Cushing's syndrome
Introduction
Introduction to Cushing's syndrome Cushingssyndrome, also known as hvpercortisolism or Cushing's syndrome, was first reported by Harvey Cushing in 1912. Intrinsic is a clinical syndrome characterized by high cortisolemia caused by multiple causes, mainly characterized by full moon face, multi-blood appearance, centripetal obesity, hemorrhoids, purple streaks, hypertension, secondary diabetes and Osteoporosis and so on. The clinical manifestations of typical Cushing's syndrome are mainly due to the long-term excessive secretion of cortisol, which causes serious disturbance of protein, fat, sugar and electrolyte metabolism and interferes with the secretion of various other hormones. In addition, excessive secretion of ACTH and excessive secretion of other adrenocortical hormones may also cause corresponding clinical manifestations. basic knowledge The proportion of the disease: the incidence rate is about 0.001% -0.003% Susceptible people: no specific population Mode of infection: non-infectious Complications: kidney stones, hypertension, cerebral arteriosclerosis, polycystic ovary syndrome
Cause
Cause of Cushing's syndrome
Iatrogenic cortisol (10%):
Long-term use of glucocorticoids in the treatment of certain diseases can lead to clinical manifestations of cortisol, which is very common in the clinic, which is caused by exogenous hormones, which can be gradually restored after stopping the drug, but long-term use of glucocorticoids can be used in large quantities. Feedback inhibits the secretion of ACTH from the pituitary gland, causing atrophy of the adrenal cortex. Once the drug is stopped, it may lead to a series of manifestations of cortical dysfunction and even crisis. Therefore, it should be noted that long-term use of ACTH can also cause cortisol.
Pituitary bilateral adrenal hyperplasia (15%):
Bilateral adrenal hyperplasia is caused by excessive secretion of ACTH in the pituitary gland. The reasons are: 1 pituitary tumor, more common basophilic tumor, also seen in chromoblastoma; 2 pituitary no obvious tumor, but increased secretion of ACTH, generally considered to be Due to excessive secretion of corticotropin releasing factor (CRF) in the hypothalamus, only about 10% of pituitary tumors can be found clinically. In this case, plasma cortisol has reached an abnormally high level due to pituitary secretion of ACTH. The increase is not sufficient to cause normal feedback inhibition, but oral high-dose dexamethasone can still have an inhibitory effect.
Bilateral adrenal hyperplasia caused by extracorporeal lesions (15%):
Bronchial lung cancer (especially oat cell carcinoma), thyroid cancer, thymic cancer, nasopharyngeal carcinoma, and tumors originating from neural crest tissue sometimes secrete an ACTH-like substance with a biological effect similar to ACTH, causing bilateral adrenal cortex Hyperplasia, so called heterologous ACTH syndrome, these patients also often have obvious muscle atrophy and hypokalemia, the secretion of ACTH substances in the lesion is autonomous, oral high-dose dexamethasone no inhibition, lesion resection or cure After that, the illness gradually subsided.
Adrenal cortical tumors (5%):
Mostly benign adrenal adenomas, a small number of malignant adenocarcinomas, tumor growth and secretion of adrenocortical hormone is autonomous, not controlled by ACTH, due to the secretion of a large number of corticosteroids, feedback inhibits the secretion of pituitary Function, so that the concentration of plasma ACTH is reduced, so that the normal adrenal cortex of the non-tumor part is obviously atrophied. In this type of patients, whether ACTH is excited or high dose of dexamethasone is inhibited, the amount of cortisol secretion will not change, and adrenal cortical tumors are especially In malignant tumors, 17 ketosteroids in urine are often significantly increased.
Adrenal cortical tumors are mostly single benign adenomas, generally less than 3 to 4 cm in diameter, with brownish-yellow color and intact capsule. The morphology and arrangement of tumor cells are similar to those of adrenal cortical cells. Adenocarcinoma is often large, fishy, and infiltrating. Or spread to the surrounding organs, often with lymph nodes and distant metastasis, the cells are characterized by malignant cells, and adrenal cortical tumors without endocrine function do not cause cortisol.
Clinically, a few cases of nodular hyperplasia of the adrenal gland are found to be an intermediate type of hyperplasia and adenoma. The plasma ACTH can be decreased, and the high-dose dexamethasone has no inhibitory effect.
According to statistics, 70% of clinical cases are bilateral adrenal hyperplasia caused by pituitary lesions, benign adenomas account for 20-30%, malignant adrenal adenocarcinomas account for 5-10%, and excessive ectopic ACTH secretion is rare. .
Pathogenesis
1. Primary adrenal cortical lesions are primary tumors of the adrenal gland. Cortical adenomas account for about 20% of adult Cushing's syndrome, and cortical adenocarcinomas account for about 5%. In children, more than 50% of adenomas are Malignant, adrenal tumors have autonomic growth and secretion functions, and are not controlled by ACTH secreted by pituitary gland. Therefore, they are not ACTH-dependent. Because of the excessive secretion of cortisol from the tumor, feedback inhibits the release of pituitary ACTH in the blood of patients. The ACTH is so low that the adrenal cortex is atrophied on the contralateral and ipsilateral tumors. The adenocarcinoma is generally large and grows rapidly. In addition to secreting too much cortisol, it also secretes other corticosteroids (aldosterone) and adrenal androgens; Cancer patients may have 11-hydroxylase involvement, and the 17-ketosteroid (17-ks) in the urine of patients is significantly increased. Patients with adrenal adenocarcinoma have mutations in the p53 gene on the long arm of chromosome 17, and the p53 gene is a Tumor suppressor gene, which can play an immune surveillance role, allows the body to clear the mutant cell line in time, and when the p53 gene is mutated or deleted, the immune surveillance effect is lost, and the mutant cell line can infinitely multiply and produce adrenal skin. Malignant tumors, benign tumors in the adrenal glands, found no problems p53 gene, it is not yet clear mechanism for benign tumors.
Some experts believe that the nature of the tumor is related to the defect of the short arm of chromosome 11; most malignant tumors have a short arm defect of chromosome 11, which can lead to overexpression of IGFII and excessive growth of atypical cells.
2, pituitary tumor or hypothalamic-pituitary dysfunction secondary to pituitary tumor or hypothalamic-pituitary dysfunction bilateral adrenal hyperplasia, called Cushing's disease, accounting for about 70% of adult Cushing's syndrome, due to pituitary tumor or Hypothalamic-pituitary dysfunction, excessive secretion of ACTH, stimulation of bilateral adrenal hyperplasia, can cause excessive secretion of cortisol, it is ACTH-dependent.
Prevention
Cushing syndrome prevention
Early diagnosis, early treatment, prevention of complications.
[health guidance]
1. Instruct patients in daily life, pay attention to prevent infection, keep skin clean, prevent trauma and fracture.
2. Instruct patients to correctly take a balanced diet and give low sodium, high potassium, and high protein foods.
3, take the medicine according to the doctor's advice, do not arbitrarily reduce the medicine or stop the medicine.
4. Regular outpatient follow-up.
Complication
Cushing syndrome complications Complications, kidney stones, hypertension, cerebral arteriosclerosis, polycystic ovary syndrome
1, high urinary calcium and kidney stones cortisol promote urinary calcium excretion, so that urinary calcium increased significantly, long-term patients can form kidney stones with urinary calculi syndrome and ectopic calcium deposition.
2, high blood pressure and hypokalemia Long-term hypertension can lead to left heart failure, cerebral arteriosclerosis, stroke and moderate.
3, Cushing's syndrome patients with childhood and child disease, growth stagnation, puberty delay.
Studies have reported that this disease can be complicated by diseases such as polycystic ovary syndrome and psychological disorders.
Symptom
Symptoms of Cushing's Syndrome Common Symptoms Fatigue Full Moon Face Heavy Obesity Melancholy Maleized Back Pain Concentric Obesity Diabetes Hair Increase Osteoporosis
The clinical manifestations of typical Cushing's syndrome are mainly due to the long-term excessive secretion of cortisol, which causes serious disorders of protein, fat, sugar, electrolyte metabolism and interferes with the secretion of many other hormones. In addition, ACTH secretion is excessive and other adrenal glands Excessive secretion of corticosteroids can also cause corresponding clinical manifestations.
1. Centripetal obesity Cushing's syndrome patients are mostly mild to moderately obese, rarely have severe obesity, some face and trunk are overweight, but the weight is in the normal range. Typical centripetal obesity refers to the fat of the face and trunk. However, the limbs including the buttocks are not fat, the full moon face, the buffalo back, the hanging belly and the supraclavicular fossa fat pad are the characteristic clinical manifestations of Cushing's syndrome. A small number of patients, especially children, may present as homogeneous obesity, the cause of central obesity. It is not clear, it is generally believed that hypercortisolemia can increase appetite and easily make patients obese, but the role of cortisol is to promote fat breakdown, so in the limbs sensitive to cortisol, fat decomposition predominates, subcutaneous fat decreases, In addition to muscle atrophy, the limbs are obviously small, insulin secretion is increased during hypercortisolemia, and insulin promotes fat synthesis. As a result, in the face and trunk sensitive to insulin, fat synthesis predominates, and adrenaline secretion is abnormal. Participated in abnormalities in fat distribution.
2, diabetes and impaired glucose tolerance, about half of patients with Cushing's syndrome have impaired glucose tolerance, about 20% have dominant diabetes, high cortisolemia strengthens gluconeogenesis, and can also fight the role of insulin, The use of glucose in cells is reduced, so that blood sugar rises and glucose tolerance is reduced, resulting in diabetes. If patients have a potential diabetes predisposition, diabetes is more likely to manifest itself, and ketoacidosis is rare.
3, the clinical manifestations of negative nitrogen balance Cushing's syndrome patients with accelerated protein decomposition, reduced synthesis, so the body is in a negative nitrogen balance for a long time, long-term negative nitrogen balance can cause: muscle atrophy, the limb muscles are more obvious; Collagen is reduced and the skin is thin, wide purple lines, skin capillary fragility increases and easy to have ecchymosis; bone matrix is reduced, bone calcium is lost and severe osteoporosis occurs, manifested as low back pain, easy pathological fracture, fracture The predilection sites are ribs and thoracolumbar spine; the wound is not easy to heal. Not every patient with Cushing's syndrome has a typical wide, flaming purple pattern. Patients with simple obesity often have small purple lines, which should be noted in the identification. .
4, hypertension and hypokalemia cortisol itself has sodium and potassium excretion, high levels of cortisol in Cushing's syndrome is the main cause of hypertension and hypokalemia, plus sometimes weakened cortisol and corticosterone Increased secretion of mineralocorticoids, the body's total sodium increased significantly, blood volume increased, blood pressure increased and mild lower extremity edema, increased urinary potassium, resulting in hypokalemia and high urinary potassium, while increased hydrogen ion excretion Alkali-induced poisoning, Cushing's syndrome is generally mild to moderate, and hypokalemia is also mild, but patients with ectopic ACTH syndrome and adrenocortical cancer have a significant increase in cortisol secretion. At the same time, the secretion of weak mineralocorticoids is also increased, so the degree of hypokalemia is often severe.
5, growth and development disorders due to excessive cortisol inhibition of growth hormone secretion and its role, inhibition of gonadal development, and thus will have a serious impact on growth and development, Cushing's syndrome patients with childhood onset, growth stagnation, puberty delay, such as There is a compression fracture of the spine and the body becomes shorter.
6. Gonadal dysfunction Hypercortisolemia not only directly affects the gonads, but also inhibits the secretion of gonadotropins in the hypothalamus-adenohypophysis. Therefore, the gonad function of patients with Cushing's syndrome is significantly lower, and the female manifests as menstrual disorders. Hair occlusion, very few normal ovulation, males with sexual dysfunction, impotence.
In addition to adrenal adenomas, other causes of Cushing's syndrome have varying degrees of adrenal weak androgen, such as dehydroepiandrosterone and androstenedione increased secretion, these hormones themselves are not strong, but can In the peripheral tissues, it is converted into testosterone. As a result, patients with Cushing's syndrome often have acne, women's hairy, and even women's masculinity. Hair loss, scalp and oil are common. These weak androgens also inhibit hypothalamic-pituitary-gonads. The axis is another cause of hypogonadism.
7, mental symptoms Most patients have psychiatric symptoms, but generally lighter, showing euphoria, insomnia, inattention, emotional instability, a small number of patients will appear similar to manic depression or schizophrenia.
8, susceptible to infection Cushing's syndrome patients with immune function is inhibited, easy to have a variety of infections, such as skin folliculitis, periodontitis, urinary tract infections, hyperthyroidism and body sputum, etc., the original stable tuberculosis It is possible to be active.
9, high urinary calcium and kidney stones, high cortisolemia, the absorption of calcium in the small intestine is affected, but bone calcium is mobilized, a large amount of calcium ions are discharged from the urine after entering the blood, thus, although the blood calcium is at a normal low or low Normal, but increased urinary calcium output, prone to urinary calculi, it has been reported that the incidence of urinary calculi in Cushing's syndrome patients is 15% to 19%.
10, eye manifestations Cushing's syndrome patients often have combined membrane edema, and some may also have mild exophthalmos.
Examine
Examination of Cushing's syndrome
1, glucocorticoids increased, the secretion rhythm of day and night disappeared.
(1) Increased urinary 17-hydroxycorticosteroid (17-OH), greater than 20mg/24h, such as more than 25mg/24h, the diagnosis is more significant.
(2) The increase of free cortisol (F) in urine exceeds 110g/24h. Because the F in urine reflects the cortisol level of 24h, it is less affected by other factors than cortisol in blood, so the diagnostic value is higher.
(3) The basic value of cortisol in plasma (8 o'clock in the morning) increased, the circadian rhythm disappeared, and the secretion of cortisol in normal human plasma has circadian rhythm, which is usually highest at 8 o'clock in the morning, and is half of 8 o'clock in the afternoon at 4 o'clock in the evening. At 12 o'clock, it was half of 4 o'clock in the afternoon, and the secretion of Cushing's disease patients at 4 o'clock and 12 o'clock at night did not decrease or even higher. The normal diurnal secretion rhythm disappeared. Of course, when measuring cortisol in blood, the time difference should be excluded. The influence of other factors on the circadian rhythm prevents the false Cushing disease.
2, ACTH assay in plasma can identify ACTH-dependent Cushing's disease and non-ACTH-dependent Cushing's disease, ACTH also has diurnal secretion rhythm, the highest at 8 o'clock in the morning (fasting base value 10 ~ 100pg / ml), the lowest in the evening; Cushing The circadian rhythm of ACTH disappeared in patients with disease, adrenal hyperplasia and ectopic ACTH syndrome, the measured value of ACTH in plasma was higher than normal, especially the latter is more obvious, usually more than 200pg/ml; and adrenal adenoma or adenocarcinoma, due to The cortisol is secreted autonomously, and the ACTH of the pituitary has obvious feedback inhibition. The measured value of ACTH in plasma is lower than normal. The ACTH measurement value is sometimes not stable. Because ACTH is pulsed secretion, the plasma concentration changes greatly and is susceptible. The temperature is affected by the peptidase and is easily adsorbed on the wall of the glass tube. Therefore, the blood sample should be collected with a plastic tube with heparin, and sent to the laboratory at a low temperature. The plasma must be separated as soon as possible, frozen for testing or measured as soon as possible. The increase in ACTH is clinically significant, and when ACTH is low, the factors influencing the operation are excluded.
3, low-dose dexamethasone inhibition test
(1) 1mg dexamethasone inhibition test at midnight: 1mg oral dexamethasone 1mg at midnight, 8 hours at 8am, free cortisol (F) in blood, such as 50% lower than the control day, said to inhibit; can not inhibit Cushing's syndrome is more likely, this method can identify most of the "Cushing" and "Non-Cushing", and the method is simple, often used as a screening test for Cushing's syndrome; false positive reaction can be seen in Those who took phenytoin, phenobarbital, and rifampicin to accelerate the metabolism of dexamethasone, those who received estrogen therapy or tamoxifen (which increased cortisol binding protein), and those who suffered from Endogenously depressed patients, because of the presence of false positives, some hospitals do midnight 1.5mg dexamethasone suppression test.
(2) 2mg dexamethasone 2-day inhibition test (Liddle test): oral dexamethasone 0.5mg for 2 consecutive days, once every 6 hours or 0.75mg, once every 8 hours, daily blood test after taking the drug Free cortisol (F) and F in 24h urine. If the F in the blood after taking the drug, the F in the urine of 24h is reduced by more than 50% before taking the drug, which can be inhibited, then the diagnosis of "Cushin" is excluded; The diagnosis was Cushing's syndrome, and further the cause of Cushing's differential diagnosis was made. The Liddle test also had a false positive reaction of 15% to 20%. It must be combined with F in 24h urine to improve the diagnostic accuracy. .
4, high-dose dexamethasone inhibition test (DST)
(1) 8mg dexamethasone 2 days method: take dexamethasone (2mg, once every 6 hours) for 2 consecutive days, the blood F and 24h urine F after administration decreased by 50% compared with the control day. For the inhibition, for proliferative Cushing, and vice versa, consider adrenal adenoma or adenocarcinoma, ectopic ACTH syndrome and some patients with nodular hyperplasia, can be combined with other tests, tests, and further identification.
(2) overnight 8mg dexamethasone inhibition test (DST) method: overnight 8mg method for simplified high-dose DST, the sensitivity to the diagnosis of Cushing's disease is 88%, and the specificity is slightly lower, about 60%, if taking medication Before 8:00, 8:30, 9:00 and dexamethasone, 7:00, 8:00, 9:00 and 10:00, the blood test ACTH and cortisol, can improve the overnight 8mg DST, so that Increased sensitivity.
5, CRH excitement test for patients with large doses of 8mg DST can not be identified, can do CRH stimulation test.
METHODS: The veins were opened by subcutaneous tunneling. The blood was measured by ACTH as a control, then CRH was injected at 1 g/kg or 100 g/time. Blood was collected 15 min before injection and 0, 15, 30, 60 min after injection. The results were as follows. Figure 1. Because adenoma patients can secrete a large amount of blood F and feedback inhibition of the pituitary gland, the baseline value is lower than normal. There is no obvious excitement after injection of CRH, that is, there is no peak. In the case of ectopic ACTH syndrome, blood ACTH Not affected by CRH, the basic value of ACTH measurement is high, and there is no peak of excitement, and patients with adrenal hyperplasia, whether it is pituitary microadenomas caused by bilateral adrenal diffuse hyperplasia, or nodular hyperplasia, the basic ACTH is more High, and can be excited by CRH, ACTH has a high peak after injection of CRH.
After summarizing the results of the CRH stimulation test, Kay et al. proposed: the percentage of peak-to-base increase: ACTH>50%, F>20% in blood is positive, suggesting pituitary Cushing's disease, and ACTH is increased by <50%. F<20% in blood is a negative reaction, suggesting ectopic ACTH syndrome, or adrenal-derived Cushing's syndrome, but it has been confirmed that there is a 10% false negative in the CRH test in adrenal hyperplasia. A vasopressin (AVP) for CRH test, our hospital used neurohypophysin (neuronin) instead of AVP combined with CRH, do excitatory test, found in pituitary Cushing (whether diffuse adrenal gland) When hyperplasia or nodular hyperplasia), after injection of neurohypophysin and CRH, ACTH can be increased, the absolute value of the increase exceeds 20pg/ml, and the absolute value of F in the blood exceeds 7g/dl. In adrenal-derived Cushing (such as adrenal adenoma), the increase in ACTH is less than 20 pg/ml, and the increase in F in blood is less than 7/g/dl.
6, other tests
(1) Metoprone (methipone, chemical name bispyridinone, Su4885, mitopirone, metyrapone) test:
This drug can inhibit the 11--hydroxylase required for the synthesis of adrenocortical hormone, increase the number of intermediates such as 11-deoxycortisol, and reduce the synthesis of cortisol and corticosterone. 17-ketosteroids in urine (17- The displacement of KGS) or 17-OHCS increased significantly.
method:
Oral method: Metoprolone 2 ~ 3g / d, 4 to 6 times orally, and even served for 1 to 2 days.
Intravenous infusion: Methadone 30mg/kg or 1.5-2.0g was added to 500ml of normal saline, and was dripped in 4h.
In patients with normal pituitary-adrenal function, the 17-KGS or 17-OHCS in the urine increased more than 2 times in the urine 24 h after the test. The results of cortical hyperplasia were the same as above, while the secretion of cortical tumors was autonomic except for a few adenomas. Generally, there is no response, and the part of heterologous ACTH syndrome can be increased.
(2) Mifepristone (trade name: Xiyin, Ru486, mifepristone) Excitatory test: Ru486 competitively inhibits the binding of glucocorticoid to its receptor, and its affinity to glucocorticoid receptor is 3 times that of dexamethasone Therefore, it can block the negative feedback effect of glucocorticoid on the hypothalamus-pituitary, making the HPA system excited.
Its mechanism of action is as follows:
1 normal blood free cortisol (F) feedback inhibition mechanism of central ACTH, the normal glucocorticoid receptor consists of three parts, namely hormone binding site, DNA binding site and antigenic site, in general, DNA binding The site is blocked by two heat shock proteins, HSP90. When the blood F binds to the hormone binding site of the glucocorticoid receptor (cytoplasmic receptor) of pituitary ACTH cells, it can block the heat shock protein (HSP90) at the DNA binding site. Shedding, exposing the site of the DNA binding site, thereby enabling it to bind to the DNA template in the nucleus, stimulating transcription and synthesis of some inhibitory "enzymes", inhibiting the regulation of ACTH transcription and synthesis.
The mechanism of action of 2 mifepristone (Ru486), in normal humans, when a certain amount of Ru486 is competitively bound to the hormone binding site of the receptor, the heat shock protein (HSP90) that blocks the DNA binding site cannot be made. Shedding, as a result, can not bind to the DNA template in the nucleus, the inhibitory "enzyme" of transcription synthesis is greatly reduced, the effect of inhibiting the regulation of ACTH synthesis is greatly reduced, the ACTH in the blood is increased, and F is correspondingly increased. high.
The one-day Ru486 test, which uses 4 mg/kg of Ru486 for normal people, can increase ACTH and cortisol after taking the drug by more than 30% than the baseline value of the pre-dose control day. Patients with Cushing's syndrome, due to cortisol in the blood. Increased, 4mg/kg of Ru486 can not completely competitively inhibit the binding of cortisol and its receptor, so the feedback inhibition is less weak, so the values of ACTH and cortisol (blood, urine F) after taking the drug and pre-dose control Compared with the basic value, it does not increase or increase by <30%, saying that it cannot be excited, so the test can identify "Cushin" and "Non-Cushing".
Some people also used Ru486 with 5mg/kg daily, or Ru486 for 3 days, to diagnose the cause of Cushing's syndrome. ACTH and cortisol in patients with adrenal hyperplasia can be given high dose of Ru486 (5mg/kg). Excited and increased, and adrenal adenomas did not respond.
(3) intravenous dexamethasone inhibition test:
1 Identification of Cushing and obesity, dexamethasone 5g / (kg · h), from 10 am to 3 pm, a total of 5h intravenous infusion, simple obese patients at night 7 in the blood F is suppressed very much Low, below 1.4g / L, the blood F is still inhibited at 8 o'clock in the morning, and the blood F in patients with Cushing's syndrome can not be suppressed to 2.5g / L at 7 o'clock in the morning, the blood at 8 o'clock in the morning Medium F should exceed 5g/L.
2 for the differential diagnosis of Cushing's syndrome, with 1mg / h dexamethasone continuous intravenous infusion, from 11 am to 3 pm, continuous infusion for 4h; normal people or simple obesity in the blood F Can be quickly suppressed to less than 3g / dl, and remain suppressed to 9 o'clock in the morning, while the blood F in patients with Cushing's syndrome can drop to more than 50% of the basic value, but soon "out of breath" Phenomenon, the 9-hour blood F value exceeds 10g / dl, ectopic ACTH syndrome and adrenal autonomous adenoma patients, in the intravenous dexamethasone inhibition test is not inhibited, so far, not yet It is possible to identify mild (or early) Cushing and obese depressed patients (Falk Cushing), and it has not been proven whether the test method is more diagnostic than the traditional, simple and inexpensive midnight 1 mg dexamethasone suppression test. value.
1, X-ray inspection
(1) Sella-in-slice method or stratified film method: Because the pituitary tumors of patients with Cushing's disease are small, the results of the plain film method are mostly negative, and some patients have only mild abnormal changes with the serrano layered method. The sensitivity is poor and the accuracy is not great, but if the saddle is found to increase, it is helpful for the diagnosis of pituitary tumor.
(2) Adrenal X-ray method: It is helpful for the localization of adrenal space-occupying lesions, but it cannot identify nodular hyperplasia and adenoma.
2, CT examination Because each layer of CT scan is about 10mm, CT resolution is good for pituitary adenomas >10mm in diameter, but for pituitary microadenomas with diameter <10mm, CT may be missed, the positive rate can reach 60 %, so CT, no pituitary tumors were found, and the possibility of microadenomas could not be ruled out.
For the examination of adrenal hyperplasia and adenoma, CT has a large effect and good resolution, because the diameter of adrenal adenoma is often >2cm.
Note: CT examination, to inject contrast agent, in order to prevent allergic reaction, generally give 10mg dexamethasone; CT examination should be arranged after a large dose of dexamethasone inhibition test, otherwise it should be more than 7 days and then do a large dose of ground The dexamethasone suppression test.
3, magnetic resonance (MRI) examination of Cushing's disease, MRI is the preferred method, compared with CT can better distinguish the hypothalamic pituitary and parasagittal structures (cavernous sinus, pituitary stalk and optic chiasm), but the diameter <5mm The resolution of the tumor is still only 50%.
4, B-ultrasound for adrenal hyperplasia and adenoma is good, is a non-invasive examination, convenient, cheap, more accurate, commonly used with MRI, CT for the location diagnosis of Cushing syndrome.
5, other
(1) 131I--iodinated cholesterol adrenal scanning: can show the location and function of adrenal adenoma; the adenoma side is concentrated, the opposite side is often not developed, the image is not as clear as CT.
(2) Measurement of lower sinus ACTH (IPSS): Selective vein blood sampling, ACTH test, if the patient biochemical examination is Cushing's disease, and CT and other scans are negative, this test can be done.
Diagnosis
Diagnosis and differentiation of Cushing's syndrome
diagnosis
The diagnosis of cortisol is divided into three aspects: the diagnosis of the disease, the diagnosis of the cause and the diagnosis of the location.
(1) Determining the diagnosis of diseases mainly depends on typical clinical symptoms and signs, such as central obesity, purple lines, increased hair, sexual dysfunction, fatigue, etc., plus a significant increase in urinary 17-hydroxycorticosteroids, low-dose dexamethasone inhibition test Can not be inhibited and blood 11 hydroxycorticosteroids above normal levels and lose the circadian rhythm can be diagnosed as cortisol, early mild cases should be differentiated from simple obesity.
Low-dose dexamethasone test: taking low-dose dexamethasone does not affect the determination of 17-hydroxysteroids in urine, but can feedback inhibition of pituitary secretion of ACTH by measuring the discharge of 17-hydroxycorticosteroids in urine for 24 hours for 6 consecutive days. On the 3rd to 4th day, oral dexamethasone 0.75mg was given once every 8 hours, and the daily measured value was marked on the coordinates and connected into a curve. The ratio of 17-hydroxycorticosteroids in urine was 2 days after the administration of normal people. Significantly reduced before administration, if it is more than half of the decline, it indicates that there is significant inhibition, which is normal, and vice versa. If the decrease is not obvious or does not exceed 50%, it is cortisol.
(B) the cause of diagnosis is the difference between the adrenal adenoma, adenocarcinoma, pituitary tumor caused by cortical hyperplasia, non-pituitary tumor or heterogeneous ACTH secretion of tumor caused by cortical hyperplasia.
Other imaging diagnostic methods are normal adrenal gland, part of the pituitary gland, the adrenal gland occupying the affected side, the adrenal gland occupying the adrenal gland is normal, and the lesions secreting heterologous ACTH may be found.
1. X-ray diagnosis of the sella The pituitary tumor can cause optic nerve compression and temporal hemianopia. The saddle bottom can be seen on the saddle X-ray film. The saddle back osteoporosis is decalcified, the anterior and posterior sacral absorption, and the sella are enlarged. The lamellar or cT can show smaller pituitary tumors, which account for about 10% of cortisol in patients with secondary adrenal hyperplasia caused by pituitary tumors.
2, ACTH stimulation test adrenal hyperplasia still have obvious response to ACTH stimulation, the method is the same as the low-dose dexamethasone test, but intravenously instilled ACTH20u on the 3rd to 4th day (add 5% glucose solution 500 ~ 1000ml Within 8 hours, when adrenal hyperplasia occurs, the discharge of urinary 17-hydroxycorticosteroids is increased by more than 50% 24 hours after injection of ACTH, and the eosinophil count in blood is often decreased by 80-90%. When the adrenal hyperplasia is accompanied by small adenoma or nodular cortical hyperplasia, the response and hyperplasia of the ACTH inhibition test are similar, but sometimes weak or not obvious. In the adrenal cortical tumor, the normal adrenal cortex is in atrophic state, so it cannot be The reaction or reaction is weak, but the course of disease is short, especially small adenoma or rapidly developing cortical cancer. Because the adrenal cortex outside the tumor has not shrunk, there is still a significant response in this test. The heterologous ACTH secretion tumor is secreted by the tumor. ACTH, the adrenal cortex has been in a persistently high state of excitement, so it does not respond to this test.
3. The high-dose dexamethasone inhibition test method is the same as the low-dose dexamethasone test, but the dexamethasone 2 mg every 6 hours on the 3rd to 4th day, and the urinary corticosteroid discharge after 24 hours of administration is reduced by 50 before the administration. More than % of the positive reactions, heterologous ACTH secretion of tumors, cortical adenomas, cortical adenocarcinoma secretion function are autonomic, this test can not respond, and cortical hyperplasia can be significantly inhibited positive, cortex Hyperplasia with small adenoma or nodular hyperplasia Although the ACTH stimulation test can be positive, high-dose dexamethasone can not inhibit its secretion (ie, excitement, but can not be inhibited), at this time need to do other tests to distinguish the cortex The tumor is still hyperplasia.
4, metyrapone (bipyridylpyrrolidine, metformin, Su4885) test metyrapone inhibits 11-hydroxylase and converts 11-deoxycorticosterone to corticosterone and 11-deoxycortisol into cortex The process of alcohol is blocked, the plasma cortisol is reduced, and the feedback inhibition is weakened, which promotes the secretion of a large amount of ACTH in the pituitary, and the increase of plasma ACTH (normal value is <100pg/ml at 8-10 o'clock in the morning), and the synthesis of 11-deoxycortisol increases. - Deoxycortisol is included in the measurement range of 17 hydroxy and 17 ketone corticosteroids, so the discharge of 17 hydroxy and 17 ketone corticosteroids in urine is also increased. Therefore, the test can determine the reserve capacity of pituitary secretion of ACTH. In the case of cortical tumors, a large amount of cortisol is secreted by the tumor autonomously, which inhibits the ability of pituitary to secrete ACTH. The excitatory effect of metyrapone cannot be revealed, and cortisol caused by pituitary adenoma At the time, the pituitary gland can secrete ACTH in large quantities, so it is also negative.
5, vasopressin test vasopressin has a similar effect of CRF, it can be used to determine the reserve function of pituitary secretion of ACTH, cortical hyperplasia was positive (blood ACTH and urinary 17-hydroxycorticosteroids increased), cortical tumors Negative reaction, vasopressin can cause coronary artery contraction, so elderly, coronary heart disease patients should not be tried.
For example, ACTH, metyrapone, and vasopressin were all unresponsive, which may be adrenocortical carcinoma; when the three tests were positive, it was cortical hyperplasia.
(C) localization diagnosis is mainly the location of adrenal cortical tumors, in order to facilitate surgical resection, but at the same time, the diagnosis of the cause is often solved.
1, X-ray chest X-ray can exclude lung cancer and lung metastases.
2, intravenous pyelography to understand the situation of the kidneys, a larger adrenal tumor can move the affected kidney down.
3, retroperitoneal angiography due to adrenal adenoma is generally not too large, and obese patients with retroperitoneal massive adipose tissue can often lead to misdiagnosis, is now rarely used.
4, B ultrasound is convenient and effective, the correct rate of localization diagnosis of adrenal cortical tumors can reach more than 90%.
5. CT can correctly locate adrenal adenomas with a diameter of 0.5 to 1 cm or more.
6, radionuclide labeled iodized cholesterol adrenal scanning normal adrenal gland development is light and symmetrical, some people do not visualize, bilateral adrenal gland imaging is symmetric but concentrated in cortical hyperplasia, cortical adenoma or adenocarcinoma adenomatous adrenal radioactivity Concentration, contralateral imaging, tumor imaging in some cases of adenocarcinoma; tumors in some cases of adenocarcinoma are not visible, may be low-function secretion hormone per unit weight of tumor tissue, less cholesterol per unit weight of tissue This method is not suitable for radioactivity. This method is also applicable to the determination of residual adrenal tissue after surgery, the transplantation of adrenal tissue and the search for vagus adrenal tissue.
7, adrenal angiography caused by cortisol adrenal cortical tumors are generally small, blood supply is not rich, so generally do not do adrenal angiography and blood samples to measure cortisol by intravenous catheter, but also useful for selective adrenal artery or venography Reports showing adrenal adenomas, adenomas that cannot be localized by other methods, especially cortical adenocarcinoma, can be diagnosed by adrenal angiography.
Differential diagnosis
Cushing's syndrome should be differentiated from other diseases, such as simple obesity, hypertension, diabetes, polycystic ovary syndrome, etc., mainly differentiated from simple obesity, according to clinical manifestations and laboratory tests can be more clearly diagnosed, abroad Recently, the maximum dose of dexamethasone inhibition test was reported, that is, the diagnostic value of 32mg method was significantly better than that of 8mg method, and 24h urinary free cortisol was used as the detection index, the result was more sensitive, and the side effects were not significant.
1. Simple obesity and type 2 diabetes: may have obesity, high blood pressure, abnormal glucose metabolism, menstrual disorders, skin white lines, etc., blood cortisol and its metabolites are increased, but can be inhibited by low-dose dexamethasone, cortex Alcohol and ACTH rhythm are normal.
Second, pseudo Cushing syndrome: alcoholic liver damage, not only various symptoms and hormone levels similar to this disease, and no response to small doses of dexamethasone or reduced response, but abstinence can be restored.
Third, depression: Although the increased hormone and its metabolites are not inhibited by small doses of dexamethasone, but no clinical manifestations of Chushing syndrome.
