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24 year old man with a chief complain of weakness.

Voxel

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    This will be the first case discussion (hopefully not the last :) ) that I will attempt to moderate. Womansurg's post in the lounge has inspired me. :) Please be patient with my responses. Everyone is welcome to participate and other case discussions are welcome by others. So here goes...

    On further questioning he also states that he has a 20 lb weight loss, a change in the color of his skin, lightheadedness and dizziness.

    What would you do next?
     

    Future GI Guy

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      We need more info, especially if this guy is stable...then there's time to ask more questions!

      1. How long has he had the symptoms, specifically weight loss? Over months? Over weeks?

      2. Is he TRYING to lose weight?

      3. Any other associated symptoms, like NIGHT SWEATS, or FEVERS, recently? (first bimodal peak of Hodgkin's occurs in this age group)

      4. What's the distribution of his weakness, is it generalized, is it located proximally or distal muscle groups? (I'm thinking Dermatomyositis, or something autoimmune) Joint pains?

      5. Does the weakness occur first thing in the morning or is it later in the day?

      These are a few questions to get us started.

      When we move to the physical, I'd live to hear more about the rash.
       
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      Future GI Guy

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        Blueintheface,

        That's an excellent thought (that is, the diagnosis of Addison's)

        However, you wouldn't use a "random" plasma cortisol to diagnose it.

        What you want is an ACTH Stimulation Test.

        With before and after plasma cortisol levels.
         

        Imhotep

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          of course, if the patient isnt crashing in front of your eyes, do h&p, stressing ROS....then basic labs: cbc, cmp, u/a and go from there, I'd add serum Fe... hemochromatosis?? "bronze diabetes" .
           

          edfig99

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            24 yo fatigue, 20 lb wt loss, skin discoloration, lightheadedness and dizziness.

            i don't believe much in ocham's razor, but that's cuz I see a lot of older and geri patients and it doesn't apply. this is a young guy so hopefully the razor can apply.

            some good replies in the thread so far.
            i dunno...i meet someone like this i'd start probably by focusing on the vague symptoms to try to get to specific etiology...

            onset? acuity?
            wt loss over what time period?
            peeing too much? peeing too little?
            fatigue - under what circumstances?
            lightheadeness and dizziness -- what type of dizziness? room spinning or "head fall to da ground?
            cough? nightsweats? chills? (I have had tons of patients with tb that presented with these vague complaints)
            shortness of breath? palpitations?
            travel history?
            sexual history?

            my phys ex would probably:
            focus on vital signs
            skin color? blue? red? yellow? pale?
            breathing effort
            thyroid exam
            lung exam
            good heart exam (congenital heart disease can present in early adulthood with these vague complaints)
            genital exam - young guys get testicular cancer.

            with info so far, differential too vague....
            congenital heart disease
            TB (for me, this is ALWAYS in the differential)
            liver disease
            endocrine (adrenal, dm (with hemochromatosis, otherwise don't expect skin color change)
            neoplasm (lymphoma, testicular, leukemia, adrenal tumor)

            bring on some mo' info....
             

            Voxel

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              Before you can get any more history or physically examine him in your office, he attempts to get up saying he needs to go to the bathroom. As he gets up he says, "I feel lightheaded again, and procedes to "pass out" in front of you. Being an astute doc you catch him before any trauma occurs. You do your ABCs, and you find that his airway and breathing are stable, but his bp is 80s/40s and his pulse is about 96, afebrile 37.0C. A quick heart and lung exam are unremarkable. You are in your office, what do you do now?
               

              edinOH

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                1. Call 911
                2. Grab smelling salts for your nurse. (she works in an office to avoid dealing with **** like this)
                3. Try to locate the crash cart that you think was last seen in the break room.
                4. Once CC located, open second drawer and grab an IV cath while trying to explain to your nurse how to prep an IV line.
                5. Start NS bolus and anxiously await EMS so they can take your pt to the ED.
                6. Ask your staff if they want sandwiches or pizza for lunch.
                 

                Voxel

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                  You call 911. They'll be here in 5 minutes.

                  You forget the about smelling salts, remember the ABCs and procede to find the crash cart. You tear through the cart to find an iv kit (a large bore iv you think to yourself) and a flush, a liter bag on NS. You realize you haven't put in an IV in 7 years since finishing residency and even in residency the nurses did most of it anyway. Your astute nurse happens to be a retired ER nurse, who got burnt out by the pace and wanted a less stressful job. As you fumble with the IV kit your nurse says let me help you. She takes the IV kit exams, his arms and puts an 16G into his left arm, flushes it and starts hanging the Normal Saline all in a matter of 45 seconds.. You tell her to adjust the flow so that it is wide-open. As the first bits of fluid drift in the EMS personel arrive. They procedure to get his vitals, which have not changed. The procede to transport him away.

                  You buy your staff a nice lunch, thanking your staff for their teamwork, with a special thank you to your nurse. You make an note to yourself to give your nurse an extra holiday bonus this year.

                  While in the ambulence they stick in a 2nd 16G iv in his other arm. As he arrives at the ER his vitals are still the same, his BP is still 80s/40s.

                  You are now the emergency room physician. You get a heads up from your local FP doc about this 24 y.o. m, the story above in the exact sequence. He's gonna be here any minute. The man arrives fully clothed and is now more more alert but still feels "dizzy" and light headed." The EMS worker mutters to you I hope he's not bleeding internally and walks away wondering what is for lunch. Vitals are unchanged and he has gotten about 1.5 L NS through his two IVs. His airway and breathing are still stable. You measure his bp laying flat and standing up and notice him to have orthostatic bp. What do you do now?
                   

                  Future GI Guy

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                    Voxel,

                    You've told us nothing about the physical exam. I realize this guy is "crashing" but can't we get some cardiac findings? What's his belly feel like? I'd cut his clothes and look at the rash. I know this thing has been going on for some time, but if he had a septic rash (Meningicoccemia), I think I'd crap my pants.

                    Given the very limited scope of history, I'd probably give him a good ole dose of Hydrocortisone. He may have adrenal insufficiency (which I'd be asking him about exogenous steroids if he is alert now).

                    With orthostatic changes and no response to a good amount of NS, I'm thinking Endocrine all the way, and I'm not sure I'd wait for electrolytes to give me the diagnosis, though I think a full compliment of labs will be drawn upon his arrival to the ER.
                     

                    edfig99

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                      there's too little info here to make good decisions....

                      i don't know if i'd jump on giving him steroids, though adr. insuff. is on the differential.

                      if he's orthostatic, i'd just keep him flat, and keep the fluids wide open -- for all we know he can be several liters dry (we don't have history on vomiting or voiding). if his mentation is worsening, however, then he needs some type of pressor support. this guy needs at the least, a physical exam, some simple labs, a urine dip, cultures and an EKG.

                      so he's in the ER and it's ADMIT TO MEDICINE ;)

                      something to wonder about, however, if he is that dry that he's orthostatic, why isn't his pulse faster?
                       
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                      Voxel

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                        Before you can do anything the ER nurses are on him like vampires, drawing all sorts of labs, lavender, speckled red, purple, green top, and extra plain red tops just in case, a set of blood cultures, and ask him to pee mid-stream in a cup, and attach 12 leads for an ekg.

                        The patient seems slightly more alert now that he is lying flat/supine, and in this position his bp improves slightly to 88/50. IV NS is still going in wide-open.

                        You procede to make him undress to look over his body as you recall the FP saying something about changes in his skin. You also begin to take a slightly more detailed history. Since in your mind (collective) there is some doubt about giving hydrocortisone, you hold off thinking you can do a quick history and physical before giving him any meds while continuing to monitor his vitals. As you procede to quickly remove the man's clothing you notice a generalized increases in pigmentation over the extensor surfaces of the knees, the face, the knuckles of both hands, in the skin creases of the palmar surfaces of his hands and in an old well healed scar on the patient's right calf. The skin does not look like generalized bronze skin, but instead has discrete areas of darkening (natural pigment, not ecchymosis or petichae, or rash like).

                        Further questioning reveals: He is in the end stages of getting over a uri and still has some nasal congestion. He started to feel really lousy about 4 days ago with the onset of URI type symptoms fever, running nose, etc (no (productive) cough).

                        The weight loss occurred over the past 2-3 weeks and he was not intentionally trying to loose weight.

                        No night sweats, no chilles, no lumps or bumps, although he did have a low grade fever about 4 days ago at the beginning of his uri. The generalized weakness/fatigue/ lightheadedness/dizzinesss (head falling to the ground) has gotten worse over the past two weeks especially since the onset of the URI.
                        No recent travel outside of the USA, he lives and works as a computer technition in philadelphia. No recent sick contacts, except his office workers who came down with same URI symptoms 2 days prior to him. He has not been sexually active for the past 6 months and only has sex with women with condoms (always).

                        His po intake has been average and denies nausea or vomiting or diarrhea. Although he says he has been feeling more depressed lately, and that this is unusual for him as he is usually a happy go lucky guy.

                        No change in his bowel or bladder habits.

                        The patient's vitals continue to be unchanged from lying supine. You start to do a quick physical noting to yourself that you can always ask more questions at a later time.

                        Gen: A/0 x3 NAD
                        HEENT: EOMI, PERRLA, NC/AT Multilpe increased areas of mucous membraine
                        pigmentation with some areas of much darker pigmentation in the mouth. Neck supple, no JVD, no palpable lympadenopathy. No neck stiffness.
                        CV: RRR (although borderline tachy) s1 s2 no m/r/g.
                        Lungs: Clear B/L
                        Abd: + NA Bowel sounds, soft, nt nd, no hepatosplenomegaly, no gaurding, no rebound.
                        Ext: No clubbing cynanosis or edema no chord, no homann's.
                        Neuro: Non-focal. CN 2-12 grossly intact, motor strength5/5 x 4, sensation grossly intact/symmetric, 2+ x4 DTR. unable to asses gait.
                        Derm: Multiple increased areas of pigmentation along the face, the extensor surfaces of the knees, the creases in the palmar surface of the hand and in an old scar in R calf. No petichae, no echymosis or other macular/papular rashes.

                        (Next time I will just give you the pertinent positives/negs).

                        You start to notice that nurses have connected the man to the EKG machine. You let them do their business. You look at it. NSR 98 BPM, normal axis, no acute ST changes, slightly high T waves.

                        The nurses also do a random finger stick: 60.

                        Labs are still cooking. Portable CXR man is here, everyone clears out as he yells XRAY and ducks behind a table holding the xray button in his hand.

                        What do you do now?
                         

                        iamubiquitous

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                          change fluids to sugar water + steroids------>sed rate cxr+ppd-------->up stairs

                          run a cortisol on some of that blood the vamps got

                          Addison was still in med school when he published a book on diseases of adrenals 1850s i think.

                          How do you test for autoimmune adrenalitis--anyone know
                          Is there a marker?


                          nice case voxel - thanks
                           

                          Voxel

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                            He is given stress doses of hydrocortisone and florinef. His BP perks up to 110/70 and he feels much better with a partial resolution of his symptoms over the next few hours. The ER attending quickly looks at the guys lab, and admits him and then attending to the next patient with crushing chest pain in room 4.

                            Our patient's chemistry is significant for Na 128, K 5.5, otherwise normal. CBC is unremarkable. UA is normal. Blood cultures, UCX, ACTH, Cortisol is pending. His repeat fingerstick is now 250. CXR-no acute cardiopulmonary disease, no infiltrates, no effusions, bony chest is unremarkable, heart magnification 2ndary to AP technique.

                            He is sent up to a regular floor on IV D5NS @ 100 cc/hr, Hyrdocortisone and Florinef around the clock. PPD is placed. HIV test is consented and sent. You are now his FP and have finished your office work and head out to the hospital to check up on your patient and do a thorough HP.

                            What would you like to know/ask/do?
                             

                            iamubiquitous

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                              ACTH is elevated so I know that his HT-Pit Axis is pleading with some unresponsive if not dead adrenals.

                              So its the adrenals, its bilateral, its not / wasnt fulminant,
                              and it is global with respect to the adrenals.

                              This didnt happen overnight

                              No significant med hx

                              These issues would help focus me.

                              Toxin exposure? Recreational/Occu
                              Autoimmune marker?
                              Fam Hx

                              I would rerequest that sed rate (and an ANA?)
                               

                              abu barney

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                                What comes to mind is what took out his adrenals:

                                "The Usual Suspects"

                                Infection: TB, HIV, CMV, not meningococcemia.

                                Maligancy: bilat adrenal metastasis.

                                Autoimmune: URI symptoms preceding presentation by few days supports this. Also, ask for personal or family history of vitiligo, anemias, joint pains & swellings, graves, hashimotos.

                                Infarction: i imagine to be very rare (besides meningococcemia), history of DVTs, arterial infaction

                                Congenital: I wonder if CAH salt-losing type can present this late into life. I would take a peek at the genitals just in case...

                                Great case Voxel, I hope there are more to come.
                                 
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                                ERMudPhud

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                                  So it looks like we are heading down the Addison's route although there are a few atypical features.

                                  1. Presence of pigmentation changes implies chronic disease but his symptoms appear to be of a shorter duration. Perhaps he has had worsening adrenal insufficiency for some time and his recent illness was just the stress he need to tip him over into symptomatic disease.

                                  2. He has no real GI complaints. Nausea, vomiting and abdominal pain are usually present, more commonly with acute Addisonian crisis then with chronic disease

                                  We now have a good H&P. I would start by checking a D-stick since these patients are often hypoglycemic as well. I don't think I would jump to pressors. His BP isn't that bad and Addison's patient are fairly refractory to sympathomimetics. Fluid and steroids should do the trick. People have mentioned hydrocortisone/fludrocortisone but there is some debate on this. Stress dose hydrocortisone has sufficient mineralocorticoid activity on its own. Acute use of decadron won't replace his missing mineralocorticoids but the hypotension in Addisons is mostly due to a requirement for glucocorticoids for sympathetic responses and initial treatment with decadron stills allows you to do an ACTH stim test which hydrocortisone will not. Use of spot ACTH or cortisol levels might help rule out Addison's but are not the gold standard. Once the patient appears to have responded to steroids and fluids I would take a look at his labs to look for other problems like hyperkalemia and admit him to medicine for the extensive workup he is going to require. The differential is huge and includes autoimmune, metastatic, granulomatous, infectious and endocrine causes. In addition to the lab work he will need imaging of his adrenals.

                                  Cool idea. I'd be glad to moderate one of these in the future.
                                   

                                  ERMudPhud

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                                    Due to my being distracted at work my first post entered the thread a bit late and out of order.

                                    At this point I would want to know what the imaging of his adrenals shows

                                    I am also eagerly awaiting the results of the cortisol and ACTH levels, or the ACTH stim test(see above).

                                    Once we have confirmed adrenal failure and that he doesn't have bleeding or mets in his adrenals the real lab testing can begin in earnest since the differential at this point is literally pages long
                                     

                                    iamubiquitous

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                                      ERMUDD..,

                                      that was a great post!!

                                      are you clairvoyant or something?

                                      you answered questions i asked and some I just thought to myself-- eg the mineralocorticoid replacement w/ fludro thing.

                                      do you know how one goes about evaluating autoimmune adrenalitis?

                                      thanks for the answers.

                                      c
                                       

                                      iamubiquitous

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                                        ERMUD..,

                                        that was a great post!!

                                        are you clairvoyant or something?

                                        you answered questions i asked and some I just thought to myself-- eg the mineralocorticoid replacement w/ fludro thing.

                                        do you know how one goes about evaluating autoimmune adrenalitis?

                                        thanks for the answers.

                                        c
                                         

                                        Voxel

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                                          The patient is switched to decadron with a slight drop in his bp 100s/60s but overall he still feels well. He remain afebrile on decadron. The pt is still getting D5NS @ 100cc/hr with good po intake. We attempt to perform a ACTH stim test. His testicular exam is unremarkable. His finger sticks continue to be in the high 200s. Cortisol from the morning comes back very low. ACTH and HIV tests are still pending and will be back probably tomorrow.

                                          He denies any family history of autoimmune disease, any high risk exposure to TB. You ask him about things when he was younger. You ask him to recall if he has any unusal past medical problems. He states that when he was younger he had slower sexual development and that his previous doctor thought he may have had a touch of an under active thyroid. He also states that since a couple of years ago he becomes thirsty once in awhile and urinates alot on occasion, but that comes and goes, and that it hasn't happened recently.

                                          On further questioning you realize that he states that he is not prescribed any medicines and has no known drug allergies, but he sheepishly admits that he sometimes takes his mother's underactive thyroid medication which makes him feel better.

                                          CT of abdomen and Pelvis is ordered with oral and iv contrast and is performed in the late evening, unfortunately the reading will not be back until the next morning since the radiologist is sleeping and you'd hate to wake him/her up over this. Also treking back to the hospital from your warm bed does not sound appealing either.

                                          What do you do next? What's on your mind at this point?
                                           

                                          AJM

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                                            This is really smelling like Schmidt's syndrome, aka autoimmune polyglandular syndrome. He has adrenal insufficiency, possibly hypothyroidism, hypogonadism, and he also may have DM. He also has a positive family history of endocrine disorders (mom with thyroid disease).

                                            Even though the ACTH level is pending, I doubt that this is hypopituitarism, as he has the classic skin changes found with high ACTH. (hypopituitarism would cause low ACTH, and no skin changes). His DM may be mild - even though his sugars are above 200, the fingersticks have been while he is on D5 and after stress dose steroids, but he does give some history of polydipsia and polyuria. His DM could also be masked by adrenal insufficiency as well as by hypothyroidism, if he does have that.

                                            I would ask if any of his family members have any endocrine disorders, alopecia, vitiligo, celiac disease, etc. I would send off a thyroid function panel, hemoglobin A1C, the anti-insulin and islet cell antibodies, testosterone, LH, and FSH to start off with. I would also check his CBC with smear, and possibly a B12 level, since he would be at risk for pernicious anemia.

                                            It sounds like his symptoms have mostly resolved, but he may require some IV or PO T4 to help out a bit more. I would start frequent blood glucose fingersticks, and have a very low threshold to start him on some insulin (250 is pretty much at my threshold).
                                             

                                            Voxel

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                                              CT of the Abdomen and Pelvis with iv and oral contrast with thin cuts through the adrenals (as you conveyed to the radiologist) demonstate small bilateral adrenal glands, no calcification, no masses, no hemorrhage. The liver, gallbadder, pancreas, stomach, kidneys, ureters, bladder are unremarkable. The bowel is unremarkable. The bony structures are unremarkable.

                                              ACTH comes back abnormally elevated. ESR is elevated (done by an nursing at the bed side and documented in the chart).

                                              From a saved pre-steriod blood samples, the TSH level in borderline high, HBA1C 6.0%, the anti-insulin and islet cell antibodies pending. Testosterone, LH, and FSH Pending. CBC with smear shows borderline anemia, with normochromic normocytic rbcs, A B12 level is within normal limits.

                                              What is your diagnosis and what is the most likely underlying pathophysiology and what treatment will this patient require?
                                               

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                                                As AJM suggested we are now heading into the world of truly exotic polyendocrinopathies. His pituitary works so everything else is defective. At this point this is well beyond my humble ER perspective and in to the range of the endocrinologist.

                                                One question though, Why the ESR? An academic internist that I really respect used to say every patient needs an ESR or a good physician but not both. I have generally found this to be true. For this case and in your real life practice every time you order an ESR ask yourself what part of the workup you will cancel with a normal ESR and what part you will cancel with an elevated ESR. Then wait and see if you actually follow your prediction or if the ESR ends up making no difference in the actual work up you do. Except in cases where you are following the ESR as a marker of disease progression/improvement I think you will find that it rarely if ever changes the workup.

                                                In this case even if his ESR had been normal we would probably have still pursued the autoimmune angle since it is so high on the differential. Then there is the added bonus of what you do with all the slightly elevated ESR's that you find.
                                                 

                                                iamubiquitous

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                                                  We got an ESR sir b/c in my infinite ignorance I ordered one.
                                                  Then when the Voxel tried to indicate that there was no point
                                                  by quietly omitting it from his replies -- I went ahead and rerequested it.

                                                  Thanks for the info;)
                                                   
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