RESUMO
Steroid cell tumors, not otherwise specified (SCT-NOS), are uncommon ovarian neoplasms accompanied by virilization symptoms due to hyperandrogenism, which are malignant in approximately one-third of the cases. Given the rarity of SCT-NOS, their molecular underpinnings have not yet been studied in depth. In this case series, we performed the first comprehensive analysis of the genetic landscape of this rare ovarian tumor. A detailed clinicopathological description of an index case is also provided. Over a 20-year period, a total of eight patients were seen at our institution. Total nucleic acids (RNA and DNA) were extracted from evaluable formalin-fixed, paraffin-embedded tumor specimens (n = 7) and subjected to TruSight Oncology 500 testing and/or exome sequencing. The results identified pathogenic variants in several hypoxia-related genes - including HIF1A, VHL, SDHB, SRC, IDH2, and FOXO4. As the first comprehensive genetic analysis of SCT-NOS, this study shows that dysregulation in the hypoxia signaling pathway is a key molecular feature of this rare tumor. Clinically, long-term follow-up with periodic measurements of androgen levels should be pursued in all cases since recurrences may occur several years after the initial diagnosis.
Assuntos
Neoplasias Ovarianas , Tumores do Estroma Gonadal e dos Cordões Sexuais , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Tumores do Estroma Gonadal e dos Cordões Sexuais/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/complicações , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Virilismo/complicações , Virilismo/diagnóstico , Hipóxia/complicações , EsteroidesRESUMO
Adrenocortical tumor (ACT) is a rare malignant tumor which usually present with Cushing syndrome and virilization. Paraneoplastic syndromes (PNS) due to neoplasms can occur with peptides or cytokines secreted by the tumor. Here, we report a 13-month-old-male presented with severe masculinization. He had signs of precocious puberty with enlarged testicles, very high testosterone levels but low levels of gonadotrophins, and elevated ß-hCG. He underwent a left nephrectomy. The histopathological evaluation revealed a diagnosis of adrenocortical neoplasm. The levels of androgens and ß-hCG normalized after the resection of tumor, and the clinical findings improved within few months. We report the first pediatric patient with peripheral precocious puberty due to an ACT that secretes ß-hCG as PNS. A ß-hCG secreting ACT can cause severe virilization due to increased gonadal androgens stimulated by ß-hCG as well as due to increased adrenal androgens from the tumor.
Assuntos
Neoplasias , Síndromes Paraneoplásicas , Puberdade Precoce , Feminino , Humanos , Criança , Masculino , Lactente , Puberdade Precoce/etiologia , Puberdade Precoce/diagnóstico , Androgênios , Virilismo/complicações , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologiaRESUMO
Sertoli-Leydig cell tumours (SLCTs) represent a rare cause of hyperandrogenic state. SLCTs are sex cord ovarian neoplasms, accounting for <0.2% of all ovarian tumours. Most of the sex cord-stromal tumours have a benign clinical course, with 10%-20% of them at risk of aggressive course. We report a case of a woman in her 30s who presented with androgenic alopecia, virilisation and secondary amenorrhoea. The evaluation revealed an extremely high testosterone level. Imaging for the localisation of source of excess testosterone with contrast-enhanced CT of the abdomen revealed a right ovarian mass. Hence, a diagnosis of testosterone-secreting ovarian tumour was considered. The patient underwent right salphingo-oophorectomy, and histopathology was reported as Sertoli cell tumour. Postoperatively, there was normalisation of serum testosterone levels with decrease in virilisation and resumption of spontaneous menstrual cycles. The patient conceived spontaneously after 2 months of surgery.
Assuntos
Neoplasias Ovarianas , Tumor de Células de Sertoli-Leydig , Tumores do Estroma Gonadal e dos Cordões Sexuais , Alopecia/complicações , Feminino , Humanos , Células Intersticiais do Testículo/patologia , Masculino , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Tumor de Células de Sertoli-Leydig/complicações , Tumor de Células de Sertoli-Leydig/diagnóstico , Tumor de Células de Sertoli-Leydig/cirurgia , Tumores do Estroma Gonadal e dos Cordões Sexuais/complicações , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia , Testosterona , Virilismo/complicaçõesRESUMO
INTRODUCTION: To describe experiences of clitoromegaly in women with congenital adrenal hyperplasia (CAH). METHODS: CAH females (46XX, ≥16 years old) from the United States and Canada were eligible for a cross-sectional online survey (2019-2020) if reporting clitoromegaly (life-long: "growing up with a larger than average clitoris," secondary: "clitoris grew over weeks or months"). A multidisciplinary team and women with CAH drafted questions assessing net effects of clitoromegaly on 10 activities and 10 life domains. Fisher's exact test was used to compare net effect (positive-negative) vs. no effect (Bonferroni p = 0.05/10 = 0.005). RESULTS: Of 97 women with CAH enrolled, 53 women (55%, median age: 36 years, advocacy group recruitment: 81%) reported recognizing clitoromegaly at median 11-13 years old, with 21% identifying it in adulthood. There was no difference in self-reported timing or clitoral shape between life-long or secondary clitoromegaly (p ≥ 0.06). There were no net positive effects of clitoromegaly. Rather, clitoromegaly had net negative effects on 7/10 activities (p ≤ 0.003) and no net effect (neutral) on 3 (Table). Women were less likely to wear tight clothing, change clothes in public locker rooms and play group sports. Women reported net negative effects for most romantic activities (dating, any sexual activity, pain-free sexual activity, having a partner see their genitalia, p=<0.003), but did not report a net effect on pleasurable sexual activity (p = 0.12). Clitoromegaly had net negative effects in 9/10 life domains (p < 0.001) and neutral on job self-perception (p = 0.25). Few women reported any positive impact (2-6%). However, 49-59% of women experienced poor self-esteem, anxiety, gender self-perception and body image, while 36% felt "down or depressed." Also, 21-23% experienced negative self-perception as friends and parents, 42-47% reported negative effects on plans for romantic and sexual relationships. Responses did not differ with advocacy group membership (p ≥ 0.02). DISCUSSION: Our findings support qualitative and case series evidence that clitoromegaly has a negative psychological outcome on women with CAH. Clitoromegaly may add to the burden of living with a chronic endocrine disease. Women with positive and negative experiences had the same opportunity to participate. Since we could not assess objective clitoral size, baseline virilization and exact nature of any childhood clitoral procedures, these data cannot be used to estimate the impact of specific clitoral size or effectiveness of early clitoral treatments. CONCLUSIONS: Clitoromegaly appears to be common among women with CAH. While experiences of clitoromegaly vary between women, the overall experience is negative in multiple social, romantic, and emotional activities and domains.
Assuntos
Hiperplasia Suprarrenal Congênita , Feminino , Humanos , Adulto , Criança , Adolescente , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/psicologia , Clitóris , Estudos Transversais , Virilismo/complicações , Hipertrofia , População Norte-AmericanaRESUMO
Hyperandrogenism with virilisation de novo in postmenopausal women is exceedingly rare, with aetiology oscillating between ovarian tumours, adrenal tumours, ovarian hyperthecosis and, less frequently, Cushing's syndrome. We report a case of a postmenopausal woman in her late 60s, referred from her primary healthcare physician to a gynaecology appointment due to hirsutism and vasomotor symptoms. At physical examination, clitoromegaly was also identified. Blood tests revealed severe hyperandrogenemia, with total testosterone above 200 ng/dL, but transvaginal ultrasound and abdominal CT were unremarkable. Three months later, abdominal CT was repeated, revealing a moderate heterogeneous enhancement with 18 mm on the left ovary, which was confirmed by transvaginal ultrasound. Total laparoscopic hysterectomy with bilateral adnexectomy was performed. Histopathological examination reported an ovarian steroid cell tumour not otherwise specified on the left ovary and bilateral ovarian hyperthecosis. Two months later, the patient had normal total testosterone and the hirsutism complaints were completely absent.
Assuntos
Hiperandrogenismo , Neoplasias Ovarianas , Síndrome do Ovário Policístico , Tumores do Estroma Gonadal e dos Cordões Sexuais , Feminino , Hirsutismo/etiologia , Humanos , Hiperandrogenismo/etiologia , Masculino , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Síndrome do Ovário Policístico/complicações , Pós-Menopausa , Testosterona , Virilismo/complicaçõesRESUMO
Postmenopausal hyperandrogenism is a state of relative or absolute androgen excess originating from the adrenal glands and/or ovaries clinically manifested by the presence of terminal hair in androgen-dependent areas of the body, and other manifestations of hyperandrogenism such as acne and alopecia or the development of virilization. In such circumstances, physicians must exclude the possibility of rare but serious androgen-producing tumors of the adrenal glands or ovaries. Worsening of undiagnosed hyperandrogenic disorders such as polycystic ovary syndrome, congenital adrenal hyperplasia, ovarian hyperthecosis, Cushing syndrome and iatrogenic hyperandrogenism should be considered for differential diagnosis. Elevated serum testosterone not only causes virilizing effects, but also will lead to hypercholesterolemia, insulin resistance, hypertension and cardiac disease. An ovarian androgen-secreting tumor, which is diagnosed in 1-3 of 1000 patients presenting with hirsutism, comprises less than 0.5% of all ovarian tumors. Adrenal tumors, including non-malignant adenomas and malignant carcinomas, are less common than ovarian tumors but cause postmenopausal virilization. Measurement of serum testosterone, sex hormone-binding globulin, dehydroepiandrosterone sulfate, androstenedione and inhibin B is necessary in postmenopausal women with the complaints and signs of hyperandrogenism. Some tests to discard Cushing syndrome should also be done. After an etiological source of androgen hypersecretion has been suspected, we recommend performing magnetic resonance imaging of the adrenal glands or ovaries. Medical management with gonadotropin-releasing hormone agonist/analogues or antagonists has been reported for women who are either unfit for surgery or in whom the source of elevated testosterone is unidentified.
Assuntos
Síndrome de Cushing , Hiperandrogenismo , Neoplasias Ovarianas , Síndrome do Ovário Policístico , Androgênios , Síndrome de Cushing/complicações , Síndrome de Cushing/etiologia , Feminino , Humanos , Hiperandrogenismo/diagnóstico , Hiperandrogenismo/etiologia , Masculino , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/etiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Pós-Menopausa , Testosterona , Virilismo/complicaçõesRESUMO
Anxiety is one of the most frequent psychiatric disorders. Despite the fact that most studies describe an anxiolytic effect of testosterone, hyperandrogenemia in mothers is assumed to be related to an increased risk of mood disorders in their offspring. An increasing body of scientific evidence suggests that an altered expression of interneuronal markers of the hippocampus may be the cause of anxiety. The aim of this study was to examine the influence of maternal hyperandrogenemia on behavioral parameters of anxiety-like behavior, neuropeptide Y (NPY) and parvalbumin (PV) expression in the hippocampus, and the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex. Pregnant female Wistar albino rats were treated with testosterone undecanoate on the 20th day of gestation. Anxiety-like behavior in adult female offspring was evaluated by the elevated plus maze test and the open field. The number of PV and NPY immunoreactive cells in the hippocampus was determined immunohistochemically. The level of BDNF expression in the hippocampus and cerebral cortex was analyzed with the Western blot test. Prenatal hyperandrogenization increased anxiety-like behavior in female offspring and decreased expression of NPY+ and PV+ in the CA1 region of the hippocampus as compared to the control group. BDNF expression in the hippocampus and cerebral cortex of prenatally androgenized female offspring was significantly increased in comparison with the controls. Prenatal hyperandrogenization may be the cause of anxiety-like behavior in female offspring. Decrease in NPY and PV expression in the hippocampus may explain the possible mechanism of hyperandrogenization induced anxiety.
Assuntos
Ansiedade/etiologia , Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Interneurônios/fisiologia , Inibição Neural/fisiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Virilismo/complicações , Animais , Ansiedade/sangue , Ansiedade/fisiopatologia , Estradiol/sangue , Feminino , Hipocampo/fisiopatologia , Aprendizagem em Labirinto , Neuropeptídeo Y/metabolismo , Parvalbuminas/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos Wistar , Testosterona/administração & dosagem , Testosterona/sangue , Testosterona/farmacologia , Virilismo/fisiopatologiaRESUMO
Background Steroid 21-hydroxylase deficiency is an autosomal recessive disorder, present in 90-95% of all cases with congenital adrenal hyperplasia (CAH). The classical simple virilizing (SV) form of the disease causes virilization of the external genitalia in newborn females and pseudo-precocious puberty in both sexes, due to reactive androgen overproduction. Case presentation We describe a 3.5-year-old girl presenting with pubarche, P2 according to Tanner, advanced bone age of 6 years and 10 months, and high serum levels of 17-hydroxyprogesterone (17-OHP). Molecular analysis of the nine most common pseudogene-derived CYP21A2 point mutations was performed in the patient and her family members using the polymerase chain reaction/amplification-created restriction site (PCR/ACRS) method. We detected the P30L/I172N genotype in the patient. She had inherited a mild P30L mutation from her mother and a severe I172N mutation from her father. Conclusions Although the CAH phenotype is determined by the allele that produces most of the enzyme activity and the mild non-classical (NC) phenotype should be expected, the mild P30L known to be more virilizing probably induced the classical SV phenotype in our patient. A continuous regimen of hydrocortisone at a recommended dose failed to decrease the 17-OHP sufficiently. Careful tapering of the dose did not help, and her pubic hair advanced to P3 according to Tanner. Individually tailored treatment is warranted in this patient.
Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Hidrocortisona/administração & dosagem , Mutação , Esteroide 21-Hidroxilase/genética , Virilismo/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/patologia , Adulto , Criança , Feminino , Genótipo , Humanos , Masculino , Linhagem , Fenótipo , Falha de Tratamento , Virilismo/complicações , Virilismo/patologiaRESUMO
We herein present the case of a 27-year-old woman with clinical and biochemical features of virilism. Imaging studies revealed the presence of a bilateral adrenal tumor. Although the secretion of androgens was remarkable, the autonomous production of cortisol was also evident because of a loss of circadian rhythm and the absence of cortisol suppression by dexamethasone. The surgical excision of both adrenal tumors was performed, and the histological examination showed no malignancy. We also report the successful pregnancy and delivery of the patient who showed evolving adrenocortical insufficiency along with virilization and Cushing's syndrome and who continued to receive glucocorticoid replacement therapy during pregnancy.
Assuntos
Neoplasias do Córtex Suprarrenal/complicações , Adenoma Adrenocortical/complicações , Síndrome de Cushing/complicações , Virilismo/complicações , Neoplasias do Córtex Suprarrenal/cirurgia , Adulto , Ritmo Circadiano , Feminino , Humanos , Hidrocortisona/biossíntese , GravidezRESUMO
BACKGROUND: Maternal virilization during pregnancy is a rare phenomenon. Polycystic ovary syndrome (PCOS), luteoma and luteinic cysts are the most frequent and benign etiologies. This article presents two cases of recurrent maternal virilization during pregnancy. CLINICAL CASES: Our reported cases were young women with Afro-Caribbean and Nigerian origins. Data were collected by history-taking, clinical examination, laboratory investigations, transabdominal ultrasonographic examination and Magnetic Resonance Imaging. Both patients were diagnosed with PCOS according to the Rotterdam criteria. During each of their pregnancies they both developed an explosive hirsutism, a deepening in the voice, a clitoromegaly. Gestational diabetes occurred during pregnancies. There was no fetal virilization, despite raising androgen levels, more than tenfold to normal. Improvement of hirsutism and normalization of androgens were described in postpartum. CONCLUSION: Only few cases of maternal virilization during pregnancy were reported in literature and even fewer concern recurrent and bilateral ovarian etiology. Hyperplasia of ovarian theca cells seems to be the most likely explanation, which would suggest that PCOS belongs to a spectrum of abnormal reactivity of the ovary to human Chorionic Gonadotrophin (hCG) stimulation along with luteoma and luteinic cyst of pregnancy. Insulin resistance could worsen hyperandrogenism but is not enough to explain virilization. Treatment should focus on protecting the fetus of possible virilization as well as its mother, but also on preserving the subsequent fertility in both.
Assuntos
Hiperandrogenismo/complicações , Síndrome do Ovário Policístico/complicações , Complicações na Gravidez , Virilismo/complicações , Adulto , Androgênios/metabolismo , Feminino , Hirsutismo/complicações , Hirsutismo/diagnóstico , Humanos , Hiperandrogenismo/diagnóstico , Síndrome do Ovário Policístico/diagnóstico , Gravidez , Recidiva , Virilismo/diagnósticoRESUMO
Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder. Evidence from women and preclinical animal models suggests that elevated perinatal androgens can elicit PCOS onset in adulthood, implying androgen actions in both PCOS ontogeny and adult pathophysiology. Prenatally androgenized (PNA) mice exhibit a robust increase of progesterone-sensitive GABAergic inputs to gonadotropin-releasing hormone (GnRH) neurons implicated in the pathogenesis of PCOS. It is unclear when altered GABAergic wiring develops in the brain, and whether these central abnormalities are dependent upon adult androgen excess. Using GnRH-GFP-transgenic mice, we determined that increased GABA input to GnRH neurons occurs prior to androgen excess and the manifestation of reproductive impairments in PNA mice. These data suggest that brain circuit abnormalities precede the postpubertal development of PCOS traits. Despite the apparent developmental programming of circuit abnormalities, long-term blockade of androgen receptor signaling from early adulthood rescued normal GABAergic wiring onto GnRH neurons, improved ovarian morphology, and restored reproductive cycles in PNA mice. Therefore, androgen excess maintains changes in female brain wiring linked to PCOS features and the blockade of androgen receptor signaling reverses both the central and peripheral PNA-induced PCOS phenotype.
Assuntos
Androgênios/metabolismo , Encéfalo/metabolismo , Neurônios GABAérgicos/metabolismo , Síndrome do Ovário Policístico/etiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Antagonistas de Receptores de Andrógenos/farmacologia , Animais , Encéfalo/citologia , Di-Hidrotestosterona/administração & dosagem , Retroalimentação Fisiológica/efeitos dos fármacos , Feminino , Neurônios GABAérgicos/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Plasticidade Neuronal/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Ovário/patologia , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Síndrome do Ovário Policístico/prevenção & controle , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Receptores Androgênicos/metabolismo , Virilismo/induzido quimicamente , Virilismo/complicaçõesRESUMO
A 40-year-old normotensive woman presented with abnormal facial hair for 4 years and amenorrhoea for 13 years. Hormonal, biochemical and haematological evaluation showed isolated elevation of serum testosterone and free testosterone. Her follicle-stimulating hormone and luteinising hormone were in the premenopausal range. Until recently she had reconciled to early 'menopause' and visited beauty clinics but never sought medical evaluation. Imaging revealed an enhancing left adrenal mass with fat densities and venous thrombus extending through the inferior vena cava to a 7 cm mass in the right atrium. She underwent left kidney-preserving surgery utilising hypothermic cardiopulmonary bypass with early clamping of the pulmonary artery without circulatory arrest. Histology showed adrenocortical carcinoma with composite incidental myelolipoma and neoplastic thrombus. At 2 months, testosterone has normalised and she is doing well. Isolated testosterone-secreting adrenocortical carcinoma with massive venous thrombus is rare as is coincidental composite macroscopic myelolipoma.
Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Carcinoma Adrenocortical/complicações , Cardiopatias/complicações , Mielolipoma/complicações , Trombose Venosa/complicações , Virilismo/complicações , Carcinoma Adrenocortical/química , Adulto , Feminino , Humanos , Testosterona/metabolismoRESUMO
Congenital adrenal hyperplasia (CAH) due to 21 hydroxylase deficiency is a genetic disorder that leads to hypocortisolism, hyperandrogenism and, in the most severe forms, also to hypoaldosteronism. Girls with classic CAH are born with virilized external genitalia. Prenatal dexamethasone (DXM) treatment can reduce virilization but may have side effects for mother and fetus. We present the first case of a girl who was born with CAH and an orofacial cleft. She was treated with prenatal DXM to prevent virilization. Oral clefts have to be considered as a potential side effect of prenatal DXM treatment.
Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Fenda Labial/tratamento farmacológico , Fissura Palatina/tratamento farmacológico , Dexametasona/uso terapêutico , Cuidado Pré-Natal/métodos , Virilismo/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/diagnóstico , Fenda Labial/complicações , Fenda Labial/diagnóstico , Fissura Palatina/complicações , Fissura Palatina/diagnóstico , Feminino , Humanos , Gravidez , Diagnóstico Pré-Natal , Virilismo/complicações , Virilismo/diagnósticoRESUMO
Mature cystic teratoma (MCT) is rarely involved in the overproduction of steroid hormones in contrast to sex cord stromal tumors. A 31-year-old woman visited our hospital with hirsutism, hoarseness, and hair loss from the scalp. Serum testosterone and free-testosterone levels were 7.3 ng/ml and 2.3 pg/ml, respectively, which were markedly in excess of the age adjusted female standard levels. Basal blood levels of steroid hormones and serum levels of 17-hydroxyprogesterone at 1 h after intravenous injection of adrenocorticotropic hormone demonstrated that 21-hydroxylase deficiency was not the underlying cause of her virilization. A subsequent chromosomal test with G-banding revealed a karyotype of 46XX. Magnetic resonance imaging revealed a mass in the left ovary, which was subsequently diagnosed as MCT. Detailed pathological analysis of the tumor indicated that it was comprised of skin components, sweat glands, with hair and fat texture, glandular epithelium and fibrous connective tissue, consistent with the characteristic composition of MCT. Immunohistochemical analysis demonstrated marked immunoreactivity of 17beta-hydroxysteroid dehydrogenase (HSD17B5), an enzyme that can convert androstenedione to testosterone. Following surgical removal of the tumor, testosterone and free testosterone levels were markedly decreased (0.3 ng/ml and 0.4 pg/ml, respectively) and other symptoms abated. In conclusion, this is the first report of an ovarian MCT associated with clinical virilization caused by the ectopic production of testosterone possibly because of an overexpression of intratumoral HSD17B5.
Assuntos
3-Hidroxiesteroide Desidrogenases/genética , Expressão Ectópica do Gene , Hidroxiprostaglandina Desidrogenases/genética , Teratoma/enzimologia , Teratoma/genética , Virilismo/enzimologia , Virilismo/genética , Adulto , Membro C3 da Família 1 de alfa-Ceto Redutase , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias Ovarianas/patologia , Teratoma/complicações , Virilismo/complicaçõesRESUMO
BACKGROUND: Bifid scrotum and hypospadias can be signs of undervirilization, yet boys presenting with these findings often do not undergo genetic evaluation. In some cases, identifying an underlying genetic diagnosis can help to optimize clinical care and improve guidance given to patients and families. OBJECTIVES: The aim of this study was to characterize current practice for genetic evaluation of patients with bifid scrotum, and to identify approaches with a good diagnostic yield. METHODS: A retrospective study of the Boston Children's Hospital electronic medical records (1993-2015) was conducted using the search term "bifid scrotum" and clinical data were extracted. Data were abstracted into a REDCap database for analysis. Statistical analysis was performed using SPSS, SAS, and Excel software. RESULTS: The search identified 110 subjects evaluated in the Urology and/or Endocrinology clinics for bifid scrotum. Genetic testing (including karyotype, microarray, or targeted testing) was performed on 64% of the subjects with bifid scrotum; of those tested, 23% (15% of the total cohort of 110 subjects) received a confirmed genetic diagnosis. Karyotype analysis, when performed, led to a diagnosis in 17% of patients. Of the ten instances when androgen receptor gene sequencing was performed, a pathogenic mutation was identified 20% of the time. CONCLUSION: This study demonstrated that the majority of individuals with moderate undervirilization resulting in bifid scrotum do not receive a genetic diagnosis. Over a third of the analyzed subjects did not have any genetic testing, even though karyotype analysis and androgen receptor (AR) sequencing were both relatively high yield for identifying a genetic etiology. Increased utilization of traditional genetic approaches could significantly improve the ability to find a genetic diagnosis.
Assuntos
Hipospadia/complicações , Hipospadia/genética , Escroto/anormalidades , Virilismo/complicações , Feminino , Testes Genéticos , Humanos , Lactente , Masculino , Seleção de Pacientes , Estudos Retrospectivos , Virilismo/genéticaRESUMO
Androgenetic alopecia (AGA) is the most common form of alopecia, affecting up to 80% of men and 50% of women in the course of their life. AGA is caused by a progressive reduction in the diameter, length and pigmentation of the hair. Hair thinning results from the effects of the testosterone metabolite dehydrotestosterone (DHT) on androgen-sensitive hair follicles. In women, AGA produces diffuse thinning of the crown region with maintenance of the frontal hairline (Ludwig pattern AGA). In premenopausal women, AGA can be a sign of hyperandrogenism, together with hirsutism and acnes. Male pattern is characterized by bitemporal recession of the frontal hairline, followed by diffuse thinning at the vertex. Today, scalp dermoscopy is used routinely in patients with androgenetic alopecia, as it facilitates the diagnosis and differential diagnosis with other diseases, allows staging of severity, and allows you to monitor the progress of the disease in time and response to treatment. AGA is a progressive disease that tends to worsen with time. Medical treatment of AGA includes topical minoxidil, antiandrogen agents, 5-alpha reductase inhibitors.
Assuntos
Alopecia , Inibidores de 5-alfa Redutase/uso terapêutico , Alopecia/diagnóstico , Alopecia/tratamento farmacológico , Alopecia/epidemiologia , Alopecia/etiologia , Alopecia/fisiopatologia , Antagonistas de Androgênios/uso terapêutico , Biópsia , Comorbidade , Contraindicações , Dermoscopia , Suplementos Nutricionais , Feminino , Folículo Piloso/patologia , Hirsutismo/etiologia , Humanos , Hiperandrogenismo/complicações , Cetoconazol/uso terapêutico , Masculino , Menopausa , Minoxidil/efeitos adversos , Minoxidil/uso terapêutico , Prognóstico , Receptores Androgênicos/metabolismo , Couro Cabeludo/patologia , Caracteres Sexuais , Testosterona/análogos & derivados , Testosterona/metabolismo , Virilismo/complicaçõesRESUMO
BACKGROUND: Steroidogenic factor-1 (SF-1) gene (NR5A1) mutations cause disorders of sexual development due to gonadal dysgenesis, particularly in 46,XY individuals. In cases exhibiting this mutation, the phenotype is heterogeneous, and it may vary within a spectrum ranging from complete female appearance to an infertile male. Virilization observed in some cases in the pubertal age group may lead to diagnostic difficulties. CASE: The present case report describes the clinical, histopathologic, and genetic characteristics of a 46,XY case, who was born with a female phenotype and raised as a girl, presented with findings of virilization in the pubertal period. She had no germ cells and very few Leydig cells with atrophic testis on biopsy and in whom a novel heterozygous mutation in the SF-1 gene (a heterozygous 7-bp deletion mutation in exon 7 [c.1308-1314del7bp] causing frameshift) was identified. SUMMARY AND CONCLUSION: Although the gonads are very dysgentic in patient with SF-1 mutations, sufficient androgen synthesis can cause severe virilization during puberty.
Assuntos
Disgenesia Gonadal 46 XY/genética , Heterozigoto , Fator Esteroidogênico 1/genética , Virilismo/genética , Criança , Feminino , Identidade de Gênero , Testes Genéticos , Disgenesia Gonadal 46 XY/complicações , Disgenesia Gonadal 46 XY/patologia , Disgenesia Gonadal 46 XY/terapia , Humanos , Mutação , Virilismo/complicações , Virilismo/patologia , Virilismo/terapiaRESUMO
OBJECTIVE: Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder in which the lack of 21-hydroxylase results in cortisol and aldosterone insufficiency and an overproduction of adrenal androgens. High levels of androgens in women may cause virilization of the larynx and a masculine voice. The purpose of the present study was to investigate subjective voice problems due to virilization in women with CAH. DESIGN/PATIENTS: Participants were 42 women with CAH between 25 and 71 years of age, and 43 age-matched female healthy control subjects. All patients, but two, were in good disease control. MEASUREMENTS: A validated Swedish version of the Voice Handicap Index (VHI) and questions related to voice virilization were used. Endocrine data were obtained from medical files. RESULTS: Patients scored significantly higher on VHI when the results were divided into no/mild, moderate and severe voice handicap as compared with the control subjects. They rated significantly higher for 'dark voice' and for 'being perceived as a man on the phone' compared with controls. Seven per cent of the women with CAH had voice problems clearly related to voice virilization. High ratings of dark voice were significantly associated with long periods of under-treatment with glucocorticoids and higher bone mineral density but not with severity of mutation. CONCLUSION: Subjective voice problems due to voice virilization may occur in women with CAH. This further emphasizes the importance of avoiding long periods of increased androgen levels to prevent irreversible voice changes. For these patients, we recommend referral to voice assessment and treatment.
Assuntos
Hiperplasia Suprarrenal Congênita/complicações , Virilismo/complicações , Distúrbios da Voz/etiologia , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/fisiopatologia , Adulto , Idoso , Androgênios/fisiologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Virilismo/fisiopatologia , Prega Vocal/fisiopatologia , Distúrbios da Voz/fisiopatologia , Distúrbios da Voz/psicologia , Qualidade da VozRESUMO
CONTEXT: Sex hormones, particularly androgens, may influence not only adipose tissue distribution but also its functions. OBJECTIVE: We explored the possibility of sexual dimorphism in adipose tissue and skeletal muscle function. DESIGN: This was a case-control study. SETTING: The setting was an academic hospital. PARTICIPANTS: Participants were severely obese men (n = 7), control women (n = 7), and hyperandrogenic women presenting with polycystic ovary syndrome (PCOS) (n = 7) submitting to bariatric surgery and an independent series of 40 patients with PCOS and 40 control women matched for age and body mass index. INTERVENTIONS: Samples of subcutaneous (SAT) and visceral adipose tissue (VAT) and skeletal muscle were obtained during bariatric surgery in severely obese subjects. MAIN OUTCOME MEASURES: Gene expression of chemerin, lipocalin-2, and omentin-1 in tissue samples was measured. We analyzed the effects of PCOS and obesity on serum concentrations of these adipokines in the larger series of women with PCOS and in control women. RESULTS: Expression of chemerin and lipocalin-2 was higher in VAT than in SAT in men and women with PCOS; the opposite was observed in control women. Omentin-1 expression was higher in VAT than in SAT in the three groups. No differences were observed in the skeletal muscle expression of these adipokines. Obesity increased serum chemerin and lipocalin-2 levels and tended to decrease omentin-1, irrespective of PCOS. CONCLUSIONS: The present results suggest that there is sexual dimorphism in some adipose tissue functions and that this dimorphism may be related to differences in androgen concentrations because women with PCOS show a masculinized pattern of expression of some adipokines.
Assuntos
Gordura Intra-Abdominal/metabolismo , Obesidade/genética , Síndrome do Ovário Policístico/genética , Caracteres Sexuais , Gordura Subcutânea/metabolismo , Virilismo/genética , Proteínas de Fase Aguda/genética , Proteínas de Fase Aguda/metabolismo , Adulto , Estudos de Casos e Controles , Quimiocinas/genética , Quimiocinas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Lectinas/genética , Lectinas/metabolismo , Lipocalina-2 , Lipocalinas/genética , Lipocalinas/metabolismo , Masculino , Obesidade/complicações , Obesidade/metabolismo , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Virilismo/complicações , Virilismo/metabolismoRESUMO
The 21-hydroxylase deficiency (21OHD) is caused by CYP21A2 mutations resulting in severe or moderate enzymatic impairments. 21OHD females carrying similar genotypes present different degrees of external genitalia virilization, suggesting the influence of other genetic factors. Single nucleotide variants (SNVs) in the CYP3A7 gene and in its transcription factors, related to fetal 19-carbon steroid metabolism, could modulate the genital phenotype. To evaluate the influence of the 21OHD genotypes and the CYP3A7, PXR and CAR SNVs on the genital phenotype in 21OHD females. Prader scores were evaluated in 183 patients. The CYP3A7, PXR and CAR SNVs were screened and the 21OHD genotypes were classified according to their severity: severe and moderate groups. Patients with severe genotype showed higher degree of genital virilization (Prader median III, IQR III-IV) than those with moderate genotype (III, IQR II-III) (p < 0.001). However, a great overlap was observed between genotype groups. Among all the SNVs tested, only the CAR rs2307424 variant correlated with Prader scores (r(2) = 0.253; p = 0.023). The CYP21A2 genotypes influence the severity of genital virilization in 21OHD females. We also suggest that the CAR variant, which results in a poor metabolizer phenotype, could account for a higher degree of external genitalia virilization.