What is considered a low Adrenocorticotropic Hormone (ACTH) level according to the Endocrine Society?

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From the Guidelines

According to the most recent evidence, a low Adrenocorticotropic Hormone (ACTH) level is generally considered to be below 5-10 pg/mL (1-2 pmol/L) 1.

Importance of ACTH Levels

This threshold is crucial in the evaluation of adrenal insufficiency and Cushing's syndrome. Low ACTH levels typically indicate secondary adrenal insufficiency, where the problem originates in the pituitary gland rather than the adrenal glands themselves.

Interpreting ACTH Results

When interpreting ACTH results, it's essential to consider them in the context of cortisol levels and clinical symptoms. For example, low ACTH with low cortisol suggests pituitary dysfunction, while low ACTH with high cortisol may indicate an adrenal tumor producing excess cortisol.

Clinical Considerations

Time of collection is also crucial as ACTH follows a diurnal rhythm with highest levels in the early morning. Blood samples should ideally be collected in the morning, placed on ice immediately, and processed quickly to prevent degradation of the hormone which could lead to falsely low results.

Key Points to Consider

  • Low ACTH levels can indicate secondary adrenal insufficiency
  • Interpretation of ACTH results should consider cortisol levels and clinical symptoms
  • Time of collection and handling of blood samples are critical to avoid falsely low results
  • The relationship between ACTH and cortisol can distinguish between primary and secondary adrenal insufficiency 1

From the Research

Definition of Low Adrenocorticotropic Hormone (ACTH) Level

According to the provided studies, there is no direct reference to the Endocrine Society's definition of a low ACTH level. However, the studies provide some information on ACTH levels in different contexts:

  • A study from 2 measured plasma ACTH levels in normal subjects and patients with hypothalamo-pituitary disorders, finding basal levels of 23.1 +/- 13.6 pg/ml in young subjects and 17.5 +/- 11.2 pg/ml in elderly subjects.
  • The same study found that plasma ACTH levels were less than the detection limit (5 pg/ml) in patients with isolated ACTH deficiency, and less than 10 pg/ml in patients with hypopituitarism.

Diagnostic Criteria for Adrenal Insufficiency

The studies discuss the diagnostic criteria for adrenal insufficiency, including:

  • A study from 3 states that low plasma cortisol and normal to low plasma ACTH indicates a pituitary origin for the deficiency.
  • A study from 4 investigates the value of basal cortisol level for prediction of adrenal insufficiency, finding that basal cortisol levels ≤100 and ≥450 nmol/L had high diagnostic accuracy.

ACTH Stimulation Test

The studies discuss the use of the ACTH stimulation test for diagnosing adrenal insufficiency:

  • A study from 5 summarizes the recent literature evidence on the conduction and interpretation of the ACTH stimulation test for the diagnosis of secondary adrenal insufficiency.
  • A study from 6 defines the effective time frame of adequate serum cortisol response to the short standard 250-microg adrenocorticotropic hormone stimulation test after initiation of high-dose glucocorticoid therapy.

Key points to consider:

  • The studies provide information on ACTH levels and diagnostic criteria for adrenal insufficiency, but do not directly address the Endocrine Society's definition of a low ACTH level.
  • The ACTH stimulation test is a useful tool for diagnosing adrenal insufficiency, but its interpretation requires careful consideration of the clinical context and laboratory results.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

DIAGNOSTIC ACCURACY OF BASAL CORTISOL LEVEL TO PREDICT ADRENAL INSUFFICIENCY IN COSYNTROPIN TESTING: RESULTS FROM AN OBSERVATIONAL COHORT STUDY WITH 804 PATIENTS.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2017

Research

Adrenocorticotropic hormone stimulation test during high-dose glucocorticoid therapy.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2009

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.

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