Primary Hyperaldosteronism (Conn’s Syndrome)

What is Primary Hyperaldosteronism (Conn’s Syndrome)?

In 1955, Conn described the syndrome, accompanied by arterial hypertension and a decrease in the level of potassium in the blood, the development of which is associated with a tumor (adenoma) of the adrenal cortex, which produces the hormone aldosterone. This pathology is called Conn syndrome.

Primary hyper aldosteronism (Conn’s syndrome) is a disease characterized by an increase in aldosterone secretion by the adrenal glands, manifested in a decrease in the activity of a specific substance, plasma renin, which plays an important role in regulating the body’s work, arterial hypertension and a decrease in the potassium content in the blood. Many other cases of hyperplasia (excessive tissue proliferation and its changes) of the adrenal cortex with an increase in aldosterone secretion were later described, and now the term “primary hyperaldosteronism” is used to describe both Conn’s syndrome itself and another pathology accompanied by hypersecretion of aldosterone, for example, hyperplasia of the cortex adrenal glands. Currently, primary hyper aldosteronism (PHA), and in particular Conn’s syndrome, is the most common cause of secondary arterial hypertension.

Causes of Primary Hyperaldosteronism (Conn Syndrome)

Currently, there are two main causes of PHA, accompanied by an increase in aldosterone secretion:

  • unilateral aldosterone-producing tumor – adenoma or Conn’s syndrome (50-60% of cases);
  • bilateral hyperplasia of the adrenal cortex or idiopathic hyper aldosteronism (40-50% of cases).

There are rare diseases and tumors that are similar in symptoms, including a hereditary disease, accompanied by an increase in aldosterone concentration.

Even less often, aldosterone-secreting adrenal cortex or ovarian tumors are found.

The most common cause of PHA is Conn syndrome, and the adenoma usually does not exceed 3 cm in diameter, is unilateral and renin-independent. This means that the secretion of aldosterone does not depend on a change in body position. Less commonly, an adenoma can be renin-dependent (that is, aldosterone levels increase in an upright position). Conn syndrome occurs in 50-60% of cases.

The remaining 40-50% of cases occur in bilateral hyperplasia of the adrenal cortex, when the level of aldosterone increases in an upright position. Less common is primary adrenal hyperplasia, in which the level of aldosterone does not depend on the position of the body, as in renin-independent adenoma.

Aldosterone can secrete tumors of extra-adrenal localization – in the kidneys or ovaries.

Symptoms of Hyperaldosteronism Primary (Conn’s Syndrome)

Complaints of patients with severe hypokalemia: fatigue, muscle weakness, muscle cramps, headaches and heart attack. Such patients may also experience increased thirst: as a result, they drink a lot, and polyuria (a lot of urine is released) due to so-called diabetes insipidus, developed as a result of hypokalemia and corresponding changes in the kidneys, due to the effect of aldosterone on them.

Relative hypocalcemia develops (a decrease in calcium in the blood) with the development of numbness in the extremities and around the mouth, muscle spasms in the hands and feet and, to an extreme degree, laryngeal spasm with the appearance of a feeling of suffocation and cramps. In this case, calcium preparations are not prescribed, since the total calcium content in the blood is normal, but due to hormonal imbalance, the balance of calcium in the body changes.

Long-existing arterial hypertension can lead to complications of the cardiovascular and nervous systems with all the accompanying symptoms.

Diagnosis of Primary Hyperaldosteronism (Conn Syndrome)

There are no specific manifestations of Conn syndrome.

When patients develop heart failure, stroke, or intracranial hemorrhage due to increased blood pressure, the corresponding symptoms appear.

Laboratory research

  • Studies of sodium, potassium and calcium in blood plasma (biochemical analysis) may show an increase in sodium in the blood, the presence of hypokalemia and “alkalization” of the blood, which is a consequence of the action of aldosterone on the kidneys. A relative decrease in blood calcium can also be easily detected. In almost 20% of patients, a violation of carbohydrate metabolism (an increase in blood glucose) can be detected, although diabetes is rare. It should be noted that the normal content of potassium in the blood does not exclude PHA. Studies show that from 7 to 38% of patients with PHA have normal serum potassium levels. Hypokalemia develops when eating a significant amount of sodium.
  • A decrease in plasma renin level in patients with PHA is characteristic, and this figure does not rise above certain values ​​with the introduction of diuretics or the transition to an upright position (which usually happens normally). Some experts suggest an analysis of the level of renin in blood plasma to be considered a special test for the detection of PHA. However, according to some reports, reduced renin levels are also found in 30% of patients with hypertension. Therefore, low plasma renin levels should not be considered a specific test for PHA.
  • A sufficiently sensitive test for PHA should be considered as determining the ratio of plasma aldosterone activity (AAP) to plasma renin activity (ARP). The possible interactions of various drugs should be considered during the test.
  • With a positive test for AAP / ARP, the ratio is carried out by additional tests: determination of the level of aldosterone in the daily portion of urine adjusted for the level of potassium in the blood serum (since these indicators affect each other).

Instrumental examination

  • Computed tomography (CT) scan of the abdomen. It is a mandatory examination method in the case of PHA. With a diagnosis of PHA, the purpose of CT is to determine the type of pathology and the possibility of its surgical treatment (adrenal adenoma or bilateral hyperplasia). With CT, the volume of the operation is determined.
  • Scintigraphy with 131-I-iodocholesterol is used to detect unilateral functional (secreting hormones) adrenal gland formation. However, this procedure is not widespread due to the need for careful preparation of the patient, high cost and the fact that the method rarely reveals the formation of more than 1.5 cm in diameter.
  • Magnetic resonance imaging (MRI). Not a more sensitive method than CT.

Other diagnostic methods
Postural test (transition from horizontal to vertical position of the body). Can be used in the clinic for the initial diagnosis of renin-dependent adrenal adenoma. Currently rarely used.

Due to the difficulty of differentiating the diagnosis between adrenal hyperplasia and adenoma after a CT scan, a procedure can be performed to take an analysis directly from the adrenal vein. In this case, a catheter is inserted into the adrenal vein through a vein on the thigh. Blood tests are taken from both adrenal veins, as well as from the inferior vena cava. The level of aldosterone after maximum stimulation of ACTH is determined.

Treatment of Primary Hyperaldosteronism (Conn Syndrome)

The main goal is to prevent the occurrence of complications due to hypokalemia and arterial hypertension.

If with Conn’s syndrome, hypertension is corrected using unilateral adrenalectomy, then bilateral lesion is most often treated conservatively, since the effectiveness of unilateral or bilateral adrenalectomy is only 19%. In the case of adenoma, drug therapy is also carried out to control blood pressure and correct hypokalemia, which reduces the risk of subsequent surgery.

The main components of therapy:

  • A diet with a restriction of sodium intake (<2 g of sodium per day), maintaining optimal body weight, regular aerobic exercise.
  • The treatment of hypokalemia and arterial hypertension is to prescribe potassium-sparing drugs such as spironolactone. Moreover, if hypokalemia disappears almost immediately, then a decrease in blood pressure may require 4-8 weeks of therapy. Additional prescription of potassium preparations is not required. If, despite treatment, high blood pressure remains, second-line drugs are added to therapy.
  • Second-line drugs are: diuretics, drugs that lower blood pressure.

Surgery is the main treatment for Conn’s syndrome. If possible, a laparoscopic adrenalectomy is performed.

In patients with Conn’s syndrome, an indicator of the effectiveness of future unilateral adrenalectomy in relation to arterial hypertension is a decrease in blood pressure in response to spironolactone in the preoperative period. Spironolactone is prescribed for at least 1-2 weeks (preferably 6 weeks) prior to surgery to reduce the risk of surgery, correct hypokalemia, and establish control of blood pressure.

It should be noted that hypertension usually does not disappear immediately after surgery. Blood pressure gradually decreases over 3-6 months. Almost all patients report a decrease in blood pressure after surgery. A prolonged therapeutic effect is observed after unilateral adrenalectomy for Conn’s syndrome in an average of 69% of patients.