Adreno-cortical Tumors in Children
Introduction to Adrenocortical Tumors in Children
Adrenocortical tumors (ACTs) are rare neoplasms arising from the adrenal cortex. In children, these tumors present unique challenges in diagnosis and management due to their rarity and potential for malignancy. ACTs can be either benign (adenomas) or malignant (carcinomas), with the latter being more common in pediatric populations compared to adults.
Epidemiology
ACTs in children are extremely rare, with an estimated incidence of 0.2-0.3 cases per million children per year. They show a bimodal age distribution, with peaks in children under 5 years and in adolescence. There is a slight female predominance (F:M ratio of 1.5-2:1). Certain genetic syndromes, such as Li-Fraumeni syndrome and Beckwith-Wiedemann syndrome, are associated with an increased risk of developing ACTs.
Pathophysiology
The pathophysiology of pediatric ACTs involves several genetic and molecular alterations:
- TP53 mutations: Present in up to 50-80% of cases, especially in younger children.
- IGF2 overexpression: Common in both benign and malignant tumors.
- Alterations in the Wnt/β-catenin pathway: Associated with more aggressive tumors.
- Chromosomal abnormalities: Including losses at 11q13, 17p13, and 2q14 and gains at 9q34.
These alterations lead to dysregulated cell growth and hormone production, resulting in the clinical manifestations of ACTs.
Clinical Presentation
The clinical presentation of ACTs in children is typically characterized by endocrine syndromes due to hormone excess:
- Virilization (50-80%): Caused by androgen-secreting tumors, leading to precocious puberty, acne, and hirsutism.
- Cushing's syndrome (20-30%): Due to cortisol-secreting tumors, resulting in weight gain, moon facies, and growth failure.
- Feminization (5-10%): Rare, caused by estrogen-secreting tumors.
- Mixed syndromes (30-40%): Combination of the above presentations.
- Non-functional tumors (10%): May present with abdominal pain, mass, or as an incidental finding.
Diagnosis
Diagnosis of ACTs in children involves a combination of clinical, biochemical, and imaging studies:
- Hormonal evaluation:
- Serum cortisol and ACTH
- Androgens (DHEA-S, testosterone)
- Estradiol (in cases of feminization)
- 24-hour urinary free cortisol
- Imaging:
- CT or MRI of the abdomen: To assess tumor size, local invasion, and metastases
- Chest CT: To evaluate for lung metastases
- 18F-FDG PET/CT: For staging and treatment response assessment
- Biopsy: Generally avoided due to the risk of tumor rupture and spread. Diagnosis is typically made based on clinical presentation, hormonal profile, and imaging findings.
Treatment
Treatment of pediatric ACTs is multidisciplinary and depends on the tumor stage and functional status:
- Surgery:
- Complete surgical resection is the primary treatment for localized disease
- Open adrenalectomy is preferred over laparoscopic approach due to the risk of rupture
- Lymph node dissection should be considered in all cases
- Chemotherapy:
- Mitotane is the primary chemotherapeutic agent, often combined with etoposide, doxorubicin, and cisplatin (EDP-M regimen)
- Used in advanced disease, unresectable tumors, or as adjuvant therapy in high-risk patients
- Radiation therapy:
- Role is controversial but may be considered in cases of incomplete resection or metastatic disease
- Targeted therapies:
- IGF1R inhibitors and mTOR inhibitors are being investigated in clinical trials
Prognosis
Prognosis for pediatric ACTs varies widely depending on tumor stage and completeness of resection:
- Overall survival rates:
- Stage I: >90%
- Stage II: 50-90%
- Stage III: 20-50%
- Stage IV: <20%
- Factors associated with poor prognosis:
- Older age at diagnosis (>4 years)
- Larger tumor size (>10 cm)
- Advanced stage
- Incomplete resection
- P53 mutations
Long-term follow-up is essential due to the risk of recurrence and the potential for treatment-related complications.
Adrenocortical Tumors in Children
- What gland is affected by adrenocortical tumors?
The adrenal gland - Which part of the adrenal gland do adrenocortical tumors originate from?
The adrenal cortex - What is the approximate incidence rate of adrenocortical tumors in children?
0.2-0.3 cases per million children per year - Which genetic syndrome is strongly associated with childhood adrenocortical tumors?
Li-Fraumeni syndrome - What gene mutation is commonly found in children with adrenocortical tumors?
TP53 gene mutation - What are the two main categories of adrenocortical tumors?
Functioning and non-functioning tumors - Which hormone is often overproduced in functioning adrenocortical tumors?
Cortisol - What is the medical term for excessive androgen production in adrenocortical tumors?
Virilization - What imaging technique is commonly used for initial evaluation of suspected adrenocortical tumors?
Abdominal CT scan - What is the gold standard treatment for localized adrenocortical tumors in children?
Complete surgical resection - Which staging system is widely used for pediatric adrenocortical tumors?
The Children's Oncology Group (COG) staging system - What is the primary determinant of prognosis in pediatric adrenocortical tumors?
Tumor stage at diagnosis - What hormone level is typically measured to monitor for tumor recurrence?
Dehydroepiandrosterone sulfate (DHEA-S) - Which chemotherapy drug is commonly used in advanced or metastatic adrenocortical tumors?
Mitotane - What is the approximate 5-year survival rate for children with stage I adrenocortical tumors?
Over 90% - What age group has the highest incidence of adrenocortical tumors in children?
Children under 5 years old - What is the most common presenting symptom in girls with functioning adrenocortical tumors?
Virilization (development of male characteristics) - What endocrine condition can result from excessive cortisol production in adrenocortical tumors?
Cushing's syndrome - Which country has a notably higher incidence of pediatric adrenocortical tumors?
Brazil (specifically southern Brazil) - What is the role of 18F-FDG PET/CT in managing adrenocortical tumors?
Detecting metastases and evaluating treatment response - What is the typical first-line treatment for inoperable or metastatic adrenocortical tumors?
Combination chemotherapy (usually including cisplatin, etoposide, and doxorubicin) - What is the approximate ratio of malignant to benign adrenocortical tumors in children?
About 9:1 (90% are malignant) - Which hormone test is useful in differentiating adrenocortical tumors from pheochromocytomas?
Plasma or urinary metanephrines - What is the name of the surgical procedure to remove an entire adrenal gland?
Adrenalectomy - Which molecular pathway is frequently altered in pediatric adrenocortical tumors?
The IGF2 signaling pathway - What is the most common site of metastasis for adrenocortical carcinomas in children?
Lungs - What is the role of adjuvant radiotherapy in pediatric adrenocortical tumors?
Limited; mainly used for local control in advanced cases - Which hormone can cause precocious puberty in boys with functioning adrenocortical tumors?
Testosterone - What is the approximate median age at diagnosis for pediatric adrenocortical tumors?
3-4 years old - What is the typical follow-up schedule for the first two years after treatment of a localized adrenocortical tumor?
Every 2-3 months
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