Hyperaldosteronism: symptoms, diagnosis and treatment. Primary hyperaldosteronism: diagnosis, treatment, causes, symptoms, signs Treatment of hyperaldosteronism

Date: 01.07.2020

Hyperaldosteronism refers to the pathology of the adrenal cortex, characterized by excessive production of the mineralocorticoid hormone - aldosterone. Previously, the disease was considered rare, now it occurs in every tenth patient with arterial hypertension.

Disease classification

Hyperaldosteronism can be primary or secondary. Primary, in turn, is subdivided into:

Adenoma of the adrenal cortex;
Carcinoma of the adrenal cortex;
Glucocorticoid-suppressed hyperaldosteronism;
Primary adrenal hyperplasia.

Each of these conditions is characterized by increased production of aldosterone, in some cases, several steroid hormones.

Primary hyperaldosteronism

The pathogenesis and symptoms of primary and secondary hyperaldosteronism are different, therefore there is a separation of their symptoms and causes.

Causes

The most common causes of aldosteronism are:

Adenoma of the adrenal cortex is a benign neoplasm that produces an excess amount of aldosterone. In 75% of cases, it is the adenoma that causes primary aldosteronism.
In 20% of cases, the disease is caused by bilateral aldosteromas.
Only in 5% of cases the disease develops as a result of adrenal cortex carcinoma.

In medicine, a hereditary cause is also distinguished, which leads to a family disease with excessive production of aldosterone. And if in one member of the family pathology can be caused by a neoplasm of any nature, then in the rest it is simply transmitted in the form of a syndrome. Hereditary transmission is realized with autosomal dominant inheritance.

Symptoms

The main symptoms of hyperaldosteronism are manifested by the cardiovascular and autonomic nervous system. This is chronic persistent arterial hypertension, overload of the left ventricle of the myocardium, sometimes hypertension reaches crises.

Other symptoms of the disease:

Lethargy, fatigue;
Muscle weakness;
Seizures;
Numbness of the limbs;

Twitching in muscles;
Headache;
Thirst and polyuria;
Feeling of numbness in the limbs;
Decreased concentration of vision.

The arterial hypertension developing against the background of the disease also manifests its own symptoms, expressed in migraines, stress on the heart, hypokalemia. One in four patients develops a pre-diabetic condition. A combination with osteoporosis is possible.

Connes syndrome

Physicians call primary hyperaldosteronism Connes syndrome in cases where excess concentrations of aldosterone are produced by an adrenal adenoma.

This is a benign neoplasm, reaching a maximum diameter of 25 mm, filled with cholesterol and therefore has a yellowish color. There is also a high content of aldosterone synthetase inside the adenoma.

Idiopathic hyperplasia

Bilateral idiopathic hyperaldosteronism in half of the cases occurs in patients aged 45 years and older and is more common than adrenal adenoma.

Essentially, hyperplasia is an increase in the cells of the adrenal cortex, while the volume of the cortex increases. Hyperplasia more than other types of primary hyperaldosteronism refers to hereditary pathologies.

Carcinoma is a malignant formation that synthesizes not only, but also estrogen, cortisol, androgens. Severe hypokalemia is noted.

The neoplasm reaches 45 mm in diameter and shows signs of growth. When neoplasms of unknown etiology are detected, with sizes more than 25 mm in diameter, it is customary to consider the patient's condition as a syndrome of an increased risk of carcinoma formation.

Secondary form of the disease

Secondary hyperaldosteronism is a separate diagnosis, although it occurs against the background of existing diseases of the systems of human internal organs.

Reasons for development

Secondary hyperaldosteronism is associated with the following pathologies:

Reactivity, which manifests itself during pregnancy, with an excess of potassium in food, with the loss of sodium from the body during diets, diarrhea, long-term drug treatment with diuretics, large blood loss.
With tumors or vascular stenosis, organic secondary hyperaldosteronism is noted.
Violation of metabolic processes with the participation of aldosterone, which is observed in chronic pathologies of the kidneys and adrenal glands, heart failure.
Long-term treatment with hormonal drugs based on estrogen, as well as during menopause, accompanied by hormonal imbalance.

The fundamental difference from primary hyperaldosteronism is that primary hyperaldosteronism entails electrolyte imbalance, while secondary hyperaldosteronism is a natural reaction to the reactivity of the renin-angiotensin-aldosterone complex.

Symptoms

Secondary hyperaldosteronism does not show its own symptomatology, since it is a compensating pathology. Therefore, its symptoms are manifested precisely in those diseases or conditions against which it manifests itself. Unlike the primary, the secondary form is not accompanied by a violation of the water-salt balance, high blood pressure and cardiac pathologies.

The only symptom with which a secondary form of aldosteronism can be associated is edema. Sodium accumulation and fluid accumulation lead to excess secretion of aldosterone, but sodium accumulation is caused by concomitant diseases.

Diagnostic methods

Diagnosis of primary or secondary hyperaldosteronism can only be carried out using a biochemical blood test. When an excess of aldosterone is detected, they proceed to the diagnosis of diseases associated with or causing excessive secretion of aldosterone.

CT and MRI

Computed tomography and magnetic resonance imaging can detect neoplasms from five millimeters in diameter. With the help of computer diagnostics, the following pathologies can be diagnosed:

An increase in the size of the adrenal glands indicates bilateral hyperplasia, or unilateral, if the size of only one adrenal gland is changed.
The presence of nodes in the adrenal cortex can be regarded as macronodular hyperplasia.
If neoplasms of more than 30 mm are detected, especially in the adrenal gland, carcinoma is suspected.
Detection of a hormonally inactive tumor may indicate essential hypertension.

It should be understood that the methods of computer diagnostics investigate morphological changes, and not functional ones, therefore, additional methods are always required that can clarify the suspected diagnosis.

- a pathological condition caused by increased production of aldosterone - the main mineralocorticoid hormone of the adrenal cortex. With primary hyperaldosteronism, arterial hypertension, headaches, cardialgia and heart rhythm disturbances, blurred vision, muscle weakness, paresthesias, and convulsions are observed. With secondary hyperaldosteronism, peripheral edema, chronic renal failure, changes in the fundus develop. Diagnostics of various types of hyperaldosteronism includes biochemical analysis of blood and urine, functional stress tests, ultrasound, scintigraphy, MRI, selective venography, examination of the state of the heart, liver, kidneys and renal arteries. Treatment of hyperaldosteronism with aldosteroma, adrenal cancer, renal reninoma - operative, with other forms - medication.

ICD-10

E26

General information

Hyperaldosteronism includes a whole complex of syndromes, different in pathogenesis, but similar in clinical signs, occurring with excessive secretion of aldosterone. Hyperaldosteronism can be primary (due to the pathology of the adrenal glands themselves) and secondary (due to renin hypersecretion in other diseases). Primary hyperaldosteronism is diagnosed in 1-2% of patients with symptomatic arterial hypertension. In endocrinology, 60-70% of patients with primary hyperaldosteronism are women aged 30-50 years; described a few cases of detection of hyperaldosteronism among children.

Causes of hyperaldosteronism

Depending on the etiological factor, several forms of primary hyperaldosteronism are distinguished, of which 60-70% of cases are attributed to Conn's syndrome, the cause of which is aldosteroma - an aldosterone-producing adenoma of the adrenal cortex. The presence of bilateral diffuse nodular hyperplasia of the adrenal cortex leads to the development of idiopathic hyperaldosteronism.

There is a rare familial form of primary hyperaldosteronism with an autosomal dominant mode of inheritance due to a defect in the 18-hydroxylase enzyme, which is out of control of the renin-angiotensin system and is corrected by glucocorticoids (occurs in young patients with frequent cases of hypertension in the family history). In rare cases, primary hyperaldosteronism can be caused by adrenal cancer, which can produce aldosterone and deoxycorticosterone.

Secondary hyperaldosteronism occurs as a complication of a number of diseases of the cardiovascular system, liver and kidney pathology. Secondary hyperaldosteronism is observed in heart failure, malignant arterial hypertension, liver cirrhosis, Barter's syndrome, renal artery dysplasia and stenosis, nephrotic syndrome, renal reninoma and renal failure.

An increase in renin secretion and the development of secondary hyperaldosteronism is caused by sodium loss (with diet, diarrhea), a decrease in circulating blood volume during blood loss and dehydration, excessive potassium intake, prolonged use of certain drugs (diuretics, COCs, laxatives). Pseudohyperaldosteronism develops when the reaction of the distal renal tubules to aldosterone is disturbed, when, despite its high serum level, hyperkalemia is observed. Extra-adrenal hyperaldosteronism is quite rare, for example, with pathology of the ovaries, thyroid gland and intestines.

Pathogenesis

Primary hyperaldosteronism (low-root) is usually associated with tumor or hyperplastic lesions of the adrenal cortex and is characterized by a combination of increased secretion of aldosterone with hypokalemia and arterial hypertension.

The basis of the pathogenesis of primary hyperaldosteronism is the effect of excess aldosterone on the water-electrolyte balance: increased reabsorption of sodium and water ions in the renal tubules and increased excretion of potassium ions in the urine, leading to fluid retention and hypervolemia, metabolic alkalosis, and a decrease in the production and activity of blood plasma renin. There is a violation of hemodynamics - an increase in the sensitivity of the vascular wall to the action of endogenous pressor factors and the resistance of peripheral vessels to blood flow. In primary hyperaldosteronism, a pronounced and prolonged hypokalemic syndrome leads to dystrophic changes in the renal tubules (potassiumpenic nephropathy) and muscles.

Secondary (vysokoreninovy) hyperaldosteronism occurs compensatory, in response to a decrease in the volume of renal blood flow in various diseases of the kidneys, liver, heart. Secondary hyperaldosteronism develops due to the activation of the renin-angiotensin system and the enhancement of renin production by the cells of the juxtaglomerular apparatus of the kidneys, which provide excessive stimulation of the adrenal cortex. The expressed electrolyte disturbances characteristic of primary hyperaldosteronism do not occur in the secondary form.

Symptoms of hyperaldosteronism

The clinical picture of primary hyperaldosteronism reflects disturbances in the water-electrolyte balance caused by the hypersecretion of aldosterone. Due to sodium and water retention in patients with primary hyperaldosteronism, severe or moderate arterial hypertension, headaches, aching pains in the heart (cardialgia), cardiac arrhythmias, changes in the fundus with deterioration of visual function (hypertensive angiopathy, angiosclerosis, retinopathy) occur.

Potassium deficiency leads to rapid fatigue, muscle weakness, paresthesias, seizures in various muscle groups, periodic pseudo-paralysis; in severe cases - to the development of myocardial dystrophy, kalepenic nephropathy, nephrogenic diabetes insipidus. With primary hyperaldosteronism in the absence of heart failure, peripheral edema is not observed.

With secondary hyperaldosteronism, a high level of blood pressure is observed (with diastolic blood pressure> 120 mm Hg), which gradually leads to damage to the vascular wall and tissue ischemia, deterioration of renal function and the development of chronic renal failure, changes in the fundus (hemorrhage, neuroretinopathy). The most common symptom of secondary hyperaldosteronism is edema; hypokalemia is rare. Secondary hyperaldosteronism can occur without arterial hypertension (for example, in Barter's syndrome and pseudohyperaldosteronism). In some patients, there is a malosymptomatic course of hyperaldosteronism.

Diagnostics

Diagnostics involves the differentiation of various forms of hyperaldosteronism and the determination of their etiology. As part of the initial diagnostics, the functional state of the renin-angiotensin-aldosterone system is analyzed with the determination of aldosterone and renin in the blood and urine at rest and after stress tests, potassium-sodium balance and ACTH, which regulate the secretion of aldosterone.

Primary hyperaldosteronism is characterized by an increase in the level of aldosterone in the blood serum, a decrease in plasma renin activity (ARP), a high aldosterone / renin ratio, hypokalemia and hypernatremia, a low relative density of urine, a significant increase in the daily excretion of potassium and aldosterone in the urine. The main diagnostic criterion for secondary hyperaldosteronism is an increased rate of ARP (with reninoma - more than 20-30 ng / ml / h).

In order to differentiate individual forms of hyperaldosteronism, a test with spironolactone, a test with a load of hypothiazide, and a "march" test are carried out. In order to identify the familial form of hyperaldosteronism, genomic typing is performed by PCR. With hyperaldosteronism, corrected by glucocorticoids, trial treatment with dexamethasone (prednisolone) is of diagnostic value, in which the manifestations of the disease are eliminated, and blood pressure is normalized.

To determine the nature of the lesion (aldosteroma, diffuse nodular hyperplasia, cancer), topical diagnostic methods are used: ultrasound of the adrenal glands, scintigraphy, CT and MRI of the adrenal glands, selective venography with simultaneous determination of the levels of aldosterone and cortisol in the blood of the adrenal veins. It is also important to establish the disease that caused the development of secondary hyperaldosteronism by examining the state of the heart, liver, kidneys and renal arteries (echocardiography, ECG, ultrasound of the liver, ultrasound of the kidneys, ultrasound and duplex scanning of the renal arteries, multispiral CT, MR angiography).

Treatment of hyperaldosteronism

The choice of the method and tactics for the treatment of hyperaldosteronism depends on the cause of the hypersecretion of aldosterone. Patients are examined by an endocrinologist, cardiologist, nephrologist, ophthalmologist. Drug treatment with potassium-sparing diuretics (spirolactone) is carried out for various forms of hyporeninemic hyperaldosteronism (hyperplasia of the adrenal cortex, aldosteroma) as a preparatory stage for surgery, which helps to normalize blood pressure and eliminate hypokalemia. Shown is a low-salt diet with an increased content in the diet of foods rich in potassium, as well as the introduction of potassium preparations.

Treatment of aldosteroma and adrenal cancer is operative, it consists in removing the affected adrenal gland (adrenalectomy) with preliminary restoration of the water-electrolyte balance. Patients with bilateral adrenal hyperplasia are usually treated conservatively (spironolactone) in combination with ACE inhibitors, calcium channel antagonists (nifedipine). In hyperplastic forms of hyperaldosteronism, complete bilateral adrenalectomy and right-sided adrenalectomy in combination with subtotal resection of the left adrenal gland are ineffective. Hypokalemia disappears, but the desired hypotensive effect is absent (blood pressure is normalized only in 18% of cases) and there is a high risk of developing acute adrenal insufficiency.

With hyperaldosteronism, amenable to correction of glucocorticoid therapy, hydrocortisone or dexamethasone is prescribed to eliminate hormonal and metabolic disorders and normalize blood pressure. In secondary hyperaldosteronism, combined antihypertensive therapy is carried out against the background of pathogenetic treatment of the underlying disease under the obligatory control of the ECG and the level of potassium in the blood plasma.

In the case of secondary hyperaldosteronism due to stenosis of the renal arteries, percutaneous X-ray endovascular balloon dilation, stenting of the affected renal artery, and open reconstructive surgery are possible to normalize blood circulation and kidney function. If renal reninoma is detected, surgical treatment is indicated.

Prediction and prevention of hyperaldosteronism

The prognosis of hyperaldosteronism depends on the severity of the underlying disease, the degree of damage to the cardiovascular and urinary systems, timeliness and treatment. Radical surgical treatment or adequate drug therapy provides a high likelihood of recovery. With adrenal cancer, the prognosis is poor.

In order to prevent hyperaldosteronism, constant dispensary observation of persons with arterial hypertension, liver and kidney diseases is necessary; compliance with medical recommendations regarding medication intake and diet.

Sometimes PHA is equated with Connes syndrome, which is only one of the forms of the disease - an aldosterone-producing adenoma of the adrenal cortex, first described by J.W. Conn in 1955

Prevalence... Initially, Connes syndrome was considered a rare disease. Primary hyperaldosteronism is found in approximately 10% of patients with arterial hypertension.

Classification of primary hyperaldosteronism

PHA is subdivided into aldosterone-producing adrenal adenoma, aldosterone-producing adrenal cortex cancer, glucocorticoid-suppressed hyperaldosteronism, and primary adrenal hyperplasia.

Causes of primary hyperaldosteronism

In most cases, the cause of an excess of mineralocorticoids in the body is the overproduction of aldosterone, which can be primary or secondary and is usually manifested by arterial hypertension and hypokalemia.

The etiology of PHA is different for each of its forms. Often the cause of PHA (60-70% of cases) is an aldosterone-producing adenoma - a benign neoplasm of the glomerular adrenal cortex. Bilateral and multiple aldosteromas are rare (5-10%), aldosterone-producing adrenal cortex cancer is even rarer.

Pathogenesis... Hypernatremia leads to an increase in blood osmolarity, hypersecretion of vasopressin. As a result, an increase in blood pressure is observed - a cardinal symptom of PHA. Hypokalemia and hypomagnesemia lead to neuromuscular disorders, impaired insulin secretion (usually mild or moderate), and occasionally visual disturbances. Prolonged hypokalemia and metabolic alkalosis lead to the formation of a "hypokalemic kidney".

Symptoms and signs of primary hyperaldosteronism

System	Complaints	Objective signs of complaints (complaint analysis / examination / tests)
General signs / symptoms	Fast fatiguability. Severe general weakness, acute / chronic	-
Skin, appendages of the skin and subcutaneous fatty tissue and muscles	Acute / chronic muscle weakness. Muscle spasms. Spasms / cramps in both legs. Muscle twitching	Bilateral edema of the eyelids. Peripheral edema
The cardiovascular system	Headache (due to arterial hypertension)	Arterial hypertension, often diastolic. Accent II tone on the aorta
Digestive system	Thirst	Polydipsia (secondary, due to polyuria)
Urinary system	Frequent, profuse urination, including at night	Polyuria. Nocturia
Nervous system, sense organs	Numbness, tingling in the limbs. Lower limb spasms. Acute bilateral hand spasm. Acute / chronic blurred vision	Paresthesias. Hyporeflexia / decreased deep tendon reflexes. Weak reflexes. Diffuse motor deficits. Myoclonic twitching on examination. Khvostek's symptom is positive. Beating symptom Trousseau is positive. Carpopedal spasm. Retinal vascular sclerosis. Signs of retinopathy

The overwhelming majority of patients have a persistent increase in blood pressure with all the typical features of symptomatic hypertension. Hypertrophy and overload of the left ventricle of the heart develops. In 30-40% of patients with PHA, arterial hypertension can be of a crisis nature, and in some cases it acquires a malignant course. Hypokalemia manifests itself as a neuromuscular syndrome (50-75%) in the form of general muscle weakness, fatigue, weakness in the lower extremities, paresthesias, muscle pains, seizures, and short-term mono- or paraplegia (20-25%). Changes in renal tubular function are accompanied by polyuria, hypoisostenuria, nocturia, polydipsia, and thirst. More than half of patients with PHA have asymptomatic impairment of carbohydrate tolerance, which in about a quarter of patients reaches the degree of mild diabetes.

If we single out diagnostically significant (specific) signs of primary hyperaldosteronism, then they are as follows:

moderate or severe arterial hypertension, which is often resistant to conventional treatment; disproportionate left ventricular hypertrophy is possible;
hypokalemia is usually asymptomatic; sometimes, against the background of severe hypokalemia, patients may develop tetany, myopathy, polyuria and nocturia;
can be combined with osteoporosis.

Aldosteroma (Connes syndrome)

Conn's syndrome is an adrenal adenoma producing aldosterone, benign, less than 2.5 cm in diameter and yellowish on the cut due to high cholesterol content. The adenoma has a very high concentration of the enzyme aldosterone synthetase. It has recently been established that an inactivating mutation in the KCJN5 potassium channel is the cause of aldosterone-producing tumors in 40% of cases.

Bilateral idiopathic adrenal hyperplasia (bilateral idiopathic hyperaldosteronism)

This pathological condition, the most common cause of primary hyperaldosteronism (60%), occurs in an older age group than Conn's syndrome. Adrenal hyperplasia is usually bilateral and can manifest as micronodular or macronodular hyperplasia. The pathophysiological mechanism is unknown, but it is noted that the secretion of aldosterone is very responsive to an increase in the level of angiotensin II in the blood.

Adrenal carcinoma

Adrenal carcinoma is a rare disease in which the tumor most often synthesizes not only aldosterone, but also other corticosteroids (cortisol, androgens, estrogens). In this case, hypokalemia can be very pronounced and is associated with very high levels of aldosterone. The tumor is usually 4.5 cm or more in diameter, with signs of local invasive growth. The combination of an adrenal tumor larger than 2.5 cm with an elevated aldosterone content is recommended as a high-risk state of adrenal carcinoma.

Glucocorticoid-suppressed hyperaldosteronism

Glucocorticoid-suppressed hyperaldosteronism is a very rare pathology of childhood, genetically determined. As a result of a genetic defect, the enzyme aldosterone synthetase is expressed in the fascicular and glomerular zones of the adrenal glands, therefore, the secretion of hormones in both zones is under the control of ACTH. This circumstance determines the only possible treatment with glucocorticoids. This disease is characterized by the onset in childhood, a similar pathology in relatives and increased secretion of 18-OH-cortiosol and 18-oxocortisol.

Diagnosis of primary hyperaldosteronism

After the diagnosis of primary hyperaldosteronism has been verified with the help of a biochemical examination, the topical and differential diagnosis of diseases accompanied by hyperaldosteronism is started.

Computed / magnetic resonance imaging

With the help of CT or MRI, nodules with a diameter of more than 5 mm can be found in the adrenal glands. Since the frequency of detection of adrenal glands by an incident increases with age, the question of the advisability of taking venous blood for aldosterone often arises. On CT or MRI, the following changes in the adrenal glands can be detected:

with bilateral adrenal hyperplasia, both adrenal glands may be enlarged or of normal size;
with macronodular hyperplasia, it is possible to detect nodes in the adrenal glands;
a tumor with a diameter of more than 4 cm is not typical for Connes syndrome and is suspicious of carcinoma;
It should always be borne in mind that a hormone-inactive tumor in the adrenal gland can be detected by CT / MRI in a patient with essential hypertension, i.e. CT and MRI are methods of morphological, not functional diagnostics, therefore, the results of the study of the adrenal glands by these methods do not provide information about the function of the identified pathological formations.

Blood sampling from the veins of the adrenal glands

This test is one of the standard procedures used to differentiate unilateral adenoma from bilateral hyperplasia. With unilateral adrenal lesions, the concentration of aldosterone on the side of the tumor is significantly higher (4 times or more). In the blood samples obtained from the adrenal glands, in addition to aldosterone, the cortisol content is also examined as an indicator of the adequate position of the catheter: in the vein flowing from the adrenal gland, the cortisol level is 3 times higher than in the peripheral blood. The study should be performed only in those clinical centers where the number of adrenal vein catheterizations per year exceeds 20. Otherwise, the study failure is 70%.

The study is shown in the following cases:

bilateral changes in the adrenal glands detected by CT / MRI;
primary hyperaldosteronism at the age of more than 50 years, when a single adenoma is visible on CT / MRI of the adrenal glands, since with age the number of incidental adrenal glands increases sharply. In some clinical centers, in this case, it is recommended to take blood from the veins of the adrenal glands for patients over 35 years old, since at a younger age, against the background of primary hyperaldosteronism, a unilateral adenoma is almost always functioning;
Surgical treatment of an adrenal tumor can, in principle, be performed, and the patient is not opposed to a potentially possible operation.

Radioisotope scanning

Cholesterol labeled with iodine does not have any advantages over CT / MRI.

The diagnosis of aldosteroma or adrenal hyperplasia should not be made on the basis of elevated aldosterone levels alone. However, with primary hyperaldosteronism, renin activity decreases; in more rare cases, the threshold values are 20 and 40 times).

On the eve of the test, it is necessary to compensate for hypokalemia. Spironolactone, eplerenone, triamterene, loop diuretics, and products containing licorice should be discontinued 4 weeks prior to plasma renin studies. If it is diagnostically insignificant, and arterial hypertension responds to treatment with verapamil, hydralazine or α-adrenergic blockers, 4 weeks before the second study, β-adrenergic blockers, central a2-adrenostimulants, NSAIDs, ACE inhibitors should be discontinued.

Daily excretion of aldosterone in urine of more than 10-14 μg (28-39 nmol) against the background of a sodium load test is considered a sign of primary hyperaldosteronism if sodium excretion exceeds 250 mmol / day. In the sample with saline, the level of aldosterone in plasma after infusion falls below 5 ng%; if the level of aldosterone is more than 10 ng%, the diagnosis of primary hyperaldosteronism is highly probable.

Diagnosis of PHA, due to the low specificity of clinical symptoms, is based on laboratory and instrumental research methods. Diagnostic measures are carried out in three stages: screening, confirmation of the autonomy of aldosterone hypersecretion, and topical diagnosis with differential diagnosis of certain forms of PHA.

At the screening stage, each patient with hypertension should at least twice determine the level of potassium in the blood serum. Patients with one of the following signs should undergo a more in-depth examination: spontaneous hypokalemia; hypokalemia while taking diuretics; lack of normalization of potassium levels within 4 months after discontinuation of diuretics. Detection at the screening stage of a normal or increased level of plasma renin activity in a patient not taking diuretics and antihypertensive drugs practically excludes PHA. If the plasma renin activity is reduced, the diagnosis is helped by determining the ratio of plasma aldosterone to plasma renin activity. Its value of more than 20 is considered tentative, and more than 30 is diagnostic.

In order to confirm the autonomy of aldosterone hypersecretion, a test is carried out with an intravenous drip of 2 liters of saline solution for 4 hours. Maintaining the concentration of aldosterone in the blood at a level of 10 ng / dl and more confirms the diagnosis of aldosteronism. Family history and determination of aldosterone excretion play an important role in the diagnosis of glucocorticoid-suppressed hyperaldosteronism.

In the topical diagnosis of PHA, computer X-ray or MRI is used, which allows visualizing aldosteromas in the form of unilateral solitary formations of low density (0-10 units) with an average diameter of 1.6-1.8 cm.In idiopathic hyperaldosteronism, the adrenal glands look normal or symmetrically enlarged, with nodes or not.

Hormonal testing and diagnostic signs

Screening

Indications

Resistance to antihypertensive therapy (for example, patients do not respond to a combination of three antihypertensive drugs).
Arterial hypertension, combined with hypokalemia.
Arterial hypertension developed before the age of 40.
Incidentaloma of the adrenal glands.

Method

If the patient is not specially prepared for the test, you can get false positive and false negative results, in particular:

the diet should not be limited to table salt;
you should stop treatment with drugs for the recommended period that affect the results of the study of renin and aldosterone;
Blood pressure is recommended to be controlled with doxazosin (α-blocker) or verapamil (recommended calcium channel blocker).

Aldosterone / Renin Ratio:

a high coefficient value indicates primary hyperaldosteronism:

aldosterone / plasma renin activity> 750;
aldosterone / plasma renin activity> 30-50;

the higher the value of the coefficient, the more likely the diagnosis of primary hyperaldosteronism is;
false negative values are observed in patients with chronic renal failure due to the very high activity of renin.

Diagnosis verification tests

The main purpose of verification tests is to show the impossibility of suppressing aldosterone secretion in response to salt load.

before the test, the patient should be on a normal diet, without restriction of table salt;
patients are given instructions explaining how to include in the diet a high salt content of up to 200 mmol / day for 3 days;
if necessary, you can prescribe tablets containing salt;

The level of aldosterone in daily urine less than 10 μg practically excludes primary hyperaldosteronism.

Fludrocortisone suppression test:

prescribe 100 mcg of fludrocortisone every 6 hours for 4 days;
measure the plasma aldosterone level at baseline and on the last day of the test;
a decrease in aldosterone levels on day 4 indicates primary hyperaldosteronism.

Differential diagnosis of primary hyperaldosteronism

Differential diagnosis of PHA is carried out with a low-root form of hypertension, secondary hyperaldosteronism, pseudohyperaldosteronism, Lidzl and Barter syndromes, some congenital disorders of steroid synthesis (deficiency of 17α-hydroxylase, 1 10-hydroxylase), adrenal cortex cancer.

After the diagnosis is established, the cause of hyperaldosteronism is found out in order to choose the right treatment. The most common causes of primary hyperaldosteronism are adrenal hyperplasia and aldosteroma. Unfortunately, the presence or absence of masses of the adrenal glands does not allow to unambiguously confirm or exclude the presence of aldosteroma. If laboratory data indicate an aldosteroma, and no tumor is found with radiological diagnosis, blood samples are taken from the adrenal veins. This complex procedure is performed in a specialized center with extensive experience in conducting such analyzes. In unilateral lesions, a 4: 1 ratio of cortisol-adjusted aldosterone levels in different adrenal veins is considered diagnostically significant.

A rare but important case of hereditary hyperaldosteronism is glucocorticoid-dependent hyperaldosteronism. It manifests itself as persistent arterial hypertension in childhood, adolescence and adolescence, is often not accompanied by hypokalemia and can lead to early hemorrhagic strokes. Glucocorticoid-dependent hyperaldosteronism occurs due to non-equilibrium crossing over between the genes CYP11B1 (codes for 11β-hydroxylase) and CYP11B2 (codes for 18-hydroxylase). As a result, the expression of 18-hydroxylase begins to be regulated by the ACTH-dependent promoter of the CYP11B1 gene. The diagnosis of this disease can be established by the presence in the urine of hybrid metabolites - 18-oxocortisol and 18-hydroxycortisol. In addition, you can contact the International Registry for Glucocorticoid-Dependent Hyperaldosteronism for gene diagnostics. Elimination of arterial hypertension and metabolic disorders during the treatment with dexamethasone also helps in the diagnosis.

Pathogenesis of symptoms and signs

The symptom complex, which develops as a result of an increased level of mineralocorticoids in the blood or an increased sensitivity of target tissues to them, is called hyperaldosteoronism (aldosteronism, hypermineralocorticoidism). At the same time, two forms of it are distinguished:

primary hyperaldosteronism, including endocrinopathy of the glomerular layer of the adrenal cortex;
secondary hyperaldosteronism, complicating the course of a number of non-endocrine diseases due to stimulation of mineralocorticoid synthesis against the background of increased activity of the renin-angiotensin system.

Secondary hyperaldosteronism is associated with many diseases in which peripheral edema develops. The secretion of aldosterone is stimulated in these cases by a normally functioning physiological mechanism. In patients with liver disease, hyperaldosteronism develops due to insufficient destruction of aldosterone in the liver. Secondary hyperaldosteronism also occurs with the salt-wasting form of nephropathy.

With the above diseases and conditions, hyperaldosteronism usually does not lead to arterial hypertension. However, arterial hypertension always accompanies secondary hyperaldosteronism caused by overproduction of renin in renal artery stenosis and renin-secreting tumors (Barter's syndrome). The cardinal differential diagnostic laboratory criterion of primary and secondary hyperaldosteronism is the blood plasma renin level, which is reduced only in the first case.

With hyperaldosteronism, potassium is excreted in the urine in an increased amount, and its content in the extracellular fluid decreases. This stimulates the release of potassium from the cells, which is accompanied by the entry of hydrogen ions into the cells, and against the background of increased excretion of hydrogen ions in the urine with hyperaldosteronism, alkalosis develops. Moderate depletion of potassium reserves in the body is accompanied by impaired glucose tolerance and resistance to the biological action of ADH (vasopressin). Severe potassium deficiency inhibits the activity of baroreceptors, which is sometimes manifested by orthostatic arterial hypotension. Against the background of increased synthesis of aldosterone, the production of other mineralocorticoids, precursors of aldosterone: deoxycorticosterone, corticosterone, 18-hydroxycorticosterone, is often activated.

Complaints in hyperaldosteronism - weakness, fatigue, loss of stamina and nocturia - are nonspecific and are caused by hypokalemia. With severe hypokalemia, accompanied by alkalosis, thirst and polyuria (with a predominance of nocturia) develop, as well as paresthesias and symptoms of Trousseau and / or Chvostek. Headaches are often troubling.

The increased synthesis of mineralocorticoids does not have any characteristic physical signs. Edema, noticeable to the eye, rarely develops.

Increased blood pressure is recorded in most patients.

Retinopathy is moderately expressed, and fundus hemorrhages are rare.

The heart slightly increases in size to the left.

Since hypokalemia develops most often during treatment with diuretics, they should be canceled 3 weeks before the study of potassium. In addition, the patient's diet should not be fortified with potassium or sodium. A low-salt diet, while promoting the maintenance of potassium stores in the body, may mask hypokalemia.

Since a modern person consumes a lot of sodium as part of salt (on average 120 mmol / day), hypokalemia is usually not masked in the usual dietary regimen. And if hypokalemia is detected in a subject who does not limit himself in salt consumption or even additionally regularly adds salt to food, then the diagnosis of hyperaldosteronism is excluded without additional research. When there is no certainty that the subject is consuming a sufficient amount of salt, it should be recommended to add up to 1 g of salt (1/5 tablespoon) to each of the main meals in his usual (without restrictions) diet. Blood electrolytes are tested on the 5th day of this dietary regimen. If hypokalemia is detected, then the activity of plasma renin is examined first of all. When renin activity is normal or high in a patient who has not received diuretic treatment for at least 3 weeks, the likelihood of primary hyperaldosteronism is extremely low.

In patients with hypokalemia and low plasma renin levels, it is necessary to investigate the level of aldosterone in urine and blood, which are elevated with hyperaldosteronism.

Associated conditions, illnesses and complications

Related conditions / diseases and complications are listed below.

Primary hyperaldosteronism (aldosteroma).
Hemorrhagic stroke.
Arrhythmias.
Hypervolemia.
Sudden cardiac death.
Intoxication with cardiac glycosides.
Benign / malignant arteriolar nephrosclerosis.
Kidney cyst.
Nephrogenic ND.
Diabetes.
Periodic paralysis syndrome.
Tetany.
Electrolyte myopathy.
Hypokalemia.
Hypokalemic nephropathy.
Metabolic alkalosis, hypokalemic.
Hypernatremia.
Hypomagnesemia.
Drug-induced electrolyte disturbances.
Isotenuria.

Diseases and conditions from which hyperaldosteoronism is differentiated

Differential diagnosis is carried out with the following diseases / conditions.

Adrenogenital Syndrome.
Cushing's Syndrome / Disease.
Iatrogenic Cushing's syndrome.
Secondary hyperaldosteronism.
Diuretic intoxication.
Medication-induced electrolyte disturbances.
Medication-induced arterial hypertension.
Electrolyte disturbances.
Hypokalemic periodic paralysis.
Intake of licorice root / glycyrrhizic acid.
Familial periodic paralysis.
Renal artery stenosis.
Barter's Syndrome.

Treatment of primary hyperaldosteronism

Treatment of PHA should take into account the etiology of the syndrome, include the correction of hypertension and metabolic disorders. In order to normalize potassium homeostasis, aldosterone antagonists are prescribed - spironolactone or eplerenone.

Adrenal aldosteroma and primary adrenal hyperplasia are successfully treated surgically. With idiopathic hyperaldosteronism, continuation of conservative therapy is indicated; if it is ineffective, subtotal adrenalectomy can be performed. Patients with glucocorticoid-suppressed aldosteronism are prescribed dexamethasone in an individually selected dose.

Conservative treatment of primary hyperaldosteronism, regardless of etiology, consists primarily in the appointment of a low-salt diet (containing less than 80 meq sodium). This reduces the loss of potassium in the urine, as it reduces the amount of sodium exchanged for potassium in the distal renal tubules. In addition, such a diet helps to lower blood pressure, since intravascular volume decreases against its background.

Diet therapy is complemented by treatment with spironolactone, a competitive mineralocorticoid receptor antagonist. After reaching the therapeutic effect, the dose of spironolactone is reduced to a maintenance dose of 100 mg / day. The expected increase in blood potassium levels under the influence of spironolactone therapy is 1.5 mmol / L. Side effects of spironolactone are manifested in 20% of patients in the form of gastrointestinal disorders, general weakness.

Along with or instead of spironolactone, potassium-sparing diuretics can be used, which block sodium channels in the distal renal tubule. The initial dose of amiloride is 10 mg per day, if necessary, it is increased by 10 mg / day to a maximum of 40 mg / day. The hypotensive effect is more pronounced with aldosteroma.

When surgical treatment is indicated for hyperaldosteronism syndrome (apdosteroma, adrenal carcinoma, primary hyperaldosteronism, etc.), then preoperative preparation consists in normalizing potassium and blood pressure, which may require conservative therapy (diet and drugs) for hyperaldosteronism syndrome up to 1-3 months. Such treatment prevents the development of postoperative hypoaldosteronism, since against its background the renin-angiotensin system and, accordingly, the glomerular layer of the unaffected adrenal gland are activated. During the operation, the level of potassium in the blood plasma is regularly examined, since the function of the adrenal gland retained is sometimes suppressed so much that massive steroid replacement therapy may be required. To prevent rebound mineralocorticoid insufficiency after surgical removal of the affected tissue during the operation, hydrocortisone is infused at a rate of 10 mg / h. After the operation, glucocorticoids are prescribed, the dose of which is gradually reduced until completely canceled within 2-6 weeks.

In some patients, despite the preoperative preparation, hypoaldosteronism develops after the operation, the symptoms of which are usually eliminated with adequate (without restriction) intake of salt and fluids. If dietary treatment does not correct hypoaldosteronism, mineralocorticoid replacement therapy is indicated.

Surgery

Laparoscopic adrenalectomy is currently the treatment of choice for aldosterone-secreting adenomas and is associated with a significantly lower complication rate than open-access surgery. Arterial hypertension disappears in 70% of cases, but if it remains, it turns out to be more manageable with antihypertensive drugs. Normalization of blood pressure after surgery occurs in 50% of patients within the first month and in 70% after a year.

Surgical treatment is not indicated for patients with idiopathic hyperaldosteronism, since even bilateral removal of the adrenal glands does not eliminate arterial hypertension.

Primary hyperaldosteronism prognosis

In patients with idiopathic hyperaldosteronism, complete recovery is not observed, patients need constant therapy with aldosterone antagonists.

Which doctors should be consulted if you have primary hyperaldosteronism

What is Primary Hyperaldosteronism

The syndrome of primary hyperaldosteronism was described by Conn (1955) in connection with an aldosterone-producing adenoma of the adrenal cortex (aldosteroma), the removal of which led to a complete recovery of the patient. Currently, the collective concept of primary hyperaldosteronism unites a number of diseases similar in clinical and biochemical characteristics, but different in pathogenesis, based on excessive and independent (or partially dependent) on the renin-angiotensin system, aldosterone production by the glomerular zone of the adrenal cortex, accompanied by arterial hypertension and myasthenia gravis.

What provokes Primary hyperaldosteronism

The cause of hyperaldosteronism can be hormonally active adenoma of the adrenal cortex (aldosteroma), bilateral hyperplasia of the glomerular zone of the adrenal cortex, multiple microadenomas of the adrenal cortex. Hyperaldosteronism can develop in chronic kidney disease, hypertension, and in some kidney tumors.
The cause of hyperaldosteronism can be long-term use of drugs (diuretics, laxatives, contraceptives).
A transient state of hyperaldosteronism is observed during the luteal phase of the menstrual cycle, during pregnancy, with sodium restriction in the diet.

Depending on the cause in clinical practice, there are:
1) aldosteronism with low renin secretion:
a) primary hyperaldosteronism as a result of a tumor of the glomerular layer of the adrenal cortex (Conn's syndrome);
b) idiopathic hyperaldosteronism (diffuse hyperplasia of the adrenal cortex);
c) dexamethasone-dependent hyperaldosteronism (suppressed by glucocorticoids);
d) hyperaldosteronism caused by ectopic tumors.

2) aldosteronism with normal or increased renin secretion (secondary hyperaldosteronism):
a) symptomatic arterial hypertension in renovascular pathology, kidney disease, hypertension;
b) renin-secreting kidney tumors (Wilms tumor);
c) iatrogenic and physiological hyperaldosteronism:
- hyperaldosteronism during the luteal phase of the menstrual cycle, during pregnancy;
- hyperaldosteronism as a result of sodium restriction in the diet, excessive intake of diuretics, laxatives;
- conditions accompanied by hypovolemia (bleeding and taking contraceptives).

Pathogenesis (What Happens?) During Primary Hyperaldosteronism

The pathogenesis of the disease is associated with excessive secretion of aldosterone. The action of aldosterone in primary hyperaldosteronism is manifested by its specific effect on the transport of sodium and potassium ions. By binding to receptors located in many secretory organs and tissues (kidney tubules, sweat and salivary glands, intestinal mucosa), aldosterone controls and implements the cation exchange mechanism. In this case, the level of secretion and excretion of potassium is determined and limited by the volume of reabsorbed sodium. Overproduction of aldosterone, enhancing sodium reabsorption, induces a loss of potassium, which, in its pathophysiological effect, overrides the effect of reabsorbed sodium and forms a complex of metabolic disorders underlying the clinical picture of primary hyperaldosteronism.

The general loss of potassium with the depletion of its intracellular reserves leads to universal hypokalemia, and the excretion of chlorine and the replacement of potassium inside cells by sodium and hydrogen contribute to the development of intracellular acidosis and hypokalemic, hypochloremic extracellular alkalosis.
Potassium deficiency causes functional and structural disorders in organs and tissues: in the distal renal tubules, in smooth and striated muscles, in the central and peripheral nervous system. The pathological effect of hypokalemia on neuromuscular excitability is aggravated by hypomagnesemia as a result of inhibition of magnesium reabsorption. By suppressing insulin secretion, hypokalemia reduces carbohydrate tolerance, and by affecting the epithelium of the renal tubules, it makes them refractory to the effect of antidiuretic hormone. At the same time, a number of renal functions are disrupted and, first of all, their concentration ability decreases. Retention of sodium causes hypervolemia, suppresses the production of renin and angiotensin II, increases the sensitivity of the vascular wall to various endogenous pressor factors and, ultimately, contributes to the development of arterial hypertension. In primary hyperaldosteronism, caused by both adenoma and hyperplasia of the adrenal cortex, the level of glucocorticoids, as a rule, does not exceed the norm, even in cases where the morphological substrate of aldosterone hypersecretion includes not only elements of the glomerular zone, but also the bundle. A different picture in carcinomas, which are characterized by mixed intense hypercortisolism, and the variability of the clinical syndrome is determined by the predominance of certain hormones (gluco- or mineralocorticoids, androgens). Along with this, true primary hyperaldosteronism may be due to highly differentiated adrenal cortex cancer with normal glucocorticoid production.

Pathological anatomy. Morphologically, at least 6 variants of the form of hyperaldosteronism with a low level of renin are distinguished:
1) with an adenoma of the adrenal cortex in combination with atrophy of the surrounding cortex;
2) with an adenoma of the adrenal cortex in combination with hyperplasia of elements of the glomerular and / or fascicular and reticular zones;
3) on the basis of primary cancer of the adrenal cortex;
4) with multiple adenomatosis of the cortex;
5) with isolated diffuse or focal hyperplasia of the glomerular zone;
6) with nodular diffuse-nodular or diffuse hyperplasia of all areas of the cortex.
Adenomas are, in turn, of a varied type of structure, as well as changes in the adrenal tissue surrounding them. Changes in the adrenal glands of patients with non-neoplastic forms of low-rootin hyperaldosteronism are reduced to diffuse or diffuse-nodular hyperplasia of one, two or all areas of the cortex and / or to pronounced phenomena of adenomatosis, in which focal hyperplasia is accompanied by hypertrophy of cells and their nuclei, increased nuclear-plasma ratio, increased oxyphilia of the cytoplasm and a decrease in the content of lipids in it. Histochemically, these cells are characterized by high activity of steroidogenesis enzymes and a decrease in the content of cytoplasmic lipids, mainly due to cholesterol esters. Nodular formations are formed most often in the bundle zone, mainly from the elements of its outer parts, which form pseudoacinar or alveolar structures. But the cells in the nodular formations have the same functional activity as the cells of the surrounding cortex. Hyperplastic changes lead to a two- and three-fold increase in adrenal mass and to hypersecretion of aldosterone by both adrenal glands. This is observed in more than 30% of patients with hyperaldosteronism and low plasma renin activity. The cause of this pathology may be the aldosterostimulating factor of pituitary origin, isolated in a number of patients with primary hyperaldosteronism, although there is no solid evidence of this.

Symptoms of Primary Hyperaldosteronism

The clinical features of primary hyperaldosteronism are composed of severe electrolyte disturbances, renal dysfunctions and arterial hypertension. Along with general and muscle weakness, which is often the first reason for going to a doctor, patients are worried about headaches, thirst and increased, mainly nocturnal, urination. Changes in potassium and magnesium levels increase neuromuscular excitability and cause recurrent seizures of varying intensity. Characterized by paresthesias in various muscle groups, twitching of the muscles of the face, positive symptoms of Khvostek and Trousseau.
Calcium metabolism, as a rule, does not suffer. There are periodic attacks of severe muscle weakness, up to complete immobility of the lower extremities (pseudoparalysis), lasting from several hours to several days. One of the indirect symptoms of diagnostic value is a significant increase in the electrical potential in the colon. Most of the symptoms of hyperaldosteronism (excluding hypertension) are nonspecific and are determined by hypokalemia and alkalosis.

The main symptoms of hyperaldosteronism and their frequency based on the materials of Conn's works:
1) hypertension - 100%;
2) hypokalemia — 100%;
3) hypochloremic alkalosis - 100%;
4) an increase in the level of aldosterone - 100%;
5) low level of renin - 100%;
6) proteinuria - 85%;
7) hypostenuria resistant to vasopressin - 80%;
8) violation of urine oxidation - 80%;
9) ECG change - 80%;
10) increased level of potassium in urine - 75%;
11) muscle weakness - 73%;
12) nocturnal polyuria - 72%;
13) hypernatremia - 65%;
14) decreased glucose tolerance - 60%;
15) headaches - 51%;
16) retinopathy - 50%;
17) thirst - 46%;
18) paresthesia - 24%;
19) periodic paralysis - 21%;
20) tetany - 21%;
21) general weakness - 19%;
22) muscle pain - 10%;
23) asymptomatic forms - 6%;
24) edema — 3%.

Attention is drawn to the asymptomatic course of the disease in 6% of patients and hypokalemia in 100%. At the same time, normokalemic forms of primary hyperaldosteronism are now known. It has also been reported about casuistic normotensive variants of the disease, which retains all the other features of typical primary hyperaldosteronism. The most important, and in the early stages is often the only symptom is arterial hypertension. Dominant in the clinical picture for many years, it can mask the signs of hyperaldosteronism. The existence of low-root hypertension (10-420% of all hypertensive patients) makes it especially difficult to recognize primary hyperaldosteronism. Hypertension can be stable or combined with paroxysms. Its level increases with the duration and severity of the disease, but the malignant course is noted infrequently. Hypertension does not respond to orthostatic load, and during the Valsalva test, its level in primary hyperaldosteronism does not increase, in contrast to hypertension of a different etiology. The introduction of spironolactones (veroshpiron, aldactone) in a daily dose of 400 mg for 10-15 days reduces hypertension simultaneously with the normalization of potassium levels. The latter occurs only in patients with primary hyperaldosteronism. The absence of this effect casts doubt on the diagnosis of primary hyperaldosteronism, excluding those patients who have pronounced symptoms of atherosclerosis. Half of the patients have retinopathy, but its course is benign, usually without signs of proliferation, degeneration and hemorrhage. Left ventricular hypertension and signs of its overload on the ECG are noted in most cases. However, cardiovascular failure is not common in primary hyperaldosteronism.

Serious vascular changes occur only with a long-term unknown diagnosis. Although hypokalemia and hypokalemic alkalosis underlie many of the symptoms of primary hyperaldosteronism, blood potassium levels can fluctuate and retest is necessary. Its content increases and even normalizes with a prolonged low-salt diet and taking spironolactones. Hypernatremia is much less common than hypokalemia, although sodium metabolism and its content in cells are increased.
The absence of pronounced and stable hypernatremia is associated with a decrease in the sensitivity of the renal tubules to the sodium inhibiting effect of aldosterone with increased secretion and excretion of potassium. However, this refractoriness does not apply to the cation exchange mechanism of the salivary, sweat glands and intestinal mucosa. The excretion of potassium is carried out mainly by the kidneys and to a lesser extent through sweat, saliva, and the gastrointestinal tract. This loss (70% of intracellular stores) reduces the level of potassium not only in plasma, but also in erythrocytes, in cells of smooth and striated muscles. Its urinary excretion exceeding 40 mEq / 24 h raises suspicion of primary hyperaldosteronism. It should be noted that patients are not able to retain potassium in the body, its intake is ineffective, and a diet rich in sodium, forcing the release of potassium and aggravating clinical symptoms. Conversely, a sodium-depleted diet limits the excretion of potassium, and its level in the blood increases markedly. Hypokalemic damage to the epithelium of the renal tubules against the background of general hypokalemic alkalosis disrupts a number of renal functions and mainly the mechanisms of oxidation and concentration of urine. The "Kaliopenic kidney" is insensitive to endogenous (and exogenous) vasopressin, the level of which increases compensatory and due to high plasma osmolarity. Patients have mild periodic proteinuria, polyuria, nocturia, hypoisostenuria with a relative density of individual portions of urine 1008-1012. Refractoriness to the administration of vasopressin is noted. The urine reaction is often alkaline. In the initial stages of the disease, renal impairment may be minor. Characterized by polydipsia, which has a complex genesis: compensatory - in response to polyuria, central - as a result of the effect of low potassium levels on the thirst center and reflex - in response to sodium retention in cells. Edema is not typical for primary hyperaldosteronism, since polyuria and sodium accumulation inside the cells, and not in the interstitium, do not contribute to fluid retention in the intercellular spaces.

Along with this, for primary hyperaldosteronism, an increase in intravascular volume and its invariability with the introduction of an isotonic saline solution and even albumin are specific. Stable hypervolemia combined with high plasma osmolarity suppresses plasma renin activity. Histochemical studies reveal the disappearance of renin granulations in vas efferens secretory cells, a decrease in renin activity in renal homogenates and in renal biopsy in patients. Low unstimulated plasma renin activity is a cardinal symptom of primary hyperaldosteronism in aldosteromas. The levels of secretion and excretion of aldosterone vary significantly in patients with primary hyperaldosteronism, but in most cases they are elevated, and the levels of glucocorticoids and androgens are normal. The level of aldosterone and its closest precursor, 18-oxycorticosterone, is higher in aldosteromas and lower in hyperplastic variants of primary hyperaldosteronism.
Prolonged hypokalemia can cause a gradual decrease in aldosterone secretion. In contrast to healthy people, its level paradoxically falls with orthostatic exercise (4-hour walk) and spironolactone therapy. The latter block the synthesis of aldosterone in the tumor. In the study after surgery in patients who received veroshpiron for a long time, the removed aldosterone-producing tissue did not respond to the addition of angiotensin II and adrenocorticotropic hormone. There are known cases of aldosterones producing not aldosterone, but 18-oxycorticosterone. The possibility of the development of primary hyperaldosteronism in connection with the increased production of other mineralocorticoids: corticosterone, DOK, 18-hydroxycorticosterone or still unknown steroids is not rejected. The severity of primary hyperaldosteronism is determined by the intensity of metabolic disorders, their duration and the development of vascular complications. In general, the disease is characterized by a relatively benign course.
With the development of secondary hyperaldosteronism, its course is closely related to the underlying disease.

Complications. Complications are mainly due to hypertensive and neuromuscular syndromes.
Possible heart attacks, strokes, hypertensive retinopathy, severe myasthenia gravis. Malignancy of the tumor is occasionally noted.

Diagnosis of Primary Hyperaldosteronism

Diagnostic criteria:
1) a combination of arterial hypertension and myasthenic syndrome;
2) hypernatremia, hypokalemia, hyperkaliuria, hyponatriyuria;
3) polyuria, iso- and hypostenuria. The urine reaction is alkaline;
4) an increase in the level of aldosterone in plasma and its excretion in the urine;
5) an increase in the size of the adrenal glands with ultrasound sonography (computed tomography or angiography);
6) signs of hypokalemia on the ECG.
To clarify the diagnosis, functional tests are performed.

A test with veroshpiron is done by a patient receiving a sufficient amount of sodium chloride (up to 6 g per day). The initial serum potassium content is determined, after which veroshpiron is administered orally for 3 days (400 mg / day). An increase in potassium content of more than 1 mmol / L confirms hyperaldosteronism.

Sodium chloride load test. Within 3-4 days the patient receives at least 9 g of sodium chloride per day. With hyperaldosteronism, there is a decrease in serum potassium.

Test with furosemide. The patient takes 0.08 g of furosemide inside, and after 3 hours the content of renin and aldosterone is determined. An increase in aldosterone levels and a decrease in renin are indicative of primary hyperaldosteronism.
The differential diagnosis is carried out with diseases accompanied by the syndrome of arterial hypertension.

Hypertonic disease. General signs: headache, arterial hypertension, left ventricular hypertrophy. Differences: with hyperaldosteronism, there is a combination of arterial hypertension and myasthenic syndrome with transient paralysis, an increase in aldosterone in the blood plasma and its excretion in the urine, mass formation or hyperplasia of the adrenal cortex.
Arterial hypertension of renal origin. General signs: persistent arterial hypertension. Differences: with arterial hypertension of renal origin, there are no neuromuscular symptoms, there is resistance to antihypertensive drugs from diastolic blood pressure. Expressed urinary syndrome (proteinuria, hematuria). It is possible to increase the level of creatinine in the blood, accelerate the rate of erythrocyte sedimentation.

Treatment of Primary Hyperaldosteronism

Treatment depends on the underlying causes of hyperaldosteronism. With primary hyperaldosteronism, surgical treatment is indicated (one- or two-sided adrenalectomy followed by replacement therapy). Preoperative preparation is carried out with aldosterone antagonists (verospiron), potassium preparations. With secondary hyperaldosteronism, long-term drug treatment is carried out with spironolactones, potassium preparations, glucocorticoid synthesis inhibitors (elipten, aminoglutetiamide).
Idiopathic and uncertain aldosteronism creates an alternative situation in which the feasibility of surgical treatment is disputed by many authors. Even total adrenalectomy of one adrenal gland and subtotal adrenal gland, eliminating hypokalemia in 60% of patients, does not give a significant hypotensive effect. At the same time, spironolactones, against the background of a low-salt diet and the addition of potassium chloride, normalize potassium levels and reduce arterial hypertension. In this case, spironolactones not only eliminate the effect of aldosterone on the renal and other potassium-secreting levels, but also inhibit the biosynthesis of aldosterone in the adrenal glands. In almost 40% of patients, surgical treatment is completely effective and justified. Arguments in its favor may be the high cost of lifelong use of large doses of spironolactones (up to 400 mg daily), and in men the incidence of impotence and gynecomastia due to the antiandrogenic effect of spironolactones, which have a structure close to steroids and suppress testosterone synthesis by the principle of competitive antagonism. The effectiveness of surgical treatment and restoration of the disturbed metabolic balance to a certain extent depends on the duration of the disease, the age of the patients and the degree of development of secondary vascular complications.
However, even after successful removal of aldosteroma, hypertension remains in 25% of patients, and in 40% it recurs after 10 years.
With a solid tumor size, a long duration of the disease with intense metabolic disorders, some time after the operation, episodes of hypo-aldosteronism (weakness, tendency to fainting, hyponatremia, hyperkalemia) may appear.
Surgical treatment should be preceded by long-term treatment with spironolactones (1-3 months, 200-400 mg daily) until the level of electrolytes is normalized and hypertension is eliminated. Along with them or instead of them, potassium-sparing diuretics (triampur, amiloride) can be used.
The hypotensive effect of spironolactones in primary aldosteronism is potentiated by captopril.
Prolonged administration of spironolactones somewhat activates the suppressed renin-angiotensin system, especially in bilateral hyperplasia, and thereby prevents postoperative hypoaldosteronism.
Regardless of the etiology of the disease, the diet should contain a limited amount of table salt and foods rich in potassium (potatoes, dried apricots, rice, raisins).