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True Precocious Puberty Following Treatment of a Leydig Cell Tumor: Two Case Reports and Literature Review

View Article: PubMed Central

ABSTRACT

Leydig cell testicular tumors are a rare cause of precocious pseudopuberty in boys. Surgery is the main therapy and shows good overall prognosis. The physical signs of precocious puberty are expected to disappear shortly after surgical removal of the mass. We report two children, 7.5 and 7.7 year-old boys, who underwent testis-sparing surgery for a Leydig cell testicular tumor causing precocious pseudopuberty. During follow-up, after an immediate clinical and laboratory regression, both boys presented signs of precocious puberty and ultimately developed central precocious puberty. They were successfully treated with gonadotropin-releasing hormone (GnRH) analogs. Only six other cases have been described regarding the development of central precocious puberty after successful treatment of a Leydig cell tumor causing precocious pseudopuberty. Gonadotropin-dependent precocious puberty should be considered in children treated for a Leydig cell tumor presenting persistent or recurrent physical signs of puberty activation. In such cases, therapy with GnRH analogs appears to be the most effective medical treatment.

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(A) Hematoxylin–eosin (H/E), original magnification 10x. Well-circumscribed nodule with solid/lobular architecture. (B) H/E, original magnification 200x. Neoplasm characterized by solid growth of polygonal cells with eosinophilic granular cytoplasm. No evidence of mitosis and/or necrosis. (C) IHC polymeric horseradish peroxidase (HRP)-linker antibody, original magnification 200x. Neoplastic cells are positive (brown) for gonadal hormone a-inhibin immunostain. (D) IHC polymeric horseradish peroxidase (HRP)-linker antibody, original magnification 200x. Neoplastic cells are negative for vimentin immunostain.
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Figure 1: (A) Hematoxylin–eosin (H/E), original magnification 10x. Well-circumscribed nodule with solid/lobular architecture. (B) H/E, original magnification 200x. Neoplasm characterized by solid growth of polygonal cells with eosinophilic granular cytoplasm. No evidence of mitosis and/or necrosis. (C) IHC polymeric horseradish peroxidase (HRP)-linker antibody, original magnification 200x. Neoplastic cells are positive (brown) for gonadal hormone a-inhibin immunostain. (D) IHC polymeric horseradish peroxidase (HRP)-linker antibody, original magnification 200x. Neoplastic cells are negative for vimentin immunostain.

Mentions: The patient was first evaluated at our Paediatric Endocrinology Department. Aged 7.5 years with a history of progressive appearance of secondary sexual characteristics for 4 months. He had pubic hair (Tanner stage PH2), enlarged testicular volume (Tanner stage G2: left testis 4 mL, right testis 6 mL) and an accelerated growth velocity. Pubertal stage has been performed according to Tanner-Marshall method on physical examination (1). Family history of precocious puberty was negative. His height was 134.6 cm (90th–97th centile, 1.63 SDS) and his body mass index (BMI) was 17.7 (1.17 SDS). Serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were suppressed, also after administration of gonadotropin-releasing hormone (GnRH) stimulation test. FSH and LH were measured by chemiluminescent immunoassay. His biological data at diagnosis are shown in Table 1. Tumor markers [alpha-fetoprotein (AFP), β-human chorionic gonadotropin (β-HCG)] were within the normal range. Adrenal function was normal. Ultrasound of the testis demonstrated an inhomogeneous hypoechogenic tumor located at the upper pole of the enlarged right testis (measuring 18.8 mm × 12 mm × 14 mm). Surgical enucleation of the testicular mass was performed. Histological examination revealed a Leydig cell tumor. Inhibin was expressed immunohistochemically and the index of proliferation (Ki67–MIB1) was <3% (Figure 1). Following surgery, levels of plasma sexual hormones rapidly returned to the normal prepuberal range and there was no sexual progression. Four months later, the patient presented with increased pubic hair (Tanner stage PH2) and increased bilateral testicular volume (Tanner stage G3: left and right testis 8 mL). Recurrent erections and ejaculations were observed. Bone age was accelerated to 12.5 years. Ultrasonographic examinations ruled out testicular tumor recurrence and brain magnetic resonance imaging (MRI) excluded a tumor of the hypothalamus or pituitary gland. The patient showed a pubertal response to GnRH stimulation test and the hormonal values are reported in Table 2. Therefore, non-organic central precocious puberty was diagnosed. Treatment with triptorelin (3.75 mg every 28 days) was started, resulting in clinical and laboratory regression; normal values of testosterone and normal, basal, and GnRH stimulated FSH and LH values were observed. At the last follow-up (2 years from the beginning of triptorelin therapy), the patient still continues treatment without adverse effects.


True Precocious Puberty Following Treatment of a Leydig Cell Tumor: Two Case Reports and Literature Review
(A) Hematoxylin–eosin (H/E), original magnification 10x. Well-circumscribed nodule with solid/lobular architecture. (B) H/E, original magnification 200x. Neoplasm characterized by solid growth of polygonal cells with eosinophilic granular cytoplasm. No evidence of mitosis and/or necrosis. (C) IHC polymeric horseradish peroxidase (HRP)-linker antibody, original magnification 200x. Neoplastic cells are positive (brown) for gonadal hormone a-inhibin immunostain. (D) IHC polymeric horseradish peroxidase (HRP)-linker antibody, original magnification 200x. Neoplastic cells are negative for vimentin immunostain.
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Related In: Results  -  Collection

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Figure 1: (A) Hematoxylin–eosin (H/E), original magnification 10x. Well-circumscribed nodule with solid/lobular architecture. (B) H/E, original magnification 200x. Neoplasm characterized by solid growth of polygonal cells with eosinophilic granular cytoplasm. No evidence of mitosis and/or necrosis. (C) IHC polymeric horseradish peroxidase (HRP)-linker antibody, original magnification 200x. Neoplastic cells are positive (brown) for gonadal hormone a-inhibin immunostain. (D) IHC polymeric horseradish peroxidase (HRP)-linker antibody, original magnification 200x. Neoplastic cells are negative for vimentin immunostain.
Mentions: The patient was first evaluated at our Paediatric Endocrinology Department. Aged 7.5 years with a history of progressive appearance of secondary sexual characteristics for 4 months. He had pubic hair (Tanner stage PH2), enlarged testicular volume (Tanner stage G2: left testis 4 mL, right testis 6 mL) and an accelerated growth velocity. Pubertal stage has been performed according to Tanner-Marshall method on physical examination (1). Family history of precocious puberty was negative. His height was 134.6 cm (90th–97th centile, 1.63 SDS) and his body mass index (BMI) was 17.7 (1.17 SDS). Serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were suppressed, also after administration of gonadotropin-releasing hormone (GnRH) stimulation test. FSH and LH were measured by chemiluminescent immunoassay. His biological data at diagnosis are shown in Table 1. Tumor markers [alpha-fetoprotein (AFP), β-human chorionic gonadotropin (β-HCG)] were within the normal range. Adrenal function was normal. Ultrasound of the testis demonstrated an inhomogeneous hypoechogenic tumor located at the upper pole of the enlarged right testis (measuring 18.8 mm × 12 mm × 14 mm). Surgical enucleation of the testicular mass was performed. Histological examination revealed a Leydig cell tumor. Inhibin was expressed immunohistochemically and the index of proliferation (Ki67–MIB1) was <3% (Figure 1). Following surgery, levels of plasma sexual hormones rapidly returned to the normal prepuberal range and there was no sexual progression. Four months later, the patient presented with increased pubic hair (Tanner stage PH2) and increased bilateral testicular volume (Tanner stage G3: left and right testis 8 mL). Recurrent erections and ejaculations were observed. Bone age was accelerated to 12.5 years. Ultrasonographic examinations ruled out testicular tumor recurrence and brain magnetic resonance imaging (MRI) excluded a tumor of the hypothalamus or pituitary gland. The patient showed a pubertal response to GnRH stimulation test and the hormonal values are reported in Table 2. Therefore, non-organic central precocious puberty was diagnosed. Treatment with triptorelin (3.75 mg every 28 days) was started, resulting in clinical and laboratory regression; normal values of testosterone and normal, basal, and GnRH stimulated FSH and LH values were observed. At the last follow-up (2 years from the beginning of triptorelin therapy), the patient still continues treatment without adverse effects.

View Article: PubMed Central

ABSTRACT

Leydig cell testicular tumors are a rare cause of precocious pseudopuberty in boys. Surgery is the main therapy and shows good overall prognosis. The physical signs of precocious puberty are expected to disappear shortly after surgical removal of the mass. We report two children, 7.5 and 7.7 year-old boys, who underwent testis-sparing surgery for a Leydig cell testicular tumor causing precocious pseudopuberty. During follow-up, after an immediate clinical and laboratory regression, both boys presented signs of precocious puberty and ultimately developed central precocious puberty. They were successfully treated with gonadotropin-releasing hormone (GnRH) analogs. Only six other cases have been described regarding the development of central precocious puberty after successful treatment of a Leydig cell tumor causing precocious pseudopuberty. Gonadotropin-dependent precocious puberty should be considered in children treated for a Leydig cell tumor presenting persistent or recurrent physical signs of puberty activation. In such cases, therapy with GnRH analogs appears to be the most effective medical treatment.

No MeSH data available.


Related in: MedlinePlus