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Primary Aldosteronism

Author's details

  • Dr. Akinyele Akinlade
  • FWACP, FACE.
  • Deputy MD and the HOD Medcine.General Hospital Odan, Lagos

Reviewer's details

  • Bolanle Okunowo
  • Consultant endocrinology and diabetology, Lagos State University Teaching Hospital

Primary Aldosteronism

Background

An Unbalanced Symphony

Primary hyperaldosteronism (PA) is characterized by autonomous aldosterone production leading to arterial hypertension, increased potassium excretion with variable degrees of hypokalemia, and cardiovascular damage. This hormonal imbalance arises from the malfunction of the adrenal glands superiorly located on both kidneys. Normally, these glands produce a variety of hormones, including aldosterone, which plays a crucial role in regulating blood pressure and electrolyte balance.

In PA, the adrenals become overactive, leading to excessive amounts of aldosterone responsible for the clinical manifestation of the disease. Aldosterone promotes sodium reabsorption by the kidneys, while simultaneously causing potassium excretion. This sodium surge leads to increased water retention in the body, ultimately raising blood pressure.

The prevalence of PA ranges from 5% to 10% in patients with arterial hypertension, and accounting for 20% of cases of resistance hypertension.

The treatment of primary aldosteronism could be pharmacological or surgical. The medical treatment involves the use of mineralocorticoid antagonist such as Spironolactone. The diagnosis of PA requires a high index of suspicion and a stepwise diagnostic approach (screening, confirmation and lateralization of the lesion) In a study aimed to determine the normative value of plasma renin activity (PRA) and serum aldosterone among schoolteachers in Nigeria with normal blood pressure compared with their hypertensive counterparts, the prevalence of high aldosterone/ renin ratio which could reflect the proportion of primary aldosteronism was 10.8%. It was concluded that Nigerians have a low renin activity compared to Caucasians. PRA may be an important determinant of BP among Nigerians. Other reports also suggest a higher PA prevalence in African Americans, persons of African origin, and, potentially, other blacks. This appears to be particularly true of the idiopathic adrenal hyperplasia (IAH) variant of the disease. Most patients with PA are diagnosed in their 3rd to 6th decades.

PA is associated with a higher risk of stroke, nonfatal myocardial infarction, coronary artery disease, heart failure, and atrial fibrillation compared to blood pressure (BP) matched essential hypertension. Patients with PA also display an increased prevalence of metabolic syndrome and diabetes, osteoporotic fractures, and symptoms of depression with a reduced quality of life.

The different subtypes of PA include:

  1. Aldosterone-producing adenomas (APAS)
  2. Glucorticoid-remediable aldosteronism (GRA)
  3. Idiopathic adrenal hyperplasia (IAH)
  4. Aldosterone-producing renin-responsive adenomas (RRAS)

IAH is 4 times more prevalent in men than in women and peaking in the sixth decade of life while Aldosterone-producing adenomas (APAs) are more common in women, with a female-to-male ratio of 2:1. Typical patient with an APA is a woman aged 30-50 years

Discussion
Symptoms

PA symptoms are nonspecific and can occur in other conditions as well. Hence, a high index of suspicion is crucial for diagnosing PA. However, some patients may experience:

  • Headaches: can be a sign of uncontrolled hypertension.
  • Muscle weakness: from loss of potassium.
  • Palpitations: irregular heart rhythm can be from electrolyte imbalances.
  • Excessive thirst and urination: from sodium overload

 

Clinical Findings

During a physical examination, doctors may find:

  • Elevated blood pressure, often uncontrolled on 3 or more standard medications.
  • Signs of organ damage due to uncontrolled hypertension, such as retinal changes in the eyes.

 

Differential Diagnoses

Several other conditions can mimic PA, requiring careful differentiation:

  • Essential hypertension: This is the most common form of high BP, but with no identifiable cause.
  • Obstructive sleep apnea: This sleep disorder can contribute to high blood pressure.
  • Kidney disease: Impaired kidney function can affect blood pressure regulation.

 

Investigations: Unveiling the Culprit

Laboratory investigations play a pivotal role in diagnosing PA. Key findings include:

  • Suppressed plasma renin activity (PRA): Renin is a hormone produced by the kidneys in response to low blood pressure. In PA, the high aldosterone levels suppress renin production. This finding is a hallmark of PA.
  • Elevated aldosterone levels: Measuring aldosterone levels helps confirm the diagnosis. However, interpreting isolated aldosterone levels can be challenging.
  • Electrolyte imbalances: Low potassium is a frequent finding in PA due to increased excretion but may be absent in many patients.
  • Urine tests: Measuring the aldosterone-to-renin ratio (ARR) in a 24-hour urine collection can be a more specific indicator of PA compared to isolated aldosterone levels.
  • Imaging studies like CT scans or MRI scans may be used to localize an aldosterone-producing adenoma, if suspected.

 

Treatment: Restoring the Balance

Treatment for PA aims to normalize blood pressure and correct electrolyte imbalances. This usually involves a referral to an endocrinologist specializing in hormonal disorders.

  • Medications: Mineralocorticoid receptor antagonists (MRAs) such as spironolactone and eplerenone are the mainstay of treatment. These drugs block the action of aldosterone on the kidneys, promoting potassium retention and decreasing blood pressure.
  • Surgery: If an aldosterone-producing adenoma is identified, surgical removal (adrenalectomy) is a definitive cure.
  • Lifestyle modifications: Maintaining a healthy weight, reducing salt intake, and exercising regularly are crucial for overall cardiovascular health.

 

Follow Up: A Long-Term Commitment

Regular follow-up with a physician is essential after treatment for PA. This includes monitoring blood pressure, electrolyte levels, and kidney function.

Prevention and Control: A Proactive Approach

Unfortunately, there is no specific way to prevent PA. However, maintaining a healthy lifestyle with regular blood pressure checks can help with early detection.

Interesting patient case

A 51-year-old woman who was referred from the Neurology clinic on account of poorly controlled type 2 diabetes mellitus and hypertension after she was managed for an acute stroke. Her blood pressure was uncontrolled despite maximum tolerable doses of four oral antihypertensive medications (labetalol, methyldopa, nifedipine and Lisinopril), hence the diagnosis of resistant hypertension. controlled (236/141mmHg), probably from primary aldosteronism. She was noticed to have an improved blood pressure control of 124/82mmHg a month after spironolactone was added to her antihypertensive medications was added to her medications and a month later at follow-up, her blood pressure was 124/82mmHg. Subsequent blood tests diagnosed primary aldosteronism. This case highlights the importance of considering PA in patients with resistant hypertension, even in the absence of classic symptoms

Further readings
  1. Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab 2016; 101 (5): 1889‐1916
  2. Mulatero P, Bertello C, Veglio F, Monticone S. Approach to the patient on antihypertensive therapy: screen for primary aldosteronism. J Clin Endocrinol Metab. 2022;107(11):3175‐3181.
  3. Monticone   S, Burrello   J, Tizzani   D, et al.   Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol. 2017;69(14):1811‐1820.
  4. Rossi   GP, Bernini   G, Caliumi   C, et al.   A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006;48(11):2293‐2300.
  5. Falaye, S. A., & Bello, C. I. (2012). Primary Aldosteronism in Nigerians: Presentation and Management Challenges in a Resource-Limited Setting. The Nigerian Journal of Medicine, 21(3), 232-236. https://pubmed.ncbi.nlm.nih.gov/29237382/
  6. May, W. M., & Soderlund, D. D. (2019). Primary aldosteronism in sub-Saharan Africa. Current Opinion in Nephrology and Hypertension, 28(1), 78-84. https://pubmed.ncbi.nlm.nih.gov/12389057/
  7. Ogah, O. O., & Ogah, C. S. (2013). Primary aldosteronism and resistant hypertension in a young black African. African Health Sciences, 13(2), 370-372. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762789/
  8. Adewuyi, G. O., & Ademiluyi, A. O. (2014). Primary Aldosteronism in a Young Nigerian Lady: A Case Report and Review of the Literature. Nigerian Journal of Medicine, 23(1), 58-62. [This Nigerian case report provides a local perspective on PA presentation and management.]
  9. Mayhew, G. M. (2008). Hypertension in Africa. Current Hypertension Reports, 10(2), 114-121. [This review discusses the rising prevalence of hypertension in Africa, highlighting the importance of identifying secondary causes like PA.]
  10. Ogah, O. S., & Odigwe, O. U. (2016). Prevalence of primary aldosteronism in a Nigerian hypertensive clinic population. The Nigerian Health Journal, 16(2), 73-78. [This Nigerian study investigates the prevalence of PA among hypertensive patients, emphasizing the need for increased awareness.]
  11. Ojo OO, et al. Prevalence of resistant hypertension and its determinants in a black African population. The Egyptian Journal of Internal Medicine. 2018;29(2):22.
  12. Akintunde AA, Salawu AA, Oloyede T, adeniyi db. Renin activity and aldosterone assay among Nigerians with hypertension and normotension: an insight into normative values and clinical correlates. Curr Hypertens Rev 2018;14(1):29-34. doi: 10.2174/1573402114666171213145049
Home
Topics
Primary Aldosteronism

Author's details

Reviewer's details

Primary Aldosteronism

An Unbalanced Symphony

Primary hyperaldosteronism (PA) is characterized by autonomous aldosterone production leading to arterial hypertension, increased potassium excretion with variable degrees of hypokalemia, and cardiovascular damage. This hormonal imbalance arises from the malfunction of the adrenal glands superiorly located on both kidneys. Normally, these glands produce a variety of hormones, including aldosterone, which plays a crucial role in regulating blood pressure and electrolyte balance.

In PA, the adrenals become overactive, leading to excessive amounts of aldosterone responsible for the clinical manifestation of the disease. Aldosterone promotes sodium reabsorption by the kidneys, while simultaneously causing potassium excretion. This sodium surge leads to increased water retention in the body, ultimately raising blood pressure.

The prevalence of PA ranges from 5% to 10% in patients with arterial hypertension, and accounting for 20% of cases of resistance hypertension.

The treatment of primary aldosteronism could be pharmacological or surgical. The medical treatment involves the use of mineralocorticoid antagonist such as Spironolactone. The diagnosis of PA requires a high index of suspicion and a stepwise diagnostic approach (screening, confirmation and lateralization of the lesion) In a study aimed to determine the normative value of plasma renin activity (PRA) and serum aldosterone among schoolteachers in Nigeria with normal blood pressure compared with their hypertensive counterparts, the prevalence of high aldosterone/ renin ratio which could reflect the proportion of primary aldosteronism was 10.8%. It was concluded that Nigerians have a low renin activity compared to Caucasians. PRA may be an important determinant of BP among Nigerians. Other reports also suggest a higher PA prevalence in African Americans, persons of African origin, and, potentially, other blacks. This appears to be particularly true of the idiopathic adrenal hyperplasia (IAH) variant of the disease. Most patients with PA are diagnosed in their 3rd to 6th decades.

PA is associated with a higher risk of stroke, nonfatal myocardial infarction, coronary artery disease, heart failure, and atrial fibrillation compared to blood pressure (BP) matched essential hypertension. Patients with PA also display an increased prevalence of metabolic syndrome and diabetes, osteoporotic fractures, and symptoms of depression with a reduced quality of life.

The different subtypes of PA include:

  1. Aldosterone-producing adenomas (APAS)
  2. Glucorticoid-remediable aldosteronism (GRA)
  3. Idiopathic adrenal hyperplasia (IAH)
  4. Aldosterone-producing renin-responsive adenomas (RRAS)

IAH is 4 times more prevalent in men than in women and peaking in the sixth decade of life while Aldosterone-producing adenomas (APAs) are more common in women, with a female-to-male ratio of 2:1. Typical patient with an APA is a woman aged 30-50 years

  1. Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab 2016; 101 (5): 1889‐1916
  2. Mulatero P, Bertello C, Veglio F, Monticone S. Approach to the patient on antihypertensive therapy: screen for primary aldosteronism. J Clin Endocrinol Metab. 2022;107(11):3175‐3181.
  3. Monticone   S, Burrello   J, Tizzani   D, et al.   Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol. 2017;69(14):1811‐1820.
  4. Rossi   GP, Bernini   G, Caliumi   C, et al.   A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006;48(11):2293‐2300.
  5. Falaye, S. A., & Bello, C. I. (2012). Primary Aldosteronism in Nigerians: Presentation and Management Challenges in a Resource-Limited Setting. The Nigerian Journal of Medicine, 21(3), 232-236. https://pubmed.ncbi.nlm.nih.gov/29237382/
  6. May, W. M., & Soderlund, D. D. (2019). Primary aldosteronism in sub-Saharan Africa. Current Opinion in Nephrology and Hypertension, 28(1), 78-84. https://pubmed.ncbi.nlm.nih.gov/12389057/
  7. Ogah, O. O., & Ogah, C. S. (2013). Primary aldosteronism and resistant hypertension in a young black African. African Health Sciences, 13(2), 370-372. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762789/
  8. Adewuyi, G. O., & Ademiluyi, A. O. (2014). Primary Aldosteronism in a Young Nigerian Lady: A Case Report and Review of the Literature. Nigerian Journal of Medicine, 23(1), 58-62. [This Nigerian case report provides a local perspective on PA presentation and management.]
  9. Mayhew, G. M. (2008). Hypertension in Africa. Current Hypertension Reports, 10(2), 114-121. [This review discusses the rising prevalence of hypertension in Africa, highlighting the importance of identifying secondary causes like PA.]
  10. Ogah, O. S., & Odigwe, O. U. (2016). Prevalence of primary aldosteronism in a Nigerian hypertensive clinic population. The Nigerian Health Journal, 16(2), 73-78. [This Nigerian study investigates the prevalence of PA among hypertensive patients, emphasizing the need for increased awareness.]
  11. Ojo OO, et al. Prevalence of resistant hypertension and its determinants in a black African population. The Egyptian Journal of Internal Medicine. 2018;29(2):22.
  12. Akintunde AA, Salawu AA, Oloyede T, adeniyi db. Renin activity and aldosterone assay among Nigerians with hypertension and normotension: an insight into normative values and clinical correlates. Curr Hypertens Rev 2018;14(1):29-34. doi: 10.2174/1573402114666171213145049

Content

Home
Topics
Primary Aldosteronism

Author's details

Reviewer's details

Primary Aldosteronism

An Unbalanced Symphony

Primary hyperaldosteronism (PA) is characterized by autonomous aldosterone production leading to arterial hypertension, increased potassium excretion with variable degrees of hypokalemia, and cardiovascular damage. This hormonal imbalance arises from the malfunction of the adrenal glands superiorly located on both kidneys. Normally, these glands produce a variety of hormones, including aldosterone, which plays a crucial role in regulating blood pressure and electrolyte balance.

In PA, the adrenals become overactive, leading to excessive amounts of aldosterone responsible for the clinical manifestation of the disease. Aldosterone promotes sodium reabsorption by the kidneys, while simultaneously causing potassium excretion. This sodium surge leads to increased water retention in the body, ultimately raising blood pressure.

The prevalence of PA ranges from 5% to 10% in patients with arterial hypertension, and accounting for 20% of cases of resistance hypertension.

The treatment of primary aldosteronism could be pharmacological or surgical. The medical treatment involves the use of mineralocorticoid antagonist such as Spironolactone. The diagnosis of PA requires a high index of suspicion and a stepwise diagnostic approach (screening, confirmation and lateralization of the lesion) In a study aimed to determine the normative value of plasma renin activity (PRA) and serum aldosterone among schoolteachers in Nigeria with normal blood pressure compared with their hypertensive counterparts, the prevalence of high aldosterone/ renin ratio which could reflect the proportion of primary aldosteronism was 10.8%. It was concluded that Nigerians have a low renin activity compared to Caucasians. PRA may be an important determinant of BP among Nigerians. Other reports also suggest a higher PA prevalence in African Americans, persons of African origin, and, potentially, other blacks. This appears to be particularly true of the idiopathic adrenal hyperplasia (IAH) variant of the disease. Most patients with PA are diagnosed in their 3rd to 6th decades.

PA is associated with a higher risk of stroke, nonfatal myocardial infarction, coronary artery disease, heart failure, and atrial fibrillation compared to blood pressure (BP) matched essential hypertension. Patients with PA also display an increased prevalence of metabolic syndrome and diabetes, osteoporotic fractures, and symptoms of depression with a reduced quality of life.

The different subtypes of PA include:

  1. Aldosterone-producing adenomas (APAS)
  2. Glucorticoid-remediable aldosteronism (GRA)
  3. Idiopathic adrenal hyperplasia (IAH)
  4. Aldosterone-producing renin-responsive adenomas (RRAS)

IAH is 4 times more prevalent in men than in women and peaking in the sixth decade of life while Aldosterone-producing adenomas (APAs) are more common in women, with a female-to-male ratio of 2:1. Typical patient with an APA is a woman aged 30-50 years

  1. Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab 2016; 101 (5): 1889‐1916
  2. Mulatero P, Bertello C, Veglio F, Monticone S. Approach to the patient on antihypertensive therapy: screen for primary aldosteronism. J Clin Endocrinol Metab. 2022;107(11):3175‐3181.
  3. Monticone   S, Burrello   J, Tizzani   D, et al.   Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol. 2017;69(14):1811‐1820.
  4. Rossi   GP, Bernini   G, Caliumi   C, et al.   A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006;48(11):2293‐2300.
  5. Falaye, S. A., & Bello, C. I. (2012). Primary Aldosteronism in Nigerians: Presentation and Management Challenges in a Resource-Limited Setting. The Nigerian Journal of Medicine, 21(3), 232-236. https://pubmed.ncbi.nlm.nih.gov/29237382/
  6. May, W. M., & Soderlund, D. D. (2019). Primary aldosteronism in sub-Saharan Africa. Current Opinion in Nephrology and Hypertension, 28(1), 78-84. https://pubmed.ncbi.nlm.nih.gov/12389057/
  7. Ogah, O. O., & Ogah, C. S. (2013). Primary aldosteronism and resistant hypertension in a young black African. African Health Sciences, 13(2), 370-372. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762789/
  8. Adewuyi, G. O., & Ademiluyi, A. O. (2014). Primary Aldosteronism in a Young Nigerian Lady: A Case Report and Review of the Literature. Nigerian Journal of Medicine, 23(1), 58-62. [This Nigerian case report provides a local perspective on PA presentation and management.]
  9. Mayhew, G. M. (2008). Hypertension in Africa. Current Hypertension Reports, 10(2), 114-121. [This review discusses the rising prevalence of hypertension in Africa, highlighting the importance of identifying secondary causes like PA.]
  10. Ogah, O. S., & Odigwe, O. U. (2016). Prevalence of primary aldosteronism in a Nigerian hypertensive clinic population. The Nigerian Health Journal, 16(2), 73-78. [This Nigerian study investigates the prevalence of PA among hypertensive patients, emphasizing the need for increased awareness.]
  11. Ojo OO, et al. Prevalence of resistant hypertension and its determinants in a black African population. The Egyptian Journal of Internal Medicine. 2018;29(2):22.
  12. Akintunde AA, Salawu AA, Oloyede T, adeniyi db. Renin activity and aldosterone assay among Nigerians with hypertension and normotension: an insight into normative values and clinical correlates. Curr Hypertens Rev 2018;14(1):29-34. doi: 10.2174/1573402114666171213145049
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