Adrenocortical tumors (ACT) develop from clonal transformation of an adrenal cortex cell and commonly displays signs and symptoms related to increased adrenocortical hormone production. However, in about 10% of pediatric ACT cases, these signs and symptoms are not present. Non-functioning ACT is generally not discovered until the tumor mass is sizable and patients complain of abdominal pain or discomfort from pressure applied to the abdominal organs.
Signs and symptoms associated with adrenocortical tumors vary significantly. The signs and symptoms of adrenal gland tumors may include, but are not limited to, early onset of pseudopuberty, such as secondary hair growth, increase in genital size, and voice changes, as well increased weight, high blood pressure, low potassium, palpitations, anxiety, and hyperglycemia. Signs and symptoms can often be defined by adrenocortical hormonal syndromes that are very often associated with ACTs (Ribeiro R et al. 2010; Rodriguez-Galindo C et al. 2005).
Hormonal syndromes associated with ACT are:
- Virilization – caused by excessive secretion of androgen hormones, leading to high levels of the male hormone testosterone. Virilization includes early onset of pubic hair (pseudopuberty), male odor, facial acne, clitorimegaly, voice change, facial hair, hirsutism, muscle hypertrophy, growth acceleration, and an increase in penis size. Virilization is observed either alone (40% of patients) or accompanied by clinical manifestations of the overproduction of other adrenal cortical hormones, including glucocorticoids, aldosterone, or estrogens (mixed type, 45%).
- Cushing syndrome – caused by ACT that produces excess of cortisol (glucocorticoids). Cortisol performs vital tasks in the body such as maintaining blood pressure and controlling the function of the cardiovascular system. Cortisol excess may produce weight gain, muscle wasting, purple lines on the abdomen, a fatty “buffalo hump” on the neck, a “moonlike” face, and thinning/fragile skin. Overproduction of glucocorticoids alone (Cushing syndrome) occurs in only 3% of patients.
- Conn syndrome – caused by excessive production of aldosterone, a mineralocorticoid that is secreted by the adrenal gland. It regulates electrolyte balance. Common presenting clinical manifestations of hyperaldosteronism include headache, weakness of proximal muscle groups, polyuria, and tachycardia with or without palpitation, hypocalcemia, and hypertension. Rarely, seizures resulting from hypertensive encephalopathy are the first clinical manifestations of ACT. Fatalities due to hypertensive crisis have been reported. Hypertension should be treated promptly in these patients. In general, patients have responded well to captopril, although in some cases it has been necessary to add other drugs, such as ketoconazole. Conn syndrome occurs very rarely in pediatric ACT.
- Feminization – caused by increased estrogen production. The most frequent sign of feminization is gynecomastia or premature thelarche. Decreased libido and impotence are also related. This syndrome occurs very rarely in pediatric ACT.
Signs and symptoms of virilization are the most common presenting endocrine features (>80% of patients) (Michalkiewica et al. 2004). Clinical manifestations of ACT can be present before or at birth. An acute abdomen due to spontaneous tumor rupture is rarely the presenting clinical manifestation of ACT. To avoid delaying the diagnosis of ACT, any child less than 4 years with pubarche should be considered to have ACT. Cushing syndrome should be considered highly indicative of ACT in children younger than 10 years.