Diagnosis – Adrenal Insufficiency

by Carlo Raj, MD

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    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.

    About the Lecture

    The lecture Diagnosis – Adrenal Insufficiency by Carlo Raj, MD is from the course Adrenal Gland Disorders.

    Included Quiz Questions

    1. Prostate cancer
    2. Cerebrovascular disease
    3. Coronary artery disease
    4. Seizure disorder
    5. Patients over 60 years old
    1. Many of these patients have low albumin levels, which can interfere with the interpretation of the cortisol level.
    2. A low magnesium level will interfere with the test result.
    3. High sodium levels are commonly present and interfere with cortisol levels.
    4. Low potassium levels are commonly present and interfere with cortisol levels.
    5. Critically ill patients do not have diurnal hormonal cycles.
    1. 11-beta-hydroxylase
    2. The first enzyme in the pathway from cholesterol to pregnenolone
    3. The last enzyme before the synthesis of aldosterone
    4. The last enzyme in the step of the formation of dehydroepiandrosterone (DHEA)
    5. An enzyme in the zona reticularis of the adrenal gland
    1. Secondary (pituitary) or tertiary (hypothalamus) adrenal insufficiency
    2. Mixed primary and secondary adrenal insufficiency
    3. Normal adrenal gland function
    4. Elevated cortisol
    5. Hyperplastic adrenal glands

    Author of lecture Diagnosis – Adrenal Insufficiency

     Carlo Raj, MD

    Carlo Raj, MD

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    wow wow wow Dr Raj the Magician
    By Hamed S. on 22. February 2017 for Diagnosis – Adrenal Insufficiency

    Amazing explanation of the diagnostic pathway for adrenal insufficiency. The talk was clear and concise! Thank you