Tetrahydrocortisol (a-THF) is a metabolite of cortisol. Cortisol is metabolized into 5-alpha-Tetrahydrocortisol (5aTHF) and 5-beta-Tetrahydrocortisol (5b-THF). These will often reflect a chronic adrenal picture if levels are out of normal limits. Urine contains free cortisol, but it also contains many cortisol metabolites, like cortisone or 5- alpha- tetrahydrocortisol, 5-beta-tetrahydrocortisol, tetrahydrocortisone, etc. Metabolized cortisol reflects the total cortisol produced and clearing through the liver, while free-cortisol results tell us how much cortisol is free to bind to receptors and allows for assessment of the circadian rhythm.
The ratio of cortisol metabolites and cortisone metabolites best represent the overall dominance of either active cortisol or inactive cortisone.
Cortisol is made from cholesterol in the Zona fasciculata layer of the adrenal cortex. 80-90% of cortisol is bound to cortisol-binding globulin (CBG); much like thyroid is bound to thyroid-binding globulin (TBG) and testosterone is bound to sex hormone-binding globulin (SHBG). A very small percentage of cortisol is free and unbound, while the remaining is in transition. The human body produces cortisol first, and then different glands have the ability to keep it as cortisol or convert it into cortisone, which is biologically inactive, through the enzyme 11-beta-hydroxysteroiddehydrogenase (11bHSD).
Cortisol is then metabolized into 5-alpha-Tetrahydrocortisol (5a-THF) and 5-beta-Tetrahydrocortisol (5b-THF) and cortisone is metabolized into 5-beta-Tetrahydrocortisone (5b-THE). Since all production and output originally started as cortisol, the cortisone metabolites are added to the cortisol metabolites when evaluating the “total metabolized cortisol”. It essentially reflects how much cortisol was made in the body and has been processed out through the liver, into the kidney, and onto the DUTCH Test.
Two of the 3 metabolites are the active form of cortisol (THF). The other metabolite is in the inactive form cortisone.
This particular marker (a-THF) hence is an active cortisol metabolite.
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If cortisol is low, ideally its leaning towards cortisol metabolites (THF)
If cortisol is high, ideally it's not leaning against cortisol metabolites as it could exacerbate a high cortisol situation potentially.
References:
Vantyghem MC, Ghulam A, Hober C, Schoonberg C, D'Herbomez M, Racadot A, Boersma A, Lefebvre J. Urinary cortisol metabolites in the assessment of peripheral thyroid hormone action: overt and subclinical hypothyroidism. J Endocrinol Invest. 1998 Apr;21(4):219-25. doi: 10.1007/BF03347306. PMID: 9624595.
Cortisol is metabolized by 5a/5b reductase (and 3a-HSD) to a/b-THF & THE for excretion. This process is slowed in cases of hypothyroidism, anorexia or poor liver function.
Lower than optimal totals can signal decreased adrenal function.
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Cortisol is metabolized by 5a/5b reductase (and 3a-HSD) to a/b-THF & THE for excretion. This process is particularly increased in obesity, high insulin and hyperthyroid.
Higher than optimal totals suggest an excessive cortisol response.
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