▎ WuXi AppTec content team editor
It is reported that in 2019, there were reportedly 1.28 billion people aged 30-79 years old worldwide. Although hypertension is a major risk factor for cardiovascular disease and premature death, adherence to antihypertensive medications and adherence to a healthy lifestyle can help control the condition and improve quality of life.
However, there may be some patients, although they take medicine every day according to the doctor's instructions, but their blood pressure has not been well controlled; even if the dose of the drug is increased and a variety of antihypertensive drugs are taken at the same time, it still has little effect.
Recently, a case published in the British Medical Journal (BMJ) tells the story of a patient whose blood pressure has been poorly controlled, and after examination, the patient was diagnosed with primary hyperaldosteronism, and after treatment, the patient's blood pressure is currently stable. This case also highlights the importance of screening and identifying primary hyperaldosteronism in patients with refractory hypertension.
The study's corresponding author is Jun Yang, director of the Department of Endocrinology at Monash Health Centre at Monash University in Australia.
Screenshot source: The BMJ
Case sharing
The patient, a 57-year-old woman, was admitted to the hospital due to poor control due to an increase in blood pressure found to be elevated for more than 3 years.
Three years ago, patients noticed an increase in blood pressure during a physical examination, specifically 150 mmHg/100 mmHg. Patients were given oral therapy with pedopril, amlodipine, and mosonidine, with poor results. The dose of the drug was increased to the patient, but the average blood pressure remained above 140 mmHg/90 mmHg.
Patients report fluctuating weight without obvious precipitating factors, feeling exhausted during exercise, memory loss, sudden allergies and food intolerances that manifest as itching around the face and neck, and symptoms such as joint and bone pain, blurred vision, and insomnia.
Past and family history
Patients report no associated history of hypertension or family history.
Laboratory tests
Laboratory test results are as follows:
Serum potassium is 3.7 mmol/L (reference range 3.5-5.2 mmol/L);
Glomerular filtration rate (eGFR) of 90 mL/min/1.73 m2;
Plasma aldosterone is 377 pmol/L (reference range 70-1090 pmol/L);
Direct renin is 4.2 mU/L (reference range 4.4-46.0 mU/L).
Saline tests confirmed primary hyperaldosteronism, and both adrenal CT and adrenal vein sampling were consistent with bilateral adrenal disease.
diagnosis
After comprehensive judgment, the case was confirmed as primary hyperaldosteronism.
Primary hyperaldosteronism (also known as oligospermia) is the most specific, potentially curable cause of secondary hypertension, but many high-risk patients do not routinely screen for primary hyperaldosteronism. Recent studies have reported that at least 4% of the 1,020 patients newly diagnosed with hypertension in China are related to primary hyperaldosteronism; 17.5% of patients with primary hyperaldosteronism may develop hypokalemia.
Specifically, primary hyperaldosteronism refers to the spontaneous secretion of aldosterone by the adrenal cortex, resulting in sodium excretion in the body, increased blood volume, inhibition of renin-angiotensin system activity, and clinical manifestations of hypertension and hypokalemia (low sensitivity and specificity of serum potassium).
As shown in the figure below, renin usually stimulates aldosterone secretion to increase sodium reabsorption and promote volume dilation, usually during volume depletion. However, in patients with primary hyperaldosteronism, the production of aldosterone is independent of renin (e.g., from one or both adrenal glands). Renin levels are suppressed, while aldosterone levels increase sodium reabsorption and lead to hypertension; patients may develop hypokalemia, associated muscle spasms, weakness, or arrhythmias due to potassium excretion and renal sodium reabsorption.
▲ Pathophysiology of primary hyperaldosteronism (Image source: Reference[1])
In addition, studies have found that excessive aldosterone is an important risk factor for myocardial hypertrophy, heart failure and impaired renal function, and the damage to the heart and kidneys of hypertensive target organs in patients with primary hypertension is more serious than that of patients with primary hypertension.
treat
Prior to ARR testing, the patient's perdopril and amlodipine were converted to verapamil for 4 weeks, and the ARR was elevated to 90 pmol/L. Patients are now treated with spironolactone 37.5 mg/day monotherapy, and blood pressure is maintained at 37.5 mg/day.
Principle of treatment: The treatment plan depends on the patient's etiology and the patient's response to the drug, and there are two methods: surgery and medication.
Patients with confirmed aldosteronoma or PAH undergo laparoscopic unilateral adrenalectomy and are recommended if there are contraindications to surgery or reluctance to operate, while drug therapy is preferred for extraordinarial disease. Aldosterone-secreting adrenal cortex carcinoma develops rapidly and metastasizes earlier, and the primary tumor should be removed as early as possible. If local metastases are present, the primary and metastatic lesions should be removed as much as possible and treated with mitotan after surgery.
It is recommended that spironolone be used as a first-line agent and eplerenone as a second-line agent. Aldosterone receptor antagonist with an initial therapeutic dose of 20 mg/day and can be gradually increased to a maximum dose of 100 mg/day if required. For patients treated with drugs, it is necessary to regularly review kidney function, electrolytes, and detect blood pressure, and adjust the dose of drugs according to blood potassium, blood pressure and other indicators.
Case study points
Aldosterone excess can lead to cardiovascular and cerebrovascular diseases and kidney diseases;
Patients considering moderate to severe hypertension, refractory hypertension, hypertension with adrenal masses, or hypokalemia may present with primary hyperaldosteronism.
A small number of patients have hypokalemia, and most cases resemble essential hypertension, leading to missed diagnoses or delayed diagnosis.
Plasma aldosterone-to-renin ratio (ARR) is the primary test for screening for primary hyperaldosteronism, but testing may be interfered with by medications, and it is recommended to change medications temporarily prior to screening.
Unilateral disease is recommended with adrenectomy; bilateral disease is recommended with mineralocorticoid receptor antagonists.
Image credit: 123RF
Content expansion
Screening for primary hyperaldosteronism
The Expert Consensus on the Diagnosis and Treatment of Primary Hyperaldosteronism (2020 Edition) recommends plasma aldosterone-to-renin ratio (ARR) as the preferred screening indicator for orthoalism, and recommends screening for the following populations:
Persistent hypertension: refers to patients with a blood pressure > 150 mmHg/100 mmHg; patients who cannot control blood pressure with 3 conventional antihypertensive drugs (including diuretics) (> 140/90 mmHg); patients who use ≥ 4 antihypertensive drugs to control blood pressure; and patients with newly diagnosed hypertension.
Hypertension in patients with spontaneous or diuretic hypokalemia.
Hypertension in patients with adrenal accidental tumors.
Family history or early onset of hypertension (
There are first-degree relatives with hypertension in patients with orthodonal disease.
Hypertension in patients with obstructive apnea of breathing
Image credit: 123RF
Diagnosis and classification of primary hyperaldosteronism
The Expert Consensus on the Diagnosis and Treatment of Primary Hyperaldosteronism (2020 Edition) recommends that ≥ 1 confirmatory test be performed to confirm the diagnosis in patients with ARR positivity. At present, there are four main confirmatory tests, including oral high-sodium diet, fludrocortisone test, normal saline test and captopril test. Each of the four trials has its own advantages and disadvantages, and clinicians can choose according to the actual situation of the patient.
In patients with spontaneous hypokalemia, plasma renin levels below detectable levels, and aldosterone > 20 ng/dl, direct diagnosis of orthoalism is recommended without additional confirmatory testing.
Primary hyperaldosteronism is divided into 6 types: aldosteronoma, tetrialosis, primary adrenal hyperplasia (also known as unilateral adrenal hyperplasia, PAH), familial hyperaldosteronism, aldosterone-secreting adrenal cortical carcinoma, and ectopic aldosterone-secreting tumors.
The classification diagnosis of primary hyperaldosteronism has always been a clinical difficulty, which greatly affects the choice of treatment plan, clinicians can not rely solely on imaging to determine the type of lesions, but to combine biochemical indicators, imaging performance and bilateral adrenal vein blood collection (AVS) results for comprehensive analysis.