Excessive formation of aldosterone is accompanied. Hyperaldosteronism is secondary. Errors and unreasonable assignments

Primary hyperaldosteronism should be understood as a clinical syndrome based on increased secretion of aldosterone, which is the result of a tumor or hyperplastic process in the adrenal glands. A characteristic feature of this pathology is primary damage to the adrenal cortex.

Causes

Depending on the cause, it is customary to distinguish the following variants of primary hyperaldosteronism:

• idiopathic;
• ACTH-dependent;
• unilateral hyperplasia of the adrenal cortex;
• syndrome of ectopic aldosterone production.

Aldosteroma is a solitary tumor of the adrenal cortex that secretes aldosterone. This is the most common reason for the primary increase in this hormone in the body. In 80% of cases, the tumor loses contact with and autonomously produces hormones. And only in 20% of cases sensitivity to angiotensin 2 remains.

In rare cases, aldosterone-producing tumors are located in other organs (for example, in the thyroid gland or ovaries in women).

In the idiopathic variant of the disease, a person has bilateral hyperplasia of the adrenal cortex. At the same time, the functional dependence of these cells on angiotensin 2 remains.

The ACTH-dependent variant of the disease is extremely rare and is inherited. It is characterized by a pronounced therapeutic effect after the use of corticosteroids.

Development mechanisms

Normally, the most significant regulators of aldosterone secretion are the renin-angiotensin system and the potassium-sodium pump. In primary hyperaldosteronism, such regulation is impossible or insufficient. A large amount of aldosterone accumulates in the body, which has a negative effect on the organs:

• heart and blood vessels (promotes diastolic overload and dilatation of the left atrium, as well as the development of fibrosis in the heart muscle);
• kidneys (damage to the inner surface of the renal tubules due to a lack of potassium in the blood leads to inflammatory infiltration and sclerotic changes in the interstitium).

The action of this hormone causes an increase in the reabsorption of sodium in the nephron tubules, an increase in its concentration in the blood and, accordingly, a decrease in the potassium content in it (as a result of increased secretion). This leads to an increase in plasma osmotic pressure and an increase in intravascular blood volume (sodium draws water onto itself). Also, a large amount of sodium in the blood sensitizes the vascular wall to the action of catecholamines. The result of such pathophysiological changes is an increase in blood pressure.

Clinical manifestations

Primary hyperaldosteronism can have a different course, the severity of which varies from asymptomatic to obvious with a characteristic clinical picture. The main signs of this disease are:

• arrhythmia (usually);
• frequent;
• muscle weakness;
• burning sensation, tingling sensation in various parts of the body;
• convulsions;
• impaired renal function (thirst, increased amount of daily urine, frequent urination at night).

A relatively constant sign of primary hyperaldosteronism is arterial hypertension. It often has a severe course with resistance to most antihypertensive drugs. Moreover, the higher the concentration of aldosterone in the blood serum, the higher the blood pressure numbers. However, in some patients the course of the disease is mild and can be easily corrected with small doses of medications.

Diagnostics

The diagnosis of “primary hyperaldosteronism” is based on clinical data and the results of laboratory and instrumental examinations. First of all, the following persons are subject to examination:

• with malignant resistant hypertension;
• with early onset of the disease;
• burdened family history;
• a combination of high blood pressure and hypokalemia.

During the examination, in addition to standard general clinical examinations, such patients are prescribed:

• determination of the level of aldosterone and renin in the blood;
• calculation of aldosterone-renin ratio;
• functional tests.

Currently, the most accessible and reliable screening method is the determination of the aldosterone-renin ratio. To reduce the possibility of obtaining false results during testing, certain conditions must be observed:

• 2 weeks before the proposed study, it is recommended to stop taking all medications that can affect the result (aldosterone antagonists, diuretics, β-blockers, α-adrenergic agonists, angiotensin receptor and renin blockers, ACE inhibitors);
• on the eve of blood sampling, correction of electrolyte disorders is carried out;
• During the 3 days before the study, salt intake is not limited.

The interpretation of the results is carried out individually, taking into account all possible external influences and long-term. If after the study a positive result is obtained, then proceed to one of the confirmatory tests:

• with a sodium load (increase salt intake to more than 6 g per day; on the third day, aldosterone excretion is determined, if it is more than 12-14 mg, then the diagnosis is highly likely);
• saline solution (carried out 4 hours after a slow intravenous infusion of 0.9% sodium chloride solution with a volume of about 2 liters; the diagnosis is confirmed when the concentration of aldosterone in the blood is more than 10 ng/dl);
• captopril (blood sampling is carried out an hour after taking captopril; normally the level of aldosterone is reduced by 30%; with primary hyperaldosteronism it remains elevated with a low ratio to renin);
• fludrocortisone (the drug is taken every 6 hours in combination with potassium supplements and sodium chloride infusion; a study is performed on the fourth day; the test is considered positive if the aldosterone level is more than 6 ng/dl).

Instrumental diagnostic methods make it possible to visualize the adrenal glands and identify the pathological process in them. For this purpose:

• ultrasound examination (a safe and informative method that allows you to identify adenomas measuring 1-2 cm);
• computed tomography and (have greater sensitivity and make it possible to examine the organ in more detail);
• scintigraphy (based on the ability of gland tissue to accumulate radiopharmaceuticals);
• (helps to distinguish the tumor process from hyperplasia).

Treatment

The management of patients with primary hyperaldosteronism depends on its cause.

• The main treatment method for adrenal adenoma is its surgical removal along with the affected adrenal gland. At the stage of preparation for surgery, such patients are recommended to have therapeutic nutrition (potassium-rich foods), the water-electrolyte balance is corrected, and drug treatment with aldosterone antagonists or calcium channel blockers is prescribed.
• For idiopathic aldosteronism, lifelong therapy with aldosterone antagonists in minimally effective doses is prescribed. However, resistant hypertension with a high risk of complications is considered an indication for unilateral adrenalectomy.
• The ACTH-dependent variant of the disease responds well to treatment with dexamethasone.

Which doctor should I contact?

If hyperaldosteronism is suspected, you should consult an endocrinologist. Depending on the cause of the pathology, treatment by a surgeon or oncologist, as well as consultation with a neurologist and cardiologist, may be required.

The content of the article

Etiology and pathogenesis of primary hyperaldosteronism

Clinic of primary hyperaldosteronism

Diagnosis and differential diagnosis of primary hyperaldosteronism

Primary hyperaldosteronism should be suspected in patients with diastolic hypertension without edema and low plasma renin levels, which do not increase under the influence of various stimuli, in particular with an increase in dietary sodium. Urinary aldosterone excretion is increased and does not decrease with sodium loading. Characterized by persistent hypokalemia. It should be remembered that hypokalemia in patients with arterial hypertension can develop quickly when treated with diuretics (thiazides, furosemide), therefore the level of potassium in the blood should be determined before starting treatment. If diuretic treatment has already been started, it should be stopped and the patient should be prescribed potassium chloride orally for 1-2 weeks. It should be borne in mind that plasma renin levels are low, in approximately 1/4 of hypertensive patients without hyperaldosteronism. However, in this case, it increases under the influence of various stimuli that reduce plasma volume. If there are laboratory signs of hyperaldosteronism, computed tomography of the adrenal glands is performed to clarify the possible location of the adenoma.

Arterial hypertension, close to malignant, can occur with hypokalemia and hyperaldosteronism. However, unlike primary hyperaldosteronism, the plasma renin level is increased. Primary adrenal hyperplasia with aldosteronism is accompanied, in contrast to adrenal adenoma, by less pronounced hypokalemia, lower aldosterone secretion and a higher level of plasma renin activity. A reliable method for their differential diagnosis is computed tomography of the adrenal glands.
Adrenal cortical adenomas that secrete deoxycorticosterone, in contrast to aldosterone, are characterized by normal plasma aldosterone levels, although plasma renin activity is reduced. Increased mineralocorticoid secretion may be associated with a hereditary defect of certain enzymes. Deficiency of 11-(3- and 17-a-hydroxylases leads to impaired secretion of hydrocortisone with an increase in the release of ACTH and a secondary increase in the production of deoxycorticosterone. With a deficiency of 17-a-hydroxylase, the biosynthesis of androgens and estrogens is disrupted by both the adrenal glands and the gonads. As a result, the biosynthesis of androgens and estrogens is impaired. development of secondary sexual characteristics. In these conditions, arterial hypertension and hypokalemia can be corrected by the administration of glucocorticoids. To clarify the diagnosis, the level of precursors of hydrocortisone biosynthesis is determined both in the blood and urine. In some patients with increased mineralocorticoid function and ACTH levels, the administration of glucocorticoids improves the condition and absence of hydroxylase defect.

Secondary hyperaldosteronism develops in response to activation of the renin-angiotensin system. This condition occurs during normal pregnancy, arterial hypertension with a tendency to a malignant course, especially renovascular hypertension, edema syndrome, liver cirrhosis, nephrotic syndrome, congestive heart failure. In these situations, increased aldosterone secretion is due to arterial hypovolemia and hypotension.

Hyperaldosteronism is a syndrome caused by hypersecretion of aldosterone (mineralocorticoid hormone of the adrenal cortex), accompanied by arterial hypertension and severe electrolyte disturbances. It is customary to distinguish primary and .

Primary hyperaldosteronism is a consequence of primary excess production of aldosterone directly in the glomerular layer of the adrenal cortex.

In secondary hyperaldosteronism, stimulation of the production of excess aldosterone occurs due to the influence of pathological factors located outside the adrenal glands. In addition, there is a group of diseases that are characterized by similar symptoms that are not accompanied by increased levels of aldosterone (syndromes that mimic hyperaldosteronism).

Primary hyperaldosteronism, first described by Conn in 1956, is in most cases the result of an autonomous solitary aldosterone-producing adrenal adenoma ( Conn's syndrome), less commonly - macronodular or micronodular bilateral hyperplasia (idiopathic hyperaldosteronism) or adrenal cancer. In most cases, a unilateral adrenal adenoma is detected, usually small in size (up to 3 cm in diameter), occurring with equal frequency on both sides.

Etiology and pathogenesis

The disease occurs more often in women (2 times more often than in men), usually between the ages of 30 and 50 years. Since the main symptom of hyperaldosteronism is arterial hypertension, it is of fundamental importance that primary hyperaldosteronism is detected in approximately 1% of the general population of patients with arterial hypertension. The cause of the disease is unknown. It should be remembered that hyperaldosteronism, caused by hyperplasia of the zona glomerulosa of the adrenal cortex, is characterized by maintaining sensitivity to stimulation by angiotensin II.

In addition, familial hyperaldosteronism is distinguished, suppressed by glucocorticoids and with preserved sensitivity to pituitary ACTH (familial hyperaldosteronism type I), which develops due to the formation of a defective enzyme during crossing over of the 11-β-hydroxylase and aldosterone synthetase genes located on the 8th chromosome. As a result of this breakdown, both genes become sensitive to ACTH and aldosterone synthesis is initiated not only in the zona glomerulosa, but also in the zona fasciculata of the adrenal cortex, which is accompanied by an increase in the production of aldosterone and 11-deoxycorticortisol metabolites (18-oxocortisol and 18-hydroxycortisol).

The pathogenesis of primary hyperaldosteronism is associated with excessive accumulation of sodium in the blood serum and increased excretion of potassium in the urine. As a result, intracellular hypokalemia and partial replacement of potassium ions in the cell with hydrogen ions from the extracellular fluid are observed, which is accompanied by stimulation of the excretion of chlorine in the urine and causes the development of hypochloremic alkalosis. Persistent hypokalemia leads to damage to the renal tubules, which lose the ability to concentrate urine, and clinically this is accompanied by hyposthenuria and secondary polydipsia. At the same time, hypokalemia leads to a decrease in sensitivity to ADH (antidiuretic hormone - vasopressin), which aggravates polyuria and polydipsia.

At the same time, hypernatremia causes water retention with the development of hypervolemia and arterial hypertension. The important fact is that, despite the retention of sodium and fluid, with primary hyperaldosteronism edema does not develop (the escape phenomenon), which is explained by an increase in cardiac output, arterial hypertension and hypertensive diuresis.

The long-term presence of hyperaldosteronism is accompanied by complications caused by arterial hypertension (myocardial infarction, stroke) and specific myocardial hypertrophy. As mentioned above, constant hypersecretion of aldosterone leads to progressive hypokalemia, which determines the development of hypokalemic myopathy, which leads to the appearance of degenerative changes in the muscles.

Symptoms

Most patients have arterial diastolic hypertension, accompanied by headaches (arterial hypertension syndrome) and not amenable to treatment with antihypertensive drugs in average therapeutic doses; hypertensive crises can be provoked by thiazide or loop diuretics and accompanied by cardiac or cerebral symptoms.

An increase in blood pressure in combination with hypokalemia causes electrocardiographic abnormalities: flattening or inversion of the T wave appears, a decrease in the S-T segment, the Q-T interval lengthens, a pronounced U wave (wave) appears. Cardiac arrhythmias and extrasystole and signs of left ventricular hypertrophy are recorded. In primary hyperaldosteronism, there is no edema, while in secondary hyperaldosteronism, edema syndrome is the pathogenetic basis of the disease.

Hypokalemia, a characteristic symptom of hyperaldosteronism, predetermines the development of muscle weakness (myopathic syndrome), fatigue and decreased performance. Muscle weakness increases sharply with physical activity or suddenly (for no reason). At the same time, the severity of weakness at the time of the attack limits the possibilities of movement or minimal physical work. Paresthesia and local convulsions are possible.

As a result of impaired ability of the kidneys to concentrate urine, polyuria with hyposthenuria develops, often accompanied by secondary polydipsia. A characteristic symptom is with a predominance of night diuresis over daytime diuresis.

Depending on the degree of manifestation of the above symptoms, various options for the course of the disease are possible before diagnosis is made:

• crisis variant - accompanied by hypertensive crises with pronounced neuromuscular symptoms (adynamia, paresthesia, convulsions);
• a constant form of arterial hypertension with constant muscle weakness, the degree of which is inferior to the crisis form;
• option without significant arterial hypertension with a predominance of transient neuromuscular disorders at the time of crisis.

Diagnostics

Diagnosis of primary hyperaldosteronism includes two mandatory stages: proof of hyperaldosteronism and diagnosis of the nosological form of the disease.

The following indicators serve as evidence of primary hyperaldosteronism:

1. serum potassium level
2. renin level is reduced (plasma renin activity);
3. blood aldosterone levels are increased;
4. daily excretion of aldosterone metabolites in urine (aldosterone-18-glucoronite) is increased.

The listed studies can be used when examining patients with arterial hypotension as screening techniques to identify the target group and conduct a special examination. In difficult cases, pharmacodynamic tests can be used:

1. test with an isotonic sodium chloride solution: the patient in a horizontal position is injected with 2 liters of 0.9% sodium chloride solution slowly (for at least 4 hours) and after the end of the test, the level of aldosterone is determined, which does not decrease with primary hyperaldosteronism;
2. test with spironolactone: for 3 days the patient receives 400 mg/day of spironolactone orally. An increase in potassium levels of more than 1 mmol/l confirms hyperaldosteronism;
3. test with furosemide: the patient is prescribed 0.08 g of furosemide orally. After 3 hours, there is a decrease in plasma renin activity and an increase in aldosterone levels with hyperaldosteronism;
4. test with 9α-fluorocortisol: for 3 days the patient receives 400 mcg/day orally of 9α-fluorocortisol (Cortinef) and the level of aldosterone is examined before and after the test. With bilateral hyperplasia of the glomerular layer of the adrenal cortex, a decrease in aldosterone levels is observed, and with aldosteroma, there is no decrease in aldosterone levels:
5. dexamethasone test: used to differentiate glucocorticoid-suppressed hyperaldosteronism, administration of 0.5 - 1.0 mg 2 times a day for a week leads to a decrease in the manifestations of the disease;
6. orthostatic test (allows you to differentiate primary hyperaldosteronism from unilateral aldosteroma and bilateral adrenal hyperplasia): after 3-4 hours of the patient staying in an upright position (standing, walking), the level of aldosterone and plasma renin activity are assessed. With autonomous aldosterome, plasma renin activity does not change (it remains low), and aldosterone levels decrease or change slightly (normally, plasma renin activity and aldosterone increase by 30% above basal values).

Indirect signs of hyperaldosteronism:

• hypernatremia;
• hyperkaliuria, hypokalemia;
• polyuria, iso- and hyposthenuria;
• metabolic alkalosis and increased bicarbonate levels in the blood serum (the result of loss of hydrogen ions in the urine and impaired bicarbonate reabsorption), as well as alkaline urine;
• with severe hypokalemia, the level of magnesium in the blood serum also decreases.

Criteria for the diagnosis of primary hyperaldosteronism include:

• diastolic hypertension in the absence of edema;
• reduced secretion of renin (low plasma renin activity) without a tendency to adequately increase under conditions of volume reduction (orthostasis, sodium restriction);
• hypersecretion of aldosterone, which is not sufficiently reduced under conditions of increased volume (salt load).

As mentioned above, the cause of primary hyperaldosteronism can be established by performing certain functional tests (orthostatic test, test with 9α-fluorocortisol). In addition, in familial hyperaldosteronism, suppressed by glucocorticoids and with preserved sensitivity to pituitary ACTH (familial hyperaldosteronism type I) and bilateral adrenal hyperplasia, there is an increase in the levels of the precursor in aldosterone synthesis - 18-hydroxycorticosterone > 50 - 100 ng/dl and increased excretion from urine 18-hydroxycortisol > 60 mg/day and 18-hydroxycortisol > 15 mg/day. These changes are most pronounced in familial hyperaldosteronism, suppressed by glucocorticosteroids.

After verification of hyperaldosteronism, additional examination is carried out aimed at clarifying the nosological form of primary hyperaldosteronism and topical diagnosis. The first step is to visualize the adrenal gland area. The preferred methods are CG, MRI and PET. Detected bilateral symmetrical pathology or unilateral space-occupying formation in the adrenal gland allows us to establish the cause of primary hyperaldosteronism. It should be remembered that imaging of the adrenal glands is only relevant in relation to the identified metabolic abnormalities.

In recent years, the list of possible evidence of primary hyperaldosteronism has been supplemented by the possibility of isolated blood sampling from the inferior hollow foam and adrenal veins with the study of aldosterone levels in samples. An increase in aldosterone levels by 3 times is considered characteristic of aldosteroma, less than 3 times is a sign of bilateral hyperplasia of the zona glomerulosa of the adrenal cortex.

Differential diagnosis is carried out with all conditions accompanying hyperaldosteronism. The principles of differential diagnosis are based on examination and exclusion of various forms of hyperaldosteronism.

Syndromes that mimic primary hyperaldosteronism include a number of diseases characterized by arterial hypertension and myopathic syndrome caused by hypochloremic alkalosis and low renin levels (pseudohyperaldosteronism), are rare and are caused by various enzymopathies. In this case, there is a deficiency of enzymes involved in the synthesis of glucocorticosteroids (11-β-hydroxylase, 11-β-hydroxysteroid dehydrogenase, 5α-reductase, P450c11, P450c17).

In most cases, syndromes that mimic primary hyperaldosteronism appear in childhood and are characterized by persistent arterial hypertension, as well as other laboratory signs of hyperaldosteronism.

Treatment

Treatment of primary hyperaldosteronism is carried out taking into account the cause that caused it.

When aldosteroma is detected, the only treatment option is surgical treatment (adrenalectomy). Preoperative preparation is carried out for 4 - 8 weeks with spironolactone at a dose of 200 - 400 mg / day. With unilateral adrenalectomy, glucocorticosteroid replacement therapy is not indicated in the vast majority of cases. After removal of the adenoma, cure of hypertension is observed in 55-60% of patients. However, hypertension may persist in approximately 30% of operated patients.

If bilateral adrenal hyperplasia is suspected, surgical intervention is indicated only in cases where severe hypokalemia accompanied by clinical symptoms cannot be controlled medically with spironolactone. Bilateral adrenalectomy, as a rule, does not improve the course of hypertension associated with idiopathic hyperplasia of the zona glomerulosa of the adrenal glands, therefore, in such cases, complex antihypertensive therapy with the obligatory use of maximum doses of spironolactone is recommended.

For familial glucocorticoid-suppressed hyperaldosteronism, suppressive therapy with dexamethasone is used at a dose of 0.5-1.0 mg/day.

Hyperaldosteronism is a fairly frequently diagnosed pathological condition that develops against the background of increased secretion of an adrenal hormone such as aldosterone. The pathology most often occurs in adults, but can also affect children.

Provoking factors will differ depending on the form of the disease, ranging from burdened heredity and ending with the course of ailments of an endocrinological or other nature.

Clinical signs for the primary and secondary forms of the disease will be different. The basis of the symptoms are impaired functioning of the heart, muscle weakness, seizures and development.

Only an endocrinologist can make a correct diagnosis and differentiate between the different types of disease, based on data from a wide range of instrumental and laboratory examinations.

Treatment tactics can be either conservative or surgical, which is directly dictated by the type of such pathology. In any case, the lack of therapy is fraught with life-threatening complications.

Etiology

Hyperaldosteronism is a complex of syndromes with different mechanisms of occurrence, but similar symptoms, that develop due to increased secretion of aldosterone.

Since there is primary and secondary hyperaldosteronism, it is natural that the predisposing factors will be somewhat different.

The first type of disease in extremely rare cases occurs against the background of a genetic predisposition. The familial form can be inherited in an autosomal dominant manner - this means that to diagnose such a disease in a child, it is enough for him to inherit the mutant gene from one of the parents.

The defective segment is the enzyme 18-hydroxylase, which for unknown reasons goes beyond the control of the renin-angiotensin system and is corrected by glucocorticoids.

Rare provocateurs of primary hyperaldosteronism include cancer of the adrenal glands.

However, in the vast majority of situations, this variant of the course of the disease is caused by the formation of aldosteroma - this is a neoplasm, which, in fact, is an aldosterone-producing adenoma of the adrenal cortex. Such a tumor is diagnosed in approximately 70% of cases of the primary form of pathology.

Secondary hyperaldosteronism is characterized by the occurrence of another disease in the human body, which means that dysfunction of the endocrine system in such situations acts as a complication.

The following pathological conditions can lead to the development of a secondary type of disease:

• Barter syndrome;
• dysplasia and stenosis of the arteries in the kidneys;
• formation of reninoma in the kidneys;

In addition, the following can lead to secondary hyperaldosteronism:

• sodium deficiency, which is very often provoked by strict diets or excessive diarrhea;
• a decrease in the volume of circulating blood - this is often observed against the background of heavy blood loss and dehydration;
• excess potassium;
• uncontrolled use of certain medications, in particular diuretics or laxatives.

It is worth noting that the main risk group is female representatives in the age category from 30 to 50 years. However, this does not mean that the disease does not occur in other categories of patients.

Classification

Endocrinologists distinguish the following main types of such pathology:

• primary hyperaldosteronism- considered one of the most common variations of the disease;
• secondary hyperaldosteronism- is a complication of diseases that negatively affect the heart, liver and kidneys;
• pseudohyperaldosteronism- is a consequence of impaired perception of aldosterone by the distal renal tubules.

At the same time, primary hyperaldosteronism has its own classification, which includes:

• Conn's syndrome;
• idiopathic hyperaldosteronism - develops only against the background of diffuse nodular hyperplasia of the adrenal cortex, which is bilateral. Diagnosed in approximately every third patient who seeks qualified help when symptoms arise;
• unilateral or bilateral adrenal hyperplasia;
• glucocorticoid-dependent hyperaldosteronism;
• aldosterone-producing carcinoma - in total, no more than 100 patients with a similar diagnosis have been registered;
• pseudohyperaldosteronism - is a consequence of impaired perception of aldosterone by the distal renal tubules;
• congenital insufficiency of the adrenal cortex or caused by drug overdose.

As a separate form, it is worth highlighting extra-adrenal hyperaldosteronism - it is the most rare. Among the provoking factors, the main place is occupied by diseases of the endocrine system, for example, the ovaries and thyroid gland, as well as the gastrointestinal tract, in particular the intestines.

Symptoms

As mentioned above, the symptomatic picture will differ depending on the type of disease. Thus, with primary hyperaldosteronism, the expression of the following symptoms is observed:

• increased blood tone - a symptom observed in absolutely all patients, but recently clinicians have noted an asymptomatic course of the disease. Blood pressure is constantly elevated, and this can lead to hypertrophy of the left ventricle of the heart. Against the background of this manifestation, half of the patients experience vascular damage to the fundus, and 20% have a decrease in visual acuity;
• muscle weakness - similar to the previous sign, typical for 100% of patients. In turn, it becomes the cause of decreased performance, the development of a pseudoparalytic state and convulsions;
• change in the shade of urine - it becomes cloudy due to the presence of a large amount of protein in it. Composes the clinical picture for 85% of people;
• an increase in the daily volume of urine excreted - occurs in 72% of patients;
• constant thirst;
• persistent headaches;
• development ;
• causeless anxiety.

It is worth considering that the above symptoms refer to the most common form of primary hyperaldosteronism - Conn's syndrome.

Symptoms of secondary type hyperaldosteronism are presented:

• an increase in blood pressure, especially diastolic, which over time leads to the appearance of chronic renal failure, kidney dysfunction and damage to the walls of blood vessels;
• neuroretinopathy leading to optic nerve atrophy and complete blindness;
• hemorrhages in the fundus of the eye;
• severe swelling.

Some patients do not show signs of arterial hypertension, and in rare cases, a low-symptomatic course of such a pathology is observed.

In children, hyperaldosteronism often manifests itself before the age of 5 and is expressed in:

• bright manifestation;
• increasing arterial hypertension;
• retardation in physical development;
• psycho-emotional disorders.

Diagnostics

The implementation of a whole range of diagnostic measures is aimed not only at establishing the correct diagnosis, but also at differentiating various forms of the disease in women and men.

First of all, the endocrinologist must:

• get acquainted with the medical history of not only the patient, but also his close relatives - to detect pathologies that may cause secondary hyperaldosteronism or confirm the hereditary nature of the disease;
• collect and study a person’s life history;
• carefully examine the patient - a physical examination is aimed at assessing the condition of the skin and measuring blood pressure. This should also include an ophthalmological examination of the fundus;
• interview the patient in detail - to draw up a complete symptomatic picture of the course of hyperaldosteronism, which can actually indicate the type of its course.

Laboratory diagnosis of hyperaldosteronism involves:

• biochemical blood test;
• general clinical study of urine;
• measuring the daily volume of urine excreted;
• PCR tests - to diagnose the familial form of the disease;
• tests with spironolactone and hypothiazide load;
• "march" test;
• serological tests.

The following instrumental examinations are of greatest value:

In addition to the basic diagnosis, the patient should be examined by an ophthalmologist, nephrologist and cardiologist.

Treatment

The tactics of treating the disease are dictated by its type, however, there are several treatment methods inherent in all forms of hyperaldosteronism. These include:

• maintaining a gentle diet aimed at reducing the consumption of table salt and enriching the menu with foods enriched with potassium;
• taking potassium-sparing diuretics;
• injection of potassium preparations.

Treatment of hyperaldosteronism caused by the formation of aldosteroma or cancer of the adrenal glands is only surgical. The operation involves excision of the affected segment, which first requires restoration of the water and electrolyte balance.

Bilateral hypoplasia of the adrenal cortex is eliminated in a conservative way. Through the use of ACE inhibitors and calcium channel antagonists.

The hyperplastic form of hyperaldosteronism is treated with complete bilateral adrenalectomy.

Patients with secondary hyperaldosteronism are advised to eliminate the underlying disease and mandatory intake of glucocorticoids.

Possible complications

Due to the rapid progression of clinical signs, hyperaldosteronism quite often leads to the following complications:

• chronic renal failure;
• complete loss of vision;
• nephrogenic diabetes insipidus;
• hearts;
• cardiac ischemia;
• destruction of the walls of blood vessels;
• paresthesia;
• malignant arterial hypertension.

Prevention and prognosis

To ensure that a man, woman and child does not have problems with the formation of such a disease, it is necessary to adhere to the following general clinical recommendations:

• maintaining a healthy lifestyle;
• proper and nutritious nutrition;
• consultation with geneticists - this is necessary for couples who decide to have children to find out the likelihood of giving birth to a baby with hyperaldosteronism;
• constant clinical observation - indicated for patients with hypertension;
• taking only those medications prescribed by the clinician - with strict adherence to the daily dosage and duration of treatment;
• undergoing a full preventive examination in a medical institution - for early detection of ailments that can lead to the appearance of secondary hyperaldosteronism.

As for the prognosis of the disease, it is dictated by the severity of the underlying disease and the degree of damage to internal organs, as well as timely diagnosis and adequate therapy.

Radical surgical intervention and adequate drug treatment guarantee a complete recovery. The outcome of adrenal cancer is often unfavorable.

Is everything in the article correct from a medical point of view?

Answer only if you have proven medical knowledge

Primary hyperaldosteronism (PHA, Conn's syndrome) is a collective concept that includes pathological conditions that are similar in clinical and biochemical characteristics and differ in pathogenesis. The basis of this syndrome is the excessive production of the hormone aldosterone, which is produced by the adrenal cortex, autonomous or partially autonomous from the renin-angiotensin system.

General information

For the first time, a benign unilateral adenoma of the adrenal cortex, which was accompanied by high arterial hypertension, neuromuscular and renal disorders, manifested against the background of hyperaldosteronuria, was described in 1955 by the American Jerome Conn. He noted that removal of the adenoma led to the recovery of the 34-year-old patient, and called the identified disease primary aldosteronism.

In Russia, primary aldosteronism was described in 1963 by S.M. Gerasimov, and in 1966 by P.P. Gerasimenko.

In 1955, Foley, studying the causes of intracranial hypertension, suggested that the disturbance of water and electrolyte balance observed with this hypertension is caused by hormonal disorders. The connection between hypertension and hormonal changes was confirmed by studies by R. D. Gordone (1995), M. Greer (1964) and M. B. A. Oldstone (1966), but the cause-and-effect relationship between these disorders was not finally identified.

Research conducted in 1979 by R. M. Carey et al. on the regulation of aldosterone by the renin-angiotensin-aldosterone system and the role of dopaminergic mechanisms in this regulation showed that aldosterone production is controlled by these mechanisms.

Thanks to experimental studies on rats conducted in 1985 by K. Atarachi et al., it was found that atrial natriuretic peptide inhibits the secretion of aldosterone by the adrenal glands and does not affect the levels of renin, angiotensin II, ACTH and potassium.

Research data obtained in 1987 -2006 suggest that hypothalamic structures influence hyperplasia of the zona glomerulosa of the adrenal cortex and hypersecretion of aldosterone.

In 2006, a number of authors (V. Perrauclin and others) revealed that vasopressin-containing cells are present in aldosterone-producing tumors. Researchers suggest the presence of V1a receptors in these tumors, which control the secretion of aldosterone.

Primary hyperaldosteronism is the cause of hypertension in 0.5–4% of cases of the total number of patients with hypertension, and among hypertension of endocrine origin, Conn’s syndrome is detected in 1–8% of patients.

The incidence of primary hyperaldosteronism among patients with arterial hypertension is 1-2%.

1% of incidentally detected adrenal tumors are aldosteromas.

Aldosteromas are 2 times less common in men than in women, and are extremely rarely observed in children.

Bilateral idiopathic adrenal hyperplasia as the cause of primary hyperaldosteronism is detected in most cases in men. Moreover, the development of this form of primary hyperaldosteronism is usually observed at a later age than aldosteromas.

Primary hyperaldosteronism is usually observed in adults.

The ratio of women to men aged 30-40 years is 3:1, and in girls and boys the incidence of the disease is the same.

Forms

The most common is the classification of primary hyperaldosteronism according to nosological principle. In accordance with this classification, the following are distinguished:

• Aldosterone-producing adenoma (APA), which was described by Jerome Conn and called Conn's syndrome. It is detected in 30–50% of cases of the total disease.
• Idiopathic hyperaldosteronism (IHA) or bilateral small- or large-nodular hyperplasia of the zona glomerulosa, which is observed in 45 - 65% of patients.
• Primary unilateral adrenal hyperplasia, which occurs in approximately 2% of patients.
• Familial hyperaldosteronism type I (glucocorticoid-suppressed), which occurs in less than 2% of cases.
• Familial hyperaldosteronism type II (glucocorticoid-unsuppressible), which accounts for less than 2% of all cases of the disease.
• Aldosterone-producing carcinoma, detected in approximately 1% of patients.
• Aldosteronectopic syndrome occurs with aldosterone-producing tumors located in the thyroid gland, ovary or intestines.

Reasons for development

The cause of primary hyperaldosteronism is excessive secretion of aldosterone, the main mineralocorticosteroid hormone of the human adrenal cortex. This hormone promotes the transition of fluid and sodium from the vascular bed to the tissues by enhancing the tubular reabsorption of sodium cations, chlorine anions and water and the tubular excretion of potassium cations. As a result of the action of mineralocorticoids, circulating blood volume increases and systemic blood pressure increases.

1. Conn's syndrome develops as a result of the formation of an aldosteroma, a benign adenoma that secretes aldosterone, in the adrenal glands. Multiple (solitary) aldosteromas are detected in 80 - 85% of patients. In most cases, aldosteroma is unilateral, and only in 6–15% of cases do bilateral adenomas form. The size of the tumor in 80% of cases does not exceed 3 mm and weighs about 6–8 grams. If the aldosteroma increases in volume, there is an increase in its malignancy (95% of tumors larger than 30 mm are malignant, and 87% of tumors of smaller size are benign). In most cases, adrenal aldosteroma consists primarily of cells of the zona glomerulosa, but in 20% of patients the tumor consists primarily of cells of the zona fasciculata. Damage to the left adrenal gland is observed 2–3 times more often, since anatomical conditions predispose to this (compression of the vein in the “aorto-mesenteric forceps”).
2. Idiopathic hyperaldosteronism is presumably the last stage in the development of low-renin arterial hypertension. The development of this form of the disease is caused by bilateral small- or large-nodular hyperplasia of the adrenal cortex. The zona glomerulosa of hyperplastic adrenal glands produces excess amounts of aldosterone, as a result of which the patient develops arterial hypertension and hypokalemia, and plasma renin levels decrease. The fundamental difference between this form of the disease is the preservation of sensitivity to the stimulating influence of angiotensin II in the hyperplastic zona glomerulosa. The formation of aldosterone in this form of Conn's syndrome is controlled by adrenocorticotropic hormone.
3. In rare cases, the cause of primary hyperaldosteronism is adrenal carcinoma, which is formed during the growth of an adenoma and is accompanied by increased excretion of 17-ketosteroids in the urine.
4. Sometimes the cause of the disease is genetically determined glucocorticoid-sensitive aldosteronism, which is characterized by increased sensitivity of the zona glomerulosa of the adrenal cortex to adrenocorticotropic hormone and suppression of hypersecretion of aldosterone by glucocorticoids (dexamethasone). The disease is caused by an unequal exchange of sections of homologous chromatids during meiosis of the 11b-hydroxylase and aldosterone synthetase genes located on chromosome 8, resulting in the formation of a defective enzyme.
5. In some cases, aldosterone levels increase due to the secretion of this hormone by extra-adrenal tumors.

Pathogenesis

Primary hyperaldosteronism develops as a result of excessive secretion of aldosterone and its specific effect on the transport of sodium and potassium ions.

Aldosterone controls the cation exchange mechanism through communication with receptors located in the kidney tubules, intestinal mucosa, sweat and salivary glands.

The level of potassium secretion and excretion depends on the amount of sodium reabsorbed.

With hypersecretion of aldosterone, sodium reabsorption is enhanced, resulting in induced potassium loss. In this case, the pathophysiological effect of potassium loss overrides the effect of reabsorbed sodium. Thus, a complex of metabolic disorders characteristic of primary hyperaldosteronism is formed.

A decrease in potassium levels and depletion of its intracellular reserves causes universal hypokalemia.

Potassium in cells is replaced by sodium and hydrogen, which, in combination with the excretion of chlorine, provoke the development of:

• intracellular acidosis, in which there is a decrease in pH less than 7.35;
• hypokalemic and hypochloremic extracellular alkalosis, in which there is an increase in pH above 7.45.

With potassium deficiency in organs and tissues (distal renal tubules, smooth and striated muscles, central and peripheral nervous system), functional and structural disorders occur. Neuromuscular irritability is aggravated by hypomagnesemia, which develops with a decrease in magnesium reabsorption.

In addition, hypokalemia:

• suppresses insulin secretion, so patients have reduced tolerance to carbohydrates;
• affects the epithelium of the renal tubules, so the renal tubules are exposed to antidiuretic hormone.

As a result of these changes in the functioning of the body, a number of renal functions are disrupted - the concentrating ability of the kidneys decreases, hypervolemia develops, and the production of renin and angiotensin II is suppressed. These factors help to increase the sensitivity of the vascular wall to a variety of internal pressor factors, which provokes the development of arterial hypertension. In addition, interstitial inflammation with an immune component and interstitial sclerosis develop, so a long course of primary hyperaldosteronism contributes to the development of secondary nephrogenic arterial hypertension.

The level of glucocorticoids in primary hyperaldosteronism caused by adenoma or hyperplasia of the adrenal cortex in most cases does not exceed the norm.

In carcinoma, the clinical picture is complemented by impaired secretion of certain hormones (gluco- or mineralocorticoids, androgens).

The pathogenesis of the familial form of primary hyperaldosteronism is also associated with hypersecretion of aldosterone, but these disorders are caused by mutations in the genes responsible for encoding adrenocorticotropic hormone (ACTH) and aldosterone synthetase.

Normally, the expression of the 11b-hydroxylase gene occurs under the influence of adrenocorticotropic hormone, and the aldosterone synthetase gene occurs under the influence of potassium ions and angiotensin-P. When mutation (unequal exchange during the process of meiosis of sections of homologous chromatids of the 11b-hydroxylase and aldosterone synthetase genes, localized on chromosome 8), a defective gene is formed, including the 5ACTH-sensitive regulatory region of the 11b-hydroxylase gene and a 3′-nucleotide sequence that encodes the synthesis of the enzyme aldosterone synthetase . As a result, the zona fasciculata of the adrenal cortex, whose activity is regulated by ACTH, begins to produce aldosterone, as well as 18-oxocortisol, 18-hydroxycortisol from 11-deoxycortisol in large quantities.

Symptoms

Conn's syndrome is accompanied by cardiovascular, renal and neuromuscular syndromes.

Cardiovascular syndrome includes arterial hypertension, which may be accompanied by headaches, dizziness, cardialgia and heart rhythm disturbances. Arterial hypertension (AH) can be malignant, resistant to traditional antihypertensive therapy, or correctable even with small doses of antihypertensive drugs. In half of the cases, hypertension is of a crisis nature.

The daily profile of hypertension demonstrates an insufficient decrease in blood pressure at night, and if the circadian rhythm of aldosterone secretion is disturbed at this time, an excessive increase in blood pressure is observed.

With idiopathic hyperaldosteronism, the degree of nocturnal decrease in blood pressure is close to normal.

Sodium and water retention in patients with primary hyperaldosteronism also causes hypertensive angiopathy, angiosclerosis and retinopathy in 50% of cases.

Neuromuscular and renal syndromes manifest themselves depending on the severity of hypokalemia. Neuromuscular syndrome is characterized by:

• attacks of muscle weakness (observed in 73% of patients);
• convulsions and paralysis affecting mainly the legs, neck and fingers, which last from several hours to a day and are characterized by a sudden onset and end.

Paresthesia is observed in 24% of patients.

As a result of hypokalemia and intracellular acidosis in the cells of the renal tubules, dystrophic changes occur in the tubular apparatus of the kidneys, which provoke the development of kaliopenic nephropathy. Renal syndrome is characterized by:

• decreased concentration function of the kidneys;
• polyuria (increased daily diuresis, detected in 72% of patients);
• (increased urination at night);
• (extreme thirst, which is observed in 46% of patients).

In severe cases, nephrogenic diabetes insipidus may develop.

Primary hyperaldosteronism can be monosymptomatic - in addition to elevated blood pressure, patients may not show any other symptoms, and potassium levels may not differ from normal.

With aldosterone-producing adenoma, myoplegic episodes and muscle weakness are observed more often than with idiopathic hyperaldosteronism.

Hypertension in the familial form of hyperaldosteronism manifests itself at an early age.

Diagnostics

Diagnosis primarily involves identifying Conn's syndrome among individuals with arterial hypertension. The selection criteria are:

• The presence of clinical symptoms of the disease.
• Blood plasma test data to determine potassium levels. The presence of persistent hypokalemia, in which the potassium content in plasma does not exceed 3.0 mmol/l. It is detected in the vast majority of cases with primary aldosteronism, but normokalemia is observed in 10% of cases.
• ECG data that can detect metabolic changes. With hypokalemia, a decrease in the ST segment, inversion of the T wave is observed, the QT interval is prolonged, a pathological U wave and conduction disturbances are detected. Changes detected on the ECG do not always correspond to the true concentration of potassium in the plasma.
• The presence of urinary syndrome (a complex of various disorders of urination and changes in the composition and structure of urine).

To identify the connection between hyperaldosteronemia and electrolyte disturbances, a test with veroshpiron is used (veroshpiron is prescribed 4 times a day, 100 mg for 3 days, with at least 6 g of salt included in the daily diet). A potassium level increased by more than 1 mmol/l on the 4th day is a sign of aldosterone overproduction.

To differentiate various forms of hyperaldosteronism and determine their etiology, the following is carried out:

• a thorough study of the functional state of the RAAS system (renin-angiotensin-aldosterone system);
• CT and MRI, which allow us to analyze the structural state of the adrenal glands;
• hormonal examination to determine the level of activity of the identified changes.

When studying the RAAS system, stress tests are carried out aimed at stimulating or suppressing the activity of the RAAS system. Since the secretion of aldosterone and the level of plasma renin activity are influenced by a number of exogenous factors, 10-14 days before the study, drug therapy that could affect the result of the study is excluded.

Low plasma renin activity is stimulated by walking for an hour, a hyposodium diet, and diuretics. With unstimulated plasma renin activity in patients, aldosteroma or idiopathic adrenal hyperplasia is assumed, since with secondary aldosteronism this activity is subject to significant stimulation.

Tests to suppress excess aldosterone secretion include a high-sodium diet, deoxycorticosterone acetate, and intravenous isotonic saline. When performing these tests, aldosterone secretion does not change in the presence of aldosterone, which autonomously produces aldosterone, and with adrenal hyperplasia, suppression of aldosterone secretion is observed.

Selective adrenal venography is also used as the most informative x-ray method.

To identify the familial form of hyperaldosteronism, genomic typing is used using the PCR method. In familial hyperaldosteronism type I (glucocorticoid-suppressed), trial treatment with dexamethasone (prednisolone) to eliminate signs of the disease is of diagnostic value.

Treatment

Treatment of primary hyperaldosteronism depends on the form of the disease. Non-drug treatment includes limiting the use of table salt (less than 2 grams per day) and a gentle regimen.

Treatment of aldosteroma and aldosterone-producing carcinoma involves the use of a radical method - subtotal or total resection of the affected adrenal gland.

For 1-3 months before surgery, patients are prescribed:

• Aldosterone antagonists - the diuretic spironolactone (initial dose is 50 mg 2 times a day, and subsequently it is increased to an average dose of 200-400 mg/day 3-4 times a day).
• Dihydropyridine calcium channel blockers, which help lower blood pressure until potassium levels normalize.
• Saluretics, which are prescribed after normalization of potassium levels to lower blood pressure (hydrochlorothiazide, furosemide, amiloride). It is also possible to prescribe ACE inhibitors, angiotensin II receptor antagonists, and calcium antagonists.

For idiopathic hyperaldosteronism, conservative therapy with spironolactone is justified, which, when erectile dysfunction occurs in men, is replaced with amiloride or triamterene (these drugs help normalize potassium levels, but do not reduce blood pressure, so it is necessary to add saluretics, etc.).

For glucocorticoid-suppressed hyperaldosteronism, dexamethasone is prescribed (the dose is selected individually).

In the event of a hypertensive crisis, Conn's syndrome requires emergency care in accordance with the general rules for its treatment.

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