Introduction to Cortisol and Hypercortisolism – Adrenal Gland

00:02 The topic is hypercortisolism, a very important topic for us.

00:06 A very important topic because Prednisone, a type of cortisol, is administered excessively in practice.

00:16 But, before we get into any of that though, we will first take a look at the normal functioning of your cortisol so that when we take a look at the pathology, it will all come together.

00:27 The normal effects physiologically of cortisol on metabolism as a stress hormone, we’ve talked about this plenty, is to make sure if one is in a state of fasting that cortisol will do everything in the power to increase the amount of glucose in circulation.

00:45 If it comes down to what is happening to uptake of glucose by a tissue, understand that cortisol decreases the uptake of glucose, thus [Inaudible 00:00:56] glucose in circulation.

01:00 If you are thinking about the balance in biochemistry between glycolysis and gluconeogenesis, it obviously will lean towards gluconeogenesis resulting in more of a “hyperglycemic state”.

01:15 Next, cortisol, it permits for redistribution of fat from the legs to the trunk.

01:25 Doesn’t it sound like an awful lot like Cushing, which we will get into later on in our discussion, where you have heard of trunk obesity and you have heard of wasted extremities in Cushing? Well, cortisol seems to-seems to do that on a physiologic basis, visceral adiposity.

01:48 Cortisol causes bone demineralization.

01:50 In other words, it is going through a move, your hydroxyapatite from the bone, bone reabsorption resulting in excessively look for, once again, long term corticosteroid use resulting in premature osteoporosis.

02:11 Immunologically, cortisol has interesting effects.

02:17 It could attenuate immune response.

02:20 Now, this is rather confusing to some, but will bring clarity here, huh! If it is cortisol and you are dealing with acute inflammation, it causes demargination of your neutrophils.

02:32 What does that mean? Whenever there is cortisol administration, you are not going to have cortisol staying on the bench, it will come off the bench, come into the circulation, thus may then cause neutrophilic leukocytosis.

02:48 On the same token, cortisol and its effect with lymphocytes would be apoptosis, so it may actually bring about and it does lymphopenia.

03:00 So, the immunomodulation effects of cortisol quite interesting, keep those separate.

03:09 As we know, cortisol could be used as an inflammatory, thus used quite randomly and effectively for Prednisone inhibiting phospholipase A2.

03:20 So, therefore, you are now going to have the prostaglandin branch being created and so, therefore, may then exert your anti-inflammatory effects.

03:36 This picture here is referring to your diurnal release of your cortisol.

03:42 What does that mean again? It means that, as you wake up in the morning… let’s take a look at your X axis and your Y axis.

03:51 Your X axis represents days, the Y axis represents concentration of cortisol.

04:00 What you are seeing here at the very top with that orange curve at point 20, shall we say approximately, the highest concentration of cortisol, that would indicate when you first wake up in the morning, as you go throughout the entire day and let’s say that you get to about, oh, 6-7 o’clock in the evening, your levels of cortisol will decrease, this is physiologically.

04:27 Therefore, at the end of the day, your cortisol levels are the lowest.

04:32 You go to sleep at night and as you do, this is the area that you are seeing in dark shade literally meaning night time and as you sleep throughout the entire evening, you wake up in the morning, you will notice please that the cortisol level will then peak.

04:47 This fluctuation of cortisol during day and night, day and night is known as your diurnal type of pattern.

04:57 This becomes very important to us when we go onto discuss our dexamethasone suppression test.

05:02 Once again, the point that you want to take out of this, let me ask you, when is your cortisol level the highest? Good, in the morning.

05:12 Quickly, once again, this time, up until this point, we have looked at cortisol synthesis.

05:20 Where is this cortisol synthesis taking place? Be as specific as possible please.

05:26 Zona fasciculata of the adrenal cortex.

05:30 We have talked about how close [Inaudible 00:05:31] in there, we have talked about the various enzymes in which that you require so that you can form a cortisol.

05:38 Remember that when cortisol comes into circulation, which is the blood, this time, what this picture is showing us is now cortisol being delivered to the target cell, okay, to the target cell; example may be hepatocyte.

05:54 When cortisol enters circulation, remember that it is a lipid soluble substance thus requires a chaperone, a cortisol binding globulin.

06:04 The cortisol will then be released, it goes into or passes through your membrane.

06:10 In the meantime, remember that the receptor for cortisol is within your target cell, cytoplasm to be exact, you have a heat-shock protein that is now controlling the receptor.

06:24 But, once cortisol comes in, which is that circle that you see here, the heat-shock protein will be released, you have a receptor and cortisol complex together will enter the nucleus, as you see here.

06:37 If it is a hepatocyte then you should understand that cortisol along with-along with glucagon, as an example, may then bring about certain DNA changes in transcription so that you then create the necessary enzymes that are responsible for gluconeogenesis just as an example and cortisol, of course, express hormone.

07:05 Once you have reached the nucleus, you will have transcription; mRNA being produced, translation depending as to which protein is necessary and that protein will then bring about a physiologic response, in this case, we got to use an example such as effective glucose being increased in circulation.