Podcast Summary: Diagnosing Adrenal Insufficiency
Podcast: Endocrine Feedback Loop
Host: Dr. Chase Hendrickson (A)
Guests: Dr. Katie Guttenberg (B), Dr. Anand Vaidya (C)
Fellows: Natalia Freitas, Nikola Gorajevic, Rinky Panya, a kind (various institutions)
Episode: EFL063
Date: July 24, 2025
Timestamps: Approximate, in MM:SS format
Overview: Main Theme and Purpose
This episode of Endocrine Feedback Loop examines a forthcoming JCEM (Journal of Clinical Endocrinology & Metabolism) study on diagnostic strategies for adrenal insufficiency, with a focus on the combined use of baseline cortisol and dehydroepiandrosterone sulfate (DHEAS) measurements. The discussion aims to unpack whether DHEAS, a stable and widely available marker, can supplement or even replace the need for dynamic testing (such as the cosyntropin stimulation test) in certain clinical situations. Hosted by Dr. Chase Hendrickson, with expert insights from Dr. Katie Guttenberg and Dr. Anand Vaidya, the episode contextualizes the clinical utility, limitations, and practical adoption of updated diagnostic algorithms for adrenal insufficiency.
Key Discussion Points and Insights
1. Challenges in Diagnosing Adrenal Insufficiency
- Diagnostic Difficulty: Symptoms are vague, and traditional testing is complex and time-sensitive (02:28).
- Morning Cortisol Testing: Classic cortisol cutoffs (<3 µg/dL consistent with AI, >15 µg/dL excludes AI) may no longer be reliable due to changes in assay technologies (02:28).
- Dynamic Testing: Cosyntropin stimulation is standard but inherently limited by lack of a true gold standard and practical barriers (03:41).
Quote (Anand Vaidya, 03:41):
“The term accuracy is a tricky one... there is no gold standard for adrenal insufficiency. We don’t have an international biomarker or histopathology that makes the diagnosis.”
2. DHEAS – Physiology and Diagnostic Rationale
- Characteristics of DHEAS: Secreted mainly by the adrenal cortex; ACTH-dependent; long half-life; stable (no diurnal variation) (05:25, 06:23).
- Comparison to Cortisol: Both are ACTH-dependent; both low in all forms of adrenal insufficiency (06:23).
- Surrogate Marker Analogy: DHEAS as a “long stable surrogate” for ACTH effect on the adrenals, akin to how A1C reflects blood glucose over time (06:23).
Quote (Anand Vaidya, 06:23):
“To summarize it, DHEAS is an ACTH-dependent, highly abundant, long half-lived, stable surrogate for cortisol... kind of like how we use A1C for glucose.”
3. The Study: Design, Methods, and Key Variables
- Study Type: Retrospective, single-center (Mayo Clinic), using data from 2005–2023 (09:45).
- Inclusion Criteria: Adults with cosyntropin test and DHEAS measurement within 3 months before or 1 week after the test (09:45).
- Exclusion Criteria: Recent hospitalization, estrogen use, congenital adrenal hyperplasia (CAH), or recent death (15:26).
- Gold Standard: Cortisol <18 µg/dL at 60 minutes after cosyntropin as definition of adrenal insufficiency (17:06).
- Subgroup Analyses: Timing of test, glucocorticoid use, age/sex-standardized DHEAS (20:19).
Quote (Anand Vaidya, 17:06):
“A cosyntropin-stimulated cortisol value of 18... has been around for many, many decades... but if you measured cortisol now on a modern assay, isn’t 18 saying you’re going to overcall adrenal insufficiency? ... Maybe the findings of this study are even stronger than stated.”
4. Key Results and Statistical Findings
Baseline Characteristics
- n ≈ 1100; 78% women; AI patients were older with higher comorbidity index (21:49).
Diagnostic Accuracy
- Baseline Cortisol:
- AUC: 0.81.
- <10 µg/dL: Sensitivity 96%, Specificity 30%.
- DHEAS:
- AUC: 0.81 (overall); Better accuracy (AUC 0.83) without recent glucocorticoid use (vs. 0.72).
- <100 µg/dL: Sensitivity 90%, Specificity 43%.
- In postmenopausal women: Sensitivity 98%, but very low specificity (12%).
Quote (Katie Guttenberg, 21:49):
“Baseline cortisol and DHEAS cut off levels... Baseline cortisol less than 10 had a sensitivity of 96%... a DHEAS level less than 100 demonstrated a sensitivity of 90% for diagnosing adrenal insufficiency.”
Combined Algorithm (28:19)
- Cortisol ≥10: AI excluded, no further testing.
- Cortisol 5–9.9 + DHEAS ≥60: AI unlikely, no further testing.
- Cortisol 5–9.9 + DHEAS <60: Proceed to stimulation test.
- Cortisol <5 + DHEAS <25: Treat as AI.
- Cortisol <5 + DHEAS ≥25: Stimulation test recommended.
Quote (Chase Hendrickson, 28:19):
“If your baseline cortisol is 10 or above, no further testing is required... If you have indeterminate cortisol and DHEAS is 60 or above, again, AI is pretty unlikely.”
5. Limitations and Potential Pitfalls
- Generalizability: Single-institution; patient populations and testing practices may differ elsewhere (12:56).
- Assay Effect: Modern vs. older immunoassays significantly affect cutoffs (17:06).
- DHEAS in Elderly/Postmenopausal Women: Age-related decline makes low values less specific; must interpret cautiously (25:09).
- Effect of Glucocorticoids: Recent use lowers DHEAS independently of adrenal status (31:51).
- No Adjustment Necessary: Age/sex standardization of DHEAS did not improve diagnostic accuracy (30:55).
- Secondary AI: Study less well validated for secondary adrenal insufficiency (34:05).
Quote (Anand Vaidya, 25:09):
“DHES changes over time... As you get older, the lower you get the DHES... you have to think twice about what a low DHES means in a 75-year-old woman.”
6. Clinical Practice Implications
- Simplified Workup: Adding DHEAS to morning cortisol may reduce need for dynamic testing (34:05).
- Resource Stewardship: Cosyntropin stimulation is costly and logistically challenging; DHEAS/cortisol can often suffice (37:57).
Quotes:
- Katie Guttenberg (40:27):
"I would [advocate routine DHEAS use]... the more we can get towards using other markers instead of dynamic testing... that's going to improve patient care."
- Anand Vaidya (41:31):
"If you're going to assess for adrenal insufficiency, you should measure morning cortisol. With that a DHEAS and... add on an ACTH. With those three values you can almost always make the assessment..."
Notable Quotes & Memorable Moments
| Timestamp | Speaker | Quote & Context | |-----------|------------------------|------------------------------------------------------------------------------------| | 03:41 | Anand Vaidya | “There is no gold standard for adrenal insufficiency...” Discussing assay issues | | 06:23 | Anand Vaidya | “DHEAS represents ACTH-dependent steroidogenesis in a long stable manner...” | | 17:06 | Anand Vaidya | “A cosyntropin-stimulated cortisol value of 18... has been around for decades...” | | 25:09 | Anand Vaidya | “The older you get, the lower the DHEAS... less prognostic value for AI diagnosis.” | | 34:05 | Chase Hendrickson | "The diagnosis of adrenal insufficiency is unlikely to be missed..." | | 37:57 | Anand Vaidya | “This algorithm... can be thought of in a more holistic way; you don’t want to be memorizing cutoffs.” |
Timeline of Important Segments
| Timestamp | Segment | |-----------|----------------------------------------------------------------------------------------------------------| | 00:00–03:41 | Introduction, background, and challenges in diagnosing adrenal insufficiency | | 03:41–06:23 | Dynamic testing and physiology of DHEAS vs. cortisol | | 09:45–15:26 | Study methods, inclusion/exclusion criteria, and generalizability concerns | | 17:06–20:19 | Cosyntropin test cutoffs, assay issues, and the “gold standard” debate | | 21:49–28:19 | Results overview: diagnostic accuracy, statistical findings | | 28:19–34:05 | Interpretation, summary scheme for diagnosis, limitations (age, glucocorticoids, etc.) | | 34:05–37:57 | Strengths, limitations, and concluding discussion | | 40:27–42:31 | Should this approach become standard of care? Experts’ practical recommendations |
Flow and Tone
The conversation is collegial, evidence-oriented, and draws on both academic rigor and pragmatic clinical experience. Both Dr. Guttenberg and Dr. Vaidya emphasize an evolving, nuanced approach to endocrine diagnostics, balancing clear statistical data with real-world implementation. The tone is supportive, educational, and optimistic about improving care and reducing unnecessary procedures for patients.
Final Takeaways & Practice Pearls
- DHEAS + Cortisol: The combination of morning cortisol and DHEAS measurements can safely eliminate the need for dynamic testing in many patients suspect for adrenal insufficiency, particularly if cortisol is ≥10 µg/dL or DHEAS is robust.
- Indeterminate Range Adjudication: Patients with low-normal cortisol and low DHEAS may still need dynamic testing; older age and recent glucocorticoid use may limit DHEAS’s utility.
- Assay Awareness: Practitioners should ensure assay cutoffs are updated for their local lab technology; classic thresholds may overdiagnose AI with modern immunoassays.
- Broader Adoption: Both experts advocate for widespread adoption of this approach, with proper education and understanding of limitations.
Practice-Changing Quote (Anand Vaidya, 41:31):
"For those of you who are specialists, I would strongly recommend this. For those of you who interface with non-specialists... I would advise your colleagues to do that so... you can use those values to make the full adjudication..."
For further study:
- See the cited JCEM article for details and figures
- Review recent guidelines (Endocrine Society/European Society of Endocrinology) on glucocorticoid-induced AI
Episode Summary Prepared for Clinicians and Trainees – Endocrine Feedback Loop, July 2025