primary aldosteronism
Introduction
Introduction to primary aldosteronism Primary aldosteronism (primary aldosteronism) is caused by the lesion of the adrenal cortex, which secretes excessive aldosterone, resulting in retention of water and sodium, increased blood volume, and inhibition of the activity of the renin-angiotensin system. A syndrome characterized by hypertension and hypokalemia. Most are caused by adrenal aldosterone adenomas, and may also be idiopathic aldosteronism. basic knowledge The proportion of illness: 0.07% Susceptible people: no special people Mode of infection: non-infectious Complications: Hypertension, cerebral infarction
Cause
Causes of primary aldosteronism
(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. Adrenal aldosterone-producing adenoma (APA): a benign tumor that occurs in the spheroidal band of the adrenal cortex and secretes aldosterone, the classic Conn syndrome, which is the main cause of primary aldosteronism, the most common type of clinical, accounting for 65 %80%, the most common adenoma, left side more than the right side; bilateral or multiple adenomas only account for 10%; individual patients can be adenoma on one side, hyperplasia on the other side, tumor diameter 1 ~ 2cm Between the average, 1.8cm, the weight is between 3 ~ 6g, more than 10g are rare, the tumor is mostly round or oval, the capsule is intact, there is a clear boundary with the surrounding tissue, the cut surface is golden yellow, the adenoma is mainly It consists of large transparent cells, which are 2 to 3 times larger than normal bundled cells. Under light microscopy, adrenal cortical spheroid cells, reticular or dense cells, and "hybrid cells" of different sizes, "miscellaneous" "Combined cells" showed the characteristics of globular bands and bundled cells. Some adenoma cells can simultaneously have diffuse proliferation of spheroidal cells. The mitochondrial ridges of tumor cells under electron microscope are small plate-like, showing the characteristics of spheroidal cells, aldosteronoma. Unknown cause Patients with plasma aldosterone concentration and plasma ACTH circadian rhythm in a parallel, but no significant response to changes in plasma renin, patients with this type of biochemical abnormalities and clinical symptoms than other types of primary aldosteronism and typically significantly.
2. Idiopathic hyper aldosteronism (IHA): 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 an increasing trend, and the pathological changes are cell proliferation of bilateral adrenal spheroidal bands, which may be diffuse or focal, hyperplastic cortex visible micronodules and large nodules, hyperplastic adrenal gland volume, thickness, Increased weight, large nodular hyperplasia on the surface of the adrenal gland can be seen as golden nodular bulge, as small as sesame, as large as soybeans, no nodules in the nodules, which is the fundamental difference between pathological and adenoma, visible under the light microscope Cells, similar to normal bundled cells, most of which are scattered or clustered. The etiology of aldosteronism is still unclear. The aldosteronism has histologically stimulated adrenal gland, and the aldosterone synthase gene There is no mutation, but the expression of this gene is increased and the enzyme activity is increased. Some scholars believe that the spheroidal band of patients with aldosteronism is oversensitive to ATII, and the use of ACEI drugs can reduce the secretion of aldosterone. Scholars have proposed the hypothesis of the pathogenesis of aldosteronism: abnormal activity of some serotonergic neurons in the central nervous system, stimulation of pituitary aldosterone stimulating factor (ASF), -endophage (-endorphin, -END) and -melanocyte stimulating hormone (-MSH), 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 make this The levels of aldosterone in the blood of patients with various types of patients decreased significantly, suggesting that serotonin activity is enhanced, which may be related to the pathogenesis of this disease, but there is no evidence that any of the former pro-opiomelanocortin (POMC) products are In patients with aldosteronism, the concentration of spheroid cells can be stimulated in the blood circulation. The biochemical abnormalities and clinical symptoms of patients with aldosteronism are not as obvious as those of APA patients. The concentration of blood aldosterone is not parallel with the circadian rhythm of ACTH.
3. Glucocorticoid-remediable aldosteronism (GRA): also known as dexamethasone suppressible hyperaldosteronism (DSH), since 1966 Suther-land DJA reported first Since the case, there have been more than 50 cases reported in foreign literature in 1990. There are also cases and family reports in China. It is a special type of primary aldosteronism, accounting for about 1%, more than adolescent onset, but may be familial or sporadic. Familial individuals are inherited in an autosomal dominant manner. The adrenal gland is large and small nodular hyperplasia. The plasma aldosterone concentration is parallel to the circadian rhythm of ACTH. This disease is characterized by exogenous ACTH that can stimulate aldosterone secretion. Low-dose dexamethasone can inhibit the excessive secretion of aldosterone and restore the patient's blood pressure, serum potassium and renin activity to normal. The molecular biological mechanism of the disease found that the gene encoding aldosterone synthase and the encoding 11-hydroxylase The gene is non-equivalically exchanged and a new chimeric gene is generated. The 5' end of the chimeric gene is the sequence regulated by ACTH for the 11 hydroxylase. Its 3' end is the coding sequence of aldosterone synthase. The chimeric gene transcriptional translation product has aldosterone synthase activity, but its 5' end contains ACTH-regulated sequences, which can lead to the regulation and synthesis of aldosterone by ACTH. It is mainly expressed in the fascicular zone. 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, so the patient is given exogenous dexamethasone. The condition can be controlled more satisfactorily.
4. Primary adrenal hyperplasia (PAH): about 1% of the original aldosteronism, Kater et al found in 1982 four cases between APA and IHA, its pathological morphology and IHA Similarly, it can 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, accounting for about 1% to 2% of primary aldosteronism, and can be found 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.
(two) pathogenesis
Regardless of the cause or type of primary aldosteronism, its pathophysiological changes are caused by a large amount of aldosterone in super-physiological requirements, mainly hypernatremia, hypokalemia, renin-angiotensin system inhibition and alkali Poisoned.
Aldosterone is the most important mineralocorticoid in human body. Its main physiological function is to promote the reabsorption of sodium ions by the distal convoluted tubules and collecting ducts of the kidney and excretion of potassium ions. The patients with primary aldosteronism can secrete a large amount of aldosterone to exert the above physiological effects. :1 increased sodium reabsorption, decreased sodium excretion, sodium metabolism was "positively balanced", sodium retention in the body caused extracellular fluid to dilate, blood volume increased; 2 increased concentration of Na in the extracellular fluid, Na transferred to the cell Increased sodium concentration in the blood vessel wall cells can enhance the reaction of the wall to norepinephrine and other pressurized substances in the blood; 3 the sodium concentration in the smooth muscle cells of the arterial wall increases, causing the water to remain in the cells and the blood vessel wall to swell The lumen is narrow and the peripheral resistance is increased. Due to the combined effects of the above factors, hypertension is formed.
When the blood sodium concentration increases and the extracellular fluid expands to a certain extent, the atrial pressure receptor is stimulated, and the atrial natriuretic peptide (ANP) is atrial natriuretic peptide (ACP). Atrial natriuretic peptide is a kind of sodium, diuretic, The blood pressure lowering circulating hormone, its secretion is affected by the sodium concentration and blood volume in the blood. The increase of blood sodium concentration or blood volume can stimulate the atrial pressure receptor, release atrial natriuretic peptide and atrial natriuretic factor secretion from atrial myocytes. Increased and then inhibited the reabsorption of sodium by the renal proximal convoluted tubules, increasing the concentration of sodium ions reaching the distal convoluted tubules, surpassing the ability of the distal convoluted tubules to reabsorb sodium under the action of aldosterone, and increasing the excretion of urinary sodium, thereby compensating for the large amount of sodium aldosterone. The retention effect makes the sodium metabolism reach a near-balance state, no longer continue to sputum sodium, thus avoiding or reducing the occurrence of malignant hypertension, edema, heart failure, etc. caused by further expansion of extracellular fluid, such a kidney under the action of a large amount of aldosterone The small tube breaks away from the effects of aldosterone, and no longer appears to have significant sodium sputum, which is called the "escape" phenomenon of mineralocorticoid. Can also inhibit hormone-secreting cells of the juxtaglomerular renin secretion and adrenal aldosterone, and can antagonize the vasoconstrictor angiotensin (AT) a.
The potassium excretion of aldosterone is closely related to the effect of sodium reabsorption. The effect of aldosterone on potassium excretion in the distal convoluted tubules is affected by the concentration of Na in the distal convoluted tubule. The higher the content of Na in the distal convoluted tubule, the higher the K in the urine. In contrast, the content of Na in the renal distal convoluted tubule is reduced, the K secretion is reduced, and the K excretion in the urine is also reduced, so when the sodium intake decreases or the sodium reabsorption of the proximal convoluted tubule increases, the sodium that reaches the distal convoluted tubule decreases, the aldosterone The potassium excretion is obviously weakened, and the urinary potassium excretion is a passive process. When the Na in the distal convoluted lumen is reabsorbed, the electrical ions in the renal tubule are negative, and the intracellular The cations K and H are excreted in the urine as the electrochemical gradient is secreted into the intraluminal fluid. In patients with primary aldosteron, the sodium reabsorption of the distal convoluted tubule is increased due to the large amount of aldosterone, so the excretion of potassium is also increased. A large amount of potassium loss leads to severe potassium deficiency in the body, and a series of dysfunctions of nerves, muscles, heart, kidneys and pancreas caused by potassium deficiency, and potassium excretion is not affected by "offset". Since sodium "release" is caused by atrial natriuretic peptide, the sodium reabsorption of the proximal convoluted tubule is reduced, but not by the decrease of sodium reabsorption in the distal convoluted tubule. Therefore, sodium reabsorption and Na-K exchange in the distal convoluted tubule are not Change, potassium is still lost, so the high blood sodium of patients with primary aldosteron is often not obvious, but hypokalemia is very common, after the loss of a large amount of potassium ions in the cell, at this time the extracellular fluid Na and H enter the cell, Na and The efficiency of H ion excretion from the cells is reduced, so Na and H in the cells increase, and the extracellular fluid H decreases, causing the pH of the intracellular fluid to decrease to be acidemia, the pH of extracellular fluid to rise, and the increase in CO2CP to be alkalemia.
In the clinical common cause of potassium deficiency in the body caused by other causes (such as anorexia, vomiting, diarrhea), the K content of renal tubular epithelial cells is reduced, so Na-K exchange in the distal convoluted tubule is reduced, Na-H exchange is increased, and urine is acidic. In patients with primary aldosteronism, although potassium is deficient in renal tubular epithelial cells, Na-K exchange in the distal convoluted tubules is promoted due to a large amount of aldosterone potassium excretion, and Na-H exchange is inhibited, and renal tubules are inhibited. Cell secretion H is reduced, so urine is not acidic, but neutral, even alkaline or weakly alkaline, so intracellular acidosis, extracellular fluid alkalosis and alkaline urine become the characteristics of primary aldosteronism, alkalosis When the extracellular fluid free calcium is reduced, and the aldosterone promotes the discharge of urinary magnesium, the blood magnesium is lowered, and the high blood volume of the patients with primary aldosteronism increases the excitability of the cell pressure receptors of the adjacent small arteries and inhibits the glomerulus. The side cells secrete renin, which reduces the production of angiotensin, and thus presents a typical clinical manifestation of low prorennin.
Prevention
Primary aldosteronism prevention
Prevention of aldosteronism prevention should be done 1 normal potassium, sodium fixed diet 2 after 2 to 3 days of adaptation to potassium, sodium fixed diet, 4 to 4 days to stay 24h urine determination of potassium, sodium, simultaneous determination of potassium, blood sodium and Carbon dioxide binding. 3 First, according to the specific circumstances of the patient, the daily intake of the staple food (the flour made by adding alkali or baking powder can not be used in the main sugar). 4 When the non-staple food is arranged, the required amount of K+ is first guaranteed. An appropriate amount of sodium chloride is then used as a seasoning to make up the total amount of sodium required.
Complication
Primary aldosteronism complications Complications Hypertensive cerebral infarction
Patients with primary aldehyde can be concurrently with a benign hypertension because of their renin secretion. For example, high blood pressure persists for a long time, which can cause heart, brain and kidney damage. Long-term hypokalemia can also cause heart involvement. Ventricular fibrillation, it is reported that 34% of 58 patients with primary aldehyde have cardiovascular complications, and 15.5% of patients have stroke, of which 6.9% are cerebral infarction, 8.6% are cerebral hemorrhage, and 9.4% of patients with high heart disease, uremia 1.9% of stroke, 13.2% of stroke (5.79% of cerebral infarction, 9.4% of cerebral hemorrhage).
Symptom
Symptoms of primary aldosteronism Common symptoms Metabolic hypokalemia, polyuria, polydipsia, fatigue, tinnitus, diarrhea, bloating, dizziness, dysphagia, metabolic alkalosis
Hypertension
For the earliest symptoms. Generally, there is no malignant evolution, but as the disease progresses, the blood pressure is gradually higher at around 22.6/13.3 kg (170/100 mmHg) and at high time at 28/17.3 kPa (210/130 mmhg).
2. Neuromuscular dysfunction
(1) Myasthenia and periodic paralysis are very common. Generally speaking, the lower the blood potassium level, the heavier the muscles are, the more common because of fatigue, or the use of hydrochlorothiazide, furosemide and other diuretics to promote potassium, paralysis is more involved in the lower limbs, severely involved in the limbs, breathing can also occur, swallowing Difficulties, the time of paralysis is short, the elders are several days or longer, and the paralysis after potassium supplementation is temporarily relieved, but often relapses.
(2) numbness of the extremities, hands and feet. In the case of severe hypokalemia, due to decreased neuromuscular stress, the hand, foot and ankle may be lighter or less, and after potassium supplementation, the hand, foot and ankle tend to become apparent.
3. Kidney performance
Due to a large loss of potassium, renal tubular epithelial cells are vacuolated, the concentration function is reduced, accompanied by polyuria, especially nocturia, secondary thirst, polydipsia, often complicated by urinary tract infection. Increased urinary protein, a small number of renal dysfunction can occur.
4. Cardiac performance
(1) The electrocardiogram is a hypokalemia pattern.
(2) arrhythmia: more common is paroxysmal supraventricular tachycardia, ventricular fibrillation can occur in the most severe cases.
5. Other performance
Child patients have growth and development disorders, which are related to long-term potassium deficiency and other metabolic disorders. When potassium is deficient, the release of insulin is reduced, and the effect is weakened, and glucose tolerance may be reduced.
Examine
Examination of primary aldosteronism
Laboratory inspection
1. General inspection
(1) hypokalemia: Most patients have lower blood potassium than normal, more than 2 to 3 mmol / L, but also less than 1 mmol / L, low potassium is persistent.
(2) High blood sodium: mildly increased.
(3) Alkaliemia: The intracellular pH decreases, the extracellular pH increases, and the blood pH and carbon dioxide binding force rises at a normal high or slight.
(4) high urinary potassium: disproportionate with hypokalemia. In the case of low potassium, the daily urinary potassium excretion is still >25mmol, and those with hypokalemia caused by potassium loss in the gastrointestinal tract are lower than 15mmol/24h.
(5) urine specific gravity and urine osmotic pressure decreased: kidney concentration function decreased, nocturia more than 750ml.
2. Plasma aldosterone (PAC): renin activity (PRA) determination and lying, standing test Peking Union Medical College Hospital to determine plasma aldosterone, renin activity by: in the general food overnight, the next morning at 8 o'clock in the empty position Immediately after the blood was taken, 40 mg of furosemide was injected intramuscularly, and then the blood was taken at 2 o'clock in the standing position for 2 h. The plasma aldosterone, renin activity concentration and plasma aldosterone normal position were determined by radioimmunoassay. The position was 58.2-376.7 pmol/ L, standing position 91.4 ~ 972.3pmol / L, plasma renin activity normal position lying position 0.2 ~ 1.9ng / (ml · h), standing position 1.5 ~ 6.9ng / (ml · h), primary aldosteron patient lying plasma Aldosterone levels were elevated, and renin activity was inhibited, and the renin activity was not significantly elevated after activity and diuretic stimulation.
Because plasma aldosterone levels overlap in patients with primary aldosteronism and essential hypertension, most scholars have proposed a ratio of plasma aldosterone to renin activity (PAC/PRA) to identify primary aldosteronism and essential hypertension. PAC (ng / dl) / PRA (ng / ml · h) > 25, highly suggestive of the possibility of primary aldosteronism, while PAC / PRA 50 can confirm the original aldosteronism.
3. Determination of urine aldosterone levels
The urinary aldosterone excretion in normal people under normal food conditions was 9.4 ~ 35.2nmol / 24h, and the patients with primary aldosteron were significantly elevated.
4. Saline drip test
The patient was placed in a supine position with an intravenous infusion of 0.9% normal saline at a rate of 300-500 ml/h for 4 h in normal subjects and patients with essential hypertension. After 4 h of saline infusion, plasma aldosterone levels were inhibited to 277 pmol/L (10 ng/dl). In the following, plasma renin activity is also inhibited. In patients with primary aldosteronism, especially in adrenal cortical aldosteronoma, plasma aldosterone levels are still greater than 277 pmol/L (10 ng/dl), which are not inhibited, but patients with adrenal spheroidal hyperplasia may A false negative reaction occurs, that is, the secretion of aldosterone is inhibited, but it should be noted that patients with higher blood pressure and older age and cardiac insufficiency should be banned from this test.
5. Captopril (opening) test
In normal or patients with essential hypertension, plasma aldosterone levels were inhibited to below 416 pmol/L (15 ng/dl) after captopril, whereas plasma aldosterone was not inhibited in patients with primary aldosteronism.
6. Spironolactone test
(spirolactone) patients with aldosteronism, generally take 1 week after the increase of serum potassium, blood sodium decreased, urinary potassium decreased, symptoms improved, continue to take medication for 2 to 3 weeks, most patients can drop blood pressure, blood potassium basically returned to normal, alkali poisoning corrected, This test can only be used to identify the presence or absence of increased aldosterone secretion, but not to identify whether the increase in aldosterone is primary or secondary.
7. Sodium load test low sodium test
Urinary potassium excretion was significantly reduced in patients with primary aldehyde, hypokalemia and hypertension were alleviated, urinary sodium was rapidly reduced and the balance was balanced, and renin activity was still inhibited; there was no significant change in serum potassium in normal and hypertensive patients. In patients with aldosteronism, serum potassium can be reduced to below 3.5mmol/L liter, symptoms and biochemical changes are aggravated, and plasma aldosterone is still higher than normal.
8. Determination of plasma 18-hydroxycorticosterone (18-OH-B)
Plasma levels of 18-OH-B (precursor of aldosterone) in patients with adrenal cortical aldosterone secretory tumors were significantly higher, >2.7 mmol/L (100 ng/dl), whereas patients with idiopathic aldosteronism and essential hypertension were lower. At this level.
Film degree exam
It is of great value in the diagnosis of primary aldosteronism, the diagnosis of etiological types, and the diagnosis of location.
1. Adrenal B-ultrasound : Tumors with a diameter >1.3 cm or more can be detected, but it is difficult to diagnose and differentiate from IHA for small adenomas.
2. Adrenal CT scan: listed as the first choice for the diagnosis of adrenal lesions, and recommended for identification of its type, it can observe the normal adrenal morphology, and can detect APA diameter of 7 ~ 8mm, APA is round Or oval, marginal integrity, because the adenoma cells are rich in lipids, it is characterized by low density (-33 ~ 28Hu), when the unilateral adrenal gland diameter > 1cm of equal density or low density tumor shadow, prompt APA, but should pay attention to identify small cysts protruding from the upper pole of the kidney, distorted splenic vessels, nodules due to partial volume effect, and CT examination should be performed after the diagnosis of primary aldosteronism, in order to exclude some non-functional adrenal accidental tumors. The diagnostic accuracy rate is 70% to 90%, and the diameter of the tumor is >3cm (especially >6cm). The shape is irregular, and the adrenal gland is not homogeneous inside the tumor. The APC is extremely likely, such as the tumor in the non-enhancement film. The CT value is lower than 11Hu, and there is no obvious enhancement after enhancement. It indicates adenoma. The CT value of aldosteronoma adenoma is lower than the adenoma and pheochromocytoma secreting cortisol. Most IHA patients can show normal or one side of adrenal gland. , adrenal glands on both sides Increases, full or straight edges, the density denser, such as nodular hyperplasia and adenoma is difficult to identify, the diagnostic positive rate of about 50% to 70%.
3. Magnetic resonance imaging (MRI) : The specificity of APA diagnosis is high, the accuracy is about 85%. It is considered that MRI is not superior to CT scan. Some people think that the evaluation of the type of primary aldosteron is a promising technology. But it is better to check the economy than CT.
4.131I cholesterol adrenal gland scan: This test is suitable for patients with biochemical examination suggesting primary aldosteronism, but CT examination can not be diagnosed, and has certain value for the identification of APA and IHA. According to 131I cholesterol, the adrenal gland is converted into corticosteroid. Principle, scanning method can be used to show the concentration of 131I in adenoma and hyperplastic tissue. If one side of the adrenal gland is found to have radioactive concentration, it indicates that there is adenoma on the side. Generally, 90% of adenomas can be correctly positioned. If there are radioactive concentrations on both sides, suggesting bilateral hyperplasia, the coincidence rate is 70%, and sometimes the radioactive concentration of the adrenal glands on both sides is asymmetric, one thick and one light, can be given oral dexamethasone 1mg, 4 times / d, After 3 days, the radionuclide tracer dose was given. During the examination, dexamethasone was continued. After 48-72 hours, the affected adrenal gland was radioactively concentrated and contralateral. The patients with primary aldosteron showed a double performance after 72-120 hours. The lateral adrenal gland has a slight radioactive concentration. This test lacks sensitivity to adrenal nodules <1 to 1.5 cm in diameter. It is not diagnosed in patients with APC due to the absence of nuclide concentration in the tumor.
5. Bilateral adrenal vein intubation: Separate blood test for aldosterone This test has become the gold standard for the classification of primary aldosteronism. The primary aldosteronism negative for the basic challenge test includes angiotensin II reactive APA, or CT scan. For a small APA with a normal diameter <5 mm, this test is required. If the aldosterone in the blood of one adrenal venous blood is more than twice the contralateral side, or the concentration difference between the two sides is 554 pmol/L (20 ng/dl), the high one is The side is APA. If the aldosterone in the bilateral adrenal venous blood is increased, but the concentration is only 20% to 50%, it can be diagnosed as IHA. Because it is invasive, there are complications such as thrombosis and hemorrhage. Clinical manifestations and CT, MRI or radionuclide scans can be confirmed in cases that are not required. This test is limited to patients with diagnosed difficulties.
APC is rarely seen as characterized by markedly high aldosteronism, severe hypokalemia <2.5mmol/L, and metabolic alkalosis, which is autonomic, non-responsive to body position, ACTH and sodium load excitability, often secreted at the same time. Glucocorticoids and sex hormones are mixed and have clinical manifestations and endocrine abnormalities. There are also reports of aldosterone secretion alone, but it is rare. About half of them have functional malignant tumors, which are easy to find in clinical practice, while the other half have local symptoms. Abdominal mass or lymphatic, lung, liver, bone and other distant metastasis were diagnosed by imaging examination. B-ultrasound, CT and MRI were the main means of APC diagnosis and clinical staging. The cancer was large and the diameter was more than 3cm. Such as >6cm, weight 90g is an auxiliary diagnostic index, the section can have hemorrhagic necrosis, mitotic figures, atypical mitosis, venous invasion is the three important pathological diagnosis basis, under the electron microscope, cancer cells often have no basement membrane, 131I cholesterol scan can be used in tumor The body is excessively dispersed without the concentration of nuclide, which is not easy to visualize.
Diagnosis
Diagnosis and diagnosis of primary aldosteronism
diagnosis
Hypertensive patients, especially children and adolescents, are mostly secondary hypertension, including primary aldosteronism; hypertensive patients with general antihypertensive drugs are not effective, accompanied by polydipsia, polyuria, especially with Have spontaneous hypokalemia and periodic paralysis, and there are still hypokalemia or electrocardiogram with hypokalemia after paralysis; patients with hypertension can induce hypokalemia with potassium diuretic; suspected of primary aldosteron Probably, further examination is needed to confirm or rule out. Since many drugs and hormones may affect the regulation of the renin-angiotensin-aldosterone system, all drugs, including spironolactone and estrogen, must be stopped for more than 6 weeks before the test. Cyproheptadine, indomethacin, diuretic for more than 2 weeks, vasodilator, calcium channel antagonist, sympathomimetic and adrenergic blocker for more than 1 week, individual patients such as high blood pressure, during the examination Use prazosin, guanethidine and other drugs to ensure the safety of patients, the diagnosis of primary aldosteronism should first determine the presence of primary aldosteronism, and then determine the cause of the original aldosteronism.
1. Diagnosis conditions
If it can be confirmed that the patient has the following three conditions, the original aldosteronism can be diagnosed.
(1) hypokalemia and inappropriate increase of urinary potassium excretion: laboratory examination, most patients with potassium in 2 ~ 3mmol / L, or slightly less than 3.5mmol / L, but the disease is short and the condition is mild, blood Potassium can be in the normal range. If the serum potassium screening standard is set below 4.0mmol/L, the diagnostic sensitivity can be increased to 100%, and the specificity can be reduced to 64%; the blood sodium is mostly in the normal range or slightly higher. Normal; blood chloride normal or low, blood calcium, phosphorus more normal, people with hand and foot sputum free Ca2 is often low, but total calcium is normal; blood magnesium often mildly decreased.
1 Balanced meal test: Due to the early onset or mild condition and the difference in sodium intake, the blood potassium level can fluctuate significantly: the blood potassium level is low when the high sodium intake is high, and the blood potassium rises when the sodium is strictly restricted, in order to exclude different diets. Habits of the effects of potassium and sodium metabolism, this test should be used, that is, under normal dietary conditions, the daily intake of sodium and potassium is controlled at 160mmol and 60mmol, respectively, for 8 days, blood is taken on the 5th, 6th, 7th day. Na, K, CO2CP, and urine 24, urine, Na, K, pH; 8 days 8AM (8 am) blood test aldosterone and 24h urine test urinary aldosterone, patients with primary aldosteron blood sodium is normal Level or slightly higher than normal, urinary sodium <150mmol/24h, can also be >160mmol/24h, showing "dislocation" phenomenon, while blood potassium metabolism shows a negative balance, blood potassium <3.5mmol / L, urinary potassium > 30mmol / 24h (or blood potassium <3.0mmol / L, urinary potassium > 25mmol / 24h), suggesting that patients have inappropriate urinary potassium excretion, urinary tract loss of potassium, in addition, blood CO2CP can be higher than normal, with alkaliemia, and urine The pH is neutral or weakly alkaline, and it is characterized by abnormal alkaline urine. The results of various tests during the balanced meal test can be used as future items. The control comparisons are used to compare the results of subsequent tests to aid in the diagnosis of this disease.
2 high sodium test: According to the literature, 12% of APA patients and 50% of IHA patients have blood potassium levels higher than 3.5mmol/L, so the balanced meal test has no obvious hypokalemia and suspected primary aldosteronism. When high sodium test should be selected to stimulate hypokalemia, the daily sodium intake is increased to 240mmol, potassium is still 60mmol, for 7 days, blood pressure is measured every day, on the 5th, 6th, 7th day blood test Na+, K+, CO2CP, and 24h urine test for Na+, K+, pH in urine, simultaneous measurement of blood and aldosterone excretion in 24h urine on day 7, due to the autonomy of aldosterone secretion in patients with primary aldosteron, not high Inhibition of sodium intake, when the sodium intake increases, the amount of sodium ions reaching the renal distal convoluted tubule increases, sodium reabsorption increases under the action of aldosterone, sodium and potassium exchange promotes increased urinary potassium excretion, blood potassium decreases, and blood pressure rises. High, the symptoms and biochemical changes of the original aldehyde became significant, blood and 24h urine aldosterone were not inhibited, such as urinary sodium excretion >250mmol/24h, suggesting that the supplementation of sodium salt is sufficient, at this time the blood potassium is still normal, and no renal function Evidence of failure can basically rule out primary aldosteronism, if blood potassium <3.5mmol / L, urinary potassium <30mmol / 24h, Insufficient potassium intake, potassium loss in the gastrointestinal tract or incomplete collection of urine, if blood potassium <3.5mmol/L, urinary potassium>30mmol/24h, it is in line with the original aldosteronism, if the blood potassium is >4.1mmol/L, the high can be ruled out Aldosteroneemia, patients with severe hypertension should pay attention to monitoring blood pressure and heart function when giving high sodium test to avoid danger.
3 low sodium test: low urinary potassium or balanced meal test with significant hypokalemia, should be tested for low sodium, which is to limit the daily sodium intake of patients to 10 ~ 20mmol, while the potassium intake is normal, 60mmol For 7 consecutive days, blood pressure was measured every day, and Na+, K+, CO2CP in blood was measured on the 5th, 6th, and 7th days, and Na+, K+, pH in urine was measured for 24 hours, and aldosterone in blood was measured simultaneously on the 7th day. And the aldosterone excretion in 24h urine, the amount of sodium in the patients with primary aldosteron reaching the distal convoluted tubules under low salt conditions is very small, the sodium and potassium ion exchange is reduced, the urinary potassium excretion is reduced, the blood potassium is increased, and the kidney disease is accompanied. In patients with sodium loss and potassium loss, due to the destruction of renal tubular function and inability to sputum sodium, even if sodium intake is restricted, urinary sodium excretion is not reduced, and urinary potassium excretion is not significantly reduced, such as potassium loss. In patients with kidney disease, there was no significant change in urinary sodium and potassium excretion.
4 Spironolactone (Anti-Shutong) test: After the balanced meal test, such as patients with hypokalemia, this test was given to oral spironolactone 25 ~ 75mg, 4 times / d, and even served for 7 days, on the 5th to 7th day, Daily measurement of Na+, K+, CO2CP and Na+, K+, pH in urine, and observation of hypertension and clinical symptoms. Spironolactone can antagonize the action of aldosterone on the sodium and potassium retention of the distal convoluted tubule, so that patients with increased aldosterone usually take the drug. In the past week, there was a significant decrease in urinary potassium, followed by an increase in blood potassium, a decrease in blood sodium, a decrease in blood CO2CP, an increase in urinary pH, an improvement in muscle weakness and paralysis, and a high blood pressure in patients with primary aldosteron for 3 to 5 weeks. Can be reduced, about 28/16mmHg, patients with potassium loss nephropathy, little change before and after taking the drug, the blood pressure of patients with secondary aldosteronism associated with renal vascular hypertension can not be reduced.
(2) Increased and unrestricted aldosterone secretion: Due to the effect of aldosterone secretion, blood volume and sodium concentration, the determination of basic aldosterone levels alone has limited diagnostic value for primary aldehydes, and inhibition tests are needed to confirm aldosterone secretion. Increased and not inhibited, it has a greater diagnostic value, often used to inhibit aldosterone secretion:
1 high sodium inhibition test: normal human urinary aldosterone <28nmol / (L · 24h), blood aldosterone <276.7pmol / L (10ng / dl), patients with primary aldosteron higher than this value, compared patients during balanced meal and high sodium test Blood and urine aldosterone measurements, such as no significant change between the two, suggest that the patient's aldosterone secretion is not inhibited by high sodium.
2 saline infusion inhibition test: on the basis of balanced meals, early morning patients in the supine position blood test aldosterone, plasma renin activity, ATII, blood potassium control, and then 0.9% NaCl solution 2000ml within 4h by intravenous infusion The subject kept the blood in the supine position and reviewed the above items. After the normal person instilled the saline, the plasma aldosterone level decreased by more than 50%, usually decreased to 276.7 pmol/L (10 ng / dl), and the plasma renin activity was also inhibited. However, in patients with primary aldehydes, especially APA, plasma aldosterone levels are still >276.7 pmol/L (10 ng/dl), which are not inhibited. In patients with IHA, false negative reactions may occur, that is, the secretion of aldosterone is inhibited. The blood potassium must be supplemented to 3.5mmol/L or more before the test, because severe hypokalemia (<3mmol/L) can inhibit the secretion of aldosterone, making the measured value of aldosterone at a critical level, or even the normal range, for malignant hypertension, This test is not suitable for patients with congestive heart failure.
39-fluorohydrocortisone test: blood basal aldosterone level and aldosterone excretion in 24h urine, oral 9-fluorohydrocortisone 1mg/24h for 3 days, re-measure blood and urine aldosterone levels Compared with pre-medication, blood and urine aldosterone levels were significantly lower in normal subjects, but there was no significant change in patients with primary aldosteronism. The aldosterone secretion in patients with primary aldosteronism was autonomic and was not inhibited by blood volume expansion.
4 captopril (captopril) inhibition test: early morning blood test for aldosterone and plasma renin activity, captopril 25mg orally, 2h after the blood in the seat Re-measurement of aldosterone and renin activity in blood. Since captopril inhibits the production of angiotensin II, plasma aldosterone levels in normal or essential hypertension patients are suppressed to below 416 pmol/L (15 ng/dl). Patients with primary aldosteronism are not inhibited, which helps to identify primary aldosteronism and essential hypertension. Most scholars consider this test to be safe, effective, and economical.
(3) Reduced plasma renin activity and no excitement: increased blood, urinary aldosterone levels and decreased renin activity are characteristic changes in primary aldosteronism, but renin activity is susceptible to multiple factors, standing position, blood volume Both lowering and lower sodium can stimulate the increase, so the ratio of basic renin activity or plasma aldosterone concentration (ng/dl) to plasma renin activity [ng/(ml·h)] (A/PRA) alone The results of the second measurement are normal, and the original aldosteronism is still not enough. The changes of plasma renin activity, postural stimulation test (PST) and low sodium test are the most commonly used methods. They are not only the original aldosteronism. The diagnosis is based on one of the methods for the diagnosis of the cause of the original aldosteronism.
1 position stimulation test: overnight in the general food position, the next morning at 8:00 in the empty stomach position, immediately after the blood injection of furosemide (furosemide) 40mg (apparently thinner according to 0.7mg / kg body weight, overweight also No more than 40mg), then let it stand for 4h and then take blood. The blood sample should be placed at low temperature (4 °C). After separating the plasma, store it at -20 °C until the measurement, and measure the plasma by radioimmunoassay. Renin activity, angiotensin II and aldosterone.
2 low sodium test: in the morning, supine blood test renin activity, angiotensin II and aldosterone as a control, give patients a low sodium diet (sodium intake 20mmol / d) for 5 days, and let patients on the 5th day After standing for 4 hours, blood was taken for the above examinations. In normal people and most patients with essential hypertension, the plasma concentration increased after the above test, and the level of blood aldosterone in patients with primary aldosteronism increased, and the plasma renin-angiotensin system was affected. Inhibition, and no receptor position, diuretic and low sodium diet stimulation, still does not rise.
If renin activity and angiotensin II increase, it suggests an increase in secondary aldosterone. Most scholars have proposed the use of plasma aldosterone (A) concentration and plasma renin activity (R) ratio as the original aldosteronism and essential hypertension Diagnostic screening method, the ratio is not affected by sodium intake, total potassium deficiency and treatment of hypertension drugs (except spironolactone), can be used for taking antihypertensive drugs, refractory hypertension, hypokalemia and normal potassium Screening of patients with primary aldosteronism can improve the diagnosis rate of primary aldosteronism. The upper limit of A(ng/dl)/R[ng/(ml·h)] is 17.8, and about 89% of APA patients are considered to be normal. And 70% of IHA patients exceed this upper limit, the A/R ratio of primary aldosteron is usually >20 to 25, and when A/R50, the specificity of diagnosis of primary aldosteronism is 100%, and the sensitivity is 92%. The ratio of A(pmol/L)/R[ng/(L·s)] under the stimulation of furosemide and the standing test was used as a method for screening aldosteronoma. The A/R value was considered to be 3200 at the cut point for APA. The diagnosis is highly sensitive and the specificity is low; if the A/R ratio exceeds 10,000, APA can be considered; the A/R ratio <3200 can exclude APA, and many studies have affirmed that A/R is Aldosteronism diagnostic sensitivity and specificity, but there are also completely the opposite conclusion, in short, after the above checks, meet three criteria, the primary aldosteronism can be confirmed.
2. Cause diagnosis
Because most patients with primary aldosteron do not need surgery, and patients with adrenal aldosterone adenoma have satisfactory surgical results, the diagnosis of etiological types is very important. There is no single specific method. It is necessary to comprehensively analyze multiple test results to improve the diagnosis. rate.
(1) Overall condition: the clinical symptoms, signs and biochemical changes of patients with cortical tumors (APA, APC) are more serious than those of IHA patients, while those with PAH are between the two types. GRA patients have a family history and the clinical manifestations are lighter. Spontaneous hypokalemia occurs less frequently.
(2) Postural test: After 1 week of balanced diet, blood was taken from 8AM, then stood for 4h, and then blood was taken to measure aldosterone concentration. The basic plasma aldosterone of APA patients increased significantly, more than 554pmol/L (20ng/dl). After taking the standing position, there is no obvious increase or decrease. This is due to the large secretion of aldosterone in APA patients, the obvious expansion of blood volume, and the inhibition of the activity of renin-angiotensin system. Even if it is standing for 4 hours, it is not enough to stimulate the production of renin, IHA. The patient's basal plasma aldosterone increased only slightly, and increased significantly after standing position, at least 33% of the baseline value. The positional test of PAH and GRA patients was similar to that of APA patients, and a small number of APAs that responded to renin may also behave. IHA is the same.
(3) Determination of 18-hydroxycorticosterone in plasma: APA patients in the morning 8AM blood test for plasma levels of 18-hydroxycorticosterone > 28.86 nmol / L (100 ng / dl), [normal human (10.1 ± 6.5) ng / Dl], IHA patients below this value, due to the severe lack of potassium in APA patients, the final step of aldosterone synthesis, 18-hydroxycorticosterone dehydrogenation to aldosterone slows down, so that 18-hydroxycorticosterone increases, while IHA Patients with potassium deficiency are relatively light and less affected by this.
(4) cyproheptadine test: the patient was given 8 ml of cyproheptadine in the morning, and the blood aldosterone concentration was measured 30 min before taking the drug and 30, 60, 90, 120 min after taking the drug. After taking the drug, the plasma aldosterone concentration decreased by 0.11 nmol. /L (4ng / dl) or more than 30% lower than the baseline value is positive, most IHA patients decreased more significantly 90 minutes after taking the drug, an average of 50% decline, some patients may have blood pressure drop, this cyproheptadine is serotonin (serotonin) antagonists, while serotonin can stimulate the secretion of aldosterone. In patients with primary aldosteronism, serotonin can increase the activity of neurons, resulting in increased aldosterone secretion in the adrenal globular zone. When serotonin is inhibited after taking cyproheptadine, The plasma aldosterone concentration decreased, while the aldosterone secretion in APA patients was autonomic, not regulated by serotonin, and there was no change in blood aldosterone concentration after administration.
(5) Dexamethasone inhibition test: When the patient who has been diagnosed with primary aldosteronism is considered to be a GRA type patient, this test is carried out, and 2 mg of dexamethasone is orally administered to the patient every day. After a few days, the concentration of aldosterone in the blood can be lowered to a normal level. The performance of hypertension and hypokalemia can be improved within 10 days of taking the drug, or even return to normal. After treatment with a small dose of dexamethasone (0.5mg/24h), the patient can maintain normal condition. Some scholars believe that taking the drug After plasma aldosterone level is lower than 4ng/dl, the sensitivity and specificity of GRA are 92% and 100%, respectively. Plasma aldosterone in APA and IHA patients can be transiently inhibited, but generally cannot be reduced to normal levels. And the time of inhibition was short. After taking the drug for 2 weeks, the secretion of aldosterone was no longer inhibited by dexamethasone, and the aldosterone in the blood increased again.
In addition, patients with primary aldosteron such as normal CT examination, plasma aldosterone levels in the body position test is similar to APA, showing a downward trend, and dexamethasone can not inhibit aldosterone secretion should consider PAH.
Differential diagnosis
1. Essential hypertension: This disease uses potassium-sparing diuretics, but it does not promptly supplement potassium, or due to diarrhea, vomiting and other causes of hypokalemia, especially in patients with low-renin type, need to be identified, but primary Hypertensive patients, blood, urine aldosterone is not high, common antihypertensive drugs are 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: refers to the increase in aldosterone due to activation of the renin-angiotensin system, and the occurrence of hypokalemia, which should be distinguished from the original aldosteronism:
(1) renal artery stenosis and malignant hypertension: these patients generally have higher blood pressure than primary 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, kidney About 1/3 of patients with arterial stenosis are in the middle of the upper abdomen. Renal vascular murmurs can be heard on both sides of the umbilicus or in the rib angle area. Radioactive kidney map, venous pyelography and lateral renal function tests can show signs of renal dysfunction. Kidney angiography can confirm the location, extent and nature of the stenosis. In addition, the patient's renin-angiotensin system activity is increased, which can be differentiated 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 early stage of primary aldosteronism, but renal inflammation or pyelonephritis is often severely damaged by kidney function. With acidosis and hyponatremia, low sodium test can not reduce urinary potassium, blood potassium does not rise, blood pressure does not drop, spironolactone test can not correct potassium loss and high blood pressure, plasma renin activity increased to confirm secondary aldosteronism.
3. Other adrenal diseases
(1) hypercortisolism: especially caused by adenocarcinoma or ectopic ACTH syndrome, but there are various 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 hypertension, hypokalemia caused by a large number of deoxycorticosterone, in women Caused by masculinity, causing precocious puberty in men, the latter estrogen and androgen, cortisol decreased, female sexual insufficiency, males with pseudohermaphroditism, clinically difficult to identify.
4. Others: Pseudoaldosteronism (Liddle syndrome), renin secretory tumor, Batter syndrome, licorice preparation, carbenoxolone (progesterone) and birth control pills can cause high blood pressure and hypokalemia. Plasma renin-angiotensin II-aldosterone system examination, current medical history and family history are helpful in identification.
