Hormone Biomarkers: Aldosterone

Optimal Takeaways

Aldosterone is an adrenal hormone that regulates sodium and potassium levels and plasma volume. It increases sodium retention and levels in the blood, increases potassium excretion in the urine, and decreases potassium in the blood.

Low serum aldosterone is associated with low blood sodium, high blood potassium, Addison’s disease, pregnancy, steroids, anti-hypertensive therapy, and excess licorice intake.

High serum aldosterone is associated with high blood sodium, low blood potassium, hypertension, fluid retention, stress, anxiety, depression, excessive exercise, and increased cardiovascular risk. Hyperaldosteronism may be suspected if levels don’t decrease following a challenge with sodium or aldosterone-suppressing medication.

Standard Range: 0.00 – 28.00 ng/dL (0.777 nmol/L, 776.72 pmol/L)

The ODX Range: 4 – 14 ng/dL (0.111 - 0.388 nmol/L, 110.96 – 388.36 pmol/L)  

Note: These ranges are for an AM blood test sample (8:00 – 10:00 am), in an upright position, i.e., not supine.

Low aldosterone may be associated hyponatremia, hyperkalemia, excess licorice intake, renin deficiency, Addison’s disease, toxemia of pregnancy, steroid therapy, anti-hypertensive therapy, angiotensin-converting inhibitors, fludrocortisone, and propranolol. A high-sodium diet can trigger a reduction in serum aldosterone (Pagana 2022). Low aldosterone may also be associated with age-related hearing loss (Tadros 2005).

High aldosterone is associated with stress, anxiety, depression (Kubzansky 2010), obstructive sleep apnea (Pratt-Ubunama 2007), renal vascular stenosis/occlusion, hypernatremia, hypokalemia, hypovolemia, hemorrhage, pregnancy, malignant hypertension, potassium loading, excessive exercise, weakness, polyuria, Cushing syndrome, and edematous states including congestive heart failure, nephrotic syndrome, and cirrhosis. Certain medications can increase aldosterone levels, including laxatives, estrogen, diuretics, hydralazine, diazoxide, nitroprusside, potassium, and spironolactone. Increased serum aldosterone can be triggered by low sodium intake (Pagana 2022).

Primary hyperaldosteronism is associated with spontaneous hypokalemia, cardiovascular risk, kidney damage, suppressed plasma renin (Funder 2016), stroke, atrial fibrillation, coronary artery disease, heart failure, left ventricular hypertrophy, metabolic syndrome, and diabetes (Monticone 2018).

Overview

Aldosterone is a mineralocorticoid the adrenal cortex produces from the precursor pregnenolone, a cholesterol derivative (Craig 2021). Aldosterone production is regulated by the renin-angiotensin system and stimulated by low serum sodium, high serum potassium, and to some extent, adrenocorticotropic hormone (ACTH). Aldosterone helps maintain serum sodium and potassium levels and plasma volume by increasing renal retention of sodium and water and renal excretion of potassium. Increased serum aldosterone may be caused by primary or secondary hyperaldosteronism. Non-adrenal secondary hyperaldosteronism may occur with low salt intake, hyponatremia due to diuretic or laxative use, potassium loading, renal vascular stenosis, malignant hypertension, pregnancy, hypovolemia, certain medications, and edematous conditions, including congestive heart failure, nephrotic syndrome, and cirrhosis (Pagana 2022). Under acute stress and increased aldosterone, the sodium-to-potassium ratio in the blood may increase due to sodium retention and potassium loss (Wardle 2019).

Aldosterone levels, in general, are influenced by diurnal variations, pregnancy, diet, posture, upright positioning, and supine positioning, which yields notably lower results. In adults, aldosterone levels range from 5-30 ng/dL (0.14-0.80 nmol/L, 138.70-832.20 pmol/L) in the upright position, while lower levels are seen when measuring in the supine position, i.e., 3-10 ng/dL (0.083-0.277 nmol/L, 83.22-277.40 pmol/L) (Pagana 2022).

Screening for hyperaldosteronism typically involves measuring serum aldosterone after a challenge with sodium, salt, or medications that suppress aldosterone levels. Healthy individuals will maintain serum aldosterone below 15 ng/dL (0.416 nmol/L, 416 pmol/L) following the challenge, whereas a persistently higher level may indicate hyperaldosteronism (Dominguez 2023).

However, some researchers suggest that serum aldosterone persistently above 10 ng/dL (0.277 nmol/L, 277.40 pmol/L) following a sodium challenge has a high probability of being associated with primary hyperaldosteronism (PHA) and should be evaluated further (Shidlovskyi 2019).

Researchers note that aldosterone variability may be substantial in those with and without aldosteronism, and repeat testing is indicated. Some individuals with confirmed PHA may have an aldosterone result below 10 ng/dL (0.277 nmol/L, 277.40 pmol/L), leading researchers to consider “more permissive screening recommendations for primary hyperaldosteronism” (Yozamp 2021).

Primary hyperaldosteronism is an adrenal disorder characterized by unregulated aldosterone production resistant to chemical suppression. It is most commonly due to adrenal hyperplasia or tumor secretion, especially from an adenoma. Sodium retention, potassium excretion, hypokalemia, hypertension, and suppressed plasma renin are observed in this disorder. The Endocrine Society Clinical Practice Guidelines indicate that PHA is a public health issue that should be screened for regularly, especially in those with hypertension (Hanna 2016). The prevalence of primary aldosteronism may be as high as 30% in those with resistant hypertension (Yozamp 2021).

The risk of atrial fibrillation, non-fatal myocardial infarction, and stroke is much higher in hypertensives with PHA than without it. The risk of kidney damage increases with hyperaldosteronism as well. A persistently elevated upright aldosterone above 19.83 ng/mL (0.550 nmol/L, 550.08 pmol/L) in conjunction with undetectable renin and spontaneous hypokalemia likely indicates primary hyperaldosteronism. However, lower aldosterone levels may be present in PAH, and high-risk individuals should be evaluated further, especially with an aldosterone of 15 ng/dL (0.416 nmol/L, 416 pmol/L) or above. Additional testing includes plasma aldosterone/renin ratio (ARR), urine aldosterone, and other confirmatory tests (Funder 2016). The ARR test is the most sensitive approach to differentiating primary from secondary hyperaldosteronism (Pagana 2022).

A prospective study of 71 subjects with resistant hypertension revealed a significantly higher median aldosterone in subjects compared to controls: 11 ng/dL (0.305 nmol/L, 305.14 pmol/L) versus 5.5 ng/dL (0.153 nmol/L, 152.57 pmol/L), respectively. Higher aldosterone was also significantly associated with obstructive sleep apnea in hypertensive subjects (Pratt-Ubunama 2007).

A low-salt diet can stimulate aldosterone production by activating the sympathetic nervous system. A study of 152 healthy subjects found that a low-salt diet was associated with significantly increased serum aldosterone with a mean of 21 ng/dL (0.583 nmol/L, 582.54 pmol/L) in those on a low-salt diet versus 3.4 ng/dL (0.094 nmol/L, 94.32 pmol/L) on a high-salt diet. Researchers associated a low-salt diet with insulin resistance in this cohort (Garg 2011).

Data from 4,095 African American subjects participating in the prospective Jackson Heart Study found that optimizing Life’s Simple 7 (LS7) metrics was associated with a significant and beneficial decrease in aldosterone. The LS7 categories include four health behaviors (smoking, dietary intake, physical activity, BMI) and three health factors (total cholesterol, fasting glucose, and blood pressure) (Kesireddy 2019).

Serum aldosterone, renin, and cortisol patterns (Lab Tests Online UK)

References

Craig, Micah, et al. “Biochemistry, Cholesterol.” StatPearls, StatPearls Publishing, 18 August 2021.

Dominguez, Alejandro, et al. “Hyperaldosteronism.” StatPearls, StatPearls Publishing, 12 February 2023.

Funder, John W et al. “The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.” The Journal of clinical endocrinology and metabolism vol. 101,5 (2016): 1889-916. doi:10.1210/jc.2015-4061

Garg, Rajesh et al. “Low-salt diet increases insulin resistance in healthy subjects.” Metabolism: clinical and experimental vol. 60,7 (2011): 965-8. doi:10.1016/j.metabol.2010.09.005

Hannah-Shmouni, Fady, et al. “Testing for Endocrine Hypertension.” Endotext, edited by Kenneth R Feingold et. al., MDText.com, Inc., 30 December 2016.

Kesireddy, Veena et al. “The Association of Life's Simple 7 with Aldosterone among African Americans in the Jackson Heart Study.” Nutrients vol. 11,5 955. 26 Apr. 2019, doi:10.3390/nu11050955

Kubzansky, Laura D, and Gail K Adler. “Aldosterone: a forgotten mediator of the relationship between psychological stress and heart disease.” Neuroscience and biobehavioral reviews vol. 34,1 (2010): 80-6. doi:10.1016/j.neubiorev.2009.07.005

LabTestsOnline UK https://labtestsonline.org.uk/tests/aldosterone-and-renin.

Monticone, Silvia et al. “Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis.” The lancet. Diabetes & endocrinology vol. 6,1 (2018): 41-50. doi:10.1016/S2213-8587(17)30319-4

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Pratt-Ubunama, Monique N et al. “Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension.” Chest vol. 131,2 (2007): 453-9. doi:10.1378/chest.06-1442

Shidlovskyi, Viktor O et al. “Topical Diagnosis and Determination of the Primary Hyperaldosteronism Variant.” Journal of medicine and life vol. 12,4 (2019): 322-328. doi:10.25122/jml-2019-0072

Tadros, Sherif F et al. “Higher serum aldosterone correlates with lower hearing thresholds: a possible protective hormone against presbycusis.” Hearing research vol. 209,1-2 (2005): 10-8. doi:10.1016/j.heares.2005.05.009

Wardle, Jon, and Jerome Sarris. Clinical naturopathy: an evidence-based guide to practice. Elsevier Health Sciences, 2019. 3rd edition

Yozamp, Nicholas et al. “Intraindividual Variability of Aldosterone Concentrations in Primary Aldosteronism: Implications for Case Detection.” Hypertension (Dallas, Tex. : 1979) vol. 77,3 (2021): 891-899. doi:10.1161/HYPERTENSIONAHA.120.16429