Primary aldosteronism

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Primary aldosteronism
Other namesPrimary hyperaldosteronism, Conn's syndrome
low salt diet[1]
Frequency10% of people with high blood pressure[1]

Primary aldosteronism (PA), also known as primary hyperaldosteronism, refers to the excess production of the hormone aldosterone from the adrenal glands, resulting in low renin levels and high blood pressure.[1] This abnormality is caused by hyperplasia or tumors. About 35% of the cases are caused by a single aldosterone-secreting adenoma, a condition known as Conn's syndrome.[7][8]

Many patients experience fatigue,

abnormal heart rhythms.[3][4]

Primary

adrenal cancer and an inherited disorder called familial hyperaldosteronism.[6] PA is under diagnosed; the Endocrine Society recommends screening people with high blood pressure who are at increased risk,[9] while others recommend screening all people with high blood pressure for the disease.[3] 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.[1] While low blood potassium is classically described in primary hyperaldosteronism, this is only present in about a quarter of people.[1] To determine the underlying cause, medical imaging is carried out.[1]

Some cases may be cured by removing the adenoma by surgery after localization with adrenal venous sampling (AVS).

low salt diet, e.g. DASH diet, may also be needed.[1][4] Some people with familial hyperaldosteronism may be treated with the steroid dexamethasone.[1]

Primary aldosteronism is present in about 10% of people with high blood pressure.

endocrinologist who first described adenomas as a cause of the condition in 1955.[11][12]

Signs and symptoms

People often have few or no symptoms.[1] They may get occasional muscular weakness, muscle spasms, tingling sensations, or excessive urination.[1]High blood pressure, manifestations of muscle cramps (due to hyperexcitability of neurons secondary to low blood calcium), muscle weakness (due to hypoexcitability of skeletal muscles secondary to hypokalemia), and headaches (due to low blood potassium or high blood pressure) may be seen.[citation needed]

Secondary hyperaldosteronism is often related to decreased cardiac output, which is associated with elevated renin levels.[13]

Causes

Two slices of an adrenal gland with a cortical adenoma, from a person with Conn's syndrome

The condition is due to:[14]

Genetics

40% of people with an adrenal aldosterone producing adenoma have somatic gain-of-function mutations in a single gene (KCNJ5).[15] This gene is mutated in inherited cases of early onset primary aldosteronism and bilateral adrenal hyperplasia, albeit less frequently.[16] These mutations tend to occur in young women with the adenoma in the cortisol secreting zona fasciculata. Adenomas without this mutation tend to occur in older men with resistant hypertension.[citation needed]

Other genes commonly mutated in aldosterone producing adenomas are

CTNNB1.[19]

Pathophysiology

Aldosterone has effects on most or all cells of the body but, clinically, the most important actions are in the

intercalated cells to stimulate an apical proton ATPase, causing proton secretion that acidifies urine and alkalizes extracellular fluid.[citation needed
]

In summary, hyperaldosteronism causes hypernatremia, hypokalemia, and metabolic alkalosis.[13]

Finer notes on aldosterone include the fact that it stimulates sodium-potassium ATPase in muscle cells, increasing intracellular potassium and also increases sodium reabsorption all along the intestine and nephron, possibly due to widespread stimulation of sodium-potassium ATPase. Finally, epithelial cells of sweat gland ducts and distal colon surface respond exactly the same as the principal cells of the nephron. These responses are important in climate adaptation and as a cause of constipation with elevated aldosterone[citation needed].

The sodium retention leads to plasma volume expansion and

angiotensin II) will not lead to a decrease in aldosterone levels (a very helpful clinical tool in diagnosis of primary hyperaldosteronism).[13]

Diagnosis

Screening may be considered in people with high blood pressure presenting with low blood potassium, high blood pressure that is difficult to treat, other family members with the same condition, or a mass on the adrenal gland.[1]

Measuring aldosterone alone is not considered adequate to diagnose primary hyperaldosteronism. Rather, both renin and aldosterone are measured, and a resultant aldosterone-to-renin ratio (ARR) is used for case detection.[20][21] 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.[22]

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.[23][24] Its results have to be confirmed by calculating the ARR.[citation needed]

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

CYP11B2 the patient needs pre-treatment with dexamethasone to downregulate the expression of CYP11B1.[26][27][28]

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.[citation needed]

Classification

Some people only use Conn's syndrome for when it occurs due to an adrenal adenoma (a type of benign tumor).[29] In practice, however, the terms are often used interchangeably, regardless of the underlying physiology.[1]

Differential diagnosis

Other causes of treatment-resistant hypertension include

Liddle syndrome can cause secondary aldosteronism or pseudohyperaldosteronism.[9]

Treatment

The treatment for hyperaldosteronism depends on the underlying cause. In people with a single benign tumor (

laparoscopically, through several very small incisions. For people with hyperplasia of both glands, successful treatment is often achieved with spironolactone or eplerenone, drugs that block the aldosterone receptor. With its antiandrogen effect, spironolactone drug therapy may have a range of side effects in males and females, including gynecomastia and irregular menses. These symptoms occur less frequently with eplerenone drug therapy.[30]

In the absence of treatment, individuals with hyperaldosteronism often have poorly controlled high blood pressure, which may be associated with increased rates of

heart disease, and kidney failure. With appropriate treatment, the prognosis is considered good.[31]

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[32]

Epidemiology

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.[33] Very low rates of compliance with screening guidelines lead to the underdiagnoses of primary aldosteronism.[34][35]

Society and culture

The Primary Aldosteronism Foundation[36] 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.[citation needed]

Eponym

Conn's syndrome is named after

endocrinologist who first described the condition at the University of Michigan in 1955.[11]

References

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  21. ^ "Renin/Aldosterone Protocol". United Bristol Healthcare NHS Trust. Archived from the original on 2007-08-13.
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  30. ^ "Inspra (eplerenone) [prescribing information]". Archived from the original on 2011-08-08. Retrieved 2011-07-17.
  31. ^ "Hyperaldosteronism (Conn's Syndrome)". Columbia Adrenal Center. Archived from the original on 2011-05-26.
  32. ^ "Spark-PA – Spark-PA is a clinical research study exploring an investigational study drug that may help people with primary aldosteronism (PA) lower their blood pressure". Archived from the original on 2021-08-02. Retrieved 2021-03-05.
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  36. ^ "Welcome to the Primary Aldosteronism Foundation". Retrieved 2021-03-05.

External links

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