Higher levels of sex corticosteroid hormones — such as testosterone — and an enzyme called lactate dehydrogenase may predict malignancies of adrenal masses in children, according to a study.
Findings also revealed that malignant tumors — known as adrenocortical carcinomas (ACCs) — were larger and associated with a worse prognosis than benign ones, called adrenocortical adenomas (ACAs), in these patients.
The study, “Clinical characteristics and prognosis of adrenocortical tumors in children,” appeared in the journal Pediatric Surgery International.
Tumors in the adrenal glands — small structures that sit on top of each kidney and produce cortisol and other hormones — are among the most frequent in humans and are often the cause of excess cortisol in circulation and consequent Cushing’s syndrome.
While these tumors can be malignant or benign, each of which have markedly different clinical outcomes, the absence of definitive pathological criteria to determine malignancy makes distinguishing between them and predicting prognosis in children difficult.
To address this, a team in China set out to describe the management and prognosis of children with adrenal masses by analyzing disease features, imaging data, treatment approach, and outcomes. All 28 patients attended the Children’s Hospital of Fudan University in Shanghai between March 2010 and March 2017.
The study included 10 boys and 18 girls, with a mean age at diagnosis of 5.25 years. The average age of the patients with ACAs was 6.8, and 2.7 in children with ACCs. Of the patients, 26 had tumors in only one gland (15 ACAs and 11 ACCs), while the other two had tumors in both glands.
Most of the patients (75%) had some sort of hormonal dysfunction, with 60.7% experiencing precocious puberty — defined as early development of pubic and axillary hair, deepened voice, accelerated height, acne, and enlarged genitals — 53.3% having signs of Cushing’s syndrome, and 39.2% showing signs of both virilization and Cushing’s.
In addition, five patients (17.8%) showed symptoms of hyperaldosteronism — excessive production of the hormone aldosterone by the adrenal glands — with hypertension, and two had an abdominal mass.
Overall, 89% of patients had functional tumors, characterized by an increased release of hormones. Testosterone levels were elevated in 16 of the 19 patients tested, and higher in ACC than in ACA patients. Also, levels of dehydroepiandrosterone, which may be converted into testosterone, were above the upper limit for detection in six of the seven patients tested, and also higher in children with ACCs.
Patients with ACCs also had excess amounts of 17Α-hydroxyprogesterone (derived from progesterone) and serum LDH cholesterol. The level of lactate dehydrogenase — an enzyme involved in energy production in cells — was above normal in eight of nine patients with ACCs and in two of 10 with ACAs.
According to the researchers, “the discordantly elevated serum levels of sexual corticosteroid hormones and lactate dehydrogenase may predict the malignant nature of these tumors.”
Computed tomography (CT) imaging revealed large, well-defined tumors containing calcifications — buildups of calcium — with a thin capsule and central cell and tissue death or bleeding.
In agreement with the literature, tumors were larger in the 12 patients with ACCs than in the 16 with ACAs. Expression of Ki-67, an indicator of cellular proliferation, was also higher in ACCs than ACAs.
All patients underwent complete surgical removal of their tumors. After a median follow-up of 40 months, all ACA patients were alive and without signs of tumor recurrence.
Adjuvant chemotherapy was started post-surgery in five patients with ACCs. After a median follow-up of 27 months, seven patients had developed distant metastasis after surgery, five died within two years, and seven were still alive. Two-year overall survival was 44.6%.