adrenocortical carcinoma ( acc ) is an extremely rare neoplasm in children and adolescents with an annual incidence of 0.3 cases per million children younger than 15 years old.1 ) although the molecular pathogenesis of acc is poorly understood , it is strongly associated with inactivating mutation of the tumor suppressor gene p53 and alteration of the 11p15 locus leading to insulin - like growth factor 2 overexpression.2 ) acc is often associated with the li - fraumeni and beckwith - wiedemann syndromes.3 ) adrenocortical tumors in children and adolescents are frequently hormone - secreting tumors , and virilization alone or in combination with signs of overproduction of adrenocortical hormones is the most common endocrine syndrome.1 ) hormonally inactive accs , which are common in adults , usually induce abdominal discomfort or back pain caused by the mass effect of the large tumor .
any virilizing symptoms that were resolved after surgical removal of the tumor could theoretically trigger true precocious puberty because of the maturation of the hypothalamic - pituitary - gonadal axis .
therefore , we report a case of virilizing acc in an 8-year - old boy who subsequently developed central precocious puberty following surgery with reviews of the literature .
an 8-year , 2-months - old boy presented to our pediatric clinic with early development of pubic hair and penile growth for the past 3 months .
he was born after 40 weeks of gestation through vaginal delivery with a birth weight of 3,600 g. his past medical and surgical histories were unremarkable .
none of his family members had endocrine tumors or genetic diseases . on physical examination , his height was 137.6 cm ( 95th percentile ) , and his body weight was 40.1 kg ( 95 - 97th percentile ) .
he had no other abnormalities , such as hypertension , cushingoid symptoms , hyperpigmentation , or macroglossia .
follicle - stimulating hormone ( fsh ) and luteinizing hormone ( lh ) levels were below the limit of detection ( < 0.07 miu / ml ) .
the levels of serum dehydroepiandrosterone sulfate ( dheas , 584 g / dl ) , 17-ohp ( 4.05 ng / ml ) , testosterone ( 3.82 ng / ml ) , and urinary 17-ketosteroid ( 58.8 mg / d ) were markedly elevated . the serum morning cortisol level ( 15.2 g / dl ) was not elevated , and his adrenocorticotropic hormone level was within the normal range ( 7.89 pg / ml ) . meanwhile ,
in addition , his daily urinary free cortical excretion ( 106.9 g / d ) was increased .
his bone age was 9 to 10 years based on the greulich - pyle method .
both abdominal ultrasonography and computed tomography ( ct ) demonstrated a large right suprarenal heterogeneous mass measuring 7.45.7 cm with poor enhancement ( figure 1 ) .
the lungs , bone , and liver were free from metastases on magnetic resonance imaging or high - resolution ct .
a provisional diagnosis of adrenocortical tumor was made , and resection of the right adrenal gland with the tumor mass was performed .
grossly , there was no metastasis to regional lymph nodes or vessels detected during the operation .
the adrenalectomy specimen was partially encapsulated and soft , measuring 7.86.14.0 cm and weighting 86 g. the cut section was bright brownish with areas of focal hemorrhage .
the tumor cells were arranged in a nodular and diffuse architecture , and they had high mitotic activity ( 9/10 high - power fields ) .
a histological diagnosis of acc was made ( weiss score was 6 of 9 ) .
the staging of adrenocortical tumors in this patient ( modified from sandrini et al . ) was stage i.2 ) after the operation , serum dhea - s , 17-ohp , and testosterone levels rapidly decreased to the normal levels . however , penis enlargement and the presence of pubic hair persisted at the same level after surgery .
two months after the operation , testicular enlargement and frequent penile erections were noticed by his mother .
the volumes of both testes were increased to 5 ml , and his height velocity was increased ( 10.0 cm per year ) .
the serum dhea - s level was not elevated , whereas fsh ( 1.8 miu / ml ) , lh ( 5.9 miu / ml ) , and testosterone ( 3.34 ng / ml ) levels were elevated to pubertal levels .
the peak values of fsh and lh based on a gonadotropin - releasing hormone ( gnrh ) stimulation test were at pubertal levels ( basal fsh / lh , 2.3/4.4 miu / ml ; peak fsh / lh , 4.5/34.7 miu / ml ) , suggesting secondary central precocious puberty .
treatment with a gnrh agonist was initiated , and his pubertal state did not progress further .
although an exceptionally high incidence of acc has been reported for children in southern brazil and los angeles , ca , the worldwide incidence has been estimated at approximately 0.4 cases per million children younger than 4 years of age .
acc has a peak incidence in children younger than 4 years.4 ) in addition , acc comprises approximately 0.2% of all childhood neoplasms in the united states according to surveillance epidemiology and end results data from the national cancer institute.1,4 ) a slight female preponderance and a bimodal age distribution have been noted.4 ) acc can arise as an either nonfunctional or functional tumor . non - functional acc is most common in adults , whereas more than 90% of childhood accs are functional.2 ) virilization alone or in combination with signs of overproduction is the most common presenting endocrine syndrome in pediatric patients.1 ) isolated cushing 's syndrome , the major symptom of adult acc , is extremely rare , as well as conn 's syndrome . our male patient presented with pubic hair , penile growth , and facial acne .
his hormonal findings were characterized by the overproduction of androgens in serum and urine analysis .
although his serum dhea - s levels had remarkably decreased to normal after the operation , the physical signs of precocious puberty were persistent and indicative of progression .
in addition , the peaks of fsh and lh in gnrh stimulation testing were at pubertal levels , suggesting secondary central precocious puberty .
several causes of peripheral precocious puberty have been recognized , including adrenal tumors.5 ) peripheral precocious puberty may result in the activation of pulsatile gnrh secretion and central precocious puberty .
in addition , effective treatment of the primary disease causes the development of secondary central precocious puberty by activating the hypothalamic gnrh pulse generator via a feedback system , as observed in congenital adrenal hyperplasia and familial or sporadic male - limited precocious puberty.6 ) the period of development for secondary central precocious puberty is various , and other reports illustrated that central precocious puberty may develop as early as 1 month after the initiation of treatment for peripheral precocious puberty.7 ) gnrh agonists are indicated for the treatment of progressive central precocious puberty , and this therapy was initiated in our male patient to prevent pubertal progressions .
all accs are highly malignant tumors , and hence , surgical intervention is the mainstay of treatment for acc . because of the friability of these tumors and the potential for tumor spillage ,
open adrenalectomy is recommended for children with acc . when metastatic disease can not be removed or a high risk of recurrence is identified , chemotherapy is often considered .
however , the benefits and risks of chemotherapy for acc in children , including mitotane or other chemotherapeutic agents , have not yet been established.8 ) because of the tumor stage in our patient , he was only treated with surgery . in conclusion , we suggest that in functioning accs , clinical follow - up for potential secondary effects of excessive hormone secretion or recurrence after surgical removal is important , and hormonal marker or sexual maturity should be assessed at least every 1 or 2 months after surgery .
 adrenocortical carcinoma ( acc ) in pediatric and adolescent patients is rare , and it is associated with various clinical symptoms . 
 we introduce the case of an 8-year - old boy with acc who presented with peripheral precocious puberty at his first visit . 
 he displayed penis enlargement with pubic hair and facial acne . 
 his serum adrenal androgen levels were elevated , and abdominal computed tomography revealed a right suprarenal mass . 
 after complete surgical resection , the histological diagnosis was acc . 
 two months after surgical removal of the mass , he subsequently developed central precocious puberty . 
 he was treated with a gonadotropin - releasing hormone agonist to delay further pubertal progression . in patients with functioning acc and surgical removal , clinical follow - up and hormonal marker examination for 
 the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery . 
INTRODUCTION
CASE REPORT
DISCUSSION