SocialMedicine Posted March 10, 2011 Share Posted March 10, 2011 This would be one of my top cases of 2011 .... My apologies if this is the wrong section for this ..... The case is still in progress but am confident tomorrow will confirm my suspect. 40 something with HIV stable - CD4 nadir 200's without Opportunistic Infection Hx. (current CD4 520, HIV viral load udnetectable on ART), chronic hip osteoarthritis, major depression, presents with "sweats", fever subjective, mild nauseu, and constipation for 2-3 days starting the day after a triamcinolone epidural for arthritis pain mgmt. he says "something feels wrong" and identified no other symptoms in a thorough ROS. Whats next? Link to comment Share on other sites More sharing options...
Just Steve Posted March 10, 2011 Share Posted March 10, 2011 "what next"...a million things come to mind. I know nothing of HIV medicine...would a white count be beneficial in this patient to help identify a new infection or are those numbers always skewed due to the HIV? You mention no sx on ROS...so bowel sounds present? Hem negative guiac? Any stool in the rectal vault? Urinary pattern normal? Appetite? Normal physical activity? No obvious swelling/induration at injection site? No organmegly? Link to comment Share on other sites More sharing options...
SocialMedicine Posted March 10, 2011 Author Share Posted March 10, 2011 Exam was normal. HEENT, Resp, Cardiac, Abd exam WNL. BS Normal, nontender abd exam without mass. No vertebral tenderness. No skin findings at sit eof injection or anywhere else. Lab work was ordered because he was due for f/u given a medication change few months prior. CBC was WNL WBC 5.7 with normal shift. His CD4 count declined from 500's to 200's which is considered a significant change. Chem WNL, viral load undetectable. It is unlikely HIV Itself would cause a rapid decline in T Cell count over a short period while the viral load remains undetectable so it seems as though something else is in play. The PA treating this patient felt the lab work and Sx suggested a "viral infection" - the patient agreed as the Sx were minimal. PMHX: HIV, Depression, OA Meds: Darunavir, Norvir, Truvada, Lexapro. All: PCN PShx: Hip Replacement 1 week after this encounter he returns to clinic with the following account .... "Night sweats are worse. I am nauseus, and have had 1BM in the last 5 days and there is a sharp pain in my epigastrum" The pain is 6/10 and burns. He says "I feel SOB" but denies chest pain, wheeze, chest congestion, or dyspnea. He says it feels like a shortness of breath when I am anxious. Also, hehas not been able to sleep the last few days and wakes up at 4AM after falling asleep at 11pm. He borrows a friends Ambien and feels it has no effect. Says he craves carbs but isnt hungry. EXAM on 2nd visit: Vitals: 150/86 (prev 130s systolic), temp 98.6, RR 18, HR 67, weight 180 HEENT WNL Cardiac exam WNL, including NSR EKG Abd Exam reveals +epigastric tenderness, no megaly, BS normoactive. GUIAC negative and DRE normal. No stool in rectal vault. Normal motor/sensory exam, A+OX3, nl gait. Nl sphincter tons. No rash. Also, No GU symptoms. Urinating "fine". What labs should we order? What is the differential at this point? Sorry if I am not very good at moving through a case hah. Link to comment Share on other sites More sharing options...
rcdavis Posted March 10, 2011 Share Posted March 10, 2011 So... Negative w/undo far... Need to compile at least a starting ddx to explain rather sudden onset of sx which seem to include night sweats, constipation and shortness of breath w/o cough nor wz, all of which occurred shortly after epidural (epidural?..) for "arthritis" presumably d/t the total hip, and an inexplicable decrease in his Cd4 count with an indictable viral load. So.. Atypical infection.. Mycobacterium avium intracellular, mycobacterium Tb, kansaii, yersinia, formerly quiescent fungal opportunistic infection activated by the steroid. It would seem that obstructive rectal lesion is not probable d/t no tenderness on rectal, nor stricture nor prostate hypertrophy Epidural abscess? Unlikely without pain, incr count.. Malignancy? Tumor in the gi track... Lymphoma? HIV-1?? Hyper-Parathyroid. Mycetomatous pulmonary Vascular: compensated rhf Pulmonary: hypoxemia?Do any of these medications cause methemoglobinemia....? Neuro.. Doubt HIV neuropathy involving sacral nerve roots, or mesenteric ganlionopathy... Endo.. Except parathyroid.. Maybe occult hypothyroid At this point I would be looking for primarily a malignant process..Though opportunistic process is also high on the list. I think I would get a chest X-ray right now, and at least two view and.... Sed rate, calcium, tsh. Crp. ABG, meth and carboxyhemoglobin levels. If there are Any afl on upright in the small bowel, I would not hesitate to get a triple contrast and and pelvic CT. Davis Link to comment Share on other sites More sharing options...
SocialMedicine Posted March 10, 2011 Author Share Posted March 10, 2011 in f/.u visit CBC reveals a WBC of 11.7 with neutrophil shift 78%, H. Pylori + IGG and IGM Ab, CD4 remains in the 200's, Chem WNL, Amylase/Lipase WNL, LDH and TSH WNL. CT ABD/PELVIS reveals impressive constipation without any other abn findings, CXR clear. Treatment ordered Prev Pac and Constipation relief with milk of magnesia and increased fluids/stoof softener. Also recommend f/u with neurologist to determine what potential neurologic issue could result from epidural placement that could explain this. When we discussed TR over the phone he reports no improvement in Sx says he is waking up very early and cannot sleep, still sweating but has no fever, muscle pains, and feeling very week. The focus of Sx appears to be Abdominal with Nauseu and the epigastric pain. What else should I be doing at this moment? My though process is similar to the above with the exception of the ID concerns. I was not convinced H. Pylori was the culprit but perhaps contributing alongside some other process. Link to comment Share on other sites More sharing options...
rcdavis Posted March 10, 2011 Share Posted March 10, 2011 Obstipation can make you feel...umm sh*ty... But usually does not cause Sleep pattern disturbance. Can cause elevation of WBC and a mild neutrophilia as increased colonic pressures probably do cause low grade bacteremia. So.. CT and/pelvis essentially rules out obstructive process, or anything causing mesenteric or Omental lymphadenopathy. Still dont know why the increased transient time though.. But if I read you right, was reversed with mom and softener.. So constipation is put to be for now unless becomes recurrent. A lot of endocrinopathies are ruled out with the normal chemistries nd tsp. Doubtful adrenocortical insufficiency even subclinical being caused by aristocort epidurally.. Nowhere near enough systemic absorption... Though is nothing else works out am cortisols might be worthwhile.. Cxr makes ptb unlikely ( though still could have renal tb... But normal urine w/o sterile pyuria makes that also unlikely. Also, no evidence pulmonary hypertension or infiltrate is encouraging. Other chemistries help r/o sarcoid or hiv-1. Is doubtful that epidural is causing mechanical problem...the absence of localized pain or neurve root neuropathy makes abscess, compressors lesion, arachnoiditis or infectious myelitis unlikely. Unless near thinks there was an inadvertent epidural veinous injection of the triamcinolone.. ( Made unlikely without resultant significant leukocytosis in 16-20k range), I think he will beg off as a probably cause. Sooo. Drugs? Has he started any new drugs which could be giving him a subclinical allergic reaction. How about a seratonin syndrome with either the Prozac along, or Prozac plus antivirals? What is his CPk. I agree with you that the h.pylori is a red herring. But treatment of the prEsumed gastritis is reasonable. I would at his point Ck am cortisols Discuss possibly stopping the Prozac in consideration of serotonin syndrom , Check drug drug interactions Also,I would ck immuno and protein electrophoresis patterns to ck allergic rsn, b cell lymphocytes, etc Male menopause? ( bad joke) From ID point of view, what can lower the cd4 w/o commensurate viral load other than a progression of HIV ? I am thinking about this. Still am concerned about lymphoma or occult malignancy, however Link to comment Share on other sites More sharing options...
Moderator ventana Posted March 10, 2011 Moderator Share Posted March 10, 2011 CT abd pelvis with contrast to look closer - just my own personal practice - if someone gets an epidural and then gets s/s of anything in that region of the body I get a spine CT to r/o bleed.... at site of injection constipation - splenic nerve irritation - but you would think lots of abd pain. not sure timing around epidural is all that critical but r/o bleed with CT then think about effects of steroids on him.... cushinoid v addison??? (crazy thoughts) also that THR needs a looking at to ensure no seeding from the epidural or from IVDA how about a bone scan? r/o osteo? Link to comment Share on other sites More sharing options...
rcdavis Posted March 10, 2011 Share Posted March 10, 2011 CT abd pelvis with contrast to look closer - just my own personal practice - if someone gets an epidural and then gets s/s of anything in that region of the body I get a spine CT to r/o bleed.... at site of injection constipation - splenic nerve irritation - but you would think lots of abd pain. not sure timing around epidural is all that critical but r/o bleed with CT then think about effects of steroids on him.... cushinoid v addison??? (crazy thoughts) also that THR needs a looking at to ensure no seeding from the epidural or from IVDA how about a bone scan? r/o osteo? Van.. Wouldn't an MRI e better in this case? W/ contrast, it would show arachnoiditis, abscess, or cord impingement.. However, in absence of local pain, sn sx inflammation, or neuropathy, I would discount epidural abscess, subdural bleed, or myeliitis.. And, mr would avoid the exposure to ionizing radiation ( I know your passionate feelings about this).. Plus, a review of the and/pelvic CT should show SOME posterior swelling, even though the cuts are probably 5-10 mm vs 2mm. Link to comment Share on other sites More sharing options...
Moderator ventana Posted March 10, 2011 Moderator Share Posted March 10, 2011 MR would be better, but we all seem to just order CT's to r/o - also - not sure long term rad exposure is of great concern on this patient - lots of comorbitities that are likely going to shorten lifespan under what the CT rad exposure would provide. As well the risk of missing Dx is large in this patient after an epidural. but now I see that he has already gotten an abd pel CT - oops - no huge lymph nodes seen, no masses, no epidural or subdural seen. do we know cholesterol panel? hypertrig with some of the antivirals - maybe pancreatitis or AMI (mild angina? sweats, cp.....), place a ppd or do that fancy new blood test for it. QuantiFERON-TB Gold Honestly I had to go look up some of RC's thougths - holly crud he knows some way out there dx and that is great ahh this is where I refer..... running out of thoughts...... Link to comment Share on other sites More sharing options...
SocialMedicine Posted March 10, 2011 Author Share Posted March 10, 2011 Neurologist said maybe an effect of the steroid or nerve irritation and either way Sx should resolve in few weeks gradually. He felt that Sx were enhanced by an H Pylori infection. He did not have many ideas and felt he should be f/u with me or a GI MD next. RESPONSE TO QUESTIONS?... 1) He has OA. This did not seem like a arthritic flare. No joing swelling or tenderness. Just diffuse myalgias and fatigue. 2) He has been stable on Lexapro for awhile. Only change in medication was Darunavir/Norvir from another HIV medicine which is Ph dependent, and this was a FEW months ago. He was switched because an ENT was concerned he had a silent acid reflux and should do a trial of PPI for a sinusitis. This is unrelated. The only other new medication would be the triamcinolone epidural of which the neurologist reports no complications. 3) Amylase/Lipase WNL on second visit. 4) Blood Sugar non fasting a 160 and total chol is a 220. Both were WNL fasting few months prior. Trig are at a 180. 5) I did not run a CK, electrophoresis, now did I screen for TB. All fine ideas .... live and learn I guess. 5) NO IVDA, no rec drug use, minimal alcohol, no recent trauma or major life events. Says he felt fine before all this and is convinced the epidural had something to do with it. His Sx all started about 2 weeks ago at this point ... and then a I get a phone call from him stating his Abd pain is a 10/10 and he is sweating profusely and he is very anxious. He also says at this point he has not had a BM in another few days. I was concerned about SBO, acute abdominal infection or perforation .... He was advised to go to the ER which repeated CT ABD PELVIS, ordered CXR, CBC/CHEM and all were WNL. They advised him Sx were due to acute constipation and prescribed an enema. He felt relief of Sx with an enema and when we spoke overthe phone he scheduled a f/u in 5 days to check in on Sx. His exam on that visit revealed what was going on .... i think some of you guys touched on it already :p. Any other ideas? What else should I of been doing during this time? Link to comment Share on other sites More sharing options...
bradtPA Posted March 10, 2011 Share Posted March 10, 2011 Any thoughts about running an SPEP and UPEP? Any splenomegaly? Link to comment Share on other sites More sharing options...
SocialMedicine Posted March 10, 2011 Author Share Posted March 10, 2011 At this point I have ...... Abd Pain, Constipation, H.Pylori AB IGG IGM +, Dec T Cell CD4 without any other CBC changes, increase in systolic BP but maybe thats from anxiety surrounding the situation, increased anxiousness and insomnia (waking up during the night), sweating without documented fever, also an ER visit for acute pain in the abd and a useless neurologist with an even more useless opinion. Link to comment Share on other sites More sharing options...
deborah212 Posted March 11, 2011 Share Posted March 11, 2011 It almost sounds like pheochromocytoma... I would have expected to see something on CT but not 100% sensitive. Link to comment Share on other sites More sharing options...
Moderator ventana Posted March 11, 2011 Moderator Share Posted March 11, 2011 thinking addison constipation - interaction check with fentanyl (if he had sedation for injection) and darunavir says to decrease dose of fentanyl due to hepatic metabolism inhibited - constipation is an opiate SE - did he just get toxic on fentanyl and is now having some withdrawl ? sweating makes sense but typcially diarrhea HIV and stress is #1 cause in the USA - what about porphyria and abd pain and constipation and HIV?? my head hurts...... but in rereading everything - what about a simple slow cooking appy? immuno supression with steroids, then a slow cook appy - consitpation, abd pain....... relieved somewhat with an bowel prep..... you state the exam gave the answer - was the finding and visual finding or a palpable finding?? ie way to tan, or RLQ tenderness? Link to comment Share on other sites More sharing options...
SocialMedicine Posted March 11, 2011 Author Share Posted March 11, 2011 Does pheo produce pain symptoms?? He returns to clinic on the day described above ... about 3 weeks since the start of Sxs and 3 weeks and few days following the triamcinolone epidural. he reports an 8lb weight gain and has a bulkier face than I last saw him. A cushingoid appearance as no fat distribution seems to be on his periphery. His hyperhidrosis, insomnia, anxiousness, nausea and loss of appetite remain. He is fatigued and has systemic myalgias. In a "house" television moment the story seemed to connect. I grew suspicous of cushings syndrome. Initially i thought this odd given a recent brain MRI and CT ABD did not reveal mass. I immediately ordered AM Cortisol and ACTH levels, set up a 24 hour cortisol urine collection and triamcinolone level. Cushings would make sense ..... it is notorious for GI disturbance including increased gastric acid secretion which could bring on the H Pylori Sx maybe? it explains the reduced CD4 count with a normal WBC count. All symptoms fit a cushings diagnosis although none are very specific. Except the physical manifestations. Lab work is still pending ..... but here is what i think happened. December 2008 marksthe first report of an HIV + patient taking norvir (a potent CYP 450 3A4 inhibitor- culprit of numerous drug interactions ) receiving a triam epidural and experiencing an iatrogenic cushings syndrome. Since then 3 other cases have been reporting in the literature. It seems quite rare outside of academic reports as the neurologist/pain mgmt seemed stunned it was being considered. I stopped the norvir/darunavir and started him on a different third drug as part of his ART, an integrase inhibitor known as raltegravir. I also started him on Vit D and Ca - every case reports of iatrogenic cushings in an HIV patient from epiduram triam resulting in avascular necrosis of the femoral head several months later. I explained my suspect diagnosis could be iwrong he did not care and wanted to take on the rx plan before lab work returns. The treatment plan will not hurt him if the Dx is wrong ... well very unlikely to cause harm ... and will likely give him some pscyh relief for the next few days. Link to comment Share on other sites More sharing options...
deborah212 Posted March 11, 2011 Share Posted March 11, 2011 Interesting case! Does pheo produce pain symptoms?? Yes... GI complaints are relatively common including nausea, constipation, and epigastric pain. Link to comment Share on other sites More sharing options...
rcdavis Posted March 11, 2011 Share Posted March 11, 2011 Fascinating, I did not think cushings could occur with such innocuous dosing so infrequently.as you said recent CT of head essentially r/o pituitary adenoma and CT and r/o adrenal tumors. So, if the sx is right, then all this from an occasional dosage of triamcinolone??? Pls f/u with 24 hr cortisol levels and dex suppression test results. As an aside, what is the rationale for epidural steroid injection as treatment for OA. The pain of OA is local, not radicular, and usually tx'd w/ intra-articular steroid or synthetic synovium injection, not epidurals... Any comments on the neurologists thinking? That treatment does not make sense. I will be educated, and surprised, if the cortisol levels are elevated. Pls keep the data coming. Thanks for the presentation. Link to comment Share on other sites More sharing options...
Moderator ventana Posted March 11, 2011 Moderator Share Posted March 11, 2011 I am such a geek... sitting here with my morning coffee reading over this case scratching my head....... gotta love medicine - can be oh so humbling..... clearly not addison's and in fact the exact opposite... really appreciate these cases - thanks guys and gals! the steroid injections for OA are resonable if they are in the facet joint (think knee steroid injections), but in epidural region.....? Have had a few patients on long term antivirals that get horrible neuropathy of legs and we tend to try an epidural then move to an epidural nerve stim..... but might just be the case of the pain doc trying something to help (either the patient or his procedure count) Link to comment Share on other sites More sharing options...
SocialMedicine Posted March 11, 2011 Author Share Posted March 11, 2011 AM Cortisol level came in this morning and was .2 normal range is 7-20 I believe ..... so this supports the diagnosis. Otherlabs pending. Link to comment Share on other sites More sharing options...
SocialMedicine Posted March 11, 2011 Author Share Posted March 11, 2011 His hip pain is more than an OA, there is a neuropathy longstanding as well. My apologies for not being clear. Also, in this case wedonot expectthe cortisol level to be high. We expect it tobe zero because the iatrogenic source of steroid has shut the system down. The triamcinolone serum / urine levelbeing high and an ACTH/cortisol level being very low iswhat I expect to find. Link to comment Share on other sites More sharing options...
SocialMedicine Posted March 11, 2011 Author Share Posted March 11, 2011 The potential for adrenal insufficiency ... or maybe to some degree he is in this already as well ..... is high so I am recommending he be followed by an endocrinologist. Link to comment Share on other sites More sharing options...
rcdavis Posted March 11, 2011 Share Posted March 11, 2011 Hmmm. Wait a minute. Definitionally, cushings is an EXCESS of cortisol, either from too much Cortotropin Releasing Hormone( CRH)from the hypothalmus stimulating the anterior pituitary to release acth which stimulates the zona fasciculata of the adrenal gland to release cortisol. The presence of physiologic levels of cortisol provides a negative feed back to the hypothalamus, which in turn decreases CRH, hence decreasing ACTH, DECREASING ADRENAL STIMULATION..etc. Cushings Disease is what happens when there is ACTH production independent of the negative feed ache... and there is a failure of teh feedback loop This occurs in pituitary adenoids, ACTH tumors, hypothalamic tumors producing cry, etc Cushings Syndrome occurs when there is cortisol production from the adrenals independent of the absent ACTH, or non pituitary stimulation.. Adrenocortical tumors, cortisol production by small cell carcinoma, etc, or EXOGENOUS glucocorticoids ( really is pseudo-cushings, or iatrogenic cushings-), or stress, alcoholism, oral contraceptives, drugs (eg phenytion) which bind the crh stimulator sites) Regardless.. In EVERY CASE OF CUSHINGS THERE IS AN EXCESS OF CORTISOL ( sorry to yell.. Caps lock.. Am typing fast in mcdonalds) not a deficiency. And is proven first by screening with an AM cortisol, which has to be by definition, HIGH, to warrant further investigation as to why it is high... If high, then a dexamethasone suppression test is done... Which in cushings disease has persistent high cortisol levels dispite the presumed ACTH suppression by the dexamethasone. Urinary cortisol levels are also determined. If that test is positive, then to further localize the lesion, further testing is done... Not necessary for this discussion because the PT does NOT have cushings defintionally What the PT MAY have is addisons.. Or adrenocortical insufficiency or early failure.. Which also has almost the same constellation of sx. Addisons can be caused by an inhibitionadrenals by exogenous steroids taken for a long time [ or if high dosed for acute illness say asthma, then in the subsequent 6 months PT is subject to severe stress, say sepsis, and the adrenals cannot mount an adequate cortisol response. This is diagnosednby an ACTH STIMULATION TEST and a CRH stimulation test.with cortisol levels drawn serially over several hours to measure the adrenal response to the ACTH ( back in the day, when ACTH was not so readily available, I would use insulin and purposely drop the sugars to 30mg% to stimulate a stress response, and then measure cortisol.. Which test is still infrequently used to diagnose panhypopituitarism, schmidts or shehans syndrome..) What I suspect you are meaning to say is that , because his cortisol levels are low, you are worried about addisons, or adrenocortical insufficiency. Aren't you? v/r davis Link to comment Share on other sites More sharing options...
SocialMedicine Posted March 11, 2011 Author Share Posted March 11, 2011 the steroid from the epidural is directly causing the iatrogenic cushings syndrome. this would explain the cushings like symptoms. his Sx do not suggest adrenal insufficiency (HTN, elevated glucose, low CD4 count). The half life of this steroid have been found to be 170X greater in susceptible patients on norvir. He does not have obvious symptoms of adrenal insufficiency certainly not adrenal crisis. I get what you are saying ... his blood work withour cortisol is a major risk for adrenal crisis/insufficiency if it does not return to normal levels as the triamcinolone level metabolizes following removal of norvir. If you google "iatrogenic cushing syndrome after triamcinolone epidural in and HIV type 1 infected patient receiving therapy with Ritonavir - Lopinavir by Roshan Ramanathan an interesting description is given. triamcinolone provides the negative feedback against the HPA axis. If my suspicion is accurate we would expect serum triamcinolon levels HIGH and cortisol / ACTH levels LOW. if you follow the paper as the iatrogenic steroid tapers the HPA axis starts up and cortisol production resumes. No patient needed steroid treatment for the resulting adrenal insufficiency - addisons is a specific type of adrenal insufficiency caused by an autoimmune process against the adrenal glands and i think only becomes symptomatic after the process has been in place awhile. So ... maybe we are both correct. His symptoms seem more in line with cushings ... but he has laboratory evidence to support both. Hence the endocrinology involvement to monitor him to see if his HPA axis returns to normal operation following removal of the iatrogenic steroid Link to comment Share on other sites More sharing options...
rcdavis Posted March 11, 2011 Share Posted March 11, 2011 I did read the reference. Thanks.. very very interesting.. goes back to one of my suspicions that he was having a drug drug reaction, but I would not have ever guessed that the drug changed the pharmokinetics of trimancinolone from 2-3 hr clearance in systemic injection and 2 weeks for intrarticular, to 70 or so days!!! So, we have a semantic problem,. The pt is cushing-oid in his appearance and sx, and has hyperglucocoid d/t decreased clearance, creating increased cushing-lioke risks for cataracts, avn, etc... all based on ONE epidural shot. But.. and I am a stickler on this, he does not meet the definition of cushings... which, definitionally, HAS to have elevated cortisol. In fact, in his case the feedback loop is working.. the hyperglucocorticoid is supressing the pit-adrenal-hypothalmic axis.. and the cortisol level is low. so, we do agree.. cushing-oid .. yes.. cushing's syndrome .. no.. pseudo-cushing's d/t iatrogenic clucostreoids.. yes at risk for inadequate adreno-cortical response while triamcinolone levels are elevated...(addisons), probably... the adrenals have been quiescant for almost 10 weeks by the high aristocort levels.. will probably need to be slowly "awakened" by a careful ( and maybe in his case, a year long) withdrawal of steroids.. This case is extremely improtant for ED guys and hospitalists.. who will see HIV patients in stressful situations, such as sepsis, asthma, shock... we need to reconize that the possible interaction of triamcinolone (which is rarely used in sepsis, or shock) warrants extremely close dosing attention.. and- according to the article, these antiviral boosters will similarliy DECREASE the metabolic clearance of prednisolone.. and presumably the whole class of glucocsteroids, hydrocortisone, prednisone, betamethasones, etc thank you thank you for such a teaching case. davis Link to comment Share on other sites More sharing options...
bradtPA Posted March 11, 2011 Share Posted March 11, 2011 Yes, thank you. I know I have at least one patient on Norvir, and will reserve steroids for her for respiratory failure based on this case. Link to comment Share on other sites More sharing options...
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