eMedicine Specialties > Pediatrics: General Medicine > Oncology

Adrenal Carcinoma

Updated: Nov 26, 2008

Introduction

Background

Adrenocortical carcinoma is a rare tumor in the pediatric population (0-21 y). In a study of the incidence of functioning adrenal tumors in patients aged 4-20 years, 59 were identified at a single referral institution over a period of years. Only 2 of these patients had adrenocortical carcinoma. The authors underreported the overall incidence of adrenocortical carcinoma because 20-40% of patients present with a palpable mass and no symptoms of adrenal hormone hypersecretion. Because of the relative rarity of these tumors, little is known about their cause and the influence of genetic factors, although adrenocortical carcinomas are associated with numerous constitutional syndromes, including Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Carney complex, multiple endocrine neoplasia 1, and hemihypertrophy syndrome.

Data have suggested an increased incidence in female individuals, especially at age 0-3 years or after age 13 years. No racial predominance for this diagnosis has been established; however, in southern Brazil, the incidence of adrenal tumors is 10-15 times that of the general population. This incidence is associated with a mutation in the P53 gene. Based on data from the International Pediatric Adrenocortical Tumor Registry, the median age when children develop adrenal carcinomas is 3.2 years; 60% are younger than 4 years, and 14% are older than 13 years.¹

Mortality/Morbidity

The prognosis of patients with adrenocortical carcinoma is always guarded. Cures were reported in patients who underwent complete removal of a small (<9 cm, <200 g) encapsulated tumors. Reports of remission of metastatic disease are only anecdotal. Aggressive surgical and medical treatments have prolonged mean survival times by approximately 18 months and, occasionally, by longer than 48 months. Studies of aggressive surgical and early adjuvant therapy are limited by the rarity of this illness in childhood.

Race

No racial predilection has been identified.

Sex

As data accumulate, especially in international registries, the incidence of adrenal tumors in female individuals has risen higher than previously thought.

Age

Adrenocortical carcinoma is a rare tumor among individuals aged 0-21 years.

Clinical

History

Children with adrenal tumors often present with a history of adrenocortical hormone production. Virilization due to increased androgen production is most common, whereas cushingoid features are relatively uncommon.
In most cases, the patient’s history includes elements of adrenocortical hormone production and a palpable mass. The presence of both findings raises the likelihood of adrenocortical carcinoma because most functioning adrenal tumors with a palpable mass are carcinomas rather than adenomas.
Approximately 20-40% of patients with adrenocortical carcinoma present without any history of adrenocortical hormone overproduction.

Physical

Physical findings almost always include a palpable mass in the abdomen that usually involves the center of the abdomen rather than the flanks. The mass is hard and nonmovable.
Approximately 50-80% of children with adrenocortical carcinoma present with virilization.
- Findings in males include premature puberty with enlargement of the penis and scrotum, pubic hair, acne, and deepening voice.
- Findings in females include premature appearance of pubic and axillary hair, clitoral hypertrophy, acne, deepening voice, premature increase in growth velocity, lack of appropriate breast development, and lack of menarche.
Signs of Cushing syndrome are present in about 10% of affected children. These signs include a round face, a double chin, buffalo-hump fat distribution, generalized obesity, failure of growth velocity, and hypertension.
In rare cases, feminization may occur.
- Findings in male patients include gynecomastia and hypertension.
- Findings in female patients include precocious sexual development and hypertension.

Causes

When patients present with adrenocortical hormone overproduction, the differential diagnosis usually includes carcinoma, adenoma, and hypothalamic pituitary error.
The patient's history and physical findings often indicate functioning or nonfunctioning neuroblastoma, especially in young children.
For patients who present with only a palpable mass, the differential diagnoses vary with age, and the range is broad.
In children younger than 5 years, neuroblastoma and Wilms tumor are the most likely malignant diagnoses. In older patients, lymphoma, germ cell tumors, sarcoma, undifferentiated tumors, and neuroblastoma are possible.

Workup

Laboratory Studies

Laboratory studies of adrenocortical carcinoma include determinations of serum glucose, serum cortisol, serum adrenal androgen, urine adrenal hormone, urine vanillylmandelic acid (VMA), and urine homovanillic acid (HVA) levels.
Laboratory studies enable the physician to distinguish between functioning and nonfunctioning adrenal neoplasms. The results may also help in distinguishing between a neoplasm of the adrenal cortex and a neuroblastoma. Adrenocortical tumors should not be confused with adrenal medullary tumors, also known as pheochromocytomas, which secrete catecholamines, similar to neuroblastomas.

Imaging Studies

Imaging studies are the best nonoperative methods to predict which adrenal tumors are affecting the patient.
Abdominal and retroperitoneal ultrasonography is usually followed with abdominal CT and MRI.
Chest CT should also be performed when metastatic disease is present. Affected lung parenchyma strongly suggests an adrenocortical carcinoma over a neuroblastoma.
Bone scanning should also be performed to detect metastatic disease. However, the presence of bone disease does not allow for the differential diagnosis of malignancies.
In a recent comparison of imaging findings in pediatric patients with adrenal carcinoma, carcinoma was highly suspected when adrenal lesions had a thin tumoral capsule, a stellate zone of central necrosis, and evidence of the production of adrenocortical hormone. Surgical biopsy or removal should be performed following definitive imaging (see Surgical Care ).

Histologic Findings

Histologic findings include numerous mitoses, scant cytoplasm, and none of the rosettes observed in neuroblastoma.
The histologic features are characteristic and usually not confused with those of neuroblastoma.
Differentiation of adenoma and adenocarcinoma may be difficult. In addition, standard histopathologic staging scales (eg, the Weiss scale) may not be effective in predicting outcome in pediatric adrenocortical tumors.

Staging

Staging for adrenocortical carcinoma follows the stage I-IV pattern for most solid tumors.
Stages are defined as follows:
- Stage I is an encapsulated tumor of less than 5 cm that is completely removed.
- Stage II is a tumor of more than 5 cm that is completely removed.
- Stage III is a tumor associated with local invasion or with positive lymph nodes but no distant metastasis.
- Stage IV is a solid tumor with local invasion and positive lymph nodes or metastasis to the liver, lung, or bone.
Given the key role of resectability in prognostication and given the lack of consistent efficacy with adjuvant chemotherapy, current staging may best be divided as stage I and II (resectable lesions) and stage III and IV for (unresectable lesions).

Treatment

Medical Care

Medical care in patients with adrenal carcinomas is supportive or adjuvant to surgical resection.

Chemotherapy is as follows:
- When metastatic disease cannot be removed or when biochemical evidence of tumor secretion persists after surgical removal, chemotherapy is often considered. At present, no data suggest that chemotherapy can fulfill a truly adjuvant role that improves patient survival and prevents relapse after incomplete or total resection.
- Anecdotal data suggest that at least 2 drugs have single-agent activity that may prolong survival. If these drugs are thoroughly studied, they may ultimately demonstrate the possibility of having an adjuvant role. The 2 drugs are mitotane (trivial name, o,p’-DDD; trade name, Lysodren) and cisplatin (trivial name, CDDP; trade name, Platinol). Researchers have long known that mitotane dramatically decreases the production of adrenocortical hormone and ultimately ablates the adrenal cortex. As a single agent, cisplatin can shrink metastatic disease. In recent studies, etoposide and doxorubicin were added to cisplatin and mitotane.
- Mitotane and cisplatin are most commonly used for palliation. Mitotane is used to decrease residual cortical hormonal production, and cisplatin is used to shrink metastases in the lung and elsewhere to prolong survival after the disease becomes unresectable.
- Small studies have been conducted to examine etoposide and platinum or etoposide, doxorubicin, and platinum for adjuvant use.
- Although no program of conventional chemotherapy appears curative in metastatic adrenal carcinoma, prolonged survival has been seen with the use of mitotane and other chemotherapy drugs and surgery.²
Radiation therapy may be helpful in the palliation of unresectable disease that is unresponsive to medical therapy.
An anecdotal case of successful autologous transplantation, chemotherapy, and surgically reduced disease in a young child was reported, with 2-year follow up.³

Surgical Care

Treatment of adrenocortical carcinoma begins with surgical care. Surgery is the mainstay of treatment and currently appears to be the major hope for cure. Every reasonable attempt should be made to render the patient disease-free at the primary site, at sites of local invasion, and at sites of metastatic disease.
In the author’s experience, aggressive surgical care led to survival for longer than 10 years in 2 patients, one of whom was concurrently treated with medical therapy. This patient had a large, bulky tumor with no local invasion; the other patient had a stage II tumor and underwent several follow-up thoracotomy procedures.
Case reports indicate that repeated thoracotomy can allow for more than 10 years of high-quality survival despite recurring crops of metastatic disease. In a study at Memorial Sloan-Kettering Cancer center, investigators evaluated patients with adrenocortical carcinoma.⁴ Aggressive primary surgical removal and aggressive surgical treatment of local or distant relapse led to long-term survival rates far superior to reported in previous studies, regardless of the patients' ages. One important feature of this study was that patients who underwent a complete second resection had a median survival of 74 months (5-y survival rate, 57%). The current role of surgical resection in the treatment of adrenocortical carcinoma cannot be overemphasized.
Patients with symptoms of hormone overproduction and biochemical evidence of adrenocortical hormone overproduction should be supported in the postoperative period after major resection. These patients have suppressed endogenous adrenocortical hormone production. Stress doses of hydrocortisone that ultimately lead to maintenance doses and tapering (should the patient not be given further therapy) are indicated.

Consultations

Optimal care of pediatric patients with adrenocortical carcinoma includes consultation with a pediatric surgeon who has extensive experience in cancer surgery and consultation with a pediatric oncologist who may have managed cases of adrenocortical carcinoma.

Medication

Adjuvant or palliative treatment has been studied by using mitotane, cisplatin, etoposide, and doxorubicin. Mitotane leads to autodestruction of the adrenal cortex. Therefore, it is used in almost all protocols in the hope that it will decrease any autonomous hormone production and suppress tumor growth. Chemotherapy has focused on 3 antineoplastics given alone or in combination: cisplatin, etoposide, and doxorubicin. Studies have focused on etoposide and cisplatin or etoposide, doxorubicin, and cisplatin.

Antineoplastic agents

Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (phase G1), followed by DNA synthesis (phase S). The next phase is a premitotic phase (phase G2). Finally, a period of mitotic cell division (phase M) occurs.

Rates of cell division vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the rate may decrease if tumors are large. This difference allows healthy cells to recover from chemotherapy more quickly than do malignant cells, and this is the rationale for current cyclic dosage schedules.

Antineoplastic agents interfere with cell reproduction. Some agents are specific to certain phases of the cell cycle, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis (ie, programmed cell death) is another potential mechanism of many antineoplastic agents.

Mitotane (Lysodren)

Decreases production of cortisol by causing adrenal atrophy and affecting mitochondria in adrenocortical cells. No pediatric standards or dosages established, and doses in children must be individualized.

Dosing

Adult

Pediatric

500 mg PO qid initially; may increase to 10 g/m²/d

Interactions

CNS depressants may increase toxicity; may increase metabolism of warfarin, decreasing levels; spironolactone may decrease effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

GI toxicity (eg, anorexia, nausea, vomiting, diarrhea), neurotoxicity (eg, lethargy, somnolence, dizziness, vertigo, depression), or dermatologic toxicity (eg, evanescent papular erythematous rash) may limit dose escalation; dose escalation may precede toxicity; blood levels of mitotane associated with response as opposed to PO dose; clinical response may not occur for up to 3 mo at maximum tolerated dose; exogenous administration of adrenocortical hormones (hydrocortisone and/or fludrocortisone) required

Cisplatin (Platinol)

Inhibits DNA synthesis and, therefore, cell proliferation by causing DNA crosslinking and denaturation of double helix.

Dosing

Adult

Pediatric

<10 kg: 2.5-3.3 mg/kg IV q3wk
>10 kg: 75-100 mg/m² IV q3wk

Interactions

Increases toxicity of bleomycin and ethacrynic acid

Contraindications

Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Administer only under care of experienced pediatric oncologist using conventional procedures to prevent ototoxicity and nephrotoxicity; in addition to usual monitoring with intensive chemotherapy, observe and treat renal tubular defects, renal loss of electrolytes (eg, magnesium, potassium), renal insufficiency, ototoxicity, myelosuppression, and neurotoxicity; adequately hydrate before and 24 h after dosing to reduce risk of nephrotoxicity

Doxorubicin (Adriamycin)

Cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius. Blocks DNA and RNA synthesis by inserting between adjacent base pairs and binding to sugar-phosphate backbone of DNA, inhibiting DNA polymerase. Binds to nucleic acids presumably by specific intercalation of anthracycline nucleus with DNA double helix. Can also cause DNA strand breakage because of effects on topoisomerase II.
Powerful iron chelator. Iron-doxorubicin complex induces production of free radicals that can destroy DNA and cancer cells.
Maximum toxicity during S phase of cell cycle.
Has multiphasic disappearance curve, with half-lives up to 30 h. Does not cross blood-brain barrier but taken up rapidly by heart, lungs, liver, kidney, and spleen.
Both mutagenic and carcinogenic. Dosage related to body surface area.
Antiproliferative drugs may be useful for patients with diffuse metastases to palliate symptoms.
Liposomes in different drug products can vary in chemical and physical properties, which can substantially affect functional properties.

Dosing

Adult

Pediatric

<10 kg: 0.6-1.5 mg/kg IV q3wk
>10 kg: 20-45 mg/m² IV q3wk

Interactions

May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity

Contraindications

Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function, preexisting myelosuppression; previous complete cumulative doses of doxorubicin, daunorubicin, idarubicin, or other anthracyclines and anthracenes

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function

Etoposide (Toposar, VePesid)

Glycosidic derivative of podophyllotoxin that exerts cytotoxic effect by stabilizing normally transient covalent intermediates formed between DNA substrate and topoisomerase II. Leads to single-strand and double-strand DNA breaks that arrest cellular proliferation in late S or early G2 phase of cell cycle.

Dosing

Adult

Pediatric

<10 kg: 3.3 mg/kg/d IV for 3 d q3wk
>10 kg: 100 mg/m²/d IV for 3 d q3wk

Interactions

May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells

Contraindications

Documented hypersensitivity; clinically significant hypotension

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

IT administration may cause death; bleeding and severe myelosuppression; withhold or suspend therapy if platelet count <50,000 or if absolute neutrophil count <500/μL; reduce dose by 20% if patient has granulocytic fever or had previous radiation therapy; reduce dose in hepatic impairment (increased total bilirubin) or renal impairment (decreased creatinine clearance)

Follow-up

Further Inpatient Care

Patients with adrenal carcinomas who undergo complete surgical resection with no evidence of continuing functional hormone production do not require further inpatient care.
If the patient has evidence of local or distant metastases during ambulatory follow-up, aggressive attempts at repeat resection should be undertaken. These attempts leads to additional inpatient care.
If treatment includes intensive chemotherapy, further inpatient care is necessary to deliver chemotherapy or to treat chemotherapy-related toxicity.
If lesions seem particularly sensitive to chemotherapy, with dramatic diminishment of tumoral masses in the chest or elsewhere, autologous transplantation might be a consideration. However, only anecdotal data suggest that transplantation is helpful in managing this disease. One study reported the use of chemotherapy, surgical debulking of lung metastases, and autologous transplantation; 2 years of continuous complete remission was reported.³

Further Outpatient Care

Ambulatory follow-up should occur every month for the first 2 years after treatment because repeat resection of locally recurring disease and resection of metastatic lung disease can substantially affect long-term survival.
Scanning of the local area in the abdomen or pelvis and of sites of metastatic disease should continue every 3 months for the first 2 years, every 4 months for the next 2 years, and every 6 months during the fifth year.
Patients should be monitored for the reappearance of adrenocortical hormone hyperactivity, along with scanning, unless their history suggests that Cushing syndrome or autonomous adrenocortical hormonal production is present. If this is the case, the physician should immediately search for recurrence.

Prognosis

The overall prognosis for patients with adrenal carcinoma is poor.

In a study of pediatric patients with adrenocortical tumors, overall survival was 54.2%.¹ The investigators did not distinguish adenoma from adenocarcinoma because of the difficulty (even with expert review) of separating these diagnoses at early stages. The excellent survival rate of patients with stage I tumors, the group who have adenomas, affects this rate. However, numerous valuable prognostic indicators have emerged; these serve to comfort patients with completely resected disease and suggest experimental or palliative care for those without.
- Stage: By far the most important prognostic variable is the clinical stage. Because adenoma is usually stage I by definition, the observation that stage I survival rates approach 90% because of complete resection is no surprise. However, adenocarcinomas are noted in this group as well, and many investigators believe that a small (<200 g) stage I carcinoma can be associated with a favorable prognosis when it is completely removed without tumor spill. With stage II disease, the survival rate decreases to close to 40%, even with complete resection. Stage III and IV disease result in equally poor survival rates of less than 20%.
- Age: In the aforementioned study, patients younger than 4 years had an event-free survival rate of more than 70%. The event-free survival rate for patients aged 4-12 years decreased to 30-40%.
- Function: Tumors that virilize alone or nonfunctioning tumors improve the prognosis compared with tumors that produce Cushing syndrome due to an overproduction of glucocorticoid.
In a study of 31 patients at the Lahey Clinic over 30 years, mean survival was 17 months (range, 1-205 mo). The 5-year survival rate was 26%.⁵
As surgical procedures for tumor removal improve, patients' prognoses should also improve.
At present, medical therapy has a palliative role. A well-conducted series of clinical trials is needed to prove that adjuvant therapy helps to prolong survival.

Miscellaneous

Medicolegal Pitfalls

In general, children older than 4 years present with retroperitoneal tumors in a bulky or advanced form. This presentation may lead to an inappropriate placement of blame on the primary care physician for not detecting the tumor early, especially if the patient has had nonspecific signs (eg, constipation, mild abdominal pain).
The prognosis of patients with adrenocortical carcinoma is grave even when the tumor is discovered early.

References

Michalkiewicz E, Sandrini R, Figueiredo B, et al. Clinical and outcome characteristics of children with adrenocortical tumors: a report from the International Pediatric Adrenocortical Tumor Registry. J Clin Oncol. Mar 1 2004;22(5):838-45. [Medline].
Hermsen IG, Gelderblom H, Kievit J, Romijn JA, Haak HR. Extremely long survival in six patients despite recurrent and metastatic adrenal carcinoma. Eur J Endocrinol. Jun 2008;158(6):911-9. [Medline].
Hah JO. Intensive chemotherapy with autologous PBSCT for advanced adrenocortical carcinoma in a child. J Pediatr Hematol Oncol. Apr 2008;30(4):332-4. [Medline].
Schulick RD, Brennan MF. Long-term survival after complete resection and repeat resection in patients with adrenocortical carcinoma. Ann Surg Oncol. Dec 1999;6(8):719-26. [Medline].
Tritos NA, Cushing GW, Heatley G, Libertino JA. Clinical features and prognostic factors associated with adrenocortical carcinoma: Lahey Clinic Medical Center experience. Am Surg. Jan 2000;66(1):73-9. [Medline].
Berruti A, Terzolo M, Sperone P, et al. Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer. Sep 2005;12(3):657-66. [Medline].
Bonfig W, Bittmann I, Bechtold S, et al. Virilising adrenocortical tumours in children. Eur J Pediatr. Sep 2003;162(9):623-8. [Medline].
Bukowski RM, Wolfe M, Levine HS, et al. Phase II trial of mitotane and cisplatin in patients with adrenal carcinoma: a Southwest Oncology Group study. J Clin Oncol. Jan 1993;11(1):161-5. [Medline].
Haak HR, Hermans J, van de Velde CJ, et al. Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients. Br J Cancer. May 1994;69(5):947-51. [Medline].
Hovi L, Wikstrom S, Vettenranta K, et al. Adrenocortical carcinoma in children: a role for etoposide and cisplatin adjuvant therapy? Preliminary report. Med Pediatr Oncol. May 2003;40(5):324-6. [Medline].
Lee P, Witchel SS. Disorders of the adrenal gland. In: Burg FD, Polin RA, Ingelfinger JR, et al, eds. Gellis and Kagan's Current Pediatric Therapy. Philadelphia, PA: WB Saunders; 1995:338-41.
Ribeiro J, Ribeiro RC, Fletcher BD. Imaging findings in pediatric adrenocortical carcinoma. Pediatr Radiol. Jan 2000;30(1):45-51. [Medline].
Ribeiro RC, Figueiredo B. Childhood adrenocortical tumours. Eur J Cancer. May 2004;40(8):1117-26. [Medline].
Rodriguez-Galindo C, Figueiredo BC, Zambetti GP, Ribeiro RC. Biology, clinical characteristics, and management of adrenocortical tumors in children. Pediatr Blood Cancer. Sep 2005;45(3):265-73. [Medline].
Sredni ST, Alves VA, Latorre Mdo R, Zerbini MC. Adrenocortical tumours in children and adults: a study of pathological and proliferation features. Pathology. Apr 2003;35(2):130-5. [Medline].
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Keywords

adrenal carcinoma, adrenal cortical carcinoma, adrenocortical carcinoma, adrenal cancer, abdominal mass, adrenal hormone hypersecretion, Li-Fraumeni complex, Cushingoid features, virilization, androgen production, premature puberty, premature pubic hair, acne, tumor, cancer, P53 gene, Beckwith-Wiedemann syndrome, Carney complex, multiple endocrine neoplasia 1, hemihypertrophy syndrome, hypertension, obesity, gynecomastia, precocious sexual development, neuroblastoma, Wilms tumor

Contributor Information and Disclosures

Author

Lawrence C Wolfe, MD, Professor, Department of Pediatrics, Tufts University School of Medicine; Chief of Transfusion Service, Chief, Division of Pediatric Hematology/Oncology, New England Medical Center, Floating Hospital for Infants and Children
Lawrence C Wolfe, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association of Blood Banks, American Society of Hematology, Children's Oncology Group, and Eastern Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida, Clinical Professor, Department of Pediatrics, UNC, Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Timothy P Cripe, MD, PhD, Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center
Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Professor of Clinical Pediatrics, State University of New York at Stony Brook; Director of Children's Sleep Services, Winthrop University Hospital
Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians
Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Department of Oncology, Division of Pediatric Oncology, Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Further Reading