How the heck does cortisol deficiency lead to weight loss?

[CBG23]

My understanding was that cortisol was a pro-gluconeogenic hormone.

It normally increases lipolysis in adipose tissue, protein breakdown in muscle, and gluconeogenesis in the liver. The combined effect of these three things is to increase the blood [glucose].

Assuming a fixed caloric intake, I would assume that a decrease in cortisol levels would result in reduce protein breakdown in muscle, reduced lipolysis in the adipose tissue, and reduced blood glucose levels. So you would be relatively hypoglycemic. But, if you are consuming the same amount of calories you were before a cortisol deficiency developed, why would you still lose weight? Protein and adipose breakdown are inhibited so you wouldn't be able to lose lean body mass or fat mass? Am I missing something here?

---

Members don't see this ad.

 

[qmcat]

To my understanding, the reason that decreased cortisol leads to weight loss and increased cortisol leads to weight gain has to do with insulin.

You're right that cortisol is pro-gluconeogenic. But, when you have gluconeogenesis, you get hyperglycemia. And, when you have hyperglycemia, more insulin is released. Insulin stimulates glucose uptake but also storage of fat and triglycerides leading to obesity.

So, if you have less cortisol, that means less gluconeogenesis, thus less glucose, thus less insulin release, thus less storage of fat.

 

[gracie369]

To my understanding, the reason that decreased cortisol leads to weight loss and increased cortisol leads to weight gain has to do with insulin.

You're right that cortisol is pro-gluconeogenic. But, when you have gluconeogenesis, you get hyperglycemia. And, when you have hyperglycemia, more insulin is released. Insulin stimulates glucose uptake but also storage of fat and triglycerides leading to obesity.

So, if you have less cortisol, that means less gluconeogenesis, thus less glucose, thus less insulin release, thus less storage of fat.

This person makes a good point. Also, one would not be hypoglycemic if glucagon and growth hormone were sufficient.

 

[CBG23]

That does make sense. One thing that bothers me though is the following:

In Addision's disease, there is weight loss due to increased fat breakdown and muscle weakness due to increased protein breakdown, both apparently driven by a secondary decrease in insulin/ increase in epinephrine and glucagon.

In Cushing's syndrome, there is weight gain due to increased fat deposition driven by a secondary increase in insulin, but there is also muscle wasting/ weakness due to increased protein breakdown!

So, it seems that for both a low cortisol state and a high cortisol state there is going to be muscle breakdown/ weakness (Based on a few texts I looked at), BUT by different mechanisms?

Hypocortisolism

- Low cortisol --> Decreased protein breakdown and lipolysis.

- Also, Low cortisol --> Dec. gluconeogenesis --> Low blood glucose --> Dec. Insulin/ Inc. epinephrine --> Increased protein breakdown and lipolysis.

- So, on net, it seems like the secondary effects of insulin/ epinephrine on protein and lipid metabolism outweigh the effects of cortisol on protein and lipid metabolism.


Hypercortisolism

- High cortisol --> Increased protein breakdown and lipolysis.

- Also, High cortisol --> Inc. gluconeogenesis --> Increased blood glucose --> Inc. insulin/ decreased epinephrine release --> Increased fat storage and protein synthesis.

- For hypercortisolism, it seems like the secondary effects of insulin/ epinephrine on LIPID METABOLISM outweigh the effects of cortisol. BUT, the effects of cortisol on PROTEIN METABOLISM outweigh the effects of insulin/ epinephrine on protein metabolism?

Is this correct?

 

[qmcat]

For Cushing's, you're breaking down muscles in the extremities to get fuel for gluconeogenesis, and the insulin release in response to hyperglycemia leads to storage of fat in the trunk. That's why people with Cushing's have thin/weak extremities and "truncal obesity".

For Addison's, I think the weakness and fatigue has more to do with hyponatremia and hypoglycemia than with protein breakdown and metabolism. I might be wrong on that though.

 

[IHeartNerds]

this thread makes me happy that i matched into a surg sub-specialty that cares not for such things. yikes 😕

 

[Instatewaiter]

this thread makes me happy that i matched into a surg sub-specialty that cares not for such things. yikes 😕

Sometimes I wish I chose surgery too...

So to answer the question, it actually has nothing to do with the interaction of the hormones but I love all the thought. Adrenal insufficiency (hypocortisolism) presents commonly with nausea and vomiting. The anorexia associated with the n/v is the thing that causes the weight loss not the breakdown of tissues or lack of anabolic effects of insulin. To be honest I have no idea why low cortisol causes anorexia.

Furthermore, there is concomitant diarrhea which further causes diuresis and weight loss.

 

[myhandsarecold]

this thread makes me happy that i matched into a surg sub-specialty that cares not for such things. yikes 😕

haha, don't be so sure, we had a patient in M&M whose Addison's crisis was mismanaged by the surgeons...moral of the story, be a good, astute doc in general

 

[RySerr21]

Sometimes I wish I chose surgery too...

So to answer the question, it actually has nothing to do with the interaction of the hormones but I love all the thought. Adrenal insufficiency (hypocortisolism) presents commonly with nausea and vomiting. The anorexia associated with the n/v is the thing that causes the weight loss not the breakdown of tissues or lack of anabolic effects of insulin. To be honest I have no idea why low cortisol causes anorexia.

Furthermore, there is concomitant diarrhea which further causes diuresis and weight loss.

the anorexia/n&v thing is true (double checked uptodate 😀), but to say it has nothing to do w/ the hormones mentioned is contradictory to the sources I'm lookin at (Goljan and Robbins). At the least, it contributes a little 🙂

 

[BobbyE]

One of the reasons athletes try to keep cortisol in check is because it's effect on catabolism of muscle. You want to the right balance of cortisol and insulin sensitivity in order to gain and maintain lean mass. Lean mass is beneficial in fat loss, as per conventional wisdom.

 

[fado]

The situation you've given us is incorrect, because a constant caloric intake for a person suffering from hype/hyper-cortisolism is impossble, mainly because cortisol is a Orexigenic hormone, i.e it stimulates the appetite. Hence, decreased cortisol levels -->decreased appetite --> decreased caloric intake --> decreased fat mobilization and deposition = weight loss

 

[fado]

Sometimes I wish I chose surgery too...

So to answer the question, it actually has nothing to do with the interaction of the hormones but I love all the thought. Adrenal insufficiency (hypocortisolism) presents commonly with nausea and vomiting. The anorexia associated with the n/v is the thing that causes the weight loss not the breakdown of tissues or lack of anabolic effects of insulin. To be honest I have no idea why low cortisol causes anorexia.

Furthermore, there is concomitant diarrhea which further causes diuresis and weight loss.

Cortisol is orexigenic (appetite stimulant). It works in the following way, quoting Guyton :-

Cortisol is transported to the 3rd ventricle of the brain where it stimulates the agouti-related protein (AGRP) and neuropeptide Y (NPY) neurons, increasing food intake and reducing energy expenditure by inhibiting melanocortin receptors (MCR) 3 and 4 in the paraventricular nuclei of the hypothalamus. Thus, if looking at the direct effect of cortisol on weight, excluding other hormones, this is the mechanism to keep in mind.

So if this pathway is inhibited (cortisol deficiency), there will be decreased intake of food, increased energy expenditure by the body and decreased insulin (increased glucagon and epinephrine) which activates hormone sensitive lipase (causes lipolysis) hence weight loss.

 

[WhippleWhileWeWork]

Hahaha. Nice bump.

 

[mcloaf]

Well, really a nice forum of topic weight-loss. I read the posts of several users and found some very interesting and useful information through it. Liked it very much. Thank you for the information.

 

[Psai]

It makes me sad when I realize how much I've learned and forgotten already.

 

[Kahreek]

lack of appetite,
lack of anabolism.
lack of lean mass . Eg:muscle and water

 

[CherryRedDracul]

wats a cortisol????