Symptoms of primary hyperaldosteronism

The clinical features of primary hyperaldosteronism consist of severe electrolyte imbalance, renal dysfunction, and arterial hypertension. Along with general and muscular weakness, which is often the first reason for seeking medical attention, patients are bothered by headaches, thirst, and increased, mainly nocturnal, urination. Changes in potassium and magnesium levels increase neuromuscular excitability and cause periodic seizures of varying intensity. Paresthesias in various muscle groups, twitching of facial muscles, positive Chvostek and Trousseau symptoms are characteristic.

Calcium metabolism is usually not affected. Periodic attacks of severe muscle weakness occur, up to complete immobilization of the lower extremities (pseudoparalysis) lasting from several hours to several days. One of the indirect symptoms that have diagnostic value is a significant increase in the electrical potential in the colon. Most symptoms of hyperaldosteronism (excluding hypertension) are nonspecific and are determined by hypokalemia and alkalosis.

The table summarizes the main symptoms of hyperaldosteronism (E. Glaz, based on Conn's works, 1971). Noteworthy is the asymptomatic course of the disease in 6% of patients and hypokalemia in 100%. At the same time, normokalemic forms of primary hyperaldosteronism are currently known. Casuistic normotensive variants of the disease, which retain all other features of typical primary hyperaldosteronism, are also reported. The most important, and in the early stages often the only symptom, is arterial hypertension. Dominant in the clinical picture for many years, it can mask the signs of hyperaldosteronism. The existence of low-renin hypertension (10-20% of all patients with hypertension) especially complicates the recognition of primary hyperaldosteronism. Hypertension can be stable or combined with paroxysms. Its level increases with the duration and severity of the disease, but malignant course is observed infrequently. Hypertension does not respond to orthostatic load, and during the Valsalva test its level in primary hyperaldosteronism does not increase, unlike hypertension of other etiologies. The introduction of spironolactones (veroshpiron, aldactone) in a daily dose of 400 mg for 10-15 days reduces hypertension simultaneously with normalization of the potassium level. The latter occurs only in patients with primary hyperaldosteronism. The absence of this effect casts doubt on the diagnosis of primary hyperaldosteronism, excluding those patients who have pronounced atherosclerosis. Half of the patients have retinopathy, but its course is benign, as a rule, without signs of proliferation, degeneration and hemorrhage. Hypertension of the left ventricle and signs of its overload on the ECG are noted in most cases. However, cardiovascular failure is not characteristic of primary hyperaldosteronism. Serious vascular changes occur only when the diagnosis has not been established for a long time. Although hypokalemia and hypokalemic alkalosis underlie many symptoms of primary hyperaldosteronism, the potassium level in the blood may fluctuate, so it is necessary to repeat the analysis. Its content increases and even normalizes with a long-term low-salt diet and the use of spironolactones. Hypernatremia is much less characteristic than hypokalemia, although sodium metabolism and its content in cells are increased.

Symptoms of Primary Hyperaldosteronism (Conn's Syndrome)

Symptoms	Frequency, %	Symptoms	Frequency, %
Hypertension	100	Hypernatremia	65
Hypokalemia	100	Decreased glucose tolerance	60
Hypochloremic alkalosis	100
Increased aldosterone levels	100	Headaches	51
Low renin levels	100	Retinopathy	50
Proteinuria	85	Thirst	46
Vasopressin-resistant hyposthenuria	80	Paresthesia	24
		Periodic paralysis	21
Urine oxidation disorder	80	Tetany	21
ECG changes	80	General weakness	19
Elevated potassium levels in urine	75	Muscle pain	10
Muscle weakness	73	Asymptomatic forms	6
Nocturnal polyuria	72	Edema	3

The absence of pronounced and stable hypernatremia is associated with a decrease in the sensitivity of the renal tubules to the sodium-retaining effect of aldosterone with increased secretion and excretion of potassium.

However, this refractoriness does not extend to the cation exchange mechanism of the salivary, sweat glands and intestinal mucosa. Potassium is excreted mainly by the kidneys and to a lesser extent through sweat, saliva, and the gastrointestinal tract. This loss (70% of intracellular reserves) reduces the potassium level not only in plasma, but also in erythrocytes, in smooth and striated muscle cells. Its excretion with urine exceeding 40 mEq/24 h raises suspicion of primary hyperaldosteronism. It should be noted that patients are unable to retain potassium in the body, its intake is ineffective, and a diet rich in sodium accelerates the excretion of potassium and aggravates clinical symptoms. On the contrary, a diet depleted in sodium limits the excretion of potassium, its level in the blood increases significantly. Hypokalemic damage to the renal tubular epithelium against the background of general hypokalemic alkalosis disrupts a number of renal functions, primarily the mechanisms of oxidation and concentration of urine. The "kalopenic kidney" is insensitive to endogenous (and exogenous) vasopressin, the level of which increases compensatorily and in connection with the high osmolarity of the plasma. Patients develop mild, periodic proteinuria, polyuria, nocturia, hypoisosthenuria with a relative density of individual portions of urine of 1008-1012.

Refractoriness to vasopressin administration is noted. Urine reaction is often alkaline. In the initial stages of the disease, renal impairment may be minor. Polydipsia is characteristic, which has a complex genesis: compensatory - in response to polyuria, central - as a result of the effect of low potassium levels on the thirst center, and reflex - in response to sodium retention in cells. Edema is not characteristic of primary hyperaldosteronism, since polyuria and sodium accumulation inside cells, and not in the interstitium, do not contribute to fluid retention in the intercellular spaces. Along with this, an increase in intravascular volume and its invariability upon administration of isotonic saline solution and even albumin are specific for primary hyperaldosteronism. Stable hypervolemia in combination with high plasma osmolarity suppresses ARP. Histochemical studies reveal the disappearance of renin granulations in the secretory cells of the vas efferens, a decrease in renin activity in renal homogenates and in renal biopsy of patients. Low, unstimulated ARP is a cardinal symptom of primary hyperaldosteronism in aldosteromas. The levels of secretion and excretion of aldosterone vary significantly in patients with primary hyperaldosteronism, but in most cases they are elevated, and the content of glucocorticoids and androgens is normal. The level of aldosterone and its immediate precursor, 18-hydroxycorticosterone, is higher in aldosteromas and lower in hyperplastic variants of primary hyperaldosteronism.

Long-term hypokalemia may cause a gradual decrease in aldosterone secretion. Unlike healthy individuals, its level paradoxically decreases with orthostatic load (4-hour walk) and spironolactone therapy. The latter block aldosterone synthesis in the tumor. In postoperative studies in patients who have received veroshpiron for a long time, the removed aldosterone-producing tissue does not respond to the addition of angiotensin II and ACTH. There are known cases of aldosterone producing 18-hydroxycorticosterone rather than aldosterone. The possibility of developing primary hyperaldosteronism due to increased production of other mineralocorticoids is not ruled out: corticosterone, DOC, 18-hydroxycorticosterone or as yet unknown steroids. The severity of primary hyperaldosteronism is determined by the intensity of metabolic disorders, their duration and the development of vascular complications. In general, the disease is characterized by a relatively benign course.

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