n e w e ng l a n d j o u r na l


m e dic i n e

clinical problem-solving

When Past Is Prologue
Nihar R. Desai, M.D., M.P.H., Susan Cheng, M.D., Anju Nohria, M.D., Florencia Halperin, M.D., and Robert P. Giugliano, M.D., S.M.
In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors’ commentary follows.
From the Department of Medicine (N.R.D.) and the Divisions of Cardiovascular Medicine (S.C., A.N., R.P.G.) and Endocrinology (F.H.), Department of Medicine — all at Brigham and Women’s Hospital, Boston. Address reprint requests to Dr. Giugliano at the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, 350 Longwood Ave., 1st Fl. Offices, Boston, MA 02115, or at N Engl J Med 2009;360:1016-22.
Copyright © 2009 Massachusetts Medical Society.

A 36-year-old man presented to the emergency department with a 2-week history of lower-extremity edema, progressive fatigue, and exertional dyspnea. Edema reflects a disruption of interstitial-fluid homeostasis and typically indicates a cardiac, renal, hepatic, venous, or lymphatic pathology. Particularly important features on examination would include an estimation of central venous pressure, the presence or absence of pulmonary edema, the location of the edema, and whether the edema is pitting or nonpitting. Fatigue and dyspnea on exertion are nonspecific but may be a consequence of pulmonary edema and raise concern for a cardiac cause. The patient’s medical history was notable for a fall from a roof 10 months before this presentation. He had traumatic head injury with multiple cranial fractures, including a basal skull fracture, and underwent bifrontal craniotomies. After an extensive rehabilitation period, he achieved almost full functional recovery. Eight months before this presentation, dyslipidemia was diagnosed; the level of total cholesterol was 383 mg per deciliter (9.9 mmol per liter), of low-density lipoprotein 236 mg per deciliter (6.1 mmol per liter), of triglycerides 461 mg per deciliter (5.2 mmol per liter), and of high-density lipoprotein 56 mg per deciliter (1.4 mmol per liter). Metabolic screening tests revealed normal levels of glucose and albumin and normal hepatic and renal function. Atorvastatin was started but then discontinued because of myalgias and elevated levels of creatine kinase (794 U per liter) and aspartate aminotransferase (40 U per liter; normal range, 9 to 30); the alanine aminotransferase level was normal. One month later, his symptoms had improved, but the creatine kinase level had risen to 1200 U per liter. The thyrotropin level was 0.32 mIU per liter (normal range, 0.30 to 5.00), and an antinuclear antibody (ANA) test was negative. The onset of exertional dyspnea, fatigue, and edema led to his presentation at the emergency department before a scheduled rheumatology consultation. He was taking ferrous sulfate, which had been prescribed for anemia at the time of hospital discharge, and a stool softener that was prescribed in association with the iron. He reported that his parents and siblings were in good health, and he reported no use of tobacco, alcohol, or illicit drugs. His marked hyperlipidemia raises concern for a familial or secondary dyslipidemia, as can occur with hypothyroidism, the nephrotic syndrome, or certain medications (e.g., thiazide diuretics, atypical antipsychotic agents, and in women, oral contraceptives containing estrogen), but his laboratory evaluation and history were unrevealing. The new onset of myalgias and documentation of an elevated creatine kinase level while the patient was taking atorvastatin pointed initially to a statin-related myopathy, but the further elevation in the creatine kinase level after the statin was discon-


n engl j med 360;10  march 5, 2009

Downloaded from by JOAN LLEVADOT MD on March 9, 2009 . Copyright © 2009 Massachusetts Medical Society. All rights reserved.

with dullness to percussion at the bases. ICM REG F AUTHOR Giugliano RETAKE 1st 2nd 1 FIGURE 3rd CASE TITLE Revised n engl j med 360.6 mmol per liter). the heart rate 80 beats per minute. The neurologic examination was remarkable only for mild weakness of the left arm and leg. the creatinine level 1. which was chronic. Initial 12-Lead Electrocardiogram. a prolonged QT interval. the hemoglobin level 13. S3 gallop. The oxygen saturation was 91% while the patient was breathing ambient air.6 mg per deciliter (141 µmol per liter) (elevated from a previous baseline value of 0. PLEASE NOTE: Society. The apical impulse was nonpalpable. The creatine kinase level was 1110 U per liter with a creatine kinase MB value of 12 ng per milliliter. There was no abdominal organomegaly or evidence of by JOAN LLEVADOT MD on March 9. the blood pressure 80/60 mm Hg. a prolonged QT interval. the patient appeared chronically ill and in mild respiratory distress. The serum sodium level was 129 mmol per liter. The arms and legs were cool.8 to 1. 1). Car- diogenic shock may be caused by an acute fulminant process or decompensation of a subacute or chronic cardiomyopathy. Despite the absence of a pericardial knock.000 per cubic millimeter. this constellation of findings could also be consistent with constrictive pericardial disease. and diffuse T-wave flattening (Fig. The current presentation. suggest a subacute or chronic cardiomyopathy. All rights reserved. The Figure 1. 1017 . troponin I was  march 5. The rales. low voltage in the limb leads.4 mmol per liter (13.10  nejm. requires consideration of conditions that can lead to both cardiac and skeletal myopathy. the potassium level 3. the blood urea nitrogen level 10 mg per deciliter (3. The first priority is to stabilize the patient. The erythrocyte sedimentation rate was 8 mm per hour. Rales were noted halfway up the lung fields bilaterally. and elevated jugular venous pressure indicate severe left ventricular dysfunction with volume overload. 2009 EMail Line 4-C SIZE Enon ARTIST: mst H/T H/T FILL 33p9 Combo Downloaded from www. poor R-wave progression across the precordial leads.clinical problem-solving tinued suggests an alternative cause. The initial 12lead electrocardiogram (ECG) showed sinus rhythm.3 mg per deciliter). 2009 . Please check carefully. poor R-wave progression across the precordial leads. and the platelet count 150. The heart sounds were distant.0 g per deciliter. Elements of the presentation. suggestive of heart failure. On examination. accompanied by a soft S3 gallop but no murmurs or rubs. which is a type of cardiogenic shock. The constellation of hypotension. The jugular venous pressure was 14 cm of water. The temperature was 36°C. and the alanine aminotransferase level 61 U per liter (normal range. The white-cell count was 6800 per cubic millimeter with a normal differential count.2 mg per deciliter [71 to 106 µmol per liter]). including a minimal oxygen requirement and profound edema. with 1+ peripheral pulses and 3+ pitting edema in the legs to the level of the knee bilaterally. narrow pulse pressure. and the respiratory rate 22 breaths per minute. Figure has been redrawn and type has been reset. and diffuse T-wave flattening. and cool extremities is consistent with what has been described as the “cold and wet” classification of acute heart failure. The initial 12-lead electrocardiogram was notable for low voltage in the limb leads.nejm. the aspartate aminotransferase level 109 U per liter. 7 to 52). Copyright © 2009 Massachusetts Medical AUTHOR.

I would favor performing cardiac catheterization. dilated left ventricle with JOB: an ejection 15% (Fig. diuretics. Chest Radiograph. The initial transthoracic echocardiogram revealed biventricular enlargement. The patient’s elevated creatine kinase level and normal creatine kinase MB and troponin levels (as well as a disproportionate rise in aspartate aminotransferase as compared with alanine aminotransferase) are features that continue to suggest a skeletal myopathy. with left ventricular end-diastolic and SIZE Enon ARTIST: mst measuring H/T H/T end-systolic diameters 59 mm and 46 mm. immunosuppression). severely depressed systolic RETAKE 1st Giugliano AUTHOR ICM with function an estimated ejection fraction of 15%. The presenting chest radiograph was notable for cardiomegaly with a globular cardiopericardial silhouette. AUTHOR. pulmonary edema.nejm. LV left ventricle. 2009 . Please check carefully. familial and genetic causes. The patient underwent cardiac catheterization. Figure 3. during which the hemodynamic profile can be further characterized and mechanical ventricular support may be initiated. and endocrine causes. 2). RETAKE 1st AUTHOR Giugliano ICM REG F CASE EMail B PE LV RV FIGURE TITLE 2 Revised 2nd 3rd Line 4-C chest radiograph revealed cardiomegaly with SIZE pulEnon ARTIST: mst H/T H/T monary effusions FILL edema and bilateral Combo pleural 16p6 (Fig. and tachycardia-induced cardiomyopathy. infectious and inflammatory processes. ventricle. FILL Combo 16p6 respectively. been reset. ISSUE: RA LA The presence of hyponatremia and pleural effusions further suggests that the patient’s cardiomyopathy reflects a subacute process rather than an acute fulminant process. LA denotes left atrium. PLEASE NOTE: Figure effusion. The broad differential diagnosis for a dilated cardiomyopathy includes ischemic heart disease. This distinction is helpful. and bilateral pleural effusions. Right heart catheterization revealed a 1018 n engl j med 360. Aggressive treatment with inotropes. metabolic. Angiography revealed normal epicardial coronary arteries. Copyright © 2009 Massachusetts Medical Society. 2nd REG F FIGURE 3 a&b effusion. The apical fourand a moderate pericardial 3rd CASE TITLE chamber views are shown in diastole (Panel A) and Revised EMail Line 4-C systole (Panel B). JOB: 36010 ISSUE: 3-5-09 and vasodilators is warranted. it is not unreasonable to perform coronary angiography.  march 5. whereas a subacute process is more likely to respond to aggressive medical therapy. RA right NOTE: atrium. All rights reserved. particularly if we suspect a fulminant process or a cause that might require specific therapy ( by JOAN LLEVADOT MD on March 9. and a globally hypokinetic. as confirmed by the echocardiogram. pericardial no valvular Please check carefully. 36010 fraction of 10 to 3-5-09 3).. An echocardiogram revealed a moderate AUTHOR. 2009 Downloaded from www.The n e w e ng l a n d j o u r na l of m e dic i n e A PE LV RV RA LA Figure 2. . Endomyocardial biopsy can be helpful in a newly diagnosed cardiomyopathy. has been redrawn and type has abnormalities. Despite the absence of regional wallmotion abnormalities on the echocardiogram. Initial Transthoracic Echocardiogram.10  nejm. and RV right Figure has been redrawn and type has been reset. The low voltages on ECG in combination with a delayed transition point across the precordial leads suggest a dilated cardiomyopathy with apical displacement. since an acute fulminant process may require placement of a ventricular assist device and prompt evaluation for possible cardiac transplantation.g. PLEASE PE pericardial effusion.

and insulin-like growth factor I (IGF-I) below 25 ng per milliliter (normal range.2 pmol per liter]). This differential diagnosis includes inflammatory myopathies. Copyright © 2009 Massachusetts Medical Society. cytomegalovirus. gonadotrophic. further endocrinologic evaluation was undertaken. infiltrative disease.5 mU per milliliter (normal range.nejm. Because the patient continued to require inotropic and mechanical support. Since inflammatory and infectious myopathies and endocrinopathies remain in the differential diagnosis. These findings raise concern for central hypothyroidism.2). and coxsackievirus were all negative. 7 to 69 pg per milliliter [1. As the patient is being medically stabilized.3 to 23. the serum free thyroxine level was low at 0. 2009 . The next step in the evaluation should include further assessment of hypothalamic–pituitary function with tests of the adrenal. Reduction of afterload and augmentation of cardiac output can be achieved with placement of an intraaortic balloon pump and inotropic support. which can occur from destruction of the pituitary or hypothalamus by tumor. echovirus. and iron studies.6). Electromyography and nerve-conduction studies were unremarkable. 1.9 mIU per milliliter (normal range.9 ng per milliliter (normal range. coxsackievirus.3 ng per deciliter (3. The level of follicle-stimulating hormone (FSH) was 0.7 to 8. The age at onset lessens the likelihood of dystrophies. cytomegalovirus. Serologic tests for HIV. infarction. An evening serum cortisol level was 3. a pulmonary-artery pressure of 40/28 mm Hg.6 to 13. luteinizing hormone 0. Lyme disease. and somatotrophic axes.21 mIU per liter. . testosterone undetectable (normal range. and the serum total triiodothyronine was undetectable (normal range. hepatitis A.1). consistent with the examination findings of leftsided heart failure and cardiogenic shock. given his elevated creatine kinase level.4 pmol per liter) (normal range.clinical problem-solving right atrial pressure of 15 mm Hg. A morning corticotropin level was below 2 pg per milliliter (0. B.9 pmol per liter) (normal range. or trauma. Serum protein electrophoresis with immunofixation was normal.6 µg per deciliter (99 nmol per liter) and increased to  march 5. The right heart catheterization reveals elevated filling pressures and compromised forward flow. 0. although hemochromatosis is not likely given the unremarkable family history. and there is no reported history of alcohol or illicit-drug use. Epstein–Barr virus. and Lyme disease). However. by JOAN LLEVADOT MD on March 9. and metabolic myopathies (particularly disorders of fatty acid metabolism). 2009 1019 Downloaded from www. An ANA test was negative. Ventricular ectopy and tachyarrhythmias are common in this context and often respond to amiodarone or lidocaine.8 to 1. as were iron studies. Magnetic resonance imaging of the brain revealed n engl j med 360. The patient had several episodes of polymorphic and monomorphic ventricular tachycardia that required multiple cardioversions. 1800 to 6650 pg per milliliter [6 to 23 nmol per liter]). However. All rights reserved. An intraaortic balloon pump was placed and dobutamine and dopamine were started for inotropic support. serum and urine protein electrophoresis to assess for AL amyloidosis. drug-induced myopathies. 70 to 170 ng per deciliter [1 to 3 nmol per liter]).8 liters per minute per square meter of body-surface area.10  nejm. prolactin 0. I would repeat an ANA test and thyroid-function studies and also order viral studies. The result of a repeat thyrotropin test was low at 0. and C viruses. Distinguishing between these diagnostic possibilities may be difficult in acutely ill patients. ongoing investigations of the underlying disease process should continue to focus on possible causes of both his clinically evident cardiomyopathy and a skeletal myopathy. and a cardiac index of 1. the patient’s history of traumatic brain injury (a recognized cause of hypothalamic–pituitary dysfunction) increases my suspicion for central hypothyroidism. as well as muscular dystrophies and endocrinopathies.2 pmol per liter]).5 µg per deciliter (262 nmol per liter) 60 minutes after the administration of 250 µg of cosyntropin. a right ventricular pressure of 43/14 mm Hg.5 to 15.1 to 12. a mean wedge pressure of 32 mm Hg. transient depression of the hypothalamic–pituitary–thyroid axis in nonthyroidal illness (formerly called euthyroid sick syndrome) is characterized by a similar laboratory profile. infectious myopathies (including those caused by human immunodeficiency virus [HIV]. 3.8 ng per deciliter [10. 88 to 474). a diagnosis that could explain many features of his clinical presentation. The laboratory evaluation is most remarkable for the low thyrotropin level accompanied by low free thyroxine and triiodothyronine levels.

routine ative testing with arginine plus growth hormone– screening for disorders of the hypothalamic–pituitary axis is recommended initially and then 3 to releasing hormone. quence of traumatic brain injury. and loss of pubic hair during the preceding 3  march 5.3 Therefore. he reported decreased sexual drive.The n e w e ng l a n d j o u r na l of m e dic i n e The patient’s hemodynamic status stabilized once thyroid. 2009 . the clinical presentation and laboratory tricular arrhythmias.7 µg per kilogram of the context of a dilated cardiomyopathy and a hisbody weight) once he appeared euvolemic. intravenously every 8 hours) and levothyroxine (100 µg daily).nejm.tance of the patient’s history with respect to the rhythmias despite treatment with amiodarone current presentation. luteinizing hormone. .2 the developAfter his discharge. The continued presence of malignant ventricular arrhythmias necessitating the placement of an implantable cardioverter–defibrillator before hospital discharge was not unexpected. dry skin and hair loss involving the lateral eyebrows and the legs. His echocarin the context of previous head trauma and other diogram showed a left ventricular ejection fraction pituitary deficiencies is strongly suggestive of ac. Copyright © 2009 Massachusetts Medical Society. He remains asymptomatic and duced by traumatic brain injury.tory of an elevated creatine kinase level suggesment with testosterone (7. and testosterone levels.1 the unifying diagnosis cal improvement.10  nejm. Growth hormone supplementation was reasonably withheld while the patient was acutely ill in the hospital but was initiated once growth hormone deficiency was confirmed in the outpatient setting. nal insufficiency. the patient was followed clini. All rights reserved. impotence.5 g daily of a topical tes.approximately 25% of cases. Growth hormone ing possible common causes of both cardiac and was not initially administered because of his clini. is consistent with secondary adre. Taken Serial Holter monitoring showed no further ventogether.and he had normal creatine kinase.basal skull fracture. his ejection fraction had further improved to 64% (Fig. On reviewtosterone gel) was also initiated. and androgen therapy was initiated.charge. cholesterol. and IGF-I levels can be de. Although FSH. which highlights the imporcurrent episodes of nonsustained ventricular ar. the patient’s pressed in patients with critical illness (just as the symptoms of heart failure had completely resolved results of thyroid tests can be depressed). together with should continue to have close follow-up including the inadequate cortisol response to exogenous both laboratory testing and echocardiographic corticotropin. In addition. At 20 months after disdata are consistent with panhypopituitarism in. glucocorticoid. he was determined to be multiple hormonal deficienwas successfully weaned from the intraaortic bal. postsurgical findings consistent with the patient’s previous partial bifrontal craniotomies and a partially empty sella.peripheral myopathies. The patient The low baseline corticotropin level.evaluation to monitor his response to therapy. He was also noted to have coarse. 2009 Downloaded from www. made more apparent after improvement of superimposed pitting edema. Although panhypopituitarism is a rare conseand ongoing hormone supplementation.tive of a peripheral skeletal myopathy. initially intravenously to avoid possible impaired oral absorption in the context of C om men ta r y mucosal edema.cies arising from panhypopituitarism caused by a loon pump and inotropic supports. since normalization of left ventricular function in such cases may take several months.Within 9 months after discharge. clinically well on a multiple-hormone–replaceThe patient was started on hydrocortisone (100 mg ment regimen. tory of sexual dysfunction and loss of pubic hair free by JOAN LLEVADOT MD on March 9. his regimen was changed to prednisone (5 mg orally daily) and levothyroxine (125 µg Our patient presented with cardiogenic shock in orally daily. serial physical examinations during the initial course of diuresis revealed the presence of nonpitting edema. Because of re. quired hypogonadotrophic hypogonadism. On further questioning. an implantable cardioverter–defibrillator was placed. Treat.ment of at least one neuroendocrine disorder after cally and with serial injury serious enough to cause temporary or mentation with growth hormone was begun once permanent neurologic dysfunction is reported in the deficiency was confirmed by means of provoc. the his. Supple. 4). 1020 n engl j med 360. testosterone. equivalent to 1.of 52% with normal ventricular cavity dimensions. Over the course of 2 weeks.

severe cardiomyopathy as a clinical consequence is even rarer. A follow-up transthoracic echocardiogram revealed markedly improved systolic function with an estimated RETAKE 1st Giugliano AUTHOR ICM fraction ejection of 64%.clinical problem-solving A RV LV RA LA B RV LV RA LA Figure 4. replacement therapy typically leads to rapid clinical improvement. appropri- n engl j med 360. including 3-5-09 age or ISSUE: older basal skull fracture. primarily through the effects of IGF-I. including torsades de pointes. Although growth hormone deficiency rarely leads to severe cardiomyopathy. TITLE (Panel with left ventricular end-diastolicRevised and endEMail Line 4-C systolic diameters measuring 46 mm and 27 mm. Nevertheless. deficiency of thyroid4. 6 months after the injury. Follow-up Transthoracic Echocardiogram.3 Because the thyrotropin level may be in the normal range in patients with central hypothyroidism. active form of thyroid hormone. because of the potential for reversibility. in rare cases. and the transcription of various contractile proteins. adrenal insufficiency has been  march 5. and stimulate calcium–calmodulin–dependent protein kinase II in cardiac sarcoplasmic reticulum. stroke volume. LA denotes LV left ventricle. particularly for persons with JOB: higher-risk 36010 features.10  nejm.11 As with our patient. Accordingly. betaadrenergic–receptor function. to cause a reversible dilated cardiomyopathy. H/T H/T spectively. replacement therapy in such patients is associated with increased left ventricular mass.6 Physiologic growth hormone levels are also required to maintain normal cardiac function and structure. glucocorticoids have been shown to augment cardiac myocyte contraction and relaxation. 2009 . androgen levels are inversely related to the severity of heart failure and to mortality. testosterone replacement in patients who have at least moderately severe left ventricular dysfunction is associated with improved functional capacity. rather than frank cardiovascular collapse. enters cardiomyocyte nuclei and modulates calcium flux. Marked deficiencies of gonadal7 and growth8 hormones may also adversely affect cardiovascular function and contribute to heart failure.13 Testosterone deficiency is common among patients with long-standing heart failure14.7 perhaps accounted for by the antiinflammatory or vasodilatory effects of testosterone. 2009 1021 Downloaded from www. Although panhypopituitarism is uncommon. a serum thyroxine level must be measured when screening for this condition. as this case illustrates. RA FILL Combo 16p6 right atrium. and RV right ventricle. Copyright © 2009 Massachusetts Medical Society. reSIZE Enon ARTIST: mst left atrium. Patients with secondary adrenal insufficiency usually present with fatigue and orthostatic hypotension. and increased systemic vascular resistance. decreased cardiac output. severe hypothyroidism is associated with ventricular dysrhythmias. However.12 Moreover. hypothyroidism is associated with depressed chronotropy. and contractility in addition to improved endothelial function and diminished systemic vascular by JOAN LLEVADOT MD on March 9. . the AUTHOR. Fortunately. Thyroid hormone has widespread effects on cardiovascular function9: triiodothyronine. PLEASE NOTE: Figure has been redrawn and type has been reset.5 In this case.4.5 or adrenal6 hormone.8 Patients with growth hormone deficiency tend to have at least subtle abnormalities in left ventricular mass and function8.10 In addition. hypothyroidism was also associated with dyslipidemia and peripheral myopathy that likewise resolved with thyroid hormone–replacement therapy. thyroid hormone supplementation in hypothyroid-associated cardiomyopathy typically results in recovery of myocardial function. in such patients. should always be considered in a patient with an unexplained cardiomyopathy.nejm. or both. The apical four-chamber REGare F shown 4 a&b (Panel A) and systole 2nd FIGUREin diastole views 3rd CASEB). increase calcium ATPase activity. All rights reserved. Please check carefully.15 Furthermore.14.

often by appreciating that what is past is prologue.4. Baughman KL. 51:319-23. Schenck JB. Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism. 6. Circulation 1997. West JN. Circulation 2006.152:679-91.10  nejm.108:2648-52.89:5251-5.344:501-9. et al. Lin T.114: 1829-37. Galbraith AJ. Phillips J. Jankowska EA. Ann Intern Med 1992. Meyers DE. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Xu A. Kawazoe N. Eaton RP. Bondanelli M.117:1014-5. therefore. . Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Ladenson PW. Chua TP. 14. Osborn LA. No other potential conflict of interest relevant to this article was reported. Chanson P. relies largely on making the correct diagnosis. Myxedema-associated cardiogenic shock treated with intravenous triiodothyronine.5 The overall outcome. Sherman SI.89:8856.] 11.clinical problem-solving ate treatment of even a severe cardiomyopathy due to the deficiency of one or more hormones carries a good prognosis. 4. Pugh PJ.24:110-4. 27:57-64. MacKerrow SD. Ojamaa K.281:H325-H333.79:753-9. Circulation 2008. Atlas of heart diseases.117(3):e18. Copyright © 2009 Massachusetts Medical  march 5. This regular feature considers the step-by-step process of clinical decision making. J Heart Lung Transplant 2005. Agha A. Proc Natl Acad Sci U S A 1992. 9. J Neurol Neurosurg Psychiatry 2008. Maddicks-Law J. ed. 7. Circulation 2007. Adult reversible cardiomyopathy with pituitary adrenal insufficiency caused by empty sella — a case report. Rao MK. 2009 . Cuneo RC. 3. Economou P. Klein I. Klein I. [Erratum. Sakamoto A. Ponikowski P. De Marinis L. Am J Physiol Heart Circ Physiol 2001.] 5. 10. and Schering-Plough. Angiology 2000. Giugliano reports receiving grant support from ScheringPlough and Merck. Malkin CJ. Eur Heart J 2006. Eur J Endocrinol 2005. Ray PE. 12. Rizvi AA. Severe primary hypothyroidism manifesting with torsades de pointes. We thank Dr. Feldman AM. Anker SD. Majda J. Gluco- corticoid modulation of protein phosphorylation and sarcoplasmic reticulum function in rat myocardium. 1022 n engl j med 360. Neuroendocrine disorders after traumatic brain injury. myocarditis and pericardial disease. please see authors. Ambrosio MR. Abelmann WH. Seaton DM. Hypopituitarism after traumatic brain injury. Onoyama K. Brian Won-Sik Kim for his assistance with the preparation and review of the manuscript. Koga T. Levy H. and consulting and lecture fees from Pfizer. Cardiomyopathies. All rights reserved. In: Abelmann WH. Dr. Zatelli MC.116:1725-35. 8. Narayanan N. van Beek EJ. Copyright © 2009 Massachusetts Medical Society. Am J Med Sci 2006. Cardiac effects of growth hormone in adults with growth hormone deficiency: a meta-analysis. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Biel B. 2009 Downloaded from www. For more information.96:526-34. Merck. degli Uberti EC. Sadoshima S. References 1. Thompson CJ. Eto by JOAN LLEVADOT MD on March 9. Danzi S. Behan LA. Philadelphia: Current Medicine.NEJM.nejm. Thyroid hormone and the cardiovascular system. [Erratum. 1995:1. Proc Natl Acad Sci U S A 1992. N Engl J Med 2001. 15. Jones TH. 2. Maison P. Circulation 2003. Thyroid disease and the heart. 13. 331:154-6. et al. CLINICAL PROBLEM-SOLVING SERIES The Journal welcomes submissions of manuscripts for the Clinical Problem-Solving series. The role of growth hormone replacement in a growth hormone deficient patient with underlying cardiomyopathy and severe congestive heart failure. Channer KS.