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Renal Insufficiency

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Female Urogenital Diseases and Pregnancy Complications

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Channel Blockers

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Mineralocorticoids

Patients treated with mineralocorticoid antagonists or potassium sparing diuretics for primary aldosteronism

Unilateral adrenalectomy in patients with unilateral disease

Troy Puar, MRCP

Troy Puar

Majority of patients with hypertension have primary hypertension (without an underlying cause). Primary aldosteronism (PA) is the most common cause of secondary hypertension, and can be found in 5-10% of patients locally. PA is caused by excessive release of a hormone (aldosterone) from the adrenal glands, which can be unilateral (one gland) or bilateral (both glands).

It has been shown that excess aldosterone has other harmful effects in addition to hypertension, such as directly affecting the heart, blood vessels, kidneys, leading to increased cardiovascular morbidity and mortality. This is supported by studies showing reversal of these effects after treatment for PA.

The investigators aim to assess the long-term cardiovascular, and renal outcomes of patients with PA, compared to patients with essential hypertension.

Outcome of Patients With Primary Aldosteronism

Long-term Outcomes in Patients With Primary Aldosteronism After Treatment

incidence of new cardiovascular events including acute myocardial infarction, revascularisation percutaneously, coronary artery bypass graft, stroke, admission for congestive cardiac failure, atrial fibrillation

incidence of worsening chronic kidney disease, decline of glomerular filtration rate by 15ml/min from at least 60m/min

rate of decline of glomerular filtration rate

Identify variables that are more common in patients with unilateral disease

Identify variables that are more common in patients with positive blood pressure response

Singapore General Hospital

Changi General Hospital

Vasoconstrictor Agents

Respiratory System Agents

Natriuretic Agents

Antihypertensive Agents

Epinephrine

Amiloride

Spironolactone

Racepinephrine

Epinephryl borate

Eplerenone

Hormones

Hormone Antagonists

Patients who undergo medical treatment, in view of bilateral PA, or unilateral PA not keen for surgery, or indeterminate (lack of localisation on tests)

Patients with unilateral PA who underwent adrenalectomy

Adrenalectomy for unilateral adrenal hyperplasia / adenoma

Adrenalectomy

Troy Puar, MRCP (UK)

Majority of patients with hypertension have primary hypertension (without an underlying cause). Secondary hypertension (due to an underlying disease) is important to recognize, as treatment can lead to cure of hypertension. Primary aldosteronism (PA) is the most common cause of secondary hypertension, and can be found in 5-10% of patients locally.

PA is caused by excessive release of a hormone (aldosterone) from the adrenal glands, which can be unilateral (one gland) or bilateral (both glands). Distinction between two is crucial as unilateral disease is treated with the aim of cure by surgery, and bilateral disease is treated by medication.

It has been shown that excess aldosterone has other harmful effects in addition to hypertension, such as directly affecting the heart, blood vessels, kidneys, diabetes and quality of life. This is supported by studies showing reversal of these effects after treatment for PA. In addition, improvements after surgery appears to be superior to medical treatment, although studies have found variable results.

Hence, the investigators aim to accurately subtype patients with PA into unilateral or bilateral disease and study the post-treatment response after both surgery and medicine with regards to the effects on blood pressure, cardiovascular, renal, metabolic and quality of life.

Peripheral blood samples Adrenal vein blood samples (during adrenal vein sampling) Adrenal tissue (post-adrenalectomy)

Prospective Study Assessing Blood Pressure and Other Outcomes Post-treatment in Patients With Primary Aldosteronism

Prospective Study Assessing Blood Pressure, Cardiovascular, Endothelial and Other Outcomes poSt-surgical and Medical Treatment in Patients With Primary Aldosteronism

Blood pressure assessed by 24hr ambulatory BP

Use of antihypertension medications as expressed in daily defined dosages and total number of medications

change in serum creatinine, calculated GFR, albuminuria (prevalence and severity)

Proportion of patients reaching normal BP (ambulatory /home BP \<135/85 or clinic BP \<140/90)

Proportion of patients with cure of PA after adrenalectomy

Adrenocortical Adenoma

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Endocrine Gland Neoplasms

Adrenal Cortex Diseases

Adenoma of the Adrenal Gland

Histopathology shows a clear boundary between adrenal adenoma and surrounding normal tissue.

Histopathology shows no clear boundary between adrenal hyperplasia and surrounding normal tissues.

There is a clear boundary between adrenal adenoma and surrounding normal tissue. There is no clear boundary between adrenal hyperplasia and surrounding normal tissues.

histopathology

Yan Zhencheng, MD

Zhencheng Yan, MD

Primary aldosteronism (PA) is a common cause of secondary hypertension, which is characterized by excessive aldosterone production by the adrenal gland. Excessive aldosterone can significantly increase the risk of cardiovascular disease and stroke. Patients with aldosterone-producing adenoma (APA) or unilateral hyperplasia (UAH) can be cured by unilateral adrenalectomy. The adrenal cortex is the outer part of the adrenal gland and is subdivided into three layers- the zona glomerulosa, the zona fasciculata, and the zona reticularis. And the outermost layer is the zona glomerulosa, and it's full of cells that make the hormone aldosterone. Although it has been investigated that the main cause of APA or UAH is the mutations of different calcium ion channels, including KCNJ5, CACNA1D, CLCN2 et al, it is still unknown whether there are any other changes of other proteins in different layers. Therefore, the investigators designed the study to characterize the proteomics profiles of adrenal adenoma/hyperplasia leading to primary aldosterone and identify biomarkers for early identification of PA by using spatial proteomics. The samples from adrenal adenoma or hyperplasia will be collected and analyzed by spatial proteomics in Hangzhou Jingjie Biotechnology Co., Ltd. The differentially expressed proteins in different layers will be screened out between APA and UAH, APA and its adjacent normal tissues, and UAH and its adjacent normal tissues, respectively. And KEGG analysis will be conducted to determine enriched pathway in these differentially expressed protein, respectively.

Samples of adrenal collected from aldosterone-producing adenoma and unilateral hyperplasia by operation.

Spatial Proteomics Profiles of Aldosterone-producing Adenoma and Unilateral Hyperplasia

Spatial Proteomics Profiles of Adrenal Adenoma/Hyperplasia Leading to Primary Aldosterone

Histological validation of the CYP11B2 positive area in APA and UAH by immunohistochemical staining (IHC). Some specimens will be characterized more deeply with advanced spatial proteomics technologies to identify the biomarkers.

Verifying the relationship between biomarkers and clinical presentations, including plasma aldosterone concentrations (PAC), aldosterone to rein ratio (ARR), direct renin concentration (DRC), and serum potassium, etc. Comparing the relationships between biomarkers and risk factors, including osas and family history, etc. Establishing a mathematical model for diagnosing PA through machine learning and studying the pathogenesis of PA through corresponding animal models.

The alteration of blood pressure and medication status are investigated through 3 months followed up. Verifying the relationship between the biomarkers and the function of APA and UAH, as well as the prognosis of PA.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Outcome of Patients With Primary Aldosteronism	NCT04428827	Primary Aldoste... Primary Aldoste... Primary Aldoste... Adrenalectomy; ... Mineralocortico... Mineralocortico... Cardiovascular ... Chronic Renal D... Hypokalemia	Unilateral adre...	14 Years - 100 Years	Changi General Hospital
Prospective Study Assessing Blood Pressure and Other Outcomes Post-treatment in Patients With Primary Aldosteronism	NCT03174847	Primary Aldoste... Primary Aldoste... Primary Aldoste...	Adrenalectomy Mineralocortico...	21 Years - 80 Years	Changi General Hospital
Spatial Proteomics Profiles of Aldosterone-producing Adenoma and Unilateral Hyperplasia	NCT05927961	Primary Aldoste... Primary Aldoste...	histopathology	18 Years - 70 Years	Third Military Medical University
Prospective Study Assessing Blood Pressure and Other Outcomes Post-treatment in Patients With Primary Aldosteronism	NCT03174847	Primary Aldoste... Primary Aldoste... Primary Aldoste...	Adrenalectomy Mineralocortico...	21 Years - 80 Years	Changi General Hospital

Spots Global Cancer Trial Database for primary aldosteronism due to adrenal hyperplasia (bilateral)