Interpretation of the latest guide: Primary aldosteronism (PA), worth learning and collecting

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Here comes the latest guide of the Italian Hypertension Association (SIIA) 2020 version of Primary Aldosteronism (PA)! Come and pick! Scan the code to download the original text of the guide~1.
Introduction to PA Primary aldosteronism (PA) is caused by excessive secretion of aldosterone from the adrenal cortex, which leads to sodium retention, potassium excretion, increased blood volume, and inhibition of renin-angiotensin system activity, etc.
The main clinical manifestations of the disease are high blood pressure and hypokalemia.
However, in recent years, many patients with PA often lack the manifestations of hypokalemia, resulting in the underestimation of the incidence of PA.
In addition, the prevalence of PA is positively correlated with blood pressure.
The prevalence of PA in patients with blood pressure 1, 2, and 3 stages were 3.
9%, 9.
7%, and 11.
8%, respectively.

2.
Straightforward: PA diagnosis ■ 2.
1 PA diagnostic index Hypokalemia is a traditional sign of PA, but now only a small part (9% -37%) of PA patients have this symptom, so we should also pay attention to the addition of hypokalemia.
Other testing indicators besides serum potassium.

The diagnostic indicators of PA include low or lower levels of renin, and high plasma aldosterone (PAC) concentration.

Attached are the 4 tips when interpreting PAC levels: 1.
If the PAC concentration of PA patients is normal, low renin is the only indication at this time; 2.
If the patient’s daily sodium intake is higher than 200mEq, it is close to the critical value at this time The level of PAC can also diagnose PA; 3.
Individual differences lead to different sensitivity of PAC.
For example, American races and African races have higher sensitivity; 4.
PAC has volatility, and in patients with diagnosed PA, The PAC level may also fluctuate to within the normal range.
Therefore, once again, a high PAC level is not a necessary indicator of PA.

When the patient has no obvious clinical manifestations of PA, such as vomiting, diarrhea, etc.
, hypokalemia can be used as a powerful indicator of PA.

Another important indicator is the aldosterone-renin ratio (ARR), which has been proven to be more advantageous than any single indicator of PAC, plasma renin activity (PRA), and direct renin concentration (DRC).
ARR has both High sensitivity, high accuracy and high reproducibility.

This guideline strongly promotes ARR as the first choice for diagnosis of hypertension (recommendation level I, level of evidence B).

In addition, DRC is easy to operate and can show high accuracy even at low renin levels.
It can now widely replace PRA assays and has the advantages of short analysis time and low cost (recommendation level II, evidence level B).

When ARR detection is not possible, DRC can be used as an alternative detection method.

Table 1 Summary of key points of case testing ■ 2.
2 Diagnostic interference factors When we get a diagnosis result, we should consider the standardization of sampling and potential interference factors (recommendation level II, level of evidence A), such as the secretion of renin and aldosterone It presents a rational law of birth, reaching the highest value when waking up in the morning, so the time point of sampling should be standardized and taken into account when analyzing the data.

In addition, posture can also affect results.
Standing posture raises renin levels, which affects PAC.

Therefore, the guidelines recommend taking a blood sample after 60 minutes of rest in the supine or sitting position (recommendation level II, level of evidence B).

Other precautions include: women's menstrual period may lead to false positives in the ARR test; the speed of blood sampling should be slow to avoid hemolysis, resulting in artificial normal serum potassium; if the DRC test method is used.

It should be noted that the samples should be kept at room temperature during transportation; women who are in the luteal phase before menopause and women who receive hormone replacement therapy after menopause may have false positive ARR results because the increase in PAC is much greater than that of renin.

Table 2 Influencing factors of PAC/renin/ARR ■ 2.
3 Renin and aldosterone assays Plasma renin can be obtained by detecting angiotensin I (PRA, ng/ml/h) or by directly detecting active renin ( DRC, mIU/L or pg/mL).

A controlled study compared PRA and DRC, and the results showed that both methods can be used to screen PA patients with low renin levels.

But when the renin is too low, the accuracy of all detection methods will decrease, so it is necessary to establish a minimum detection limit (PRA: 0.
2 ng/mL/h, DRC: 2 mIU/L) to exclude false positive results.

PAC detection values ​​from different laboratories are often different, which may be caused by the plasma extraction process or the cross-immune reaction of antibodies.

At this time, if conditions permit, the use of mass spectrometry can greatly improve the accuracy of PAC.

Table 3 Summary of test points for renin and aldosterone ■ 2.
4 Primary aldosterone and pregnancy Table 4 Summary of PA during pregnancy Although hypertension accounts for about 6%-8% of pregnant women, only 41 cases of PA during pregnancy have been reported.
Patient cases, this also reflects the difficulty of diagnosing PA during pregnancy.

The body is in a state of high renin and high aldosterone during pregnancy, which can greatly increase the level of renin and PAC.

Therefore, patients who have been diagnosed with aldosterone adenoma (APA) should undergo surgery before pregnancy.

3.
Comparison of diagnosis and treatment methods: CT method VS AVS method is generally recommended for PA patients to use medical imaging methods, such as computerized tomography (CT), which can not only screen out tumor patients, but also clarify the location of adrenal veins.
For subsequent adrenal vein sampling (AVS) operation.

However, the probability that the CT method and AVS will get consistent diagnosis results is only 50%, and the AVS method can diagnose about 22% of CT-negative unilateral adrenal hyperplasia patients and about 25% of bilateral or contralateral hyperplasia patients.

Table 5 Summary of the main points of imaging diagnostics Although this sampling method is expensive, technically demanding and has a 0.
7% risk of adrenal vein rupture, AVS is still an important indicator to determine whether a patient can undergo unilateral adrenalectomy.

Table 6 Summary of AVS Sampling Methods IV.
Complications ■ 4.
1 Obstructive sleep apnea (OSA) According to a polysomnography study, OSA is ubiquitous in PA patients, with an incidence rate of up to 79%, in Chinese patients and Among white patients, this value was 67%.

In addition, the incidence of PA in OSA patients is 2-3 times higher than that in patients without OSA.
Animal experiments have shown that intermittent hypoxia will cause an increase in plasma endothelin-1, which in turn will increase the secretion of PAC.

■ 4.
2 Atrial Fibrillation (AF) Hypertension is the main risk factor for AF.
About 50%-90% of AF patients suffer from hypertension.
Therefore, PA is considered to cause changes in the heart structure, such as inflammation, fibrosis, myocardial hypertrophy, Myocardial remodeling, as well as changes in function and electrophysiology, eventually cause AF.

■ 4.
3 Cardiomyopathy PA damages the cardiovascular system even more than hypertension.
The probability of suffering from left ventricular hypertrophy (LVH) in PA patients is significantly increased.
There is MRI evidence showing the progression of left ventricular fibrosis.

■ 4.
4 Renal and metabolic complications PA can greatly increase the incidence of renal diseases and metabolic disorders through excessive activation of mineralocorticoid receptors.

In addition, compared with essential hypertension, PA has a higher glomerular filtration rate (eGFR) regulated urinary albumin filtration rate (UAE), and therefore has a higher risk of causing kidney failure.

■ 4.
5 Bone metabolism experiments and clinical data show that increased aldosterone can cause hypocalcemia by promoting the elimination of urinary calcium, and then induce secondary hyperthyroidism to aggravate bone mineral loss and decrease bone density.

Compared with patients with non-functional adrenal tumors, PA patients are more prone to osteoporosis, have lower bone mineral density (BMD) and trabecular bone mass, and have a higher risk of vertebral fractures.

Table 7 Summary of the main points of PA complications 5.
Treatment options.
Studies have pointed out that adrenalectomy can reduce the dosage of antihypertensive drugs in patients with PA; in the Adrenal Vein Sampling International Study-2 (AVIS-2) trial, adrenalectomy can be found Relieve or even completely cure refractory hypertension; in addition, surgery can also improve many physiological indicators.

Therefore, adrenalectomy is also recommended as the first choice, while medical therapy is recommended for patients with bilateral adrenal hyperplasia (BAH) or exclusion of unilateral adrenal hyperplasia (level of recommendation II, level of evidence B).

For patients with unilateral adrenal hyperplasia, transperitoneal and retroperitoneal laparoscopic adrenalectomy under the instruction of AVS is more recommended, which can guarantee a success rate of up to 98% and a cure rate of 40%-50%.

In order to preserve the function of the remaining part of the adrenal glands, mildly invasive surgical procedures and partial adrenalectomy have become new options for patients, and AVS must be used as a guide, but currently only a few clinical centers in Japan have practiced cases (recommended level Ⅱ, Level of Evidence C).

Before surgery, the patient’s hypertension and hypokalemia must be corrected.
Mineralocorticoid receptor resistance agents (MRAs) and/or potassium supplements can be used.
Obesity is also recommended before elective surgery.
Correct, because obese patients are at higher risk and require intensive special care, or may not be able to completely remove the adrenal glands (recommendation level II, level of evidence C).

The use of MRAs alone or in combination with other antihypertensive drugs can be used to stabilize patients with bilateral adrenal hyperplasia.

At the same time, it can also be used for the blood pressure and serum potassium concentration of patients with unilateral hyperplasia diagnosed by AVS who are not suitable for adrenalectomy (recommendation level II, level of evidence A).

Table 8 Summary of PA treatment methods.
References: Rossi GP, Bisogni V, Bacca AV, Belfiore A, Cesari M, Concistrè A, Del Pinto R, Fabris B, Fallo F, Fava C, Ferri C, Giacchetti G, Grassi G, Letizia C, Maccario M, Mallamaci F, Maiolino G, Manfellotto D, Minuz P, Monticone S, Morganti A, Muiesan ML, Mulatero P, Negro A, Parati G, Pengo MF, Petramala L, Pizzolo F, Rizzoni D, Rossitto G , Veglio F, Seccia TM.
The 2020 Italian Society of Arterial Hypertension (SIIA) practical guidelines for the management of primary aldosteronism.
Int J Cardiol Hypertens.
2020 Apr 15;5:100029.
doi: 10.
1016/j.
ijchy.
2020.
100029.
PMID : 33447758; PMCID: PMC7803025.