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".

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: 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.

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 guideline 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 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.

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 someone 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.

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 of fatigue, poor sleep, weight gain or feeling burned out, this is the honest answer.

For persistent fatigue, the Dutch primary-care guideline starts with a short list, and the shortness is precisely the point:

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

Among people presenting to a GP with fatigue, roughly 4% turn out to have a serious physical illness. The largest categories are musculoskeletal complaints, infections and psychological or social causes. In more than half, no physical explanation is found even after a year.

If you feel burned out, there is no blood value that demonstrates it. Burnout is a clinical diagnosis your GP makes from your story, and the Dutch guideline says of additional investigation, literally: "not indicated". What does work is day structure, paced recovery and addressing the cause, together with your GP or occupational physician. That costs you nothing here, and it is the only thing that genuinely moves you forward.

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 order 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 order the single cortisol test from us. If they ask for ACTH or DHEA-S, that measurement belongs in your doctor's request, not in a panel you pick out yourself.

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

• 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.
• Cadegiani FA, Kater CE. Adrenal fatigue does not exist: a systematic review. BMC Endocr Disord. 2016;16(1):48. PMID 27557747.
• Koch H et al. Ordering blood tests for patients with unexplained fatigue in general practice: what does it yield? Br J Gen Pract. 2009;59(561):e93-100. PMID 19341544.
• 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. NHG-Standaard Overspanning en burn-out (M110).