Case Conference #2: 2-6-03

[Kalel]

This is a relatively simple outpatient case of a patient that I saw in a community clinic 2 hrs ago, but I thought that it might be fun to discuss anyways.

68 yo AAM with PMHx of Graves disease s/p radioactive iodine ablation therapy 3 yrs ago now hypothyroid, htn, prostate ca s/p surgical resection with no evidence of recurrence, DVT 3 yrs ago while prostate ca was active, sleep apnea with non-compliance with CPAP secondary to patient discomfort, and asthma presents to a community clinic with c/o b/l LE edema. He states that the dorsum of both feet have been swelling up for the past 3 yrs, ever since he had his DVT, and the swelling has gotten progressively worse. Pt states that the swelling is worse at night and after prolonged periods of standing, and is relieved when he props his feet up or lies down.

Meds: Levothyroxine, Leuprolide, Hydrazaar, Hyzaar (Hctz/Losartan)

SHx: denies any previous tob use, reports social EtOH use, denies any previous drug use. He works as a social worker

All: NKDA

PE: Obese AAM, sitting upright, NAD
HEENT: NC/AT, + Exopthalamos, PERRL, EOMi, unable to see any JVD secondary to patient's obesity, no LAD, unable to palpate thyroid
CVS: RRR, no m/r/g, distant heart sounds
Chest: CTA b/l, + gynecomastia
Abd: obese, s/NT, +BS
Ext: +2 pitting pretibial edema, no edema over dorum of feet but patient reports that there is no edema because he hasn't been standing for very long
Neuro: CN II-XII grossly in tact, no neuro deficits notes, strength 5/5 throughout, +2 reflexes throughout

Questions:
1. What further questions do you want to ask this patient?
2. What further diagnostic tests would you want to order for this patient? (keeping in mind that you are seeing the patient in an outpatient settting)
3. What do you think is the most likely cause of the of his LE edema and pretibial edema? Explain the pathophysiology behind it and say what you would use to treat this.

Anyways, because this is a real patient, there is no "right" answer, but I will post what we did, my thoughts on the patient, and further information about the patient as requested later. Have fun!

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[JungleBoy]

Interesting case,
So you have a Pt with PMHx of Graves>rad Iodine>hypothyroidism, sleep apnea, prostate CA and DVT presenting with bilat LE dependent pitting edema.
I think there are a few things I'd consider for his differential diagnosis: sleep apnea > cor pulmonale> right-sided heart failure, pericardial effusion due to hypothyroidism causing symptoms of right-sided heart failure, side effect of medication (any calcium channel blockers?), HTN causing CHF, hypothyroidism itself causing edema. Of course you should also consider the other causes of edema such as chronic liver disease, renal disease etc, but these seem less likely to me because I don't see anything suggestive in the pt's hx. DVT could also cause edema due to chronic venous insufficiency, but the fact that it's bilateral, dependent, and there is no stasis dermatitis makes it less likely.
I would like to know whether this pt has any symptoms of left-sided heart failure. What about other signs of right-sided failure such as increased abd girth, signs of ascites, hepato-jugular reflux, and RUQ tenderness?
As far as exams in an outpatient setting, I'd ask a CBC, especially to look at the hematocrit. EKG, to look for p wave abnormalities ("p pulmonale") and signs of right ventricular strain. Chest Xray PA-Lat to see the right ventricle and pulmonary artery. Echocardiography for the same reason, plus to check for any pericardial effusion, EF etc. Pulse oximetry to check O2sat. I'd also do a UA, serum albumin, and BMP.
If I had to pick one dx possibility it would be Cor Pulmonale. The pt has sleep apnea, which causes chronic hypoxemia > pulmonary vasoconstriction (increased pulmonary resistance) > right-sided cardiac failure > signs & symptoms of right-sided heart failure.
If that is the dx, I'd manage the pt 1-stress the importance of CPAP 2-home oxigen 3-Diuretics 4-salt and fluid restriction.

Again, interesting case! Let me know about your diagnosis and management for this case.

 

[lurkerboy]

I agree with what you say but would also check a TSH to see how well he's doing on the synthroid.

 

[Kalel]

Interesting thoughts. I think that I will wait a little while longer before posting my thoughts and the outcome of this case though. I can post actual labs (or approximate), because the patient did have his blood drawn in the office.

TSH: 1.5 (normal)
CBC: WBC: 3.2 L, Platelets: 130,000L, Hgb: 11.0L, Hct: 35.6L
Chem-7 revealed a fasting glucose of 130, total Cholesterol: 187, HDL: 84, LDL: 73, Trig: 120. All other values were wnl.

A review of his past medical record revealed that his Hgb had been running on the low side at 11.5 over the past ~2 yrs, and he has had a mild thrombocytopenia for the past ~2 yrs as well.

Any further questions for that patient or thoughts on the case? Why might the patient be anemic or thrombocytopenic? Also, why does the patient have pre-tibial edema but no edema in the dorsum of his foot (where he described normally getting edema)?

 

[JungleBoy]

Well, a hct of 35% doesn't support my dx of cor pulmonale due to sleep apnea, although it certainly doesn't exclude it. Anemia and mild thrombocytopenia associated with edema makes me wonder about the pt's hepatic function. Any hx of hepatitis, blood tranfusions (eg during the prostate surgery) in the past? Any stigmata of chronic liver disease (spider nevi, caput medusae/collateral circulation in the abd, dupuytren contracture, palmar erythema etc)?

 

[Kalel]

Nope, no stigmata of any liver disease (except for the gynecomastia which could have been accounted for by his current medication of leuprolide) and there was no history of any exposure of hepatitis. I was confused by his anemia and thrombocytopenia at first, because I had the same thoughts that you had, but the clue that I will give you to this patient is that I did not tell you all of the history and that he has more then one disease process going on (I could be mistaken, but I believe that he violates "occum's razor").

 

[lurkerboy]

Did you intentionally leave out the vitals? I am wondering if they might be relevant. Any h/o kidney disease? Does the swelling occur daily?

 

[Kalel]

Vitals:
BP: 118/75, P: 75, R: 10, T: 98.5
No h/o kidney disease.

Pt does report that the swelling has gotten worse over the past few weeks. The swelling does occur daily, but as stated previously, it is worse when he walks or stands for long periods of time.

 

[sanfilippo]

what's most alarming is this anemia evolving into pancytopenia.

broad differential here:
infection (TB, HIV, viral hep)
PNH
aplasia
myleodysplasia/ malignancy
folate/b12 def.
drug toxicity
lupus
sarcoid
hypersplenism (various causes)

nothing on his meds that screams myleotoxicity. leupron easily could explain the true gynecomastia

what i would like next:
chemistries, lft's, cbc with DIFF, retic count, peripheral smear

i think the edema is lesser of 2 evils here. unlikely cardiac without sx (e.g, orthopnea, PND, cough, nocturia) and lack of S3 or rales on exam. you could be cover-ass and order a CXR, and if you're really lacking on clinical acumen like some folks in the ER, ask for a BNP

things to clarify on history:
family history?
other surgical history?
was he treated with casodex or other antiandrogens for his prostate ca besides leupron shots? (think pulm fibrosis)

how was his DVT treated in the past? was he heparinized? what was the clinical scenario in which the DVT developed? is he or does he have family with hypercoagulability?

give the pancytopenia, edema, i would strongly be worried about malignancy first. prostate cancer and lymphomas can cause lymphedema.
obviously there are other causes as well...will mull it over some more...
-s.

 

[JungleBoy]

First of all, tell your patient he's not supposed to violate Occum's razor. He can be arrested for that.
Second, this case is getting really interesting. You said it was pretty simple, but it's not looking that simple to me.
I really don't know where to go from here. Are you saying the pt has something I didn't even mentioned yet? You'll have to give me some hint... don't give away the dx, though. I'm kind of intrigued by the fact that the edema started right after the DVT..., but it's unlikely that it would be bilateral if it was due to chronic venous insufficiency. You'll have to help me out!

 

[Kalel]

FHx: Father has CAD, Mother's health is unknown. Both are alive and otherwise healthy. He is an only child.

Surgical Hx: Surgery for resection of the prostate ca. I'm not 100% certain, but I believe that post-op is when he developed his DVT. He had a very thick chart with a lot of messy handwriting that I didn't read completely. I do know that he was heparnized, then coumandinized and was followed for a brief period of time by a heme onc doctor for his DVT. I do not know what else he has used for his prostate ca. He gets his leuprolide shots q 3 months. I had to suggest the name leuprolide after he said that he was getting "leu-something" shots q 3 months, so he wasn't the best historian regarding his medications. It's possible he may have been taking something else.

Other labs: Sorry, they weren't done . I just saw this patient today, and I had my own suggestions on labs and tests that I wanted to order that I will discuss later but the attending didn't want to get the labs that I wanted. Also, the labs that I have listed here were only availabe because they were completed at a lab within the clinic building. Many of the labs that you are asking for would need to be sent out, so we wouldn't have the results today anyways .

"Pancytopenia": I guess that I will tell you my thoughts on it before we get too far down this path because my original history wasn't very "fair", but I wrote it that way because that's how I first elicited it and I thought that it brought out a great point. My thought was that it was related to his alcohol consumption. I actually interviewed this particular patient right after I interviewed his wife while his wife was still in the room. I asked the patient whether or not he drank alcohol or not, and he responded yes, he was a social drinker (a term that I had used to describe his wife's drinking of occasional alcohol when out with her friends). On further questioning though, I discovered that he actually drank at least several shots almost every day. I ran through the CAGE questions with him, and I even asked his wife if she thought that his alcohol drinking was a problem, but both of them said that they did not believe that his alcohol drinking was a problem despite his heavy drinking history. I didn't pursue this matter any further because I didn't think that I needed to, but I do believe that his EtOH consumption would account for his chronic thrombocytopenia and anemia. However, given his age, the attending gave him several heme stool cards and wanted him to see a GI doctor to get his screening colonoscopy (even though that would not account for his thrombocytopenia). Anyways, the MCV was normal, so it's not like he had a megaloblastic anemia, but my understanding is that chronic alcohol consumption is one of the causes of thrombocytopenia and normocytic anemia. I don't know the pathophysiology behind this. Anyways, this is an actual case that I saw today, and these are only my thoughts, so I'm certainly not ruling out some sort of malignancy or lymphoma/leukemia being the cause of his symptoms. He denied any B-type symptoms though (no night sweats, afebrile), and he did not mention any weight loss.

Anyways, I appreciate all the detailed thoughts you guys have been listing. I will write more about my thoughts on this case a little later. Again, this is an actual patient that I saw today, and since I saw him in a community clinic and not in an inpatient university setting, I wasn't able to order the million dollar work-up I know that most of us would like to see.

 

[JungleBoy]

Interesting thoughts, Sanfilippo,
Just a few points: if the pt has pulmonary hipertension due to sleep apnea/hypoxemia, causing right-sided failure, he would have no pulmonary findings on physical examination. But if as for CHF, you're absolutely right. Second, I thought your lymphedema hypothesis was good, but I it's usually a nonpitting, non dependent type edema. But who knows...
I totally agree with the rest. Malignancy should be a major concern in this case. Recurrent prostate CA would probably be the first that would have to be excluded, both PSA and acid phosphatase would be helpful, as well as pelvic/lumbar Xray. Anemia of cronic disease is a possibility, but that's a dx of exclusion. As for the thrombocytopenia, thiazides are a well-established cause.

 

[Kalel]

PSA: <1 (normal)
Chest x-ray and abdominal CT done within the last year looking for recurrence of prostate ca were read as negative.

 

[JungleBoy]

Nice, Kalel, let us know about this pt's follow up.
BTW, what do you think is causing the edema, afterall?

 

[Docxter]

5-30% of patients with lower extremity DVT go on to develop chronic venous insufficiency. Untreated ones and recurrent DVTs have a higher rate.

 

[Kalel]

Chronic venous insufficiency secondary to DVT's is a good thought. I actually had not considered this diagnosis. Had the edema been unilateral, I think that this would have been the most likely diagnosis, but I am more inclined to agree with the poster who posted about cor pulmonale and right-sided heart failure. He also was appropriately treated with anticoagulation following his DVT, thus decreasing his risk for venous insufficiency as the previous poster noted. This patient has several risk factors for cor pulmonale. He has asthma, and his DVT may have been caused a PE which would account for the sudden onset. Sleep apnea was previously thought to be associated with pulmonary hypertension as well, but according to emedicine.com; it is currently not thought to be an independent risk factor when it is not associated with other pulmonary conditions. In the ROS, the patient also mentioned that he has been having DOE after walking 2-3 blocks for the past 2-3 yrs as well. He denied any CP. DOE could have been consistent with pulmonary hypertension causing his cor pulmonale. The edema that I described on the dorsum of his feet (although not seen on exam) was consistent with a dependent type edema which could be consistent with cor pulmonale or chronic venous insufficiency, but I was hoping someone would bite on the pre-tibial edema. I believe that was actually pretibial myxedema. Given his slight exopthalamatous with pretibial myxedema despite his thyroid ablation therapy for his Graves disease, I thought that it would be useful in pointing out that pretibial myxedema and exophthalmatous is actually not caused by hyperthyroidism but rather by the underlying autoimmune pathology of Graves disease. Therefore, just because the thyroid has been ablated, that doesn't mean that his pretibial myxedema or exopothalmatous would have been resolved even with his hypothyroidism. Anyways, I would have liked to order an ECG, echo, start the patient on diuretics/lasix for symptomatic relief, get a BNP, but my attending only wanted to reccomend pressure stockings for the patient in addition to getting the labs that I have already mentioned. Anyways, these are only my thoughts on the case, and as I stated previously, this was a real patient that I saw yesterday so I don't know if my assessment and plan was better then any of yours. Thanks for participating in my case though, I will be sure to post future interesting cases as I encouter them so that we can keep up with the optho forum .

 

[tofurious]

I actually had a somewhat similar patient on my service and cardiac was the most likely DDx until abd CT to r/o mets found a giant liver met causing Budd Chiari Syndrome. His pancytopenia and likely alcoholic cirrhosis (plus his high likelihood of having non-alcoholic cirrhosis due to obesity) also predispose him to non-mass BCS, despite the normal LFTs.

 

[Docxter]

- Pretibial myxedema gives nonpitting edema. Of course, if you press hard enough, all cases of nonpitting edema will become "pitting".

- Some sort of increased right heart pressure (chronic PE +/- sleep apnea) is also a good thought. The fact that he has bilateral edema but only a history of unilateral DVT doesn't mean much. The DVT on the other side could easily have gone undiagnosed and now he presents with bilateral chronic venous insufficiency.

 

[Kalel]

Originally posted by Docxter
Pretibial myxedema gives nonpitting edema. Of course, if you press hard enough, all cases of nonpitting edema will become "pitting".

Hmmm. Well, I just looked this up on emedicine and now I'm thinking that my patient didn't have pretibial myxedema at all. It was definitely pitting, and I didn't see any of the bilateral infiltrative plaques over his tibial region either. Oh well, so much for one of the main teaching points of this case . I'm still a med student, so I certainly do appreciate being corrected whenever I am wrong. Normally, as a med student, I wouldn't try to run cases here, but the senior people who frequent this board don't seem interested in running them either, and cases are fun to discuss and learn stuff from. I had thought that this was the first case of pretibial myxedema I had seen, but I guess that I was wrong.

 

[Kalel]

Originally posted by tofurious
I actually had a somewhat similar patient on my service and cardiac was the most likely DDx until abd CT to r/o mets found a giant liver met causing Budd Chiari Syndrome. His pancytopenia and likely alcoholic cirrhosis (plus his high likelihood of having non-alcoholic cirrhosis due to obesity) also predispose him to non-mass BCS, despite the normal LFTs.

Budd Chiari is a thought. However, this case presented with chronic (2-3 yr) symptoms. The 2 yr mortality of budd chiari treated medically is 80-85%. Untreated, most patients die in 3 months to 3 yrs. If his liver enzymes were normal and he had budd chiari, I think that would mean that he had ESLD/cirrhosis and would therefore be a lot sicker then he was (sx of hepatic encepholopathy, variceal hemmorhages, hepatorenal syndrome, death).. That being said, he was obese so it wasn't really possible to tell if there was any ascities (studies have shown physical exam to be very poor in predicting ascities in obese patients), and I do agree that you would have to consider budd chiari had this patient presented more acutely.

 

[tofurious]

> this case presented with chronic (2-3 yr) symptoms

> Untreated, most patients die in 3 months to 3 yrs

Mutually exclusive?

Good job looking up the 2 year mortality though. Keep up the good work and you'll be a great internist.

The question I had was: is pretibial myxedema position dependent? I didn't think it was...

 

[Kalel]

Originally posted by tofurious

The question I had was: is pretibial myxedema position dependent? I didn't think it was...

I don't think that pretibial myxedema is position dependent. That's one of the reasons that I first thought that my patient had pretibial myxedema, because the edema was still present when the rest of his LE edema was not present; but I guess that can be a charectoristic of regular LE pretibial edema too. Pretibial myxedema is caused by the deposition of hyaluronic acid in the dermis and subcutis, and therefore, it's probably not susceptible to the same hydrostatic forces that other forms of edema are. Anyways, thanks for the internist compliment.

 

[JungleBoy]

I have a couple of comments on the previous posts: First, I thought pulmonary hypertension and cor pulmonale are well-established complications of sleep apnea. I've recently done a rotation in pulm/crit care and we had several patients being treated for that. I'd be interested to know the source you got that information from, though.
About the pretibial mixedema, take a look at the mini-atlas inside Harrisson's, they have a picture of a pt with that. It really has nothing to do with edema per se, just the name. Mixedema is accumulation of mucopolysaccharides in subcutaneous tissues, forming plaques and skin infiltration. It resembles necrobiosis lipoidica diabeticorum, at least for me. And mixedema is not dependent.
Regarding BCS, I think it's an interesting possibility. The pt could have hypercoagulability due to his malignancy (assuming he has not been cured). What speaks against it is that the pt has had the edema for 3 years, and besides he shows no evidence of recurrent prostatic CA. I think this makes this dx unlikely.

 

[Kalel]

Here is a link to one abstract that I was able to find on the association between sleep apnea and pulmonary hypertension. I think that what the article (which is availabe through a link on that abstract page) is saying is that things like COPD and chronic hypoxia are more associated with pulmonary hypertension then OSA is; and that sleep apnea is not an independent risk factor for PH, patients must have other comorbidities in order to develop PH. The author points out that those patients who did not have COPD or those other risk factors, but still had OSA and PH were obese and had restrictive ventilatory patterns that could account for their PH too. Regarding the pretibial myxedema, thanks for pointing me to those pictures. I saw some additional pictures on the internet as well. I guess that I will know what to look for when considering pretibial myxedema now. It really does look different then your run of the mill pitting edema.

http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&dopt=Abstract&list_uids=96187657

 

[JungleBoy]

Thanks for the article, Kalel.

 

[sanfilippo]

I agree with PHTN and OSA...they are well correlated to eventual cardiomyopathy.

I did not list pretibial myxedema as a cause of edema because i thought that was truly a dermopathy.