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AbstractExcessive androgen levels in women after menopause often result from an imbalance in ovarian steroid secretion: a rapid decline in estrogen secretion associated with a slow decrease in androgen secretion, compounded by a physiological decrease in sex hormone-binding globulin. Hyperandrogenism is associated with a higher risk of cardiovascular events and gynecological neoplasms, also impacting the emotional well-being of affected women. Therefore, the aim of these guidelines is to guide the clinical physician in the appropriate clinical and biochemical evaluation of hyperandrogenism after menopause, thus optimizing therapeutic outcomes. The most frequent consultation in this stage of life is facial hirsutism associated with hair loss. If the onset of signs is abrupt, severe, associated with virilization and accompanied by serum testosterone levels in the male range, it is necessary to rule out a tumoral origin. A thorough medical history guides the diagnosis. Determination of total testosterone using reliable methods and imaging studies are valid tools to assist when doubts arise in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The virilizing ovarian tumors represent less than 1% of ovarian tumors, with the most common being Sertoli-Leydig cell tumor (SLCT). This stufy is a case series. Methods: We present the diagnosis, treatment, and evolution of 2 Peruvian women who developed virilization. Results: Case 1 is a 27-year-old woman with a history of polycystic ovary syndrome (PCOS), whose usual treatment was combined oral contraceptives, which she discontinued in the last year; she presented with voice changes, increased muscular strength, and acne of 6 months duration. Physical examination revealed only clitoromegaly. Tests showed elevated total testosterone, normal dehydroepiandrosterone sulfate (DHEA-S), and transvaginal ultrasound with isoechoic image in frosted glass in the left ovary. Left salpingo-oophorectomy was performed, revealing SLCT. Case 2 is a 48-year-old woman with a history of PCOS since the age of 25, prediabetes, and dyslipidemia; she noticed progression of hirsutism, increased libido, deepened voice, alopecia, weight gain, and amenorrhea over the last 5 years. Physical examination revealed hirsutism, alopecia, and clitoromegaly. Tests showed markedly elevated total testosterone (1,080 ng/dl) and normal DHEA-S. Transvaginal ultrasound showed a larger right ovary, without tumor. Ovarian venous sampling showed lateralization towards the right ovary. Bilateral salpingo-oophorectomy plus hysterectomy was performed, revealing SLCT in the right ovary. In both post-surgery patients, there was normalization of androgens and clinical improvement. Conclusions: SLCT s can occur at any age, with rapidly evolving hyperandrogenism and/or virilization symptoms, the cases described were of unusual presentation, which posed a diagnostic challenge. [ABSTRACT FROM AUTHOR]

Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) or 11-hydroxylase deficiency (11OHD) is characterized by underproduction of cortisol and overproduction of adrenal androgens. These androgens lead to a variable degree of virilization of the female external genitalia in 46,XX individuals. Especially in developing countries, diagnosis is often delayed and 46,XX patients might be assigned as males. This study aims to describe the clinical and biochemical characteristics of a unique cohort of untreated male-reared 46,XX classic CAH patients from Indonesia and discusses treatment challenges. Methods: Nine untreated classic CAH patients with 46,XX genotype and 21OHD (n=6) or 11OHD (n=3), aged 3-46 years old, were included. Biometrical parameters, clinical characteristics, and biochemical measurements including glucocorticoids, renin, androgens, and the pituitary-gonadal axis were evaluated. Results: All patients had low early morning serum cortisol concentrations (median 89 nmol/L) without significant increase after ACTH stimulation. Three patients with salt wasting 21OHD reported one or more periods with seizures and/or vomiting in their past until the age of 6, but not thereafter. The remaining patients reported no severe illness or hospitalization episodes, despite their decreased capacity to produce cortisol. In the 21OHD patients, plasma renin levels were elevated compared to the reference range, and in 11OHD patients renin levels were in the low-normal range. All adult patients had serum testosterone concentrations within the normal male reference range. In 21OHD patients, serum 11-oxygenated androgens comprised 41-60% of the total serum androgen concentrations. Glucocorticoid treatment was offered to all patients, but they refused after counseling as this would reduce their endogenous androgen production and they did not report complaints of their low cortisol levels. Discussion: We describe a unique cohort of untreated classic 46,XX male CAH patients without overt clinical signs of cortisol deficiency despite their cortisol underproduction and incapacity to increase cortisol levels after ACTH stimulation. The described adolescent and adult patients produce androgen levels within or above the normal male reference range. Glucocorticoid treatment will lower these adrenal androgen concentrations. Therefore, in 46,XX CAH patients reared as males an individual treatment approach with careful counseling and clear instructions is needed. [ABSTRACT FROM AUTHOR]

Context Adrenocortical carcinomas are very rare malignancies in childhood associated with poor outcome in advanced disease. Most adrenocortical tumors (ACT) are functional, causing signs and symptoms of adrenal hormone excess. In most studies, endocrine manifestations were reported 4 to 6 months prior to diagnosis. Objective We sought to extend knowledge on endocrine manifestations with regard to age and sex to facilitate early diagnosis. Methods We retrospectively analyzed features of adrenal hormone excess in children and adolescents with ACT registered with the GPOH-MET studies between 1997 and 2022. Stage of puberty was defined as prepubertal in females < 8 years of age and males < 9 years. Results By December 2022, 155 patients (110 female, 45 male) with data on endocrine manifestations had been reported. Median age at ACT diagnosis was 4.2 years [0.1-17.8], median interval from first symptoms was 4.2 months [0-90.7]. In 63 girls of prepubertal age, the most frequently reported manifestations were pubarche (68.3%), clitoral hypertrophy (49.2%), and weight gain (31.7%); in 47 pubertal female patients, the most frequent manifestations were excessive pubic hair (46.8%), acne (36.2%), and hypertension (36.2%). Leading symptoms in 34 boys of prepubertal age were pubarche (55.9%), penile growth (47.1%), and acne (32.4%), while in 11 pubertal male patients, leading symptoms were weight gain (45.5%), hypertension (36.4%), excessive pubic hair (27.3%), and cushingoid appearance (27.3%). In pubertal patients, symptoms of androgen excess were mainly unrecognized as part of pubertal development, while symptoms of Cushing syndrome were more frequently apparent. Conclusion The endocrine phenotype induced by pediatric ACT is age- and sex-dependent. [ABSTRACT FROM AUTHOR]

Objective: To provide a reference for the diagnosis and treatment of ovarian steroid cell tumors, not otherwise specified (SCTs-NOS). Methods: We retrospectively analyzed the clinicopathological data of three patients with SCTs-NOS admitted to the Tianjin Medical University General Hospital from 2012 to 2022 and reviewed literature reports related to this disease. Results: A total of 3 cases in our center and 70 cases searched in literature reports were included. The age at diagnosis ranged from 3 to 93 years (median, 34 years). The common clinical manifestations were hirsutism, acne, deepened voice, clitoromegaly, amenorrhea, and excessive weight gain. Tumor sizes ranged from 1.2 to 45 cm, with an average diameter of 6.5cm. Most of SCTs-NOS were benign, but some of them exhibited malignant behavior. Surgery was the main treatment and close follow-up was required. The follow up time of 73 cases ranged from 3 to 132 months (median, 21.3 months). Disease recurrence or progression occurred in 14 cases (19.2%). Three of the 73 patients had a successful pregnancy. Conclusion: SCTs-NOS usually occur in women of reproductive age, which are mainly manifested as androgen excess symptoms. Surgery is an appropriate treatment for SCTs-NOS and should be individualized. Final diagnosis depends on pathology. SCTs-NOS have malignant potential, and the treatments for patients with malignant tumors and disease recurrence or progression were cytoreductive surgery, adjuvant chemotherapy, and gonadotrophin-releasing hormone agonists (GnRHa) therapy. [ABSTRACT FROM AUTHOR]

Objectives: To establish gestation-wise normative data of external genitalia measurements in North Indian term and preterm female newborns. Methods: In this cross-sectional descriptive study, institutionally-born female neonates between 28-42 wk gestation were consecutively enrolled between 24-72 h of life. Newborns with major congenital malformations, chromosomal anomalies, multifetal gestation and birth injuries were excluded. Data on various genital measurements were collected [Clitoral length (CL), clitoral width (CW), ano-clitoral distance (AGDAC), ano-fourchette distance (AGDAF) and anogenital ratio (AGR)]. Results: One hundred ninety-eight of 508 neonates (39%) were preterm and 310 (61%) were term. Mean (± SD) CL and CW were 4.6 ± 1.8 mm and 3.9 ± 1.6 mm, respectively. Mean (± SD) values for AGDAF, AGDAC and AGR were 9.3 ± 1.8 mm, 30.2 ± 3.9 mm, and 0.31 ± 0.05, respectively. According to these results, term female newborns with CL more than 7 mm and/or CW more than 6 mm (95th centile) warrant evaluation for clitoromegaly. An anogenital ratio greater than 0.45 should be considered as a sign of virilization in a female neonate. Gestation-wise percentile charts for CL, CW, AGDAF, AGDAC and AGR were generated. Conclusions: The percentile values defined in the study can serve as local normative data for accurate interpretation of genital measurements in North Indian female newborns and enable health care professionals for early identification of genital virilization. [ABSTRACT FROM AUTHOR]

Most adrenal incidentalomas are benign neoplasms of the adrenal cortex. While the majority are nonfunctional, many secrete cortisol. Androgen- or estrogen-secreting adenomas are rare. A 44-year-old female, with history of hypertension and prediabetes, presented with worsening acne, hirsutism, secondary amenorrhea for 2 years, and a 40-pound weight gain. Laboratory evaluation showed high 24-hour urine free cortisol, suppressed adrenocorticotropic hormone (ACTH) level, indicative of ACTH independent Cushing syndrome, and elevated testosterone and androstenedione. Abdominal computed tomography (CT) revealed a 6.3 × 5.2 × 5.6 cm left adrenal mass. Patient underwent left open adrenalectomy. Pathology revealed benign adrenocortical adenoma. Postoperatively there was a significant improvement in her blood pressure and blood sugar levels, resumption of menses, and complete resolution of hyperandrogenism and hypercortisolism. We describe a patient with an adrenal adenoma cosecreting cortisol and androgen, leading to Cushing syndrome and significant virilization. Adrenal masses secreting androgens are less common and concerning for adrenocortical carcinoma (ACC). Patients with adrenal masses cosecreting multiple hormones should undergo workup expediently since ACC confers poor outcomes. [ABSTRACT FROM AUTHOR]

IntroductionCongenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) or 11-hydroxylase deficiency (11OHD) is characterized by underproduction of cortisol and overproduction of adrenal androgens. These androgens lead to a variable degree of virilization of the female external genitalia in 46,XX individuals. Especially in developing countries, diagnosis is often delayed and 46,XX patients might be assigned as males. This study aims to describe the clinical and biochemical characteristics of a unique cohort of untreated male-reared 46,XX classic CAH patients from Indonesia and discusses treatment challenges.MethodsNine untreated classic CAH patients with 46,XX genotype and 21OHD (n=6) or 11OHD (n=3), aged 3-46 years old, were included. Biometrical parameters, clinical characteristics, and biochemical measurements including glucocorticoids, renin, androgens, and the pituitary-gonadal axis were evaluated.ResultsAll patients had low early morning serum cortisol concentrations (median 89 nmol/L) without significant increase after ACTH stimulation. Three patients with salt wasting 21OHD reported one or more periods with seizures and/or vomiting in their past until the age of 6, but not thereafter. The remaining patients reported no severe illness or hospitalization episodes, despite their decreased capacity to produce cortisol. In the 21OHD patients, plasma renin levels were elevated compared to the reference range, and in 11OHD patients renin levels were in the low-normal range. All adult patients had serum testosterone concentrations within the normal male reference range. In 21OHD patients, serum 11-oxygenated androgens comprised 41-60% of the total serum androgen concentrations. Glucocorticoid treatment was offered to all patients, but they refused after counseling as this would reduce their endogenous androgen production and they did not report complaints of their low cortisol levels.DiscussionWe describe a unique cohort of untreated classic 46,XX male CAH patients without overt clinical signs of cortisol deficiency despite their cortisol underproduction and incapacity to increase cortisol levels after ACTH stimulation. The described adolescent and adult patients produce androgen levels within or above the normal male reference range. Glucocorticoid treatment will lower these adrenal androgen concentrations. Therefore, in 46,XX CAH patients reared as males an individual treatment approach with careful counseling and clear instructions is needed.

Introduction: Adrenocortical carcinoma (ACC) is rare, aggressive, and metastasizes mainly to the lungs, liver, and regional lymph nodes. This is the first reported case of a pediatric patient with adrenohepatic fusion (AHF) and functional ACC that solely invaded the liver. Case presentation: The patient was a 2 year and 9 month old female, with a 3-month history of weight gain, signs of virilization, Cushing's syndrome, hypertension, and a palpable mass in the right hypochondrium and epigastrium. Blood tests revealed the following: hemoglobin, 16.3 g/dL; cortisol, 25.3 μg/dL; and total serum testosterone, 1489.01 ng/mL. Ultrasonography and computed tomography initially revealed a hepatic tumor measuring 100 × 111 × 106 mm, with a volume of 615 mL. The patient was diagnosed with functional ACC. Curative resection (R0 resection) was performed, involving partial resection of the right hepatic lobe. The resected tumor was 12 × 10 × 7 cm and 650 g, with evidence of invasion into the liver capsule, which was consistent with ACC stage III (T4N0M0). Management included mitotane, cisplatin, etoposide, and doxorubicin, and favorable progress was noted at the 2-year and 3-month follow-up. Conclusion: In cases with AHF, a sufficient portion of the right hepatic lobe must be resected to ensure complete removal of the tumor.

Hormone-producing ovarian tumors in girls are an actual problem in modern gynecology, which is associated with certain difficulties in managing patients. Firstly, it is worth taking into account the higher anatomical mobility of tumors in girls than in adults, due to the high location of the ovaries, weakness of the ligamentous apparatus and the active lifestyle of the child, which causes a higher incidence of torsion of the volumetric mass in children. Secondly, surgical treatment of hormone-producing ovarian tumors leads to a decrease in ovarian reserve and irreversible consequences in the reproductive health of patients in the future, which is an extremely undesirable complication in childhood. Therefore, methods of fertility preservation should be discussed with girls and their parents. It is also important to note that hormone-producing ovarian tumors have a certain degree of malignancy and a tendency to recur. Thus, the relevance of this topic lies in the complexity of management of pediatric patients with this pathology due to the clinical features of the course and a higher probability of complications. Hormone-producing ovarian masses should also include follicular cysts and corpus luteum cysts, but the above structures are excluded from the discussion in this article.

Steroid cell tumors (SCT) of the ovary are rare, which has limited advances in the understanding of this enigmatic neoplasm. In this review, we summarize currently known clinicopathologic information on SCT. SCT are frequently hormonally active, leading to elevated serum and/or urine levels of androgenic hormones or their metabolites, and associated symptomatology, including virilization. The reported age at diagnosis is broad and has ranged from as young as 1 year old to 93 years old, although most patients were between ages 20 and 40 years. Most tumors are stage I and unilateral. The tumors are usually well circumscribed with a solid or solid to cystic cut surface. The tumors in one series reportedly ranged in size from 1.2 to 45 cm (average 8.4 cm). MRI is a useful imaging modality, typically showing a well delineated mass with contrast enhancement and lipid content on T2 and T1 weighted images, respectively. Microscopically, SCT display polygonal to epithelioid cells with abundant eosinophilic to vacuolated/clear cytoplasm and display an immunoprofile that is consistent with sex cord-stromal differentiation. Most cases are benign, without any recurrences after primary resection, but a subset - probably less than 20% of cases -are clinically malignant. Pathologic criteria that can specifically predict patient outcomes remain elusive, although features that correlate with adverse outcomes have been proposed based on retrospective studies. The molecular characteristics of SCTs are similarly under characterized, although there is some evidence of an enrichment for hypoxia-signaling gene mutations in SCT. In malignant SCT, the tumors generally show greater global genomic instability, copy number gains in oncogenes, and occasional BAP1 mutation. Future studies involving multiinstitutional cohort and unbiased molecular profiling using whole exome/transcriptome sequencing are needed to help advance our molecular understanding of SCTs. [ABSTRACT FROM AUTHOR]

All girls presenting with virilization (which signifies severe hyperandrogenism) warrant thorough investigation. Ovarian hyperthecosis (OHT) is a rare cause of virilization in premenopausal women. Here, we report the case of a previously healthy 12-year-old Chinese girl with signs of virilization at puberty. Her serum total testosterone was elevated at 5.1 nmol/L (146.97 ng/dL) (normal: <1.4 nmol/L, <40.35 ng/dL). Workup for Cushing syndrome, sex development disorders, congenital adrenal hyperplasia, and adrenal and ovarian androgen-secreting tumors was unrevealing. Ovarian and adrenal venous sampling demonstrated ovarian hyperandrogenism without lateralization. Ovarian biopsy revealed nests of theca cells in the stroma of the right ovary, substantiating the diagnosis of OHT. A single dose of a GnRH analog resulted in the complete suppression of serum testosterone, supporting the diagnosis of OHT. Medical treatment with hormonal replacement therapy normalized serum testosterone levels. Our case report illustrates the diagnostic approach to virilization among girls at puberty and the diagnosis of OHT as the underlying pathology. [ABSTRACT FROM AUTHOR]

Copyright of Pediatric Endocrinology, Diabetes & Metabolism is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The literature review is dedicated to the topical subject in current endocrinology and gynecology – clitoromegaly. At present, clitoromegaly is considered as a symptom of an endocrinological disease associated with impaired testosterone or androgen production. However, in most cases, the cause of the disease cannot be determined. A condition described in the clitoromegaly classification as an "idiopathic clitoromegaly" holds a leading place. Despite an opportunity to perform a successful clitoroplasty in childhood, adult patients with clitoromegaly quite often seek specialists` help. Such girls and women often suffer from anxietydepressive disorders related to social maladjustment associated due to sexological and psychological problems, which requires a sexologist or psychotherapist` supervision and treatment. Here, we provide the data on genetic syndromes accompanied by clitoromegaly. Differential diagnostics algorithms for neonates, young and adult women are proposed.

The Spanish artist, Jusepe de Ribera, painted a portrait of a virilized woman in 1631. He provided a brief clinical history on stone tablets, which indicates that the woman most likely harbored a benign, androgen-secreting ovarian tumor for 15 years. [ABSTRACT FROM AUTHOR]

Introduction: Children with 45X/46XY difference/disorder of sex development (DSD) have varying internal/external genitalia/gonads, Turner-like features, and increased risk of gonadal malignancy. We present a case of concomitant virilization and feminization as a unique feature of gonadoblastoma in a boy with 45X/46XY DSD. Case presentation: The patient was born with ambiguous genitalia (phallus of 2cm, perineal urethra) and a Turner-like phenotype. Ultrasound scan revealed horseshoe kidneys, intra-abdominal gonads, and Mullerian remnants. His karyotype was 45X/46XY with atypical Y chromosome. Initial gonadotrophin levels were very high. Biopsy of the bilateral gonads revealed testicular tissue. It was decided to raise the baby as a boy. Staged orchidopexy and hypospadias repair were done between 4 and 6 years of age. He remained under close clinical, biochemical and radiological follow-up for the potential development of gonadal malignancies. He developed penile enlargement at the age of11 years. Within a few months, he developed bilateral gynecomastia and rapid cystic enlargement of the gonads. Hormone quantification revealed elevated serum estrogen, a peri-pubertal testosterone level, and normal tumor marker levels. After a multidisciplinary team discussion, he underwent surgical exploration and removal of a bulky uterus and both gonads. Histology showed evidence of gonadoblastoma within the testicular and the ovarian stroma. Conclusion: Children with DSD are at high risk for developing gonadoblastomas, which can present as rapid concurrent isosexual and heterosexual pubertal development. It is critical that patients with DSD remain under close oncologic surveillance.

Steroid cell tumors (SCT) of the ovary are rare, which has limited advances in the understanding of this enigmatic neoplasm. In this review, we summarize currently known clinicopathologic information on SCT. SCT are frequently hormonally active, leading to elevated serum and/or urine levels of androgenic hormones or their metabolites, and associated symptomatology, including virilization. The reported age at diagnosis is broad and has ranged from as young as 1 year old to 93 years old, although most patients were between ages 20 and 40 years. Most tumors are stage I and unilateral. The tumors are usually well circumscribed with a solid or solid to cystic cut surface. The tumors in one series reportedly ranged in size from 1.2 to 45 cm (average 8.4 cm). MRI is a useful imaging modality, typically showing a well delineated mass with contrast enhancement and lipid content on T2 and T1 weighted images, respectively. Microscopically, SCT display polygonal to epithelioid cells with abundant eosinophilic to vacuolated/clear cytoplasm and display an immunoprofile that is consistent with sex cord-stromal differentiation. Most cases are benign, without any recurrences after primary resection, but a subset – probably less than 20% of cases –are clinically malignant. Pathologic criteria that can specifically predict patient outcomes remain elusive, although features that correlate with adverse outcomes have been proposed based on retrospective studies. The molecular characteristics of SCTs are similarly under characterized, although there is some evidence of an enrichment for hypoxia-signaling gene mutations in SCT. In malignant SCT, the tumors generally show greater global genomic instability, copy number gains in oncogenes, and occasional BAP1 mutation. Future studies involving multi-institutional cohort and unbiased molecular profiling using whole exome/transcriptome sequencing are needed to help advance our molecular understanding of SCTs.

Key Clinical Message: Jacobs syndrome and congenital adrenal hyperplasia are separate entities but share common clinical features such as ambiguous genitalia. Further studies are needed to conclude the relationship between Jacobs syndrome and congenital adrenal hyperplasia. A 5‐month‐old male infant was evaluated for ambiguous genitalia. Examination revealed cryptorchidism, inguinal hernia, long phallus, and Grade 3 scrotal hypospadias. Serum 17‐OH progesterone was high and chromosomal analysis showed 47XYY/45XO. A diagnosis of Jacobs and CAH was made. The parents were counseled about the patient's condition. He was given hydrocortisone and referred to the pediatric surgeon for further management. [ABSTRACT FROM AUTHOR]

Adrenal tumors are very rare causes of hyperandrogenism. Androgensecreting adrenal tumors are usually malignant; however, benign tumors have also been described in women. Adrenocortical carcinoma is very rare with incidence of 1 2 million per year. The androgen secreting type of adrenocortical carcinoma can be presented with hirsutism, acne, alopecia and virilization symptoms such as cliteromegaly. This case was presented with hyperandrogenism and virilization symptoms and it was diagnosed as having a very rare cause, namely androgen secreting adrenal tumor. Because the symptoms are related to gynecological complaints such as menstrual irregularities and cliteromegaly, these patients would first need to apply to their gynecologists, who may play an important role in the early diagnoses of these rare diseases.

Key Clinical Message Jacobs syndrome and congenital adrenal hyperplasia are separate entities but share common clinical features such as ambiguous genitalia. Further studies are needed to conclude the relationship between Jacobs syndrome and congenital adrenal hyperplasia. Abstract A 5‐month‐old male infant was evaluated for ambiguous genitalia. Examination revealed cryptorchidism, inguinal hernia, long phallus, and Grade 3 scrotal hypospadias. Serum 17‐OH progesterone was high and chromosomal analysis showed 47XYY/45XO. A diagnosis of Jacobs and CAH was made. The parents were counseled about the patient's condition. He was given hydrocortisone and referred to the pediatric surgeon for further management.

Virilization is a rare condition in postmenopausal women, usually attributed to androgen excess of ovarian or adrenal origin. A 62-year-old woman presented with excessive hair loss of 3 months' duration and was investigated for an endocrine cause of alopecia. The hormonal evaluation revealed increased testosterone but normal levels of androstenedione and dehydroepiandrosterone sulfate, while the results of transvaginal ultrasonography and abdominal computed tomography were unremarkable. Based on these findings, the possibility of an adrenal androgen-secreting tumor was ruled out and suspicion of Leydig cell hyperplasia was raised. A bilateral laparoscopic salpingo-oophorectomy was performed due to the age of the patient and the diagnosis of Leydig cell hyperplasia was confirmed by histopathological examination. The postoperative course of the patient was uneventful and a repeat hormonal evaluation after the operation showed a normalization of androgen levels. In conclusion, Leydig cell hyperplasia should be considered as a likely cause of hyperandrogenism of ovarian origin in women who develop virilization. In postmenopausal women, bilateral oophorectomy will treat the disorder and provide a conclusive diagnosis via histopathological examination.

Background: Congenital Adrenal Hyperplasia (CAH) is a chronic disease that requires lifelong treatment. Patients may face stigmatization, which may affect their quality of life (QoL). Therefore, we assessed the clinical characteristics and QoL of patients with CAH in the Middle East. Methods: This case-control study included patients with CAH aged >5 years from two tertiary centers (2020-2021). The patients were matched to a healthy control group and were then divided into pediatric and adult groups. Data were collected fromtheir electronicmedical records. Additionally, the EQ-5D-5L QoL questionnaire was completed by both the patients and control group to assess five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Results: The study included 248 patients with CAH (females: 58.8%), with a family history of the condition (57.3%) and/or parental consanguinity (68.1%). The most frequently reported gene defect was CYP21A2, while the most commonly reported symptoms/signs were ambiguous genitalia and obesity. Almost all female patients had received corrective surgery. The questionnaire response rate was 86.3% (n=214/248). The CAH patient group's mean total QoL score was 85.2 compared with 99.8 in the control. Further, CAH patients had lower QoL scores in all domains compared to those in the control group (p = 0.0001-0.0023). The pain/discomfort and anxiety/depression domains were affected significantly more than the other domains were, with 47.7% and 44.4% participants, respectively, p<0.0001. Additionally, obesity was found to be a predictor of reduced mobility following a logistic regression analysis (p = 0.04, OR (0.18-0.98)). Conclusion: Patients with CAH reported lower QoL overall, particularly in the pain/discomfort and anxiety/depression domains. Based on this, we recommend the early involvement of psychologists in a multidisciplinary team approach, premarital screening, and the implementation of awareness programs for people diagnosed with CAH in communities with high consanguineous mating. [ABSTRACT FROM AUTHOR]

Postmenopausal hyperandrogenism is a condition caused by relative or absolute androgen excess originating from the ovaries and/or the adrenal glands. Hirsutism, in other words, increased terminal hair growth in androgen-dependent areas of the body, is considered the most effective measure of hyperandrogenism in women. Other symptoms can be acne and androgenic alopecia or the development of virilization, including clitoromegaly. Postmenopausal hyperandrogenism may also be associated with metabolic disorders such as abdominal obesity, insulin resistance, and type 2 diabetes. Mild hyperandrogenic symptoms can be due to relative androgen excess associated with menopausal transition or polycystic ovary syndrome, which is likely the most common cause of postmenopausal hyperandrogenism. Virilizing symptoms, on the other hand, can be caused by ovarian hyperthecosis or an androgen-producing ovarian or adrenal tumor that could be malignant. Determination of serum testosterone, preferably by tandem mass spectrometry, is the first step in the endocrine evaluation, providing important information on the degree of androgen excess. Testosterone >5 nmol/L is associated with virilization and requires prompt investigation to rule out an androgen-producing tumor in the first instance. To localize the source of androgen excess, imaging techniques are used, such as transvaginal ultrasound or magnetic resonance imaging (MRI) for the ovaries and computed tomography and MRI for the adrenals. Bilateral oophorectomy or surgical removal of an adrenal tumor is the main curative treatment and will ultimately lead to a histopathological diagnosis. Mild to moderate symptoms of androgen excess are treated with antiandrogen therapy or specific endocrine therapy depending on diagnosis. This review summarizes the most relevant causes of hyperandrogenism in postmenopausal women and suggests principles for clinical investigation and treatment. [ABSTRACT FROM AUTHOR]

Copyright of Bagcilar Medical Bulletin / Bağcılar Tıp Bülteni is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BackgroundCongenital Adrenal Hyperplasia (CAH) is a chronic disease that requires lifelong treatment. Patients may face stigmatization, which may affect their quality of life (QoL). Therefore, we assessed the clinical characteristics and QoL of patients with CAH in the Middle East.MethodsThis case-control study included patients with CAH aged >5 years from two tertiary centers (2020–2021). The patients were matched to a healthy control group and were then divided into pediatric and adult groups. Data were collected from their electronic medical records. Additionally, the EQ-5D-5L QoL questionnaire was completed by both the patients and control group to assess five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).ResultsThe study included 248 patients with CAH (females: 58.8%), with a family history of the condition (57.3%) and/or parental consanguinity (68.1%). The most frequently reported gene defect was CYP21A2, while the most commonly reported symptoms/signs were ambiguous genitalia and obesity. Almost all female patients had received corrective surgery. The questionnaire response rate was 86.3% (n=214/248). The CAH patient group’s mean total QoL score was 85.2 compared with 99.8 in the control. Further, CAH patients had lower QoL scores in all domains compared to those in the control group (p ≤ 0.0001–0.0023). The pain/discomfort and anxiety/depression domains were affected significantly more than the other domains were, with 47.7% and 44.4% participants, respectively, p

Background: We presented the clinical and genetic features of a male ambiguity due to 17-beta-hydroxysteroid dehydrogenase 3 (17B-HSD3) deficiency. Methods: The proposita was an 11-year-old girl and the first child of a consanguineous family. The external genitalia were completely female and had a short vaginal pouch. She had palpable gonads in her inguinal area and underwent bilateral gonadectomy at the age of two. At the age of 10, she was referred to our clinic for more evaluation. In pelvic sonography, uterine and ovarian were not seen. Her karyotype was 46, XY, and her LH and FSH levels were elevated, and three of the patient’s aunts and one of the mother’s aunts had similar signs. Conclusions: We identified a novel homozygous missense variation (c.731T>A, p. Ile244Lys) in the HSD17B3 gene. This alteration changes Isoleucine to Lysine in exon 10.

Pediatric adrenocortical tumors (ACTs) are rare entities with an incidence of 0.2% of all pediatric tumors. Only two cases of antenatally detected ACT have been reported in the literature. Our case is the first report of an antenatally detected suprarenal mass which manifested with postnatal virilizing features and was proven to be adrenocortical adenoma on histology.

Pediatric adrenocortical tumors (ACTs) are rare entities with an incidence of 0.2% of all pediatric tumors. Only two cases of antenatally detected ACT have been reported in the literature. Our case is the first report of an antenatally detected suprarenal mass which manifested with postnatal virilizing features and was proven to be adrenocortical adenoma on histology. [ABSTRACT FROM AUTHOR]

Gonadoblastoma is a rare ovarian tumor composed of sex cord cells and primitive germ cells. While the majority of gonadoblastomas are found in individuals with 46,XY gonadal dysgenesis, they are also rarely seen in patients with a 46,XX karyotype. We report a case of a fourteen-year-and-six-month-old girl presenting with an uncommon cause of virilization due to a virilizing ovarian tumor. The patient underwent bilateral salpingo-oophorectomy. Upon histopathological examination, the excised tumor was confirmed to be bilateral gonadoblastoma, with dysgerminoma on the left side. Malignant gonadal tumors should be considered in cases of primary gonadal insufficiency with a 46,XX karyotype and progressive virilization. Even when laboratory and imaging tests show no abnormalities, a gonadal biopsy should be considered.

Introduction: The occurrence of ectopic prostate tissue in the female genital tract is rare and has only been described sporadically. The origin of these lesions is unclear, but their appearance seems to be associated with various forms of androgen excess, including androgen therapy for transgender treatment or disorders of sex development, such as classic congenital adrenal hyperplasia (CAH). This is the first described case of ectopic prostate tissue in the cervix uteri of a 46,XX patient with a confirmed diagnosis of non-classic CAH due to 21-OHD and a history of mild adrenal androgen excess. Case presentation: We describe a 34-year-old patient with a genetic diagnosis of non-classic CAH due to 21-hydroxylase deficiency (21-OHD) with a female karyo- and phenotype and a history of mild adrenal androgen excess. Due to dysplasia in the cervical smear, conization had to be performed, revealing ectopic prostate tissue in the cervix uteri of the patient. Conclusions: An association between androgen excess and the occurrence of prostate tissue is likely and should therefore be considered as a differential diagnosis for atypical tissue in the female genital tract. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) is rare, aggressive, and metastasizes mainly to the lungs, liver, and regional lymph nodes. This is the first reported case of a pediatric patient with adrenohepatic fusion (AHF) and functional ACC that solely invaded the liver. The patient was a 2 year and 9 month old female, with a 3-month history of weight gain, signs of virilization, Cushing's syndrome, hypertension, and a palpable mass in the right hypochondrium and epigastrium. Blood tests revealed the following: hemoglobin, 16.3 g/dL; cortisol, 25.3 μg/dL; and total serum testosterone, 1489.01 ng/mL. Ultrasonography and computed tomography initially revealed a hepatic tumor measuring 100 × 111 × 106 mm, with a volume of 615 mL. The patient was diagnosed with functional ACC. Curative resection (R0 resection) was performed, involving partial resection of the right hepatic lobe. The resected tumor was 12 × 10 × 7 cm and 650 g, with evidence of invasion into the liver capsule, which was consistent with ACC stage III (T 4 N 0 M 0). Management included mitotane, cisplatin, etoposide, and doxorubicin, and favorable progress was noted at the 2-year and 3-month follow-up. In cases with AHF, a sufficient portion of the right hepatic lobe must be resected to ensure complete removal of the tumor. • Pediatric patient diagnosed with mixed functional adrenal carcinoma that invaded the liver in adrenohepatic fusion. • Understanding adrenohepatic fusion will aid in devising an appropriate surgical approach. • Resecting tumor with sufficient hepatic lobule is essential in adrenohepatic fusión. [ABSTRACT FROM AUTHOR]

Androgen-producing steroid cell ovarian tumors are rare, comprising less than 1% of ovarian neoplasms, and can present with infertility and rapid virilization. Here we discuss the case of a 28-year-old woman who presented with an unusually insidious 2-year history of infertility, hirsutism, and clitoromegaly who was found to have an elevated serum testosterone and a left ovarian mass. She underwent oophorectomy and pathology revealed a steroid cell tumor, not otherwise specified (NOS), with no malignant features. Following surgery, the patient's hyperandrogenic symptoms resolved with normalization of testosterone within 6 months, and she was able to conceive spontaneously. In reproductive-aged women with progressive hyperandrogenic symptoms, androgen-producing tumors, including those of ovarian origin, should be suspected. Thorough investigation, including plasma hormone levels and tumor histology, can lead to accurate diagnosis and management. Treatment should be guided by histology and surgical staging, with consideration for future fertility desires. Women who have not completed childbearing can undergo unilateral oophorectomy or tumor resection for benign tumors, with close monitoring of sex hormone levels postoperatively. [ABSTRACT FROM AUTHOR]

Purpose: Mutations in the NR5A1 gene, encoding the transcription factor Steroidogenic Factor-1, are associated with a highly variable genital phenotype in patients with 46,XY differences of sex development (DSD). Our objective was to analyse the pubertal development in 46,XY patients with NR5A1 mutations by the evaluation of longitudinal clinical and hormonal data at pubertal age. Methods: We retrospectively studied a cohort of 10 46,XY patients with a verified NR5A1 mutation and describe clinical features including the external and internal genitalia, testicular volumes, Tanner stages and serum concentrations of LH, FSH, testosterone, AMH, and inhibin B during pubertal transition. Results: Patients who first presented in early infancy due to ambiguous genitalia showed spontaneous virilization at pubertal age accompanied by a significant testosterone production despite the decreased gonadal volume. Patients with apparently female external genitalia at birth presented later in life at pubertal age either with signs of virilization and/or absence of female puberty. Testosterone levels were highly variable in this group. In all patients, gonadotropins were constantly in the upper reference range or elevated. Neither the extent of virilization at birth nor the presence of Müllerian structures reliably correlated with the degree of virilization during puberty. Conclusion: Patients with NR5A1 mutations regardless of phenotype at birth may demonstrate considerable virilization at puberty. Therefore, it is important to consider sex assignment carefully and avoid irreversible procedures during infancy. [ABSTRACT FROM AUTHOR]

Luteoma is a benign ovarian neoplasm, usually incidentally found during pregnancy. It can produce androgenic hormones. Most cases are asymptomatic, while a few present with maternal and/or neonatal virilization. Its etiology is still unclear and may relate to human chorionic gonadotropin (hCG) stimulation. Pregnancy luteoma will resolve spontaneously after childbirth. The early recognition and prompt diagnosis can save the ovary from unnecessary surgery. [ABSTRACT FROM AUTHOR]

Increasing life expectancy makes the issue of medical management of hormonal, cardiometabolic and cosmetic changes caused by menopause increasingly relevant. The manifestations and consequences of hyperandrogenism (HA) in women of perimenopausal and menopausal age, both in context of cardiometabolic disorders and dermatopathies, often cause difficulties in diagnosis and uncertainty in management among medical specialists. This literature review presents data from current studies on differences of synthesis, transport, and peripheral conversion of androgens in menopause in healthy women and in women with polycystic ovary syndrome, as well as on tumorous and non-tumorous causes of HA in menopause. Most menopausal women have a relative HA due to increased ovarian synthesis caused by high luteinizing hormone levels and progressive estrogen decline, as well as increase of bioavailable testosterone fraction caused by a decrease in sex hormone binding globulin. The causes of true (pathological) HA in menopause can be divided into non-neoplastic, represented by genetically determined syndromes (polycystic ovary syndrome, non-classical forms of congenital adrenal hyperplasia), ovarian hypertechosis, iatrogenic causes; and neoplastic causes – adrenal and ovarian tumors. Diagnosis of the causes of HA in menopause can be a difficult task, successfully solved by a comprehensive approach with the use of next steps: careful analysis of anamnestic data, the details of which may indicate the presence of pre-existing polycystic ovary syndrome or non-classical congenital adrenal hyperplasia; history of the disease (gradual or sudden development of HA as signs of tumorous or non-tumorous origin) examination and physical examination (objective assessment of the degree of HA, signs of insulin resistance or endocrinopathy), use of laboratory diagnostics (confirmation of biochemical hyperandrogenism and use of oncologic markers in case of suspicion of certain types of tumors); additional methods of examination (ultrasound, MRI) and in some cases functional tests.

Objective: To provide a reference for the diagnosis and treatment of ovarian steroid cell tumors, not otherwise specified (SCTs-NOS)., Methods: We retrospectively analyzed the clinicopathological data of three patients with SCTs-NOS admitted to the Tianjin Medical University General Hospital from 2012 to 2022 and reviewed literature reports related to this disease., Results: A total of 3 cases in our center and 70 cases searched in literature reports were included. The age at diagnosis ranged from 3 to 93 years (median, 34 years). The common clinical manifestations were hirsutism, acne, deepened voice, clitoromegaly, amenorrhea, and excessive weight gain. Tumor sizes ranged from 1.2 to 45 cm, with an average diameter of 6.5cm. Most of SCTs-NOS were benign, but some of them exhibited malignant behavior. Surgery was the main treatment and close follow-up was required. The follow up time of 73 cases ranged from 3 to 132 months (median, 21.3 months). Disease recurrence or progression occurred in 14 cases (19.2%). Three of the 73 patients had a successful pregnancy., Conclusion: SCTs-NOS usually occur in women of reproductive age, which are mainly manifested as androgen excess symptoms. Surgery is an appropriate treatment for SCTs-NOS and should be individualized. Final diagnosis depends on pathology. SCTs-NOS have malignant potential, and the treatments for patients with malignant tumors and disease recurrence or progression were cytoreductive surgery, adjuvant chemotherapy, and gonadotrophin-releasing hormone agonists (GnRHa) therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Tian, Meng and Liu.)

Ovarian Sertoli-Leydig cell tumors (SLCT) are extremely rare malignant tumors deriving from the sex cord stroma. An abdominal mass and a virilization syndrome dominate the clinical symptoms. This particular tumor poses diagnostic and therapeutic problems. Prognosis depends on staging (the International Federation of Gynecology and Obstetrics (FIGO)/tumor, node, metastasis (TNM)) and differentiation. The treatment is surgical, combined with adjuvant chemotherapy in certain cases. We report the case of a three-year-old girl admitted to our department for signs of virilization with an abdominal mass. The literature does not contain any reports of a younger case. Ovarian SLCTs should be considered in every girl presenting with signs of virilization and a lower abdominal mass. The prognosis and management depend on the results of the histological analysis and extension evaluation in order to define therapeutic management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Jabri et al.)

We present a case report of a 55-year-old male patient with congenital adrenal hyperplasia (CAH) and a large neoplastic mass in the abdomen. The patient presented with an abdominal mass and discomfort, along with a bilateral empty scrotum since birth. A diagnostic workup revealed the mass to be a uterine leiomyoma associated with CAH, a simple virilizing type. Treatment involved an exploratory laparotomy and excision of the mass, including the removal of the entire uterus. Complete removal of the mass and uterus was ensured. The patient's response to treatment was satisfactory. This case highlights how pre-operative and post-operative diagnoses can vary, along with the importance of early diagnosis of CAH and disorders of sexual differentiation (DSD), emphasizing the significance of unusual presentations and resultant complications, as they might go unnoticed. CAH in XX females may have unusual presentations, such as short stature and a male phenotype (Prader 5). The patient exhibited a normal pattern of male sexual function. This condition might go unnoticed, resulting in leiomyoma, adrenal tumors, prostate tumors if prostate tissue is present, and so on. Healthcare providers must watch out for such rare presentations., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Qureshi et al.)

Background: Adrenocortical carcinoma is a rare, isolated malignancy. Case: A 13-year-old girl presented with secondary amenorrhea, hirsutism, and hypertension. Her clinical manifestations were interpreted as polycystic ovary syndrome and hyperinsulinemia. The rapid progression of this pubertal girl's virilization should have, but did not draw clinical attention to her malignancy. Because her condition worsened, she ultimately was transferred to our hospital because of an abdominal mass. She was diagnosed with a very large adrenal cortical carcinoma with pulmonary metastasis. The child was in the advanced stage and presented adrenal crisis after chemotherapy and mitotane treatment. Summary and Conclusion: Rapidly progressive masculinization, with a marked increase in adrenal-derived androgens, might indicate rare adrenal neoplasms. [ABSTRACT FROM AUTHOR]

Objective: To evaluate a rare case of a postmenopausal woman with hirsutism and virilization due to Leydig cell tumors (LCTs) of both ovaries. Methods: In this challenging case, the diagnostic studies included the detection of total/free testosterone, hemoglobin, and estradiol levels; adrenal computed tomography; and pelvic magnetic resonance imaging. Results: A 61-year-old woman presented for the evaluation of hirsutism. Physical examination revealed normal vital signs and evidence of virilization. The baseline laboratory findings were hemoglobin level of 16.2 g/dL (reference, 12.0-15.5 g/dL), total testosterone level of 803 ng/dL (reference, 3-41 ng/dL), and free testosterone level of 20.2 pg/mL (reference, 0.0-4.2 pg/mL). Pelvic magnetic resonance imaging showed bilateral homogeneous ovarian enhancement. Based on the magnetic resonance imaging findings and clinical presentation, the patient was diagnosed with ovarian hyperthecosis and underwent laparoscopic bilateral oophorectomy. Pathology confirmed LCTs in both ovaries. Six months later, testosterone levels normalized, with significant improvement in hirsutism and virilization. Conclusion: Clinicians should be aware of androgen-secreting tumors, including rare bilateral LCTs in postmenopausal women presenting with progressing hirsutism and virilization. Marked hyperandrogenemia with total testosterone level of >150 ng/dL (5.2 nmol/L) or serum dehydroepiandrosterone sulfate level of >700 μg/dL (21.7 mmol/L) is typically found. It should be recognized that diffuse stromal Leydig cell hyperplasia and small LCTs may be missed on imaging, and in some cases only pathology can confirm the result.

Steroid cell tumors of the ovary are rare sex-cord stromal tumors, accounting for approximately 0.1% of all ovarian neoplasms. Majority of these tumors are benign, occur in pre-menopausal women and are associated with hyperandrogenism. However, around one-third of cases are malignant and do not present with hormonal manifestations. A 48-year-old post-menopausal woman presented with complaints of gradually increasing progressive abdominal distension over the past 3 months. She had a history of weight gain but denied any symptoms of virilization. On examination, abdominal distension associated with ascites was noted. Serum CA125 level was raised. Contrast-enhanced computed tomography revealed a solid right adnexal mass. Based on the clinical impression of epithelial ovarian malignancy, the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy. Histopathological examination revealed steroid cell tumor of the not otherwise specified type in the right ovary with the capsular breach. However, all other organs, including the omentum were free of tumor. The index case is unique for its presentation in a post-menopausal woman, association with ascites, elevated CA125 levels and lack of any virilization manifestations. Establishing an early and accurate tissue diagnosis is essential so that appropriate surgical management can be done to prevent the development of metastases in potentially malignant cases.