Clitoromegaly Research Articles

A Rare Entity of Idiopathic Clitoromegaly with HBsAg Positive Status Managed with Dorsal Nerve Sparing Clitoroplasty

Clitoromegaly, defined as an enlarged clitoris with a clitoral index of more than 35 mm2 is a frequently seen congenital malformation but an idiopathic entity is a rare one. The most acceptable method of treatment of clitoromegaly is clitoroplasty with preservation of neurovascular pedicle to glans to achieve normal genital anatomy and to preserve tactile sensation. We present a rare case of idiopathic clitoromegaly managed by dorsal nerve sparing reduction clitoroplasty in an HBsAg-positive patient.

Congenital Adrenal Hyperplasia with Poor Virilization at the Onset: A Case Report

Objective: Congenital adrenal hyperplasia (CAH) is a relatively rare disorder. This case report aims to highlight the diagnostic challenges faced by clinicians when typical characteristics of the disease are not fully evident. Case: The patient, a 2-month-old infant, presented at the emergency room with vomiting, diarrhea, dehydration, and lethargy. Physical examination revealed mild clitoral hypertrophy. Laboratory tests showed sodium levels at 121 mEq/L and potassium at 5.8 mEq/L, without hyperpigmentation or genital ambiguity. CAH was suspected. Due to resource constraints, 17-hydroxyprogesterone levels could not be measured. Treatment was initiated with oral prednisone (1 mg) and sodium chloride supplementation. One month later, after another hospital discontinued the treatment, the patient was readmitted with vomiting, dehydration, hyponatremia, and hyperkalemia, but still showed no significant clitoral enlargement or hyperpigmentation. The patient was stabilized and discharged after resuming treatment. Subsequent consultations revealed poor weight and height gain. At one year of age, the mother reported clitoral enlargement and morning erections. Treatment with fludrocortisone and oral hydrocortisone led to significant improvement. A genetic study confirmed a CYP21A2 gene mutation. Conclusion: This case underscores the diagnostic complexity of CAH in patients who do not initially exhibit typical virilization. It also emphasizes the importance of clinical suspicion and tailored treatment in resource-limited settings.

Sexual development disorder in a dog

A 1-year intact, phenotypic female Doberman Pinscher dog, was evaluated for suspected sexual development disorder. Patient had a history of white mucoid vaginal discharge with no estrous signs or behavior. Clitoral hypertrophy with a palpable os clitoris were noted. Transabodminal ultrasonography revealed a right gonad and tubular structures (possibly uterus). Exploratory laparotomy revealed 2 underdeveloped gonads in caudodorsal abdomen and a markedly underdeveloped right uterine horn. Histopathology confirmed bilateral ovotestes. Karyotyping (number and morphology of chromosomes) and fluorescence in situ hybridization (XX and XY cells) results were normal. Samples were PCR positive for sex-determining region Y (SRY) and X-linked androgen receptor gene. We concluded that the patient was either a mosaic or chimera with normal female 78,XX and normal male 78,XY cells and genetically a mix of male and female. Final diagnosis was sex chromosome (78,XX/XY), SRY-positive, ovotesticular, disorder of sexual development with female phenotype.

The Batalha Clitoropexy: Shortening an Elongated Clitoris - A Minimally Invasive Technique.

Female cosmetic genital surgery is becoming increasingly sought after by women who are concerned with the appearance of their vulva. Labiaplasty for the labia minora is undoubtedly the most commonly performed female cosmetic genital surgery. However, an increasing number of patients seen in our clinics in both Brazil and the United States are presenting with clitoral hypertrophy, specifically clitoral elongation. The elongated clitoris will usually protrude beyond the labia minora and majora and from the patient's perspective will give a less feminine appearance as they will often describe the protruding clitoris as feeling like they have a small penis. The surgical technique described here, Batalha Clitoropexy, is a minimally invasive surgical technique for clitoral length-reduction that does not require amputation or debulking. This technique is presented in the form of the detailed sequential steps needed to achieve satisfactory results. Photos taken before and after the procedure in a representative case show that the clitoral length has been shortened from 5.0 cm to 1.5 cm without the need of an invasive amputation or debulking clitoroplasty. Many patients with clitoromegaly or an elongated protruding clitoris do not need to undergo an invasive clitoroplasty. Specifically, patients with clitoral elongation or clitoral ptosis can be surgically treated with a less-invasive clitoropexy surgical procedure which can restore normal anatomic position to treat a protruding clitoris.

Female virilization related to congenital adrenal hyperplasia and psychological distress

Introduction In females, congenital adrenal hyperplasia (CAH), a spectrum of inherited genetic conditions related to the disruption of adrenal steroidogenesis, is among the most common conditions leading to inappropriate virilization. For adolescent and adult women, progression of hirsutism may have many psychological concerns.Objectives To explore the psychological distress of a young Tunisian woman who sought medical help and psychological support at a late stage, after suffering from genital ambiguity and severe virilization.MethodsHarboring phenotypic male transformation at puberty, our patient attended genetic counselling for cytogenetics assessment. Clinical, biological, psychological and genetic explorations were thus carried out.Results A 17-year-old female was born from first-degree consanguineous parents, and had healthy siblings (a sister and three brothers). After a single menstrual episode at puberty, she developed amenorrhea and an unexpected progressive virilization, including hirsutism with an inappropriate beard that she had to shave every day and a male voice. Clinical examination revealed a male morphotype with an enlarged clitoris that resemble a penis, male-type pubic hair, underdeveloped of breasts, abnormal cutaneous hyperpigmentation, and a short stature. Pelvic ultrasound revealed a small uterus, but with no visualized gonads. Genetic exploration showed a female 46,XX karyotype and the absence of Y chromosome sequences. Diagnosis of a non-classic CAH was confirmed. Psychological assessment found that the psychological development of the sexual identity corresponded to the assignment of the female sex. A severe psychological suffering due to the non-acceptance of her virile appearance impaired the quality of her daily personal and social life. Stigmata of a depressive syndrome were also revealed.ConclusionsParticular attention to the psychological assessment of patients with CAH is recommended, as changes in physical appearance have a detrimental impact on psychological and mental well-being.Disclosure of InterestNone Declared

Clinical, Ovulatory and Histological Effect of a Postnatal Testosterone Treatment in Female Dogs.

It has been described in some female mammalian species that postnatal androgenization causes reproductive structural and functional abnormalities. The objective of this study was to describe the clinical, ovulatory and genital effects of postnatal androgens in female dogs. Ten newborn female crossbred puppies were randomly assigned to: testosterone enanthate 18 mg/100 g sc (TE; n = 5) or placebo sc (PL; n = 5). The puppies were physically followed up until puberty when ovulation was tested by serum progesterone. Then, ovariohysterectomies were performed, and genital tracts were grossly and histomorphometrically examined. At puberty, all the females had normal estrous behavior and ovulated without age and body weight differences. All TE puppies presented mild clitoris enlargement. Gross and microscopical ovarian examination did not reveal differences. Conversely, the endometrial area occupied by uterine glands as well as the height of the glandular and luminal epithelium were higher in the TE than in the PL group (<0.01). The height of the endometrium and myometrial thickness did not differ between groups. It was concluded that a supraphysiological postnatal dose of testosterone did not affect ovulatory capacity, nor did it provoke gonadal histological alterations, although it caused an increased area of endometrial glands and a higher uterine epithelium.

The Endocrine Phenotype Induced by Pediatric Adrenocortical Tumors Is Age- and Sex-Dependent.

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. We sought to extend knowledge on endocrine manifestations with regard to age and sex to facilitate early diagnosis. 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. 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. The endocrine phenotype induced by pediatric ACT is age- and sex-dependent.

Heterosexual precocious puberty due to virilizing adrenocortical adenoma

ABSTRACT This case details a 5-year-old girl with a 3-month history of heterosexual precocious puberty, presenting with clitoral enlargement and pubic hair development. In our patient, the clinical and hormonal characteristics were suggestive of adrenocortical carcinoma. However, radiological and histopathological findings indicated adrenocortical adenoma. This case highlights the diagnostic complexities that exist in pediatric adrenocortical tumors.

Reproductive health assessments in female polar bears: Anatomy, pathology, and diagnostic techniques

The reproductive success of polar bears (Ursus maritimus) in U.S. zoos is poor and the underlying causes of reproductive failure remain elusive. It is evident that new methodologies for evaluating fertility are needed, along with baseline information about species-specific reproductive anatomy and physiology. Between 2012 and 2024, 25 examinations of 17 female polar bears were conducted opportunistically, and included vulvar measurements, vaginal cytology, vaginoscopy, hysteroscopy with endometrial biopsy, and/or ultrasonography. Additionally, reproductive tracts (n = 10) harvested post-mortem were examined shortly after collection, allowing for inspection of anatomy ex vivo. The outcomes of these activities yielded detailed measurements and descriptions of reproductive anatomy. Vaginal cytology patterns demonstrated shifts in vaginal epithelial cell type associated with estrus and vaginoscopy enabled systematic evaluation of internal reproductive structures, including the vestibule, vestibulo-vaginal junction, urethral os, vaginal canal, and cervix. Hysteroscopy allowed visualization of the uterine endometrium and facilitated endometrial biopsy collection. Additionally, ultrasonography was utilized to identify ovaries in several bears, offering insights into ovarian dynamics and follicular development. Several abnormalities were noted during examinations of both in vivo and ex vivo tracts; these included clitoral hypertrophy, vaginal strictures, uterine polyps, endometritis, and cystic hyperplasia, although it is unclear if these aberrations significantly impacted fertility. Findings contribute to a better understanding of polar bear reproductive anatomy, highlight the utility of diagnostic techniques for monitoring reproduction, and elucidate potential causes of reproductive failure in polar bears.

NR5A1-related 46,XY partial gonadal dysgenesis: A case report and literature review

Rationale: Disorders/differences of sex development (DSD) include a diverse group of congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is discordant. It involves several variant genes, and one of them is NR5A1. NR5A1 encodes a signal transduction regulator in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal pathway, and pathogenic mutation in this gene is a cause of 46,XY DSD. Patient concerns: A 12-year-old individual raised as a girl was admitted to the hospital due to hirsutism and a deep voice that began at 11 years old. The individual exhibited testicular hypoplasia, clitoral hypertrophy, and female external genitalia. Diagnoses: The patient was diagnosed 46,XY partial gonadal dysgenesis. The cytogenetics revealed a 46,XY karyotype and DNA sequencing shown a variant in NR5A1. Pelvic magnetic resonance imaging showed absence of uterus and ovaries. The abdominopelvic ultrasound revealed bilateral testicle in bilateral groin. Pathology confirmed testes dysgenesis. Interventions: The patient underwent bilateral orchiectomy at age 12 years and was given a feminizing hormonal treatment of 0.5 mg/day of estradiol valerate tablets. Outcomes: The patient recovered well after surgery and hormonal treatment and had a regression in hirsutism and clitoromegaly. Lessons: 46,XY DSD is a rare disease that the development of chromosomal, gonadal, or anatomical sex is discordant, when diagnosed 46,XY DSD, the identification of an NR5A1 variant should be considered.

Disorders of sexual differentiation. A clinical case

The biological sex of a person is anatomical, physiological, and genetic features that help distinguish a male organism from a female one. One distinguishes genetic, gonadal, and phenotypic sex of a person. Sexual differentiation is a process of development, during which the biological male or female sex is formed, it occurs under the influence of genetic and hormonal factors during fetal development. In this regard, any damage at this stage can lead to disorder of sexual development of a newborn. Disorder of sexual differentiation is a complex of medical conditions in which there is a mismatch between a person’s genetic, gonadal and phenotypic sex.Sometimes it is difficult to visually determine the sex of a child born with disorder of the sexual development due to an abnormal, undefined structure of the external genitalia. For example, they may have the appearance of hypertrophied labia majora and/or a hypertrophied clitoris and the absence of testicles, or vice versa, the child’s genitals may have a normal appearance, but at the same time the internal genitals may be improperly developed.To determine which gender to choose for a child with disorder of sexual differentiation, a number of examinations, including genetic ones, should be carried out. Disorder of sexual differentiation is a complex medical and social problem involving a multidisciplinary team of doctors and the patient’s family. This article describes a clinical case of a child with disorder of sexual differentiation at the stage of diagnosis verification. An interdisciplinary approach is an integral part of accompanying a child with disorder of sexual differentiation, where the joint efforts of doctors, psychologists, teachers and other specialists contribute to the creation of inclusive and safe conditions for the development of each person.

Subtunical Reduction Clitoroplasty of a 22 years old Female for Clitoromegaly with Congenital Adrenal Hyperplasia-Case Report

Clitoromegaly is an abnormal condition commonly related to congenital adrenal hyperplasia. We presented a 22 years old adult female patient with chief complaint of enlarged clitoris since birth, other female secondary sexual characteristics were normal. The karyotype test result was 46 XX. Subtunical resection of erectile cavernous tissue of the enlarged clitoris with preservation of intact blood supply to the glans is a safe method of diminishing shaft and glans size and allow the patient to do sexual activity after marriage during a two-years follow up. Bangabandhu Sheikh Mujib Med. Coll. J. 2023;2(2):127-130.

THU187 Genotype-Phenotype Correlation, Clinical Presentation And Feminizing Surgery In Children With Congenital Adrenal Hyperplasia Due To 21-Hydroxylase Deficiency: A Nationwide Multi-Center Study

Abstract Disclosure: M. Lind-Holst: None. A. Berglund: None. M. Duno: None. G. Hvistendahl: None. M. Fossum: None. A. Juul: None. N. Jørgensen: None. K.M. Main: None. C.H. Gravholt: None. D. Hansen: None. Background: Congenital adrenal hyperplasia (CAH) due to 21 hydroxylase deficiency (21OHD) is a common autosomal recessive disorder caused by pathogenic variants in CYP21A2. Genotype cannot always predict severity and clinical consequences, and genotype-phenotype is only well correlated in the most severe clinical cases of CAH. Furthermore, non-classical CAH suffers from non-diagnosis, especially in males. Objective: Describe the genotype-phenotype correlation in Danish children with 21OHD and identify the most frequent pathogenic CYP21A2 variants. We describe the clinical manifestations at time of diagnosis and present data on virilization and feminizing surgery of females, stratified by genotype group during 20 years. Method: A national population-based study of all Danish children diagnosed with 21OHD, combining health registries and medical record data. We identified pathogenic variants in CYP21A2 and genotype-phenotype correlation. Clinical presentation at diagnosis and feminizing surgery in females was stratified by genotype group: Null, A, B, C and D, reflecting the preserved 21-hydroxylase activity in increasing order. Results: Variants frequency of 494 unique alleles: Deletion (31.8%) followed by I2G, Q318X, I172N, V281L, P30L, Cluster-E6, R356W and insT by 25.9%, 9.1%, 8.6%, 8.7%, 6.5%, 1.4%, 1.4% and 0.6%, respectively. Genotype-phenotype correlations: Null: 98%, A: 94%, B: 50%, C: 76%. Overall, 62 of the 159 children (67%) had evidence of pseudo-precocious puberty at time of diagnosis which was the most frequent group of symptoms in genotype group B: 8.2%, C: 23.3% and D: 3.8%. Bone age advancement was significantly more advanced at the time of diagnosis in males compared to females (p=0.0009). The most frequently reported symptom at diagnosis in the genotype group null (n=20) and A (n=31) were: clitoral hypertrophy in females: 62.7%, failure to thrive: 29% and salt-wasting crisis: 22%. Clitoral hypertrophy was also present in genotype group B, C and D and feminizing surgery was performed in 85% of prenatally virilized females and overall in 40% of females at a median age of 0.9 years [IQR 0.5-1.6]. Conclusion: Genotype groups only predict phenotype with high certainty in the null and A genotype groups. In a national cohort evidence of virilization in females and feminizing surgery were observed in every genotype group. Delayed or non-diagnosis in children with SV and NC CAH was substantial, especially in males. We suggest that children with even mild hyperandrogenic symptoms and normal biochemical markers for 21OHD may benefit from genetic testing for CAH to establish a diagnosis. Presentation: Thursday, June 15, 2023

Morris syndrome (Androgen Insensitivity Syndrome)

Morris syndrome, also known as Androgen Insensitivity Syndrome (AIS), is an intriguing and extraordinary genetic condition that exerts a remarkable influence on individuals with male sex chromosomes (XY). Within the realm of this rare syndrome, the body displays a captivating indifference to androgens, the very essence of male hormones like testosterone, leading to the emergence of physical characteristics typically associated with the female gender. It is an occurrence that befalls a mere fraction of the population, affecting around 1 in 20,000 individuals. Morris syndrome is caused by a genetic mutation located on the sex X chromosome affecting the AR (androgen receptor) gene. Androgen insensitivity syndrome is characterized by the presence of external female phenotype, 46,XY karyotype, and intraabdominal testes. This syndrome is the third most frequent cause of primary amenorrhea, after gonadal dysgenesis and congenital absence of the vagina. In approximately 40% of AIS patients, there is no family history of the disease. Morris syndrome unfolds with an intricate interplay of internal and nonfunctional testicles, which, despite their presence, fail to fulfill their intended biological purpose of sperm production. Meanwhile, on the external front, the genitalia manifest a striking semblance to that of the female anatomy, featuring a vagina and labia. Additionally, some individuals with Morris syndrome may witness the existence of an enlarged clitoris, bearing an uncanny. Comprehending Morris syndrome is vital for healthcare professionals to offer accurate diagnoses and appropriate treatment modalities. Increased awareness among the general populace can foster an inclusive and supportive environment for individuals navigating life with Morris syndrome. Objective: The objective of this article is to provide a comprehensive understanding of Morris syndrome, also known as Androgen Insensitivity Syndrome (AIS), including its genetic basis, clinical manifestations, challenges faced by individuals with the syndrome, and the importance of accurate diagnosis and appropriate treatment modalities. Methods: To achieve the objective, the article will employ a literature review approach, drawing information from scientific and medical sources. Peer-reviewed research articles, medical textbooks, and authoritative online resources will be consulted to gather relevant information on Morris syndrome.

Neurovascular bundle-sparing ventral clitoroplasty in adult patients: description of the technique and long-term outcome on clitoral functions

To describe the technique and assess long term effects of neurovascular bundle-sparing adult clitoroplasty on clitoral functions in patients. A case series study enrolling three patients diagnosed with adult clitoromegaly who underwent neurovascular bundle-sparing ventral clitoroplasty operation. All of the patients were examined at the first, third, sixth, twelfth and twenty-fourth months post-operatively to evaluate clitoral functions. Three patients diagnosed with adult clitoromegaly, aged 17, 21 and 24 years, were enrolled in the study. The primary complaint of all patients was unpleasant enlarged appearance and hypersensitive clitoris. Mean calculated clitoral index was 143 mm2, 150 mm2, and 120 mm2. Operation time was 90, 140 and 120 minutes, respectively. No major complication occurred during the operation but moderate ecchymosis and edema of the vulva occurred in all patients, lasting up to three weeks. On follow up examination, partial sensorial loss was noted at the first month in one patient, which completely resolved by the third month and beyond. Two patients who were sexually active reported that they were very comfortable with intercourse and cosmetic appearance. No clitoral enlargement or pain were reported by patients through the 24-month follow up period. Neurovascular bundle-sparing ventral clitoroplasty is a safe and cosmetically acceptable procedure, which effectively preserves the neurovascular bundle and long-term clitoral functions.

Masculinizing and defeminizing gender-affirming surgery.

Transmasculine transgender and gender-diverse individuals may request gender-affirming surgery, standalone or in addition to other interventions. The choices and preferred outcomes of surgery can be highly individual. Besides surgeons' technical skills and patient physique, professionals in this field should be able to cooperate with other disciplines and with patients. The most requested surgery is masculinizing chest surgery, aiming to create a masculine chest with minimal scarring. For genital surgery, metoidioplasty refers to the procedure where the hypertrophic clitoris is released and possibly a scrotum is created from local labia flaps, whereas phalloplasty refers to a procedure in which a neophallus is created from a flap. Possible other surgeries include hysterectomy/oophorectomy, colpectomy, and the implants of scrotal or erection prostheses. In order to guide patients and clinicians, standardized outcome measures as well as evidence-based decision aids have been developed. Such aids, in combination with collaborative medical and psychosocial care, may further leverage the long-term outcomes of these surgeries.

Gender-Affirming Hormone Therapy: Physical and Sociopsychological Effects, Impact and Satisfaction.

Background Gender dysphoria treatment includes gender-affirming hormone therapy (GAHT). Studies are still lacking on how tocharacterize its effects and impacton transgender people's lives more effectively. Aim To study the physical and psychological effects of GAHT on transgender individuals, assess its impact on their lives, and rate their overall satisfaction. Methods Participants (n = 114; ages 18-62 years; median age 24.0 (21.0 - 33.0) years) included transgender adultsresiding in Portugalwho were undergoing or had undergone hormonal therapy for at least one uninterrupted year. Participants completed an original questionnaire. For most items, an ordinal Likert-style scaleranging from 0 (worst result) to 6 (best result) was used. Descriptive statistics and non-parametric tests, including Pearson's chi-squared test, Wilcoxon signed-rank test, and Mann-Whitney U test were used to analyze categorical and continuous variables, with a significance level set at 0.05. Outcomes The outcomes included desired physical changes rating (perception and satisfaction with changes); side effects of GAHT; the sociopsychological impact of GAHT (on self-esteem, body image, psychological wellbeing, social and family relations); overall satisfaction (with treatment results and medical follow-up). Results The changes classified as the most perceptible in those undergoing masculinizing treatment (Group M) were amenorrhea (6 (5.0-6.0) points) and clitoris enlargement (6 (5.0-6.0) points). These were also the ones rated as the most satisfactory (6 (6.0-6.0) points for amenorrhea and 6 (4.0-6.0) points for clitoris enlargement). On those undergoing feminizing therapy (Group F), the alteration voted as the most perceptible was sperm production decrease (6 (2.0-6.0) points), and the ones classified as the most satisfactory were sperm production decrease (6 (4.0-6.0) points) and spontaneous erections decrease (6 (5.0-6.0) points). Side effects were reported by 89.7% ofGroup M(mood swings were the most common) and 96.3% ofGroup F(decreased libido was the most frequent). The sociopsychological impact of hormonal treatment was significantly positive in all analyzed variables (p<0.001). Overall satisfaction with treatment results and medical follow-up were rated with 5 points and 4.5 points, respectively. Clinical implications This study provides clinicians with more evidence that GAHT may improve the physical, psychological and social health of transgender people seeking medical transition. Strengths and limitations The strengths of the current study include a high participant count relative to the target population, the acquisition of data on previously unexplored variables, and the significance of being one of the few investigations of its kind conducted in Portugal. However, the study has limitations, including differences in participant characteristics, a small sample size for some variables, potential bias due to the retrospective nature of the study, individualized treatment regimens, and the inclusion of participants from different countries, which limit the generalization of the results. Conclusions This study provides further evidence that GAHT is effective, and that its physical effects are satisfactory while resulting in mostly non-severe nor life-threatening side effects. GAHT is an important therapy in gender dysphoria and has consistent results in improving numerous sociopsychological variables.

Clinical characteristics and offspring developmental malformation of 126 patients with septate uterus.

Clinical characteristics and offspring developmental malformation of 126 patients with septate uterus.

Pubertal and Gonadal Outcomes in 46,XY Individuals with Partial Androgen Insensitivity Syndrome Raised as Girls

Introduction: Although it was common in the 1970s–1990s to assign female gender of rearing to 46,XY infants with limited virilization of varying etiologies, including those with partial androgen insensitivity syndrome (PAIS), long-term data on outcomes for these individuals are sparse. Therefore, our goal was to use the power of an international registry to evaluate clinical features, surgical management, and pubertal data in patients with a molecularly confirmed diagnosis of PAIS who were born before 2008 and were raised as girls. Methods: The current study interrogated the International Disorders of Sex Development Registry for available data on management and pubertal outcomes in individuals with genetically confirmed PAIS who were raised as girls. Results: Among the 11 individuals who fulfilled the key criteria for inclusion, the external masculinization score (EMS) at presentation ranged from 2 to 6 (median 5); 7 girls underwent gonadectomy before the age of 9 years, whereas 4 underwent gonadectomy in the teenage years (≥ age 13). Clitoral enlargement at puberty was reported for 3 girls (27%) who presented initially at the time of puberty with intact gonads. In the 9 individuals (82%) for whom gonadal pathology data were provided, there was no evidence of germ cell tumor at median age of 8.1 years. All girls received estrogen replacement, and 8/11 had attained Tanner stage 4–5 breast development at the last assessment. Conclusion: In general, although it appears that female assignment in PAIS is becoming uncommon, our data provide no evidence to support the practice of prophylactic prepubertal gonadectomy with respect to the risk of a germ cell tumor.

Androgen-secreting adenoma – a possibility in hyperandrogenism differential diagnosis

Abstract Introduction Hirsutism affects almost 10% of women of reproductive age. The two most common causes of hirsutism are polycystic ovary syndrome (PCOS) and idiopathic hirsutism. Virilizing adrenocortical tumors are rare, nonetheless, it is a differential diagnosis that physicians must consider. Clinical Case We present the case of a 23-year-old woman that was referred from the Dermatology Department due to the abrupt and progressive appearance of hirsutism and facial acne. Her menstrual cycles were regular. She had a BMI of 21.7 kg/m2, facial acne, and a Ferriman-Gallwey scale of 11 points. She did not have hypertension, nor alopecia, clitoris hypertrophy or any other virilizing sign. Table 1 summarizes the analytical determinations requested in the early follicular phase of the menstrual cycle. Pelvic ultrasound scan did not revealed abnormalities. Computed tomography (CT) scan of the abdomen revealed a well-delimited and solid mass of 4.9 × 3.8 cm in the right adrenal gland, with an average density of 48 UH with enhancement on the portal phase without the presence of fat, hemorrhage or calcifications suggesting malignancy more likely (Figure 1). After multidisciplinary assessment, laparoscopic right adrenalectomy was advised. Pathology revealed an adrenal cortex adenoma which showed cytoplasmic immunoreactivity of the cells against inhibin and Melan-A with a KI-67 of 1%, negative for anti-p53 without atypical mitotic figures, necrosis, venous invasion, sinusoidal invasion nor capsular invasion. The post-surgical evolution was satisfactory with an early normalization of androgens and resolution of the virilizing signs. The most common cause of hirsutism in premenopausal women is PCOS; another cause, and far from the first, is the non-classical form of congenital adrenal hyperplasia; and even more uncommon, androgen-secreting ovarian and adrenal tumours (1,2). Adrenal tumours, unlike ovarian, usually secrete DHEAS. Most tumours are carcinomas, which commonly also secrete cortisol (3). A very high DHEAS level (&amp;gt;7 µg/mL) is suggestive of adrenal carcinoma. Pure virilizing adrenal tumours are extremely rare (4). Independently from hormone secretion, the suspicion of malignancy depends on radiological CT characteristics of the tumour: size (&amp;gt;4–6 cm), density (&amp;gt;10 HU with slow contrast washout), homogeneity, and shape (5). Magnetic resonance may assess local invasion (6). Adrenalectomy is the treatment of choice when virilizing adrenal tumours with malignant characteristics are found (7). In the surgical piece, it is useful to determine the Ki 67 (carcinomas: &amp;gt;5%) (8). Somatic mutations in the TP53 gene are associated with aggressive phenotypes(9). Conclusion Malignant ovarian and adrenal pathology should be ruled out in the scenario of new-onset hirsutism. Adrenal malignancy is usually related with tumor size, type of hormones secreted, and the velocity of the tumor progression. Exceptionally, benign adrenal tumours are producers of virilizing hormones.