Diagnosis – Adrenal Insufficiency

00:01 Let’s see diagnosis of adrenal insufficiency.

00:03 Begin at the very top, we’ll go through kind of like what we did earlier with Cushing’s.

00:07 Speaking of which, be careful when you go through this.

00:10 I would highly recommend that you quickly, after our lecture here, go back and take a look at the algorithm for Cushing’s please because students always get these two algorithms confused because there might be a little bit of time delay before reviewing.

00:24 It’s important that you have these firmly etched in your head, this is specific in algorithm for adrenal insufficiency; there is no dexamethasone suppression test, there’s no high dose/low dose and such.

00:35 So, what are we looking at here? Diagnosis of adrenal insufficiency can’t… can be based on the following, excuse me, can be based on the following.

00:43 Peak cortisol, obviously here it will be less.

00:47 Technically speaking, now, clinically be careful, you might get a little bit of trouble because how often are you going to find a research committee that is… I’m just being practical here.

00:58 How often can you find a research board or committee who will give you permission to then give your patient as much insulin as you would like? Do you know what I mean? Because if you give too much insulin, you might actually bring about a patient that has hypoglycemia coma.

01:12 So, be careful.

01:13 But, for exam purposes, if you give insulin, are you not creating stress? How? Because now, you’ve created a hypoglycemic fasting state.

01:26 As soon as you’ve created a fasting state, what should you be releasing from the adrenals? There you go, cortisol.

01:32 Do you understand that point now? If your patient has adrenal insufficiency, theoretically what you want to know here is you give insulin, you’re not going to have cortisol.

01:42 What if you diagnosed? Oh, adrenal insufficiency.

01:44 How does that occur? We don’t know yet, maybe it was the adrenal gland primary, maybe it’s secondary, so let’s keep going.

01:51 Contraindicated patients with coronary arterial disease, seizure disorders or patients that are older than 60, so really be practical, take a look at the second bullet point.

02:00 If you find your patient to be older or they have heart disease, you want to stay away from insulin.

02:06 AM cortisol… AM cortisol less than three micrograms, that’s important.

02:12 Now, once again, this comes make… this comes to understand your diurnal rhythm of cortisol.

02:21 Before we move on, what’s the significance of this bullet point? We wake up in the morning, what does your cortisol levels be? It should be high.

02:28 Normally, physiologically, if you find your cortisol levels to be low when you wake up in the morning, then obviously this is adrenal insufficiency and that technically less than three micrograms.

02:40 Random cortisol less than 18; examples hypotensive ICU, patients with an albumin greater than two and a half of grams per decilitre.

02:51 If diagnosed in ICU should retest adrenal function status after recovery.

02:58 Those of you that are going to emergency medicine will especially appreciate that little comment there for ICU.

03:04 Peak cortisol less than 15 micrograms after ACTH stimulation test.

03:12 So, here, we have an ACTH stimulation test, but still you’re not having proper cortisol release.

03:19 What is this? All this is used for laboratory testing for diagnosis.

03:25 This test is insensitive for diagnosis of adrenal insufficiency shortly after pituitary injury for obvious reasons… test is insensitive.

03:37 Metyrapone test… metyrapone test technically means that you’re inhibiting 11-beta-hydroxylase and so, therefore, if you block 11-beta-hydroxylase… at least work through with this, can you picture this? We’ve had this discussion before.

03:52 Metyrapone… let me ask you this, this you should be able to understand.

03:57 If you block or inhibit 11-beta-hydroxylase in your adrenal cortex, you’re not producing any cortisol.

04:03 If you’re not producing cortisol, then your ACTH levels should be increased, right? If you’re doing metyrapone testing and you’re inhibiting 11-beta-hydroxylase and you don’t find a rise in ACTH, what’s your diagnosis? Secondary adrenal insufficiency.

04:19 Although ACTH response to metyrapone can, in theory, distinguish between primary and secondary adrenal insufficiency, such application of this test is not recommended.

04:31 Think about what I said, maybe perhaps first pause here.

04:34 Repeat what I just said about what this test is actually inhibiting.

04:39 I said that after inhibiting the enzyme 11-beta-hydroxylase, you still find depressed ACTH.

04:45 Diagnosis - secondary, secondary, secondary adrenal insufficiency.

04:49 Those are the type of patho-physiologic questions that you’ll get on every single exam.

04:55 If adrenal insufficiency, low cortisol is diagnosed based on any of the above test high ACTH suggest primary adrenal insufficiency.

05:05 Adrenal imaging for next step of management, you would then expect your adrenals to be small, atrophic.

05:11 Low, inappropriate normal ACTH suggests secondary adrenal insufficiency.

05:18 Clear? Diagnosis… what’s your next step? How or why is your cortisol decreased? You find the ACTH to be high, most likely it’s going to be atrophy of the adrenals.

05:30 Next step of management, CT image of the abdomen.

05:36 If you find your ACTH to be low, most likely problem up in the pituitary.

05:40 In the algorithm here from top to bottom, serum cortisol, my problem low, next step serum ACTH.

05:48 If you find it to be high, it’s adrenal failure.

05:52 If you find it to be low, it’s pituitary failure.

05:53 Stop there, that should be your priority.

05:56 In the algorithm, you go as far as that and you firmly imprint those bullet points.

06:03 Once you’ve understood that, clinically speaking, as you move on from step one into step two CK and step three in your boards, then you have further issues.

06:14 You might get results that are equivocal.

06:15 What equivocal means is that it is non-confirmatory, so you want to go a little bit further and then you do ACTH stimulation test.

06:24 If you do an ACTH stimulation test and you find low cortisol, then now you diagnose adrenal failure.

06:33 You find ACTH stimulation test and you find your cortisol levels to be high then you know that you have normal adrenal.

06:40 If it’s still once again equivocal, you come to this entire concept - if either metyrapone, which is in the US not really used; it’s more so in the-more so-more so in the United Kingdom but nonetheless, it’s a fact that it’s a-it’s a type of test that inhibits 11-beta-hydroxylase and insulin intolerance.

07:00 We talked about this being gold standard, maybe perhaps you’re not releasing enough cortisol.

07:05 Important algorithm, I’ve walked you through the verbiage, let us now continue.

07:10 Here is, in fact, a metyrapone on your left is perfectly normal… on your left is normal.

07:17 Where are you? You’re in your adrenal cortex.

07:20 So, now you have pituitary, ACTH, you’re in your adrenal, there’s your 11-deoxycortisol and there’s the enzyme 11-beta-hydroxylase.

07:30 Metyrapone will work there to inhibit that enzyme.

07:33 In a normal individual, normal on the left.

07:36 If you inhibit that enzyme, cortisol will be depressed.

07:40 Take a look, ACTH is increased.

07:42 I want you to get into the pathology patient on the right.

07:47 So, this is your patient with the disease, what kind? At this point, all we know is that cortisol is decreased.

07:55 All we know is that adrenal insufficiency is taking place.

07:59 You give equivocal… you get equivocal results, equivocal meaning it’s not confirmatory, so you need to keep investigating, investigating.

08:07 Here, metyrapone inhibits 11-beta-hydroxylase, you have decreased cortisol, but this time take a look at ACTH, ha, it doesn’t rise.

08:18 Diagnosis - your patient on the right, his or her diagnosis, is it primary or secondary adrenal insufficiency? Secondary, secondary, secondary adrenal insufficiency.

08:32 Is there hyperpigmentation in this patient? No because it is not Addison’s.

08:39 What is Addison’s? Primary adrenal insufficiency.

08:42 Do you see the amount of patho-physiology that’s involved in these conditions? Treatment: first step, you have to give glucocorticoid.

08:55 You want to give mineralocorticoid replacement, especially if it’s primary adrenal insufficiency.

09:00 Secondary, you have to give glucocorticoid.

09:03 Why only? Because in secondary, if you do not have ACTH, your aldosterone levels should be relatively normal, therefore your blood pressure is normal.

09:14 Usually lower doses than used in primary; lowest dose of glucocorticoid improves patient’s symptoms and should be used.