AUTHOR INFORMATION

Section 1 of 10

Authored by Lawrence C Wolfe, MD, Associate Professor, Department of Pediatrics, Associate Professor of Pediatrics Tufts University School of Medicine, Chief, Div of Pediatric Hematology/Oncology, New England Med Center, Floating Hospital for Infants and Children

Lawrence C Wolfe, MD, is a member of the following medical societies: American Academy of Pediatrics, American Association of Blood Banks, American Society of Hematology, and Eastern Society for Pediatric Research

Edited by Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida, Clinical Professor, Department of Pediatrics, UNC, Adjunct Professor, Department of Pediatrics, Duke University; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Timothy P Cripe, MD, PhD, Associate Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center; Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Associate Professor, Department of Clinical Pediatrics, State University of New York at Stony Brook; and Robert J Arceci, MD, PhD, King Fahd Professor, Division of Pediatric Oncology, Johns Hopkins University School of Medicine

Author's Email:	Lawrence C Wolfe, MD
Editor's Email:	Samuel Gross, MD

eMedicine Journal, July 13 2006, VOLUME 7, Number 7

INTRODUCTION

Section 2 of 10

Background: Adrenal cortical carcinoma is a rare tumor in the pediatric population (0-21 y). In a study on the incidence of functioning adrenal tumors in patients aged 4-20 years, 59 children were identified by a single referral institution over a period of years. Only 2 of these patients had adrenal cortical carcinoma. This study underreports the overall incidence of adrenal cortical carcinoma because 20-40% of affected 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 causation and the influence of genetic factors, although adrenal cortical carcinoma has been associated with a number of constitutional syndromes including the Li-Fraumeni complex, Beckwith-Wiedemann syndrome, Carney complex, multiple endocrine neoplasia type I, and hemihypertrophy syndrome.

More recent studies have suggested an increased incidence in females, especially in those aged 0-3 years or older than 13 years. Although no racial predominance for this diagnosis has been established, 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 for children to develop adrenal carcinomas is 3.2 years, with 60% younger than 4 years and 14% older than 13 years.

Mortality/Morbidity: Prognosis of adrenocortical carcinoma is always guarded. Cures have been reported in patients who underwent complete removal of a small (<9 cm, <200 g) encapsulated tumor. Reports of remission of metastatic disease are only anecdotal. More aggressive surgical and medical treatments have led to an expansion of mean survival time of approximately 18 months to, occasionally, longer than 48 months. Studies of aggressive surgical and early adjuvant therapy are limited by the rarity of the illness in childhood.

Race: No racial predilection has been identified.

Sex: As more data is accumulated, especially in international registries, a higher incidence of adrenal tumors in females has been noted.

Age: Adrenal cortical carcinoma is a rare tumor in children (0-21 y).

CLINICAL

Section 3 of 10

History:

• Children with adrenal tumors often present with a history of adrenal cortical hormone production. Virilization from increased androgen production is most common, while Cushingoid features are less common.



• In most cases, the patient’s history includes elements of adrenal cortical hormone production and a palpable mass. The presence of both findings raises the likelihood of adrenal cortical carcinoma because most functioning adrenal tumors with a palpable mass are carcinoma rather than adenoma.



• Approximately 20-40% of patients with adrenal cortical carcinoma present without any history of adrenal cortical hormone overproduction.

Physical:

• Physical examination findings almost always include a palpable mass in the abdomen that usually involves the center of abdomen rather than the flanks. The mass is hard and nonmovable.



• Approximately 50-80% of children with adrenal cortical carcinoma present with virilization. Findings in males include premature puberty with enlargement of the penis and scrotum, pubic hair, development of acne, and deepening voice. Findings in females include premature eruption 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 may be present (around 10% of children), including a rounded face, double chin, buffalo-hump fat distribution, generalized obesity, failure of growth velocity, and hypertension.



• In rare cases, feminization may occur. Findings in males include gynecomastia and hypertension. Findings in females include precocious sexual development and hypertension.

Causes:

• When patients present with adrenal cortical hormone overproduction, the differential diagnoses usually include carcinoma, adenoma, and hypothalamic pituitary error.



• In addition, especially in younger children, the history and physical examination findings often indicate neuroblastoma, either functioning or nonfunctioning.



• For patients presenting with only a palpable mass, the differential diagnoses vary with age and the range is quite 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

Section 4 of 10

Lab Studies:

• Laboratory studies of adrenal cortical carcinoma include serum glucose, serum cortisol, serum adrenal androgens, urine adrenal hormones, urine vanillylmandelic acid (VMA), and urine homovanillic acid (HVA).



• These studies enable the physician to distinguish between functioning and nonfunctioning adrenal neoplasms. They may also help distinguish between a neoplasm of the adrenal cortex and a neuroblastoma. Note that adrenal cortical tumors should not be confused with adrenal medullary tumors, also known as pheochromocytomas, which secrete catecholamines similar to neuroblastomas.

Imaging Studies:

• Imaging studies offer the best nonoperative way to predict which adrenal tumors are affecting the patient.



• Usually, abdominal and retroperitoneal ultrasonography is followed by abdominal CT scanning and MRI.



• Chest CT scanning should also be performed in the presence of metastatic disease. Specifically, affected lung parenchyma strongly incriminates adrenal cortical carcinoma over neuroblastoma.



• A bone scan should also be performed to detect metastatic disease, but the presence of bone disease does not allow discrimination among the malignant differential diagnoses.



• In a recent study comparing imaging study findings in pediatric adrenal carcinoma, carcinoma was highly suspected in adrenal lesions where the tumor capsule was thin, a stellate zone of central necrosis was present, and evidence of adrenal cortical hormonal production existed. At this point in diagnosis, surgical biopsy or removal is the next step (see Surgical Care).

Staging:

• Staging for adrenal cortical carcinoma follows the stage I-IV pattern for most solid tumors: In practice, given the key role of resectability in prognosis and the lack of consistent efficacy of adjuvant chemotherapy, staging at this time may better be thought of as stage I and II (resectable lesions) and stage III-IV (unresectable lesions).


• • Stage I is a small ( <5 cm) encapsulated tumor that is completely removed.
  
  
  
  • Stage II is a larger tumor (>5 cm) that is completely removed.
  
  
  
  • Stage III is associated with local invasion or positive lymph nodes with no distant metastasis.
  
  
  
  • Stage IV is a solid tumor with local invasion and positive lymph nodes or metastasis to liver, lung, or bone.
  
  
  

TREATMENT

Section 5 of 10

Medical Care:

• Medical care is supportive or adjuvant to surgical resection.



• Chemotherapy is discussed as follows:


• • When metastatic disease cannot be removed or if biochemical evidence of tumor secretion persists after surgical removal, chemotherapy is often considered. Currently, no studies suggest that chemotherapy can fulfill a truly adjuvant role that improves patient survival and prevents relapse following incomplete resection or total resection.
  
  
  
  • Nonetheless, 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 an adjuvant role. The 2 drugs are mitotane (o,p’-DDD, Lysodren) and cisplatin (CDDP, Platinol). For a long time, researchers have known that mitotane dramatically decreases adrenal cortical hormone production and ultimately ablates the cortical part of the adrenal gland. Cisplatin as a single agent has shrunk metastatic disease. More recent studies have added etoposide and doxorubicin to cisplatin and mitotane.
  
  
  
  • These drugs 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 in order to prolong survival once the disease becomes unresectable. Small studies have examined the use of etoposide and platinum or etoposide, doxorubicin, and platinum for adjuvant use.
  
  
  
• Radiation therapy may be helpful in palliation of unresectable disease that is unresponsive to medical therapy.

Surgical Care:

• Treatment of adrenal cortical 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 this author’s experience, aggressive surgical care has led to survival 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 with several follow-up thoracotomies.



• In addition, some case reports indicate that multiple thoracotomies can allow more than 10 years of high-quality survival despite recurring crops of metastatic disease. In a recent study from Sloan-Kettering analyzing patients with adrenal cortical carcinoma regardless of age, aggressive primary surgical removal and aggressive surgical treatment of local or distant relapse led to far superior long-term survival rates than reported in previous studies. One important feature of this article was that patients who had a complete second resection had a median survival time of 74 months (5-y survival rate, 57%). The current role of surgical resection in the treatment of adrenal cortical carcinoma cannot be overemphasized.



• Patients with symptoms of hormone overproduction and biochemical evidence of adrenal cortical hormone overproduction should be supported in the postoperative period following a major resection. These patients have suppressed their own endogenous adrenal cortical hormone production. Stress doses of hydrocortisone that ultimately lead to maintenance doses and tapering (should the patient not be placed on any further therapy) are indicated.

Consultations: Optimum care of pediatric patients with adrenocortical carcinoma includes consultation with a pediatric surgeon with extensive experience in cancer surgery as well as a pediatric oncologist who may have seen cases of adrenocortical carcinoma.

MEDICATION

Section 6 of 10

Adjuvant or palliative treatment has been studied using mitotane, cisplatin, etoposide, and doxorubicin. Mitotane leads to autodestruction of the adrenal cortex and, thus, is used in almost all protocols in the hope that it will decrease any autonomous hormone production, as well as suppress tumor growth. Chemotherapy has centered on single administrations or groupings of 3 antineoplastics: cisplatin, etoposide, and doxorubicin. Recent studies have focused on etoposide and cisplatin or etoposide, doxorubicin, and cisplatin.

Drug Category: 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), then finally a mitotic cell division (phase M).

Cell division rates vary for different tumors. Most common cancers increase very slowly in size compared to normal tissues, and the rate may decrease further in large tumors. This difference allows healthy cells to recover more quickly from chemotherapy than malignant cells, and this is the rationale behind current cyclic dosage schedules.

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

Drug Name	Mitotane (Lysodren) -- Decreases production of cortisol by causing adrenal atrophy and affecting mitochondria in adrenal cortical cells. No actual pediatric standards or dosages have been promulgated, and doses in children must be individualized.
Pediatric Dose	500 mg PO qid initially; may escalate dose up to 10 g/m2/d
Contraindications	Documented hypersensitivity
Interactions	CNS depressants may increase toxicity; may increase metabolism of warfarin, causing a decrease in levels; spironolactone may decrease effects of mitotane
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Dose escalation may be limited by GI toxicity (eg, anorexia, nausea, vomiting, diarrhea), neurotoxicity (eg, lethargy, somnolence, dizziness, vertigo, depression), or dermatologic toxicity (eg, evanescent papular erythematous rash); dose escalation proceeds to toxicity, reports exist in the literature of blood levels of mitotane being associated with response as opposed to PO dose; clinical response may take up to 3 mo at the maximum tolerated dose; exogenous administration of adrenal cortical hormones is required (ie, hydrocortisone and/or fludrocortisone)

Drug Name	Cisplatin (Platinol) -- Inhibits DNA synthesis and, thus, cell proliferation by causing DNA crosslinks and denaturation of double helix.
Pediatric Dose	<10 kg: 2.5-3.3 mg/kg IV q3wk >10 kg: 75-100 mg/m2 IV q3wk
Contraindications	Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment
Interactions	Increases toxicity of bleomycin and ethacrynic acid
Pregnancy	D - Unsafe in pregnancy
Precautions	Administer only under the care of an experienced pediatric oncologist using conventional procedures to prevent ototoxicity and nephrotoxicity; in addition to the usual monitoring of those receiving intensive chemotherapy, must observe and treat for renal tubular defects, renal loss of electrolytes (ie, magnesium, potassium), renal insufficiency, ototoxicity, myelosuppression, and neurotoxicity; administer adequate hydration before and 24 h after cisplatin dosing to reduce risk of nephrotoxicity

Drug Name	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, which causes DNA polymerase inhibition. Binds to nucleic acids presumably by specific intercalation of anthracycline nucleus with DNA double helix. Also a powerful iron chelator. Iron-doxorubicin complex induces production of free radicals that can destroy DNA and cancer cells. Can also cause DNA strand breakage through effects on topoisomerase II. Maximum toxicity occurs during the S phase of the cell cycle. Has multiphasic disappearance curve, with half-lives ranging up to 30 h. Does not cross blood-brain barrier but is taken up rapidly by the heart, lungs, liver, kidney, and spleen. This drug is both mutagenic and carcinogenic. Dosage related to body surface area. Antiproliferative drugs may be useful for patients with diffuse metastases to palliate symptoms. Functional properties of drug can be substantially affected by liposomal encapsulation. Liposomes used in different drug products can vary in their chemical and physical properties. These differences can substantially affect functional properties among liposomal drug products.
Pediatric Dose	<10 kg: 0.6-1.5 mg/kg IV q3wk >10 kg: 20-45 mg/m2 IV q3wk
Contraindications	Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function, pre-existing myelosuppression; previous complete cumulative doses of doxorubicin, daunorubicin, idarubicin, or other anthracyclines and anthracenes
Interactions	May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels of doxorubicin; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity of doxorubicin; cyclophosphamide increases cardiac toxicity of doxorubicin
Pregnancy	D - Unsafe in pregnancy
Precautions	Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function

Drug Name	Etoposide (Toposar, VePesid) -- Glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect through stabilization of the normally transient covalent intermediates formed between DNA substrate and topoisomerase II, leading to single- and double-strand DNA breaks. This causes cell proliferation to arrest in late S or early G2 portion of the cell cycle.
Pediatric Dose	<10 kg: 3.3 mg/kg/d IV for 3 d q3wk >10 kg: 100 mg/m2/d IV for 3 d q3wk
Contraindications	Documented hypersensitivity; significant hypotension; IT administration may cause death
Interactions	May prolong the effects of warfarin and increase the clearance of methotrexate; cyclosporine and etoposide have additive effects in the cytotoxicity of tumor cells
Pregnancy	D - Unsafe in pregnancy
Precautions	Bleeding and severe myelosuppression may occur; withhold therapy or suspend therapy if platelet counts are <50,000 or absolute neutrophil counts are <500/mm3; reduce dose by 20% for granulocytic fever or previous radiotherapy; reduce dose with hepatic impairment (increased total bilirubin [TB]) or renal impairment (decreased CrCl)

FOLLOW-UP

Section 7 of 10

Further Inpatient Care:

• Patients who undergo complete surgical resection with no evidence of continuation of functional hormone production do not require any further inpatient care.



• If the patient demonstrates evidence of local or distant metastases on ambulatory follow-up, aggressive attempts at repeat resection should be undertaken. This leads to additional inpatient care.



• In addition, 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 tumor masses in the chest or elsewhere, autologous transplant might be a consideration, although only anecdotal data suggests that transplant is helpful for this disease.

Further Outpatient Care:

• Ambulatory follow-up should occur every month for the first 2 years after treatment. This is because repeat resection of local recurring disease and resection of metastatic lung disease offers such a potential impact on long-term survival.



• Scanning of the local area in the abdomen or pelvis and sites of metastatic disease should continue every 3 months for the first 2 years, every 4 months for the subsequent 2 years, and every 6 months during the fifth year.



• Monitoring for the reappearance of adrenal cortical hormone hyperactivity should be performed along with scanning unless a patient’s history suggests that Cushing syndrome or autonomous adrenal cortical hormonal production is present. If this is the case, the physician should immediately search for recurrence.

Prognosis:

• Overall prognosis is poor.



• In a recent study of pediatric patients with adrenocortical tumors, overall survival was 54.2%. This particular study did not distinguish adenoma from adenocarcinoma because of the difficulty (even with expert review) of separating these diagnoses in low-stage disease. This overall number is affected by the excellent survival of patients with stage I tumors, which is the group that contains adenoma. A number of valuable prognostic indicators have emerged, however, 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 clinical stage. Given that adenoma, by definition, is usually in stage I, that stage I disease approaches 90% survival because of complete resection is no surprise. However, adenocarcinomas are noted in that group as well, and many investigators believe that a small (<200 g) stage I carcinoma also carry an excellent prognosis when completely removed without tumor spill. Stage II disease drops survival to close to 40%, even with complete resection. Stage III and IV disease have equally poor prognoses of less than 20%.
  
  
  
  • Age: In the study referenced above, patients younger than 4 years had an event-free survival rate of over 70%. The event-free survival rate for patients aged 4-12 years dropped to 30-40%.
  
  
  
  • Function: Tumors that virilize alone, or nonfunctioning tumors, carry a better prognosis than tumors that produce Cushing syndrome through overproduction of glucocorticoid.
  
  
  
• Resection: As surgical procedures for tumor removal improve, prognosis should also improve.



• Medical therapy: Currently, medical therapy has a palliative role. Proof that adjuvant therapy helps to prolong survival requires a well-conducted series of clinical trials.

MISCELLANEOUS

Section 8 of 10

Medical/Legal Pitfalls:

• In general, children older than 4 years present with retroperitoneal tumors in a bulky or advanced form. This may lead to inappropriate blame of the primary care physician, especially if nonspecific signs (eg, constipation, mild abdominal pain) have been present. Because the prognosis of adrenocortical carcinoma is grave even when discovered early, all practitioners must recognize the insidious nature of these tumors.

TEST QUESTIONS

Section 9 of 10

CME Question 1: In a pediatric patient with Cushing syndrome, which of the following may indicate that adrenal cortical carcinoma is the source of the Cushing syndrome?

A: Absence of virilization
B: History of diarrhea
C: Palpable mass
D: Calcification on the kidneys, ureters, and bladder
E: None of the above

The correct answer is C: Approximately 20- 40% of patients with adrenal cortical carcinoma present with a palpable mass and no symptoms of adrenal hormone hypersecretion. In 60% of cases, the patient’s history includes elements of adrenal cortical hormone production (usually virilization) and a palpable mass. The presence of both findings raises the likelihood of adrenal cortical carcinoma because most functioning adrenal tumors with a palpable mass are carcinoma rather than adenoma. Physical examination findings almost always include a palpable mass in the abdomen that usually involves the center of abdomen rather than the flanks. The mass is hard and nonmovable.

CME Question 2: Which of the following is not associated with adrenal cortical carcinoma?

A: Adrenal cortical hormone overproduction
B: Lung metastasis
C: Improved survival with complete resection
D: Decreased androgen production
E: Palpable mass

The correct answer is D: Patients with adrenal tumors often present with a history of adrenal cortical hormone production, including physical changes, virilization from increased androgen production, and more rarely, Cushingoid features. In 60% of cases, the patient’s history includes elements of adrenal cortical hormone production and a palpable mass. The presence of both findings raises the likelihood of adrenal cortical carcinoma because most functioning adrenal tumors with a palpable mass are carcinoma rather than adenoma. Underproduction of adrenal hormones is not seen.

Pearl Question 1 (T/F): Adrenal cortical carcinoma is very responsive to chemotherapy.

The correct answer is False: When metastatic disease cannot be removed or if biochemical evidence of tumor secretion persists after surgical removal, chemotherapy is often considered. Currently, no studies suggest that chemotherapy can fulfill a truly adjuvant role that improves patient survival and prevents relapse following incomplete resection or total resection.

Pearl Question 2 (T/F): The pathology of adrenal cortical carcinoma is difficult to differentiate from that of neuroblastoma.

The correct answer is False: Laboratory studies of adrenal cortical carcinoma include serum glucose, serum cortisol, serum adrenal androgens, urine adrenal hormones, urine vanillylmandelic acid (VMA), and urine homovanillic acid (HVA). These studies enable the physician to distinguish between functioning and nonfunctioning adrenal neoplasms. They may also help distinguish between a neoplasm of the adrenal cortex and neuroblastoma. Histologic findings include numerous mitoses, scant cytoplasm, and none of the rosettes observed in neuroblastoma. The histology is quite characteristic and is not usually confused with neuroblastoma, although differentiation of adenoma and adenocarcinoma may be difficult.

Pearl Question 3 (T/F): Adrenal cortical carcinoma is most commonly diagnosed in patients younger than 5 years.

The correct answer is False: Adrenal cortical carcinoma is a rare tumor in the pediatric population (0-21 y). In a study on the incidence of functioning adrenal tumors in patients aged 4-20 years, 59 children were identified by a single referral institution over a period of years. Only 2 of these patients had adrenal cortical carcinoma. This study underreports the overall incidence of adrenal cortical carcinoma because 20-40% of affected patients present with a palpable mass and no symptoms of adrenal hormone hypersecretion. Adrenal cortical carcinoma does not appear to have a peak incidence related to age in children.

Pearl Question 4 (T/F): Adrenal cortical carcinoma has a poor 5-year survival rate and a poor overall survival rate ( <50%).

The correct answer is True: Some case reports indicate that multiple thoracotomies can allow more than 10 years of high-quality survival despite recurring crops of metastatic disease. In a recent study from Sloan-Kettering analyzing patients with adrenal cortical carcinoma regardless of age, aggressive primary surgical removal and aggressive surgical treatment of local or distant relapse led to far superior long-term survival than reported in previous studies. One important feature of this article was that patients who had a complete second resection had a median survival of 74 months (5-y survival rate, 57%). Overall prognosis for patients with adrenal cortical carcinoma is poor. In a recent study of 31 patients at the Lahey Clinic over a 30-year period, the mean survival was 17 months with a range of 1-205 months. The 5-year survival rate was 26%. As surgical procedures for tumor removal improve, prognosis should also improve.

BIBLIOGRAPHY

Section 10 of 10

• 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 2005 Sep; 12(3): 657-66[Medline].
• Bonfig W, Bittmann I, Bechtold S, et al: Virilising adrenocortical tumours in children. Eur J Pediatr 2003 Sep; 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 1993 Jan; 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 1994 May; 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 2003 May; 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. 15th ed. Philadelphia, Pa: WB Saunders Co; 1995: 338-341.
• 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 2004 Mar 1; 22(5): 838-45[Medline].
• Ribeiro J, Ribeiro RC, Fletcher BD: Imaging findings in pediatric adrenocortical carcinoma. Pediatr Radiol 2000 Jan; 30(1): 45-51[Medline].
• Ribeiro RC, Figueiredo B: Childhood adrenocortical tumours. Eur J Cancer 2004 May; 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 2005 Sep; 45(3): 265-73[Medline].
• Schulick RD, Brennan MF: Long-term survival after complete resection and repeat resection in patients with adrenocortical carcinoma. Ann Surg Oncol 1999 Dec; 6(8): 719-26[Medline][Full Text].
• Sredni ST, Alves VA, Latorre Mdo R, Zerbini MC: Adrenocortical tumours in children and adults: a study of pathological and proliferation features. Pathology 2003 Apr; 35(2): 130-5[Medline].
• Stewart JN, Flageole H, Kavan P: A surgical approach to adrenocortical tumors in children: the mainstay of treatment. J Pediatr Surg 2004 May; 39(5): 759-63[Medline].
• Stratakis C, Chrousos G: Endocrine Tumors. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1997: 947-76.
• Tritos NA, Cushing GW, Heatley G, Libertino JA: Clinical features and prognostic factors associated with adrenocortical carcinoma: Lahey Clinic Medical Center experience. Am Surg 2000 Jan; 66(1): 73-9[Medline].
• Zidan J, Shpendler M, Robinson E: Treatment of metastatic adrenal cortical carcinoma with etoposide (VP-16) and cisplatin after failure with o,p'DDD. Clinical case reports. Am J Clin Oncol 1996 Jun; 19(3): 229-31[Medline].

eMedicine Journals > Pediatrics > Oncology > Adrenal Carcinoma

Please email us with any comments you have on our new chapter format.

Author Information | Introduction | Clinical | Workup | Treatment | Medication | Follow-up | Miscellaneous | Test Questions | Bibliography