10/25/14 ¡ A Rock and a Hard Place A C A Clinic linical Prob al Problem S lem Solv olving C ing Cas ase e Gurpreet Dhaliwal, MD Professor of Medicine University of California, San Francisco 1 ¡
10/25/14 ¡ Ground Rules for CPS Exercise � Goop has never heard these cases � Not a trivial undertaking � Goal is to make the thought process of a master clinician transparent � It ’ s not magic � You don ’ t have to “ know everything ” � “ Getting it right ” is cool, but relatively unimportant in the grand scheme � Enjoy – this is the fun part of medicine 2 ¡
10/25/14 ¡ History � A 52-year-old man with HIV and chronic hepatitis B presented with a six month history of fatigue, polyuria, nausea, and a 12 pound weight loss Goop ’ s Initial Thoughts 3 ¡
10/25/14 ¡ History of Present Illness � The patient’s HIV was diagnosed in 1989 � No opportunistic infections except for possible thrush � CD4 nadir in the low 200s � Numerous ARVs in past (truvada/atazanavir/ritonavir) but changed to Complera (emtricitabine/rilpivirine/tenofovir) six months ago for ease of dosing � Also has history of hepatitis B but quiescent, nl LFTs � Was well until about 2 months ago when he noticed subacute onset of fatigue, polyuria, nausea, and a 12 pound weight loss � He self-discontinued his ARVs (as well as his atorvastatin) 2 months ago and sought medical attention Labs Two Months Ago � Labs at the time (2 months ago) included: 139 | 105 | 28 / Ca 12.4 --------------------------- 92 4.1 | 29 | 1.91 \ \ 12.5 / TP 5.9 4.6 ----------- 143 Alb 3.9 / 37.4 \ Alk phos 57 Vitamin D 30 CD4 444 (31%), Viral Load undetectable 4 ¡
10/25/14 ¡ What do you think is going on? 1. I think his kidney problem has led to hypercalcemia 2. I think his hypercalcemia has led to his kidney problem 3. I think his kidney problem and his hypercalcemia represent two different processes Ockham’s Razor vs. Hickam’s Dictum � “Entities must not be multiplied beyond necessity.” -- William of Ockham � “Patients can have as many diseases as they damn well please.” -- John Hickam 5 ¡
10/25/14 ¡ My Leading Diagnosis Is… 1. Side effect of his HIV medications 2. A complication of his HIV disease 3. Sarcoid 4. Tuberculosis 5. Ebola 6. Hyperparathyroidism 7. Multiple myeloma 8. Something else 6 ¡
10/25/14 ¡ Two Months Ago � The hypercalcemia and kidney injury were felt to be complications of his new HIV medication � Patient was told to stay off the medication and drink more fluids � No medical attention in the subsequent two months � Symptoms persisted New UCSF PCP (1 st visit) � Complains of persistent nausea, polyuria, weight loss � Notes increasing fatigue with climbing steps, as well as more weakness � Denies fevers, chills, sweats, cough, abdominal pain, bone pain, muscle aches, dysuria, confusion � On no meds (d/ced 2 months ago) 7 ¡
10/25/14 ¡ Remainder of History � Social History � Born and raised in Eureka, CA, now lives in SF � Works as a firefighter � Homosexual � Never smoked, Denies illicit drug use, Drinks one glass of wine a week � FH: Father w/ prostate cancer, Mother w/ salivary gland cancer � ROS otherwise negative Physical Examination � NAD, appears well nourished � Afebrile, 118/78, HR 60, RR normal � Eyes: EOMI, PERRL, anicteric � Neck: normal without masses � CV: RRR, no murmurs, rubs, gallops � Lungs: Normal breath sounds � Abdomen: Non-tender, no masses or HSM � Musculoskeletal: Normal tone, no edema WITHIN NORMAL � Neuro: 5/5 strength throughout, Alert/oriented x 3 LIMITS � Psych: Normal mood, affect, thought content, memory 8 ¡
10/25/14 ¡ Repeat Labs (now) 137 | 103 | 29 / Ca 13.3 --------------------------- 94 4.4 | 29 | 2.18 \ \ 9.9 / Phos 2.3 4.6 ---------- 84 Alb 3.3 / 28.1\ UA spec grav1.012 Prot/Cr ratio 0.33 Hospital Course � The patient was admitted and treated with IV fluids and pamidronate � Additional labs returned: � PTH <3 � Vitamin D (25-OH) 22 (low) � TSH 2.5 � Cortisol 13 � CXR normal 9 ¡
10/25/14 ¡ Now I Want… 1. An SPEP/UPEP 2. Some other Vitamin D thingy 3. A chest CT 4. A parathyroid scan 5. A vacation 6. My mother Goop’s Riff on the Labs 10 ¡
10/25/14 ¡ Additional Labs � SPEP/UPEP negative � IFE negative, normal immunoglobulins � Kappa 65, lambda 48: both high, but normal ratio � Vitamin D 1,25-OH: 128 (normal = 18-72) � Chest CT: two 4 mm pulmonary nodules, slightly increased number of normal-sized LNs in mediastinum/axilla: “non-specific” � CT Abdomen: normal abdomen/pelvis; “nodular soft tissue density in the subcutaneous fat of both buttocks” Now My Leading Dx Is… 1. Sarcoid 2. An occult malignancy producing PTH-related peptide 3. An occult malignancy producing something else 4. Isinglass syndrome 5. Castleman’s disease 6. Tuberculosis 7. A non-sarcoid granulomatous disease 8. Milk-alkali syndrome 11 ¡
10/25/14 ¡ Inisglass � Fish bladder, used in the process of making beer 12 ¡
10/25/14 ¡ Hospital Course � Within a couple of days of receiving IV fluids and pamidronate, calcium down to ~10.5 � A diagnostic procedure was performed PET/CT Scan 13 ¡
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10/25/14 ¡ Diffuse FDG uptake noted within muscles of the upper extremities and the subcutaneous tissue corresponding to the proximal thighs and buttocks. Now I’m Worried About… 1. Sarcoid 2. An occult malignancy 3. Trichinosis 4. Ebola 5. Atorvastatin-induced myositis 6. Something else 18 ¡
10/25/14 ¡ Another Diagnostic Procedure Was Performed I’ll Take Another Shot 19 ¡
10/25/14 ¡ Additional History � After seeing the results of the PET/CT scan, the physicians asked the patient about whether he had done anything to his deltoids and buttocks � He told them that he received cosmetic injections in Mexico to his buttocks (5 years ago) and deltoids (about 6 months ago) to treat muscle wasting Doesn’t anybody take histories anymore? 20 ¡
10/25/14 ¡ Patient Returns to see PCP � A few weeks after discharge, the patient came to see his PCP � He noted that his thirst and polyuria had returned � A calcium level was 12.4 � He received bisphosphonates and IV fluids via an outpatient infusion Yet Another Diagnostic Procedure Was Performed 21 ¡
10/25/14 ¡ Gurpreet Dhaliwal, what is your… final answer? 22 ¡
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10/25/14 ¡ Florid giant cell reaction and histiocytic infiltrate surrounding globules of foreign material. Similar histologic findings to those described for subcutaneous injection of polymethyl methacrylate Final Diagnosis: � Calcitriol-Mediated Hypercalcemia due to foreign body reaction to PMMA 24 ¡
10/25/14 ¡ A Few Key Points � Calcitriol-mediated hypercalcemia resulting from high extrarenal 1,25 hydroxylase activity is associated with granulomatous disease and has been described to accompany foreign body reactions (such as with silicone implants). � Polymethyl methacrylate is a nonbiodegradable compound often injected w/collagen which over time may become encapsulated contributing to the bulking effect. Granulomatous reactions to PMMA have previously been described. � This phenomenon of hypercalcemia 2/2 foreign body reaction to PMMA has not previously been described. A Few More Points � Hypercalcemia requires a stepwise diagnostic plan PTH mediated or not � � Differential Diagnosis of PTH-independent processes: � Hypercalcemia of malignancy � PTHrP � Activation of extrarenal 1 alpha-hydroxylase (increased calcitriol) � Osteolytic bone metastases and local cytokines) � Vitamin D intoxication � Chronic granulomatous disorders � Activation of extrarenal 1 alpha-hydroxylase (increased calcitriol) � Meds: � Thiazide, lithium, teiparatide, excess vitamin A, theophylline toxicity � Misc: � Hyperthyroidism, acromegaly, pheochromocytoma, adrenal insufficiency, immobilization, parenteral nutrition, milk alkali syndrome 25 ¡
10/25/14 ¡ Probably Best to Avoid This Polymethylmethacrylate Sometimes the Best Diagnostic Test is a Good History 26 ¡
10/25/14 ¡ Thank you � Gioia Iezza, UCSF Pathology for slide preparation � Matt Cascino and Anna Neumeier, 2013-14 Chief Residents, for case preparation � Goop!!! 27 ¡
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