Clinical and Health Affairs
2009 American College of Physicians Poster Competition Winners
Each year, the state chapters of the American College of Physicians invite medical students, residents, and fellows to take part in a scientific poster competition. Last year, the Minnesota Chapter received more than 140 entries from students and residents taking part in the internal medicine training programs at Abbott Northwestern Hospital, Hennepin County Medical Center, Mayo Clinic, and the University of Minnesota.
Posters were judged by practicing internists as well as by internists from the state’s academic medical centers. Each judge conducted poster rounds with a group of residents, allowing the judge as well as the presenter’s peers to view the poster being presented. Criteria used by the judges included clinical relevance, originality, visual presentation, and written presentation. The winners will be eligible to enter their posters in the national competition April 22-24 in Toronto.
Congratulations to the winners and all of the participants for their excellent work.
■ Research Winner
Impact of Prescription Drugs on Thyroid Physiology and Thyroid Hormone Therapy
By Rozalina Grubina, M.D., Mayo Clinic
Thyroid dysfunction ranks among the most prevalent metabolic derangements, and thyroid hormone preparations are among the most commonly prescribed medications. Medical literature abounds with reports of drugs interacting with thyroid gland regulation and function, and with thyroid hormone absorption, transport, and clearance. Although a few drugs have been studied extensively, evidence implicating others has been weaker.
Methods: We conducted a comprehensive search of MEDLINE for manuscripts published between 1990 and 2008 describing effects of FDA-approved drugs on thyroid physiology, thyroid hormone therapy, and thyroid function tests in humans. We categorized the reported drug interactions and assessed the strength of supporting evidence according to USPSTF-proposed guidelines.
Results: Based on review of 37,170 citations, we identified 416 that described relevant interactions with 176 pharmaceutical agents; 377 (91%) of the interactions were clinically significant. Of 120 distinct drugs affecting thyroid gland function or regulation, there was high-level evidence for 85. Similarly, thyroid hormone replacement therapy was affected by 38 (total) and 20 (high-level) distinct agents, and thyroid function tests by 18 (total) and four (high-level) agents. Many drugs were noted to have multiple effects, with the following number of references to these modes of interference: hypothalamic-pituitary function (82; 19.7%); iodine handling (24; 5.8%); and thyroid hormone synthesis (45; 10.8%), bioavailability (39; 9.4%), deiodination (46; 11%), and degradation (40; 9.6%). Direct and TBG level-mediated drug interactions with thyroid hormone therapy were reported in 52 (12.5%) and 33 (7.9%) studies, respectively. Isolated interference with thyroid function tests was detected in 27 studies (9.6%). The levels of supporting evidence ranged from placebo-controlled studies in 14% (level I) and prospective interventional studies in 38.8% (level II) to purely observational data in 19% (levels III and IV). Relevant in vitro studies comprised 9.8%.
Conclusion: A large number of FDA-approved drugs have been implicated as altering thyroid gland function, hormone homeostasis and therapy, as well as thyroid function tests. Many of these effects are clinically significant. A comprehensive and critical review of recent literature describing these drug interactions has identified a variety of potential mechanisms and a spectrum of supporting evidence validity. The medical community would benefit from creation and maintenance of an up-to-date database of such agents.
■ Clinical Vignette Winner
Unusual Cause of Personality Change in an HIV-Positive Patient
By Kelly Cawcutt, M.D., University of Minnesota
A 50-year-old HIV-positive male treated with HAART who had a recent CD4 count of 572 presented after two weeks of a productive cough associated with dyspnea and a two-day history of chest pain. On admission, the patient was noted to have 2/6 systolic murmur and belligerent behavior. The initial chest X-ray was significant for an infiltrate of the left lung base. A transthoracic echocardiogram was performed and was significant for mitral regurgitation without evidence of vegetation. The patient was diagnosed with pneumonia. Blood cultures were drawn and the patient was treated empirically. The blood culture returned positive for gram-positive cocci, and a diagnosis of pneumococcal pneumonia was presumed.
The patient continued to exhibit aggressive and belligerent behavior, and the patient’s primary doctor was contacted. This change in his baseline behavior seemed to be significant. A head CT was performed, which demonstrated a hyperdensity in the left frontal lobe concerning for an embolic lesion. MRI confirmed the lesion, along with a second area of hyperdensity. Subsequent transesophageal echocardiogram revealed moderate to severe mitral regurgitation with a round echodensity noted on the anterior mitral leaflet consistent with a vegetation. The speciation on the blood cultures was reported as Abiotrophia defectiva with a final diagnosis of infective endocarditis with septic emboli to the brain and lung. The patient was treated with antibiotics followed by valve replacement surgery.
Abiotrophia defectiva is a gram-positive bacteria previously known as a nutritionally variant streptococci. These are considered normal flora of the oral cavity, upper respiratory tract, urogenital tract, and gastrointestinal tract. Abiotrophia defectiva is clinically important as it is known to cause approximately 5% of cases of infective endocarditis (IE). The IE caused by A. defectiva is likely subacute based on the slow growth and relatively small-but-destructive vegetations. Most cases are associated with known heart abnormalities or with recent dental manipulation. Additionally, A. defectiva has a higher rate of mortality and morbidity when compared with other streptococci secondary to refractory congestive heart failure, frequency of septic emboli, and failure of antimicrobial therapy.
The most common treatment for A. defectiva-related IE is a combination of penicillin and gentamicin with surgical intervention. Unfortunately, A. defectiva is a fastidious, slow-growing organism with a resultant bacteriologic failure rate of 41% leading to a relapse rate of 17%. At this time, there is no clearly preferred treatment for relapsing cases of A. defectiva infective endocarditis.
■ Medical Student Winner
Hemolysis: The Zebra of Mitral Valve Repair
By T.K. Pandian, Peter P. Stanich, M.D., and Jason A. Post, M.D., Mayo Clinic
Insertion of intracardiac prosthetic materials places patients at risk for ischemic nephropathy intraoperatively and hemolytic anemia postoperatively. Perfusion injuries to the kidney may present with hyperkalemia, anemia, or other sequelae of acute renal failure. Mechanical hemolysis also can result in anemia and hyperkalemia but is a very uncommon complication following mitral valve repair. Although physicians frequently hear the aphorism “When you hear hoof beats, think horses, not zebras,” the use of basic history and physical exam can sometimes lead to the discovery of rare etiologies.
Case: A 75-year-old man with a history of atrial fibrillation, multiple myocardial infarctions, mitral regurgitation, renal insufficiency, and quiescent ulcerative colitis s/p proctocolectomy with end ileostomy, presented with anemia, hyperkalemia, worsening renal function, and progressive shortness of breath with exertion. He had undergone an atrial maze procedure, two-vessel CABG, and mitral valve annuloplasty three months prior to presentation and was adequately anticoagulated with warfarin. A recent outpatient workup attributed his worsening renal function to dehydration in the setting of ileostomy losses and postoperative diuretic use. Examination revealed a lean gentleman with normal vital signs. A harsh 3/6 systolic murmur was heard across the precordium with radiation to the axilla. There were no pulmonary crackles or lower extremity edema.
Laboratory studies showed an Hgb of 7.1 (13.5-17.5 g/dL), an MCV of 100.2 (81.2-95.1 fL), and an appropriately elevated reticulocyte count. An electrolyte panel was notable for K 5.5 (3.6-5.2 mmol/L). Renal studies revealed a creatinine of 2.3 (0.8-1.3 mg/dL) and BUN of 85 (8-24 mg/dL), which were elevated from his baseline of 1.5 and 36, respectively. Further evaluation showed a normal B12 level, normal serum iron, elevated ferritin, and schistocytosis on peripheral smear. Haptoglobin levels were less than 14 [30-200 mg/dL], LDH 1,797 [122-222 U/L], total bilirubin was marginally elevated, and coagulation studies revealed a therapeutic INR of 2.0.
Collectively, his evaluation was consistent with an intravascular hemolytic process. With the prominent murmur on physical exam and no other obvious source of hemolysis, attention was turned to his recent annuloplasty. A TEE revealed severe mitral valve regurgitation with eccentric jets and annuloplasty dehiscence. He subsequently underwent a complete mitral valve replacement. Postoperatively, his hemoglobin and potassium levels stabilized, and an echocardiogram demonstrated only trivial residual prosthetic regurgitation. He was discharged 13 days after surgery.
Discussion: Etiologies of specific symptoms and laboratory values can be unclear in complicated patients with multiple comorbidities and recent cardiac valve manipulation. Specifically, when anemia and hyperkalemia are present in this population, clinicians should not immediately attribute the findings to worsening renal function caused by intra-operative ischemia. Although mitral valve repair has a low incidence of inducing mechanical hemolysis, a careful history and physical examination can prevent the clinician from missing a rare-but-treatable diagnosis. MM