Синдром Конна: диагностика, симптомы и лечение гиперальдостеронизма.

Many patients experience fatigue, potassium deficiency and high blood pressure which may cause poor vision, confusion or headaches. Symptoms may also include: muscular aches and weakness, muscle spasms, low back and flank pain from the kidneys, trembling, tingling sensations, dizziness/vertigo, nocturia and excessive urination. PA is under diagnosed; the Endocrine Society recommends screening people with high blood pressure who are at increased risk, while others recommend screening all people with high blood pressure for the disease. Screening is usually done by measuring the aldosterone to renin ratio in the blood (ARR) whilst off interfering medications and a serum potassium over 4, with further testing used to confirm positive results. Some cases may be cured by removing the adenoma by surgery after localization with adrenal venous sampling (AVS). A single adrenal gland may also be removed in cases where only one is enlarged. In cases due to enlargement of both glands, treatment is typically with medications known as aldosterone antagonists such as spironolactone or eplerenone. Conn's syndrome is named after Jerome W. Conn (1907–1994), an American endocrinologist who first described adenomas as a cause of the condition in 1955.

People often have few or no symptoms.

Aldosterone has effects on most or all cells of the body but, clinically, the most important actions are in the kidney, on cells of the late distal convoluted tubule and medullary collecting duct. In the principal cells aldosterone increases activity of basolateral membrane sodium potassium ATPase and apical epithelial sodium channels, ENaC, as well as potassium channels, ROMK. These actions increase sodium reabsorption and potassium secretion. Since more sodium is reabsorbed than potassium secreted, it also makes the lumen more electrically negative, causing chloride to follow sodium. Water then follows sodium and chloride by osmosis. In Conn syndrome, these actions cause increased extracellular sodium and fluid volume and reduced extracellular potassium. Aldosterone also acts on intercalated cells to stimulate an apical proton ATPase, causing proton secretion that acidifies urine and alkalizes extracellular fluid. In summary, hyperaldosteronism causes hypernatremia, hypokalemia, and metabolic alkalosis. A high aldosterone to renin ratio suggests the presence of primary hyperaldosteronism. The diagnosis is made by performing a saline suppression test, ambulatory salt loading test, or fludrocortisone suppression test. Measuring sodium and potassium concentrations simultaneously in serum and urine specimens has been suggested for screening purposes. Calculating the serum sodium over urinary sodium to serum potassium over urinary potassium (SUSPUP) and the (serum sodium to urinary sodium to (serum potassium)2 (SUSPPUP) ratios delivers calculated structure parameters of the RAAS, which may be used as a static function test. Its results have to be confirmed by calculating the ARR. If primary hyperaldosteronism is confirmed biochemically, CT scanning or other cross sectional imaging can confirm the presence of an adrenal abnormality, possibly an adrenal cortical adenoma (aldosteronoma), adrenal carcinoma, bilateral adrenal hyperplasia, or other less common changes. Imaging findings may ultimately lead to other necessary diagnostic studies, such as adrenal venous sampling, to clarify the cause. It is not uncommon for adults to have bilateral sources of aldosterone hypersecretion in the presence of a nonfunctioning adrenal cortical adenoma, making adrenal venous sampling (AVS) mandatory in cases where surgery is being considered. or PET/CT with 11C Metomidate is an option. Since 11C Metomidate is unspecific for CYP11B1/CYP11B2 the patient needs pre treatment with dexamethasone to downregulate the expression of CYP11B1. The diagnosis is best accomplished by an appropriately trained subspecialist, though primary care providers are critical in recognizing clinical features of primary aldosteronism and obtaining the first blood tests for case detection.

Some people only use Conn's syndrome for when it occurs due to an adrenal adenoma (a type of benign tumor). In practice, however, the terms are often used interchangeably, regardless of the underlying physiology. In the absence of treatment, individuals with hyperaldosteronism often have poorly controlled high blood pressure, which may be associated with increased rates of stroke, heart disease, and kidney failure. With appropriate treatment, the prognosis is considered good. Esaxerenone, the first non steroidal mineralocorticoid blocker, was approved in 2019 in Japan to treat essential hypertension. Finerenone, a drug belonging to the same class, reached phase 3 clinical trial in 2020, but is not yet considered for hypertension. More importantly, next generation Aldosterone Synthase Inhibitors have entered the research pipeline with CIN 107 undergoing Phase 2 clinical trial as of 2021

In the past, the prevalence of primary aldosteronism was considered to be less than 1% of patients with hypertension. More recent studies have reported much higher prevalence of primary aldosteronism, up to 12.7% in primary care and to 29.8% in referral centers. Very low rates of compliance with screening guidelines lead to the underdiagnoses of primary aldosteronism.

The Primary Aldosteronism Foundation is a patient driven initiative committed to creating the paradigm shift that will lead to optimum diagnosis and treatment of primary aldosteronism by raising awareness, fostering research, and providing support to patients and healthcare professionals worldwide.

Conn's syndrome is named after Jerome W. Conn (1907–1994), the American endocrinologist who first described the condition at the University of Michigan in 1955.