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Th e n e w e n g l a n d j o u r n a l o f medicine

n engl j med 357;25 www.nejm.org december 20, 20072636

increased requirements for transfusion of packedred cells in the first 2 days after randomization inthe main SAFE study and on the second day in theSAFETBI study.

Ultimately, the selection of resuscitation fluidfor patients with traumatic brain injury will de-pend on the attending clinicians preference and

experience, the cost and availability of specificfluids, and the interpretation of published evi-dence, to which our study adds new data.

John A. Myburgh, M.D., Ph.D.D. James Cooper, M.D.Simon Finfer, M.D.Australian and New Zealand Intensive Care SocietyMelbourne 3000, Australiaj.myburgh@unsw.edu.au

for the SAFE Study Investigators

The SAFE Study Investigators. A comparison of albumin andsaline for fluid resuscitation in the intensive care unit. N Engl JMed 2004;350:2247-56.

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Gynecomastia

To the Editor:In his review of gynecomastia,Dr. Braunstein (Sept. 20 issue)1includes numer-ous medications that may be associated with gy-necomastia but does not mention a potential link

of statins to gynecomastia. The only medicationused by the patient described in the clinical vignettewas a statin, and case reports have suggested thatstatins might induce gynecomastia.2,3In one casereport, the gynecomastia was reversed after achange in statin medication.2A possible mecha-nism for this relationship is a reduction in adre-nal or gonadal steroid production through the ef-fects of statins on the cholesterol pathway.2

Isabela Romao, M.D.Evan Klass, M.D.

North ShoreLong Island Jewish Health SystemLake Success, NY 11042

Braunstein GD. Gynecomast ia. N Engl J Med 2007;357:1229-37.

Hammons KB, Edwards RF, Rice WY. Golf-inhibiting gyne-comastia associated with atorvastat in therapy. Pharmacotherapy2006;26:1165-8.

Aerts J, Karmochkine M, Raguin G. Gynecomastia due to prav-astatin. Presse Med 1999;28:787. (In French.)

To the Editor:Braunstein stresses the impor-tance of physical examination in the diagnosis ofa breast mass in men and the addition of mam-

mography in selected cases but does not discussthe role of fine-needle aspiration cytology and corebiopsy in the diagnostic workup. In our hospital,fine-needle aspiration cytology or core biopsy isused in the evaluation of lesions that are equivo-cal or suggestive of cancer on physical examina-tion, mammography, or both. In our experienceand in the experience of others, fine-needle aspi-ration cytology has a negative predictive value thatis close to 100% and, in almost all studies, a posi-

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tive predictive value of 100%.1In a small study ofcore biopsy, no false positive or false negative re-sults were found.2With the use of this strategy,diagnostic operations for gynecomastia may be

avoided, and for men in whom breast cancer isdiagnosed, appropriate treatment may be facili-tated.3

Pieter J. Westenend, M.D.Laboratory for Pathology3317 DA Dordrecht, the Netherlandspwestenend@paldordt.nl

Remmert Storm, M.D.Rob J. Oostenbroek, M.D.Albert Schweitzer Hospital3300 AK Dordrecht, the Netherlands

Westenend PJ, Jobse C. Evaluation of fine-needle aspiration

cytology of breast masses in males. Cancer 2002;96:101-4.Westenend PJ. Core needle biopsy in male breast lesions.

J Clin Pathol 2003;56:863-5.Giordano SH. A review of the diagnosis and management of

male breast cancer. Oncologist 2005;10:471-9.

The author replies:Romao and Klass raise thepossibility that the patient in the case vignette haddrug-induced gynecomastia from a statin. The onlyevidence of a relationship between the statin andthe gynecomastia in the two patients in the casereports they referenced was the appearance of gy-

necomastia after treatment with pravastatin wasstarted in one patient and after a switch was madefrom simvastatin to atorvastatin in the other; thebreast enlargement resolved after withdrawal ofthe drug in the first patient and after a switchback to simvastatin in the second patient. Neitherpatient was rechallenged with the presumed cul-prit, and both patients were taking other medi-cations that have been implicated in other casereports of gynecomastia. This illustrates the dif-

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The New England Journal of Medicine

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correspondence

n engl j med 357;25 www.nejm.org december 20, 2007 2637

ficulty of evaluating most of these types of casereports, since they show only a temporal relation-ship. As to the postulated statin-induced reductionin adrenal or gonadal steroid production, multiplestudies have shown no significant differences be-tween basal or stimulated hormone levels in menbefore and after statin use or in men using statins

versus those not using the drugs.1,2In addition,double-blind, placebo-controlled trials of statinuse in children and adolescents have not showndifferences in adrenal or gonadal steroid levelsor alterations in pubertal development betweenpatients receiving statins and those receivingplacebo.3,4

Westenend and colleagues advocate the use offine-needle aspiration and core biopsy in the evalu-ation of breast masses. In most cases, one shouldbe able to discriminate between gynecomastia andother breast lesions on physical examination. If

not, the next step should be diagnostic (notscreening) mammography, ultrasonography, orboth. If the diagnosis is still uncertain, then fine-needle aspiration is reasonable as long as thepathologists have sufficient experience in inter-preting the results of breast fine-needle aspiration.Unfortunately, there is a high rate of unsatisfac-

tory specimens, and florid gynecomastia may bemistaken for breast cancer with this technique.5Finally, Westenends report on core biopsy in menwith breast lesions demonstrates the potentialusefulness of this technique. However, there isinsufficient information from other centers to ad-vocate widespread use at this time.

Glenn D. Braunstein, M.D.CedarsSinai Medical CenterLos Angeles, CA 90048braunstein@cshs.org

Travia D, Tosi F, Negri C, Faccini G, Moghetti P, Muggeo M.Sustained therapy with 3-hydroxy-3-methylglutaryl-coenzyme-Areductase inhibitors does not impair steroidogenesis by adrenalsand gonads. J Clin Endocrinol Metab 1995;80:836-40.

Hall SA, Page ST, Travison TG, Montgomery RB, Link CL,McKinlay JB. Do statins affect androgen levels in men? Resultsfrom the Boston area community health survey. Cancer Epide-miol Biomarkers Prev 2007;16:1587-84.

de Jongh S, Ose L, Szamosi T, et al. Efficacy and safety ofstatin therapy in children with familial hypercholesterolemia:a randomized, double-blind, placebo-controlled trial with sim-vastatin. Circulat ion 2002;106:2231-7.

Stein EA, Illingworth DR, Kwiterovich PO Jr, et al. Efficacyand safety of lovastatin in adolescent males with heterozygousfamilial hypercholesterolemia: a randomized controlled trial.JAMA 1999;281:137-44.

Siddiqui MT, Zakowski MF, Ashfaq R, Ali SZ. Breast massesin males: multi-institutional experience on f ine-needle aspiration.Diagn Cytopathol 2002;26:87-91.

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Reversal of Pacing-Induced Heart Failure

by Left Ventricular Apical Pacing

To the Editor:Children with congenital com-plete atrioventricular block often require lifelongpacemaker therapy. Although such therapy restoresa normal heart rate, it also results in dyssynchro-nous left ventricular activation and contraction andcompromises left ventricular function.1-3These ef-fects are most pronounced during right ventricu-lar pacing, the predominant pacing site in chil-dren and adults. Eventually, heart failure develops

in 6 to 7% of children who undergo long-termright ventricular pacing.2The harmful effects of right ventricular pacing

initiated the search for pacing modes that wouldmaintain or restore synchronous activation inother words, biventricular pacing and alternativesingle-site ventricular pacing. In previous stud-ies,3,4we showed that the physiologic apex-to-base sequence of electrical activation during leftventricular apical pacing resulted in a hemody-

namic response that was as good as the responsewith multisite pacing in dogs; we also showed thatsuch activation had favorable acute hemodynamiceffects in children.4

On the basis of these findings, we used leftventricular apical pacing to treat a 2-year-old girlwith congenital complete atrioventricular blockand heart failure induced by right ventricular pac-ing. In this patient, single-chamber right ventricu-

lar epicardial pacing had been started 1 day afterbirth to treat symptomatic bradycardia. Duringright ventricular pacing, echocardiography showeddyssynchronous left ventricular contraction, whichwas associated with progressive left ventriculardilatation (Fig. 1). After 2 years of right ventricu-lar pacing, rapid deterioration occurred, with thedevelopment of congestive heart failure (afterloadreduction with lisinopril had been started): theshortening fraction decreased to approximately

The New England Journal of Medicine

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Copyright 2007 Massachusetts Medical Society. All rights reserved.