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Archives of Disease in Childhood Jan 1999Androgen secreting adrenocortical tumours are rare in children and the determination of their malignant potential can be difficult.
BACKGROUND
Androgen secreting adrenocortical tumours are rare in children and the determination of their malignant potential can be difficult.
OBJECTIVES
To assess the presentation, histology, and clinical behaviour of these tumours.
SETTING
Two tertiary referral centres.
STUDY DESIGN
Retrospective analysis of children diagnosed with an androgen secreting adrenocortical tumour between 1976 and 1996.
PATIENTS
Twenty three girls and seven boys aged 0-14 years.
RESULTS
Pubic hair was observed in all children, clitoromegaly or growth of the phallus in 23 children, acceleration of linear growth in 22 children, and advanced bone age (> 1.5 years) in 18 children. Hypersecretion of androgens was detected by assessment of serum androgen concentrations alone in four patients and by 24 hour urine steroid excretion profiles in 22 patients. All 16 tumours measuring < 5 cm in diameter were benign. Of the tumours measuring 5-9 cm, three were malignant and seven were benign, whereas all four tumours > 10 cm were malignant. Histological slides were available for reassessment in 25 children. Although mitoses and necrosis were more characteristic of tumours with malignant behaviour, no exclusive histological features of malignancy were seen.
CONCLUSION
Histological criteria for malignancy are not reliable, whereas tumour size is important in assessing malignant potential.
Topics: Adolescent; Adrenal Cortex Neoplasms; Androgens; Androsterone; Biomarkers; Child; Child, Preschool; Female; Follow-Up Studies; Growth Disorders; Humans; Hydrocortisone; Infant; Male; Necrosis; Puberty, Precocious; Retrospective Studies; Virilism
PubMed: 10325758
DOI: 10.1136/adc.80.1.46 -
Archives of Sexual Behavior Feb 200846,XX individuals with classical congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme, 21-hydroxylase, show variable degrees of masculinization of body... (Review)
Review
46,XX individuals with classical congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme, 21-hydroxylase, show variable degrees of masculinization of body and behavior due to excess adrenal androgen production. Increased bisexuality and homosexuality have also been reported. This article provides a review of existing reports of the latter and presents a new study aimed at replicating the previous findings with detailed assessments of sexual orientation on relatively large samples, and at extending the investigation to the mildest form, non-classical (NC) CAH. Also, this is the first study to relate sexual orientation to the specific molecular genotypes of CAH. In the present study, 40 salt-wasters (SW), 21 SV (simple-virilizing), 82 NC, and 24 non-CAH control women (sisters and female cousins of CAH women) were blindly administered the Sexual Behavior Assessment Schedule (SEBAS-A, 1983 ed.; H. F. L. Meyer-Bahlburg & A. A. Ehrhardt, Privately printed). Most women were heterosexual, but the rates of bisexual and homosexual orientation were increased above controls not only in women with classical CAH, but also in NC women, and correlated with the degree of prenatal androgenization. Classifying women by molecular genotypes did not further increase the correlation. Diverse aspects of sexual orientation were highly intercorrelated, and principal components analysis yielded one general factor. Bisexual/homosexual orientation was (modestly) correlated with global measures of masculinization of non-sexual behavior and predicted independently by the degree of both prenatal androgenization and masculinization of childhood behavior. We conclude that the findings support a sexual-differentiation perspective involving prenatal androgens on the development of sexual orientation.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adult; Androgens; Bisexuality; Female; Genotype; Homosexuality, Female; Humans; Middle Aged; Phenotype; Pilot Projects; Pregnancy; Prenatal Exposure Delayed Effects; Psychosexual Development; Sex Characteristics; Sexual Behavior; Steroid 21-Hydroxylase; Virilism
PubMed: 18157628
DOI: 10.1007/s10508-007-9265-1 -
Endocrine Practice : Official Journal... Apr 2017Pure androgen-secreting adrenal tumors (PASATs) are extremely rare, most reports involving only a single case. This study examined 9 cases of PASAT, with an attempt to...
OBJECTIVE
Pure androgen-secreting adrenal tumors (PASATs) are extremely rare, most reports involving only a single case. This study examined 9 cases of PASAT, with an attempt to characterize its clinical features and to explore the pathogenesis.
METHODS
Clinical data of 9 patients with PASAT were retrospectively reviewed. Immunostaining was conducted, and the aryl hydrocarbon receptor-interacting protein gene (AIP) was amplified and directly sequenced.
RESULTS
The onset age of the patients ranged from 3.5 to 64 years. All 8 female patients had virilization, whereas the 7-year-old male patient presented with sexual precocity. Serum testosterone levels were elevated (4.1 to 52.3 nmol/L). Adrenal masses were detected and removed in all patients and histologically diagnosed as adrenocortical adenoma or carcinoma. Two patients had both PASATs and growth hormone (GH)-secreting pituitary adenomas (GH pituitary adenoma). Immunohistochemistry revealed nuclear immunoreactivity for p53 in 3 of 7 patients and nuclear immunoreactivity for cyclin D1 in 2 of 7 patients. Immunostaining of β-catenin showed nuclear, cytoplasmic, and membrane immunoreactivity (2 of 7 patients) or merely cytoplasmic immunoreactivity (1 of 7 patients). The adrenocortical carcinoma showed positive staining for both p53 and cyclin D1 and a high Ki-67 index of 60%. Mutations p.Lys177Argfs*19 and p.Asp287Val in the AIP gene were identified in PASATs of the 2 patients with concomitant presence of GH pituitary adenoma.
CONCLUSION
Clinical features of PASATs vary with gender and age of the patients. Abnormal p53 and β-catenin expression might be involved in the tumorigenesis of these tumors. AIP mutations might be responsible for the concomitant presence of PASATs and GH pituitary adenoma.
ABBREVIATIONS
ACA = adrenocortical adenoma ACC = adrenocortical carcinoma AIP = aryl hydrocarbon receptor-interacting protein DHEAS = dehydroepiandrosterone sulfate; GH growth hormone PASAT = pure androgen-secreting adrenal tumor.
Topics: Adolescent; Adrenal Cortex Neoplasms; Adrenocortical Adenoma; Adult; Androgens; Child; Child, Preschool; DNA Mutational Analysis; Female; Humans; Male; Middle Aged; Puberty, Precocious; Retrospective Studies; Virilism; Young Adult
PubMed: 28095038
DOI: 10.4158/EP161580.OR -
Annals of Internal Medicine Jan 1987Excess body hair, or hirsutism, is usually only a problem in women and can cause considerable psychological distress. The disorder is usually androgen mediated. Because... (Review)
Review
Excess body hair, or hirsutism, is usually only a problem in women and can cause considerable psychological distress. The disorder is usually androgen mediated. Because androgens come only from the adrenal glands or gonads or by conversion in peripheral tissues of precursor steroids from these organs, the causes of hirsutism are found in these two organs. Adrenal causes include Cushing's disease, adrenal tumors, and congenital adrenal hyperplasia. Ovarian causes include tumors, polycystic ovarian syndrome, and most cases of idiopathic hirsutism. The clinical evaluation is designed to differentiate between these diagnostic possibilities. When an underlying abnormality can be identified, such as an ovarian tumor, the treatment course is clear. When the diagnosis is idiopathic hirsutism, however, the best treatment is uncertain and several available regimens are possible.
Topics: Androgens; Diagnosis, Differential; Female; Hair; Hirsutism
PubMed: 3538969
DOI: 10.7326/0003-4819-106-1-95 -
Hormone Research 1994A case of massive edema of the left ovary with virilization is described. Microscopically, massive interstitial edema with luteinization of theca and stromal cells was... (Review)
Review
A case of massive edema of the left ovary with virilization is described. Microscopically, massive interstitial edema with luteinization of theca and stromal cells was found. A few stromal cells contained Reinke-type crystalloids--an original observation. Peripheral concentrations of testosterone, dihydrotestosterone and androstenedione were increased. Ratios of left ovarian vein to peripheral vein concentrations were increased for all these steroids as well as for estradiol and estrone, showing that the left ovary was the source of excess androgen and estrogen secretion. The patient showed impaired gonadotropin secretion in basal conditions and after an intravenous luteinizing-hormone-releasing hormone (LHRH) stimulation test. After left oophorectomy, all steroids and gonadotropin response to LHRH returned to normal, and virilization regressed. Analysis of the endocrine changes associated with this ovarian tumor brings additional arguments for a primary role of hyperandrogenism in the impairment of gonadotropin secretion, as was also observed in other hyperandrogenic disorders including polycystic ovarian syndrome.
Topics: Adolescent; Androgens; Edema; Female; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Menstrual Cycle; Ovarian Diseases; Ovariectomy; Virilism
PubMed: 7959622
DOI: 10.1159/000183925 -
Molecular and Cellular Endocrinology Sep 2017Children with adrenocortical tumors (ACTs) often present with virilization due to high tumoral androgen production, with dihydrotestosterone (DHT) as most potent...
Children with adrenocortical tumors (ACTs) often present with virilization due to high tumoral androgen production, with dihydrotestosterone (DHT) as most potent androgen. Recent work revealed two pathways for DHT biosynthesis, the classic and the backdoor pathway. Usage of alternate routes for DHT production has been reported in castration-resistant prostate cancer, CAH and PCOS. To assess whether the backdoor pathway may contribute to the virilization of pediatric ACTs, we investigated seven children suffering from androgen producing tumors using steroid profiling and immunohistochemical expression studies. All cases produced large amounts of androgens of the classic and/or backdoor pathway. Variable expression of steroid enzymes was observed in carcinomas and adenomas. We found no discriminative pattern. This suggests that enhanced androgen production in pediatric ACTs is the result of deregulated steroidogenesis through multiple steroid pathways. Thus future treatments of ACTs targeting androgen overproduction should consider these novel steroid production pathways.
Topics: Adolescent; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Androgens; Child; Dihydrotestosterone; Female; Humans; Immunohistochemistry; Infant; Li-Fraumeni Syndrome; Male; Ovarian Neoplasms; Tumor Suppressor Protein p53; Virilism
PubMed: 28501574
DOI: 10.1016/j.mce.2017.05.014 -
The Journal of Clinical Endocrinology... Sep 1995Although hirsutism is more a cosmetic and psychosocial problem than a disease, hirsute women are often some of the most grateful patients in an endocrinologist's... (Review)
Review
Although hirsutism is more a cosmetic and psychosocial problem than a disease, hirsute women are often some of the most grateful patients in an endocrinologist's practice. The combination of mechanical hair removal and judicious use of medications will improve hair growth in most women. Unfortunately, no drug is approved by regulatory agencies in North America for treatment of hirsutism. Well designed comparative studies with objective end points are needed to demonstrate which drugs work best in which hirsute women. Because pharmaceutical companies are reluctant to market drugs for women of child-bearing age, there has been little industry support for such studies.
Topics: Adrenal Glands; Androgen Antagonists; Androgens; Contraceptives, Oral; Female; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Ovary
PubMed: 7673394
DOI: 10.1210/jcem.80.9.7673394 -
BMJ Case Reports Jun 2021Adrenocortical carcinoma (ACC) is a rare malignancy, with an estimated annual incidence of 0.7-2 cases per million and a median overall survival of 3-4 years....
Adrenocortical carcinoma (ACC) is a rare malignancy, with an estimated annual incidence of 0.7-2 cases per million and a median overall survival of 3-4 years. Hormone-secreting ACCs represent most cases; of these, only a small minority presents with virilisation alone. Early diagnosis is key to increase the chances of a better outcome. Here, we report a case of a 41-year-old woman who presented with menstrual irregularities, hirsutism and virilising symptoms, associated with abdominal discomfort and constitutional symptoms. On physical examination, there was a palpable mass in the right upper quadrant. Laboratory workup revealed elevated serum androgens. The imaging study showed a 163×110×122 cm right adrenal mass with features consistent with ACC and suggested potential hepatic invasion. Our patient underwent surgical resection, and the histopathological findings confirmed the diagnosis. She was referred to a specialised centre for follow-up and adjuvant therapy.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Adult; Androgens; Female; Humans; Liver; Virilism
PubMed: 34083198
DOI: 10.1136/bcr-2021-242895 -
The Journal of Clinical Endocrinology... Oct 2020Epidemiologic studies of polycystic ovary syndrome (PCOS) are limited, especially in populations where diagnostic resources are less available. In these settings, an...
CONTEXT
Epidemiologic studies of polycystic ovary syndrome (PCOS) are limited, especially in populations where diagnostic resources are less available. In these settings, an accurate, low-cost screening tool would be invaluable.
OBJECTIVE
To test the use of a simple questionnaire to identify women at increased risk for PCOS and androgen excess (AE) disorders.
STUDY DESIGN
Prospective cohort study from 2006-2010.
SETTING
Community-based.
PARTICIPANTS
Women aged 14 to 45 years.
INTERVENTION
A screening telephone questionnaire consisting of 3 questions was tested, where participants were asked to self-assess the presence/absence of male-like hair and menstrual irregularity. Participants were then invited to undergo a direct examination, including completing a medical history and undergoing a modified Ferriman-Gallwey (mFG) hirsutism score, ovarian ultrasound, and measurement of circulating total and free testosterone, DHEAS, TSH, prolactin and 17-hydroxyprogesterone levels.
MAIN OUTCOME MEASURE
Accuracy of questionnaire in predicting PCOS, AE, and irregular menses.
RESULTS
Participants with self-assessed irregular menses and/or excess hair were labeled "Possible Androgen Excess (Poss-AE)" and those self-assessed with regular menses and no excess hair were labeled "Probable Non-Androgen Excess (Non-AE)." The study was completed in 206/298 (69%) of the Poss-AE and in 139/192 (73%) of the Non-AE. Of Poss-AE and Non-AE subjects, 82.5% and 15.8%, respextively, presented with PCOS. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of the 3-question telephone survey to predict PCOS was 89%, 78%, 85%, and 83%, respectively.
CONCLUSIONS
A simple telephone questionnaire, based on self-assessment of body hair and menstrual status, can be used with a high predictive value to identify women at risk for AE disorders, including PCOS, and to detect healthy controls. This approach could be an important tool for needed epidemiologic studies.
Topics: Adolescent; Adult; Androgens; California; Female; Hirsutism; Humans; Menstruation Disturbances; Middle Aged; Polycystic Ovary Syndrome; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Self Report; Self-Assessment; Telephone; Young Adult
PubMed: 32442282
DOI: 10.1210/clinem/dgz264 -
Seminars in Reproductive Medicine Mar 2022Hyperandrogenism-clinical features resulting from increased androgen production and/or action-is not uncommon in peripubertal girls. Hyperandrogenism affects 3 to 20% of...
Hyperandrogenism-clinical features resulting from increased androgen production and/or action-is not uncommon in peripubertal girls. Hyperandrogenism affects 3 to 20% of adolescent girls and often is associated with hyperandrogenemia. In prepubertal girls, the most common etiologies of androgen excess are premature adrenarche (60%) and congenital adrenal hyperplasia (CAH; 4%). In pubertal girls, polycystic ovary syndrome (PCOS; 20-40%) and CAH (14%) are the most common diagnoses related to androgen excess. Androgen-secreting ovarian or adrenal tumors are rare (0.2%). Early pubic hair, acne, and/or hirsutism are the most common clinical manifestations, but signs of overt virilization in adolescent girls-rapid progression of pubic hair or hirsutism, clitoromegaly, voice deepening, severe cystic acne, growth acceleration, increased muscle mass, and bone age advancement past height age-should prompt detailed evaluation. This article addresses the clinical manifestations of and management considerations for non-PCOS-related hyperandrogenism in adolescent girls. We propose an algorithm to aid diagnostic evaluation of androgen excess in this specific patient population.
Topics: Acne Vulgaris; Adolescent; Androgens; Female; Hirsutism; Humans; Hyperandrogenism; Polycystic Ovary Syndrome
PubMed: 35052005
DOI: 10.1055/s-0041-1742259