In particular, attention should be paid to the presence or absence of this disease.
2 Find the cause of the precautions:
A. Women are more common in Sheehan syndrome, secondary to postpartum hemorrhage or postpartum infection. Therefore, in addition to detailed general medical history, women with amenorrhea during birth are especially required to collect menstrual history and childbirth history, and ask about onset and childbirth. Relationship, a comprehensive and detailed physical examination to find the performance of target gland hypofunction, patients with postpartum hemorrhage coma should be followed up, if there is no postpartum milk, fatigue, irregular menstruation or amenorrhea, body failure can not use other The explanation of the cause, the suspect and the disease.
B. Male pituitary tumor is the most common cause, followed by pituitary surgery, caused by radiation damage, pay attention to the corresponding medical history.
C. Traumatic pituitary dysfunction is clinically rare, and is more likely to be missed and misdiagnosed. For patients with traumatic brain injury, especially those with cerebrospinal fluid rhinorrhea, be alert to systemic symptoms caused by pituitary injury.
D. Other less common causes are parasagittal tumors, vacuolar sella, invasive or infectious diseases such as leukemia, hemochromatosis, granuloma, sarcoidosis, autoimmune pituititis, etc. caused by infiltration of the hypothalamus or pituitary gland, Diabetic vascular disease, arteriosclerosis, etc. can also cause dysfunction of pituitary avascular necrosis, each with its own special history, and unexplained idiopathic.
(2) Treatment:
1 should inform the patient and family members, adhere to lifelong medication after diagnosis, sedative sleeping pills before hormone replacement therapy.
2 etiology treatment: such as tumor-induced hypopituitarism should be taken surgery or radiotherapy and other measures, pay attention to the perioperative period can not stop hormone replacement therapy, should increase the amount of hormones, especially adrenal cortex hormones.
3 adrenal hormone replacement therapy: is the primary measure for the treatment of hypopituitarism, should be replaced by thyroid hormone and sex hormones, hydrocortisone is preferred, the dose should be individualized according to the condition, prednisone or prednisolone Secondly, if there is infection, surgery, etc., or when the condition is severe, the dose should be increased to 2 to 3 times or hydrocortisone 100 to 200 mg/d. Intravenous drip to avoid crisis, hormone replacement needs long-term Use, because glucocorticoids have the effect of antagonizing vasopressin, diabetes supplements may be more obvious after supplementing enough glucocorticoids.
4 thyroid hormone replacement therapy: it is important to apply this drug to patients with hypothermia, but should be used after adrenal cortex hormone or both drugs, so as not to aggravate the burden of adrenal cortex and induce crisis. If thyroid hormone is used alone, Can aggravate adrenal insufficiency, and even induce pituitary crisis, generally with thyroid powder (tablet) or levothyroxine sodium (L-T4), should start from a small dose, the initial dose of levothyroxine sodium (L-T4) 12.5 ~ 25g /d, increase 25g every 2 weeks until the daily dose is 100-150g and the thyroid hormone level is normal. When the dose is larger, it is taken 3 times. The age is older or there is coronary heart disease. The patients with myocardial ischemia increase the dose during the replacement process. Should be slower, and pay attention to heart rate, when there is severe cold or worsening of the condition, you can increase the amount of thyroid hormone, and also adjust the amount of glucocorticoids, so as not to aggravate adrenal insufficiency.
5 gonadotropin replacement therapy: female patients of childbearing age should establish artificial menstrual cycle, so that secondary sexual characteristics and sexual function recovery, to prevent osteoporosis, mild patients can restore the pituitary function if it can be pregnant again, but because of its function There has been a recession and the possibility of miscarriage is high.
6 Unless the men's gonadal function is combined at the same time, the general androgen should not be applied prematurely in children to prevent the premature healing of the epiphysis to affect the growth. The testosterone has side effects due to liver damage, and should not be used as a long-term substitute.
7 Suspected crisis cases are strictly prohibited to use morphine, chlorpromazine, barbital and other central inhibitors and anesthetics, try to limit the use of insulin and other hypoglycemic agents, the rescue of pituitary crisis should be timely, once the clinical diagnosis is to use the foot The amount of glucocorticoids, and then the right amount of thyroid hormone, while paying special attention to correct hypoglycemia, maintain water, electrolyte balance, treatment of other causes or complications, the prognosis of patients with crisis and whether the rescue is timely, whether the treatment is correct, adrenal cortex hormones commonly used Hydrocortisone 100 ~ 200mg intravenously, 2 times a day, if there is serious infection, shock, blood sodium is significantly reduced, the daily dose can be increased to 300 ~ 500mg, such as low body temperature type, while using thyroid hormone To use appropriate amount of hydrocortisone, in order to avoid the adrenal insufficiency, but the dose should be reduced to about 200mg per day, otherwise it may inhibit thyroid function, make the coma worse, while giving heat, can use hot water bath (24 ~ 35 ° C ), slowly warming, the temperature should not be too fast, the hourly heating rate should not exceed 0.5 ° C, the temperature rise too fast can cause circulation Depletion, when the body temperature has reached 35 ° C, you can stop heating, dry and keep warm.
8 pituitary dwarfism with GH replacement therapy when growing less than 5cm per year should be discontinued, adult pituitary dysfunction with GH deficiency has not been paid attention to. In recent years, foreign studies have considered that such patients also need GH replacement therapy, which can be further enhanced Physical strength, improve the quality of life of patients, but due to the high price of hGH, it is still difficult to use it widely in China.
Symptom
Non-functional pituitary adenoma symptoms Common symptoms Menstrual scarcity, dizziness, increased intracranial pressure, convulsions, amenorrhea, hydrocephalus, coma, sleepiness, pituitary dysfunction, visual impairment
Pituitary adenomas without bioactive hormone secretion mainly include two aspects of clinical manifestations: 1 the tumor expands to the outside of the saddle and compresses the adjacent tissue structure. These symptoms are the most common, often the main reason for patients to seek medical treatment; The compression and destruction of normal pituitary tissue cause different degrees of pituitary dysfunction. The pituitary tumor with bioactive hormone secretion has clinical manifestations of hypersecretion of one or several pituitary hormones.
Compression symptoms
(1) Headache: Patients found in 1/3 to 2/3, the initial stage is not very severe, mainly pain, and may be intermittently aggravated. The headache area is mostly in the two ankles, the forehead, the back of the eye or the base of the nose. The main cause of headache is that the saddle and the surrounding dura mater are caused by the tumor's upward growth. When the tumor wears the saddle, the pain can be alleviated or disappeared. For example, the saddle hole is larger and the tumor growth is more resistant. Small, headache can not be obvious.
Tumor compression adjacent pain-sensitive tissues such as the dura mater, large blood vessel wall, etc., can cause severe headache, diffuse, often accompanied by vomiting, tumor invasion into the hypothalamus, third ventricle, obstruction of interventricular pores can cause increased intracranial pressure, Increase headaches.
(2) oppression of the optic nerve pathway: pituitary adenoma spread to the saddle, oppression of the optic chiasm can cause different types of visual field defects with or without vision loss, which is due to different tumor growth direction and / or optic chiasm and pituitary gland Due to the variation of anatomical relationship, pituitary tumors 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 about 80%, due to pituitary tumor compression of the leading edge of the chiasm, damage From the nerve fibers below the nasal side of the retina, and then above the nasal side, the visual field of a wedge-shaped region that begins to be in the outer upper quadrant is impeded, and then the visual field defect gradually expands to the entire outer quadrant, and then extends to the outer lower quadrant. The formation of bilateral hemianopia, the visual loss of red in the early stage, the use of red optotype for early detection of the presence of visual field defects, the patient's visual acuity is generally unaffected; 2 bilateral sacral central visual field dark spots (dark point field of view Defect), this type of visual field defect accounts for 10% to 15%, because the pituitary tumor oppresses the posterior part of the optic chiasm, which damages the macular nerve fibers. Check the peripheral and central vision to avoid missed diagnosis, this type of visual field defect does not affect vision; 3 isotropic hemianopia, less common (about 5%), because the tumor expands to the upper rear or because the patient is a front-facing chiasm (about 15%) caused by compression of one side of the beam, the patient's visual acuity is normal, this type and the former type of visual field defect can also be seen in hypothalamic tumors such as craniopharyngioma, hypothalamic neuroglandoma and germ cell tumor; 4 Single eye blindness, this situation is seen in the pituitary tumor spread forward or upward or the patient is a posterior optic chiasm variant (about 5%), the extended tumor oppression side optic nerve causes the central vision loss or even blindness, contralateral field of vision, vision All of them are normal; 5 visual acuity declines to the upper temporal side of the visual field defect, this type and the former type are rare, the reason is that the upward expansion of the tumor compression side of the optic nerve near the end of the optic chiasm junction, in this part There are nasal retinal nerve fibers from the contralateral side, where these nerve fibers form a sputum (anatomically called the Wilbrand knee) and enter the optic chiasm.
Due to oppression of the optic nerve, blood circulation disorder, optic nerve gradually shrinking, leading to vision loss, visual loss and visual field defects are not necessarily paralleled in time and severity. A small number of patients with obstructive hydrocephalus and optic disc edema due to increased intracranial pressure, Retinal venous return disorder.
(3) Other symptoms: When the tumor expands to the cavernous sinus on both sides of the sella, it can cause the so-called cavernous sinus syndrome (the third, IV, V and VI damage to the brain), and damage the eyeball motor located in it. Double vision may occur. Generally, unilateral eye movement nerve palsy is rare. If it occurs, it may suggest that invasive tumors may invade the cavernous sinus. The sixth nerve is protected by the internal carotid artery. The fourth group has fewer cranial nerves, and the skin sensation loss in the trigeminal ocular branch and the maxillary branch is also caused by the invasion of the cavernous sinus. Some patients may still have olfactory loss due to olfactory nerve damage. The huge adenoma can invade the hypothalamus. The tumor compresses the hypothalamus without invading it, and there is no significant hypothalamic dysfunction. If it invades, a series of symptoms such as diabetes insipidus, lethargy, and thermoregulatory disorder may occur, such as tumor compression of the third ventricle. Blocking the interventricular space, causing increased hydrocephalus and intracranial pressure, increased headache, tumor can occasionally spread to the frontal lobe, temporal lobe caused by epileptic seizures, hemiplegia, pyramidal tract signs and mental symptoms When the tumor erosion of sellar and sphenoid sinus, can cause cerebrospinal fluid rhinorrhea, some patients with pituitary tumors found in the cerebrospinal fluid pressure as a lumbar puncture, protein and increase the number of cells does not increase, increase in cerebrospinal fluid sugar content.
2. Hormone secretion abnormalities
(1) decreased secretion of pituitary hormones: the reduction of pituitary hormone secretion in patients with pituitary tumors is generally mild, and the progress is slow. After 3/4 of the glands are destroyed, clinical signs of hypopituitarism appear even after clinical symptoms, even The tumor volume is large, and the symptoms of hormone deficiency rarely reach the severity of pituitary resection. Therefore, in general, pituitary tumors have fewer symptoms of pituitary hormone secretion, especially functional adenomas, but sometimes pituitary hormones. Reduced secretion can also be a prominent manifestation of this disease, especially in childhood, manifested as short stature and sexual dysplasia, sometimes tumors can affect the hypothalamus and neurohypophysis, vasopressin synthesis and excretion disorders cause urine Injury.
In patients with pituitary adenoids with hypopituitarism, hypogonadism is seen in 3/4 patients, hypothyroidism is not as common as hypogonadism, but subclinical hypothyroidism (only laboratory basis for hypothyroidism) Without clinical symptoms, it is still more common. If there is no serious stress, the adrenal function can usually be maintained normally. However, due to insufficient ACTH reserve in the pituitary, acute adrenal insufficiency (adrenal crisis) may occur during stress. Patients with pituitary adenoids with hypopituitarism have pale face and light skin pigmentation, which may be related to the decreased secretion of melanocyte stimulating hormone. Male patients are slightly obese, and their fat distribution is similar to that of female body type, mane, pubic hair is sparse, hair is sparse. Fine, male patients with pubic hair distribution, weight loss, sometimes weight loss or even increase, which is related to hypothalamic dysfunction, female patients with amenorrhea or menstrual scarcity, loss of libido; men in addition to loss of sexual desire, sexual dysfunction , genital atrophy, testicles are softer, smaller, patient wisdom Generally not affected, in times of stress (such as infection, surgery) occurs, the patient resistance is very low, prone to crisis and even coma.
Pituitary adenomas can sometimes cause pituitary acute bleeding due to bleeding, infarction (pituitary apoplexy), the incidence rate is 5% to 10%, pituitary apoplexy has a rapid onset, manifested as severe pain in the front or side of the ankle. Radiation to the face, and rapid emergence of varying degrees of vision loss, severe cases can be blinded within hours, often with extraocular muscle paralysis, especially the third to the cranial nerve involvement is most common, can also involve the IV, VI For the cranial nerves, severe cases may appear blurred, disorientation, neck stiffness or even coma, and some patients have acute adrenal insufficiency. Most patients have clear cerebrospinal fluid, some may be bloody, and CT shows enlargement of the sella. Pituitary adenomas are prone to intratumoral hemorrhage, especially those with larger tumors. Most of the predisposing factors are trauma, radiation therapy, etc., and there is no obvious incentive. Those with acute visual impairment should be treated as soon as possible under the protection of glucocorticoids. There is no consensus on whether radiotherapy can be performed in patients who have had a pituitary apoplexy.
(2) increased secretion of pituitary hormones: clinical manifestations vary due to different pituitary hormones secreted by different functional adenomas.
Examine
Examination of nonfunctioning pituitary adenoma
The pituitary gland mainly synthesizes and secretes 6 kinds of pituitary hormones, which act on different target glands or target organs and tissues, respectively, and are regulated by the corresponding hypothalamic hormones or secretory regulation and negative feedback regulation of target gland hormones. The functional status of the pituitary gland must be related to both the target gland hormone level and the hypothalamic hormone level. However, since the latter are mostly small molecular weight peptide substances, the antigenicity is poor, so the detection technology is highly demanded, and the content in the blood circulation is very small. (Main reason), so the level of hypothalamic hormone in circulating blood is not directly detected clinically.
1. Determination of plasma ACTH: ACTH is synthesized by pituitary ACTH cells (corticotroph), the precursor of which is POMC, POMC is cleaved into -LPH, ACTH (139), linker peptide and 1 amino terminal polypeptide in the pituitary gland. In human embryonic stage and female end-pregnancy, ACTH (1~39) can be further cleaved into ACTH (1~13) in the middle of the pituitary, namely -melanocyte stimulating hormone (-MSH) and ACTH (18-39). The latter is also known as the ACTH-like polypeptide; -LPH is further cleaved into LPH and -endorphin, all of which are secreted into the blood circulation in equimolar proportions.
ACTH mainly acts on the bundles and reticular bands of the adrenal cortex, promotes the production of glucocorticoids and sex hormones, and also promotes the production of mineralocorticoids to a lesser extent. Both pituitary and adrenocortical diseases can cause changes in plasma ACTH levels. Due to technical limitations, ACTH levels cannot be detected mainly by changes in plasma cortisol levels and dynamic tests (such as high-dose dexamethasone inhibition test) indirectly reflect ACTH changes. With the continuous improvement of hormone detection technology, the list is now available. The cloned antibody was used to detect different components of ACTH in plasma. The concentration of ACTH in normal human plasma was low (ACTH 24h yield was the least among 6 kinds of pituitary hormones, only 25-50g/24h), and ACTH in its different components (1 18) The most biologically active, other components are ACTH (1 ~ 39), amino terminal polypeptide, ACTH-like peptide (the latter two have no biological activity), POMC (also known as macromolecular ACTH substance) in the blood circulation The content is very small. Generally, the peak concentration of ACTH in normal humans is 6:00 to 10:00 in the morning, showing a significant circadian rhythm. The normal reference value is 2.64~13.2pmol/L (12-60pg/ml). Constant reference values are different.
ACTH secretion disorder is caused by hypothalamic-pituitary disease on the basis of excluding adrenal diseases. Only a few are found in ectopic ACTH syndrome. If ACTH is significantly increased, but there is no clinical manifestation of cortisol, the presence of ACTH components should be considered. The problem of heterogeneity can be confirmed by ACTH component analysis.
ACTH increase is mainly seen in ACTH tumor (Cushing disease), ectopic ACTH syndrome, Nelson syndrome, hypothalamic amenorrhea, primary adrenal insufficiency and ACTH insensitivity syndrome, hypothalamic amenorrhea caused by elevated ACTH The cause may be related to the decreased sensitivity of CRH receptors. The ACTH level of subclinical ACTH tumors may be slightly elevated or normal, but the dexamethasone suppression test is abnormal. In addition, ACTH is physiologically increased during pregnancy, during pregnancy. During the period and 12 weeks after delivery, it is generally inappropriate to perform dynamic function tests on the hypothalamic-pituitary-adrenal axis. During stress, CRH and AVP (with weaker ACTH secretion, often synergistic with CRH) increase, leading to an increase in ACTH levels. High, ACTH reduction is mainly seen in pituitary dysfunction, non-ACTH pituitary tumor, pituitary stalk syndrome, adrenal Cushing syndrome and long-term use of glucocorticoid patients, the latter two due to increased negative feedback of target gland hormone.
ACTH has a short plasma half-life of only 3 to 9 minutes. Therefore, it is best to use a cold syringe when taking a plasma specimen. The specimen is placed in a test tube containing EDTA and the plasma is quickly separated at 4 ° C, and immediately chilled for testing. For the impact, the specimen is best taken from an intravenous catheter that has been indwelled for more than 2 hours, and the specimen is also taken to detect plasma cortisol levels.
2. Determination of serum GH: GH is produced by GH cells (somatotroph) of pituitary gland, with a yield of 1000-2000 g in 24 h. GH in circulating blood includes 22 kD (76%), 20 kD (16%) and acidic GH (8%). The main biological function is the 22kD component, which accounts for 55% of the total, the dimers account for 27%, the oligomers (including the three, four, and pentamers) account for 18%, and the 45% of the 22kD. The component binds to its binding protein, and the 20kD component binds 25%. It is presumed that the GH of different components in the blood circulation are secreted by the pituitary gland in equimolar proportions, except for the middle and late pregnancy, various other physiological and pathological factors. The factors do not affect their proportion in the blood circulation. It must be noted that although the biological activities of dimers and oligomers are low, they account for 10% to 30% of the plasma immunological activity. GH acts extensively on the liver and grows in the epiphysis. Plates, fat and muscle tissue and other sites are mediated by IGF-1 to promote bone growth and metabolic regulation.
The amount of CH basal secretion is greatly affected by a variety of physiological factors, such as eating, sleep, exercise, stress and growth and development, CH pulse secretion is more unique, its pulse amplitude is larger, and the interval of secretion peak It is not fixed. In the intermittent phase of pulsed secretion, GH is almost undetectable (generally <3g/L), and its secretion peak is up to 40g/L. Therefore, random detection of serum GH levels is of little value, especially in growth. In children and adolescents at developmental stage, pituitary GH reserve function test is particularly important. If GH deficiency is suspected, it can be used as GH stimulation test. If GH secretion is suspected, GH inhibition test and serum IGF-1 level detection are selected. It also helps to fully reflect the functional status of the pituitary GH reserve and can be used as a screening and diagnosis method for acromegaly.
3. Serum PRL assay: PRL is synthesized and secreted by pituitary PRL cells (lactoroph). Human PRL is considered to be derived from a common "ancestor" gene together with GH and hPL (placental membrane prolactin). Source, often referred to as prolactin-growth hormone family, mainly in the form of PRL monomer (23kD) in the blood circulation, partially in the form of dimers and multimers, the latter two have lower biological activity, monomeric form It can be lysed into 8kD and 16kD. Therefore, attention should be paid to its component heterogeneity in the PRL radioimmunoassay. PRL has a wide range of physiological effects. In humans and most mammals, PRL mainly acts on the mammary gland, and estrogen and progesterone. Synergistic action promotes breast development, so that pregnant women have lactation ability, start and maintain lactation after childbirth, normal non-pregnant, lactating women and normal males have a basic PRL secretion of less than 20g / L, because the pulse frequency of PRL secretion is fixed and The magnitude is not large. Therefore, unlike GH, the detection of random serum PRL levels has diagnostic value. The time of patient feeding or sampling is less affected by the test results and is generally not considered. However, it is necessary to consider the influence of pulse and stress on the test results as much as possible. If the serum PRL level is slightly increased in routine blood sampling, in order to eliminate the influence of stress and pulse, it is best to place the intravenous catheter for the patient to rest for 2 hours before pumping. Blood re-test, should be retained multiple times, each time interval of about 20min, a total of about 6 times to take the average value, if the above physiological factors, the retest results will be <20g / L.
There are many diseases that can cause high PRL. The most common disease is PRL tumor. The analysis results should first exclude physiological and drug-induced PRL. If the PRL level is below 20g/L, high PRL can be ruled out. At 200g/L combined with clinical and pituitary imaging examinations can generally be confirmed as PRL tumors, physiological PRL increase will not exceed 60g / L, greater than 60g / L should be considered drug-induced or pathologically high PRL, must be further examined To determine the cause of high PRL.
4. Determination of serum TSH: TSH and LH, FSH are glycoprotein hormones, which are composed of two glycoprotein subunits - and subunits in a non-covalent bond. The three -subunits are the same and - Different subunits, the latter have their own biological activities, the -subunit and the respective -subunit are produced by different genes respectively, and the pituitary cells secreting TSH are TSH cells (thyrotroph), and the pituitary gland produces 50~ per day. 200g of TSH has a half-life of 53.4min. Previously, RIA detection technology can only distinguish between the upper limit of TSH and the high level of TSH. Because the normal lower limit of serum TSH is very low, RIA is difficult to detect. Now high sensitivity detection technology IRMAs (immuno radiometric assay, also known as double antibody immunoradiography) can distinguish between TSH decline and normal lower limit. The normal reference value of serum TSH is 0.3-5 mU/L (IRMAs), and the lowest detectable value of IRMAs is 0.04 mU/L. The sensitivity and specificity of the detection are obviously improved, which is called sensitive TSH (sTSH). It can be used to replace the TRH stimulation test for the diagnosis of hyperthyroidism. The sensitivity of the TSH is detected by immuno-chemi-luminometric assay (ICMA). Up to 0.01mU/L Not only the sensitivity is further improved, but also the method is simple, fast and reliable, and there is no need to worry about radioactive contamination. The time-resolved immune of luorometric assay (TRIFA) overcomes the instability of the enzyme label, and the chemiluminescent label can only emit light once. And the fluorescent label is subject to many disadvantages, and the non-specific signal is reduced to a negligible degree. The analytical detection limit and functional detection limit are 0.001 mU/L and 0.016 mU/L, respectively. The sensitivity of ICMA and TRIFA is higher than that of IRMAs. Many times, it is also called ultra sensitive TSH (uTSH).
Elevated serum TSH is mainly seen in TSH tumors, primary hypothyroidism, rare TSH insensitivity syndrome and ectopic TSH syndrome, serum TSH decline is common in Craves disease and other thyroid hyperthyroidism (such as autonomous high function) Thyroid nodules or adenomas, iodine-derived hyperthyroidism, thyroid cancer, etc.), secondary hypothyroidism, rare ovarian goiter and iatrogenic hyperthyroidism, in addition to secondary hypothyroidism, these diseases cause TSH The reason for the decline is due to excessive secretion of thyroid hormone, increased negative feedback, inhibiting the secretion of pituitary TSH, and some patients with hypothalamic-pituitary disease caused by pituitary TSH reserve dysfunction, serum TSH levels can be in the lower limit of the normal range However, thyroid hormone levels have been reduced, and a TRH stimulation test should be performed to confirm the diagnosis.
5. Determination of serum LH and FSH: LH and FSH are produced and secreted by glandular gonadotropin (gonadotroph), both of which are glycoprotein hormones, which are secreted mainly by the secretory regulation of hypothalamic hormone GnRH and gonadotropins, inhibin And negative feedback inhibition regulation of follistatin, LH acts on Leydig cells and ovarian follicles, regulates the production of gonadal steroid hormones, and the secretion of LH before ovulation in women helps promote ovulation and follicular luteinization, physiological role of FSH It mainly acts on the trophoblasts of the gonads, promotes spermatogenesis and ovarian follicle development. In addition, FSH can also regulate the number of LH receptors on Leydig cells.
The first method of FSH is to use biological method, that is, to observe the change of uterus weight in immature mice, and to express the activity of FSH in urine in mouse uterus unit. Since the result is inaccurate, it has been eliminated. Currently, serum is determined by labeled immunoassay. Or the content of FSH and LH in urine, the concentration of normal males and females in puberty is not constant. Before the puberty, the FSH and LH levels of the two sexes are not much different. The females have a regular menstrual cycle after sexual maturity. Cyclical changes, male FSH and LH levels did not change much after sexual maturity, generally relatively stable in a narrow range.
For males and women before sexual maturity, the detection of serum LH and FSH levels is diagnostic. Because LH and FSH are pulsed, it is best to take blood samples at intervals of 20 minutes, for a total of 3 times. Specimens were measured for LH and FSH levels, combined with clinical manifestations, testosterone or estrogen levels for comprehensive analysis, male patients can also be used for semen analysis if necessary, for women after sexual maturity, if menstruation is normal and no contraceptives are taken, single test serum LH and FSH levels usually have little help for diagnosis. If menstruation is normal and serum progesterone levels are normal in the luteal phase, it is not necessary to detect LH and FSH levels to judge the function of glandular secretion of gonadotropin. Children with precocious puberty LH And FSH increased, common in pineal tumor, inter-brain hamartoma, brain trauma and other diseases, false precocious puberty LH and FSH decreased, puberty delay often LH, FSH and gonadotropin levels decreased, primary Hypogonadal levels in patients with hypogonadism and decreased gonadotropin, gonadotropin secondary to hypothalamic-pituitary disease Hormone levels decreased gonadal hormone also reduced.
Secondary amenorrhea should be measured serum FSH / LH, estrogen, prolactin and HCG levels must also be tested, if necessary, female, progesterone sequential test and LHRH stimulation test to assist differential diagnosis.
6. Dynamic test of pituitary function:
(1) Joint Excitation Test:
1 Principle: The production and excretion of pituitary hormones are regulated by the dual or secretory secretion of hypothalamic hormones, and the function of the hypothalamic-pituitary-target gland axis is normal. When the hypothalamic-pituitary disease causes hypopituitarism, it can be passed. Exogenous hypothalamic pituitary hormone is given to excite the pituitary cells, and the degree of reaction is observed to judge the reserve function of the pituitary gland. In addition, the hypothalamic or pituitary function caused by the pituitary itself can be identified to some extent. Decreased, this combined excitatory test is often used in the evaluation of pituitary function after pituitary surgery and radiotherapy to determine whether alternative treatment is needed.
(GnRHTRHCRHGHRH)5ml2030sGnRH 100µgTRH 200µgCRHGHRH1µg30015306090120minACTHTSHLHFSHGH8:00T3T4IGF-1
TRHTRH30minTSH1030mU/LTRHTSH;TSH60minGraves
GnRHLHFSH1/22LH410FSH1/22LH3435810;FSH1/22LH/FSHGnRHGnRH()GnRHGnRH(250µg8h)3045min LH(1)6090min24hLH24hLH/FSH;LH/FSH12;12();GnRH8hGnRHLH/FSHGnRHGnRH 400µg5GnRH 250µg(8h)3LHLH/FSHGnRH
CRHACTH241015min4.422pmol/L(20100pg/ml)3060min550690nmol/L(2025µg/dl)ACTHACTHACTHCushingACTHACTHNelsonCRHACTHACTHCRHCushingCushingACTHCRH
GRHGHRHGH7µg/L<5µg/LGH78GHRH(1µg/kg)78()GH7µg/LGH
CRH44h
(2)
GHGHRHGHGHRHGHACTH
a.()1h(0.15U/kg)300min30456090120min(ACTH)GH3045min2.2mmol/L0.3U/kg580nmol/LGH10µg/LACTHGH8:0048:0140nmol/L(5µg/dL);;;ACTHCRHCRH
b.0.5g3006090120minGH90min
c.(0.5g/kg30g)300306090120minGH60minGH7µg/L3µg/LGH37µg/LGH
GH()GHGHGH1()1h75g()300306090120minGH12hGH23µg/LIRMAGH1µg/L()0.71µg/L()0.06µg/L()GH()
TRHGHTRHTRHGHTRH 500µg(5ml)30s-3003060120minGHGHGH50%10µg/L
(3)PRLPRLPRLPRLPRLPRLPRLPRLPRLTRH()PRL
(4)--GnRH
7.AVP
(1)AVPAVPAVPAVP0.51.5ng/LAVPAVP
(2)AVPAVPAVP
8.XX20%40%35%5%CTXX
9.CTMRICTCTMRI
-MRI(1.5mm)CTCTMRIMRICTMRICT
5mmCT(1.5mm)CT90CTCT3mm9mm67mm(1836)(3770)18%
MRIGd-DTPA(-)30minMRI(75%)AVP80%MRI12
MRI1T1T214T1T24T1T21
T11T2Gd-DTPAMRI
10.Goldmann70%
11.-XCTMRI
Diagnosis
diagnosis
1.
2.
3.(PRL)
4.
5.PRLPRL()TSHGHACTHGHACTH24hIGF-1
(1)TRHTRHTRHLHFSH1/3TRHTRH40%TRH()
(2)GnRHGnRHGnRHGnRHGnRHGnRHGnRHGnRHKlibanski(1989)GnRHDTrp6-Pro9-NEt-
LHRHLHFSH
6.
Differential diagnosis
PRLPRLPRL6.825nmol/L(150ng/ml)PRLPRL9.1nmol/L(200ng/ml)ACTHPRL
