Epidemiology

Adrenocortical tumors are rare in childhood, with an incidence of 0.3-0.5 cases per million child-years. They occur in all age groups but most commonly in children younger than 6 yr of age, and are more frequent (1.6-fold) in girls. In 2-10% of cases, the tumors are bilateral. Symptoms of endocrine hyperfunction are present in more than 90% of children with adrenal tumors (see Table 571-1). Tumors may be associated with hemihypertrophy, usually occurring during the 1st few years of life. They are also associated with other congenital defects, particularly genitourinary tract and central nervous system abnormalities and hamartomatous defects.

Etiology

Germline mutations in p53 (on chromosome 17p13.1) have been found in patients with isolated adrenal carcinoma as well as in patients with familial clustering of unusual malignancies; this latter condition is termed Li-Fraumeni syndrome. A 15-fold increased incidence of childhood adrenocortical tumors is found in southern Brazil, associated with a R337H mutation in p53. Overexpression of IGF2 (chromosome 11p15.5) occurs in 80% of sporadic childhood adrenocortical tumors, as well as in those associated with Beckwith-Wiedemann syndrome, in which there is loss of the normal imprinting of genes in this chromosomal region.

Clinical Manifestations

Virilization is the most common presenting symptom in children with adrenocortical tumors, occurring in 50-80%. In males, the clinical picture is similar to that of simple virilizing congenital adrenal hyperplasia: accelerated growth velocity and muscle development, acne, penile enlargement, and the precocious development of pubic and axillary hair. In females, virilizing tumors of the adrenal gland cause masculinization of a previously normal female with clitoral enlargement, growth acceleration, acne, deepening of the voice, and premature pubic and axillary hair development.

Conversely, adrenal tumors can occasionally (7%) secrete high levels of estrogens due to overexpression of CYP19 (aromatase). Gynecomastia in males or premature thelarche in girls is often the initial manifestation. Growth and development may be otherwise normal, or concomitant virilization may occur.

In addition to virilization, 15-40% of children with adrenocortical tumors also have Cushing syndrome (Chapter 571). Although virilization may occur alone, children with adrenal tumors usually do not have Cushing syndrome alone.

In adults, adrenal tumors are frequently detected incident to CT or MRI imaging of the abdomen for other reasons; these are often referred to as incidentalomas.