Hi, this is Dr. Marie Baldessari. Today's discussion will be about endocrine emergencies. Obviously, this is a pretty intense lecture because we've included just about everything that you want to know about endocrine. So we'll go through it pretty quickly, but all of this information of course is available to you as well as in your textbook. So I'm at the University of Pittsburgh, professor of critical care, neurocritical care. So let's start with some of the things we're going to talk about today, from thyroid storm all the way to DI. Thyroid storm is, I think, is the first topic of discussion. As you know, this is a rare, potentially fatal complication of hyperthyroidism. It occurs in patients with untreated or partially treated thyrotoxicosis with a precipitating event, and we'll talk about what those events could be. So causes of thyrotoxicosis, obviously the list is quite long, Graves' disease by far is the most common cause of thyrotoxicosis and thyroid storm. Precipitating factors include everything from stress, surgery, infection, et cetera, to gestation. And really, when you look at the precipitating factors for thyroid storm and thyrotoxicosis, they're very similar to all the precipitating factors, which are ubiquitous to most of the endocrinologic emergencies and urgencies. All right. Signs and symptoms of hyperthyroidism, secondary due to increased catabolism as well as metabolism, increased stress. I think most of you are very familiar with this. Thyroid storm is a medical emergency characterized by severe acute exacerbation of the signs and symptoms of hyperthyroidism, which we just described, but you certainly have end organ dysfunction here with tachycardia, arrhythmias, high output failure, neurologic GI symptoms, fever, hypertension. So thyroid function tests, you need at least two tests required for the diagnosis. Most commonly, free T4 index, as well as a decrease in TSH. So the treatment is interesting. I think that the best way of thyroid storm to describe it is sort of step one to step three. So PTU, methamazole, methamazole is used for step one. PTU advantage, early onset of action inhibits the conversion of T4 to T3. The doses are usually 200 mgs every four hours of methamazole, 20 mgs every four to six hours. Usually thyroidectomy, radioactive iodine are not considered in the algorithm for acute treatment. When we talk about blunting the end organ effects, that is the end organ damage, we talk about beta blockers, calcium blockers, certainly these will decrease the adrenergic effects seen in thyroid storm. Step three is when you block the thyroid hormone release and the conversion of T4 to T3, you have a pretty wide armamentarium of drugs here, iodine compounds, Lugol's, potassium iodide, intravenous dyes, corticosteroids. The corticosteroids basically decrease the conversion, as we've said, from T4 to T3, they improve actually the vasomotor symptoms associated with thyroid storm. Once again, we try not to use iodine unless synthesis is stopped in treatment step one, since it will stimulate hormone production. If you're going to give any iodine appropriation, usually wait one hour after giving PTU or methamazole. All right, so supportive care, obviously these patients are mostly in the ICU, ICU monitoring, et cetera, treat fever, electrolyte abnormalities, arrhythmias, and respiratory insufficiency. Let's move on now to a different myxedema coma. So when we talk about myxedema coma, it's the opposite of thyroid storm, right? So precipitating factors, similar to what I described in a previous slide, run the gamut from stress to infection, surgery, non-compliance, et cetera, which is probably the most common cause. Signs and symptoms, sort of the opposite of what you would see in thyroid storm. Keep in mind, our patients with myxedema coma, that is hypothyroid patients, very sensitive to hypnotics and sedatives, as well as narcotics, and all of these can precipitate my myxedema coma. The symptoms are, as I said, the opposite of what you see in thyroid storm. Most of the symptoms tend to be neurologic, but certainly you see a wide variety of symptoms. About half of the patients have hyponatremia. All right, the findings can be divided into nonspecific versus specific. Hyponatremia, I focused on that in a previous slide, is present in about half the patients with myxedema coma, can be severe, and in itself can cause mental status changes. Specific changes are seen here, which would be the exact opposite of the thyroid storm. In a myxedema coma, obviously most of these patients would have to be in the ICU setting, and it ranges from monitoring, respiratory support, obviously dextrose, passive re-warming. These patients tend to be cold, as well as treatment with both T4 and T3 and stress dose steroids. Unless you've ruled out, the stress dose steroids is primarily because oftentimes you see myxedema coma in association with adrenal insufficiency. If you've ruled out adrenal insufficiency, these may not be as critical in your diagnose, in your therapeutic elementarium. So review question, which of the following patterns can be seen in patients with euthyroid six syndrome? So this is something you and I have to be very careful about because this is what we see in our patients, right, in the ICU. So really we can see all of these, all of these patterns, and that's why this becomes so difficult and why it's very complicated if you order thyroid studies in an ICU patient, because you can see decreased T4, T3, an increase in TSH, or a decrease in TSH, increase in reverse T3. But the most common of all is you'll see a decrease in T3 and an increase in reverse T3. But all of these patterns can be seen. They can be serum levels of thyroid hormones can be low in clinically euthyroid patient. You basically want to exclude hyperthyroidism and that's why the reverse T3 is an important test for you to be ordering. The general consensus is really you don't need to treat these patients. I think the best thing to do, unless you have a suspicion of hyper or hypothyroidism in your ICU patient, it's probably best just to not do these tests in the ICU setting. All right, let's talk about HHNK, hyperosmotic, hyperglycemic, non-ketotic state as it applies. These patients are non-acidotic. The glucose levels can often be quite high and not surprisingly, there are neurologic symptoms including coma in about 25 to a half of these patients. Plasma osmolality is quite high. All right, so DKA, I think we're all pretty familiar with. This is a high anion gap acidosis, metabolic acidosis, blood sugars can range anywhere from 350 to 800 to even higher, although usually don't see glucose is greater than 900 or less than 250, but it can occur. Once again, the precipitating factors similar to the precipitating factors we described before, infection, probably the number one, noncompliance, new onset of diabetes, et cetera. When we look at the symptoms of DKA, I think we're all pretty familiar with this, particularly the chrismal respirations, which are deep and labored breathing due to the metabolic acidosis, and you really have quite a wide armamentarium of symptoms here. I think you're all familiar with the how to correct the sodium level. If the patient is hyperglycemic, the corrected sodium is actually equal to the actual sodium level plus the glucose minus a hundred divided by a hundred times 1.6. So basically the serum sodium is diluted by 1.6 milliequivalents per liter for each hundred increase in the glucose. So if the corrected sodium is 140, then the hyponatremia can be explained by the hyperglycemia. If the corrected sodium is 120 or in the 160 range, then obviously a problem exists with water balance. All right. So a review question, which intravenous fluid is best for a patient who has HHS with the blood pressure of 80 over 46, serum sodium of 162, and a glucose level pretty high of a 1730 milligrams per deciliter. So the correct answer, despite the fact that the patient has a very high sodium is normal saline solution because this patient is markedly a volume depleted with a, you know, a low blood pressure. So although he's hypernatremic, it's best to give an isotonic solution because what you want to do is volume resuscitate the patient. So once you volume resuscitate the patient, treat the hypotension, the, um, sodium will decrease appropriately. So if you look at all of these solutions, obviously this is hypertonic. This is a, this is not isotonic at all, and neither is this. So the only isotonic solution offered to you in this slide is the normal saline. All right. So DKA, I think many of you are familiar with this. I mean, most hospitals have very strict protocols. You want to start the patient on normal saline. Once the glucose, um, uh, decreases with an infusion of 0.1 units per kilo per hour, less than 250, usually switch to D5, um, and certainly using insulin with initial bolus of 0.3 units per kilo. Uh, and then as I said, 0.1 units per kilo every hour, all right, potassium replacement is important. Um, and we can't forget about this. They're going to be dramatic, uh, um, uh, electrolyte abnormalities, uh, with these patients. So potassium replacement, sodium bicarb, only if the pH is 6.9, because the pH, if it's greater than this, will eventually come back to normal. Um, so see, these are some of the electrolyte deficits. So sodium, potassium, chloride, phos, uh, magnesium, uh, as well as a 6 to 7 liter deficit in water, obviously you're going to have in the, uh, hypertonic, uh, syndrome, you'll have probably a greater deficit of maybe up to 10 liters. Okay. So review question, uh, when we're switching gears here quickly, we have a lot to go through. So obviously all of this is available to you in the slides as well as your textbook. So, uh, we have a 76 year old with no history of diabetes is, uh, sodium is 114, uh, chloride is 79, the bicarb is 22, BUN is 82, and the glucose is very high at 1704 with some trace acetone. So they're basically asking you, why is the sodium low? Is it SIADH? Is it sodium dilution, renal failure? And the correct answer here is pseudohyponatremia, which is secondary to high lipids. Obviously there is a reciprocal relationship between the sodium and the glucose. If the patient is hyperglycemic, the glucose is usually trapped in the extracellular fluid, leading to hyperosmolarity. This hyperosmolarity will cause the water to move from the intracellular fluid to the extracellular fluid. And when that happens, you really pretty much dilute everything, such as the sodium, potassium, and calcium. All right, so let's move on to hypoglycemia, which is the syndrome that we worry most about when we talk about glucose in the ICU. Certainly our patients are hyperglycemic. That can be treated with fluids and insulin, but the hypoglycemia is what we worry about because this increases both morbidity and mortality. The etiologies are listed here, as you know, they're quite extensive. Manifestations of hypoglycemia, mostly neurologic, but certainly can include many other phenomenon, including cardiac. Hypoglycemia treatment, not surprisingly, ibidextrose, glucagon, octreodide, steroids are also part of the elementarium. All right, so let's talk now about adrenal insufficiency. So which laboratory findings typically occur in adrenal insufficiency? So the answer here is really azotemia. Azotemia is secondary to increased catabolism in adrenal insufficiency, and usually you'll see increased BUN and creatinine. So all of these are wrong. So the patient is hyponatremic, hyperkalemic, hypoglycemic, and hypercalcemic. So a question of memorizing and understanding the process here. All right, so the causes of adrenal insufficiency, we can divide them into primary and secondary. Primary would be an increase in ACTH with a decrease in the cortisol. Secondary is when the anterior pituitary doesn't produce enough ACTH. And the extensive list of etiologies, both primary and secondary are listed here for you. So signs and symptoms, you need to be familiar with this. This is not something you want to miss in the ICU or on the floor. As I mentioned, the azotemia is significant. Dehydration also is significant, lots of fluid losses because of the decrease in the mineralocorticoids. Laboratory findings, I mentioned azotemia, all of the things that we talked about, or phenomenon, laboratory findings that we mentioned in the prior slide. So these patients are acidotic, they're hyponatremic, they're hyperkalemic, hyperglycemic, increased BUN and creatinine, increased calcium. They tend to be neutropenic, anemic, and have an eosinophilia, all right? All right, let's move on to talking about the rapid cosentropin test. So as you know, and this is probably not done as frequently in the ICU as we used to do it, particularly for those patients with sepsis. As you know, we just tend to give them the steroids, but it can be done, and in some cases it may be totally appropriate. So basically, if you're doing the ACTH cosentropin test, you're gonna draw a baseline cortisol, give the cosentropin at 250 mics, repeat the assay at 30 and 60, and then administer hydrocortisone. As you can see here, this is a graph of what would happen if you have adrenal insufficiency versus the normal subjects where you would see an increase. And the cortisol level, and those patients with sepsis who have a very blunted response to the ACTH. So how do we treat adrenal crisis? Not surprisingly, IV hydrocortisone, we need to give them volume as well. We need to give them mineralocorticoids with fluorinef, that is, flutocortisone, IV glucose, and particularly, we need to be very vigilant about monitoring the electrolytes in these patients as described, we have a lot of electrolyte abnormalities, well, pretty much in all of the metabolic and endophenologic abnormalities. Let's move on now to our next question. Which urine osm is most consistent with complete central DI? So I give you a list here, but, oh, sorry, my bad. Let's go back, see if I can go back here. But the answer was less than 300 milliosms. These patients' urine, their urine is going to be very dilute with central DI. This is a list of both the central and nephrogenic causes of DI. The list is really quite extensive here, particularly what we worry about in my population as a neurointensivist, head trauma, brain surgery, tumors, vascular causes. You can see that many of these causes have to do with the brain. Nephrogenic DI, it's really just refractory response to the ADH, and some of the causes are listed here. When we talk about the diagnostic sort of algorithm, how we proceed differentiating between polydipsia, central DI, and nephrogenic DI, certainly the very first test that you want to check is the urine osm. If that is low, you want to give DDAVP as a test dose, then recheck the urine osm. So if there's no appreciable increase in the urine osm, the diagnosis is usually normal, or the patient's just been drinking surreptitiously. If there's an increase in 10 to 50%, the diagnosis is partial central DI. If greater than 50%, the diagnosis is complete central DI. If there's no change at all in the osm, that is the urine osmolality, the diagnosis is nephrogenic DI. All right, the treatment of DI, I'm sure you're all familiar with. You want to replace fluids, monitor the fluid status, monitor electrolytes, treat the underlying cause. Any drugs, there are many drugs which can cause DI. Thiazide diuretics are often used. They're good for both central and nephrogenic diabetes insipidus. They induce volume depletion and in conjunction with a low sodium diet, and certainly ADH replacement is the cornerstone of treatment. These are the recommendations for if you're given vasopressin, Tannate, or the Desmopressin, the doses are listed here. So let's just finish up with a little bit about pheochromocytoma. We have this, they call it the rough rule of tens. So 10% of these are malignant, familial, bilateral, multiple, and extramedullary. This is an increase in the ADA production, increase in catecholines. The manifestations are dramatic. These patients have significant refractory hypertension. They can be orthostatic, and in fact, they can have hypotension occasionally. They can be tacky usually, but they can also be bradycardic, chest pain, GI symptoms, anxiety attacks. So a lot of neurologic symptoms as well, but I think when we look at most of our patients, the sine qua non happens to be, or is, they're pretty accelerated and refractory hypertension. So this is certainly one of the issues in an ICU when you have patients who come in and you're treating them with multiple, multiple antihypertensives. You really, at some point, you need to say, you know, am I looking at a secondary cause of hypertension? So is this not essential hypertension? Could there be something else going on such as a potential pheochromocytoma? So the laboratory tests, most of us are very familiar with this, the 24-hour urine catecholamine. You can also order plasma catecholamine, the metanephrines, VMA. There are a few other tests that we do, but I think that most of us will follow with the 24-hour urine catecholamines and maybe the plasma catecholamines as a sort of first line of diagnostic modality in determining if this patient has a pheochromocytoma. Certainly radiographically, if this could be very helpful and certainly needs to be done in addition to doing the test. So looking for the tumor, CT scan, MR, any kind of the sonography tests, angiography, IVC sampling, all of these can be done. I think most of us would probably start with a CT or MR looking for and trying to localize the tumor. All right, so when we talk about the treatment of pheochromocytoma, so I think that the basis of treatment is really looking at the alpha blockers here, the short acting alpha blockers such as doxazosin, the longer alpha blockers, phenoxybenzamine are usually used prior to instituting the beta blockers, but there's obviously a pretty wide distribution of medications that you can use here, the beta blockers as well as the alpha adrenergic blockers. Most of these patients, not surprisingly, will need surgery. This is the treatment of choice. Most of these patients will use, will receive, I should say, the alpha blocker prior to surgery. So oftentimes you'll see these patients in the ICU simply because there's quite a bit of blood pressure variation and variability. Sometimes they may need hemodynamic monitoring depending upon the extent and severity of the systemic changes in terms of the blood pressure and the heart rate. So just some of the key points here. I know we've covered a tremendous amount and I was talking really quickly. It's hard to get all of this in within 30 minutes, but we've tried to touch upon the most important things in terms of critical care review in the world of endocrinology. Obviously, the need to go back and to review this in more detail is paramount. But just a couple of the key points. The most sensitive TSH assay is the single best test of thyroid function. The cosyntropin test is the best test of adrenal function. As I said, with our sepsis patients, often we will simply go ahead and give them stress dose steroids, but we're really not talking about that population in this lecture. Diabetes insipidus is one of those issues where you really need to monitor the intake and output extremely carefully. Volume resuscitate them based on the urine output. They don't usually require hemodynamic monitoring, but they do require intensive nursing monitoring of the intake and output. And as we said, alpha blockers, beta blockers to treat the hypertensive crisis and pheochromocytoma. Thank you for your attention. And I look forward to talking to you the next time. Thank you.

endocrine emergencies

thyroid storm

diabetic ketoacidosis

adrenal insufficiency

diabetes insipidus

pheochromocytoma