Pseudoprecocity Resulting from Tumors of the Testes
Chapter 578 Pseudoprecocity Resulting from Tumors of the Testes
Leydig cell tumors of the testes are rare causes of precocious pseudopuberty and cause asymmetric enlargement of the testes. Leydig cells are sparse before puberty and tumors derived from them are more common in the adult, but rare cases do occur in children and the youngest reported case was in a 1 yr old boy. These tumors are usually unilateral and benign; while up to 10% of adult tumors may be malignant, metastasizing malignant tumors have not been reported in children. Some tumors may be due to somatic activating mutations of the luteinizing hormone (LH) receptor.
The clinical manifestations are those of puberty in the male; onset usually occurs usually from 5 to 9 years of age. Gynecomastia has been described. The tumor of the testis can usually be readily felt; the contralateral unaffected testis is normal in size for the age of the patient.
Plasma levels of testosterone are markedly elevated, and follicle stimulating hormone and LH levels are suppressed. Ultrasonography may aid in the detection of small nonpalpable tumors. Fine-needle aspiration biopsy may help define the diagnosis.
Treatment consists of surgical removal of the affected testis. These tumors are generally resistant to chemotherapy. Progression of virilization ceases after removal of the tumor, and partial reversal of the signs of precocity may occur.
Testicular adrenal rests may develop into tumors that mimic Leydig cell tumors. Adrenal rest tumors are usually bilateral and occur in children with inadequately controlled congenital adrenal hyperplasia, usually of the salt-losing variety, during adolescence or young adult life. The stimulus for the growth of the adrenal rests is inadequate corticosteroid suppressive therapy, and treatment with adequate doses almost always results in their regression. These tumors are histologically similar to primary Leydig cell tumors, but definite evidence of the origin of these may be achieved by demonstrating their 21-hydroxylase activity. Misdiagnosis of these tumors as primary Leydig cell tumors may lead to unnecessary orchidectomy and should be avoided.
Fragile X syndrome (Chapter 76) is caused by the amplification of a polymorphic CGG repeat in the 5′ untranslated region of the FMRI gene at Xp17.3. The gene encodes an RNA binding protein that is highly expressed in the brain and the testis. In otherwise normal individuals, 6-50 CGG repeats are present in the gene; the presence of 50-200 repeats (permutation) is associated with mild mental retardation and other abnormalities, while the presence of more than 200 repeats (fragile X mutation) is associated with the classic fragile X syndrome. Permutations are present in 1/1,000 white males, while mutations are found in 1/4,000 to 1/8,000. A cardinal characteristic of the condition is testicular enlargement (macro-orchidism), reaching 40-50 mL after puberty. Although the condition has been recognized in a child as young as 5 mo of age, affected boys younger than 6 yr of age rarely have testicular enlargement; by 8-10 yr of age, most have testicular volumes greater than 3 mL. The testes are enlarged bilaterally, are not nodular, and are histologically normal. Results of hormonal studies are normal. Direct DNA analysis searching for CGG repeat sequences permits definitive diagnosis.
Sex cord tumors with annular tubules of the testes are an extremely rare cause of breast development in young boys. These tumors usually are associated with Peutz-Jeghers syndrome; they occur bilaterally, are multifocal, and are detectible by ultrasonography. Excessive production of aromatase (P450arom), the enzyme that converts testosterone to estradiol, causes feminization of these boys.
In boys with unilateral cryptorchidism, the contralateral testis is about 25% larger than normal for age. Testicular enlargement has also been noted in boys with Henoch-Schönlein purpura and lymphangiectasia. Epidermoid and dermoid cysts of the testes have been reported rarely.
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