Discussion: Hormonal Workup - Aldosterone

The Endocrine Society is the only organization that currently publishes guidelines on the workup of primary aldosteronism. All recommendations and statements are taken from those guidelines unless specifically cited to a different source.

Clinical Presentation

• Clinical suspicion for aldosterone-secreting tumors should be high in the following scenarios. (1)

  • Discovery of an adrenal incidentaloma on imaging in a patient with a history of hypertension

  • Sustained blood pressure above 150/100 mm Hg on each of three measurements obtained on different days

  • Hypertension (>140/90 mm Hg) resistant to three conventional antihypertensive drugs

  • Controlled blood pressure (< 140/90) on four or more anti-hypertensive drugs

  • Hypertension and spontaneous or diuretic-induced hypokalemia

  • Hypertension and sleep apnea

  • Hypertension and a family history of early onset hypertension or CVA at a young age (< 40 years)

  • Hypertensive first-degree relative of patients with primary aldosteronism

Hormonal Workup

Table

• Plasma aldosterone concentration

• Plasma renin activity

• Aldosterone/Renin Ratio (ARR)

• Proper testing conditions

  • Stop low sodium diet and replete hypokalemia

  • Best collected in the morning after patients have been out of bed for 2 hours

  • Seated for 5-15 minutes prior to blood draw

  • Mineralocorticoid receptor blockers should be stopped for 4 weeks prior

  • Other medications may interfere with ARR, but cessation is not required for many patients.

  • See table 3 from the endocrine society guidelines for a complete list of factors which may affect testing

• Interpretation

  • Most patients with unilateral primary aldosteronism have plasma aldosterone concentrations > 15 ng/dL. (2)

  • There is no single ARR cutoff that is diagnostic of primary aldosteronism. (3)

  • Posture and time of sampling should be standardized within centers

  • Most common cutoff for ARR is > 20

• Confirmatory testing

  • In patients with hypokalemia, plasma aldosterone concentration > 20 ng/dL, and plasma renin activity below limit of detection, confirmatory testing is not required. (1)

  • For all others, confirmatory testing with oral sodium loading test, saline infusion test, fludrocortisone suppression test, or captopril challenge test is recommended

  • Patients should be referred to endocrinologist if not already when confirmatory testing is being considered

Subtype Classification

• Traditionally two subtypes have been defined: (1) bilateral adrenal hyperplasia and (2) aldosterone-producing adenoma

  • This dichotomy has been challenged recently due to improved immunohistochemical staining for aldosterone-synthase (CYP11B2); however, it remains a useful model to guide clinical decision making. (4)

• If not already done, all patients with suspected primary aldosteronism should have an adrenal-protocol CT scan performed

• Adrenal venous sampling (AVS) is the gold standard test to distinguish unilateral (and therefore surgically-remediable) from bilateral primary aldosteronism

  • All patients considering surgical resection should undergo AVS with the possible exception of patients <35 years old  with spontaneous hypokalemia, marked aldosterone excess, and unilateral adrenal lesions with radiological features consistent with a cortical adenoma on adrenal CT scan.

  • Sensitivity is 95% and specificity is 100%

  • Must have a dedicated team of interventional radiology and endocrinology to perform consistently well

  • Can be done with or without continuous cosyntropin administration

  • Lateralization index (high side to low side) of ≥ 4:1 is indicative of unilateral aldosterone excess

  • Contralateral suppression (i.e. concentration of aldosterone from non-hypersecreting adrenal vein is less than peripheral circulation) can also be helpful in making the diagnosis.(5)

Last update: 7/17/2022, Ben Ristau and Marshall Strother

Image credit: Jpogi via Wikimedia Commons

 References

1.        Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, 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).

2.        Stowasser M, Gordon RD. Primary aldosteronism - Careful investigation is essential and rewarding. In: Molecular and Cellular Endocrinology. 2004.

3.        Tiu SC, Choi CH, Shek CC, Ng YW, Chan FKW, Ng CM, et al. The use of aldosterone-renin ratio as a diagnostic test for primary hyperaldosteronism and its test characteristics under different conditions of blood sampling. Vol. 90, Journal of Clinical Endocrinology and Metabolism. 2005.

4.        Miller BS, Turcu AF. Partial adrenalectomy: Ready for primetime? Vol. 169, Surgery (United States). 2021.

5.        Wolley MJ, Gordon RD, Ahmed AH, Stowasser M. Does contralateral suppression at adrenal venous sampling predict outcome following unilateral adrenalectomy for primary aldosteronism? A retrospective study. J Clin Endocrinol Metab. 2015;100(4).