Hormone Biomarkers: Cortisol, PM

Optimal Takeaways

Cortisol is a regulatory steroid hormone produced in the adrenal gland. It has effects throughout the body, especially during the stress response. Under normal circumstances, it helps to wake you up in the morning and then declines during the day. However, prolonged elevated cortisol can perpetually increase blood glucose, blood pressure, muscle breakdown, brain volume loss, and micronutrient depletion. Persistently low cortisol can lead to fatigue, exhaustion, and low blood pressure.

Low cortisol levels are associated with Addison’s disease, adrenal insufficiency, congenital adrenal hyperplasia, hypothyroidism, hypopituitarism, and liver disease. Medications that reduce cortisol include lithium, levodopa, phenytoin, androgens, and exogenous steroids (Pagana 2021).

High cortisol levels are associated with Cushing syndrome, pregnancy, obesity, adrenal carcinoma, hyperthyroidism, liver disease, and physical and emotional stress. Medications that increase cortisol include cortisone, amphetamines, spironolactone, and oral contraceptives (Pagana 2021). Higher evening serum cortisol may be associated with obesity (Al-Safi 2018), PCOS (Kiatka 2015), and subclinical hypothyroidism (Watler 2012).    

Standard Range: 3 - 17 ug/dL (82.76 - 469 nmol/L)

The ODX Range: 4 - 10 ug/dL (110.35 - 275.88 nmol/L)  

Overview

Cortisol is a glucocorticoid synthesized in the adrenal gland, though the hypothalamus and pituitary glands regulate its release. Cortisol is considered a stress hormone but also contributes to homeostasis via blood pressure regulation, immune system function, anti-inflammatory actions, and participation in protein, carbohydrate, and fat metabolism (Katsu 2021).

Measurement of plasma cortisol is considered the best way to evaluate adrenal activity. Levels typically peak between 6 am and 8 am and then decrease throughout the day, reaching nadir around midnight. A 4 pm value for serum cortisol should be just one-third to two-thirds of the 8 am value. Alterations in this diurnal rhythm may be an initial sign of adrenal hyperactivity, even without elevated serum cortisol. Cushing disease, characterized by persistently elevated cortisol, may present with high or high normal am cortisol that does not decline throughout the day and evening. High and low levels may be transposed in night shift workers (Pagana 2021).

The hyperglycemic effect of cortisol appears to be more pronounced in the evening than in the morning. Evening cortisol elevations are also associated with increased insulin secretion, insulin resistance, and decreased insulin clearance... anomalies associated with obesity, Cushing’s syndrome, aging, and hypertension (Plat 1999).

One small cross-sectional study of 22 premenopausal women found that those with obesity sustained significantly higher evening cortisol than normal-weight women and had almost double the increase in cortisol following a noon meal (Al-Safi 2018). In women with PCOS, evening cortisol was significantly higher than in women with no signs of PCOS, with a mean level of 11.8 versus 4.7 ug/dL (325 nmol/L versus 130 nmol/L). The two groups had no significant difference in morning cortisol (Kiatka 2015).    

Both evening and morning cortisol were higher in men with central serous chorioretinopathy (CSC) and elevated stress scores. Those with CSC had a mean morning cortisol of 15.46 ug/dL (427 nmol/L) and evening cortisol of 11.74 ug/dL (323.9 nmol/L), whereas controls had a mean morning cortisol of 11.73 ug/dL (323.6 nmol/L) and an evening cortisol of 10.96 ug/dL (302 nmol/L) (Argarwal 2016).

Subclinical hypothyroidism may be associated with elevated cortisol. One cross-sectional study of 54 healthy young individuals with TSH below 10 uIU/L observed significantly higher afternoon cortisol at 13.83 versus 8.66 ug/dL (381 vs. 239 nmol/L) when TSH was above 2 uIU/L versus at 2 or below. Researchers suggest that even subclinical hypothyroidism may cause elevations in cortisol, possibly due to decreased clearance and lack of negative feedback between cortisol and the HPA axis. Past research supports an association between elevated cortisol, subclinical hypothyroidism, increased depression, anxiety, and compromised cognitive function (Walter 2012).

References

Al-Safi, Zain A et al. “Evidence for disruption of normal circadian cortisol rhythm in women with obesity.” Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology vol. 34,4 (2018): 336-340. doi:10.1080/09513590.2017.1393511

Agarwal, Abhishek et al. “Evaluation and correlation of stress scores with blood pressure, endogenous cortisol levels, and homocysteine levels in patients with central serous chorioretinopathy and comparison with age-matched controls.” Indian journal of ophthalmology vol. 64,11 (2016): 803-805. doi:10.4103/0301-4738.195591

Kamba, Aya et al. “Association between Higher Serum Cortisol Levels and Decreased Insulin Secretion in a General Population.” PloS one vol. 11,11 e0166077. 18 Nov. 2016, doi:10.1371/journal.pone.0166077

Katsu, Yoshinao, and Michael E. Baker. "Cortisol." Handbook of hormones. Academic Press, 2021. 947-949.

Kiałka, Marta et al. “Evening not morning plasma cortisol level is higher in women with polycystic ovary syndrome.” Przeglad lekarski vol. 72,5 (2015): 240-2. Kazlauskaite, Rasa et al. “Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis.” The Journal of clinical endocrinology and metabolism vol. 93,11 (2008): 4245-53. doi:10.1210/jc.2008-0710

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Walter, Kimberly N et al. “Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and women.” Thyroid research vol. 5,1 13. 30 Oct. 2012, doi:10.1186/1756-6614-5-13

Wardle, Jon, and Jerome Sarris. Clinical naturopathy: an evidence-based guide to practice. Elsevier Health Sciences, 2019. 3rd edition.