When Aldosterone to Renin Ratio (ARR) is elevated

By SWA

Since 1997, I have been actively advocating for the accurate diagnosis and management of my condition, characterized by hypokalemia and an imbalance in the aldosterone-to-renin ratio.

Despite extensive efforts, achieving recognition and appropriate treatment has proven challenging. This condition, while complex in its endocrinological underpinnings, could potentially be identified and addressed through initial screening with a cortisol/ACTH test, which may lead to significant improvements in clinical outcomes. 

My prolonged journey ultimately culminated in a diagnosis of Addison’s disease and Conn’s syndrome, underscoring the need for heightened clinical awareness and timely intervention.

The earlier test results from 2007, as well as my most recent Cortisol/ACTH test results from December 2021, both indicate an elevated Aldosterone to Renin Ratio (ARR).

Patient's Results (14.12.21):

  1. ACTH: 5.3 pg/ml (slightly below normal).
  2. Aldosteron: 56.5 pg/ml (within normal range).
  3. Aldost.Ren.Quo.Index: 24.15+ (above the normal range, which might indicate an issue with aldosterone-renin balance).
  4. Blood sugar fasting: 74 mg/dl (within normal range).
  5. Cortisol:
    • 0 ug/dl: 4.7 ug/dl (slightly below normal).
    • 30 ug/dl: 11.3 ug/dl (above the expected range of 0).
    • 60 ug/dl: 13.7 ug/dl (above the expected range of 0).
  6. Kalium: 3.61 mmol/l (on the lower edge of normal).
  7. Natrium: 140 mmol/l (within normal range).
  8. Renin: 2.3 pg/ml (slightly below normal)

The cosyntropin test was conducted at 8 am but was complicated by a sudden drop in my blood pressure and low blood sugar, causing me to faint and requiring immediate glucose administration.

 Interpretation:

  • ACTH and Cortisol levels are slightly lower than normal, suggesting possible adrenal insufficiency or other related issues.
  • Aldosterone is within the normal range, but the Aldosterone to Renin Ratio (ARR) is elevated, which could indicate a condition like primary aldosteronism.
  • Renin is slightly below normal, which might be related to the elevated aldosterone-renin ratio.
  • Electrolytes (Kalium and Natrium) are within normal ranges, but Kalium is borderline low, which could be related to aldosterone's effects on potassium.
  • Genetics: TRPM2-AS, TRPM2-AS and TRPM2-AS are detected in my X 21 chromosome. 

This data suggests the need for further evaluation, particularly regarding the adrenal gland's function and the regulation of blood pressure and electrolytes.

Summary and Interpretation:

  • Hormone Levels:

    • ACTH and cortisol levels are slightly low, suggesting possible adrenal insufficiency.
    • Aldosterone is normal, but the elevated Aldosterone to Renin Ratio (ARR) suggests primary aldosteronism.
    • Renin is slightly below normal, contributing to the high ARR.
    • Electrolytes (sodium and potassium) are within normal ranges, but potassium is borderline low, likely due to aldosterone's effects.

  • Genetic Findings:

    • TRPM2-AS variants were detected on the X chromosome, which may have clinical relevance.

Significance:

  • The findings suggest further evaluation of adrenal function, blood pressure regulation, and electrolyte balance is needed, with a focus on possible primary aldosteronism and adrenal insufficiency.
  • Low cortisol causes blood glucose levels to fall, leading to hypoglycemia. This triggers the body to use proteins and fats as alternative energy sources due to increased insulin levels.
  • Hypoglycemia is a condition where blood sugar (glucose) levels drop below normal, typically below 70 mg/dL. Glucose is the body's main source of energy, so low levels can lead to symptoms like shakiness, sweating, dizziness, confusion, irritability, and, in severe cases, seizures or unconsciousness. Hypoglycemia can be caused by various factors, including excessive insulin, prolonged fasting, certain medications, adrenal insufficiency, or other metabolic disorders. Prompt treatment, usually by consuming fast-acting carbohydrates, is essential to restore blood sugar levels to normal.

Primary Aldosteronism (Conn’s Syndrome):

  • Description:

    Effects on Cortisol and Other Hormones:

  • While Conn’s Syndrome primarily involves aldosterone, it can also impact cortisol levels. Cortisol plays a crucial role in maintaining blood glucose levels by stimulating gluconeogenesis (glucose production in the liver).
  • Dysregulation of cortisol can lead to inappropriate responses to low blood sugar, contributing to hypoglycemia in some cases.
  • A condition where the adrenal glands produce excessive aldosterone, independent of renin levels, often due to an adrenal tumor or hyperplasia.
  • Symptoms: High blood pressure, low potassium, fatigue, muscle cramps, arrhythmias, and frequent urination.
  • Testing: Confirmatory tests include blood aldosterone and renin levels, 24-hour urine aldosterone, saline infusion test, and imaging (CT/MRI).

Encephalitis and CSF Leak:

  • Encephalitis causes brain inflammation, which can increase intracranial pressure and potentially lead to CSF leaks, contributing to complications like pituitary compression.

Hormone Replacement Considerations:

  • Prednisolone vs. Hydrocortisone:

    • Hydrocortisone better mimics natural cortisol rhythms, making it preferred for adrenal insufficiency management.
    • Prednisolone is more potent with longer anti-inflammatory effects, suitable for conditions like rheumatologic diseases but less ideal for adrenal replacement.

  • Switching to Hydrocortisone:

    • Hydrocortisone offers better symptom control and avoids long-term side effects associated with excessive glucocorticoid exposure from prednisolone.

Importance of Diagnosis and Treatment:

  • Proper diagnosis of primary aldosteronism is essential to manage hypertension and prevent complications such as heart attack and kidney damage.
  • If adrenal insufficiency is confirmed, switching to hydrocortisone can improve outcomes by closely replicating natural cortisol production.

Note on Testing:

  • Unfortunately, a 24-hour urine aldosterone test or MRI/CT scan for obvious CSF leak and vision problems, possible encephalitis, brain inflammation, and swelling was not ordered

Rheumatological Considerations:

  • Rheumatological Diseases: Prednisolone is often used in rheumatological conditions like rheumatoid arthritis, lupus, or vasculitis due to its strong anti-inflammatory properties.
  • Contraindications: If a patient has a rheumatological condition that absolutely requires the anti-inflammatory effects of prednisolone, switching might be more complicated. The healthcare provider must ensure that switching to hydrocortisone does not exacerbate the underlying rheumatological disease.

Conclusion:

If there's no contraindication from a rheumatological standpoint, meaning the patient’s rheumatological condition can be managed without prednisolone or with alternative therapies, switching to hydrocortisone is generally recommended to better treat corticotropic insufficiency. Hydrocortisone offers a more physiological replacement therapy that aligns with the body’s natural cortisol rhythm, reducing the risk of side effects and providing more effective management of adrenal insufficiency.

In summary, the elevated ARR in the test results suggests that the patient may have primary aldosteronism, which is leading to excess aldosterone production and low renin levels. This condition is often associated with symptoms related to high blood pressure and low potassium levels.

Reference: 

Regulation of the epithelial Na+ channel by aldosterone: Open questions and emerging answers
https://www.sciencedirect.com/science/article/pii/S008525381546867X

Addison's disease is also called primary adrenal insufficiency.
https://my.clevelandclinic.org/health/diseases/15095-addisons-disease

Primary Aldosteronism (Conn’s Syndrome)
https://my.clevelandclinic.org/health/diseases/21061-conns-syndrome

Primary Aldosteronism
https://www.hopkinsmedicine.org/health/conditions-and-diseases/primary-aldosteronism

Chapter 15 - Disorders of muscle and post-polio syndrome
https://www.sciencedirect.com/science/article/abs/pii/B978072343285250019X

Please note: The content on this blog is for informational purposes only and is not intended to provide medical diagnoses or treatment. The information shared is based on frequently asked questions and is sourced from reputable scientific studies.

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742

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