Increased aldosterone secretion

Introduction Hyperaldosteronism (abbreviated as primary aldosteronism) is hypertension and hypokalemia syndrome caused by excessive secretion of aldosterone from the adrenal cortex. Conn first pointed out in 1955 that the excessive secretion of aldosterone from adrenal adenomas is the cause of this disease, so it is also called Conn syndrome. This disease accounts for 1-2% of hospitalized hypertension cases and is a secondary hypertension that can be cured. However, if the course of disease is too long, long-term high blood pressure and severe hypokalemia can also cause serious harm. Increased aldosterone secretion has primary and secondary points. Primary aldosteronism is caused by excessive secretion of aldosterone from adrenal gland lesions, and secondary aldosteronism is caused by excessive aldosterone secretion from adrenal glands other than diseases of the adrenal gland, such as cirrhosis, congestive heart failure, nephrotic syndrome, Renal hypertension and so on.

Cause

Excessive aldosterone secretion from adrenal adenomas is the cause of this disease.

(1) Causes of the disease

The cause is still unclear. According to the pathological changes and biochemical characteristics of the cause, there are five types of primary aldosteres:

1. Aldosterone-producing adenoma (APA): A benign tumor that occurs in the spheroidal band of the adrenal cortex and secretes aldosterone, the classic Conn syndrome. Is the main cause of primary aldosteronism, the most common type of clinical, accounting for 65% to 80%, the most common with a single adenoma, the left side more than the right side; bilateral or multiple adenomas only account for 10%; individual patients can one side It is an adenoma and the other side is hyperplasia. The tumor is between 1 and 2 cm in diameter with an average of 1.8 cm. The weight is between 3 and 6 g, and it is rare to exceed 10 g. Most of the tumors are round or oval, the capsule is intact, and there is a clear boundary with the surrounding tissue. The cut surface is golden yellow. The adenoma is mainly composed of large transparent cells, which are 2 to 3 times larger than the normal bundled cells.

Under the light microscope, adrenal cortical spheroid cells, reticular bands or dense cells, and "hybrid cells" of different sizes are displayed. "Hybrid cells" are characterized by globular bands and bundles of cells, and some adenoma cells can simultaneously have diffuse proliferation of spheroidal cells. Under the electron microscope, the mitochondria of the tumor cells showed a small plate shape, showing the characteristics of the globular band cells. The cause of aldosteronoma is unknown. The plasma aldosterone concentration in patients is parallel to the circadian rhythm of plasma ACTH, but no significant change in plasma renin changes. This type of patient has obvious biochemical abnormalities and clinical symptoms compared with other types of primary aldosteronism.

2. Idiopathic hyper aldosteronism (IHA) is abbreviated as aldosteronism, i.e., idiopathic adrenal hyperplasia, accounting for 10% to 30% of adult primary aldosteronism, and accounting for the first place in children with primary aldosteronism. The incidence rate has increased in recent years. The pathological change is cell proliferation of the bilateral adrenal globular zone, which may be diffuse or focal. The hyperplastic cortex shows micro nodules and large nodules. The hyperplastic adrenal gland is larger in volume, weight and weight increase. The large nodular hyperplasia can be seen on the surface of the adrenal gland. The golden nodules are bulging, as small as sesame seeds, as large as soybeans, no nodules in nodules. This is the fundamental difference between pathology and adenoma. . Light-filled cells can be seen under light microscopy, similar to normal bundled cells. Most of the nodules are scattered or clustered. The cause of the aldosteronism is still unclear. The aldosteronism has histologically stimulated expression of the adrenal gland, while the aldosterone synthase gene has no mutation, but the expression of the gene is increased and the enzyme activity is increased. Some scholars believe that the spheroidal band of patients with aldosteronism is overly sensitive to ATII, and the use of ACEI drugs can reduce aldosterone secretion.

Other scholars have proposed the hypothesis of the pathogenesis of aldosteronism: abnormal activity of certain serotonergic neurons in the central nervous system, stimulation of pituitary aldosterone stimulating factor (ASF), -endopeptide (- Endorphin, -END) and -melanocyte stimulating hormone (-MSH) are excessive, causing the adrenal cortical spheroidal zone to proliferate and secrete a large amount of aldosterone. The study also found that the serotonin antagonist cyproheptadine can significantly reduce the level of aldosterone in the blood of this type of patient, suggesting that serotonin activity is enhanced, which may be related to the pathogenesis of this disease. However, there is no evidence that any of the aforementioned pro-opiomelanocortin (POMC) products reach a concentration that stimulates spheroidal cell function in the blood circulation of patients with aldosteronism. The biochemical abnormalities and clinical symptoms of patients with aldosteronism were not as obvious as those of APA patients, and the concentration of blood aldosterone was not parallel with the circadian rhythm of ACTH.

3. Glucocorticoid-remediable aldosteronism (GRA) Also known as dexamethasone suppressible hyperaldosteronism (DSH). Since the first case of Suther-land DJA and other reports in 1966, more than 50 cases have been reported in foreign literature in 1990. There are also cases and family reports in China, which is a special type of primary aldosteron, accounting for about 1%. More than adolescent onset, may be familial or sporadic, familial is inherited in an autosomal dominant manner. The adrenal gland showed large and small nodular hyperplasia, and its plasma aldosterone concentration was parallel to the circadian rhythm of ACTH.

The hallmark of this disease is that exogenous ACTH can stimulate the secretion of aldosterone, while low-dose dexamethasone can inhibit the excessive secretion of aldosterone and restore normal blood pressure, serum potassium and renin activity. The molecular biological mechanism of its pathogenesis revealed that the gene encoding aldosterone synthase and the gene encoding 11-hydroxylase were non-equivalent exchange, and a new chimeric gene was generated. The 5' end of the chimeric gene was 11. The hydroxylase is regulated by ACTH, and the 3' end is the coding sequence of aldosterone synthase. The chimeric gene transcriptional translation product has aldosterone synthase activity, but its 5' end contains an ACTH-regulated sequence, which results in the synthesis and secretion of aldosterone regulated by ACTH and expressed mainly in the ligament. When exogenous corticosteroids are used, the secretion of pituitary ACTH is inhibited by feedback, the expression level of the chimeric gene is decreased, and the secretion of aldosterone is also lowered. Therefore, the exogenous dexamethasone is given to the patient, and the condition can be controlled satisfactorily.

4. Primary adrenal hyperplasia (PAH) accounts for about 1% of primary aldosteronism. Kater et al. found four cases between APA and IHA in 1982. The pathological morphology was similar to that of IHA. It may be unilateral or bilateral adrenal spheroidal hyperplasia, but its biochemical changes are similar to APA. This disease has a good response to spironolactone treatment, unilateral or subtotal resection of the adrenal gland can correct the symptoms and biochemical abnormalities of aldosterone.

5. Aldosterone-producing carcinoma (APC) It is a type of adrenal cortical carcinoma that accounts for about 1% to 2% of primary aldosteronism. Can be seen in any age group, but more than 30 to 50 years old.

There is also a type in the literature that classifies ectopic aldosterone producing adenoma and carcinoma into primary aldosteronism, which is extremely rare and can occur in the kidney, adrenal residual tissue or ovary.

an examination

Related inspection

Urine routine biochemical examination of saliva sodium/potassium ratio serum aldosterone (ALD, ALS) saline infusion test

(1) Blood biochemical examination

1, blood potassium: determine whether there is hypokalemia is important for the diagnosis of this disease. For the determination of the results is more reliable, the diuretic should be stopped for 3 to 4 weeks before the examination. It has been claimed that during the examination, 6 g of sodium chloride (3 times orally) is orally administered daily for 5 to 7 days, and it is more reliable to perform multiple measurements. Blood potassium can be reduced to 2.0 to 3.0 mmol/L. However, the clinical symptoms of hypokalemia in the early stage of the disease often do not exist, and even the blood potassium is also in the normal range. At this time, only the aldosterone secretion rate is increased, the plasma renin activity is low, and hypertension is suspected. After several years, it developed into intermittent hypokalemia, with paroxysmal myasthenia and paralysis after stress. It was later developed to develop persistent hypokalemia with paroxysmal paralysis. In particular, changes in renal tubular disease are the result of long-term hypokalemia. Therefore, hypokalemia is gradually becoming clear as the condition worsens.

2, blood chloride: often lower than the normal value.

3, blood sodium: there is a slight increase.

4, carbon dioxide binding rate: often rising, suggesting metabolic alkalosis.

5, the plasma pH is often high, up to 7.6.

6, calcium, phosphorus are mostly normal. The free calcium is often low.

7, magnesium normal blood magnesium 0.85 ± 0.15mmol / L. The patient can be slightly reduced.

8, glucose tolerance test: due to potassium loss, inhibition of insulin secretion, oral glucose tolerance test can show tolerance.

9. Determination of aldosterone in venous plasma: normal person lying position is 5.2 ± 2 g / dl. The patient's disease is significantly elevated, especially in adrenal cortical tumors.

(two) urine

1, increased urine output: urine routine weight reduction, and tend to be fixed. Alkaline or neutral, sometimes with urinary tract infections.

2, urinary potassium: Although there is hypokalemia in the ordinary diet, but urinary potassium is still more, more than 30mmol / 24h, is the characteristics of this disease.

3, urinary aldosterone: often higher than normal (10g / 24h). However, the urinary aldosterone excretion is affected by many factors, and the sodium and potassium intake (sodium 160 mmol/d, potassium 60 mmol/d) should be fixed during the measurement. And repeated measurements are reliable. When blood potassium levels are severely reduced, the increase in urinary aldosterone excretion is not significant. For those with normal urinary aldosterone emission, it is necessary to measure the urinary aldosterone, aldosterone secretion rate or venous plasma aldosterone after potassium supplementation. If it increases, it has diagnostic value.

(3) Sodium/potassium ratio in saliva

Normal <2.0, <1.0 should be suspected of primary aldosteronism.

(4) Some special tests

1. Potassium load test: Under normal dietary conditions (daily sodium 160 mmol, potassium 60 mmol), after 1 week of observation, potassium metabolism was found to be negatively balanced. Following the supplementation of potassium for 1 week, the daily increase of potassium 100mmol, but still can not correct hypokalemia. However, other causes of hypokalemia, blood potassium has a significant increase.

2, the effect of changes in sodium content in food on potassium metabolism Low sodium test: normal people when the intake of sodium chloride in food is less than 20 ~ 40mmol / d, after 1 week, urine aldosterone increased, urine sodium decreased, but urine potassium is not reduce. However, in patients with hyperaldosteronism, urinary sodium is lowered due to continued storage of sodium and potassium, and the already increased aldosterone is not further increased, and urinary potassium is also lowered. The reason for the decrease in urinary potassium is due to the reduction in urinary sodium, which limits the exchange with potassium. High sodium test: For patients with suspected aldosteronism who have mild disease and no significant reduction in serum potassium, they can be tested for high sodium. Take 240 mmol of sodium daily for 1 week. In the case of mild aldosteronism, a large amount of sodium enters the distal convoluted tubule and undergoes ion exchange, which increases urinary potassium excretion and lowers blood potassium. In the typical case of severe hypokalemia, high sodium should not be tested to avoid aggravating the condition. The effect of sodium intake on renin and aldosterone.

3, spiral lactone (antisulphon, Spironolactonum) treatment test: This drug can antagonize the effect of aldosterone on the electrolyte in the renal tubules to improve symptoms, but the urinary aldosterone displacement is still significantly increased. The method is to take 300 to 400 mg of diazepam orally for 3 to 4 times a day for 1 to 2 weeks. After taking the drug, the blood potassium level returned to normal and the blood pressure dropped to normal. Patients with secondary aldosteronism have the same results as aldosteronism.

4. Determination of plasma renin activity: normal human plasma renin activity (when daily sodium intake is 200mmol, standing for 3 hours) is 3.2±0.5mg/ml, daily sodium intake is 10mmol, standing for 3 hours It was 17.6 ± 0.9 ng / ml. In aldosteronism, there is a significant decrease in both high sodium and low sodium conditions. The secondary aldosteronism was significantly increased. Therefore, it can be used to identify hyperaldosteronism and secondary aldosteronism. Normal plasma angiotensin II has the same meaning. Its normal value averaged 26±10pg/ml, and the standing position accelerated the average increase of 45±38 after urinary stimulation. It is decreased in hyperaldosteronism and increases in secondary aldosteronism.

Differential diagnosis

Essential hypertension

The disease uses potassium-sparing diuretics, but also does not promptly add potassium, or due to diarrhea, vomiting and other causes of hypokalemia, especially in patients with low-renin type, need to be identified. However, patients with essential hypertension, blood and urine aldosterone is not high, the treatment of common antihypertensive drugs is effective, caused by diuretics caused by hypokalemia, blood potassium can be restored to normal after stopping the drug, if necessary, combined with some of the above tests is not difficult to identify.

2. Secondary aldosteronism

It refers to an increase in aldosterone due to activation of the renin-angiotensin system and hypokalemia. The main differences between the two should be identified:

(1) renal artery stenosis and malignant hypertension: these patients generally have higher blood pressure than the original aldosteronism, and the disease progresses rapidly, often accompanied by obvious retinal damage. Patients with malignant hypertension often develop renal insufficiency in a short period of time. About 1/3 of patients with renal artery stenosis can be seen in the middle of the upper abdomen, on both sides of the umbilicus or in the corners of the ribs. Renal vascular murmur, radioactive kidney diagram, venous pyelography and collateral renal function tests can be seen. The kidneys shrink. Renal angiography confirms the location, extent, and nature of the stenosis. In addition, the patient's renin-angiotensin system activity is increased and can be distinguished from the original aldosteronism.

(2) Loss of salt nephritis or pyelonephritis: often high blood pressure with hypokalemia is sometimes indistinguishable from this disease, especially those with the above complications in the late stage of primary aldosteronism. However, in the late stage of nephritis or pyelonephritis, renal function damage is often severe, accompanied by acidosis and hyponatremia. Low sodium test can not reduce urinary potassium, blood potassium does not rise, blood pressure does not drop. The spironolactone test did not correct potassium loss and hypertension. Increased plasma renin activity was confirmed as secondary aldosteronism.

3. Other adrenal diseases

(1) hypercortisolism: especially caused by adenocarcinoma or ectopic ACTH syndrome, but the symptoms, signs and cachexia of the primary disease can be identified.

(2) Congenital adrenal hyperplasia: such as 11-hydroxylase and 17-hydroxylase deficiency have high blood pressure and hypokalemia. The former is caused by high blood pressure and hypokalemia caused by a large amount of deoxycorticosterone. It is masculine in women and causes precocious puberty in men. The latter has decreased estrogen and cortisol, female sexual insufficiency, and male pseudohermaphroditism. Clinically, Not difficult to identify.

4. Other

Pseudohyperaldosteronism (Liddle syndrome), renin secretory tumor, Batter syndrome, licorice preparation, carbenoxolone (tocopherol) and contraceptives can cause high blood pressure and hypokalemia. Plasma renin-angiotensin II-aldosterone system examination, current medical history and family history are helpful in identification.

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.