Conn's syndrome is primary aldosteronism. Primary hyperaldosteronism (Conn's syndrome)

Conn's syndrome is a disease endocrine system, which is characterized by a large volume of aldosterone production. In medicine it is called as primary aldosteronism. This disease can be called a consequence of the main disease, which, as it progresses, causes complications. The main diseases include adrenal tumor, adrenal cancer, pituitary neoplasm, adenoma and carcinoma.

General information

Aldosteronism is divided into primary and secondary. Both types occur due to excessive production of the hormone aldosterone, which is responsible for retaining sodium in the body and excreting potassium through the kidneys. This hormone is also called adrenal hormone and mineralocorticoid. The most common and severe concomitant of this disease is arterial hypertension. Primary and secondary aldosteronism are not two stages of the same disease, but two completely different diseases. They also differ in the reasons for their appearance, their effect on the body and, accordingly, their treatment methods.

Primary (Conn's syndrome) aldosteronism

Opened by Conn in 1955. Women suffer from aldosteronism 3 times more often. The fair sex aged 25-45 is at risk. Primary aldosteronism occurs due to neoplasms of the adrenal cortex (unilateral adenoma). Much less commonly, the cause is adrenal hyperplasia or cancer. With increased aldosterone production, the amount of sodium in the kidneys increases, and potassium, in turn, decreases.

The examination is carried out by a pathologist who diagnoses a tumor of the adrenal cortex. It can be single or multiple and affect one or both adrenal glands. In more than 95% of cases, the tumor is benign. Also, as a test, doctors often prescribe linked immunosorbent assay, where venous blood is used as a biomaterial. An ELISA is prescribed to determine the amount of aldosterone in the body and to screen for primary hyperaldosteronism.

Conn's syndrome occurs with pathology of the adrenal glands, tumor neoplasms.

Indications for research are most often high blood pressure, which does not return to normal during therapeutic manipulations, suspicion of the development of renal failure. You need to be properly prepared for donating blood. First, limit your intake of foods rich in carbohydrates for 2-4 weeks. Also, for this period, exclude diuretics, estrogens, oral contraceptives, and steroids. Stop therapy with renin inhibitors for 1 week, remove, or, as a last resort, limit moral and physical stress for 3 days. Do not smoke three hours before the procedure. Having the results in hand, taking into account the amount of hormones renin, aldosterone and cortisone, the attending physician will be able to correctly diagnose and prescribe effective drug treatment.

Secondary compensatory (symptomatic)

Unlike primary aldosteronism, secondary aldosteronism is provoked not by diseases associated with the adrenal glands, but by problems with the liver, heart and kidneys. That is, it acts as a complication of some serious illnesses. At risk are patients diagnosed with:

• adrenal cancer;
• a number of heart diseases;
• deviations in work thyroid gland, intestines;
• idiopathic hyperaldosteronism;
• adenoma of the adrenal cortex.

Also to the list should be added a tendency to bleeding, prolonged exposure medications. But this does not mean that all patients who suffer from these ailments will add a diagnosis of “secondary aldosteronism” to their medical history; they just need to be more attentive to their health.

Symptoms of the disease

Persistent arterial hypertension a characteristic symptom of Conn's syndrome.

Primary and secondary aldosteronism are associated with the following symptoms:

1. swelling that appears due to fluid retention in the body;
2. weakening muscle strength, fatigue;
3. frequent urge to go to the toilet, especially at night (pollakiuria);
4. hypertension (increased blood pressure);
5. thirst;
6. vision problems;
7. feeling unwell, headache;
8. muscle paralysis for short periods of time, numbness of body parts, mild tingling;
9. an increase in the size of the ventricles of the heart;
10. rapid weight gain - more than 1 kg per day.

Evacuation of potassium contributes to the appearance of muscle weakness, paresthesia, sometimes muscle paralysis and many other kidney diseases. The symptoms of aldosteronism are quite dangerous, but the consequences are no less dangerous. Therefore, you should not hesitate, you need to consult a doctor for help as soon as possible.

Complications and consequences

Primary aldosteronism, if symptoms are ignored and therapy is refused, leads to a number of complications. First of all, the heart begins to suffer (ischemia), heart failure and intracranial bleeding develop. In rare cases, the patient has a stroke. Since the amount of potassium in the body decreases, hypokalemia develops, which provokes arrhythmia, which, in turn, can lead to fatal outcome. Secondary hyperaldosteronism is itself a complication of other serious illnesses.

Diagnosis and differential diagnosis

Urine and blood tests are prescribed to correctly and accurately diagnose the disease.

If the attending physician suspects aldosteronism, a series of studies and tests are prescribed to confirm or refute the suspected diagnosis, as well as for correct further drug therapy. First, urine and blood tests are performed. In the laboratory, the presence of polyuria is established or refuted, or its urine density is analyzed. The concentration of aldosterone, cortisol and renin in the blood is studied. In primary hyperaldosteronism, renin is low, cortisol is normal, and aldosterone is high. For secondary aldosteronism, a slightly different situation is inherent; the presence of renin must be significant. Ultrasound is often used for more accurate results. Less often - MRI and CT scan of the adrenal glands. Additionally, the patient should be examined by a cardiologist, ophthalmologist, and nephrologist.

Treatment of aldosteronism

Treatment of primary or secondary aldosteronism should be comprehensive and include not only drug therapy, but also proper nutrition, in some cases - surgical surgical intervention. The main goal of treating Conn's syndrome is to prevent complications after The diet for Crohn's disease depends on the severity of the symptoms of the disease.

At the same time, you should follow a diet. It is based on an increase in potassium-containing products and additional potassium-containing drugs. Eliminate or limit salt intake. Potassium-rich foods include:

• dried fruits (raisins, dried apricots, prunes);
• fresh fruits (grapes, melon, apricots, plums, apples, banana);
• fresh vegetables (tomato, potato, garlic, pumpkin);
• greenery;
• meat;
• nuts;
• Black tea.

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

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Conn's syndrome

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

The concept and causes of primary and secondary hyperaldosteronism:

	Primary hyperaldosteronism	Secondary hyperaldosteronism
Definition	A syndrome that develops as a result of excessive production of aldosterone by the adrenal cortex (rarely an aldosterone-producing tumor of extra-adrenal localization), the level of which is relatively independent of the renin-angiotensin-aldosterone system (RAAS) and is not suppressed by sodium load	A syndrome resulting from a decrease in colloid osmotic blood pressure and stimulation of the RAAS (as a complication of a number of diseases)
Causes	The disease is associated with pathology of the adrenal glands: aldosterone-producing adenoma (Conn's syndrome) – 70%; bilateral hyperplasia of the zona glomerulosa of the adrenal cortex (idiopathic hyperaldosteronism) – up to 30%; rare diseases (aldosterone-producing carcinoma, unilateral hyperplasia of the zona glomerulosa of the adrenal cortex, familial hyperaldosteronism types I, II, III, MEN - I).	Associated with pathology of other organs and systems: kidney diseases (nephrotic syndrome, stenosis renal artery, kidney tumors, etc.); heart disease (congestive heart failure); other causes (hypersecretion of ACTH, taking diuretics, liver cirrhosis, fasting)

Etiology

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



CT scan of the abdomen. Adrenal adenoma



Pathogenesis

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

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






Clinic

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

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

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

Diagnostics

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

Laboratory research

After forming a risk group, patients are determined:

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

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

Medicines that affect the results of ARS:

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

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

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

Functional tests to determine aldosterone levels:

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

Instrumental studies

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

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

Differential diagnosis

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

Differential diagnosis:

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

Treatment

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

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



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

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

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

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

The syndrome of primary hyperaldosteronism was described by J. Conn (1955) in connection with an aldosterone-producing adenoma of the adrenal cortex (aldosteroma), the removal of which led to full recovery sick. Currently collective concept Primary hyperaldosteronism unites a number of diseases that are similar in clinical and biochemical characteristics, but different in pathogenesis, which are based on excessive and independent (or partially dependent) on the renin-angiotensin system production of aldosterone by the adrenal cortex.

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ICD-10 code

E26.0 Primary hyperaldosteronism

What causes primary aldosteronism?

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

Symptoms of primary aldosteronism

Clinical case of primary hyperaldosteronism

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

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

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

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

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

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

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

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

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

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

Based on the anamnesis, clinical picture, these laboratory and instrumental research methods have been established clinical diagnosis: Primary hyperaldosteronism (aldosteroma of the left adrenal gland), first identified in the form of hypokalemic syndrome, neurological symptoms, sinus tachycardia. Hypokalemic periodic seizures with generalized muscle weakness. Hypertonic disease 3 degrees, 1 stage. CHF 0. Sinus tachycardia. Infection urinary tract in the resolution stage.

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

The patient was recommended surgical treatment to remove a hormone-producing tumor of the adrenal gland - laparoscopic adrenalectomy on the left. An operation was performed - laparoscopic adrenalectomy on the left in the department abdominal surgery RKB. Postoperative period proceeded without any special features. On the 4th day after surgery (02/11/12), the blood potassium level was 4.5 mmol/l. Blood pressure 130/80 mm Hg. Art.

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Secondary aldosteronism

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

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

Diagnosis of primary aldosteronism

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

Conn's syndrome (Conn) is a complex of symptoms caused by overproduction of aldosterone by the adrenal cortex. The cause of the pathology is a tumor or hyperplasia of the glomerular zone of the cortex. In patients, blood pressure increases, the amount of potassium decreases and the concentration of sodium in the blood increases.

The syndrome has several equivalent names: primary hyperaldosteronism, aldosteroma. These medical terms combine a number of diseases that are similar in clinical and biochemical characteristics, but different in pathogenesis. Conn's syndrome is a pathology of the endocrine glands, manifested by a combination of myasthenia gravis, unnaturally strong, unquenchable thirst, high blood pressure and an increased volume of urine released per day.

Aldosterone performs vitally important functions in the human body. The hormone promotes:

• absorption of sodium into the blood,
• development of hypernatremia,
• excretion of potassium in urine,
• alkalization of blood,
• hypoproduction of renin.

When the level of aldosterone in the blood increases, the functioning of the circulatory, urinary and neuromuscular systems is disrupted.

The syndrome is extremely rare. It was first described by American scientist Conn in 1955, which is how it got its name. The endocrinologist described the main clinical manifestations syndrome and proved that the most effective method of treating the pathology is surgery. If patients monitor their health and regularly visit doctors, the disease is detected on time and responds well to treatment. Removal of an adrenal adenoma leads to a complete recovery of patients.

Pathology is more common in women aged 30-50 years. In men, the syndrome develops 2 times less often. It is extremely rare that the disease affects children.

Etiology and pathogenesis

Etiopathogenetic factors of Conn's syndrome:

1. The main cause of Conn's syndrome is the excessive secretion of the hormone aldosterone by the adrenal glands, caused by the presence of a hormonally active tumor in the outer cortical layer - aldosteroma. In 95% of cases, this neoplasm is benign, does not metastasize, has a unilateral course, is characterized only by an increase in the level of aldosterone in the blood and causes serious disorders water-salt metabolism in organism. The adenoma has a diameter of less than 2.5 cm. On section it yellowish color due to high cholesterol content.
2. Bilateral hyperplasia of the adrenal cortex leads to the development of idiopathic hyperaldosteronism. The cause of the development of diffuse hyperplasia is a hereditary predisposition.
3. Less commonly, the cause may be malignant tumor- adrenal carcinoma, which synthesizes not only aldosterone, but also other corticosteroids. This tumor is larger - up to 4.5 cm in diameter or more, and is capable of invasive growth.

Pathogenetic links of the syndrome:

• hypersecretion of aldosterone,
• decreased activity of renin and angiotensin,
• tubular excretion of potassium,
• hyperkaliuria, hypokalemia, lack of potassium in the body,
• development of myasthenia gravis, paresthesias, transient muscle paralysis,
• enhanced absorption of sodium, chlorine and water,
• fluid retention in the body,
• hypervolemia,
• swelling of the walls and constriction of blood vessels,
• increase in OPS and BCC,
• increased blood pressure,
• vascular hypersensitivity to pressor influences,
• hypomagnesemia,
• increased neuromuscular excitability,
• disturbance of mineral metabolism,
• dysfunction of internal organs,
• interstitial inflammation of the kidney tissue with an immune component,
• nephrosclerosis,
• appearance kidney symptoms- polyuria, polydipsia, nocturia,
• development of renal failure.

Persistent hypokalemia leads to structural and functional disorders in organs and tissues - in the kidney tubules, smooth and skeletal muscles, and the nervous system.

Factors contributing to the development of the syndrome:

1. diseases of cardio-vascular system,
2. concomitant chronic pathologies,
3. reduction of the body's protective resources.

Symptoms

The clinical manifestations of primary hyperaldosteronism are very diverse. Patients simply do not pay attention to some of them, which makes it difficult early diagnosis pathology. Such patients come to the doctor with an advanced form of the syndrome. This forces specialists to limit themselves to palliative treatment.

Symptoms of Conn's syndrome:

• muscle weakness and fatigue,
• paroxysmal tachycardia,
• tonic-clonic seizures,
• headache,
• constant thirst,
• polyuria with low relative density of urine,
• paresthesia of the limbs,
• laryngospasm, suffocation,
• arterial hypertension.

Conn's syndrome is accompanied by signs of damage to the heart and blood vessels, kidneys, and muscle tissue. Arterial hypertension can be malignant and resistant to antihypertensive therapy, as well as moderate and mild, responding well to treatment. It can have a crisis or a stable course.

1. High blood pressure is usually difficult to normalize with antihypertensive drugs. This leads to the appearance of characteristic clinical signs - dizziness, nausea and vomiting, shortness of breath, cardialgia. In every second patient, hypertension is of a crisis nature.
2. In severe cases, they experience attacks of tetany or the development of flaccid paralysis. Paralysis occurs suddenly and can last for several hours. Hyporeflexia in patients is combined with diffuse motor deficits, which is manifested by myoclonic twitches during examination.
3. Persistent hypertension leads to the development of complications from the heart and nervous systems. Hypertrophy of the left chambers of the heart ends in progressive coronary insufficiency.
4. Arterial hypertension disrupts the functioning of the organ of vision: the fundus of the eye changes, the disc swells optic nerve, visual acuity decreases up to complete blindness.
5. Muscle weakness reaches extreme severity, preventing patients from moving. Constantly feeling the weight of their body, they cannot even get out of bed.
6. In severe cases, nephrogenic diabetes insipidus may develop.

There are three variants of the course of the disease:

1. Conn's syndrome with rapid development of symptoms - dizziness, arrhythmia, impaired consciousness.
2. The monosymptomatic course of the disease is an increase in blood pressure in patients.
3. Primary hyperaldosteronism with mild clinical signs - malaise, fatigue. The syndrome is discovered accidentally during a medical examination. Over time, patients develop secondary inflammation of the kidneys against the background of existing electrolyte disturbances.

If signs of Conn's syndrome appear, you should visit a doctor. In the absence of correct and timely therapy are developing dangerous complications, representing real threat for the life of the patient. Due to prolonged hypertension, they can develop serious illnesses cardiovascular system, up to strokes and heart attacks. The development of hypertensive retinopathy, severe myasthenia gravis and tumor malignancy is possible.

Diagnostics

Diagnostic measures for suspected Conn's syndrome include: laboratory tests, hormonal studies, functional tests and topical diagnostics.

• Blood test for biochemical indicators - hypernatremia, hypokalemia, blood alkalization, hypocalcemia, hyperglycemia.
• Hormonal examination - increase in plasma aldosterone levels.
• General urine analysis - determination of its relative density, calculation of daily diuresis: iso- and hyposthenuria, nocturia, alkaline urine reaction.
• Specific tests - determination of the level of renin in the blood, the ratio of plasma aldosterone and renin activity, determination of the level of aldosterone in a daily urine sample.
• To increase the activity of renin in the blood plasma, stimulation is carried out by long walking, a hyposodium diet and diuretics. If renin activity does not change even after stimulation, then the patient has Conn's syndrome.
• To identify urinary syndrome carry out a test with "Veroshpiron". The drug is taken 4 times a day for three days, limiting daily salt intake to six grams. An increased level of potassium in the blood on the 4th day is a sign of pathology.
• CT and MRI of the abdominal cavity - identifying aldosteroma or bilateral hyperplasia, its type and size, determining the extent of the operation.
• Scintigraphy - detection of a tumor of the adrenal gland that secretes aldosterone.
• Oxysuprarenography allows you to determine the location and size of an adrenal tumor.
• Ultrasound of the adrenal glands with color Doppler mapping has high sensitivity, low cost and is performed to visualize aldosteroma.
• The ECG shows metabolic changes in the myocardium, signs of hypertension and left ventricular overload.
• Molecular genetic analysis - identification of familial forms of aldosteronism.

Topical methods - CT and MRI - detect tumors in the adrenal gland with great accuracy, but do not provide information about its functional activity. It is necessary to compare the detected changes on the tomogram with the data of hormonal tests. Results comprehensive examination patients allow specialists to correctly diagnose and prescribe competent treatment.

Persons with arterial hypertension deserve special attention. Experts pay attention to the presence of clinical symptoms of the disease - severe hypertension, polyuria, polydipsia, muscle weakness.

Treatment

Therapeutic measures for Conn's syndrome are aimed at correcting hypertension and metabolic disorders, as well as preventing possible complications caused by high blood pressure and sharp decline potassium in the blood. Conservative therapy is not capable of radically improving the condition of patients. They can fully recover only after removal of the aldosteroma.

adrenalectomy

Surgery is indicated for patients with adrenal aldosteroma. Unilateral adrenalectomy is a radical method consisting in partial or complete resection of the affected adrenal gland. Most patients are indicated for laparoscopic surgery, the advantage of which is minor pain and tissue trauma, short recovery period, small incisions that leave small scars. 2-3 months before surgery, patients should start taking diuretics and antihypertensive drugs different pharmacological groups. After surgical treatment, recurrence of Conn's syndrome is usually not observed. The idiopathic form of the syndrome cannot be treated surgically, since even total resection of the adrenal glands will not help normalize blood pressure. Such patients are indicated for lifelong treatment with aldosterone antagonists.

If the cause of the syndrome is adrenal hyperplasia or there is an idiopathic form of the pathology, it is indicated conservative therapy. Patients are prescribed:

1. Potassium-sparing diuretics - Spironolactone,
2. Glucocorticosteroids – “Dexamethasone”,
3. Antihypertensive drugs - Nifedipine, Metoprolol.

To treat primary hyperaldosteronism, it is necessary to follow a diet and limit the consumption of table salt to 2 grams per day. A gentle regimen, moderate physical activity and maintaining optimal body weight significantly improve the condition of patients.

Strict adherence to the diet reduces the severity of the clinical signs of the syndrome and increases the patients' chances of recovery. Patients should eat home-cooked food that does not contain flavor enhancers, flavorings or other additives. Doctors do not recommend overeating. It is better to eat small portions every 3 hours. The basis of the diet should be fresh fruits and vegetables, cereals, lean meat, and potassium-containing products. You should drink at least 2 liters of water per day. The diet excludes any type of alcohol, strong coffee, tea, and foods that increase blood pressure. Patients need to consume foods with a diuretic effect - watermelons and cucumbers, as well as special decoctions and tinctures.

• frequent walks in the fresh air,
• sports,
• smoking cessation and alcohol cessation,
• giving up fast food.

The prognosis for diagnosed Conn's syndrome is usually favorable. It depends on individual characteristics the patient’s body and the professionalism of the attending physician. It is important to apply for timely medical care, before the development of nephropathy and persistent hypertension. High blood pressure is a serious and dangerous health problem associated with primary hyperaldosteronism.

Video: aldosteroma – the cause of Conn’s syndrome, “Live Healthy!” program

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, not accompanied by increased level 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 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. Characteristic symptom- with a predominance of night diuresis over daytime.

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 option - accompanied hypertensive crises with severe 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 methods for identifying target group and conducting 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 last years the list of possible evidence of primary hyperaldosteronism is 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. Principles differential diagnosis based on examination and exclusion various forms 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 manifest 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 method is surgery(adrenalectomy). Preoperative preparation is carried out for 4 - 8 weeks with spironolactone at a dose of 200 - 400 mg / day. With unilateral adrenalectomy replacement therapy glucocorticosteroids are 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 it is severe and accompanied by clinical symptoms hypokalemia 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 dexamethasone at a dose of 0.5-1.0 mg/day.