Extended cortisol: the adrenal panel we do not sell

The combination of cortisol + ACTH + DHEA-S is not a coincidence. It is very nearly the exact panel sold under names like "adrenal stress index" to demonstrate "adrenal fatigue". The sports version has only been given a different label: the same three tubes, now packaged as recovery monitoring.

That condition does not exist. The term was coined in 1998 by a chiropractor. A 2016 systematic review searched 3,470 publications, kept 58, and found no substantiation at all. In most fatigued participants, the cortisol measurements were simply normal. The Endocrine Society is blunt: no scientific proof exists, and there is no test that can detect it.

The international guideline is also explicit about ACTH. The same sentence that advises against a random cortisol measurement also advises against a random ACTH measurement. ACTH belongs in the story only after a doctor has established, by the proper route, that something is genuinely wrong with your cortisol. As a standalone value, without that history, it cannot be interpreted.

And the cortisol-to-DHEA ratio, like the testosterone-to-cortisol ratio, does not solve the problem but doubles it: you stack the noise of two strongly fluctuating hormones on top of each other and call the output a recovery score. The joint consensus statement of the European College of Sport Science and the American College of Sports Medicine on overtraining is clear about this: many markers are in use, hormones included, but none of them meets all the criteria to be generally accepted.

It sounds logical: if one value is uncertain, measure three. But that is not how it works, and the numbers are unambiguous.

Reference ranges are usually set so that the middle 95% of healthy people fall inside them. That means every single test has roughly a 5% chance of an "abnormal" result in a healthy person that means nothing. With five tests, that chance rises to about 23%. The Dutch primary-care laboratory guidance does this arithmetic itself, and concludes that for vague complaints you should order as little as possible.

This is not theory. A Dutch randomised trial (the VAMPIRE trial) in people with unexplained fatigue compared a short blood panel with an expanded one:

• short panel: 6.4% genuine findings, 22.0% false positives
• expanded panel: 7.5% genuine findings, 55.5% false positives

You buy 1.1 percentage points more truth at the price of 33.5 percentage points more false alarms. That is the heart of why we do not sell this panel: it is not neutral, it actively makes your situation less clear. More tubes are not more answers, they are more false alarms.

The diseases this panel would be looking for are extraordinarily rare. Cushing's syndrome occurs in European population studies in around 2 to 3 people per million per year. Addison's disease in around 100 to 140 per million.

Work that through for a healthy athlete without the specific signs a doctor looks for, and the outcome is merciless: of all "abnormal" results in such a group, the overwhelming majority are false alarms. Not a few. Almost all of them.

And a false alarm is not free. An abnormal cortisol result often leads to imaging of the adrenal glands. In roughly 3% of people over 50, rising to 10% over 80, that incidentally reveals a benign nodule on the adrenal gland that has nothing to do with anything. Which then has to be investigated. That is how a cascade of tests, worry and cost begins, starting from a test you never needed to take.

The other exit is even more likely: your "abnormal" DHEA-S or cortisol becomes the on-ramp to a supplement protocol. A study in Mayo Clinic Proceedings tested twelve over-the-counter "adrenal support" supplements and found thyroid hormone that was not on the label in all twelve, and a steroid in a quarter of them. If you are drug-tested, that is not merely pointless, it is a real risk.

One more thing worth knowing: research shows that testing when the chance of disease is low does not reassure you either. The worry and the symptoms persist; the test changes little. "Let's just measure it to be sure" does not, in practice, deliver that certainty.

If you came here because your recovery is lagging, your sleep is getting worse, or you think you are heading towards overtraining, this is the honest answer.

Start with the arithmetic. Cortisol in blood has to change by around 47% (in saliva, 96 to 245%) before you can say with 95% confidence that something genuinely changed. Your value has to nearly double before it counts as a change at all. The day-to-day noise is larger than any training signal you are looking for.

Worse: the direction is not even stable. The largest meta-analysis in this field reviewed 147 studies and found that the cortisol response after waking rises with job stress, and falls with fatigue, burnout and exhaustion. And the study that argues most strongly in cortisol's favour found higher midday values in people with burnout, the exact opposite of the "exhausted adrenals" story. A systematic review of 31 biomarker studies in burnout concluded plainly that no potential biomarkers were found. So one number gives you no direction: you cannot tell "overtrained" from "stressed", and neither from "nothing is wrong".

The things that are trackable share three properties: you can measure them daily, compare them against your own baseline, and they move enough to be visible through the noise.

• HRV and resting heart rate, every morning against your own rolling average. Not a diagnosis, but a trend you can genuinely see.
• Sleep duration, sleep regularity and your subjective recovery score. Boring, free, and by far the strongest predictors of how your week will go.
• Your training load and your energy intake. Ramping up too fast and chronically under-eating explain more flat sessions than any hormone does.

If the fatigue persists, Dutch primary-care diagnostics starts with a short list, and the shortness is precisely the point:

• Haemoglobin, and if abnormal your iron stores via ferritin: low ferritin is common in endurance athletes and is genuinely treatable
• CRP, an inflammatory marker
• Fasting glucose
• TSH, your thyroid: genuinely a common and treatable cause of fatigue

We would rather earn nothing from you than sell you a panel that does not answer your question.

To avoid any misunderstanding: adrenal diseases exist, they are serious, and they are sometimes recognised too late. We are not saying your symptoms are not real.

But the route there runs through your GP, not through a panel you pick out yourself. A doctor looks for specific signs and then chooses the right test: two late-night saliva samples, two 24-hour urine collections, a dexamethasone suppression test, or an ACTH stimulation test. A diagnosis also requires two abnormal measurements, and referral to an endocrinologist.

If your doctor specifically asked for cortisol, you can come to us for the single cortisol test. If they ask for ACTH or DHEA-S, that measurement belongs in your doctor's request, not in a panel you assemble yourself.

We think you should be able to check what we base this on.

• Koch H et al. Ordering blood tests for patients with unexplained fatigue in general practice: what does it yield? Results of the VAMPIRE trial. Br J Gen Pract. 2009;59(561):e93-100. PMID 19341544. (False positives from 22.0% to 55.5%; genuine findings from 6.4% to 7.5%.)
• Chida Y, Steptoe A. Cortisol awakening response and psychosocial factors: a systematic review and meta-analysis. Biol Psychol. 2009;80(3):265-78. PMID 19022335. (147 studies: higher with job stress, lower with fatigue, burnout and exhaustion.)
• Pilger A et al. Midday and nadir salivary cortisol appear superior to cortisol awakening response in burnout assessment and monitoring. Sci Rep. 2018;8(1):9151. PMID 29904183. (The burnout group had higher, not lower, cortisol.)
• Danhof-Pont MB et al. Biomarkers in burnout: a systematic review. J Psychosom Res. 2011;70(6):505-24. PMID 21624574. ("No potential biomarkers for burnout were found.")
• Meeusen R et al. Prevention, diagnosis, and treatment of the overtraining syndrome: joint consensus statement of the ECSS and the ACSM. Med Sci Sports Exerc. 2013;45(1):186-205. PMID 23247672. (No proposed marker meets all the criteria for general use.)
• Cadegiani FA, Kater CE. Adrenal fatigue does not exist: a systematic review. BMC Endocr Disord. 2016;16(1):48. PMID 27557747.
• Akturk HK et al. Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones. Mayo Clin Proc. 2018;93(3):284-90. PMID 29502560.
• Nieman LK et al. The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-40. PMID 18334580. (Explicitly recommends against random serum cortisol and random plasma ACTH.)
• Bornstein SR et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-89. PMID 26760044.
• Rolfe A, Burton C. Reassurance after diagnostic testing with a low pretest probability of serious disease. JAMA Intern Med. 2013;173(6):407-16. PMID 23440131.
• Fassnacht M et al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas. Eur J Endocrinol. 2023;189(1):G1-G42. PMID 37318239.
• NHG/NVKC LESA Laboratoriumdiagnostiek, chapter on general blood work.