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, 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. 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 possible reason 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, laboratory data and instrumental methods research set clinical diagnosis: Primary hyperaldosteronism (aldosteroma of the left adrenal gland), first identified in the form of hypokalemic syndrome, neurological symptoms, sinus tachycardia. Hypokalemic periodic convulsions with generalized muscle weakness. Hypertension, stage 3, stage 1. 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 both a crisis course (up to 50%) and 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 in order 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 research consists of determining plasma aldosterone levels and plasma renin activity (PRA). Tests should be performed when the patient refuses medications that affect the renin-angiotensin system (for example, 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 ARP, with a ratio of plasma aldosterone (in nanograms/dL) to ARP [in nanograms/(mlh)] greater than 20.
Definition of the concept
In 1955, Cohn described a syndrome characterized by arterial hypertension and decreased serum potassium levels, the development of which is associated with aldosteroma (adenoma of the adrenal cortex that secretes aldosterone).
Primary hyperaldosteronism is more common in adults, affecting women more often (ratio 3:1) aged 30-40 years. Among children, the incidence of the disease is the same in girls and boys.
Causes of the disease
1. Aldosteromas (Conn syndrome)
2. Bilateral adrenal hyperplasia or multiple adenomatosis of the adrenal cortex (15%):
a) idiopathic hyperaldosteronism (hyperproduction of aldosterone is not suppressed);
3. Aldosterone-producing adenoma is completely suppressed by glucocorticoids.
4. Carcinoma of the adrenal cortex.
5. Extra-adrenal hyperaldosteronism
Mechanisms of occurrence and development of the disease (pathogenesis)
1. Aldosteromas (Conn syndrome)- aldosterone-producing adrenal tumor (70% of cases of primary hyperaldosteronism). Aldosterone-producing adenoma of the adrenal cortex is usually unilateral, no more than 4 cm in size. Multiple and bilateral adenomas are extremely rare. Adrenal cancer as a cause of aldosteronism is also uncommon - 0.7-1.2%. In the presence of an adenoma, aldosterone biosynthesis does not depend on ACTH secretion.
2. Bilateral adrenal hyperplasia(30% of cases) or multiple adenomatosis of the adrenal cortex (15%):
a) idiopathic hyperaldosteronism (overproduction of aldosterone, not suppressed);
b) undefined hyperaldosteronism (overproduction of aldosterone, selectively suppressed);
c) hyperaldosteronism, completely suppressed by glucocorticoids.
3. Aldosterone-producing adenoma, is completely suppressed by glucocorticoids.
4. Carcinoma of the adrenal cortex.
A relatively rare cause of primary aldosteronism is a malignant tumor of the adrenal cortex.
5. Extra-adrenal hyperaldosteronism (tumor of the ovaries, intestines, thyroid gland).
Malignant tumors account for 2-6% of all cases.
Clinical picture of the disease (symptoms and syndromes)
1. Arterial hypertension. Persistent hypertension is sometimes accompanied by severe headaches in the forehead. Hypertension is stable, but paroxysms are also possible. Malignant hypertension is very rare.
Hypertension does not respond to orthostatic load (renin-dependent reaction), resistant to the Valsalva maneuver (during the test, blood pressure does not increase, unlike other types of hypertension).
Blood pressure is corrected with spironolactone (400 mg/day for 10-15 days), as is hypokalemia.
2. "Kalipenic kidney"
In almost all cases, primary aldosteronism is accompanied by hypokalemia due to excessive renal potassium loss under the influence of aldosterone. Potassium deficiency causes the formation of a “kaliopenic kidney.” The epithelium of the distal renal tubules is affected, in combination with general hypokalemic alkalosis, leading to disruption of the mechanisms of oxidation and concentration of urine.
In the initial stages of the disease renal disorders may be insignificant.
1) Polyuria, mainly nocturnal, reaches 4 liters per day, nocturia (70% of patients). Polyuria in primary hyperaldosteronism is not suppressed by vasopressin drugs and does not decrease with fluid intake restriction.
2) Characteristic hypoisosthenuria - 1008-1012.
3) Transient, moderate proteinuria is possible.
4) The urine reaction is often alkaline, which increases the frequency of concomitant pyelitis and pyelonephritis.
Thirst and compensatory polydipsia develop as a reaction to polyuria. Polydipsia and polyuria at night, along with neuromuscular manifestations (weakness, paresthesia, myoplegic attacks) are mandatory components of the hypokalemic syndrome. Polydipsia has a central genesis (hypokalemia stimulates the thirst center) and reflex genesis (due to the accumulation of sodium in the cells).
Edema is not typical - only in 3% of patients with concomitant kidney damage or circulatory failure. Polyuria and sodium accumulation in cells do not contribute to fluid retention in the interstitial space.
3. Muscle damage. Muscle weakness, pseudoparalysis, periodic attacks of convulsions of varying intensity, tetany, obvious or latent, is observed. Possible twitching of facial muscles, positive symptoms Chvostek and Trousseau. Elevated electric potential in the rectum. Characteristic paresthesias in various muscle groups.
4. Changes in the central and peripheral nervous system
General weakness occurs in 20% of patients. Headaches are observed in 50% of patients and are intense - caused by increased blood pressure and hyperhydration of the brain.
5. Disturbance of carbohydrate metabolism.
Hypokalemia suppresses insulin secretion and contributes to the development of reduced tolerance to carbohydrates (60% of patients).
Diagnosis of the disease
1. Hypokalemia
Increased urinary potassium excretion (normal 30 mmol/l).
2. Hypernatremia
3. Hyperosmolarity
Specific stable hypervolemia and high plasma osmolarity. The 20% to 75% increase in intravascular volume is unaffected by saline or albumin administration.
Alkalosis is present in 50% of patients - blood pH reaches 7.60. Increased blood bicarbonate content up to 30-50 mmol/l. Alkalosis is combined with a compensatory decrease in the level of chlorine in the blood. The changes are enhanced by salt intake and are eliminated by spironolactone.
4. Hormonal imbalance
The level of aldosterone in the blood is often elevated from a norm of 2-16 ng/100 ml to 50 ng/100 ml. Blood sampling should be carried out when horizontal position sick. Increased levels of aldosterone metabolites in the blood. Changes in the daily profile of aldosterone secretion: determination of the level of aldosterone in the blood serum at 8 a.m. and at 12 p.m. With aldosterome, the content of aldosterone in the blood at 12 o'clock in the afternoon is lower than at 8 o'clock in the morning, while with small or large nodular hyperplasia, the concentration of aldosterone during these periods remains almost unchanged or is slightly higher at 8 o'clock in the morning.
Increased urinary excretion of aldosterone.
Reduced unstimulated plasma renin activity - cardinal symptom primary hyperaldosteronism. Renin secretion is suppressed by hypervolemia and hyperosmolarity. In healthy people, the renin content in the blood in a horizontal position is 0.2-2.7 ng/ml/hour.
The criterion for the diagnosis of primary hyperaldosteronism syndrome is a combination of reduced plasma renin activity with hyperaldosteronemia. Differential diagnostic criterion from secondary hyperaldosteronism in renovascular hypertension, chronic renal failure, renin-forming kidney tumor, malignant arterial hypertension, when both the levels of renin and aldosterone are increased.
5. Functional tests
1. Sodium load 10 g/day for 3-5 days. In practically healthy individuals with normal regulation of aldosterone secretion, the serum potassium level will remain unchanged. With primary aldosteronism, the potassium content in the blood serum decreases to 3-3.5 mmol/l, the excretion of potassium in the urine increases sharply, and the patient’s condition worsens (severe muscle weakness, cardiac arrhythmia).
2. 3-day low (20 mEq/day) sodium diet - renin levels remain unchanged, aldosterone levels may even decrease.
3. Test with furosemide (Lasix). Before the test, the patient must be on a diet with normal content sodium chloride (about 6 g per day), do not receive any antihypertensive drugs for a week and do not take diuretics for 3 weeks. During the test, the patient takes 80 mg of furosemide orally and remains in an upright position (walks) for 3 hours. After 3 hours, blood is drawn to determine renin and aldosterone levels. With primary aldosteronism, there is a significant increase in aldosterone levels and a decrease in the concentration of renin in the blood plasma.
4. Test with capoten (captopril). In the morning, blood is taken from the patient to determine the content of aldosterone and renin in the plasma. Then the patient takes 25 mg of capoten orally and remains in a sitting position for 2 hours, after which his blood is taken again to determine the content of aldosterone and renin. In patients with essential hypertension, as well as in healthy people, there is a decrease in aldosterone levels due to inhibition of the conversion of angiotensin I to angiotensin II. In patients with primary aldosteronism, the concentration of aldosterone is increased, the ratio of aldosterone/renin activity is more than 50.
5. Spironolactone test. The patient is on a diet with a normal sodium chloride content (6 g per day) and receives the aldosterone antagonist aldactone (veroshpiron) 100 mg 4 times a day for 3 days. On the 4th day, potassium content is determined in the blood serum, and an increase in its blood level by more than 1 mmol / l compared with entry level is confirmation of the development of hypokalemia due to excess aldosterone. The level of aldosterone and renin in the blood remains unchanged. Arterial hypertension is eliminated.
6. Test with non-aldosterone mineralocorticoids. The patient takes 400 mcg of fluorocortisol acetate for 3 days or 10 mg of deoxycorticosterone acetate for 12 hours. The level of aldosterone in the blood serum and the excretion of its metabolites in the urine do not change with primary aldosteronism, whereas with secondary hyperaldosteronism it decreases significantly. In some cases, there is a slight decrease in the level of aldosterone in the blood, also with aldosterome.
7. Test with DOX. Prescribe DOXA 10-20 mg/day for 3 days. In patients with secondary hyperaldosteronism, the level of aldosterone decreases, but in Cohn syndrome - not. Levels of glucocorticosteroids and androgens are normal.
8. Orthostatic test (walking for 4 hours). Unlike healthy people, aldosterone levels paradoxically decrease.
9. Topical diagnosis of adrenal lesions. Aldosteroma adenomas are small in size, less than 3 cm in diameter in 80% of patients, and are often located in the left adrenal gland.
10. Computed tomography is the most informative study with high sensitivity. In 90% of patients, tumors with a diameter of 5-10 mm are detected.
11. Scanning of the adrenal glands with I-131-iodine-cholesterol against the background of inhibition of glucocorticoid function by dexamethasone (0.5 mg every 4 hours for 4 days). Asymmetry of the adrenal glands is characteristic. Sensitivity - 85%.
12. Catheterization of the adrenal veins with bilateral selective blood sampling and determination of aldosterone levels in them. The sensitivity of the study increases after preliminary stimulation of the adenoma with synthetic ACTH - the production of aldosterone on the tumor side increases sharply. The sensitivity of the study is 90%.
13. X-ray contrast venography of the adrenal glands - the sensitivity of the method is 60%: the vascularization of the tumor is insignificant, the size is small.
14. Echography of the adrenal glands.
15. Suprarenorography under conditions of pneumoretroperitonium, combined with or without intravenous urography. The method is informative only for large tumors and more often gives false negative results. The small size of the aldosteres, located inside, rarely change the contours of the adrenal glands.
Differential diagnosis
1. Secondary aldosteronism (hyperreninemic hyperaldosteronism) - conditions in which increased formation of aldosterone is associated with long-term stimulation of its secretion by angiotensin II. Secondary aldosteronism is characterized by increased levels of renin, angiotensin and aldosterone in the blood plasma. Activation of the renin-angiotensin system occurs due to a decrease in effective blood volume while simultaneously increasing the negative balance of sodium chloride. Develops with nephrotic syndrome, liver cirrhosis in combination with ascites, idiopathic edema, which often occurs in premenopausal women, congestive heart failure, and renal tubular acidosis.
2. Barter syndrome: hyperplasia and hypertrophy of the juxtaglomerular apparatus of the kidneys with hyperaldosteronism. Excessive potassium loss in this syndrome is associated with changes in the ascending tubules and a primary defect in chloride transport. Characterized by dwarfism, delayed mental development, the presence of hypokalemic alkalosis with normal blood pressure.
3. Tumors that produce renin (primary reninism), including Wilms tumors (nephroblastoma) - secondary aldosteronism occurs with arterial hypertension. Malignant hypertension with damage to the vessels of the kidneys and retina, it is often combined with increased secretion of renin and secondary aldosteronism. Increased renin formation is associated with the development of necrotizing renal arteriolitis. After nephrectomy, both hyperaldosteronism and hypertension disappear.
4. Long-term use of thiazide diuretics for arterial hypertension causes secondary aldosteronism. Therefore, determination of the level of renin and aldosterone in the blood plasma should be carried out only 3 weeks or later after discontinuation of diuretics.
5. Long-term use of contraceptives containing estrogen leads to the development of arterial hypertension, an increase in the level of renin in the blood plasma and secondary aldosteronism. The increase in renin formation is associated with the direct effect of estrogens on the liver parenchyma and an increase in the synthesis of the protein substrate - angiotensinogen.
6. Pseudomineralocorticoid hypertensive syndrome is accompanied by arterial hypertension, a decrease in the content of renin and aldosterone in the blood plasma. It develops with excessive consumption of glycyrrlisic acid preparations (glycyram, sodium glycyrinate), contained in the rhizomes of Ural licorice or licorice glabra.
7. Liddle syndrome - hereditary disease accompanied by increased sodium reabsorption into renal tubules with the subsequent development of arterial hypertension, a decrease in the content of potassium, renin and aldosterone in the blood.
8. Ingestion or excess production of deoxycorticosterone in the body leads to sodium retention, excess potassium excretion and hypertension. With a congenital disorder of cortisol biosynthesis distal to 21-hydroxylase, namely with deficiency of 17a-hydroxylase and 11b-hydroxylase, excessive formation of deoxycorticosterone occurs with the development of the corresponding clinical picture.
9. Hypertension with a low content of renin in the blood plasma (low-renin arterial hypertension) accounts for 20-25% of all patients suffering from this disease. The use of steroidogenesis inhibitors in hypertensive patients with low renin levels led to normalization of blood pressure, whereas in hypertensive patients with normal renin levels such treatment was ineffective. Normalization of blood pressure was observed in such patients after bilateral total adrenalectomy. It is possible that low-renin hypertension is a hypertensive syndrome that develops due to excess secretion of as yet unidentified mineralocorticoids.
Increased aldosterone levels (hyperaldosteronism) are one of the causes of increased blood pressure, cardiovascular complications, decreased kidney function and changes in electrolyte ratios. Primary and secondary hyperaldosteronism are classified, based on different etiological factors and pathogenetic mechanisms. The most common cause of the development of the primary type of pathology is Conn's syndrome.
- 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).
- kidney diseases (nephrotic syndrome, renal artery stenosis, kidney tumors, etc.);
- heart disease (congestive heart failure);
- other causes (hypersecretion of ACTH, taking diuretics, liver cirrhosis, fasting)
- 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).
- 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.
- 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).
- 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.
- 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.
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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: | Associated with pathology of other organs and systems: |
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 abdominal cavity. 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.
In the pathogenesis of Conn's syndrome main role excess aldosterone plays a role. 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 volume of circulating blood (CBV), which entails an increase 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, muscle weakness. It has been noted that patients have a sharply increased risk sudden death from cardiovascular accidents (on average 10–12 times).
Clinic
Symptoms of primary hyperaldosteronism develop gradually. Patients with Conn's syndrome are diagnosed with:
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), if hypertension occurs before age 40, with a family history of cardiovascular diseases, as well as if relatives have a confirmed diagnosis of PHA. Laboratory diagnostics is quite difficult and requires confirmation using functional tests and instrumental research methods.
Laboratory research
After forming a risk group, patients are determined:
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 :
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:
Differential diagnosis of Conn's syndrome is carried out with idiopathic hyperplasia of the adrenal cortex, with secondary hyperaldosteronism, essential hypertension, endocrine diseases accompanied by increased blood pressure (Itsenko-Cushing syndrome, pheochromocytoma), with a hormonally inactive neoplasm and cancer. A malignant aldosterone-producing tumor on CT can reach large sizes and is characterized by high density, inhomogeneity, and blurred contours.
Differential diagnosis:
| Conn's syndrome (aldosterone-producing adenoma) | Idiopathic hyperaldosteronism | Secondary hyperaldosteronelowness | |
| Laboratory indicators | aldosterone, ↓↓renin, ARS, ↓potassium | aldosterone, renin, - APC, ↓potassium | |
| Orthostatic (march) test - study of aldosterone levels upon awakening in a horizontal position, repeated study after being in a vertical position (walking) for 3 hours | High aldosterone levels initially, some decrease with repeated testing, or at the same level | Increased aldosterone levels (maintained sensitivity to AT-II) | Increased aldosterone levels |
| CT | small mass formation of one of the adrenal glands | the adrenal glands are not changed, or there are small nodular formations on both sides | The adrenal glands are not enlarged, the size of the kidneys may be reduced |
| Catheterization of adrenal veins with selective blood sampling | Lateralization | - | - |
Treatment
For aldosteroma, laparoscopic adrenalectomy is performed (after 4 weeks of preoperative preparation on an outpatient basis). Drug treatment carried out in case of contraindications to surgery or other forms of hyperaldosteronism:
Spironolactone is used to treat idiopathic HA. To reduce blood pressure, it is necessary to add saluretics, calcium antagonists, ACE inhibitors and angiotensin II antagonists. If differential diagnosis reveals glucocorticoid-suppressed hyperaldosteronism, dexamethasone is prescribed.
Aldosteronism is a clinical syndrome associated with increased production of the adrenal hormone aldosterone in the body. There are primary and secondary aldosteronism. Primary aldosteronism (Conn's syndrome) occurs with a tumor of the adrenal gland. It is manifested by increased blood pressure, changes in mineral metabolism (the content in the blood sharply decreases), muscle weakness, seizures, and increased excretion of aldosterone in the urine. Secondary aldosteronism is associated with increased production of aldosterone by the normal adrenal glands due to excessive stimuli regulating its secretion. It is observed in heart failure, some forms of chronic nephritis and cirrhosis of the liver.
Disturbances of mineral metabolism in secondary aldosteronism are accompanied by the development of edema. With kidney damage, aldosteronism increases. Treatment of primary aldosteronism is surgical: removal of the adrenal tumor leads to recovery. In case of secondary aldosteronism, along with the treatment of the disease that caused aldosteronism, aldosterone blockers (aldactone 100-200 mg 4 times a day orally for a week) and diuretics are prescribed.
Aldosteronism is a complex of changes in the body caused by increased secretion of aldosterone. Aldosteronism can be primary or secondary. Primary aldosteronism (Conn's syndrome) is caused by overproduction of aldosterone by a hormonally active tumor of the adrenal gland. Clinically manifested by hypertension, muscle weakness, seizures, polyuria, a sharp decrease in potassium content in the blood serum and increased excretion of aldosterone in the urine; As a rule, there is no swelling. Removal of the tumor leads to a decrease in blood pressure and normalization of electrolyte metabolism.
Secondary aldosteronism is associated with dysregulation of aldosterone secretion in the zona glomerulosa of the adrenal glands. A decrease in the volume of the intravascular bed (as a result of hemodynamic disorders, hypoproteinemia or changes in the concentration of electrolytes in the blood serum), an increase in the secretion of renin, adrenoglomerulotropin, ACTH leads to hypersecretion of aldosterone. Secondary aldosteronism is observed in heart failure (congestion), liver cirrhosis, edematous and edematous-hypertensive forms of chronic diffuse glomerulonephritis. The increased aldosterone content in these cases causes increased sodium reabsorption in the renal tubules and thereby may contribute to the development of edema. In addition, increased aldosterone secretion during hypertensive form diffuse glomerulonephritis, pyelonephritis or occlusive lesions of the renal arteries, as well as hypertension V late stages its development and malignant course leads to the redistribution of electrolytes in the walls of arterioles and to increased hypertension. Suppression of the action of aldosterone at the level of the renal tubules is achieved by using its antagonist, aldactone, 400-800 mg per day per os for a week (under the control of the excretion of electrolytes in the urine) in combination with conventional diuretics. To suppress aldosterone secretion (in edematous and edematous-hypertensive forms of chronic diffuse glomerulonephritis, liver cirrhosis), prednisolone is prescribed.
Aldosteronism. There are primary (Conn's syndrome) and secondary hyperaldosteronism. Primary hyperaldosteronism was described by J. Conn in 1955. In the occurrence of this clinical syndrome The leading role belongs to the production of excess aldosterone by the adrenal cortex.
In the majority of patients (85%), the cause of the disease is an adenoma (synonymous with “aldosteroma”), less commonly, bilateral hyperplasia (9%) or carcinoma of the adrenal cortex of the zona glomerulosa and zona fasciculata.
More often the syndrome develops in women.
Clinical picture (symptoms and signs). With the disease, periodic attacks of convulsions are observed in various muscle groups with normal level calcium and phosphorus in the blood, but with the presence of alkalosis outside the cells and acidosis inside the cells, positive Trousseau and Chvostek signs, severe headaches, sometimes attacks of muscle weakness, lasting from several hours to three weeks. The development of this phenomenon is associated with hypokalemia and depletion of potassium reserves in the body.
The disease develops arterial hypertension, polyuria, polydipsia, nocturia, severe inability to concentrate urine during dry eating, resistance to antidiuretic drugs, etc. The level of antidiuretic hormone is normal. Hypochloremia, achylia, alkaline urine reaction, periodic proteinuria, and decreased levels of potassium and magnesium in the blood are also noted. The sodium content increases, less often remains unchanged. As a rule, there is no swelling. On ECG changes myocardium, characteristic of hypokalemia (see Hegglin syndrome).
Urinary 17-hydroxycorticoid and 17-ketosteroid levels are normal, as are plasma ACTH levels.
Children with Conn's syndrome have growth retardation.
The oxygen content in arterial blood is reduced. The content of uropepsin in patients is increased.
Diagnostic methods. Suprapneumoreno-radiography and tomography, determination of aldosterone and potassium in urine and blood.
Treatment is surgical, adrenalectomy is performed.
The prognosis is favorable, but only until malignant hypertension develops.
Secondary hyperaldosteronism. The symptoms are the same as in Conn's syndrome, which develops in a number of conditions in the form of hypersecretion of aldosterone in response to stimuli originating outside the adrenal glands and acting through physiological mechanisms that regulate aldosterone secretion. Secondary hyperaldosteronism associated with edematous conditions leads to: 1) congestive heart failure; 2) nephrotic syndrome; 3) cirrhosis of the liver; 4) “idiopathic” edema.
Loss of significant amounts of fluids with untreated diabetes insipidus and diabetes mellitus, nephritis with loss of salts, sodium restriction in the diet, use of diuretics, excessive physical stress also cause secondary hyperaldosteronism.
The adrenal cortex is responsible for the synthesis of three groups of hormones. The cells of this endocrine organ also produce mineralocorticoids. The main representative of this class of hormones is aldosterone.
Normally, aldosterone is released under the control of the renin-angiotensin system in the blood. The hormone increases urinary potassium loss and sodium retention.
If there is too much aldosterone, hyperaldosteronism is diagnosed. This condition can be caused by both adrenal pathology and systemic disorders.
Primary hyperaldosteronism is called Conn's syndrome. This disease is based on excessive secretion of the hormone in the zona glomerulosa of the adrenal cortex.
Conn's syndrome is diagnosed three times more often in women than in men. Symptoms of the disease usually appear between the ages of 30 and 40.
Causes of primary hyperaldosteronism
Conn's syndrome can develop due to various pathological processes.
Excess mineralocorticoid secretion is caused by:
- hyperplasia of the adrenal cortex;
- aldosteroma (benign tumor of the zona glomerulosa);
- carcinoma (malignant tumor).
About 30–40% of primary hyperaldosteronism is associated with cortical hyperplasia. Unilateral adenoma causes 60% of all cases of Conn's syndrome. Frequency malignant tumors accounts for 0.7–1% in the morbidity structure.
Symptoms of hyperaldosteronism are the same for everyone etiological factors. Excessive hormone secretion in Conn's syndrome leads to severe electrolyte disturbances. Both tumors and hyperplastic cortex do not respond to the regulatory action of the renin-angiotensin system. Primary hyperaldosteronism has the properties of autonomy, that is, independence.
Clinical picture of the syndrome
Primary hyperaldosteronism has three characteristic groups of symptoms.
Highlight:
- cardiovascular;
- neuromuscular;
- renal components.
Changes in the volume of circulating blood and disturbances in the functioning of the heart muscle are manifested by arterial hypertension, heart failure, and vascular accidents (stroke, heart attack).
Patients are concerned about headaches, shortness of breath, decreased tolerance to physical activity, weakness, fatigue, heaviness behind the sternum.
When monitoring blood pressure, persistent hypertension is recorded. Patients have high numbers of both systolic and diastolic pressure. Treatment of hypertension in Conn's syndrome is practically ineffective. All modern antihypertensive drugs and their combinations cannot maintain normal blood pressure in the patient.
As a result, target organ damage quickly develops. When examining the fundus, angiopathy, hemorrhages, and retinal detachment can be detected. In severe cases, these changes cause blindness. The heart muscle undergoes hypertrophy. Thickening of the myocardial wall is accompanied by a disruption of its oxygen supply and nutrients. Because of this, the heart becomes less resistant to stress. The left ventricular ejection fraction falls, and heart failure appears.
The neuromuscular component of Conn's syndrome is associated with changes in the ratio of potassium and sodium levels in the blood. Patients with primary hyperaldosteronism complain of muscle weakness, discomfort in the extremities (coldness, “goosebumps”), convulsions. Sometimes complete or partial paralysis may develop.
Kidney damage in primary hypercortisolism syndrome is explained by excess potassium in the urine. Patients are concerned about severe thirst and dry mouth. The volume of urine per day may be higher than normal. Typically, nighttime diuresis predominates over daytime diuresis.
Urine tests reveal low density, alkaline reaction, proteinuria (protein). Long-term primary hyperaldosteronism can cause chronic renal failure.
Examination for hyperaldosteronism syndrome
If the doctor suspects the patient has Conn's syndrome, then further diagnostic testing is necessary.
To clarify the status you need:
- identify high level aldosterone;
- prove the primary nature of the disease;
- assess the condition of the adrenal glands (find a tumor).
Assessing the concentration of the hormone in the blood is not always easy. Aldosterone levels, even in Conn's syndrome, are prone to rapid changes. The most accurate study is considered to be an analysis of the ratio of plasma aldosterone and renin. In addition, the patient must have their blood potassium level determined.
In primary hyperaldosteronism, aldosterone is higher than normal, potassium and renin are reduced.
For diagnostics, special tests have been proposed and successfully used. They are usually performed in a hospital setting after hospitalization.
Endocrinologists carry out tests:
- with sodium chloride;
- with hypothiazide;
- with spironolactone.
Assessment of the state of the adrenal cortex is possible different ways. Diagnosis begins with ultrasound examination. A more accurate CT scan may then be required.
If the tumor is small (up to 1 cm), then angiography is considered the most informative. It is advisable to combine it with blood samples from the vessels of the adrenal glands.
Treatment of the disease
Primary hyperaldosteronism begins to be treated conservatively. The patient is prescribed spironolactone tablets. In addition, antihypertensive drugs are used cardiovascular drugs. Further tactics depend on the results of ultrasound and tomography. If a tumor is found in the adrenal glands, then it is necessary to carry out surgery. After removing the formation, it is examined under a microscope. If signs of malignancy are found, then further tactics determined by the oncologist.
In the event that there is no bulky neoplasm in the adrenal glands, then surgery no need. The patient continues to receive medicines according to the scheme and regularly undergoes control examinations. Visits to an endocrinologist are necessary every few months. Monitoring blood tests is needed even more often. Medical observation includes assessment of symptoms, blood pressure measurement, electrocardiogram, blood sampling for electrolytes, aldosterone, plasma renin. Every year, all patients with primary idiopathic hyperaldosteronism are recommended to undergo an ultrasound scan of the adrenal glands, computed tomography or angiography. If a tumor is found in one of the control examinations, it is recommended surgery. The operation is carried out after planned training(correction of blood composition and cardiac activity).
