Cortisol

In 1936, Eduard C. Kendall (1886-1972) discovered cortisone, followed by cortisol the following year. By 1946, 39 different corticoids of the adrenal cortex had been isolated and defined (Kaiser 2002).

Philip S. Hench (1896-1965) used cortisone therapeutically for the first time in 1948 in a severely immobilized patient with chronic polyarthritis. The patient was mobile again after just one week (Kaiser 2002).

Kendall and Hench were awarded the Nobel Prize in 1950 (Kaiser 2002).

Cortisol is a steroid of the adrenal cortex that is produced in the zona fasciculata (Herold 2025). Cortisol is the most important representative of the glucocorticoids and plays a role in metabolism, the immune system and psychological behavior (Birbaumer 2010).

In addition to cortisol, the most important corticosteroids include aldosterone and, to a lesser extent, corticosterone. Cortisol is found particularly in the liver as inactive cortisone (Herold 2025).

The daily secretion rate is 20-30 mg/24 h, the plasma concentration is 6-25 µg/100 ml (Herold 2025).

The release of cortisol is regulated by one of the 4 glandotropic hormones of the anterior pituitary gland (Birbaumer 2010).

Cortisol is largely bound in the blood:

- 75 % to the transport protein transcortin

- 15 % to albumin

- in free form to 10 % (Herold 2025)

Synthetic glucocorticoids, on the other hand, are not bound to transcortin (Herold 2025).

1044 µg of cortisol is excreted in 24h urine (Kasper 2025).

The half-life of cortisol is approx. 90 min, that of synthetic cortisol is many times longer (Herold 2025).

Cortisol is excreted via the kidneys after metabolization in the liver (Herold 2025).

The circadian daily rhythm of cortisol shows an increase in the early morning hours with peak values at around 08:30. The values then fall slowly. A drop below the rhythm-corrected mean (MESOR) is found in the early evening hours, with lows around midnight (Kasper 2025).

If this secretion pattern is interrupted, the cortisol level can rise chronically. This in turn can lead to the following diseases:

- Myocardial infarction

- apoplexy

- diabetes mellitus

- mental disorders (Vignesh 2024)

Effects of cortisol:

- Stimulation of gluconeogenesis in the liver (Birbaumer 2010)

- stimulates gluconeogenesis (Neumeister 2010)

- antiphlogistic

- anti-allergic

- immunosuppressive

- lowers the excitability threshold (thus leading to an increased readiness to convulse)

- can lead to euphoria at the beginning and to depression in long-term therapy (Birbaumer 2010)

Cortisol can be measured in blood, saliva and urine. However, this only ever shows a snapshot of the cortisol value. The long-term cortisol load can be measured using a new method, the determination of the concentration of cortisol in the hair (HCC). With this measurement, the cumulative cortisol load can be measured over months and even years and thus provide important findings in the case of e.g.:

- Disorders of the HPA axis

- Cushing's syndrome

- mental health (increase in cortisol levels in the case of, for example, drastic life events, endurance training, shift work, depression and a drop in cortisol levels in the case of, for example, generalized anxiety disorders (Wester 2015).

Studies by Herrera et al. (2022) have shown that women with primary and metastatic breast cancer have basally elevated cortisol levels. Cortisol induces breast cancer metastases in vivo, but also strengthens the blood-brain barrier against microbes and peripheral immune cells. For this reason, caution is advised when treating patients with known breast cancer with glucocorticoids (Herrera 2022).

The release of cortisol is stimulated by ACTH. Cortisol has a catabolic effect, it promotes lipolysis, gluconeogenesis and protolysis (Pschyrembel).

The affinity of the glucocorticoid cortisol for the mineralocorticoid receptor (MLR) is just as high as that of aldosterone. In the distal nephron, cortisol is converted into cortisone by the enzyme 11ßHSD-2 (Kasper 2015).

- Cushing's syndrome due to excessive cortisol production, e.g. in the presence of a pituitary tumor or an ectopic tumor (Kasper 2015)

- Adrenal insufficiency in e.g. Addison's disease (Kasper 2015)

To date, there are no drugs with a therapeutic indication range comparable to that of corticoids (Kaiser 2002).

The most important indications for treatment with cortisol include rheumatic and allergic diseases (Seifert 2021), bronchial asthma and collagenoses (Schwabe 2019).

Cortisone is also used therapeutically as an immunosuppressant (Ludwig 2020)

1. Birbaumer N, Schmidt R F (2010) Biological Psychology. Springer Medizin Verlag Heidelberg 132-133
2. Herold G et al. (2025) Internal medicine. Herold Publishing House 780
3. Herrera R A, Deshpande K, Martirosian V, Saatian B, Julian A, Eisenbarth R, Das D, Iyer M, Neman J (2022) Cortisol promotes breast-to-brain metastasis through the blood-cerebrospinal fluid barrier. Cancer Rep (Hoboken). 5 (4) e1351
4. Kaiser H, Kley H K (2002) Cortisone therapy: corticoids in clinic and practice. Georg Thieme Verlag Stuttgart / New York 5-6, 116
5. Kasper D L, Fauci A S, Hauser S L, Longo D L, Jameson J L, Loscalzo J et al. (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 306, 64e-7, 1619, 1755, 2310
6. Ludwig M (2020) Repetitorium specialist examination in internal medicine. Elsevier Urban and Fischer Publishers Germany113
7. Neumeister B, Böhm B O (2010) Clinical guide to laboratory diagnostics. Urban and Fischer Publishing 310
8. Pschyrembel online. Cortisol. Doi: https://www.pschyrembel.de/Kortisol/K059R
9. Schwabe U (2019) Corticosteroids. Drug Prescription Report 623-630
10. Seifert R (2921) Corticosteroids. Drug prescription report 389-395
11. Vignesh V, Castro-Dominguez B, James T D, Gamble-Turner J M, Lightman S, Reis N M (2024) Advancements in Cortisol Detection: From Conventional Methods to Next-Generation Technologies for Enhanced Hormone Monitoring. ACS Sens. 9 (4) 1666-1681
12. Wester V L, van Rossum E F C (2015) Clinical applications of cortisol measurements in hair. Eur J Endocrinol. 173 (4) M1-10