Adrenocartical Tumors in Children

Overview

Adrenocortical tumors are rare but potentially life-threatening neoplasms that arise from the adrenal cortex. In children, these tumors are more frequently functional, producing excess hormones, as compared to adults. Approximately 60% of childhood adrenocortical tumors are malignant, with a peak incidence between the ages of 3 and 4 years.

Etiology and Risk Factors

Genetic predisposition: Certain genetic syndromes are associated with an increased risk of adrenocortical tumors, including Li-Fraumeni syndrome (TP53 mutations), Beckwith-Wiedemann syndrome, and multiple endocrine neoplasia type 1 (MEN1).
Environmental factors: Exposure to exogenous hormones, such as those found in certain pesticides and food additives, has been hypothesized as a potential risk factor, but the evidence is inconclusive.

Clinical Presentation

The clinical presentation of adrenocortical tumors in children can vary depending on the functional status of the tumor and the degree of hormonal excess.

Virilizing Tumors

Signs of virilization, including premature pubarche, hirsutism, acne, and accelerated growth and bone age
Increased muscle mass and deepening of the voice (in girls)

Cushing's Syndrome

Rapid weight gain, particularly in the face and trunk
Growth retardation
Skin changes (e.g., striae, acne, hirsutism)
Muscle weakness
Hypertension
Impaired glucose tolerance or frank diabetes mellitus

Mixed or Hypercortisolism and Virilization

Some children may present with a combination of virilizing and Cushing's symptoms.

Non-functional Tumors

In rare cases, adrenocortical tumors may be non-functional, presenting as an abdominal mass or incidental finding.

Diagnostic Evaluation

Biochemical Evaluation

Measurement of serum and urine hormone levels (e.g., cortisol, androgens, estrogens) to assess for hormonal excess
Dexamethasone suppression test to evaluate cortisol secretion

Imaging

Abdominal ultrasound: Often the initial imaging modality used to detect adrenal masses
Computed tomography (CT) or magnetic resonance imaging (MRI): Provides detailed information about the size, location, and characteristics of the adrenal mass, as well as the presence of metastatic disease

Biopsy

While not routinely performed, biopsy may be considered in select cases to confirm the diagnosis or for further molecular characterization.

Management

Surgical Resection

Complete surgical resection is the mainstay of treatment for adrenocortical tumors in children.

Open adrenalectomy: Traditionally, open surgery has been the preferred approach, allowing for complete resection and lymph node sampling.
Laparoscopic adrenalectomy: Minimally invasive techniques may be considered for smaller, localized tumors, offering potential advantages such as shorter recovery times and reduced postoperative morbidity.

Preoperative Management

Control of hormonal excess (e.g., glucocorticoids, anti-androgens, ketoconazole) to minimize perioperative complications
Correction of electrolyte imbalances and other metabolic derangements

Adjuvant Therapy

Chemotherapy: Multiagent chemotherapy regimens may be used for advanced or metastatic disease, with varying responses.
Radiation therapy: May be considered for unresectable or metastatic disease, although its role is less well-defined in children.
Targeted therapy: Emerging targeted therapies, such as inhibitors of the Wnt/β-catenin and IGF signaling pathways, are under investigation but not yet routinely used in clinical practice.

Surveillance and Follow-up

Close monitoring for recurrence or metastatic disease is essential, with regular clinical evaluations, imaging studies, and biochemical testing.

Prognosis

The prognosis for adrenocortical tumors in children is highly variable and depends on several factors, including:

Tumor stage and extent of disease at diagnosis
Completeness of surgical resection
Tumor histology and molecular characteristics
Presence of metastatic disease

Overall, the 5-year survival rate for children with localized adrenocortical tumors ranges from 50% to 80%, while the prognosis is generally poor for those with metastatic disease at diagnosis.

Conclusion

Adrenocortical tumors in children are rare but challenging entities that require a multidisciplinary approach involving endocrinologists, oncologists, surgeons, and other specialists. Early recognition and prompt management are crucial for optimizing outcomes. Continued research efforts are needed to improve our understanding of the underlying pathogenesis, develop more effective targeted therapies, and refine risk stratification and surveillance strategies.

Here are two case studies related to adrenocortical tumors in children, along with references for the notes provided earlier.

Case Study 1

A 4-year-old girl presented with progressive weight gain, facial plethora, and hirsutism over the past 6 months. Her parents also reported mood swings and decreased linear growth. Physical examination revealed a cushingoid appearance, with truncal obesity, buffalo hump, and acne. Laboratory investigations showed elevated serum cortisol levels (720 nmol/L; reference range: 138-635 nmol/L) with a lack of diurnal variation, and an unsuppressed cortisol level after a low-dose dexamethasone suppression test.

Abdominal imaging revealed a large, heterogeneous mass in the left adrenal gland, measuring 6 cm in diameter, with no evidence of metastatic disease. The patient underwent an open left adrenalectomy, and histopathological examination confirmed an adrenocortical carcinoma. Postoperatively, her clinical and biochemical parameters improved, with normalization of cortisol levels.

However, during routine follow-up 18 months after surgery, a CT scan revealed multiple pulmonary nodules consistent with metastatic disease. The patient was started on a multiagent chemotherapy regimen, but her disease progressed rapidly, and she succumbed to complications of metastatic adrenocortical carcinoma at the age of 6 years.

Case Study 2

A 7-year-old boy was referred for evaluation of premature pubarche and accelerated growth velocity. His parents reported the appearance of pubic hair and deepening of the voice over the past year. Physical examination revealed hirsutism, acne, and advanced bone age.

Laboratory testing showed elevated serum testosterone levels (1.8 ng/mL; reference range: 0.1-0.5 ng/mL) and dehydroepiandrosterone sulfate (DHEA-S) levels (>1000 μg/dL; reference range: 5-57 μg/dL). Abdominal ultrasound and subsequent CT scan revealed a 4 cm heterogeneous mass in the right adrenal gland, without evidence of metastatic disease.

The patient underwent a laparoscopic right adrenalectomy, and histopathological examination confirmed a virilizing adrenocortical adenoma. Postoperatively, his hormonal levels normalized, and the virilizing features gradually resolved over the following year. He has remained disease-free with regular follow-up for the past 3 years.

References

Michalkiewicz, E., Sandrini, R., Figueiredo, B., Miranda, E. C. M., Caran, E., Oliveira-Filho, A. G., ... & Ribeiro, R. C. (2004). Clinical and outcome characteristics of children with adrenocortical tumors: a report from the International Pediatric Adrenocortical Tumor Registry. Journal of Clinical Oncology, 22(5), 838-845.
Else, T., Hammer, G. D., & Strobel, G. D. (2022). Adrenocortical carcinoma in children: Management and prognosis. UpToDate. Retrieved from https://www.uptodate.com/contents/adrenocortical-carcinoma-in-children-management-and-prognosis
Rodriguez-Galindo, C., Figueiredo, B. C., Zambetti, G. P., & Ribeiro, R. C. (2005). Biology, clinical characteristics, and management of adrenocortical tumors in children. Pediatric Blood & Cancer, 45(3), 265-273.
Else, T. (2022). Adrenocortical tumors in children: Initial presentation and evaluation. UpToDate. Retrieved from https://www.uptodate.com/contents/adrenocortical-tumors-in-children-initial-presentation-and-evaluation
Ribeiro, R. C., & Michalkiewicz, E. L. (2000). Adrenocortical tumours in children. Brazilian Journal of Medical and Biological Research, 33(10), 1195-1201.