Thank you, Raj, and you did just under three minutes. It was perfect, actually. So, next, you met yesterday Dr. Jerry Zimmerman. He's a professor of pediatrics at Seattle Children's, and he's going to talk about pediatric endocrine issues. Thank you, Jerry. All right, ready for the whirlwind tour of endocrine issues in the ICU. No relevant conflicts of interest here, disclosures. Diabetic ketoacidosis is the most common endocrine issue that we face in the ICU, and it's caused by insulin deficiency from whatever reason in the setting of a stress response. So what's important here is lack of insulin augments with the stress response unrestrained gluconeogenesis. So there's more glucose in the system leading to hyperglycemia, hold that thought. Then there is a switch for primary energy substrate from carbohydrates to lipids, lipolysis, beta oxidation of free fatty acid. That gives you the ketosis, and we measure that typically nowadays as beta hydroxybutyrate. Elevated glucose hyperosmolality leads to wasting of water, electrolytes through the kidney. These patients become dehydrated over a couple of days, typically about 7%. So what is our treatment strategy for this? First of all is to address the fluid deficit. This is not septic shock. These patients typically do not have an elevated lactate, but they do need restoration of their circulating volume, particularly to reperfuse their kidneys, less is more. What these patients really need is insulin. That's what the problem is. The rehydration can happen over 48 hours. It doesn't all need to happen right away. Patience is a virtue here. And then replace electrolyte deficits, particularly total body potassium, which is typically low. If there is a precipitant, try to identify it and treat it. Avoid complications, particularly in this transition from continuous insulin to intermittent dosing. That's where you can get into trouble with hypoglycemia and hypokalemia. That's a stress point. And then lastly, most of the time these patients are in the ICU because someone is worried about cerebral edema. So we really need to watch these patients carefully. As glucose is falling, serum sodium has to rise. That maintains essentially the same osmolality in the blood. If that doesn't happen, if the sodium is not coming up, that is a big red flag because that is a setting for disequilibrium and a tendency for water to move out of the vascular space into tissue, including the brain, and that would be a bad thing. I want to contrast DKA with this other thing, the hyperglycemia hyperosmolar syndrome, because the latter is increasing. So DKA, typically elevated glucose, 300, 400, 500 milligrams per deciliter. There is acidosis, pH less than 7.3 or bicarbonate less than 15. That is part of the definition. We already talked about ketosis, that's the third part of the definition. It's readily detectable in the plasma as well as urine. Now for HHS, the serum glucose is typically much higher, high hundreds, 1,000 or more. There's less acidosis because insulin deficiency is not as absolute and ketosis, instead of being prominent, is more likely to be traced. Bicarbonate is not depressed as much as in DKA. What's important about HHS patients is they typically are severely dehydrated, much more than DKA patients, and their rehydration needs to happen slowly. If someone comes in with a glucose of 8, 900, that needs to be taken down slowly, 100 milligrams per deciliter per hour, not faster, and when that happens, the serum sodium is going to come up. It may come up to 150, 160. That's okay. After you get the glucose fixed, then you can address the sodium, which also will need to come down gradually. This will happen with gradual rehydration and insulin. So adrenal insufficiency, one of the religious orders in the ICU, it can happen by a number of different mechanisms, congenitally, typically in resource-adequate countries. This is identified at birth. Universal screening is in place. Autoimmune disease manifests as Addison's disease. Messed up signaling with ACTH at the adrenal gland causes this familial glucocorticoid deficiency. Waterhouse-Friedrichson syndrome, everybody's afraid of it. Adrenal hemorrhage in the setting, particularly in the old days with H-flu or meningococcal septic shock, fortunately, we just don't see it as often anymore, but everybody's still afraid of it. By far, in a way, the biggest issue regarding adrenal insufficiency are patients who've been treated with steroids, BPD, asthma, oncology, hemat, transplant patients. If these patients become stressed in any way, they should be considered for hydrocortisone stress dosing. Glucocorticoids broadly inhibit all aspects of immunity. What you see here are the effects on innate immunity, really, and it's widespread. Cytokines, chemokines, adhesion molecules, inducible nitric oxide synthase. At the same time, there's upregulation of anti-inflammatory cytokines like interleukin 10, lipocortin, broad immunosuppression. This extends also very broadly into acquired immunity. If you give a dose of corticosteroids, you are going to alter the gene expression of about 30% of your total body genes. So just remember that when you're treating somebody with steroid, and when it's no longer necessary, stop it. Moving on to the renin-angiotensin-aldosterone axis, signaling for ultimate production of aldosterone begins at the kidney, at the juxtaglomerular apparatus. And you absolutely need to know this for cocktail parties because it sounds good. The signaling is either increased sodium and chloride in the renal tubules right adjacent to the JGA signaling from the brain, beta 1 signaling directly from the brain. This results in release of renin into the blood, and renin will clip angiotensinidin or cleave it to angiotensin 1. And then angiotensin 1 is further cleaved to angiotensin 2 by angiotensin converting enzyme found in all endothelial cells. Angiotensin is the signal at the adrenal gland for production of aldosterone that works at the distal convoluted tubule to reclaim sodium. So just a couple things about angiotensin 2 because we don't talk about it very much, but it is an interesting hormone. Unlike glucocorticoids, aldosterone actually augments the inflammatory response. So pi 1 is increased, which would actually augment microvascular thrombosis. There is increased in NF-kappa B, the nuclear transcription factor that gets into the nucleus and up-regulates, not down-regulates, pro-inflammation. Angiotensin 2 augments almost all other hormones, norepinephrine, ACTH, vasopressin, and aldosterone. And of course, it has vasoactive activities and is now available, limited data in kids, as an alternative vasopressor. So a couple of words about the salt water syndromes. Cerebral salt wasting, diabetes insipidus, and SIADH. Cerebral salt wasting and DI should be considered as negative fluid electrolyte issues. Cerebral salt wasting, most people think poor data, but is caused by excessive B-type natriuretic peptide. There is a massive loss of water and sodium chloride, high urine output. If you look at the urine sodium, it's going to be 100, 200, 300 milliequivalents per kilogram. This is typically an acute event. It doesn't last very long. Initially, you have to keep up with the fluid losses with some type of isotonic fluid. And at some point, bite your lip and stop that replacement, otherwise you'll be chasing your tail. Diabetes insipidus also has large volume losses, but it's water. It has hardly any sodium in it at all. It's caused by lack of vasopressin, and ultimately, that is the intervention that needs to happen. Most hyponatremia in the ICU is caused by SIADH, excessive antidiuretic hormone. The treatment is not more sodium. That is not the issue. The treatment is less free water going in, so decrease the maintenance fluid. If you follow New England Journal, there was just a case of pheochromocytoma presented. This is an endocrine adrenergic sympathetic tumor that generates catecholamines that can be measured in the urine and plasma as metanephrines. These patients present typically with hypertension, but perhaps tachycardia and peripheral vasoconstriction as well, and the ultimate diagnosis is made by genetic testing. These children ultimately need to undergo surgical resection of their tumors, but in the days to weeks preceding this surgery, they need to first undergo a blockade of this excess of catecholamine production so that they maintain hemodynamic stability during and following surgery. The board questions always say, what do you do first? It's alpha blockade with fentolamine. This is followed then by beta blockade, and you may want to eventually use a drug that has both effects, alpha and beta blockade, like Levetilol. Occasionally you may need a tyrosine hydroxylase inhibitor as well before the surgical resection. Finally, some words about the thyroid. Most of our patients who are in the ICU and actually are critically ill have this thing called sick euthyroid or euthyroid sick. Take your choice. In this setting, these patients have a normal circulating thyroxine P4, but because they have down regulation of this enzyme 5'-deiodinase, the conversion of T4 to T3 in peripheral tissues is markedly decreased, and that's how you make the diagnosis. What's important here is thyroid stimulating hormone, TSH, is normal. These patients are not hypothyroid. The evidence of whether it's beneficial or not to replace T3 remains controversial. True hypothyroidism. There are a number of ways that this can happen, shown here. The definitive test here is that in true hypothyroidism, there is an elevation of thyroid stimulating hormone, but this can be messed up in the ICU if the patient's on corticosteroids or the patient is severely malnourished or on dopamine. All will mask the uptick of TSH. On the other hand, hyperthyroidism, a number of reasons why this can occur. Remember amiodarone? That's a test question that frequently shows up. We don't see hyperthyroidism in the PEDS ICU very often. Anybody seen this? A few people? It doesn't happen very often, but when it does happen and there is a trigger like, for example, trauma or infection, this can be life-threatening as a thyroid storm. This is treated in a variety of ways. Ultimately, this patient may need radioiodine ablation of the thyroid or surgery, but prior to that, patients receive inhibitors of thyroid hormone secretion, block the activity of thyroid hormone in peripheral tissues, treat the precipitating event if there is one, and then if these patients don't come under control with these medications, the excessive thyroid hormone can actually be cleared from the plasma with plasmapheresis. And there are case reports of hemodynamic support of these patients with ECLS as a life-saving measure. All right, Anna, I'm on time. Thank you very much.

pediatric endocrine issues

diabetic ketoacidosis

adrenal insufficiency

diabetes insipidus

thyroid dysfunction