Posted by ed_uk2010 on April 2, 2018, at 16:32:47
In reply to Re: How are you doing?, posted by farshad on April 2, 2018, at 1:22:47
Hi Farshad,
>Because it has to go like this CRH > ACTH .. So in between the two cortisol can inhibit ACTH if it gets too much.
I understand what you're saying, but... you're describing what happens in a healthy person, not someone with a tumour.
Tumours releasing CRH do cause Cushing's Syndrome because the amount of CRH released by tumours is very large compared with normal levels. Because of this, negative feedback loops aren't sufficient to prevent cortisol from becoming elevated. So, high cortisol results.
CRH-releasing tumours are extremely rare, but in reported cases, these tumours are normally not in the brain, but elsewhere in the body.
On the other hand, most tumours in the hypothalamus are due to cancer and do not release hormones. An exception is the hypothalamic hamartoma, which is a benign tumour present from birth. It does not normally release CRH, however, but other hormones instead. If you did have a tumour like this you would have physical symptoms (seizures, or very early puberty due to hormonal changes). A very rare case of a CRH-releasing hypothalamic hamartoma has been reported, which caused symptoms in the child at a very young age.
>check out this picture http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/adrenal/feedback.gif
Nice diagram. The diagram shows the release of CRH which occurs due to stress/fear/anxiety. This can happen to anyone, as part of the body's normal response to stress. In anxiety, negative feedback occurs, as shown in the diagram, so cortisol may be moderately and intermittently elevated, but not severely.
In the case of hormone-releasing tumours, negative feedback does not prevent a large rise in cortisol. The quantities of ACTH or CRH released by tumours are too large for the normal feedback system to work. This is why tumours can cause Cushing's Syndrome, but anxiety does not.
>CRH is the only cortisol type in the brain.
The brain also has receptors for cortisol, including the glucocorticoid receptors.
>So a tumor in the CRH wouldnt mean high cortisol it would just mean constant CRH release....
As far as I can tell, this situation has never been reported.
Disturbances of the HPA axis due to excessive release of CRH are believed to occur due to severe chronic stress, trauma and abuse. This situation may occur in a variety of forms of depressive illness and anxiety disorders. Because of the negative feedback loops shown in the diagram, Cushing's Syndrome does not occur due to mental health conditions. In depression, for example, the negative feedback loops may be blunted, but not entirely unresponsive. This can be shown in a 'low dose' overnight dexamethasone suppression test.
Hormone-releasing tumours are a different situation, causing prominent elevation of cortisol and physical Cushing's symptoms. It's a matter of quantity - the amount of hormones released by these rare tumours is so much higher and more continuous than the body could normally produce.
Hope you find this to be a good explanation :)
poster:ed_uk2010
thread:1097352
URL: http://www.dr-bob.org/babble/20180331/msgs/1097921.html