Excessive secretion of mineralocorticoids
Introduction
Introduction Mineralocorticoid: mainly acts on sodium, potassium, chloride and water metabolism, so it is called mineralocorticoid. Among these hormones are aldosterone and deoxycorticosterone, among which aldosterone is the strongest. Mineralocorticoids have the effect of preserving sodium and potassium, promoting the reabsorption of sodium by the renal tubules and the effect of potassium release, thereby maintaining the proper concentration of sodium and potassium in the plasma. When the adrenal cortex hyperfunction (such as Cushing's syndrome), 11-deoxycorticosterone secretion, due to retention of sodium and water in the body beyond the limits of edema, increased blood volume, elevated blood pressure, high blood sugar, hypokalemia Wait. Conversely, if the adrenal cortical function is insufficient, the metabolism of sugar and minerals is disordered, causing a bronze disease, or "Addison's disease", which shows muscle weakness, decreased blood pressure, skin pigmentation and hypoglycemia, blood. Symptoms such as decreased sodium and increased potassium, while blood loses water and concentrates, and are life-threatening in severe cases.
Cause
Cause
The cause of excessive secretion of salt corticosteroids
Adrenal hyperfunction, such as Cushing's syndrome, is caused by:
(A) iatrogenic cortisol: long-term use of glucocorticoids in the treatment of certain diseases may have clinical manifestations of cortisol, which is very common in the clinic. This is caused by exogenous hormones and can be gradually restored after stopping the drug. However, long-term use of glucocorticoids can feedback inhibition of pituitary secretion of adrenocorticotropic hormone (ACTH), 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, so it should be noted. Cortisol can also occur with long-term use of ACTH.
(B) pituitary bilateral adrenal hyperplasia: bilateral adrenal hyperplasia is caused by excessive secretion of ACTH in the pituitary. The reason: 1 pituitary tumor. More common basophils, also seen in chromoblastoma; 2 pituitary no obvious tumor, but increased secretion of ACTH. It is generally believed to be caused by excessive secretion of corticotropin releasing factor (CRF) from the hypothalamus. Clinically, only about 10% of the pituitary tumors can be found. In this type of case, due to the abnormal high level of ACTH secretion from the pituitary, the increase of plasma cortisol is not enough to cause normal feedback inhibition, but oral high-dose dexamethasone can still inhibit.
(C) bilateral adrenal hyperplasia caused by extracorporeal lesions: bronchial lung cancer (especially oat cell cancer), thyroid cancer, thymic cancer, nasopharyngeal carcinoma and tumors originating from neural crest tissue can sometimes secrete an ACTH-like substance, Similar to the biological effects of ACTH, which cause bilateral adrenal hyperplasia, it is called heterologous ACTH syndrome. These patients also often have significant muscle atrophy and hypokalemia. The secretion of ACTH substances in the lesions is autonomous, and oral high-dose dexamethasone has no inhibitory effect. After the lesion is removed or cured, the condition gradually subsides.
(4) Adrenal cortical tumors: Most of them are benign adrenal adenomas, and a few are malignant adenocarcinomas. Tumor growth and secretion of adrenocortical hormone are autonomous and not controlled by ACTH. Since the tumor secretes a large amount of corticosteroids, the feedback inhibits the secretion function of the pituitary, which lowers the plasma ACTH concentration, so that the normal adrenal cortex of the non-tumor part is obviously atrophied. In patients with this type of ACTH-induced or high-dose dexamethasone, the amount of cortisol secreted does not change. In adrenal cortical tumors, especially 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 a brownish-yellow color and a complete envelope. The morphology and arrangement of tumor cells are similar to those of adrenocortical cells. Adenocarcinoma is often large, fishy, infiltrating or spreading to surrounding organs, often with lymph nodes and distant metastases. The cells are characterized by malignant cells. Adrenal cortical tumors without endocrine function do not cause cortisol.
Clinically, a few cases of adrenal gland are nodular hyperplasia, which is an intermediate type of hyperplasia and adenoma. Patients with plasma ACTH can be reduced, 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. .
Examine
an examination
Related inspection
Adrenocorticotropic hormone (ACTH) adrenal CT examination adrenal MRI examination adrenal medullary imaging adrenal cortical imaging
Excessive secretion of salt corticosteroids
(A) to determine the diagnosis of the disease: mainly based on typical clinical symptoms and signs. Such as centripetal obesity, purple lines, increased hair, sexual dysfunction, fatigue and so on. In addition, the discharge of urinary 17-hydroxycorticosteroids was significantly increased, and the low-dose dexamethasone inhibition test could not be inhibited and the blood level of the 11-hydroxycorticosteroid was higher than normal and the circadian rhythm was lost to confirm the diagnosis of cortisol. Early mild cases should be differentiated from simple obesity.
Low-dose dexamethasone test: taking a small dose of dexamethasone does not affect the determination of 17-hydroxysteroids in the urine, but can feedback inhibition of pituitary secretion of ACTH. The method was to measure the discharge of 17-hydroxycorticosteroids in urine for 24 hours for 6 consecutive days, and to administer oral dexamethasone 0.75 mg once every 8 hours on days 3 to 4. The values measured each day are marked on the coordinates and connected to a curve. The discharge of 17-hydroxycorticosteroids in urine in normal people 2 days after administration was significantly lower than that before administration. If it decreased by more than half, it showed significant inhibition, which was normal. Conversely, if the decrease is not obvious or does not exceed 50%, it is cortisol.
(B) etiological diagnosis: that is, the difference is caused by adrenal adenoma, adenocarcinoma, pituitary tumor caused by cortical hyperplasia, non-pituitary tumor or heterogeneous ACTH secretory tumor caused by cortical hyperplasia.
1. X-ray diagnosis of the sella: Pituitary tumors can cause optic nerve compression and lateral hemianopia. On the saddle X-ray point piece, the saddle bottom and the saddle back osteoporosis were decalcified, and the anterior and posterior absorption was performed, and the sella was enlarged. Layered tablets or cT can show smaller pituitary tumors. This secondary adrenal hyperplasia caused by pituitary tumors accounts for about 10% of cortisol.
2. ACTH stimulation test: Adrenal hyperplasia still has a significant response to ACTH stimulation. The method was the same as the low-dose dexamethasone test, but intravenously dripped into ACTH20u every day on the 3rd to 4th day (into 5% glucose solution 500-1000ml, 8 hours). In adrenal hyperplasia, the discharge of urinary 17-hydroxycorticosteroids was increased by more than 50% 24 hours after injection of ACTH, and the eosinophil count in blood was often decreased by 80-90%. When adrenal hyperplasia is associated with small adenoma or nodular cortical hyperplasia, the response and hyperplasia of the ACTH inhibition test are similar, but sometimes weak or insignificant. In adrenal cortical tumors, the normal adrenal cortex is in atrophic state, so it does not respond or the reaction is weak. However, the course of the 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 relatively obvious response in this test. Heterogenous ACTH-secreting tumors have been secreted by ACTH in a large amount of tumors, and the adrenal cortex has been in a state of persistent high excitability, so this test does not respond.
3. High-dose dexamethasone inhibition test: The method is the same as the low-dose dexamethasone test, but 2 mg of dexamethasone is given every 6 hours on the 3rd to 4th day. After taking the drug for 24 hours, the discharge of 17 hydroxycorticosteroids was more than 50% lower than before administration. The secretory function of heterologous ACTH-secreting tumors, cortical adenomas, and cortical adenocarcinomas was autonomic and did not respond to this test. Cortical hyperplasia can be significantly inhibited by a positive reaction. Cortical hyperplasia with small adenoma or nodular hyperplasia Although the ACTH stimulation test can be positive, high-dose dexamethasone does not inhibit its secretion (ie, excitement, but no inhibition). At this time, other tests are needed to distinguish whether it is a cortical tumor or a hyperplasia.
4. Mepyridone (bipyridylpyrrolidone, metformin, Su4885) test: Mepyridone inhibits 11-hydroxylase and converts 11-deoxycorticosterone into corticosterone and 11-deoxycortisol into The process of cortisol is blocked, which lowers plasma cortisol, and the feedback inhibition is weakened, prompting the pituitary to secrete a large amount of ACTH. Plasma ACTH increased (normal value 8 ~ 10 o'clock <100pg / ml), 11-deoxycortisol synthesis increased. 11-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 hyperplasia, the metyrapone test was positive; in the case of cortical tumors, the carcinogen autonomously secreted a large amount of cortisol, inhibiting the ability of the pituitary to secrete ACTH, and the excitatory effects of metyrapone could not be revealed. In the case of cortisol caused by pituitary adenoma, the pituitary gland can secrete ACTH in large quantities, so it is also negative.
5. Vasopressin test: Vasopressin has a similar effect as CRF, so 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 were negative. Vasopressin can cause coronary artery contraction, so elderly, coronary heart disease patients should not be tried. For example, ACTH, metyrapone, and vasopressin were unresponsive, which may be adrenocortical carcinoma. When the three tests were positive, they were cortical hyperplasia.
(C) localization diagnosis: mainly the location of adrenal cortical tumors, in order to facilitate surgical resection. However, at the same time of positioning, the cause diagnosis is often solved.
1. X-ray chest X-ray: Excluding lung cancer and lung metastases.
2. Intravenous pyelography: understand the condition of both kidneys. Larger adrenal tumors can move the affected kidney down.
3. Retroperitoneal angiography: Because adrenal adenomas are generally not too large, and obese posterior retroperitoneal massive adipose tissue can often lead to misdiagnosis, which is now rarely used.
4.B Ultra: 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 scan: Normal adrenal gland development is light and symmetrical, and some people do not visualize. Adrenal gland imaging on both sides of the cortical hyperplasia is symmetrical but concentrated. In the case of cortical adenoma or adenocarcinoma, the adenoma side adrenal gland is radioactively concentrated, and the contralateral side is not visualized. Tumor imaging in some cases of adenocarcinoma; tumors in some cases of adenocarcinoma are not imaged, it may be that the tumor tissue per unit weight is a low-functioning secretory hormone, and the tissue per unit weight of tissue is less cholesterol, resulting in no radioactivity. This method is also applicable to the determination of residual adrenal tissue after surgery, transplanted adrenal tissue, and the search for vagus adrenal tissue.
7. Adrenal angiography: Adrenal cortical tumors that cause cortisol are generally small, and blood supply is not abundant. Therefore, blood samples are not taken for adrenal angiography and transvenous catheters.
Diagnosis
Differential diagnosis
Symptoms of excessive secretion of salt corticosteroids
1. Simple obesity and type 2 diabetes: may have obesity, hypertension, 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.
Diagnosis is based on the symptoms, etiology, and location of the disease.
