Hyperaldosteronism: definition, etiology, classification, clinical signs and syndromes, diagnosis, treatment. Secondary hyperaldosteronism: symptoms, diagnosis, treatment What symptom is characteristic of primary hyperaldosteronism

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.

Content

According to statistics, primary (idiopathic) hyperaldosteronism (IHA) occurs 3 times more often in women than in men. The disease manifests itself over the age of 30 years. Of all types of hyperaldosteronism, primary is considered predominant. It is detected in 1% of patients with arterial hypertension.

What is idiopathic hyperaldosteronism

The term “hyperaldosteronism” refers to several syndromes in which too much of the adrenal hormone (aldosterone) is released. Depending on the cause of occurrence, there are 2 forms of the disease:

• Primary, or idiopathic. It develops due to increased activity of the zona glomerulosa of the adrenal cortex, which provokes excess production of aldosterone.
• Secondary. Associated with disturbances in the functioning of other internal organs, which also lead to excessive secretion of aldosterone.

Reasons for development

The main reason for the development of idiopathic type hyperaldosteronism is an excess of mineralocorticosteroid hormone of the adrenal cortex. It is responsible for the transfer of sodium and fluid from blood vessels to body tissues.

With elevated aldosterone levels, circulating blood volume increases, which leads to increased blood pressure. Idiopathic aldosteronism develops for the following reasons:

Symptoms

Primary hyperaldosteronism is asymptomatic. In such cases, except for increased blood pressure, no other abnormalities are detected in patients. Sometimes the disease occurs without any symptoms at all. The clinical picture is characterized by a triad of syndromes:

• cardiovascular;
• neuromuscular;
• renal.

Cardiovascular syndrome

One of the constant symptoms of IHA is arterial hypertension. Against the background of hypokalemia, it causes electrocardiographic abnormalities. Hypertension can also be malignant, i.e. do not respond to traditional treatment. In half of the patients, arterial hypertension occurs in the form of crises. Other symptoms of cardiovascular syndrome:

• headache;
• dizziness;
• heart rhythm disturbances;
• the appearance of spots before the eyes;
• cardialgia - aching pain in the heart area.

Neuromuscular

Due to hypokalemia, patients with hyperaldosteronism develop neuromuscular conduction and excitability disorders. The following symptoms indicate them:

• paresthesia;
• convulsions and paralysis affecting the neck, legs, fingers (differing in sudden onset and end);
• muscle weakness (characteristic of 73% of patients);
• bradycardia;
• severe weakness, which sharply increases suddenly or with physical activity;
• tetany is an involuntary painful muscle contraction.

Renal

Excess aldosterone leads to the development of electrolyte disturbances, which negatively affects the function of the renal tubules. Dystrophic changes in the tubular apparatus of the kidneys cause kaliopenic nephropathy. The following symptoms indicate its development:

• nocturia – predominance of nocturnal diuresis;
• polyuria – an increase in the daily volume of urine;
• polydipsia is severe thirst, which is observed in 46% of patients.

Diagnostic methods

During the diagnostic process, the presence of idiopathic aldosteronism is identified and its form is determined. To do this, the following procedures are carried out:

Treatment

The choice of a specific treatment regimen depends on the cause of the development of hyperaldosteronism and the nature of its course. Main methods of treating the disease:

• taking potassium-sparing diuretics;
• following a diet with limited salt and consumption of foods containing potassium;
• injections of potassium preparations;
• surgery to excise the affected segment of the adrenal glands;
• performing bilateral adrenalectomy (removal of the adrenal glands) for the hyperplastic form of the disease;
• prescription of Dexamethasone for glucocorticoid-suppressed aldosteronism.

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RCHR (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical protocols of the Ministry of Health of the Republic of Kazakhstan - 2017

Primary hyperaldosteronism (E26.0)

Endocrinology

general information

Short description

Approved
Joint Commission on Healthcare Quality
Ministry of Health of the Republic of Kazakhstan
dated August 18, 2017
Protocol No. 26

PGA- a collective diagnosis characterized by elevated aldosterone levels, which are relatively independent of the renin-angiotensin system and do not decrease with sodium load. Increased aldosterone levels cause cardiovascular disorders, decreased plasma renin levels, arterial hypertension, sodium retention, and accelerated potassium excretion, leading to hypokalemia. Among the causes of PHA are adrenal adenoma, unilateral or bilateral adrenal hyperplasia, and in rare cases, hereditary GPH.

INTRODUCTORY PART

ICD code(s):

Date of protocol development/revision: 2013 (revised 2017).

Abbreviations used in the protocol:

Classification

Etiopathogenetic and clinical and morphological signs of PHA (E. G. Biglieri, J. D. Baxter, modification).
· aldosterone-producing adenoma of the adrenal cortex (APA) - aldosteroma (Conn's syndrome);
Bilateral hyperplasia or adenomatosis of the adrenal cortex:
- idiopathic hyperaldosteronism (IHA, unsuppressed hyperproduction of aldosterone);
- undefined hyperaldosteronism (selectively suppressed aldosterone production);
- glucocorticoid suppressed hyperaldosteronism (SHHA);
· aldosterone-producing, glucocorticoid-suppressed adenoma;
· carcinoma of the adrenal cortex;
· extra-adrenal hyperaldosteronism (ovaries, intestines, thyroid gland).

Diagnostics

DIAGNOSTIC METHODS, APPROACHES AND PROCEDURES

Diagnostic criteria

Complaints and anamnesis

: headaches, increased blood pressure, muscle weakness, especially in the calf muscles, cramps, parasthesia in the legs, polyuria, nocturia, polydipsia. The onset of the disease is gradual, symptoms appear after 40 years, most often diagnosed in the 3rd-4th decade of life.

Physical examination:
· hypertensive, neurological and urinary syndromes.

Laboratory research:
Determination of potassium in blood serum;
· determination of blood plasma aldosterone levels;
· determination of the aldosterone-renin ratio (ARR).
In patients with positive APC, prior to differential diagnosis of forms of PHA, it is recommended that one of 4 confirmatory PHA tests be performed (A).

Tests confirming PHA

· Ultrasound of the adrenal glands (however, the sensitivity of this method is insufficient, especially in the case of small formations less than 1.0 cm in diameter);
· CT scan of the adrenal glands (the accuracy of detecting tumor formations with this method reaches 95%). Allows you to determine the size of the tumor, shape, topical location, evaluate the accumulation and washout of contrast (confirms or excludes adrenocortical cancer). Criteria: benign formations are usually homogeneous, their density is low, and their contours are clear;
· scintigraphy with 131 I-cholesterol - criteria: aldosteroma is characterized by asymmetric accumulation of radiopharmaceuticals (in one adrenal gland), in contrast to bilateral diffuse small-nodular hyperplasia of the adrenal cortex;
· selective catheterization of the adrenal veins and determination of the level of aldosterone and cortisol in the blood flowing from the right and left adrenal glands (blood samples are taken from both adrenal veins, as well as from the inferior vena cava). Criteria: A fivefold increase in the aldosterone/cortisol ratio is considered to confirm the presence of aldosteroma.

Indications for consultation with specialists:
· consultation with a cardiologist to select antihypertensive therapy;
· consultation with an endocrinologist to select treatment tactics;
· consultation with a vascular surgeon to select a method of surgical treatment.

Diagnostic algorithm:(scheme)




ARS is currently the most reliable and accessible method for screening for PHA. When determining APC, as with other biochemical tests, false positive and false negative results are possible. ARS is regarded as a test used in primary diagnosis, in case of questionable results due to various external influences (taking medications, non-compliance with blood sampling conditions). The effects of medications and laboratory conditions on ARS are shown in Table 2.

Table 2. Drugs with minimal effect on aldosterone levels that can be used to control blood pressure during the diagnosis of PHA

1. Correction of hypokalemia is necessary after measuring plasma potassium. To exclude artifacts and overestimation of the real potassium level, blood sampling must meet the following conditions:
· carried out by syringe method (vacutainer is undesirable);
Avoid clenching your fist;
· draw blood no earlier than 5 seconds after removing the tourniquet;
· plasma separation for at least 30 minutes after collection.
2. The patient should not limit sodium intake.
3. Discontinue medications that affect APC parameters at least 4 weeks in advance:
· spironolactone, triamterene;
· diuretics;
· Licorice root products.
4. If the results of ARS while taking the above-mentioned drugs are not diagnostic, and if hypertension is controlled with drugs with minimal effect on aldosterone levels (see Table 2), discontinue for at least 2 weeks other medications that may affect ARS levels :
· beta-blockers, central alpha-agonists (clonidine, a-methyldopa), NSAIDs;
· ACE inhibitors, angiotensin receptor blockers, renin inhibitors, dihydropyridine calcium channel blockers.
5. If it is necessary to control hypertension, treatment is carried out with drugs with minimal effect on aldosterone levels (see table 2).
6. It is necessary to have information about taking oral contraceptives (OCs) and hormone replacement therapy, because Estrogen-containing medications may decrease direct renin concentrations, resulting in a false-positive ARS result. Do not cancel OK, use the ARP level in this case, not the RCC level.

B. Collection conditions:
· collection in the morning, after the patient has been in an upright position for 2 hours, after being in a sitting position for about 5-15 minutes.
· sampling in accordance with paragraph A. 1, stasis and hemolysis require repeated sampling.
· before centrifugation, keep the tube at room temperature (and not on ice, since cold conditions increase the APP); after centrifugation, quickly freeze the plasma component.

C. Factors affecting the interpretation of results:
· age > 65 years affects the decrease in renin levels, ARS is artificially increased;
· time of day, food (salt) diet, time period of postural position;
· medicines;
· violations of blood sampling techniques;
· potassium level;
· creatinine level (renal failure leads to false-positive APC).

Differential diagnosis

Differential diagnosis and rationale for additional studies

Table 3. Diagnostic tests for PHA

Treatment abroad

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Treatment

Drugs (active ingredients) used in treatment

Groups of drugs according to ATC used in treatment

Treatment (outpatient clinic)

TREATMENT TACTICS AT OUTPATIENT LEVEL: only in case of preoperative preparation (see the step-by-step patient management diagram):
1) prescription of an aldosterone antagonist - spironolactone at an initial dose of 50 mg 2 times a day with a further increase after 7 days to an average dose of 200 - 400 mg / day in 3 - 4 doses. If ineffective, the dose is increased to 600 mg/day;
2) in order to reduce blood pressure until potassium levels normalize, dihydropyridine calcium channel blockers can be prescribed at a dose of 30-90 mg/day;
3) correction of hypokalemia (potassium-sparing diuretics, potassium supplements);
4) spironolactone is used to treat IHA. In cases of erectile dysfunction in men, it can be replaced with amiloride* at a dose of 10 - 30 mg / day in 2 doses or triamterene up to 300 mg / day in 2 - 4 doses. These drugs normalize potassium levels, but do not reduce blood pressure, which is why it is necessary to add saluretics, calcium antagonists, ACE inhibitors and angiotensin II antagonists;
5) in the case of PHPA, dexamethasone is prescribed in individually selected doses necessary to eliminate hypokalemia, possibly in combination with antihypertensive drugs.
*apply after registration on the territory of the Republic of Kazakhstan

Non-drug treatment:
· mode: gentle mode;
< 2 г/сут.

Drug treatment(preoperative preparation)

List of essential medicines(having a 100% probability of application):

Treatment (inpatient)

TACTICSINPATIENT TREATMENT

Surgery(patient routing)

Non-drug treatment:
· mode: gentle mode;
Diet: limiting table salt to< 2 г/сут.

Drug treatment:

List of essential medicines (having a 100% probability of use):

List of additional medications (less than 100% probability of use):

Further management: blood pressure control to exclude relapses of the disease, lifelong use of antihypertensive drugs for patients with IHA and HPHA, observation by a therapist and cardiologist.

Indicators of treatment effectiveness:
· controlled blood pressure, normalization of potassium levels in the blood.

Hospitalization

INDICATIONS FOR HOSPITALIZATION, INDICATING THE TYPE OF HOSPITALIZATION

Indications for planned hospitalization:

· for surgical treatment.

Indications for emergency hospitalization:
· hypertensive crisis/stroke;
· severe hypokalemia.

Information

Sources and literature

1. Minutes of meetings of the Joint Commission on the Quality of Medical Services of the Ministry of Health of the Republic of Kazakhstan, 2017
   1. 1) Primary hyperaldosteronism. clinical recommendations. Endocrine surgery No. 2 (3), 2008, pp. 6-13. 2) Clinical endocrinology. Guide / Ed. N. T. Starkova. - 3rd ed., revised. and additional - St. Petersburg: Peter, 2002. - P. 354-364. - 576 p. 3) Endocrinology. Volume 1. Diseases of the pituitary gland, thyroid gland and adrenal glands. Saint Petersburg. SpetsLit., 2011. 4) Endocrinology. Edited by N. Lavin. Moscow. 1999. pp.191-204. 5) Functional and topical diagnostics in endocrinology. S.B. Shustov., Yu.Sh. Khalimov., G.E. Trufanov. Page 211-216. 6) Internal diseases. R. Harrison. Volume No6. Moscow. 2005. Pp. 519-536. 7) Endocrinology according to Williams. Diseases of the adrenal cortex and endocrine arterial hypertension. Henry M. Cronenberg, Shlomo Melmed, Kenneth S. Polonsky, P. Reed Larsen. Moscow. 2010. Pp. 176-194. 8) Clinical recommendations “Incidentaloma of the adrenal glands (diagnosis and differential diagnosis).” Methodological recommendations for primary care physicians. Moscow, 2015. 9) Case Detection, Diagnosis, and Treatment of Patients with Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline 10) John W. Funder, Robert M. Carey, Franco Mantero, M. Hassan Murad, Martin Reincke, Hirotaka Shibata , Michael Stowasser, William F. Young, Jr; The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016; 101(5): 1889-1916. doi: 10.1210/jc.2015-4061 11) Parthasarathy HK, Ménard J, White WB, Young WF, Williams GH, Williams B, Ruilope LM, McInnes GT, Connell JM and MacDonald TM. A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism. Journal of hypertension, 2011, 29(5), 980 12) Mulatero P, Rabbia F, Milan A, Paglieri C, Morello F, Chiandussi L, Veglio F. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Hypertension. 2002 Dec;40(6):897-902. 13) Pechère-Bertschi A, Herpin D, Lefebvre H. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 7: Medical treatment of primary aldosteronism. Ann Endocrinol (Paris). 2016 Jul;77(3):226-34. doi: 10.1016/j.ando.2016.01.010. Epub 2016 Jun 14.

Information

ORGANIZATIONAL ASPECTS OF THE PROTOCOL

List of protocol developers:

1) Laura Bakhytzhanovna Danyarova - candidate of medical sciences, endocrinologist, head of the department of endocrinology of the RSE at the Scientific Research Institute of Cardiology and Internal Diseases.
2) Raisova Aigul Muratovna - Candidate of Medical Sciences, head of the therapeutic department of the RSE at the Scientific Research Institute of Cardiology and Internal Medicine.
3) Smagulova Gaziza Azhmagievna - Candidate of Medical Sciences, Head of the Department of Propaedeutics of Internal Diseases and Clinical Pharmacology of the Western Kazakhstan State Medical University named after M. Ospanov.

Disclosure of no conflict of interest: No.

Reviewers:
Bazarbekova Rimma Bazarbekovna - Doctor of Medical Sciences, Professor, Head of the Department of Endocrinology of JSC “Kazakh Medical University of Continuing Education”.

Indication of the conditions for reviewing the protocol: review of the protocol 5 years after its publication and from the date of its entry into force or in the presence of new methods with a level of evidence.

Attached files

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Hyperaldosteronism is an endocrine pathology characterized by increased secretion of aldosterone. This mineralocorticosteroid hormone, synthesized by the adrenal cortex, is necessary for the body to maintain an optimal balance of potassium and sodium.

This condition happens primary, with it, hypersecretion is caused by changes in the adrenal cortex itself (for example, with adenoma). Also distinguished secondary form hyperaldosteronism caused by changes in other tissues and excess production of renin (the component responsible for the stability of blood pressure).

Note: about 70% of identified cases of primary hyperaldosteronism are women from 30 to 50 years old

An increased amount of aldosterone negatively affects the structural and functional units of the kidneys (nephrons). Sodium is retained in the body, and the excretion of potassium, magnesium and hydrogen ions, on the contrary, accelerates. Clinical symptoms are more pronounced in the primary form of the pathology.

Causes of hyperaldosteronism

The concept of “hyperaldosteronism” unites a number of syndromes, the pathogenesis of which is different, but the symptoms are similar.

In almost 70% of cases, the primary form of this disorder does not develop against the background of Conn's syndrome. With it, the patient develops aldosteroma, a benign tumor of the adrenal cortex that causes hypersecretion of the hormone.

The idiopathic type of pathology is a consequence of bilateral tissue hyperplasia of these paired endocrine glands.

Sometimes primary hyperaldosteronism is caused by genetic disorders. In some situations, the etiological factor is a malignant neoplasm, which can secrete deoxycorticosterone (a minor hormone of the gland) and aldosterone.

The secondary form is a complication of pathologies of other organs and systems. It is diagnosed for such serious diseases as malignant, etc.

Other causes of increased renin production and the appearance of secondary hyperaldosteronism include:

• insufficient intake or active excretion of sodium;
• large blood loss;
• excess nutritional intake of K+;
• abuse of diuretics and.

If the distal tubules of the nephrons do not respond adequately to aldosterone (with normal plasma levels), pseudohyperaldosteronism is diagnosed. In this condition, there is also a low level of K+ ions in the blood.

Note:there is an opinion that secondary hyperaldosteronism in women can provoke taking.

How does the pathological process proceed?

Primary hyperaldosteronism is characterized by low levels of renin and potassium, hypersecretion of aldosterone and.

The pathogenesis is based on a change in the water-salt ratio. Accelerated excretion of K+ ions and active reabsorption of Na+ leads to hypervolemia, water retention in the body and increased blood pH.

Note:a shift in blood pH to the alkaline side is called metabolic alkalosis.

At the same time, renin production decreases. Na+ accumulates in the walls of peripheral blood vessels (arterioles), causing them to swell and swell. As a result, resistance to blood flow increases and blood pressure rises. Long term causes muscle and renal tubule dystrophy.

In secondary hyperaldosteronism, the mechanism of development of the pathological condition is compensatory. Pathology becomes a kind of response to a decrease in renal blood flow. There is an increase in the activity of the renin-angiotensin system (as a result of which blood pressure increases) and an increase in the formation of renin. There are no significant changes in the water-salt balance.

Symptoms of hyperaldosteronism

Excess sodium leads to increased blood pressure, increased circulating blood volume (hypervolemia) and the appearance of edema. Lack of potassium causes chronic muscle weakness. In addition, with hypokalemia, the kidneys lose their ability to concentrate urine, and characteristic changes appear. Convulsive seizures (tetany) may occur.

Signs of primary hyperaldosteronism:

• arterial hypertension (manifested by increased blood pressure);
• cephalgia;
• cardialgia;
• drop in visual acuity;
• sensory disturbances (paresthesia);
• (tetany).

Important:in patients suffering from symptomatic arterial hypertension, primary hyperaldosteronism is detected in 1% of cases.

Due to the retention of fluid and sodium ions in the body, patients experience a moderate or very significant increase in blood pressure. The patient is bothered (aching and of moderate intensity). During the examination, it is often noted. Against the background of arterial hypertension, visual acuity decreases. When examined by an ophthalmologist, pathologies of the retina (retinopathy) and sclerotic changes in the vessels of the fundus are revealed. Daily diuresis (volume of urine excreted) increases in most cases.

Lack of potassium causes rapid physical fatigue. Periodic pseudoparalysis and convulsions develop in different muscle groups. Episodes of muscle weakness can be triggered not only by physical exertion, but also by psycho-emotional stress.

In particularly severe clinical cases, primary hyperaldosteronism leads to diabetes insipidus (of renal origin) and pronounced dystrophic changes in the heart muscle.

Important:If not, then in the primary form of the condition peripheral edema does not occur.

Signs of the secondary form of the condition:

• arterial hypertension;
• chronic renal failure ();
• significant peripheral edema;
• changes in the fundus.

The secondary type of pathology is characterized by a significant increase in blood pressure (“lower” > 120 mmHg). Over time, it causes changes in the walls of blood vessels, oxygen starvation of tissues, hemorrhages in the retina and chronic renal failure.. Low blood potassium levels are rarely detected. Peripheral edema is one of the most typical clinical signs of secondary hyperaldosteronism.

Note:sometimes the secondary type of pathological condition is not accompanied by an increase in blood pressure. In such cases, as a rule, we are talking about pseudohyperaldosteronism or a genetic disease - Bartter's syndrome.

Diagnosis of hyperaldosteronism

To diagnose various types of hyperaldosteronism, the following types of clinical and laboratory studies are used:

First of all, the K/Na balance, the state of the renin-angiotensin system are studied and the level of aldosterone in the urine is detected. Analyzes are carried out both at rest and after special loads (marching, hypothiazide, spironolactone).

One of the important indicators at the initial stage of the examination is the level of adrenocorticotropic hormone (aldosterone production depends on ACTH).

Diagnostic indicators of the primary form:

• Plasma aldosterone levels are relatively high;
• plasma renin activity (PRA) is reduced;
• potassium levels are low;
• sodium levels are elevated;
• the aldosterone/renin ratio is high;
• the relative density of urine is low.

There is an increase in daily urinary excretion of aldosterone and potassium ions.

Secondary hyperaldosteronism is indicated by an increase in ARP.

Note:if the condition can be corrected by the introduction of glucocorticoid hormones, the so-called. trial treatment with prednisone. With its help, blood pressure is stabilized and other clinical manifestations are eliminated.

At the same time, the condition of the kidneys, liver and heart is studied using ultrasound, echocardiography, etc.. It often helps to identify the true cause of the development of a secondary type of pathology.

How is hyperaldosteronism treated?

Medical tactics are determined by the form of the condition and the etiological factors that led to its development.

The patient undergoes a comprehensive examination and treatment by an endocrinologist. An opinion from a nephrologist, ophthalmologist and cardiologist is also required.

If excessive production of the hormone is caused by a tumor process (reninoma, aldosteroma, adrenal cancer), then surgical intervention (adrenalectomy) is indicated. During surgery, the affected adrenal gland is removed. For hyperaldosteronism of other etiologies, pharmacotherapy is indicated.

A low-salt diet and consumption of potassium-rich foods can achieve a good effect.. At the same time, potassium supplements are prescribed. Drug treatment involves prescribing potassium-sparing diuretics to the patient to combat hypokalemia. It is also practiced during the period of preparation for surgery for general improvement of the condition. For bilateral hyperplasia of the organ, in particular, Amiloride, Spironolactone and angiotensin-converting enzyme inhibitor drugs are indicated.

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

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

Classification of primary hyperaldosteronism

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

Causes of primary hyperaldosteronism

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

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

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

Symptoms and signs of primary hyperaldosteronism

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

If we highlight the diagnostically significant (specific) signs of primary hyperaldosteronism, they are as follows:

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

Aldosteroma (Conn's syndrome)

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

Bilateral idiopathic adrenal hyperplasia (bilateral idiopathic hyperaldosteronism)

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

Adrenal carcinoma

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

Glucocorticoid-suppressed hyperaldosteronism

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

Diagnosis of primary hyperaldosteronism

After the diagnosis of primary hyperaldosteronism is verified using a biochemical examination, topical and differential diagnosis of diseases accompanied by hyperaldosteronism begins.

Computed/magnetic resonance imaging

Using CT or MRI, nodules with a diameter of more than 5 mm can be detected in the adrenal glands. Since the frequency of detection of adrenal incidentalomas increases with age, the question often arises about the advisability of collecting venous blood for aldosterone. CT or MRI can detect the following changes in the adrenal glands:

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

Taking blood from the adrenal veins

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

The study is indicated in the following cases:

• bilateral changes in the adrenal glands identified by CT/MRI;
• primary hyperaldosteronism at the age of over 50 years, when CT/MRI of the adrenal glands shows a single adenoma, since with age the number of adrenal incidentalomas increases sharply. In some clinical centers, in this case, it is recommended to take blood from the veins of the adrenal glands in patients over 35 years of age, since at a younger age, against the background of primary hyperaldosteronism, a unilateral adenoma is almost always functional;
• Surgical treatment of an adrenal tumor can, in principle, be performed, and the patient is not against a potential operation.

Radioisotope scanning

Iodine-labeled cholesterol testing does not have any advantage over CT/MRI.

The diagnosis of aldosteroma or adrenal hyperplasia should not be made based solely on elevated aldosterone levels. However, in primary hyperaldosteronism, renin activity is reduced; in more rare cases, threshold values ​​of 20 and 40 times are used).

On the eve of the test, it is necessary to compensate for hypokalemia. Spironolactone, eplerenone, triamterene, loop diuretics and products containing licorice should be discontinued 4 weeks before testing plasma renin activity. If it is diagnostically insignificant, and arterial hypertension can be treated with verapamil, hydralazine or α-blockers, β-blockers, central α2-agonists, NSAIDs, and ACE inhibitors should be discontinued 4 weeks before the re-test.

Daily urinary aldosterone excretion of more than 10-14 mcg (28-39 nmol) against the background of a sodium load test is considered a sign of primary hyperaldosteronism if sodium excretion exceeds 250 mmol/day. In the saline test, plasma aldosterone levels fall below 5 ng% after infusion; When aldosterone levels are more than 10 ng%, the diagnosis of primary hyperaldosteronism is highly likely.

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

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

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

In the topical diagnosis of PHA, computer X-ray or MRI is used, which makes it possible to visualize aldosteromes in the form of unilateral solitary formations of low density (0-10 units) with an average diameter of 1.6-1.8 cm. With idiopathic hyperaldosteronism, the adrenal glands look normal or symmetrically enlarged, with nodes or without them.

Hormonal examination and diagnostic signs

Screening

Indications

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

Method

• If the patient is not specially prepared for the test, false-positive and false-negative results can be obtained, in particular:
• there should be no restriction of table salt in the diet;
• treatment with drugs that affect the results of renin and aldosterone tests should be discontinued for the recommended period;
• It is recommended to control blood pressure with doxazosin (an α-blocker) or verapamil (a recommended calcium channel blocker).
• Aldosterone/renin ratio:
• a high coefficient value indicates primary hyperaldosteronism:
• aldosterone/plasma renin activity >750;
• aldosterone/plasma renin activity >30-50;
• the higher the coefficient value, the more likely the diagnosis of primary hyperaldosteronism;
• false negative values ​​are observed in patients with chronic renal failure due to very high renin activity.

Diagnosis-verifying tests

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

• Before the test, the patient must be on a regular diet, without limiting table salt;
• patients are given instructions explaining how to include increased salt content in their diet up to 200 mmol/day for 3 days;
• if necessary, you can prescribe tablets containing salt;

An aldosterone level in daily urine of less than 10 mcg virtually eliminates primary hyperaldosteronism.

Fludrocortisone suppression test:

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

Differential diagnosis of primary hyperaldosteronism

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

Once the diagnosis is established, the cause of hyperaldosteronism is determined in order to select the correct treatment. The most common causes of primary hyperaldosteronism are hyperplasia of the adrenal cortex and aldosterome. Unfortunately, the presence or absence of adrenal masses does not allow us to unambiguously confirm or exclude the presence of aldosteroma. If laboratory test data indicate aldosteroma, and radiological diagnostics do not find a tumor, blood samples are taken from the adrenal veins. This complex procedure is performed in a specialized center with extensive experience in conducting such tests. With unilateral lesions, the ratio of aldosterone levels corrected for cortisol levels in different adrenal veins of 4:1 is considered diagnostically significant.

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

Pathogenesis of symptoms and signs

The symptom complex that develops as a result of increased levels of mineralocorticoids in the blood or increased sensitivity of target tissues to them is called hyperaldosteronism (aldosteronism, hypermineralocorticoidism). There are two forms of it:

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

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

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

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

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

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

Elevated blood pressure is recorded in most patients.

Retinopathy is moderate, and hemorrhages in the fundus rarely appear.

The heart slightly increases in size to the left.

Since hypokalemia develops most often during treatment with diuretics, they should be discontinued 3 weeks before the potassium test. In addition, the patient's diet should not be enriched with potassium or sodium. A low-salt diet, while helping to preserve potassium reserves in the body, can mask hypokalemia.

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

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

Associated conditions, diseases and complications

Associated conditions/diseases and complications are listed below.

• Primary hyperaldosteronism (aldosteroma).
• Hemorrhagic stroke.
• Arrhythmias.
• Hypervolemia.
• Unexpected cardiac death.
• Intoxication with cardiac glycosides.
• Nephrosclerosis benign/malignant arteriolar.
• Kidney cyst.
• Nephrogenic ND.
• Diabetes.
• Periodic paralysis syndrome.
• Tetany.
• Electrolyte myopathy.
• Hypokalemia.
• Hypokalemic nephropathy.
• Alkalosis is metabolic, hypokalemic.
• Hypernatremia.
• Hypomagnesemia.
• Drug-induced electrolyte disturbances.
• Isosthenuria.

Diseases and conditions from which hyperaldosteronism is differentiated

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

• Adrenogenital syndrome.
• Cushing's syndrome/disease.
• Iatrogenic Cushing's syndrome.
• Secondary hyperaldosteronism.
• Intoxication with diuretics.
• Drug-induced electrolyte disturbances.
• Drug-induced arterial hypertension.
• Electrolyte disturbances.
• Hypokalemic periodic paralysis.
• Taking licorice roots/glycyrrhizic acid.
• Familial periodic paralysis.
• Renal artery stenosis.
• Barter syndrome.

Treatment of primary hyperaldosteronism

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

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

Conservative treatment of primary hyperaldosteronism, regardless of etiology, consists primarily of prescribing a low-salt diet (containing less than 80 mEq of sodium). This reduces urinary potassium loss by reducing the amount of sodium exchanged for potassium in the distal tubules of the kidneys. In addition, such a diet helps lower blood pressure, since it reduces intravascular volume.

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

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

When surgical treatment is indicated for hyperaldosteronism syndrome (apdosteroma, adrenal carcinoma, primary hyperaldosteronism, etc.), then preoperative preparation consists of normalizing potassium and blood pressure, which may require conservative therapy (diet and medications) for hyperaldosteronism syndrome for up to 1-3 months. This treatment prevents the development of postoperative hypoaldosteronism, since against its background the renin-angiotensin system and, accordingly, the glomerular layer of the unaffected adrenal gland are activated. Plasma potassium levels are regularly monitored during surgery, as the function of the remaining adrenal gland is sometimes so suppressed that massive steroid replacement therapy may be required. To prevent rebound mineralocorticoid deficiency after surgical removal of the affected tissue, hydrocortisone is infused during surgery at a rate of 10 mg/hour. After surgery, glucocorticoids are prescribed, the dose of which is gradually reduced until completely eliminated over 2-6 weeks.

Some patients, despite preoperative preparation, develop hypoaldosteronism after surgery, the symptoms of which are usually eliminated with adequate (without restrictions) salt and fluid intake. If dietary treatment does not correct hypoaldosteronism, mineralocorticoid replacement therapy is indicated.

Surgery

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

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

Prognosis of primary hyperaldosteronism

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