Faculty Bibliography

LEARNING OBJECTIVE #1: Know the possible drug interactions of HMG CoA reductase inhibitor (statin) and commonly used antiplatelet agents LEARNING OBJECTIVE #2: Understand options for statin therapy in people with statin induced myopathy CASE: A 75-year-old man presented to his primary care physician (PCP) with two weeks of progressively worsening bilateral anterior thigh pain causing difficulty with ambulation. One month prior to presentation, he had been hospitalized for non-ST elevation myocardial infarction and in-stent thrombosis after he self-discontinued aspirin therapy. Upon discharge, he was switched to ticagrelor after he was found to be a non-responder to clopidogrel on platelet function tests. One day prior to admission his PCP discovered AST and ALT elevations to over 400 U/L (normal ranges 11-39 U/L and 11-35 U/L) and instructed the patient to present to the emergency room for further workup. In the emergency room (ED), the patient reported his symptoms started after he started taking ticagrelor, and he denied alcohol use. Past medical history includes hypertension and coronary artery disease treated with five drug eluting stents. He reported adherence medication regimen, which consisted of aspirin, ticagrelor, atorvastatin, amlodipine, hydrochlorothiazide, losartan, and metoprolol. He denied shortness of breath, dyspnea on exertion, abdominal pain, and leg edema. Vital signs were normal. Physical exam was most notable for tenderness to palpation of the thighs bilaterally. AST and ALT were 228 U/L and 158 U/L respectively, and CK was 4600 U/L (normal range: 45-245 U/L). Urinalysis revealed small blood with 0-4 red blood cells; urine culture produced no growth. Liver ultrasound found a normal liver and biliary tree. Hepatitis B and C serologies were negative. Troponin I was 0.07 ng/mL (normal range: <0.06 ng/mL), though there were no EKG changes from his prior admission. Once admitted to the floor, his atorvastatin was discontinued. The next day his AST and ALT decreased to 57 U/L and 121 U/L, and his CK fell to 715 U/L. IMPACT/DISCUSSION: Both myopathy and hepatitis occurred in this patient after initiation of ticagrelor, which is a known inhibitor of CYP P450 3A4. The levels of atorvastatin, which is metabolized by CYP P450 3A4, likely increased and caused a dose dependent toxicity, causing the patient's symptoms and lab abnormalities. He was subsequently discharged with improvement of thigh pain.
CONCLUSION(S): The drug-drug interaction of atorvastatin and ticagrelor has been established. This submission focuses on increasing knowledge of this common interaction. In this case, atorvastatin was discontinued and rosuvastatin was started as it is not metabolized by CYP P450 3A4. This combination is often better tolerated when combined with ticagrelor. The patient returned for outpatient follow-up and was started on rosuvastatin 5 mg with repeat liver function tests ordered with plans titrate as tolerated

LEARNING OBJECTIVE #1: Recognize the acute neurologic manifestations of non-ketotic hyperglycemia in adults with type 2 diabetes. LEARNING OBJECTIVE #2: Management of chronic disease in non- English speaking patient populations with low health literacy. CASE: 44 year old Mandarin speaking male with a history of hypertension and type 2 diabetes (DM2) presented with five days of intermittent episodes of involuntary right arm movement associated with urinary incontinence. Episodes occurred at least ten times daily and were not associated with alteration of consciousness. Of note, he was diagnosed with DM2 in the past year, but had limited understanding of the disease and was not taking any medications. The patient takes no medication. He has no family history of seizures or other neurological problems. He smokes rarely and does not drink alcohol or use drugs. On presentation he had stable vital signs and physical exam revealed no focal neurological deficits and was otherwise normal. Labs including a blood count, hepatic panel, urine toxicology, and metabolic panel were normal apart from a glucose at 616 mg/dL with a HbA1C at 14.1%. After a normal non-contrast head CT, these episodes were confirmed as focal seizures on EEG and were refractory to 1500mg levetiracetamtwice daily. He was placed on a basal-bolus regimen of insulin, with improvement of his glucose and cessation of his seizures with no further abnormal activity on EEG. Before discharge, the patient was counseled on his diagnosis of DM2 with culturally appropriate, Mandarin based educational materials as well as individual teaching on glucose monitoring and insulin administration using an interpreter. IMPACT/DISCUSSION: Non-ketotic hyperglycemia (NKHG) is a complication of DM2, and often is triggered by metabolic stressors. Classically, this presents as polyuria, polydipsia, lethargy, confusion, and ataxia. Other neurologic findings such as increased motor tone, hemiparesis, or focal seizures are rare. The pathophysiology of focal seizures in NKHG is not fully understood. Hypertonicity is unlikely to be the cause as these seizures are not present in diabetic ketoacidosis, and serum osmolarity is normal during these seizures. A prominent theory is that there may be increased metabolism of the neurotransmitter GABA, decreasing the seizure threshold. Managing these focal seizures is often difficult due to delay in diagnosis and treatment. Focal seizures tend to be refractory to antiepileptic drugs, and phenytoin can worsen these seizures by reducing insulin secretion. Management of focal seizures in NKHG is control of the hyperglycemic state, with insulin and rehydration.
CONCLUSION(S): In our patient, treatment of hyperglycemia was successful in terminating seizure activity, representing a rare case of focal seizures presenting as a symptom NKHG. In addition, usage of culturally and language specific educational materials is vital for the proper management of chronic conditions such as DM2, in order to prevent further complications of chronic disease

LEARNING OBJECTIVE #1: Differential diagnosis for acute onset heart failure and renal failure in a young adult LEARNING OBJECTIVE #2: Understand the natural course of HIV end-organ damage CASE: A 31-year-old woman presented with dyspnea on exertion for three months without other symptoms. Past medical history only included mild intermittent asthma. Physical exam was significant for bibasilar crackles and elevated jugular venous pressure. Initial labs found a creatinine of 2.3, total protein of 9.5 and albumin of 3.0. Troponin was negative and BNP was 1784. Urine protein was 527, urine creatinine 43.6, and urine sodium 81. Ultrasound showed enlarged kidneys. An echocardiogram an ejection fraction of 9% and a dilated left ventricle. Heart failure workup found a normal TSH, ferritin, B12, thiamine, carnitine, selenium and ANA. Hepatitis testing was negative. An HIV test was positive (last negative in spring 2017), with a viral load of 1298 and a CD4 count of 355. Cardiac MRI showed possible infiltrative cardiomyopathy without ischemia. PYP scan showed no evidence of amyloidosis, consistent with HIV-cardiomyopathy. Kidney biopsy found collapsing focal segmental glomerulosclerosis, consistent with HIVassociated nephropathy. IMPACT/DISCUSSION: Workup for new heart failure in a young adult includes evaluation for ischemic, autoimmune, infiltrative, nutritional, and infectious causes. In this patient with renal and heart failure, the differential was narrowed to infiltrative disease, viral end organ disease, lupus, or cryoglobulinemia. Cardiomyopathy in patients with HIV is typically due to cardiotoxicity of antiretroviral therapy or ischemic heart disease. This patient is unusual in developing HIV cardiomyopathy so early in the course of her disease. The pathophysiology of this process is likely multifactorial with cardiomyopathy occurring at a wide range of CD4 counts and viral loads. HIV-1 has been shown to have direct toxicity on myocardial cells through cardiac macrophages and production of inflammatory mediators. HIV-associated nephropathy (HIVAN) is likely secondary to viral infection of renal epithelial cells by HIV-1 resulting in epithelial cell proliferation and apoptosis. HIVAN is more clearly associated with CD4 counts <200 and viral load greater than 400, and usually occurs later in the disease course. This case suggests that HIVAN itself may be able to occur earlier than previously postulated, though perhaps only in conjunction with an additional insult to the kidneys such as new-onset heart failure.
CONCLUSION(S): This case illustrates the potential for the development of rapidly progressive HIV complications, and thus the importance of a robust HIV screening and treatment strategy as early detection of HIV and treatment with ART can prevent these complications

Learning Objective #1: Recognize, manage, and prevent hungry-bone syndrome (HBS) CASE: A 46-year-old male with a history of hypertension presented with urinary hesitancy and frequency for two months. His only other complaint was aching pain in his back and bilateral legs. Physical exam was significant for tenderness of his lower extremities. Labs were significant for creatinine of 3.9 mg/dL, calcium of 12.5 mg/dL, and an alkaline phospha-tase of 916 U/L. Parathyroid hormone (PTH) was 4393 pg/mL. Phosphate and 25-hydroxy vitamin D were normal, but 1,25-dihyrdoxy vitamin D was low at 9.1 pg/mL. Renal ultrasound demonstrated bilateral hydronephrosis. CT imaging revealed a left paratracheal soft tissue mass, extensive lytic bone lesions, and multiple renal calculi. Core biopsy of the mass was consistent with follicular parathyroid cancer. The patient received alendronate then underwent parathyroidectomy of the affected gland with post-operative perioral tingling and paresthesias and hypocalcemia with a nadir of 5.5 mg/dL. This patient then required 138g of oral calcium carbonate and 118g of intravenous calcium gluconate along with calcitriol and cholecalciferol over the course of thirteen days. IMPACT/DISCUSSION: This case exemplifies the potential severity of HBS. This patient's calcium requirement was 256g or an average of 20g/day, significantly higher than reported 6 to 12g/day that a typical HBS patient requires. HBS is defined as rapid and profound hypocalcemia due to an acute withdrawal of PTH after a parathyroidectomy. This is caused by a reduction of osteoclast activity and an increase in osteoblast activity leading to unopposed deposition of bone and resultant hypocalcemia. Hypophosphatemia and hypomagnesemia may also develop. These electrolyte abnormalities will last for weeks to months, but rarely have been reported to last for over a year. Patients who develop HBS are at risk of arrhythmias, heart failure, and seizures. These problems can be prevented with regular serum testing and repletion of calcium, phosphate, magnesium, and vitamin D. Preoperative bisphosphonates and vitamin D repletion have been shown to decrease the magnitude of hypocalcemia post operatively. Patients at risk of developing HBS include those with older age, higher preoperative serum calcium, alkaline phosphatase, and PTH levels, lower preoperative serum magnesium and albumin, parathyroid mass larger than 5 cm, ³ and those with evidence of brown tumors or osteitis fibrosa cystica. This patient's impressive calcium requirement may have stemmed from his preoperative kidney disease vitamin D deficiency, and extensive lytic bone lesions.
Conclusion(s): HBS is a life threatening complication that develops as a result of rapid withdrawal of PTH with subsequent electrolyte disturbances. Some evidence suggests that HBS can be prevented with preoperative administration of bisphosphonates and vitamin D. HBS can be managed with frequent electrolyte monitoring and aggressive repletion