{"version":"1.0.0","segments":[{"startTime":1.839,"endTime":3.269,"body":"♪ (music) ♪"},{"startTime":3.269,"endTime":5.669,"body":"(Cathy) Hi, welcome"},{"startTime":3.269,"endTime":5.669,"body":"to \u003ci\u003eHarrison's Podclass\u003c/i\u003e,"},{"startTime":5.669,"endTime":8.779,"body":"where we discuss important concepts"},{"startTime":5.669,"endTime":8.779,"body":"in internal medicine."},{"startTime":8.779,"endTime":11.029,"body":"- I'm Cathy Handy."},{"startTime":8.779,"endTime":11.029,"body":"- (Charlie) And I'm Charlie Wiener,"},{"startTime":11.029,"endTime":14.166,"body":"and we're coming to you"},{"startTime":11.029,"endTime":14.166,"body":"from the Johns Hopkins School of Medicine."},{"startTime":14.166,"endTime":15.796,"body":"♪ (music) ♪"},{"speaker":"Welcome to Episode 37","startTime":15.796,"endTime":19.763,"body":"A 63-Year-Old with Confusion."},{"speaker":"Welcome to Episode 37","startTime":19.763,"endTime":21.563,"body":"Here is the case."},{"speaker":"Welcome to Episode 37","startTime":21.563,"endTime":24.013,"body":"A 63-year-old woman is brought"},{"speaker":"Welcome to Episode 37","startTime":21.563,"endTime":24.013,"body":"to the emergency department"},{"speaker":"Welcome to Episode 37","startTime":24.013,"endTime":27.853,"body":"by her nephew because"},{"speaker":"Welcome to Episode 37","startTime":24.013,"endTime":27.853,"body":"of severe confusion and obtundation."},{"speaker":"Welcome to Episode 37","startTime":27.853,"endTime":30.473,"body":"The nephew says he came"},{"speaker":"Welcome to Episode 37","startTime":27.853,"endTime":30.473,"body":"to visit her from out of town"},{"speaker":"Welcome to Episode 37","startTime":30.473,"endTime":32.863,"body":"and found her confused and somnolent."},{"speaker":"Welcome to Episode 37","startTime":32.863,"endTime":34.263,"body":"He thought she was just tired,"},{"speaker":"Welcome to Episode 37","startTime":34.263,"endTime":36.343,"body":"but then when he had difficulty waking her"},{"speaker":"Welcome to Episode 37","startTime":36.343,"endTime":38.363,"body":"he brought her"},{"speaker":"Welcome to Episode 37","startTime":36.343,"endTime":38.363,"body":"to the emergency department."},{"speaker":"Welcome to Episode 37","startTime":38.363,"endTime":40.043,"body":"Her vital signs are normal,"},{"speaker":"Welcome to Episode 37","startTime":40.043,"endTime":43.253,"body":"she is difficult to arouse"},{"speaker":"Welcome to Episode 37","startTime":40.043,"endTime":43.253,"body":"and is only oriented to self."},{"speaker":"Welcome to Episode 37","startTime":43.253,"endTime":45.843,"body":"There's no focal findings"},{"speaker":"Welcome to Episode 37","startTime":43.253,"endTime":45.843,"body":"on physical examination,"},{"speaker":"Welcome to Episode 37","startTime":45.843,"endTime":47.363,"body":"and other than her mental status,"},{"speaker":"Welcome to Episode 37","startTime":47.363,"endTime":49.853,"body":"there are no localizing"},{"speaker":"Welcome to Episode 37","startTime":47.363,"endTime":49.853,"body":"neurologic findings."},{"speaker":"Welcome to Episode 37","startTime":49.853,"endTime":53.593,"body":"Cathy, what were your initial thoughts"},{"speaker":"Welcome to Episode 37","startTime":49.853,"endTime":53.593,"body":"and the initial diagnostic maneuvers?"},{"speaker":"Welcome to Episode 37","startTime":53.593,"endTime":56.213,"body":"(Cathy) Well, the differential"},{"speaker":"Welcome to Episode 37","startTime":53.593,"endTime":56.213,"body":"diagnosis here is so broad,"},{"speaker":"Welcome to Episode 37","startTime":56.213,"endTime":58.853,"body":"and it's really hard"},{"speaker":"Welcome to Episode 37","startTime":56.213,"endTime":58.853,"body":"to narrow down at this point."},{"speaker":"Welcome to Episode 37","startTime":58.853,"endTime":61.843,"body":"In situations like this,"},{"speaker":"Welcome to Episode 37","startTime":58.853,"endTime":61.843,"body":"when I'm presented with these cases,"},{"speaker":"Welcome to Episode 37","startTime":61.843,"endTime":65.773,"body":"I really just try and start broad,"},{"speaker":"Welcome to Episode 37","startTime":61.843,"endTime":65.773,"body":"and the workup should be broad too,"},{"speaker":"Welcome to Episode 37","startTime":65.773,"endTime":67.283,"body":"and you just try and get some clues"},{"speaker":"Welcome to Episode 37","startTime":67.283,"endTime":70.009,"body":"to what system"},{"speaker":"Welcome to Episode 37","startTime":67.283,"endTime":70.009,"body":"might primarily be involved."},{"speaker":"Welcome to Episode 37","startTime":70.009,"endTime":71.969,"body":"In her case, the history sounds like"},{"speaker":"Welcome to Episode 37","startTime":71.969,"endTime":74.549,"body":"it's fairly acute"},{"speaker":"Welcome to Episode 37","startTime":71.969,"endTime":74.549,"body":"over the last couple of days,"},{"speaker":"Welcome to Episode 37","startTime":74.549,"endTime":79.809,"body":"and she doesn't have any localizing signs"},{"speaker":"Welcome to Episode 37","startTime":74.549,"endTime":79.809,"body":"to make me think of a territorial stroke."},{"speaker":"Welcome to Episode 37","startTime":79.809,"endTime":82.529,"body":"So, I'm really more worried"},{"speaker":"Welcome to Episode 37","startTime":79.809,"endTime":82.529,"body":"about an infection"},{"speaker":"Welcome to Episode 37","startTime":82.529,"endTime":84.979,"body":"or metabolic derangement first."},{"speaker":"Welcome to Episode 37","startTime":84.979,"endTime":88.569,"body":"So, I mean, we can really just start"},{"speaker":"Welcome to Episode 37","startTime":84.979,"endTime":88.569,"body":"with a CMP and a CBC"},{"speaker":"Welcome to Episode 37","startTime":88.569,"endTime":91.479,"body":"because that may be helpful"},{"speaker":"Welcome to Episode 37","startTime":88.569,"endTime":91.479,"body":"in deciding the next steps."},{"speaker":"Welcome to Episode 37","startTime":91.479,"endTime":94.839,"body":"(Charlie) Okay. Her CBC is normal,"},{"speaker":"Welcome to Episode 37","startTime":91.479,"endTime":94.839,"body":"but her metabolic panel"},{"speaker":"Welcome to Episode 37","startTime":94.839,"endTime":98.839,"body":"is notable for a serum calcium"},{"speaker":"Welcome to Episode 37","startTime":94.839,"endTime":98.839,"body":"of 14.8 mg/dL,"},{"speaker":"Welcome to Episode 37","startTime":98.839,"endTime":102.309,"body":"along with minimal elevation"},{"speaker":"Welcome to Episode 37","startTime":98.839,"endTime":102.309,"body":"of BUN and creatinine."},{"speaker":"Welcome to Episode 37","startTime":102.309,"endTime":104.129,"body":"(Cathy) Okay. Well,"},{"speaker":"Welcome to Episode 37","startTime":102.309,"endTime":104.129,"body":"that really was helpful."},{"speaker":"Welcome to Episode 37","startTime":104.129,"endTime":106.009,"body":"So, she's presenting with hypercalcemia,"},{"speaker":"Welcome to Episode 37","startTime":106.009,"endTime":109.629,"body":"and this is really an extreme"},{"speaker":"Welcome to Episode 37","startTime":106.009,"endTime":109.629,"body":"presentation of hypercalcemia."},{"speaker":"Welcome to Episode 37","startTime":109.629,"endTime":112.809,"body":"So, it can definitely cause"},{"speaker":"Welcome to Episode 37","startTime":109.629,"endTime":112.809,"body":"confusion and obtundation."},{"speaker":"Welcome to Episode 37","startTime":112.809,"endTime":114.629,"body":"But, most often, it's asymptomatic,"},{"speaker":"Welcome to Episode 37","startTime":114.629,"endTime":117.909,"body":"and we recognize it usually just on"},{"speaker":"Welcome to Episode 37","startTime":114.629,"endTime":117.909,"body":"routine calcium measurements."},{"speaker":"Welcome to Episode 37","startTime":117.909,"endTime":121.299,"body":"Some patients may complain"},{"speaker":"Welcome to Episode 37","startTime":117.909,"endTime":121.299,"body":"of vague neuropsychiatric symptoms,"},{"speaker":"Welcome to Episode 37","startTime":121.299,"endTime":125.299,"body":"including trouble concentrating,"},{"speaker":"Welcome to Episode 37","startTime":121.299,"endTime":125.299,"body":"personality changes, depression."},{"speaker":"Welcome to Episode 37","startTime":125.299,"endTime":127.939,"body":"But sometimes patients"},{"speaker":"Welcome to Episode 37","startTime":125.299,"endTime":127.939,"body":"will also have peptic ulcer disease"},{"speaker":"Welcome to Episode 37","startTime":127.939,"endTime":129.579,"body":"or nephrolithiasis."},{"speaker":"Welcome to Episode 37","startTime":129.579,"endTime":131.799,"body":"(Charlie) This sounds like"},{"speaker":"Welcome to Episode 37","startTime":129.579,"endTime":131.799,"body":"pretty severe hypercalcemia."},{"speaker":"Welcome to Episode 37","startTime":131.799,"endTime":134.429,"body":"(Cathy) Yeah. It's definitely"},{"speaker":"Welcome to Episode 37","startTime":131.799,"endTime":134.429,"body":"on the severe end of hypercalcemia."},{"speaker":"Welcome to Episode 37","startTime":134.429,"endTime":139.069,"body":"And we start to see that with serum levels"},{"speaker":"Welcome to Episode 37","startTime":134.429,"endTime":139.069,"body":"that are over 12 or 13 mg/dL,"},{"speaker":"Welcome to Episode 37","startTime":139.069,"endTime":140.189,"body":"and she's surpassed that."},{"speaker":"Welcome to Episode 37","startTime":140.189,"endTime":143.049,"body":"So, her calcium is 14.8,"},{"speaker":"Welcome to Episode 37","startTime":140.189,"endTime":143.049,"body":"so that's really high."},{"speaker":"Welcome to Episode 37","startTime":143.049,"endTime":147.659,"body":"And especially if it develops acutely,"},{"speaker":"Welcome to Episode 37","startTime":143.049,"endTime":147.659,"body":"then you can get lethargy, stupor, coma,"},{"speaker":"Welcome to Episode 37","startTime":147.659,"endTime":151.859,"body":"or more severe gastrointestinal symptoms,"},{"speaker":"Welcome to Episode 37","startTime":147.659,"endTime":151.859,"body":"like nausea, anorexia, constipation,"},{"speaker":"Welcome to Episode 37","startTime":151.859,"endTime":153.609,"body":"or even pancreatitis."},{"speaker":"Welcome to Episode 37","startTime":153.609,"endTime":156.359,"body":"(Charlie) Any comment"},{"speaker":"Welcome to Episode 37","startTime":153.609,"endTime":156.359,"body":"on the elevated BUN and creatinine?"},{"speaker":"Welcome to Episode 37","startTime":156.359,"endTime":159.549,"body":"(Cathy) Well, hypercalcemia decreases"},{"speaker":"Welcome to Episode 37","startTime":156.359,"endTime":159.549,"body":"the renal concentrating ability,"},{"speaker":"Welcome to Episode 37","startTime":159.549,"endTime":162.129,"body":"so that can cause polyuria and polydipsia."},{"speaker":"Welcome to Episode 37","startTime":162.129,"endTime":163.919,"body":"But with her neurologic symptoms,"},{"speaker":"Welcome to Episode 37","startTime":163.919,"endTime":166.799,"body":"she also is probably"},{"speaker":"Welcome to Episode 37","startTime":163.919,"endTime":166.799,"body":"not accessing enough water,"},{"speaker":"Welcome to Episode 37","startTime":166.799,"endTime":168.849,"body":"so she's likely volume depleted."},{"speaker":"Welcome to Episode 37","startTime":168.849,"endTime":171.087,"body":"Another thing to remember"},{"speaker":"Welcome to Episode 37","startTime":168.849,"endTime":171.087,"body":"with hypercalcemia"},{"speaker":"Welcome to Episode 37","startTime":171.087,"endTime":174.557,"body":"is that it can result in significant"},{"speaker":"Welcome to Episode 37","startTime":171.087,"endTime":174.557,"body":"electrocardiographic changes."},{"speaker":"Welcome to Episode 37","startTime":174.557,"endTime":176.347,"body":"So, you can sometimes see bradycardia,"},{"speaker":"Welcome to Episode 37","startTime":176.347,"endTime":179.027,"body":"sometimes AV block, short QT intervals,"},{"speaker":"Welcome to Episode 37","startTime":179.027,"endTime":181.997,"body":"so you would want to check"},{"speaker":"Welcome to Episode 37","startTime":179.027,"endTime":181.997,"body":"an EKG on this patient too."},{"speaker":"Welcome to Episode 37","startTime":181.997,"endTime":184.577,"body":"(Charlie) So, now that we know"},{"speaker":"Welcome to Episode 37","startTime":181.997,"endTime":184.577,"body":"she has severe hypercalcemia,"},{"speaker":"Welcome to Episode 37","startTime":184.577,"endTime":185.947,"body":"what do you think is causing that?"},{"speaker":"Welcome to Episode 37","startTime":185.947,"endTime":188.037,"body":"(Cathy) So, you need to think"},{"speaker":"Welcome to Episode 37","startTime":185.947,"endTime":188.037,"body":"about the feedback loops"},{"speaker":"Welcome to Episode 37","startTime":188.037,"endTime":190.087,"body":"that maintain calcium homeostasis,"},{"speaker":"Welcome to Episode 37","startTime":190.087,"endTime":192.997,"body":"and this involves"},{"speaker":"Welcome to Episode 37","startTime":190.087,"endTime":192.997,"body":"the parathyroid hormone, or PTH,"},{"speaker":"Welcome to Episode 37","startTime":192.997,"endTime":194.927,"body":"which comes from the parathyroid glands,"},{"speaker":"Welcome to Episode 37","startTime":194.927,"endTime":199.336,"body":"and the active vitamin D metabolite"},{"speaker":"Welcome to Episode 37","startTime":194.927,"endTime":199.336,"body":"1,25-dihydroxyvitamin D."},{"speaker":"Welcome to Episode 37","startTime":199.336,"endTime":200.946,"body":"So that comes via the kidneys."},{"speaker":"Welcome to Episode 37","startTime":200.946,"endTime":203.606,"body":"But then also remember"},{"speaker":"Welcome to Episode 37","startTime":200.946,"endTime":203.606,"body":"the gut which absorbs the calcium,"},{"speaker":"Welcome to Episode 37","startTime":203.606,"endTime":207.006,"body":"and then the bones which are"},{"speaker":"Welcome to Episode 37","startTime":203.606,"endTime":207.006,"body":"the major storage facility in your body"},{"speaker":"Welcome to Episode 37","startTime":207.006,"endTime":208.846,"body":"and can release a lot of calcium too."},{"speaker":"Welcome to Episode 37","startTime":208.846,"endTime":212.376,"body":"(Charlie) So, you really have to think"},{"speaker":"Welcome to Episode 37","startTime":208.846,"endTime":212.376,"body":"about the bones, the kidney, and the gut,"},{"speaker":"Welcome to Episode 37","startTime":212.376,"endTime":215.736,"body":"as you're trying to understand"},{"speaker":"Welcome to Episode 37","startTime":212.376,"endTime":215.736,"body":"the pathogenesis of hypercalcemia."},{"speaker":"Welcome to Episode 37","startTime":215.736,"endTime":217.906,"body":"(Cathy) Right,"},{"speaker":"Welcome to Episode 37","startTime":215.736,"endTime":217.906,"body":"and the parathyroid glands as well."},{"speaker":"Welcome to Episode 37","startTime":217.906,"endTime":220.586,"body":"So, the most common cause"},{"speaker":"Welcome to Episode 37","startTime":217.906,"endTime":220.586,"body":"of hypercalcemia in adults"},{"speaker":"Welcome to Episode 37","startTime":220.586,"endTime":224.586,"body":"is excess PTH production"},{"speaker":"Welcome to Episode 37","startTime":220.586,"endTime":224.586,"body":"or primary hyperparathyroidism."},{"speaker":"Welcome to Episode 37","startTime":224.586,"endTime":226.896,"body":"Although, usually,"},{"speaker":"Welcome to Episode 37","startTime":224.586,"endTime":226.896,"body":"we don't see presentations"},{"speaker":"Welcome to Episode 37","startTime":226.896,"endTime":230.646,"body":"that are this acute or this severe"},{"speaker":"Welcome to Episode 37","startTime":226.896,"endTime":230.646,"body":"with calciums to this degree."},{"speaker":"Welcome to Episode 37","startTime":230.646,"endTime":233.206,"body":"(Charlie) So, what causes"},{"speaker":"Welcome to Episode 37","startTime":230.646,"endTime":233.206,"body":"are you thinking of on this patient?"},{"speaker":"Welcome to Episode 37","startTime":233.206,"endTime":234.41,"body":"(Cathy) So, in this patient,"},{"speaker":"Welcome to Episode 37","startTime":234.41,"endTime":237.42,"body":"I'd also been thinking"},{"speaker":"Welcome to Episode 37","startTime":234.41,"endTime":237.42,"body":"about a primary malignancy."},{"speaker":"Welcome to Episode 37","startTime":237.42,"endTime":239.71,"body":"So, this can be over"},{"speaker":"Welcome to Episode 37","startTime":237.42,"endTime":239.71,"body":"the parathyroid glands,"},{"speaker":"Welcome to Episode 37","startTime":239.71,"endTime":243.01,"body":"so you can sometimes get"},{"speaker":"Welcome to Episode 37","startTime":239.71,"endTime":243.01,"body":"parathyroid adenomas, or hyperplasia,"},{"speaker":"Welcome to Episode 37","startTime":243.01,"endTime":244.59,"body":"or rarely carcinomas."},{"speaker":"Welcome to Episode 37","startTime":244.59,"endTime":245.63,"body":"In someone this age,"},{"speaker":"Welcome to Episode 37","startTime":245.63,"endTime":248.36,"body":"you also have to think about"},{"speaker":"Welcome to Episode 37","startTime":245.63,"endTime":248.36,"body":"hypercalcemia of malignancy,"},{"speaker":"Welcome to Episode 37","startTime":248.36,"endTime":251.92,"body":"and this can either be"},{"speaker":"Welcome to Episode 37","startTime":248.36,"endTime":251.92,"body":"from overproduction of PTH-related peptide"},{"speaker":"Welcome to Episode 37","startTime":251.92,"endTime":254.26,"body":"or from lytic skeletal metastases."},{"speaker":"Welcome to Episode 37","startTime":254.26,"endTime":257.45,"body":"So, some solid tumors will produce PTHrP"},{"speaker":"Welcome to Episode 37","startTime":257.45,"endTime":261.69,"body":"and that shares homology"},{"speaker":"Welcome to Episode 37","startTime":257.45,"endTime":261.69,"body":"with PTH in the first 13 amino acids,"},{"speaker":"Welcome to Episode 37","startTime":261.69,"endTime":263.554,"body":"and it binds the PTH receptor."},{"speaker":"Welcome to Episode 37","startTime":263.554,"endTime":266.644,"body":"So, it mimics the effects of PTH"},{"speaker":"Welcome to Episode 37","startTime":263.554,"endTime":266.644,"body":"on the bone and the kidney."},{"speaker":"Welcome to Episode 37","startTime":266.651,"endTime":270.121,"body":"And in PTHrP-mediated"},{"speaker":"Welcome to Episode 37","startTime":266.651,"endTime":270.121,"body":"hypercalcemia of malignancy,"},{"speaker":"Welcome to Episode 37","startTime":270.121,"endTime":274.281,"body":"the native PTH levels are suppressed"},{"speaker":"Welcome to Episode 37","startTime":270.121,"endTime":274.281,"body":"by the high serum calcium levels."},{"speaker":"Welcome to Episode 37","startTime":274.281,"endTime":278.03,"body":"(Charlie) So, primary hyperparathyroidism"},{"speaker":"Welcome to Episode 37","startTime":274.281,"endTime":278.03,"body":"and hypercalcemia of malignancy"},{"speaker":"Welcome to Episode 37","startTime":278.03,"endTime":280.66,"body":"are the two top things"},{"speaker":"Welcome to Episode 37","startTime":278.03,"endTime":280.66,"body":"on your differential then at this point."},{"speaker":"Welcome to Episode 37","startTime":280.66,"endTime":281.67,"body":"(Cathy) Yeah."},{"speaker":"Welcome to Episode 37","startTime":281.67,"endTime":283.91,"body":"(Charlie) Okay. What about things"},{"speaker":"Welcome to Episode 37","startTime":281.67,"endTime":283.91,"body":"further down your list,"},{"speaker":"Welcome to Episode 37","startTime":283.91,"endTime":285.7,"body":"just for the sake of completeness?"},{"speaker":"Welcome to Episode 37","startTime":285.7,"endTime":288.54,"body":"(Cathy) Hypercalcemia"},{"speaker":"Welcome to Episode 37","startTime":285.7,"endTime":288.54,"body":"associated with granulomatous disease,"},{"speaker":"Welcome to Episode 37","startTime":288.54,"endTime":291.38,"body":"for example, with sarcoidosis"},{"speaker":"Welcome to Episode 37","startTime":288.54,"endTime":291.38,"body":"or lymphomas,"},{"speaker":"Welcome to Episode 37","startTime":291.38,"endTime":294.56,"body":"is caused by enhanced conversion"},{"speaker":"Welcome to Episode 37","startTime":291.38,"endTime":294.56,"body":"of 25-hydroxyvitamin D"},{"speaker":"Welcome to Episode 37","startTime":294.56,"endTime":297.79,"body":"to the more potent"},{"speaker":"Welcome to Episode 37","startTime":294.56,"endTime":297.79,"body":"1,25-[di]hydroxyvitamin D."},{"speaker":"Welcome to Episode 37","startTime":297.79,"endTime":298.874,"body":"In these disorders,"},{"speaker":"Welcome to Episode 37","startTime":298.874,"endTime":303.104,"body":"1,25-[di]hydroxyvitamin D"},{"speaker":"Welcome to Episode 37","startTime":298.874,"endTime":303.104,"body":"enhances intestinal calcium absorption"},{"speaker":"Welcome to Episode 37","startTime":303.104,"endTime":306.574,"body":"and that results in hypercalcemia"},{"speaker":"Welcome to Episode 37","startTime":303.104,"endTime":306.574,"body":"and suppressed PTH."},{"speaker":"Welcome to Episode 37","startTime":306.574,"endTime":309.104,"body":"Now, besides metastases,"},{"speaker":"Welcome to Episode 37","startTime":306.574,"endTime":309.104,"body":"there are other disorders"},{"speaker":"Welcome to Episode 37","startTime":309.104,"endTime":311.904,"body":"that directly increase"},{"speaker":"Welcome to Episode 37","startTime":309.104,"endTime":311.904,"body":"calcium mobilization from the bone,"},{"speaker":"Welcome to Episode 37","startTime":311.904,"endTime":313.564,"body":"such as hyperthyroidism."},{"speaker":"Welcome to Episode 37","startTime":313.564,"endTime":317.664,"body":"Less likely causes of hypercalcemia"},{"speaker":"Welcome to Episode 37","startTime":313.564,"endTime":317.664,"body":"would be exogenous calcium overload,"},{"speaker":"Welcome to Episode 37","startTime":317.664,"endTime":319.594,"body":"as in milk-alkali syndrome"},{"speaker":"Welcome to Episode 37","startTime":319.594,"endTime":323.714,"body":"or a total parenteral nutrition"},{"speaker":"Welcome to Episode 37","startTime":319.594,"endTime":323.714,"body":"with excessive calcium supplementation."},{"speaker":"Welcome to Episode 37","startTime":323.717,"endTime":327.447,"body":"Now, both of those would cause"},{"speaker":"Welcome to Episode 37","startTime":323.717,"endTime":327.447,"body":"decreased levels of PTH."},{"speaker":"Welcome to Episode 37","startTime":327.447,"endTime":330.067,"body":"The other disorder"},{"speaker":"Welcome to Episode 37","startTime":327.447,"endTime":330.067,"body":"on the differential for hypercalcemia"},{"speaker":"Welcome to Episode 37","startTime":330.067,"endTime":334.207,"body":"that would cause an inappropriately"},{"speaker":"Welcome to Episode 37","startTime":330.067,"endTime":334.207,"body":"elevated or normal PTH level"},{"speaker":"Welcome to Episode 37","startTime":334.207,"endTime":337.407,"body":"is familial hypocalciuric hypercalcemia."},{"speaker":"Welcome to Episode 37","startTime":337.407,"endTime":339.507,"body":"Now, this is an autosomal"},{"speaker":"Welcome to Episode 37","startTime":337.407,"endTime":339.507,"body":"dominant syndrome"},{"speaker":"Welcome to Episode 37","startTime":339.507,"endTime":342.357,"body":"that's most commonly involving"},{"speaker":"Welcome to Episode 37","startTime":339.507,"endTime":342.357,"body":"inactivating mutations"},{"speaker":"Welcome to Episode 37","startTime":342.357,"endTime":344.137,"body":"in the calcium-sensing receptor,"},{"speaker":"Welcome to Episode 37","startTime":344.137,"endTime":346.917,"body":"and these mutations impair"},{"speaker":"Welcome to Episode 37","startTime":344.137,"endTime":346.917,"body":"extracellular calcium-sensing"},{"speaker":"Welcome to Episode 37","startTime":346.917,"endTime":348.837,"body":"by the parathyroid glands"},{"speaker":"Welcome to Episode 37","startTime":346.917,"endTime":348.837,"body":"and the kidneys,"},{"speaker":"Welcome to Episode 37","startTime":348.837,"endTime":351.337,"body":"and that leads"},{"speaker":"Welcome to Episode 37","startTime":348.837,"endTime":351.337,"body":"to inappropriate PTH secretion"},{"speaker":"Welcome to Episode 37","startTime":351.337,"endTime":354.147,"body":"and increased renal"},{"speaker":"Welcome to Episode 37","startTime":351.337,"endTime":354.147,"body":"tubular calcium reabsorption."},{"speaker":"Welcome to Episode 37","startTime":354.147,"endTime":355.787,"body":"(Charlie) Okay. That sounds like a lot."},{"speaker":"Welcome to Episode 37","startTime":355.787,"endTime":358.967,"body":"But the differential of hypercalcemia"},{"speaker":"Welcome to Episode 37","startTime":355.787,"endTime":358.967,"body":"really is an important differential"},{"speaker":"Welcome to Episode 37","startTime":358.967,"endTime":360.437,"body":"for us to keep in mind."},{"speaker":"Welcome to Episode 37","startTime":360.437,"endTime":362.157,"body":"It sounds like"},{"speaker":"Welcome to Episode 37","startTime":360.437,"endTime":362.157,"body":"the next reasonable lab test"},{"speaker":"Welcome to Episode 37","startTime":362.157,"endTime":365.887,"body":"would be to start with the branch point"},{"speaker":"Welcome to Episode 37","startTime":362.157,"endTime":365.887,"body":"of measuring the PTH level then, right?"},{"speaker":"Welcome to Episode 37","startTime":365.887,"endTime":367.607,"body":"(Cathy) Yeah."},{"speaker":"Welcome to Episode 37","startTime":365.887,"endTime":367.607,"body":"That's the first branch point"},{"speaker":"Welcome to Episode 37","startTime":367.607,"endTime":369.667,"body":"since that's the most"},{"speaker":"Welcome to Episode 37","startTime":367.607,"endTime":369.667,"body":"common cause to consider,"},{"speaker":"Welcome to Episode 37","startTime":369.667,"endTime":371.987,"body":"although malignancy"},{"speaker":"Welcome to Episode 37","startTime":369.667,"endTime":371.987,"body":"is also a concern in this patient."},{"speaker":"Welcome to Episode 37","startTime":371.987,"endTime":374.217,"body":"So, I would also check the PTHrP."},{"speaker":"Welcome to Episode 37","startTime":374.217,"endTime":376.527,"body":"(Charlie) Okay."},{"speaker":"Welcome to Episode 37","startTime":374.217,"endTime":376.527,"body":"Well, let's get back to this patient."},{"speaker":"Welcome to Episode 37","startTime":376.527,"endTime":377.997,"body":"Subsequent laboratory testing"},{"speaker":"Welcome to Episode 37","startTime":377.997,"endTime":380.367,"body":"reveals a normal"},{"speaker":"Welcome to Episode 37","startTime":377.997,"endTime":380.367,"body":"parathyroid hormone level,"},{"speaker":"Welcome to Episode 37","startTime":380.367,"endTime":383.977,"body":"but an elevated parathyroid"},{"speaker":"Welcome to Episode 37","startTime":380.367,"endTime":383.977,"body":"hormone-related protein level."},{"speaker":"Welcome to Episode 37","startTime":383.977,"endTime":387.117,"body":"So, we then went on to imaging,"},{"speaker":"Welcome to Episode 37","startTime":383.977,"endTime":387.117,"body":"and the initial evaluation shows"},{"speaker":"Welcome to Episode 37","startTime":387.117,"endTime":391.117,"body":"a chest radiograph with multiple nodules"},{"speaker":"Welcome to Episode 37","startTime":387.117,"endTime":391.117,"body":"suggestive of metastatic disease."},{"speaker":"Welcome to Episode 37","startTime":391.117,"endTime":393.727,"body":"Unfortunately, the nephew"},{"speaker":"Welcome to Episode 37","startTime":391.117,"endTime":393.727,"body":"does not know anything about"},{"speaker":"Welcome to Episode 37","startTime":393.727,"endTime":395.547,"body":"his aunt's past medical history."},{"speaker":"Welcome to Episode 37","startTime":395.547,"endTime":397.997,"body":"He tells us that he was only"},{"speaker":"Welcome to Episode 37","startTime":395.547,"endTime":397.997,"body":"in town visiting his aunt"},{"speaker":"Welcome to Episode 37","startTime":397.997,"endTime":400.987,"body":"while he was attending"},{"speaker":"Welcome to Episode 37","startTime":397.997,"endTime":400.987,"body":"a healing yoga conference."},{"speaker":"Welcome to Episode 37","startTime":400.987,"endTime":403.517,"body":"The question asks about"},{"speaker":"Welcome to Episode 37","startTime":400.987,"endTime":403.517,"body":"the various malignancies"},{"speaker":"Welcome to Episode 37","startTime":403.517,"endTime":405.177,"body":"that can cause this syndrome."},{"speaker":"And the question reads","startTime":406.827,"endTime":407.922,"body":"\"All of the following"},{"speaker":"And the question reads","startTime":407.922,"endTime":411.707,"body":"are likely primary malignancy"},{"speaker":"And the question reads","startTime":407.922,"endTime":411.707,"body":"in this woman, except...\""},{"speaker":"And the question reads","startTime":411.707,"endTime":416.327,"body":"So, there are four possible choices"},{"speaker":"And the question reads","startTime":411.707,"endTime":416.327,"body":"that are correct and one incorrect."},{"speaker":"And the choices are","startTime":418.017,"endTime":421.067,"body":"A. adenocarcinoma of the breast;"},{"speaker":"And the choices are","startTime":421.067,"endTime":423.447,"body":"B. mantle cell lymphoma;"},{"speaker":"And the choices are","startTime":423.447,"endTime":426.807,"body":"C. squamous cell of the lung;"},{"speaker":"And the choices are","startTime":426.807,"endTime":430.127,"body":"D. squamous cell of the pyriform sinus;"},{"speaker":"And the choices are","startTime":430.127,"endTime":432.987,"body":"or E. transitional cell of the bladder."},{"speaker":"And the choices are","startTime":432.987,"endTime":435.547,"body":"(Cathy) Okay. So, we've gone through"},{"speaker":"And the choices are","startTime":432.987,"endTime":435.547,"body":"the differential diagnosis"},{"speaker":"And the choices are","startTime":435.547,"endTime":437.637,"body":"of hypercalcemia and the lab abnormalities"},{"speaker":"And the choices are","startTime":437.637,"endTime":439.727,"body":"that you would expect"},{"speaker":"And the choices are","startTime":437.637,"endTime":439.727,"body":"in the different types."},{"speaker":"And the choices are","startTime":439.727,"endTime":442.377,"body":"You can see humoral"},{"speaker":"And the choices are","startTime":439.727,"endTime":442.377,"body":"hypercalcemia of malignancy"},{"speaker":"And the choices are","startTime":442.377,"endTime":444.627,"body":"in up to 20% of patients with cancer."},{"speaker":"And the choices are","startTime":444.627,"endTime":446.967,"body":"And it's most common"},{"speaker":"And the choices are","startTime":444.627,"endTime":446.967,"body":"in cancers of the lung,"},{"speaker":"And the choices are","startTime":446.967,"endTime":450.857,"body":"head and neck, skin,"},{"speaker":"And the choices are","startTime":446.967,"endTime":450.857,"body":"esophagus, breast, GU tract,"},{"speaker":"And the choices are","startTime":450.857,"endTime":451.927,"body":"for the solid tumors."},{"speaker":"And the choices are","startTime":451.927,"endTime":453.967,"body":"And then if you think"},{"speaker":"And the choices are","startTime":451.927,"endTime":453.967,"body":"about the heme malignancies,"},{"speaker":"And the choices are","startTime":453.967,"endTime":455.797,"body":"you see it often in multiple myeloma--"},{"speaker":"And the choices are","startTime":455.797,"endTime":458.807,"body":"remember that high calcium"},{"speaker":"And the choices are","startTime":455.797,"endTime":458.807,"body":"is one of the CRAB criteria--"},{"speaker":"And the choices are","startTime":458.807,"endTime":460.507,"body":"and also in lymphomas."},{"speaker":"And the choices are","startTime":460.507,"endTime":463.727,"body":"(Charlie) Which of these"},{"speaker":"And the choices are","startTime":460.507,"endTime":463.727,"body":"will cause an elevated PTHrP?"},{"speaker":"And the choices are","startTime":463.727,"endTime":465.647,"body":"(Cathy) Yeah, so that's the key"},{"speaker":"And the choices are","startTime":463.727,"endTime":465.647,"body":"to this question."},{"speaker":"And the choices are","startTime":465.647,"endTime":468.707,"body":"So, all of the solid tumors"},{"speaker":"And the choices are","startTime":465.647,"endTime":468.707,"body":"that are mentioned in the question--"},{"speaker":"And the choices are","startTime":468.707,"endTime":471.517,"body":"so breast cancer, lung cancer,"},{"speaker":"And the choices are","startTime":468.707,"endTime":471.517,"body":"the head and neck cancer,"},{"speaker":"And the choices are","startTime":471.517,"endTime":474.787,"body":"and bladder cancer--"},{"speaker":"And the choices are","startTime":471.517,"endTime":474.787,"body":"can all cause PTHrP."},{"speaker":"And the choices are","startTime":474.787,"endTime":477.617,"body":"We talked before about"},{"speaker":"And the choices are","startTime":474.787,"endTime":477.617,"body":"how hypercalcemia from lymphoma"},{"speaker":"And the choices are","startTime":477.617,"endTime":479.817,"body":"tends to be via vitamin D conversion"},{"speaker":"And the choices are","startTime":479.817,"endTime":482.217,"body":"and not from PTHrP protein production."},{"speaker":"And the choices are","startTime":482.217,"endTime":486.317,"body":"So, in this patient, who we know"},{"speaker":"And the choices are","startTime":482.217,"endTime":486.317,"body":"has multiple metastases in her lungs"},{"speaker":"And the choices are","startTime":486.317,"endTime":488.274,"body":"and an elevated PTHrP,"},{"speaker":"And the choices are","startTime":488.274,"endTime":491.834,"body":"the least likely cancer we would find"},{"speaker":"And the choices are","startTime":488.274,"endTime":491.834,"body":"would be mantle cell lymphoma."},{"speaker":"And the choices are","startTime":491.834,"endTime":494.384,"body":"(Charlie) Great. Okay."},{"speaker":"And the choices are","startTime":491.834,"endTime":494.384,"body":"So, the teaching point of this case"},{"speaker":"And the choices are","startTime":494.384,"endTime":498.208,"body":"is that severe hypercalcemia"},{"speaker":"And the choices are","startTime":494.384,"endTime":498.208,"body":"can present with altered mental status"},{"speaker":"And the choices are","startTime":498.208,"endTime":500.188,"body":"or other neurologic findings."},{"speaker":"And the choices are","startTime":500.188,"endTime":504.468,"body":"It may be caused by an elevation"},{"speaker":"And the choices are","startTime":500.188,"endTime":504.468,"body":"of PTH-related protein"},{"speaker":"And the choices are","startTime":504.468,"endTime":506.294,"body":"emanating from solid tumors,"},{"speaker":"And the choices are","startTime":506.294,"endTime":510.934,"body":"typically from the breast, lung,"},{"speaker":"And the choices are","startTime":506.294,"endTime":510.934,"body":"head and neck, or even the bladder."},{"speaker":"And the choices are","startTime":510.934,"endTime":513.384,"body":"Lymphoma can also cause hypercalcemia,"},{"speaker":"And the choices are","startTime":513.384,"endTime":514.864,"body":"but that's via a different mechanism"},{"speaker":"And the choices are","startTime":514.864,"endTime":517.199,"body":"that relates to elevated"},{"speaker":"And the choices are","startTime":514.864,"endTime":517.199,"body":"levels of vitamin D"},{"speaker":"And the choices are","startTime":517.199,"endTime":519.054,"body":"and, therefore, gut absorption."},{"speaker":"And the choices are","startTime":519.054,"endTime":520.744,"body":"(Cathy) And if you want"},{"speaker":"And the choices are","startTime":519.054,"endTime":520.744,"body":"to read more about this,"},{"speaker":"And the choices are","startTime":520.744,"endTime":523.754,"body":"you can check out \u003ci\u003eHarrison's\u003c/i\u003e chapter"},{"speaker":"And the choices are","startTime":520.744,"endTime":523.754,"body":"on Oncology and Hematology."},{"speaker":"And the choices are","startTime":523.754,"endTime":526.334,"body":"But also within the Cardinal"},{"speaker":"And the choices are","startTime":523.754,"endTime":526.334,"body":"Manifestations of Disease,"},{"speaker":"And the choices are","startTime":526.334,"endTime":528.554,"body":"there's a chapter on hypercalcemia."},{"speaker":"And the choices are","startTime":528.554,"endTime":531.278,"body":"♪ (music) ♪"}]}