Primary hyperaldosteronism - review of information. Primary hyperaldosteronism (Conn's syndrome) Primary and secondary hyperaldosteronism

– 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, paresthesia, and convulsions are observed. With secondary hyperaldosteronism, peripheral edema, chronic renal failure, and fundus changes develop. Diagnosis of various types of hyperaldosteronism includes biochemical analysis of blood and urine, functional stress tests, ultrasound, scintigraphy, MRI, selective venography, examination of the heart, liver, kidneys and renal arteries. Treatment of hyperaldosteronism in aldosteroma, adrenal cancer, and renal reninoma is surgical; in other forms, it is medicinal.

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 (caused by pathology of the adrenal glands themselves) and secondary (caused by hypersecretion of renin 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; A few cases of hyperaldosteronism among children have been described.

Causes of hyperaldosteronism

Depending on the etiological factor, several forms of primary hyperaldosteronism are distinguished, of which 60-70% of cases are 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 type of inheritance, caused by a defect in the 18-hydroxylase enzyme, which is beyond the control of the renin-angiotensin system and corrected by glucocorticoids (occurs in young patients with frequent cases of arterial hypertension in the family history). In rare cases, primary hyperaldosteronism may 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 pathologies. Secondary hyperaldosteronism is seen in heart failure, malignant hypertension, liver cirrhosis, Barter's syndrome, renal artery dysplasia and stenosis, nephrotic syndrome, renal reninoma and renal failure.

Increased renin secretion and the development of secondary hyperaldosteronism are caused by sodium loss (due to diet, diarrhea), a decrease in circulating blood volume due to blood loss and dehydration, excessive potassium consumption, and long-term use of certain medications (diuretics, COCs, laxatives). Pseudohyperaldosteronism develops when the response of the distal renal tubules to aldosterone is impaired, when, despite its high level in the blood serum, hyperkalemia is observed. Extra-adrenal hyperaldosteronism is observed quite rarely, for example, in pathologies of the ovaries, thyroid gland and intestines.

Pathogenesis

Primary hyperaldosteronism (low-renin) is usually associated with a tumor or hyperplastic lesion of the adrenal cortex and is characterized by a combination of increased aldosterone secretion 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, decreased production and activity of plasma renin. There is a hemodynamic disturbance - increased sensitivity of the vascular wall to the action of endogenous pressor factors and resistance of peripheral vessels to blood flow. In primary hyperaldosteronism, severe and prolonged hypokalemic syndrome leads to dystrophic changes in the renal tubules (kaliopenic nephropathy) and muscles.

Secondary (high aldosteronism) hyperaldosteronism occurs compensatory, in response to a decrease in the volume of renal blood flow in various diseases of the kidneys, liver, and heart. Secondary hyperaldosteronism develops due to activation of the renin-angiotensin system and increased production of renin by the cells of the juxtaglomerular apparatus of the kidneys, which provide excessive stimulation of the adrenal cortex. Severe 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 water and electrolyte balance caused by hypersecretion of aldosterone. Due to sodium and water retention, patients with primary hyperaldosteronism experience severe or moderate arterial hypertension, headaches, aching pain in the heart (cardialgia), heart rhythm disturbances, changes in the fundus of the eye with deterioration of visual function (hypertensive angiopathy, angiosclerosis, retinopathy).

Potassium deficiency leads to rapid fatigue, muscle weakness, paresthesia, seizures in various muscle groups, periodic pseudoparalysis; in severe cases - to the development of myocardial dystrophy, kalipenic nephropathy, nephrogenic diabetes insipidus. In 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), gradually leading to damage to the vascular wall and tissue ischemia, deterioration of kidney function and the development of chronic renal failure, changes in the fundus (hemorrhages, neuroretinopathy). The most common sign of secondary hyperaldosteronism is edema; hypokalemia occurs in rare cases. Secondary hyperaldosteronism can occur without arterial hypertension (for example, with Barter syndrome and pseudohyperaldosteronism). Some patients experience asymptomatic hyperaldosteronism.

Diagnostics

Diagnosis involves differentiating various forms of hyperaldosteronism and determining their etiology. As part of the initial diagnosis, an analysis of the functional state of the renin-angiotensin-aldosterone system is carried out 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 (PRA), a high aldosterone/renin ratio, hypokalemia and hypernatremia, 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 level of ARP (for reninoma - more than 20–30 ng/ml/h).

In order to differentiate individual forms of hyperaldosteronism, a test with spironolactone, a test with a hypothiazide load, and a “marching” test are performed. In order to identify the familial form of hyperaldosteronism, genomic typing is performed using PCR. In hyperaldosteronism corrected by glucocorticoids, trial treatment with dexamethasone (prednisolone) is of diagnostic value, which eliminates the manifestations of the disease and normalizes blood pressure.

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 through studies of the condition of the heart, liver, kidneys and renal arteries (EchoCG, ECG, liver ultrasound, kidney ultrasound, Doppler ultrasound and duplex scanning of the renal arteries, multislice CT, MR angiography).

Treatment of hyperaldosteronism

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

Treatment of aldosteroma and adrenal cancer is surgical and consists of removing the affected adrenal gland (adrenalectomy) with preliminary restoration of water and 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 adrenalectomy in combination with subtotal resection of the left adrenal gland are ineffective. Hypokalemia disappears, but the desired hypotensive effect is absent (BP is normalized only in 18% of cases) and there is a high risk of developing acute adrenal insufficiency.

In case of hyperaldosteronism, which can be corrected by glucocorticoid therapy, hydrocortisone or dexamethasone is prescribed to eliminate hormonal and metabolic disorders and normalize blood pressure. In case of secondary hyperaldosteronism, combined antihypertensive therapy is carried out against the background of pathogenetic treatment of the underlying disease under mandatory monitoring of ECG and potassium levels in the blood plasma.

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

Forecast 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 probability of recovery. Adrenal cancer has a poor prognosis.

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

Increased aldosterone levels (hyperaldosteronism) are one of the causes of increased blood pressure, cardiovascular complications, decreased kidney function and changes in electrolyte ratios. Primary and secondary hyperaldosteronism are classified, based on different etiological factors and pathogenetic mechanisms. The most common cause of the development of the primary type of pathology is Conn's syndrome.

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Conn's syndrome

Conn's syndrome– a disease that occurs due to increased production of aldosterone by a tumor of the adrenal cortex. In the structure of primary aldosteronism (PGA), the incidence of this pathology reaches 70% of cases, so some people combine these concepts. According to the latest data, among patients with arterial hypertension that is difficult to treat with medication, Conn's syndrome occurs in 5-10% of cases. Women get sick 2 times more often, while the onset of the pathology is gradual, symptoms appear after 30-40 years.

The concept and causes of primary and secondary hyperaldosteronism:

Primary hyperaldosteronism

Secondary hyperaldosteronism

Definition

A syndrome that develops as a result of excessive production of aldosterone by the adrenal cortex (rarely an aldosterone-producing tumor of extra-adrenal localization), the level of which is relatively independent of the renin-angiotensin-aldosterone system (RAAS) and is not suppressed by sodium load

A syndrome resulting from a decrease in colloid osmotic blood pressure and stimulation of the RAAS (as a complication of a number of diseases)

Causes

The disease is associated with pathology of the adrenal glands:

aldosterone-producing adenoma (Conn's syndrome) – 70%;
bilateral hyperplasia of the zona glomerulosa of the adrenal cortex (idiopathic hyperaldosteronism) – up to 30%;
rare diseases (aldosterone-producing carcinoma, unilateral hyperplasia of the zona glomerulosa of the adrenal cortex, familial hyperaldosteronism types I, II, III, MEN – I).

Associated with pathology of other organs and systems:

kidney diseases (nephrotic syndrome, renal artery stenosis, kidney tumors, etc.);
heart disease (congestive heart failure);
other causes (hypersecretion of ACTH, taking diuretics, liver cirrhosis, fasting)

Etiology

The most common location of aldosterone-producing adenoma is the left adrenal gland. The tumor is solitary, does not reach large sizes (up to 3 cm), and is benign in nature (malignant aldosteromas occur extremely rarely).

CT scan of the abdomen. Adrenal adenoma

Pathogenesis

Aldosterone is a mineralocorticoid hormone produced by the adrenal cortex. Its synthesis occurs in the zona glomerulosa. Aldosterone plays a leading role in regulating water and electrolyte balance in the body. Its secretion is controlled mainly by the PAA system.

Excess aldosterone plays a major role in the pathogenesis of Conn's syndrome. It promotes increased excretion of potassium by the kidneys (hypokalemia) and sodium reabsorption (hypernatremia), leading to alkalization of the blood (alkalosis). Sodium ions accumulate fluid in the body, increasing the circulating blood volume (CBV), which entails an increase in blood pressure. High blood volume suppresses renin synthesis by the kidney. Long-term loss of potassium ions subsequently leads to nephron dystrophy (potassium-penic kidney), arrhythmias, myocardial hypertrophy, and muscle weakness. It is noted that the risk of sudden death from cardiovascular accidents increases sharply in patients (on average 10–12 times).

Clinic

Symptoms of primary hyperaldosteronism develop gradually. Patients with Conn's syndrome are diagnosed with:

persistent increase in blood pressure, resistant to drug treatment in the medical history;
headache;
heart rhythm disturbances due to potassium deficiency, bradycardia, the appearance of a U wave on the ECG;
neuromuscular symptoms: weakness (especially in the calf muscles), cramps and paresthesia in the legs, tetany may occur;
renal dysfunction (hypokalemic nephrogenic diabetes insipidus): increased urine volume per day (polyuria), predominance of nighttime diuresis over daytime (nocturia);
thirst (polydipsia).

Secondary aldosteronism is expressed in manifestations of the underlying disease; arterial hypertension and hypokalemia may not be present; the presence of edema is characteristic.

Diagnostics

Diagnosis of Conn's syndrome is recommended in persons with arterial hypertension that is not amenable to drug therapy, with a combination of increased blood pressure and hypokalemia (identified by clinical symptoms or blood test results), with the onset of hypertension before 40 years of age, with a family history of cardiovascular diseases , as well as if relatives have a confirmed diagnosis of PHA. Laboratory diagnosis is quite difficult and requires confirmation using functional tests and instrumental research methods.

Laboratory research

After forming a risk group, patients are determined:

blood plasma aldosterone level (increased by 70%);
blood potassium (decrease in 37-50% of patients);
plasma renin activity (PRA) or its direct concentration (PCR) (decrease in most patients);
Aldosterone-renin ratio (ARR) is a mandatory screening method.

Obtaining reliable results of the APC level depends on the preparation of the patient before the analysis and compliance with the blood sampling conditions according to the protocol. The patient should eliminate Veroshpiron and other diuretics, licorice medications at least a month in advance, and other medications that affect the level of aldosterone and renin about 2 weeks in advance: beta-blockers, ACE inhibitors, AR I blockers, central a-adrenergic agonists, NSAIDs, inhibitors renin, dihydropyridines. Hypertension control should be carried out using drugs with minimal effect on aldosterone levels (Verapamil, Hydralazine, Prazosin hydrochloride, Doxazosin, Terazosin). If a patient has a malignant course of hypertension and the withdrawal of antihypertensive drugs can lead to serious consequences, ARS is determined against the background of their use, taking into account the error.

Medicines that affect the results of ARS:

In addition to taking various medications, there are other factors that affect the interpretation of results :

age > 65 years (renin levels decrease, leading to overestimation of APC values);
time of day (the study is carried out in the morning);
the amount of salt consumed (usually not limited);
dependence on body position (when waking up and moving to a vertical position, the level of aldosterone increases by a third);
marked decrease in kidney function (ARS increases);
in women: the phase of the menstrual cycle (the study is carried out in the follicular phase, since physiological hyperaldosteronemia occurs in the luteal phase), taking contraceptives (decreased plasma renin), pregnancy (decreased APC).

If APC is positive, one of the functional tests is recommended. If a patient has spontaneous hypokalemia, renin is not detected, and the aldosterone concentration is above 550 pmol/l (20 ng/dl), the diagnosis of PHA does not need to be confirmed by stress testing.

Functional tests to determine aldosterone levels:

Functional tests	Methodology	Interpretation of test results
Sodium load test	Within three days, salt intake increases to 6 g per day. It is necessary to control daily sodium excretion and normalize potassium levels with the help of medications. Daily aldosterone excretion (DAE) is determined on the third day of the study in the morning	PGA is unlikely – SEA< 10 мг или 27,7 нмоль (исключить ХПН); PHA is highly probable – SEA >12 mg (>33.3 nmol)
Test with 0.9% sodium chloride solution	In the morning, administer an intravenous infusion of 2 liters of 0.9% solution over 4 hours (provided you are in a supine position one hour before). Blood test for aldosterone, renin, cortisone, potassium at the beginning of the test and after 4 hours. Monitor blood pressure and pulse rate. Option 2: the patient takes a sitting position 30 minutes before and during the infusion	PHA is unlikely with post-infusion aldosterone levels< 5 нг/дл; Doubtful - from 5 to 10 ng/dl; PGA is probable at levels > 10 ng/dL (sitting > 6 ng/dL)
Captopril test	Captopril at a dose of 25-50 mg one hour after waking up. Aldosterone, ARP and cortisol are determined before taking Captopril and after 1-2 hours (all this time the patient must be in a sitting position)	The norm is a decrease in aldosterone levels by more than a third from the initial value. PHA - aldosterone remains elevated with low ARP
Suppression test with fludrocortisone	Taking 0.1 mg fludrocortisone 4 times a day for 4 days, potassium supplements 4 times a day (target level 4.0 mmol/l) with unlimited salt intake. On the 4th day at 7.00 am, cortisol is determined, at 10.00 - aldosterone and ARP while sitting, cortisol is repeated	For PHA – aldosterone > 170 pmol/l, ARP< 1 нг/мл/ч; Cortisol at 10:00 is not lower than at 7:00 (excluding the influence of cortisol)

Instrumental studies

Carry out to all patients after receiving the results of laboratory tests:

Ultrasound of the adrenal glands - detection of tumors more than 1.0 cm in diameter.
CT scan of the adrenal glands - with an accuracy of 95% determines the size of the tumor, shape, topical location, differentiates benign neoplasms and cancer.
Scintigraphy - with aldosteroma there is a unilateral accumulation of 131 I-cholesterol, with adrenal hyperplasia - accumulation in the tissue of both adrenal glands.
Catheterization of the adrenal veins and comparative selective venous blood sampling (CVBS) - allows you to clarify the type of primary aldosteronism, is the preferred method for the differential diagnosis of unilateral aldosterone secretion in adenoma. Based on the ratio of aldosterone and cortisol levels on both sides, the lateralization gradient is calculated. The indication for this is to clarify the diagnosis before surgical treatment.

Differential diagnosis

Differential diagnosis of Conn's syndrome is carried out with idiopathic hyperplasia of the adrenal cortex, with secondary hyperaldosteronism, essential hypertension, endocrine diseases accompanied by increased blood pressure (Itsenko-Cushing syndrome, pheochromocytoma), with a hormonally inactive neoplasm and cancer. A malignant aldosterone-producing tumor on CT can reach large sizes and is characterized by high density, inhomogeneity, and blurred contours.

Differential diagnosis:

	Conn's syndrome (aldosterone-producing adenoma)	Idiopathic hyperaldosteronism	Secondary hyperaldosteronelowness
Laboratory indicators		aldosterone, ↓↓renin, ARS, ↓potassium	aldosterone, renin, - APC, ↓potassium
Orthostatic (march) test - study of aldosterone levels upon awakening in a horizontal position, repeated study after being in a vertical position (walking) for 3 hours	High aldosterone levels initially, some decrease with repeated testing, or at the same level	Increased aldosterone levels (maintained sensitivity to AT-II)	Increased aldosterone levels
CT	small mass formation of one of the adrenal glands	the adrenal glands are not changed, or there are small nodular formations on both sides	The adrenal glands are not enlarged, the size of the kidneys may be reduced
Catheterization of adrenal veins with selective blood sampling	Lateralization	-	-

Treatment

For aldosteroma, laparoscopic adrenalectomy is performed (after 4 weeks of preoperative preparation on an outpatient basis). Drug treatment is carried out for contraindications to surgery or for other forms of hyperaldosteronism:

The main pathogenetic treatment is aldosterone antagonists - Veroshpiron 50 mg 2 times a day with an increase in dose after 7 days to 200 - 400 mg / day in 3-4 doses (maximum up to 600 mg / day);
To lower blood pressure levels - Dihydropyridines 30–90 mg/day;
Correction of hypokalemia - potassium supplements.

Spironolactone is used to treat idiopathic HA. To reduce blood pressure, it is necessary to add saluretics, calcium antagonists, ACE inhibitors and angiotensin II antagonists. If differential diagnosis reveals glucocorticoid-suppressed hyperaldosteronism, dexamethasone is prescribed.

Aldosteronism is a clinical syndrome associated with excessive secretion of aldosterone in the adrenal cortex. The most powerful one produced by the adrenal glands is considered to be designed to retain sodium in the body.

The process is due to the transfer of sodium from the distal tubules to the tubular cells and its exchange with potassium and hydrogen. Similar processes are also observed in the sweat glands and intestines.

The renin-angiotensin mechanism controls secretion. Thanks to a proteolytic enzyme localized in kidney cells, it is possible to detect a sharp decrease in the volume of blood that circulates in the renal arterioles. Hypersecretion of this enzyme may also be associated with a decrease in blood flow velocity.

Increased production of aldosterone causes sodium and hydrogen retention, which normalizes blood volume in the kidneys, keeping renin secretion insignificant.

The diagnosis of primary or secondary aldosteronism is determined by what causes influence the excess production of aldosterone.

In medical practice, it is also called Conn's syndrome and is associated with the appearance. The disease is caused by disruption of the endocrine system and is quite common. A hormonally active tumor is localized in the zona glomerulosa of the adrenal cortex.

Renal arrhythmia, decreased blood volume in the kidneys, and narrowing of the renal vessels can affect the hypersecretion of the hormone, which contributes to the development of this disease. You should know that edema and hypertension do not always accompany aldosteronism; with Bartter's syndrome, these symptoms may be completely absent, but hypokalemia, alkalosis and plasma renin activity persist.

Causes

Excessive production of the hormone by the adrenal cortex leads to the formation of a tumor, in most cases it is an aldosteroma or bilateral, carcinoma is less common. It is noted that representatives of the weaker sex are more susceptible to the disease.

The male body tolerates this disease more easily; in rare cases, the help of medical personnel is required.

The causes of secondary aldosteronism can be diseases with renal ischemia, various liver diseases, heart failure, diabetes mellitus, myocardial infarction, pneumonia.

Often the disease occurs against the background of long-term diets in which the daily diet is not enriched with sodium. Hormonal imbalance also occurs with prolonged therapy in combination with.

Mechanism of nucleation

Primary aldosteronism is caused by increased secretion of aldosterone, which contributes to a significant release of potassium and hydrogen from the body. Potassium deficiency is characterized by muscle weakness, which can develop into muscle paralysis.

One of the main symptoms is considered to be in which the renal tubules undergo dystrophic changes and loss of sensitivity to antidiuretic hormone. As a result, intracellular acidosis and extracellular alkalosis develop, which are the first step in the development of hypertension. Symptoms of high blood pressure include migraines, changes in the fundus of the eye and hypertrophy of the heart muscle.

Speaking about the pathogenesis of secondary aldosteronism, one should take into account the primary role of the underlying disease. In some cases we are talking about excess renin production, in others – about oncotic pressure and hypovolemia. In this regard, hypertensive syndrome, edematous syndrome and forms without the appearance of edema and hypertension are distinguished.

Clinical picture

Signs of primary aldosteronism:

increased blood pressure
migraine
constant thirst
and excessive urination
aching pain in the heart
dyspnea
tachycardia
muscle weakness
convulsions
blood test shows a sharp decrease in potassium levels

The critical stage of the disease is characterized by the following symptoms:

muscle paralysis
vision loss
nausea
vomit
swelling of the retina or optic nerve

Signs of secondary aldosteronism:

heart failure
chronic nephritis
Botkin's disease
chronic hepatitis
cirrhosis of the liver
increased swelling

Diagnostic methods

To identify primary aldosteronism with signs of hypokalemia, a diagnostic test based on the administration of aldactone is used. To diagnose aldosteroma, radioisotope imaging of the adrenal glands is used, a radioisotope drug is first administered intravenously, and only a week later the imaging procedure is performed.

X-ray diagnostics using pneumosuprarenography and angiography are often used; this method is noted as one of the most effective.

As practice shows, diagnosing secondary aldosteronism is quite difficult. Urine excretion with aldosterone, electrolyte balance, as well as the ratio of sodium and potassium have been studied for a long time.

Methods of therapy

After a thorough diagnosis and diagnosis, treatment methods for aldosteronism are determined. For primary treatment, surgery is recommended. The tumor formed in the adrenal glands is removed surgically, after which the patient’s recovery is guaranteed.

Removal of the tumor is accompanied by normalization of blood pressure and restoration of electrolyte balance. Rehabilitation of the patient takes place in the shortest possible time, unpleasant symptoms completely disappear.

Treatment of secondary aldosteronism is fundamentally different and is associated with the elimination of all causes that cause additional stimulation of the hormone. The attending physician prescribes the most effective therapy in combination with excess hormone blockers.

Complex treatment involves the use of. Diuretics remove all excess fluid from the body, which ensures the disappearance of edema. Elimination of the underlying disease is the key to the patient’s recovery; properly selected therapy, which will be successfully combined with hormone blockers and diuretics, is determined by the degree of development of the disease.

Treatment of secondary aldosteronism occurs in parallel with the main treatment; the most popular regimens are the use of prednisolone with diuretics or aldactone.

Forecasts

If the patient contacts the patient in a timely manner, treatment of the disease of primary aldosteronism is predicted to be favorable. But only if there are no irreversible changes in the kidneys and vascular system. Surgery and removal of the formation is not accompanied by a sharp decrease in blood pressure or collapse. After the operation, there is a complete disappearance of symptoms, and the secretion of hormones is gradually restored.

Without treatment, death occurs due to progressive concomitant diseases. Malignant aldosteroma does not have a favorable prognosis.

Untimely treatment and surgical treatment in a later period in most cases is caused by loss of ability to work and assignment of group 1 disability; the duration of recovery of the body in the postoperative period is determined by the degree of reversibility of changes in the body.

Prognosis for treatment of secondary aldosteronism depends on the severity of concomitant diseases, and the extent to which the kidneys are affected is also important. Often, kidney pathology is accompanied by the formation of malignant tumors ().

Conn's syndrome (primary aldosteronism, Conn syndrome) is a syndrome caused by autonomous (that is, independent of the renin-aldosterone system) hypersecretion of aldosterone in the adrenal cortex.

Causes of Conn's syndrome

The most common direct causes of its development are aldosterone-producing adrenal adenoma or bilateral adrenal hyperplasia; much less often - unilateral hyperplasia, adrenal carcinoma, or familial hyperaldosteronism (types I and II are distinguished). In persons under the age of 40 years, the cause of Conn's syndrome is much more often an adrenal adenoma than a bilateral adrenal hyperplasia.

Causes of hypersecretion of mineralocorticoids:

Aldosterone-producing adrenal adenoma

Aldosterone-producing adenomas account for about 35-40% of cases in the structure of primary aldosteronism. Solitary benign adenomas are almost always unilateral (one-sided). In most cases they are small in size (in 20-85% of cases - less than 1 cm). Beyond the adenoma, focal or diffuse tissue hyperplasia may occur in the rest of the adrenal tissue, as well as in the contralateral adrenal gland (making differential diagnosis with bilateral hyperplasia difficult).

Bilateral adrenal hyperplasia
Primary unilateral adrenal hyperplasia (rare)
Familial hyperaldosteronism (types I and II), glucocorticoid controlled (rare)
Adrenal carcinoma (rare)

Most cases of aldosteronism (increased plasma aldosterone levels) that occur in clinical practice are secondary to increased activity of the renin-aldosterone system (in response to decreased renal perfusion, such as in renal artery stenosis or in some chronic conditions, accompanied by the development of edema). For differential diagnosis, you can use the determination of plasma renin activity (PRA):

with secondary aldosteronism this indicator is increased,
in Conn's syndrome - reduced.

Previously, the dominant point of view was the relative rarity of primary aldosteronism. However, with the increased use of the aldosterone-renin ratio (ARR) technique, which can detect milder forms of this condition (usually bilateral adrenal hyperplasia), previously existing ideas about the prevalence of Conn's syndrome have changed. It is currently believed that primary aldosteronism is one of the most common (if not the most common) causes of the development of symptomatic arterial hypertension. Thus, some reports indicate that the proportion of people with Conn's syndrome among the general population of patients with arterial hypertension can reach 3-10%, and among patients with arterial hypertension of the 3rd degree - up to 40%.

Conn's syndrome can be detected in any age group (the most typical age is 30-50 years), more often in women. Classic clinical and laboratory symptoms of primary aldosteronism include:

arterial hypertension;
hypokalemia;
excessive excretion of potassium by the kidneys;
hypernatremia;
metabolic alkalosis.

Let's take a closer look at some of these manifestations.

Arterial hypertension

Arterial hypertension is present in almost all patients with Conn's syndrome.

Mechanisms of development of arterial hypertension

The pressor effects of an excess amount of aldosterone are predominantly associated with the development of sodium retention (this effect is realized through a complex of genomic mechanisms of the action of aldosterone on the sodium channels of tubular epithelial cells) and hypervolemia; a certain role is also assigned to the increase in total peripheral vascular resistance.

Arterial hypertension in persons with Conn's syndrome is usually characterized by high levels of blood pressure, often occurring as resistant, malignant hypertension. Significant left ventricular hypertrophy may be detected, often disproportionate to the severity and duration of arterial hypertension. In its development, an important role is assigned to the intensification of the processes of myocardial fibrosis due to the effect of an excess amount of aldosterone on myocardial fibroblasts. The profibrotic effects of excessive concentrations of aldosterone (realized through its non-genomic mechanisms of action on target cells) can also be quite clearly represented in the vascular wall (with an acceleration of the rate of progression of atherosclerotic lesions) and in the kidneys (with an increase in the processes of interstitial fibrosis and glomerulosclerosis).

Hypokalemia

Hypokalemia is a common but not universal manifestation of Conn's syndrome. The presence and severity of hypokalemia may depend on a number of factors. Thus, it is almost always present and quite clearly expressed in aldosterone-producing adrenal adenoma, but may be absent in bilateral adrenal hyperplasia. Hypokalemia may also be absent or insignificant in severity in the early stages of the formation of Conn's syndrome, as well as with significant restriction of sodium intake from food (for example, during the restriction of table salt when changing the lifestyle recommended for a patient with arterial hypertension).

Experts indicate that potassium levels may increase (and hypokalemia may be eliminated/mask) when:

prolonged and painful venipuncture (mechanisms may include respiratory alkalosis during hyperventilation; release of potassium from muscle depots during repeated repeated clenching of the fist; venous stasis during prolonged compression with a tourniquet);
hemolysis of any nature;
the release of potassium from red blood cells in cases of delayed blood centrifugation and when the blood is kept in cold/ice.

Diagnosis of Conn's syndrome

Stages of diagnosing Conn's syndrome, establishing the type of adrenal lesion and choosing treatment tactics

Diagnosis of Conn's syndrome in people with arterial hypertension consists of several stages:

identification of primary aldosteronism itself, for which they use the study of blood and urine electrolytes, screening tests (primarily, determination of the aldosterone-renin ratio) and verification tests (with a sodium load, captopril, etc.);
establishing the type of adrenal gland lesion - uni- or bilateral (CT and separate study of the aldosterone content in the blood of each of the adrenal veins).

Detection of Conn's syndrome itself

Blood potassium and sodium levels are routine laboratory tests for hypertension. The detection of hypokalemia and hypernatremia already at the initial stage of the diagnostic search suggests the presence of Conn's syndrome. Diagnosis of primary aldosteronism is not very difficult in patients with a detailed picture of Conn's syndrome (primarily with clear hypokalemia not associated with other causes). However, over the past two decades, there has been a frequent possibility of primary aldosteronism among individuals with normokalemia. Taking this into account, it is considered necessary to conduct additional studies to exclude Conn's syndrome in a fairly wide category of patients with arterial hypertension:

at a blood pressure level >160/100 mm Hg. Art. (and, especially, >180/110 mmHg and);
with resistant arterial hypertension;
in persons with hypokalemia (both spontaneous and induced by the use of a diuretic, especially if it persists after taking potassium supplements);
for arterial hypertension in persons with an increase in the size of the adrenal gland according to instrumental studies (adrenal incidentaloma; however, it has been shown that only ~1% of cases of all adrenal incidentalomas are the cause of primary aldosteronism).

Assessing the excretion of electrolytes (potassium and sodium) in urine

This study occupies a fairly important place in diagnosing the causes of hypokalemia. Potassium and sodium levels are tested in urine collected over a 24-hour period from a patient who is not receiving potassium supplements and who has abstained from taking any diuretics for at least 3-4 days. If sodium excretion exceeds 100 mmol/day (this is the level at which the degree of potassium loss can be clearly assessed), a potassium excretion level >30 mmol/day indicates hyperkaliuria. Along with primary aldosteronism, increased potassium excretion may be due to a number of reasons.

Causes of hypokalemia associated with increased excretion of potassium by the kidneys:

Increased potassium excretion by nephron collecting ducts:
1. increased sodium excretion (eg, when taking a diuretic)
2. increased urine osmolarity (glucose, urea, mannitol)
High potassium concentration in the nephron collecting duct:
- with an increase in intravascular blood volume (low plasma renin level):
  - primary aldosteronism
  - Liddle syndrome
  - taking amphotericin B
- with a decrease in intravascular blood volume (high plasma renin level):
  - Bartter syndrome
  - Giletman syndrome
  - hypomagnesemia
  - increased bicarbonate excretion
  - secondary aldosteronism (eg, in nephrotic syndrome)

Once it has been established that the cause of the patient's hypokalemia is an increase in potassium excretion in the urine, it is considered advisable to attempt to correct the hypokalemia. In the absence of contraindications, potassium supplements are prescribed (potassium 40-80 mmol/day), and diuretics are discontinued. It may take from 3 weeks to several months to restore potassium deficiency after prolonged use of diuretics. After this period, potassium supplements are discontinued and blood potassium testing is repeated >3 days after discontinuation. If blood potassium levels return to normal, plasma renin and aldosterone levels should be re-evaluated.

Aldosterone-renin ratio assessment

This test is currently considered as the main screening method in the diagnosis of Conn's syndrome. Normal values for aldosterone levels when drawing blood with the patient in the supine position are 5-12 ng/dl (in SI units - 180-450 pmol/l), plasma renin activity is 1-3 ng/ml/h, aldosterone-renin ratio is up to 30 (in SI units - up to 750). It is important to note that the normal indicator values given are only approximate values; for each specific laboratory (and for specific laboratory kits) they may differ (comparison with indicators in healthy individuals and in individuals with essential arterial hypertension is required). Taking into account such insufficient standardization of the method, one can agree with the opinion that when interpreting the results of assessing the aldosterone-renin ratio, “flexibility of judgment is required from the clinician.” Below are the main recommendations for assessing the aldosterone-renin ratio.

Recommendations for assessing the aldosterone-renin ratio

Patient preparation:

Correction of hypokalemia if present.

Liberalization of table salt intake.

Discontinuing for at least 4 weeks drugs that increase renin levels and decrease aldosterone concentrations, which causes false results:
spironolactone, eplerenone, amiloride, triamterene;

products containing licorice.

Discontinuing for at least 2 weeks other drugs that may affect the test result:
β-AB, central α2-agonists (clonidine), NSAIDs (reduce renin levels);

ACE inhibitors, sartans, direct renin inhibitors, dihydropyridine calcium channel blockers (increase renin levels, reduce aldosterone levels).

If it is impossible to discontinue these medications in patients with stage 3 arterial hypertension, it is permissible to continue taking them with mandatory discontinuation of spironolactone, eplerenone, triamterene and amiloride for at least 6 weeks before the study.

Cancellation of estrogen-containing drugs.

Conditions for blood sampling:

Blood should be collected in the middle of the morning, approximately 2 hours after the patient wakes up and gets out of bed. Immediately before blood collection, the patient should sit for 5-15 minutes.

Blood must be collected carefully, avoiding stasis and hemolysis.

Before centrifugation, the blood sample should be at room temperature (not on ice, which will facilitate the conversion of inactive renin to active); After centrifugation, plasma should be quickly frozen.

Factors to consider when interpreting results

Age (in persons over 65 years of age, there is a greater age-related decrease in renin compared to aldosterone).

Time of day, recent dietary regimen, body position, length of stay in this position.

Medicines taken.

Details of the blood sample collection, including any difficulties encountered.

Blood potassium levels.

Decreased renal function (there may be an increase in aldosterone due to hyperkalemia and a decrease in renin secretion).

The recommendation of Kaplan N.M. seems important from a practical point of view:

“Recommendations for assessing the aldosterone-renin ratio should be followed as closely as possible. Next, the levels of aldosterone and plasma renin activity should be assessed separately, without yet calculating the relationship between them. If plasma renin activity is clearly low (<0,5 нг/мл/ч) и уровень альдостерона плазмы явно повышен (>15 mg/dl), then it is advisable to repeat this measurement again. If low plasma renin activity and high aldosterone levels are confirmed, verification tests should be performed.”

Studying the aldosterone-renin ratio, as well as conducting all further studies, requires discussing their purpose with the patient; A diagnostic search (with a cost of time and money) should be planned taking into account the patient’s readiness and desire to undergo a laparoscopic adrenalectomy in the future if an adrenal adenoma is detected.

Verification test - captopril test

Plasma aldosterone levels are assessed before and 3 hours after oral administration of captopril at a dose of 1 mg/kg body weight of the subject (in healthy people and in patients with essential and renovascular hypertension, aldosterone levels clearly decrease, but in Conn’s syndrome this does not happen). A normal response is considered to be a decrease in aldosterone levels by >30% of baseline values.

Treatment of Conn's syndrome

Long-term treatment using mineralocorticoid receptor antagonists (spironolactone or eplerenone), if they are intolerant - amiloride; Often, combination with a thiazide diuretic can be the treatment approach of choice in patients:

for whom surgical intervention is not possible;
who do not want to carry it out;
in whom arterial hypertension persists after surgery;
the diagnosis of Conn's syndrome, in which it remains not fully confirmed despite the examination.

The use of mineralocorticoid receptor antagonists in individuals with Conn's syndrome provides a fairly clear reduction in blood pressure and allows regression of left ventricular hypertrophy. At the initial stages of treatment, doses of 50-100 mg/day or more of spironolactone or eplerenone may be required; subsequently, lower dosages (25-50 mg/day) are quite effective. The dose of these drugs can be reduced by combining them with thiazide diuretics. For long-term treatment of Conn's syndrome, a selective representative of mineralocorticoid receptor antagonists, eplerenone, with its inherent significantly lower frequency of side effects than spironolactone, can be considered as the drug of choice.

If others are necessary, the initial choice includes calcium channel blockers (eg, amlodipine), since in high doses they have some ability to block aldosterone receptors. To control arterial hypertension, other classes of antihypertensive drugs can be used as components of treatment tactics.

In persons with adrenal carcinoma, drugs from the group of steroidogenesis antagonists can be used.

Primary aldosteronism (Conn's syndrome) is aldosteronism caused by the autonomous production of aldosterone by the adrenal cortex (due to hyperplasia, adenoma or carcinoma). Symptoms and signs include occasional weakness, increased blood pressure, and hypokalemia. Diagnosis includes determination of plasma aldosterone levels and plasma renin activity. Treatment depends on the cause. The tumor is removed if possible; in case of hyperplasia, spironolactone or related drugs can normalize blood pressure and cause the disappearance of other clinical manifestations.

Aldosterone is the most potent mineralocorticoid produced by the adrenal glands. It regulates sodium retention and potassium loss. In the kidneys, aldosterone causes the transfer of sodium from the lumen of the distal tubules into the tubular cells in exchange for potassium and hydrogen. The same effect is observed in the salivary and sweat glands, intestinal mucosal cells, and the exchange between intracellular and extracellular fluid.

Aldosterone secretion is regulated by the renin-angiotensin system and, to a lesser extent, by ACTH. Renin, a proteolytic enzyme, accumulates in the juxtaglomerular cells of the kidneys. A decrease in the volume and velocity of blood flow in the afferent renal arterioles induces the secretion of renin. Renin converts liver angiotensinogen to angiotensin I, which is converted to angiotensin II by angiotensin-converting enzyme. Angiotensin II causes the secretion of aldosterone and, to a lesser extent, the secretion of cortisol and deoxycorticosterone, which also have pressor activity. Sodium and water retention caused by increased secretion of aldosterone increases circulating blood volume and reduces renin secretion.

The syndrome of primary hyperaldosteronism was described by J. 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 that are similar in clinical and biochemical characteristics, but different in pathogenesis, which are based on excessive and independent (or partially dependent) on the renin-angiotensin system production of aldosterone by the adrenal cortex.

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ICD-10 code

E26.0 Primary hyperaldosteronism

What causes primary aldosteronism?

Primary aldosteronism may be caused by an adenoma, usually unilateral, of the glomerular layer of the adrenal cortex or, less commonly, by carcinoma or adrenal hyperplasia. In adrenal hyperplasia, which is more often observed in older men, both adrenal glands are overactive and there is no adenoma. The clinical picture can also be observed in congenital adrenal hyperplasia due to 11-hydroxylase deficiency and in dominantly inherited dexamethasone-suppressed hyperaldosteronism.

Symptoms of primary aldosteronism

Clinical case of primary hyperaldosteronism

Patient M., a 43-year-old woman, was admitted to the endocrinology department of the Kazan Republican Clinical Hospital on January 31, 2012 with complaints of headaches, dizziness when blood pressure rose to a maximum of 200/100 mm Hg. Art. (with a comfortable blood pressure of 150/90 mm Hg), generalized muscle weakness, leg cramps, general weakness, fatigue.

History of the disease. The disease developed gradually. For five years, the patient has noted an increase in blood pressure, for which she was observed by a therapist at her place of residence and received antihypertensive therapy (enalapril). About 3 years ago, I began to experience periodic leg pain, cramps, and muscle weakness that occurred without visible provoking factors and went away on their own within 2-3 weeks. Since 2009, she received inpatient treatment 6 times in the neurological departments of various medical institutions with a diagnosis of Chronic demyelinating polyneuropathy, subacutely developing generalized muscle weakness. One of the episodes involved neck muscle weakness and head drooping.

With the infusion of prednisolone and a polarizing mixture, improvement occurred within several days. According to blood tests, potassium is 2.15 mmol/l.

From 12/26/11 to 01/25/12 she was hospitalized at the Republican Clinical Hospital, where she was admitted with complaints of generalized muscle weakness and periodic leg cramps. An examination was carried out, which revealed: blood test on December 27, 2011: ALT - 29 U/L, AST - 14 U/L, creatinine - 53 µmol/L, potassium 2.8 mmol/L, urea - 4.3 mmol/L, total Protein 60 g/l, bilirubin total. - 14.7 µmol/l, CPK - 44.5, LDH - 194, phosphorus 1.27 mmol/l, Calcium - 2.28 mmol/l.

Urinalysis dated 12/27/11; specific weight - 1002, protein - traces, leukocytes - 9-10 per cell, epit. pl - 20-22 in p/z.

Hormones in the blood: T3sv - 4.8, T4sv - 13.8, TSH - 1.1 μmE/l, cortisol - 362.2 (normal 230-750 nmol/l).

Ultrasound: Left kidneys: 97x46 mm, parenchyma 15 mm, increased echogenicity, FLS - 20 mm. Echogenicity is increased. The cavity is not expanded. Right 98x40 mm. The parenchyma is 16 mm, the echogenicity is increased, the CL is 17 mm. Echogenicity is increased. The cavity is not expanded. A hyperechoic rim is visualized around the pyramids on both sides. Based on the physical examination and laboratory data, further examination was recommended to exclude endocrine pathology of adrenal origin.

Ultrasound of the adrenal glands: in the projection of the left adrenal gland an isoechoic round formation of 23x19 mm is visualized. In the projection of the right adrenal gland, pathological formations are not reliably visualized.

Urine for catecholamines: Diuresis - 2.2 l, adrenaline - 43.1 nmol/day (normal 30-80 nmol/day), norepinephrine - 127.6 nmol/l (normal 20-240 nmol/day). These results excluded the presence of pheochromocytoma as a possible cause of uncontrolled hypertension. Renin from 01/13/12-1.2 µIU/ml (N vertical - 4.4-46.1; horizontal 2.8-39.9), aldosterone 1102 pg/ml (normal: lying 8-172, sitting 30 -355).

RCT dated 01/18/12: RCT signs of a formation in the left adrenal gland (in the medial peduncle of the left adrenal gland an oval-shaped isodense formation with dimensions of 25*22*18 mm, homogeneous, with a density of 47 NU is determined.

Based on the anamnesis, clinical picture, data from laboratory and instrumental research methods, a clinical diagnosis was established: Primary hyperaldosteronism (aldosteroma of the left adrenal gland), first identified in the form of hypokalemic syndrome, neurological symptoms, and sinus tachycardia. Hypokalemic periodic convulsions with generalized muscle weakness. Hypertension, stage 3, stage 1. CHF 0. Sinus tachycardia. Urinary tract infection is in the resolution stage.

Hyperaldosteronism syndrome occurs with clinical manifestations caused by three main symptom complexes: arterial hypertension, which can have either a crisis course (up to 50%) or persistent; impairment of neuromuscular conduction and excitability, which is associated with hypokalemia (in 35-75% of cases); impaired renal tubular function (50-70% of cases).

The patient was recommended surgical treatment to remove a hormone-producing tumor of the adrenal gland - laparoscopic adrenalectomy on the left. An operation was performed - laparoscopic adrenalectomy on the left in the abdominal surgery department of the RCH. The postoperative period was uneventful. On the 4th day after surgery (02/11/12), the blood potassium level was 4.5 mmol/l. Blood pressure 130/80 mm Hg. Art.

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Secondary aldosteronism

Secondary aldosteronism is increased production of aldosterone by the adrenal glands in response to non-pituitary, extra-adrenal stimuli, including renal artery stenosis and hypovolemia. Symptoms are similar to those of primary aldosteronism. Treatment includes correction of the underlying cause.

Secondary aldosteronism is caused by a decrease in renal blood flow, which stimulates the renin-angiotensin mechanism with resulting hypersecretion of aldosterone. Causes of decreased renal blood flow include obstructive diseases of the renal artery (for example, atheroma, stenosis), renal vasoconstriction (with malignant hypertension), diseases accompanied by edema (for example, heart failure, cirrhosis with ascites, nephrotic syndrome). Secretion may be normal in heart failure, but hepatic blood flow and aldosterone metabolism are reduced, so circulating levels of the hormone are high.

Diagnosis of primary aldosteronism

The diagnosis is suspected in patients with hypertension and hypokalemia. Laboratory testing consists of determining plasma aldosterone levels and plasma renin activity (PRA). Tests should be performed when the patient is off medications that affect the renin-angiotensin system (eg, thiazide diuretics, ACE inhibitors, angiotensin antagonists, blockers) for 4-6 weeks. ARP is usually measured in the morning with the patient lying down. Typically, patients with primary aldosteronism have plasma aldosterone levels greater than 15 ng/dL (>0.42 nmol/L) and low levels of ARP, with a ratio of plasma aldosterone (in nanograms/dL) to ARP [in nanograms/(mLh)] greater than 20 .