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congenital adrenal hyperplasia ( cah ) is an autosomal recessive adrenal steroid synthesis disorder that is transferred genetically and is characterized by increased adrenocorticotropic hormone ( acth ) secretion due to glucocorticoid and mineralocorticoid deficiency .
an increase in acth synthesis can result in hyperplasia of acth - sensitive tissues in the adrenal glands and other sites such as the testes , leading to testicular masses widely known as tart , or testicular adrenal rest tumor .
tart is often an asymptomatic benign lesion that frequently occurs in male cah patients with a reported prevalence of up to 94% .
yet , the prevalence , etiology , and functional features of testicular tumors due to 11-hydroxylase deficiency are not clearly known .
the present article is a case study of bilateral tart in a patient with 11-hydroxylase deficiency - driven cah .
a 16-year - old male patient was referred from the pediatrics clinic to our clinic with a diagnosis of 11-hydroxylase deficiency - driven cah after the determination of bilateral testicular masses .
the patient 's history revealed a diagnosis of 11-hydroxylase deficiency - driven cah at a young age . although the patient 's laboratory data from an early age were not available , the patient had been using dexamethasone 10.75 mg and spironolactone 1100 mg irregularly .
the physical examination revealed multiple bilateral solid nodules in the testes of approximately 0.5 to 1.5 cm .
the results of routine hematologic and biochemical tests and the levels of prolactin , luteinizing hormone , and follicle - stimulating hormone were normal .
the values of serum markers for testis tumors , such as alpha - fetoprotein ( afp ) , beta - human chorionic gonadotropin ( hcg ) , and lactate dehydrogenase ( ldh ) , were within normal ranges .
cortisol , acth , and dehydroepiandrosterone sulfate levels were likewise normal , unlike the elevated levels of 17-hydroxyprogesterone and 11-deoxycortisol , which were 23 ng / ml ( < 2 ng / ml ) and 238 ng / ml ( < 8 ng / ml ) , respectively .
scrotal ultrasonography revealed the following testicular sizes : right , 41 mm21 mm , and left , 43 mm22 mm .
both testes contained multiple solid heterogenic hypoechoic nodules of different sizes ranging from approximately 21 mm15 mm to 14 mm10 mm with well - drawn borders and increased vascularity as indicated by the arrows ( fig .
scrotal magnetic resonance imaging revealed multiple solid nodules with the largest diameter being 18 mm in the right testis and 11 mm in the left .
after intravenous gadolinium injection , intense homogeneous contrast accumulation was seen in the nodular lesions with contoured lobes and well - drawn borders ( fig .
the patient 's sperms were cryopreserved in case he underwent bilateral orchiectomy on the basis of malignant pathological findings . because the testicular tumor could not be differentiated as malignant or benign on the basis of the laboratory and imaging findings , the patient underwent a right high inguinal testicular exploration .
because the report of the frozen section analysis was benign , orchiectomy was not performed .
after the tunica albuginea was sutured , the testis was placed back into the scrotum .
histopathological analysis revealed that the cells forming the mass were similar to leydig cells with separated fibrous tissue ; significant , nucleolus , eosinophilic cytoplasm ; and polygonal shapes forming in some areas nests and at other areas layers .
immunohistochemical analysis revealed that the tumor cells totally diffused with vimentin and melan - a but were focally immunopositive to inhibin and creatine .
placental alkaline phosphatase and ae1/ae3 were immunonegative and the tissue was defined as tart ( fig .
the patient was diagnosed with tart , glucocorticoid treatment was initiated , and the patient was followed up .
moreover , tart is generally seen in insufficiently treated or untreated patients with cah owing to the elevated acth levels .
hence , it is often detected in adolescents and young adults . in the present case ,
changes in the levels of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone were decreased owing to the defect in 11-hydroxylase activity .
a decrease in cortisol levels leads to acth stimulation and thus to growth in adrenal tissue and adrenal ectopic tissues .
tarts are very difficult to differentiate from leydig cell tumors ( lcts ) , which are mostly common in stromal testicular neoplasia leading likewise to precocious puberty and testicular masses .
the presentation of these two entities is the same , yet the therapeutic approaches differ . whereas lcts require surgical treatment , most cases of tarts respond to steroid - suppressive therapy . in the diagnosis of tart and malignant tumors ,
although the initial evaluation of the present case was in favor of testicular malignancy ( lcts ) or tart , for differentiation , biopsy results are considered to be conclusive .
the clinical manifestations of tarts are changes in blood pressure and bilateral tumors accompanied by a family history of tart .
the bilateral presence of tart is determinant in diagnosis ; however , 3% of bilateral masses consist of lcts .
precocious puberty and gynecomastia might be evident in both ; however , gynecomastia is more frequent in lct .
the laboratory findings supporting tart are hypokalemia and normal tumor indicators such as hcg , afp , and ldh . in ultrasonography ,
tart is prevalent in the form of multiple hypoechoic nodules , whereas lcts appear as single hypoechoic nodules .
the present case was a 16-year - old male patient with a history of hypertension and multiple bilateral lesions .
therefore , in the present case , a high inguinal testicular exploration with nodal excision was done to analyze frozen sections to determine the prospective treatment modality . in case
the histopathological diagnosis was malignant and bilateral orchiectomy was thus unavoidable , cryopreservation was done before the procedure . because the frozen section report was benign , orchiectomy was not performed .
, the patient was enrolled into the follow - up protocol and referred to pediatric endocrinology for glucocorticoid treatment planning .
although tart is not among the prevalent tumors , one of the most important problems is its differentiation from malignant tumors .
despite the fact that clinical , radiological , and biochemical indicators support the diagnosis , histopathological diagnosis is decisive . in patients with cah ,
early diagnosis and conservative treatment in tart patients is essential because a delayed radical approach will result in prospective infertility and testicular hypofunction . in the present case , clinical , radiological , and biochemical diagnoses supported tart ; yet biopsy to make a decisive diagnosis could not be conducted . in conclusion , to prevent irreversible testicular damage , early detection of tart is important .
cah patients should be regularly followed up for tart , and those with nodular testicular lesions should be well evaluated before any invasive treatment and diagnosis modalities are preferred by urologists .
testicular adrenal rest tumors ( tart ) occur often as asymptomatic nodules in corticotropin - dependent lesions aberrant adrenal tissue in congenital adrenal hyperplasia ( cah ) patients . 
 the present manuscript is about an unusual case of a 16-year - old cah patient due to 11-hydroxylase deficiency . 
 he underwent testicle biopsy because of testicle tumor suspicion and diagnosed with tart .