Hyperaldosteronism is a disorder in the adrenal gland, caused by excessive secretion of aldosterone, one of the active mineral corticoids. Its main feature is an increase in blood pressure. The task of the adrenal gland is the development of a number of various hormones, including mineral corticoids. With the help of the latter, the water-salt balance is regulated. The main role in this is aldosterone. Both excessive synthesis of a hormone, and insufficient leads to disturbances in the work of the body. Hyperaldosteronism - a syndrome that occurs when excessive aldosterone production.
Hyperaldosteronism
Aldosterone is the most active of mineral corticoids, produced in the glomerular zone of the adrenal cortex. The synthesis of the hormone and release into the blood causes a low concentration of sodium and a high concentration of potassium in the blood. Also, ACTH and, of course, the renin-angiotensin system may act as a stimulator of the synthesis.
Aldosterone acts according to this mechanism:
- the hormone binds to mineralocorticoid receptors in the renal tubules;
- stimulates the synthesis of protein-transporters of sodium ion and the latter is derived from the lumen of the tubule into the epithelial cell of the renal tubule;
- increases the production of protein-transporters of potassium ion. Potassium is excreted from the cells of the renal tubule into the primary urine;
- the water-salt balance is restored.
The picture looks different when, for one reason or another, the secretion of aldosterone is unjustifiably increased. The hormone promotes increased reabsorption of sodium, which leads to an increase in the content of sodium ions in the blood. This stimulates the production of antidiuretic hormone and water retention. At the same time, hydrogen ions, magnesium ions are removed, and, most importantly, potassium in the urine, which automatically leads to the development of hypernatremia and hypokalemia.
Both abnormalities contribute to a steady increase in blood pressure, in which excess mineral corticoids cause direct damage to the myocardium, blood vessels and kidneys.
Etiology and pathogenesis of
Primary hyperaldosteronism is the cause of elevated blood pressure in 10-15% of cases. Typically, they suffer from middle-aged people - 30-50 years, mostly women - up to 70%.
There are primary and secondary hyperaldosteronism. In the first case, the excessive production of aldosterone is caused by disturbances in the work of the adrenal cortex and does not depend on external factors. In the second case, the synthesis of the hormone stimulates the external factor - arterial hypertension, heart failure, cirrhosis.
The causes of the syndrome are very diverse.
Primary hyperaldosteronism causes:
- Kona syndrome - aldosterone-producing adrenal adrenal gland, accounts for more than 65% of cases;
- idiopathic hyperaldosteronism - is formed due to diffuse bilateral small-knee hyperplasia of the adrenal cortex. It causes 30-40% of cases of the disease. The etiology of it remains unclear. But unlike other forms of the disease, the glomerulus zone remains sensitive to angiotensin II.ACTH regulates the synthesis of aldosterone;
- adrenal hyperplasia - one-sided and two-sided;
- glucocorticoid-dependent hyperaldosteronism is a hereditary ailment caused by a gene defect;
- aldosterone-producing carcinoma is a very rare case, no more than 100 such patients are described;
- pseudohydaldosteronism - it is based on a congenital gene defect, which leads to inhibition of the production of angiotensin I and, eventually, to a decrease in aldosterone;
- Itenko-Cushing syndrome - an excess of aldosterone due to increased secretion of ACTH;
- congenital or drug-induced failure.
Secondary hyperaldosteronism is associated with the underlying pathology, which is the cause of its appearance:
- excessive activity of the renin-angiotensin-aldosterone system - pregnancy, excessive potassium intake, loss of sodium associated with diet, diarrhea, medication, blood loss due to blood lossand so on;
- organic secondary hyperaldosteronism - arterial stenosis, tumor;
- functional hyponatremia, hypovolemia and so on;
- a violation of the metabolism of aldosterone in heart failure, kidney disease and so on.
A characteristic difference between secondary hyperaldosteronism and primary is that it does not cause disturbances in the electrolyte balance, since it is a natural reaction to the excessive work of the renin-angiotensin-aldosterone system.
Types and symptoms of
Depending on the type of ailment, the symptoms also differ. The decisive factor here is the method of adjusting the synthesis and secretion of aldosterone. So, with primary hyperaldosteronism, the hormone is produced uncontrollably due to a violation in the adrenal cortex, whereas in the secondary form, stimulation is promoted by RAAS.Accordingly, in the first case, there is a violation of the water-salt balance, and in the second case, there is no violation. The difference in the clinical picture is precisely what is explained.
Primary
For primary hyperaldosteronism characterized by:
- arterial hypertension - observed in 100% of patients, although recently began to mark the asymptomatic course of the disease. BP is increased constantly, especially diastolic, which quickly leads to hypertrophy of the left ventricle, and, therefore, to changes in the ECG.In this case, in 50% of patients vascular lesions of the fundus are noted, and in 20% - visual impairment;
- hypokalemia - 100% of patients. The lack of potassium leads to violations of muscle and nervous functions. It manifests itself as weakness and rapid fatigue of muscles up to pseudo-paralytic conditions and seizures;
- analysis shows an increase in the level of aldosterone and a low level of renin in 100 cases out of 100. Moreover, the hormone level is not regulated;
- observed hypochloraemic alkalosis - an increase in the pH level in the blood due to the accumulation of alkaline metabolic products;
- proteinuria and nocturnal polyuria - respectively, 85 and 72%, is due to changes in the renal tubules caused by hypokalemia. The symptom is accompanied by a constant sensation of thirst;
- in 65% of cases there is hypernatremia - an increase in the concentration of sodium ions with a decrease in the concentration of potassium - a natural phenomenon. However, the sensitivity of the renal tubules to sodium retention, which is caused by aldosterone, can be significantly reduced. In the absence of hypernatremia, a suspicion of PGA causes a withdrawal of potassium in the urine, exceeding 40 meq / day;
- in 51% of cases of AD causes persistent headache;
- water-electrolyte imbalance can cause psychoemotional disorders - hypochondria, asthenic syndrome and so on.
All described symptoms are most typical for the syndrome of Cohn - the most common cause of RAG.
Other cases are much less common:
- idiopathic hyperaldosteronism with similar symptoms allows to regulate the production of aldosterone, since the glomerular zone remains sensitive to the action of angiotensin II;
- for bilateral hyperplasia is characterized by sensitivity to glucocorticosteroids: with the intake of glucocorticosteroids, potassium exchange is normalized and blood pressure decreases;
- pseudohydaldosteronism is accompanied by typical signs of PAG.However, there is no response to the drug.
Diagnosis of the disease is very difficult. Important not only the external symptoms, but the response to the introduction of certain drugs. So, the introduction of veroshpiron within 2 weeks normalizes the potassium exchange and reduces blood pressure. However, this effect is characteristic only of PGA.If it is absent, the diagnosis was erroneous.
Secondary
The clinical picture of HAV is strongly associated with the symptoms of the underlying disease. Secondary hyperaldosteronism is a kind of compensating phenomenon and does not have its own characteristic symptoms. Its clear difference from PGA is the preservation of the water-salt balance, which means the absence of high blood pressure, hypernatremia or hypokalemia.
Often secondary hyperaldosteronism is associated with the appearance of edema. The fluid retention and accumulation of sodium causes increased secretion of aldosterone. In fact, with HAV, the synthesis of aldosterone is due to hypernatremia.
Diagnosis of
The similarity of symptoms and their ambiguity makes the diagnosis of the disease very difficult and time-consuming. It requires not only studies both laboratory and instrumental, but also a number of functional tests of a different nature. Diagnosis is carried out in several stages.
Primary
Is implemented in order to exclude or confirm the PHA.To do this, at least 2 times the level of potassium in plasma is determined in all patients with high blood pressure. For primary hyperaldosteronism, a stable low level of potassium in the blood is characteristic - less than 2.7 meq / L, regardless of the intake of antihypertensive drugs. With normocalic hyperaldosteronism, the potassium level against the increased aldosterone content is above 3.5 meq / l.
Diagnosis of PGA Syndrome
At this stage, the level of hormones is investigated in order to establish the true cause of the disease.
For primary PHA are characteristic:
- low renin activity is not a 100% indicator, since its insufficiency is in principle characteristic for 25% of hypertensive patients of especially advanced age;
- high concentration of aldosterone in the blood or increased urinary excretion of the products of hormone degradation. Characteristic of 70% of patients. Thus it is necessary to consider, that the level of aldosterone decreases at a hypervolemia, a hypokalemia and so on;
- stimulation test with sodium loading can give the required response. The patient is given 2L sodium chloride solution, which normally leads to a decrease in aldosterone concentration by 50%.With primary hyperaldosteronism, this decrease does not occur, since the synthesis of the hormone is insensitive to external factors. Conducting the sample requires great care, since the sodium load significantly worsens the patient's well-being - there is weakness, disturbances in the heart rhythm.
Determination of nosological form
At this stage, functional tests and biochemical tests of blood and urine are carried out:
- Increase in the concentration of 18-hydroxycorticosterone is one of the most reliable signs of PHA.Again, with the exception of the idiomatic, where 18-hydroxycorticosterone remains normal or elevated insignificantly.
- The high urinary content of cortisone degradation products is also typical of PHA.
- Functional tests are based on the body's response to certain drugs and loads:
- orthostatic load - 4 hours of walking, combined with a 3-day low salt diet does not stimulate renin activity in the blood - ARP, and the aldosterone content may even decrease. The same response follows the reception of active saluretics. Basal ARP is measured on an empty stomach after a night's sleep against a diet containing no more than 120 meq / d of sodium;
- spironolactone test - 3-day administration of spironolactones( 600 mg / day) does not stimulate renin activity and does not affect the production of aldosterone;
- test with captopril - with aldosterone, the circadian rhythm of aldosterone is maintained after walking and at rest. Lack of rhythm is an indicator of a malignant tumor;
- sample with DOXA - every 12 hours for 3 days, 10 mg of the drug is administered. With aldosterone and in most cases with idiopathic PHA, the drug does not influence the synthesis of aldosterone.
- Idiopathic PHA because of the preservation of the sensitivity of the kidney tissue is more difficult to diagnose. In this case, all the symptoms are poorly expressed, but at the same time stimulating tests are less effective than in healthy people: the level of aldosterone is lower, much lower the concentration of 18-hydroxycorticosterone, the activity of renin is lowered, but increases after walking.
- In carcinoma, the reaction to the samples is completely absent.
- Glucocorticoid hyperaldosteronism is detected with the following symptoms: ineffectiveness of antihypertensive therapy, increased excretion of 18-oxocortisol and 18-hydroxycortisol against the background of a normal level of potassium in the blood, no change in the level of aldosterone in the orthostatic load. Trial treatment with dexamethasone or prednisolone brings a quick and lasting effect.
- Family forms of PHA can only be established through genetic diagnosis.
Instrumental methods
If the biochemical indicators of PGA can be considered proven, additional studies are being performed to determine the location of the pathology:
- Computed tomography - allows to identify aldosteron-producing adenoma with an accuracy of 62%.In addition, the method allows you to exclude tumors.
- MCT - the accuracy of adenoma detection is 100%.
- ultrasound - sensitivity is 92%.This is one of the safest methods.
- Phlebography of the adrenal glands - here the gradient of the concentration of aldosterone and renin at different levels is investigated. The method is accurate, but very complex.
- Scintigraphy of the adrenal glands is most informative for small- and large-node hyperplasia, as well as tumors and adenomas. The sample is performed against the background of a blockade of the thyroid gland.
On the video about the diagnosis of hyperaldosteronism:
Treatment of
The main method of treatment of PHA is surgical intervention, usually removal of the affected adrenal gland. But in certain cases this method is unacceptable.
- For example, with bilateral hyperplasia, the operation is indicated only when the medication is completely inadequate.
- In the idiopathic form of GPA, conservative treatment is prescribed.
- In the case of carcinoma, the operation is combined with chemotherapy.
- Glucocorticoid-independent form does not require surgical intervention. The introduction of dexomethasone completely normalizes blood pressure in 3-4 weeks.
- Secondary hyperaldosteronism of its own treatment rarely requires. Here it is necessary to eliminate the underlying disease.
Medicated
For conservative treatment, the following drugs are used:
- aminoglutethimide - 2-3 times a day. Treatment is performed against the background of blood pressure control, the level of cortisol in the urine - at least 1 time per day, thyroid hormones and so on;
- spironolactone - 2 times a day for 50 mg. Treatment can be combined with the use of potassium-sparing diuretins - so it is possible to prevent side effects;
- spironolactone - 1-2 times a day 25-50 mg with amyloid and triamterene. With severe hypokalemia, potassium preparations are added. After normalization, the potassium concentration in the plasma is reduced.
Surgical intervention
The operation is rather complicated and requires a long preparation - at least 4 weeks. Its purpose is to reduce ADL, restore the normal content of potassium in the blood and the function of RAAS.
For this purpose appoint:
- aminoglutethimide - 250 mg 2-3 per day. The dose is increased if the treatment is ineffective;
- spironolactone - 50-100 mg 2-4 times a day. A combination of spironolactone and amiloride is used. If blood pressure does not decrease, it is possible to administer antihypertensive drugs.
The most common one-sided adrenalectomy is the removal of the adrenal gland. The operation is performed through entering the abdominal cavity, without it and from the back. There are other methods - transarental introduction of alcohol, blood flow portraiture, however, they have not yet been distributed.
In the postoperative period, substitution therapy is performed: every 4-6 hours 2-3 days, 25-50 mg hydrocortisone is administered. The dose gradually decreases as the signs of adrenal insufficiency decrease.
Clinical recommendations
Clinical recommendations for this disease are only general. Treatment should be selected individually, taking into account the general condition of the patient and the characteristics of his body. Recommendations do not set standards, as they do not guarantee the result.
High blood pressure is a symptom of many diseases, which makes diagnostics extremely difficult. Complaints of patients in this case are nonspecific, so the question of referring to research remains open. Recommendations help identify those groups of patients whose PHA is more likely.
It is recommended to carry out diagnostics with the following indications:
- arterial hypertension 1 and 2 stages;
- high blood pressure, insensitive to drug treatment;
- combination of hypertension and hypokalemia, including those caused by medications;
- combination of hypertension and adrenal incidents;
- hypertension in the background of a family history - previously the development of hypertension, the next of kin with PGA and so on.
As a primary study of patients of these groups, the aldosterone-renin ratio was determined. For clarification of PHA, it is recommended to perform functional tests.
CT is assigned to exclude cancer.
Patients with early development of the disease - up to 20 years old, and having relatives with PHA, are assigned genetic testing in order to establish a glucocorticoid-dependent PHA.
Forecasts
According to statistics, surgical intervention provides 50-60% complete recovery, with adrenal adenoma. With carcinoma, the forecast is unfavorable.
The same applies to patients with bilateral hyperplasia of the adrenal cortex.
Hyperaldosteronism is a common name for a number of diseases that cause the same clinical picture. Secondary hyperaldosteronism, as a rule, disappears together with the underlying disease. Forecasts for curing PGA are not so comforting.