Cortisone/day

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Cortisone is the inactive form of cortisol.

Elevations of cortisone may reflect high cortisol production, excessive 11BHSD2 activity, or insufficient conversion by 11BHSD1.

Low levels of cortisone may reflect low cortisol production, excess conversion by 11BHSD1, or insufficient 11BHSD2 activity.

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Corticoids:

The corticoid pathway has two main branches: glucocorticoids and mineralocorticoids. While the roles of these pathways vary, they share a common enzyme, CYP21A2, also known as 21- hydroxylase. 21-hydroxylase is part of the cytochrome P450 system and is responsible for the conversion of progesterone to 21-hydroxyprogesterone in the mineralocorticoid pathway. In the glucocorticoid pathway it converts 17-OH progesterone to pregnanetriol, 11-deoxycortisol, and 21 deoxycortisol. 11-deoxycortisol and 21-hydroxyprogesterone are metabolized by CYP11B (11-beta hydroxylase) enzyme to produce cortisol and corticosterone, respectively. The major site of cortisol metabolism is the liver. There it is reduced, oxidized or hydroxylated.

The enzymes that directly metabolize cortisol are 11 beta hydroxyosteroid dehydrogenase 1 and 2 (11BHSD1 and 11BHSD2), the A-ring reductases (5 alpha and 5 beta reductases), 3 alpha hydroxysteroid dehydrogenase and 20 alpha and 20 beta hydroxysteroid dehydrogenases.

The clearance of active cortisol from circulation is largely affected by 11B HSD1 and 2 activity. Cortisone protects tissues from the effects of cortisol, therefore if 11BHSD activity is functioning properly, there should be twice as much cortisone as cortisol, measured in the cortisone (THE)/cortisol (THF) ratio. This ratio indicates 11BHSD 2 activity and infers tissue-specific concentrations of cortisol (which normally cannot be measured without a biopsy). A lower ratio suggests decreased cortisol metabolism/clearance by 11BHSD2, indicating an increased cortisol burden on tissues; whereas a higher ratio reflects optimal 11BHSD2 activity.

HSD 11B (1 and 2):

The primary function of 11BHSD2 is to protect cells with mineralocorticoid receptors (MR) from excessive cortisol by converting it to cortisone. Since cortisol has the same affinity for MR as aldosterone and is present in much higher concentrations, the conversion of cortisol to cortisone protects cells from glucocorticoid intrusion on the mineralocorticoid system. It has been shown that the cortisol pool
results not only from the production of cortisol through classic HPA Axis processes, but also from the actions of 11BHSD1 due to the re-conversion of cortisone back to cortisol. The human liver/splanchnic bed is responsible for only 20-40% of daily cortisol production rendering the inactive cortisone pool a major reservoir for systemic cortisol availability. For this reason, in cells expressing 11BHSD1, cortisone is considered just as potent as cortisol (highest in liver, adipose, CNS, skeletal muscle and the immune system).

Those with metabolic disorders (such as metabolic syndrome, obesity, diabetes, CVD, cognitive disorders, bone disorders and inflammation) may not present with elevations of serum or salivary free cortisol, yet adipose tissue has been shown to have higher levels of 11BHSD1 than controls, suggesting elevated glucocorticoid activity may be taking place despite free cortisol labs suggesting otherwise.

Pro-inflammatory cytokines have been shown to upregulate 11BHSD1 enabling a tissue-specific cortisol induced anti-inflammatory response. This effect has also been found in chronic disease such as obesity, cardiovascular and neurodegenerative diseases, and bone and joint disorders. Thyroid hormone plays a role in this conversion process.

Increased cortisol metabolism resulting in increased cortisone is associated with hyperthyroidism. Hypothyroidism has been shown to slow cortisol metabolism, resulting in lower levels of metabolized cortisol.

When evaluating the corticoids it is important to pay attention to three areas on the HuMap:

1. Graphical pattern of daily cortisol and cortisone

2. Metabolized Cortisol

3. Metabolic preference for cortisol and cortisone

What does it mean if your Cortisone/day result is too high?

Cortisone is the inactive form of cortisol. Elevations of cortisone may reflect high cortisol production, excessive 11BHSD2 activity, or insufficient conversion by 11BHSD1.

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What does it mean if your Cortisone/day result is too low?

Cortisone is the inactive form of cortisol. Low levels may reflect low cortisol production, excess conversion by 11BHSD1, or insufficient 11BHSD2 activity.

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