Carcinoma corticosuprarrenal virilizante en un niño / Virilizing adrenocortical carcinoma in a child

Introducción: Los tumores suprarrenales en niños son poco frecuentes y el carcinoma suprarrenal representa menos de un 10 %. En el prepúber, la manifestación más típica es el desarrollo de pubertad precoz. Objetivo: Describir las características clínicas, los procederes diagnósticos y terapéuticos de un paciente con carcinoma adrenal en edad pediátrica. Presentación de caso: Paciente de 8 años, masculino y de piel blanca con antecedentes de salud. Acude a la consulta por crecimiento de vello pubiano y aumento del pene en longitud y grosor de aproximadamente 2 años de evolución. En el examen físico se constatan aumento de la velocidad de crecimiento y signos sugestivos de virilización (voz gruesa, vello axilar, vello sexual púbico y genitales externos estadio III de Tanner). Se realizaron estudios hormonales que corroboraron el hiperandrogenismo por secreción endógena autónoma, con niveles de gonadotropinas suprimidas, niveles de testosterona y dehidroepiandrosterona elevados. También se realizaron estudios imagenológicos que evidenciaron edad ósea acelerada y la existencia de un tumor. Se realizó una adrenalectomía izquierda y se confirmó por anatomía patológica el carcinoma corticosuprarrenal virilizante izquierdo en estadío 2. Inició un tratamiento con quimioterapia por dicho diagnóstico y actualmente se mantiene en seguimiento. Conclusiones: Los carcinomas corticosuprarrenales en niños son mayoritariamente funcionantes y constituyen una de las causas de pubertad precoz periférica. Estos son infrecuentes y agresivos, por lo que la realización de estudios genéticos en familias con síndromes hereditarios contribuiría a su diagnóstico precoz para un adecuado tratamiento y mejor pronóstico(AU)

Introduction: Adrenal tumors in children are rare and adrenal carcinoma represents less than the 10 percent. In the prepubescent, the most typical manifestation is the development of early puberty. Objective: Describe the clinical characteristics and diagnostic and therapeutic procedures of a patient with adrenal carcinoma in a pediatric age. Case presentation: 8-year-old male, white-skinned patient with a history of health conditions. He attentds to the consultation due to pubic hair growth and penis enlargement in length and thickness of approximately 2 years of evolution. Physical examination shows increased growth rate and signs suggestive to virilization (deep voice, axillary hair, pubic sexual hair and external genitalia in Tanner's stage III). Hormonal studies were carried out that corroborated hyperandrogenism by autonomic endogenous secretion, with suppressed gonadotropin levels, elevated testosterone and dehydroepiandrosterone levels. Imaging studies were also performed that showed accelerated bone age and the existence of a tumor. A left adrenalectomy was performed and stage 2 left virilizing adrenocrotical carcinoma was confirmed by pathological anatomy studies. He began chemotherapy treatment for this diagnosis and is currently being followed up. Conclusions: Adrenocortical carcinomas in children are mostly functioning and are one of the causes of peripheral early puberty. These are uncommon and aggressive, so genetic studies in families with hereditary syndromes would contribute to their early diagnosis for adequate treatment and better prognosis(AU)

Tumor ovárico de células esteroideas sin otra especificación, durante el embarazo

Los tumores de células esteroides de ovario se clasifican en luteoma estromal, tumor de células de Leydig y tumor de células esteroideas sin otra especificación, según su origen embrionario. El tumor ovárico de células esteroideas sin otra especificación es un tumor benigno raro, pero con potencial maligno; representa menos del 0,1% de todos los tumores de ovario. Deben ser considerados como causa de virilización en mujeres adultas por la producción de testosterona. Solo un feto femenino corre riesgo de virilización. Al igual que otros tumores del estroma ovárico, los tumores deben ser tratados quirúrgicamente. La cirugía está indicada en casos de agrandamiento ovárico unilateral sólido, debido a un 50% de probabilidad de malignidad. En el embarazo, los tumores ováricos de células esteroideas sin otra especificación son excepcionalmente raros y deben ser diferenciados del luteoma del embarazo y otras neoplasias malignas del ovario. Con mayor frecuencia pueden complicarse con rotura y/o torsión. Se presenta un caso de tumor ovárico de células esteroideas sin otra especificación durante el embarazo.

Ovarian steroid cell tumors are classified into stromal luteoma, Leydig cell tumor and steroid cell tumor not otherwise specified, according to their embryonal origin. Ovarian steroid cell tumor not otherwise specified is a rare benign tumor, but with malignant potential; it accounts for less than 0.1% of all ovarian tumors. They should be considered as a cause of virilization in adult women due to testosterone production. Only a female fetus is at risk of virilization. Like other ovarian stromal tumors, the tumors must be treated surgically. Surgery is indicated in cases of solid unilateral ovarian enlargement, due to a 50% chance of malignancy. In pregnancy, ovarian steroid cell tumors not otherwise specified are exceptionally rare and should be differentiated from luteoma of pregnancy and other malignant ovarian neoplasms. More frequently they may be complicated by rupture and/or torsion. A case of nonspecific ovarian steroid cell tumor during pregnancy is presented.

Preliminary investigation of gender assignment in 46,XY disorders of sex development with severe male undermasculinisation / 中华儿科杂志

Objective@#To explore the feasibility of gender assignment in 46,XY disorders of sex development (DSD) with severe undermasculinisation mainly based on molecular diagnosis.@*Methods@#A retrospective study of 45 patients of 46, XY DSD with severe undermasculinisation were admitted between November 2015 and October 2018 at Children′s Hospital, Zhejiang University School of Medicine. The initial social gender were all female, of whom the external genital manifestations were Prader 0 to 2; the degree of masculinity was scored using external masculinisation score (EMS); the position and development of the gonads were examined by ultrasound, cystoscopy and laparoscopy, also including assessing the development of the Wolffian tube and the Müllerian tube. The level and ratio of testosterone to dihydrotestosterone before and after hCG stimulation were evaluated for the function of Leydig cell and 5α-reductase-2. Gender role scales and sandbox games were used to assess gender role behavior. Genital sensitivity to androgen stimulation was assessed; A panel including 163 genes related to gender development were determined by second-generation sequencing in all 45 patients. Finally, a multidisciplinary team (MDT) makes a gender assignment after a comprehensive analysis mainly based on the molecular etiological diagnosis.@*Results@#Thirty-nine out of 45 patients (87%) had an identifiable genetic etiology, and the remaining 6 (13%) were negative for genetic testing. Forty-five patients had EMS less than or equal to 3 points. Sexual psychological assessment was performed in 39 patients, with male dominance in 24 (62%) and female dominance in 15 (38%). The gender assignment was 23 cases (51%) for male and 19 cases (42%) for female, and 3 cases (7%) were not completely determined.@*Conclusions@#Molecular diagnosis provides a strong basis for appropriate gender assignment of 46, XY DSD children with severe undermasculinisation. Based on molecular diagnosis, each DSD should be analyzed by professional MDT to analyze the clinical symptoms/signs, gonadal development, gonad tumor risk, external genital morphology, sexual psychological assessment, potential fertility opportunities, parental views, Social and cultural factors, etc. make appropriate gender assignment.

Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: description of a new mutation, R384X / Hiperplasia suprarrenal congénita por déficit de 11-beta-hidroxilasa: descripción de una nueva mutación, R384X

Abstract Case Description: It is presented the phenotype of a new compound heterozygous mutation of the genes R384X and Q356X encoding the enzyme of 11-beta-hydroxylase Clinical Findings: Severe virilization, peripheral hypertension, and early puberty. Treatment and Outcome: Managed with hormone replacement therapy (corticosteroid) and antihypertensive therapy (beta-blocker), resulting in the control of physical changes and levels of arterial tension. Clinical Relevance: According to the phenotypic characteristics of the patient, it is inferred that the R384X mutation carries an additional burden on the Q356X mutation, with the latter previously described as a cause of 11-beta-hydroxylase deficiency. The description of a new genotype, as in this case, expands the understanding of the hereditary burden and deciphers the various factors that lead to this pathology as well as the other forms of congenital adrenal hyperplasia (CAH), presenting with a broad spectrum of clinical presentations. This study highlights the importance of a complete description of the patient's CAH genetic profile as well as their parents' genetic profile.

Resumen Descripción del Caso: Se presenta el fenotipo de una nueva mutación heterocigota compuesta en los genes Q356X y R384X que codifican la enzima 11-beta-hidroxilada Hallazgos Clínicos: Virilización severa, pubertad precoz periférica e hipertensión. Tratamiento y Resultados: Manejo con terapia de reemplazo hormonal con corticoide y antihipertensivo con beta-bloqueador con lo que se logró controlar los cambios físicos y los niveles de tensión arterial. Relevancia Clínica: Según las características fenotípicas del paciente se infiere que la mutación R384X acarrea una carga adicional a la mutación Q356X, esta última descrita como causa de deficiencia de 11-beta-hidroxilasa. La descripción de nuevos genotipos, como en este caso, permite ampliar la comprensión de la carga hereditaria y descifrar los diversos factores que llevan a que esta patología, así como las demás formas de hiperplasia suprarrenal congénita (HSC), se presenten con un amplio espectro de cuadros clínicos. Esto permite resaltar la importancia de una descripción completa del perfil genético del paciente con HSC y de sus padres.

Tumor adulto de células de la granulosa del ovario: presentación de un caso / Adult granulosa cell tumor of ovary: a case presentation

Introducción: el tumor de células de la granulosa ovárica representa del 2 al 5 % de todos los tumores de ovario. Producen hormonas esteroideas con acciones estrogénicas o androgénicas, por lo que esto facilita su diagnóstico precoz. Se reconocen dos subtipos histopatológicos, uno adulto y otro juvenil. Objetivo: describir el cuadro clínico y hallazgo histopatológico de una paciente con tumor de células de la granulosa. Caso clínico: se muestra el caso de una paciente de 49 años de edad que clínicamente presentó signos de virilización progresiva. Se le diagnosticó por estudio de imagen de ultrasonido transvaginal y tomografía axial computarizada un tumor en el ovario derecho, se realizó su intervención quirúrgica y biopsia que dio como resultado tumor de células de la granulosa. Conclusiones: los tumores que producen estrógenos son los que se encuentran con mayor frecuencia, representando las tres cuartas partes de los tumores de la granulosa. La virilización en la mujer post menopaúsica por un tumor de células de la granulosa es infrecuente, sin embargo, fue el diagnóstico histopatológico en esta paciente.

Background: ovary granulosa cell tumors represent the 2 to 5 % of all ovary tumors. It produces steroid hormones with estrogenic or androgynous actions which makes easier its early diagnosis. Two histopathological subtypes are recognized: adult and juvenile. Objective: to describe the clinical manifestation and histopathological founds in a patient with a granulosa cell tumor. Clinical case: the case of a forty-nine-year-old patient, who clinically presented signs of progressively acquiring male characteristics, is presented. She was diagnosed a tumor in the right ovary by means of a transvaginal ultrasound and a computerized axial tomography. A surgical procedure and a biopsy were conducted; the results of the biopsy confirmed the presence of a granulosa cell tumor. Conclusions: tumors that produce estrogens are more frequently found and represent the three quarters of the granulosa tumors. Acquiring male characteristics by a granulosa cell tumor in postmenopausal women is infrequent; nevertheless, it was the histopathological diagnosis for this patient.

Virilizing Adrenocortical Carcinoma Advancing to Central Precocious Puberty after Surgery / 가정의학회지

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.

Síndrome hiperandrogênica em mulher na pós-menopausa: relato de caso / Hyperandrogenic syndrome in a postmenopausal woman: a case report

RESUMO As síndromes hiperandrogênicas englobam doenças que se manifestam através de um aumento da atividade biológica dos androgênios e podem ter origem em patologias neoplásicas ou funcionais. Os tumores ovarianos secretores de androgênios constituem cerca de 1 por cento das neoplasias do ovário. O tumor de células esteroides é um dos tipos mais raros, sendo responsáveis por menos de 0,1 por cento de todos os tumores ovarianos. São habitualmente benignos, de pequenas dimensões e unilaterais. Neste relato, apresenta-se o caso raro de um tumor unilateral de células esteroides. Paciente do sexo feminino, 60 anos, por hirsutismo, hipertorfia do clitóris e elevação dos níveis séricos de estradiol, com quatro meses de evolução. Apresentava níveis elevados de testosterona total e de 17-OH-Progesterona.

ABSTRACT Hyperandrogenic syndromes include diseases that manifest through an increased biological activity of androgens and that can originate from neoplastic or functional diseases. Androgen-secreting ovarian tumors represent about 1 percent of ovarian neoplasias. Steroid cell tumors are among the more rare types which account for less than 0.1 percent of all ovarian tumors. They are usually benign, of small dimensions and unilateral. We report here a rare case of a unilateral steroid cell tumor. A 60-year-old woman was seen after four months of evolution of hirsutism, clitoris hypertrophy and elevation of serum estradiol levels. Her total testosterone and 17-OH-progesterone levels were also increased.

A sclerosing stromal tumor of the ovary with masculinization in a premenarchal girl / 소아과

A sclerosing stromal tumor of the ovary is an extremely rare benign tumor; it usually is found during the second and third decades of life. Patients present with pelvic pain or a palpable abdominal mass. Hormonal effects such as masculinization are uncommon. Here, an 11-year old premenarchal girl presented with deepening of the voice. In addition, clitoromegaly and hirsutism with a male suprapubic hair pattern were observed. The laboratory findings showed that the testosterone level was elevated to 3.67 ng/mL, andostenedione to above 10 ng/mL, dehydroepiandrosterone-sulfate to 346 microg/dL and 17-hydroxy progesterone (17-OHP) to 11.28 ng/mL. The chromosome evaluation revealed a 46,XX female karyotype. An adrenocorticotropic hormone stimulation test was performed. The 17-OHP to cortisol ratio in 30 minutes was 0.045, which suggested a heterozygote for the 21-hydroxylase deficiency. However, the CYP21A2 gene encoding steroid 21-hydroxylase showed normal. The pelvic ultrasound showed a heterogeneous mass consisting of predominantly solid tissue in the pelvic cavity. The pelvic magnetic resonance imaging revealed an 8.9x6.2x6.6 cm mass of the left ovary. A left oophrectomy was performed and microscopic examination confirmed a sclerosing stromal tumor. Immunohistochemical studies showed that the tumor was positive for smooth muscle actin and vimentin, but negative for S-100 protein and cytokeratin. Following surgery, the hormone levels returned to the normal range and the hirsutism resolved.

Virilizing Adrenocortical Oncocytoma in a Child: A Case Report

Functioning adrenocortical oncocytomas are extremely rare and most reported patients are 40-60 yr of age. To our knowledge, only 2 cases of functioning adrenocortical oncocytomas have been reported in childhood. We report a case of functioning adrenocortical oncocytoma in a 14-yr-old female child presenting with virilization. She presented with deepening of the voice and excessive hair growth, and elevation of plasma testosterone and dehydroepiandrosterone sulfate. She had an adrenalectomy. The completely resected tumor composed predominantly of oncocytes without atypical mitosis and necrosis. A discussion of this case and a review of the literature on this entity are presented.

Ovarian Thecoma with Virilizing Manifestations

A 29-year-old woman presented with secondary amenorrhea, primary infertility, and virilization, which had developed over the past 2 years was suspected to have a virilizing tumor at her left ovary. Her serum testosterone level was markedly elevated (380 ng/dL). Left salpingooophorectomy was performed, and histopathological examination revealed a thecoma of the left ovary. The postoperative serum testosterone level returned to 65 ng/dL. The patient did not have regression of virilism soon. However, the patient had a normal menstruation 29 days after surgery and gave birth to a baby 13 months after surgery.

A Case of Adrenocortical Tumor in a 16-Month-Old Boy Presenting with Virilization / 대한소아내분비학회지

A 16-month-old boy had signs of virilization such as penile enlargement and pubic hair since 13 months of age. Hormone evaluation indicated increased levels of 17-OH-progesterone, dehydroepiandrosterone- sulfate (DHEA-S) and testosterone. Initially he was diagnosed as simple virilizing type of congenital adrenal hyperplasia and hydrocortisone was given to him. After 2 months, his penile enlargement continued and we did not find gene mutation for 21-hydroxylase deficiency. Adrenal magnetic resonance imaging revealed a 3.5x2.7x4.4 cm size of adrenal mass consistent with an adrenocortical tumor. The patient underwent surgical excision of the well-encapsulated tumor with normalization of his hormone levels. Childhood adrenocortical tumors are rare and are not well characterized. Surgery is the definitive treatment for adrenocortical tumors and prognosis is often poor. We report a case of adrenocortical tumor in a 16-month-old boy presenting with virilization with review of literature.

Clinical Review of the Pediatric Primary Adrenocortical Tumors

Adrenocortical tumors are very rare in children and the clinical course is not clearly understood. The aim of this study is to review the clinical characteristics and courses of pediatric adrenocortical tumors. The medical records of patients who underwent surgery for primary adrenal tumor at the Department of Surgery, Seoul National University hospital, from Jan. 1986 to Feb. 2006 were reviewed. There were 10 adrenocortical tumor patients; 5 had adrenocortical adenoma and 5 adrenocortical carcinoma. All of the adrenocortical adenomas presented as functioning tumors, i.e., Cushing syndrome or virilization. However, only 2 patients had functioning adrenocortical carcinoma. Median size of adenoma was 5 (3.3-6) cm, and carcinoma 12.5 (6.5-13)cm. Adenomas were smaller than 6 cm and carcinomas were larger than 6.5cm. Surgical resection alone cured all adrenocortical adenoma patients, and they were all alive without recurrence. Three of 5 adrenocortical carcinoma patients died of tumor recurrence despite radical surgery and chemotherapy. There were 2 long-term survivals for adrenocortical carcinoma, one patient survived 10 years without recurrence until he died of newly developed osteosarcoma, and the other patient is alive without recurrence for 20 years. As the prognosis of pediatric adrenocortical carcinoma is poor, peri-operative aggressive chemotherapy is suggested in addition to radical surgery.

Acetato de medroxiprogesterona administrado em período pré-natal induz hipospádia em machos e virilização em fêmeas de camundongos / Medroxyprogesterone acetate administered during pre-natal period causes hypospadia in male and virilization in female mice

A fertilização in vitro tem sido associada com um aumento na incidência das hipospádias, e alguns hormônios esteróides usados em seus protocolos têm sido implicados neste processo. Para testar essas hipóteses em um modelo animal, descrevemos neste trabalho as alterações morfológicas ocorridas no tubérculo genital de camundongos, expostos à progesterona durante a vida intrauterina. Foi administrado acetato de medroxiprogesterona por via subcutânea no período pré-natal em animais normais e animais desprovidos de receptores androgênicos (Tfm). A progesterona induziu a formação de hipospádia nos animais do sexo masculino, virilização nos do sexo feminino e não causou alterações nos animais Tfm.

In vitro fertilization (IVF) has been associated with an increase incidence of hypospadias. IVF protocols require the maternal use of progesterone which may be a factor in causing hypospadias. To test these hypotheses in an animal model, we describe the effects of maternal progesterone exposure on genital development in mice. Medroxyprogesterone acetate (MPA) was administered by subcutaneous injection during the pre-natal period to wild type mice and animals knockout to androgen receptors (Tfm mice). Progesterone caused hypospadias in male mice fetuses, a virilizing effect in the female mice genitalia and didn't have any effect in Tfm animals.