Why check pregnenolone (Pregnenolone) levels?

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Last updated: March 7, 2025 • View editorial policy

From the Guidelines

Pregnenolone levels should be checked to evaluate adrenal function and hormone pathways, particularly in cases of suspected adrenal insufficiency or congenital adrenal hyperplasia, as it is a precursor to many important hormones including cortisol, DHEA, progesterone, and testosterone 1. When investigating adrenal insufficiency, such as primary adrenal insufficiency (PAI), it is crucial to follow a diagnostic approach that includes the measurement of serum cortisol and plasma ACTH, as recommended in the consensus statement on the diagnosis, treatment, and follow-up of patients with PAI 1.

Key Points to Consider

  • Pregnenolone testing can help assess overall hormonal balance, particularly in patients with fatigue, cognitive issues, mood disorders, or stress-related symptoms.
  • The test is typically done using a blood sample, and results should always be interpreted by a healthcare provider in the context of clinical symptoms and other hormone levels.
  • Normal ranges for pregnenolone vary by laboratory and patient factors like age and sex.
  • If pregnenolone levels are abnormal, treatment approaches depend on the underlying cause and may include hormone replacement, lifestyle modifications, or addressing primary conditions affecting hormone production.

Diagnostic Approach

In the context of PAI, the diagnostic test should include paired measurement of serum cortisol and plasma ACTH, and in equivocal cases, a synacthen (tetracosactide) stimulated peak serum cortisol <500 nmol L-1 is diagnostic of PAI 1.

Treatment Considerations

While pregnenolone itself has neurosteroid properties that affect brain function, memory, and mood regulation, there is insufficient evidence to recommend routine replacement of adrenal androgens, including pregnenolone, in patients with PAI 1. However, patients with adrenal insufficiency should receive sufficient education to manage daily medications and situations of minor to moderate concurrent illnesses, and supplies to allow self-injection of parenteral hydrocortisone should be provided 1.

From the Research

Importance of Pregnenolone Levels

Checking pregnenolone levels is crucial in various medical conditions, including:

  • Congenital adrenal hyperplasia (CAH) 2
  • Adrenal tumors, ACTH excess, or idiopathic hirsutism 3
  • Rheumatoid arthritis and systemic lupus erythematosus 4
  • Adrenal insufficiency 5

Diagnostic Value

Pregnenolone levels can help diagnose and monitor various conditions, such as:

  • 17 alpha-hydroxylase/17, 20 lyase deficiency, a rare form of CAH 2
  • Adrenal carcinoma, where elevated 17-OH-pregnenolone levels can indicate the presence of a tumor 3
  • Idiopathic hirsutism, where basal levels of pregnenolone and 17-OH-pregnenolone are elevated 3
  • Rheumatoid arthritis and systemic lupus erythematosus, where pregnenolone levels are similar to those in healthy controls 4

Relation to Other Adrenal Hormones

Pregnenolone levels are related to other adrenal hormones, such as:

  • Cortisol, which is elevated in response to ACTH stimulation 3, 5
  • Dehydroepiandrosterone (DHEA), which is decreased in patients with rheumatoid arthritis and systemic lupus erythematosus 4
  • Cortisone, which reacts similarly to cortisol in response to Synacthen tests 5

Diagnostic Tests

Pregnenolone levels can be measured during various diagnostic tests, including:

  • Insulin tolerance test (ITT) 5
  • Synacthen test, which can be used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis) 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.