[Feminizing genitoplasty in virilization of the external genitalia].

The review focuses on the feminizing genitoplasty of the external genitalia in patients with disorders of sex development. The opinions of various surgeons and surgical schools on the timing, stages and methods of performing feminizing genitoplasty in girls with the virilization of the genitalia are presented. The development and improvement of surgical techniques for performing clitoroloplasty in patients with virilization of genitalia are described, as well as different types of labioplasty. The main methods of reconstruction of the urogenital sinus are given.

Virilizing oncocytic adrenocortical carcinoma: clinical and immunohistochemical studies.

CONTEXT: Oncocytic tumors of the adrenal cortex are rare, mostly nonfunctioning and benign. SETTING: Report virilizing oncocytic adrenocortical carcinoma in a 50-year-old woman. PATIENT: She presented a recent and progressive virilization syndrome, associated with high blood pressure. Hormonal evaluation showed elevated serum testosterone and delta-4-androstenedione levels, normal urinary free cortisol level and incomplete suppression of cortisol at the 1 mg dexamethasone suppression test. CT scan of the abdomen revealed a 35 mm left adrenal mass. INTERVENTION: The patient underwent a left adrenalectomy, and the histological study showed a 3 cm oncocytic adrenocortical carcinoma with signs of malignancy. RESULTS: Immunohistochemical study revealed that tumor cells expressed the steroidogenic enzymes involved into androgen synthesis (3ßHSD and P450c17α), P450 aromatase and luteinizing hormone (LH) receptors. Post-operatively, signs of virilization improved rapidly, serum testosterone and delta-4-androstenedione levels returned to normal, as did the dexamethasone suppression test. During follow-up CT-scan and 18-FDG PET/CT showed a right ovary mass, corresponding to a follicular cyst associated with hyperthecosis. The patient is alive with no recurrence 48 months after adrenal surgery. CONCLUSION: Oncocytic adrenocortical carcinomas, although extremely rare, should be considered in women with a virilization syndrome. In this woman immunohistochimical studies revealed the presence of steroidogenic enzymes involved into androgen synthesis and aromatization, and LH receptors could be implicated in this pathology.

Surgical aspects in the treatment of adrenocortical carcinomas in children: data of the GPOH-MET 97 trial.

Adrenocortical carcinomas (ACCs) are a rare entity, with an incidence of 1.5 per million population per year. The prognosis of ACC is poor. Complete surgical resection is essential for a curative approach and significantly determines overall prognosis. Tumor resection is sophisticated and complicated by the vulnerability of the tumor and its invasive growth. Chemotherapy and Mitotane are additional therapeutic approaches that are combined with surgery in an interdisciplinary strategy. In this study, 59 patients between 2 months and 18 years of age with histologically verified ACC were analyzed retrospectively with respect to oncosurgical aspects. Patients were registered in the GPOH-MET 97 trial of the Society of Pediatric Oncology and Haematology. Preoperative management, factors influencing surgical severity, and operative complications were assessed.The gender ratio was 1:2 (m:f). A total of 58 patients showed increased hormonal activity and associated clinical signs of hormonal excess. Tumor volume was ≥ 300 mL in 25 patients. These patients showed an increased rate of operative complications and a poorer overall survival (OS) rate (p<0.01). A total of 14 patients showed metastatic spread, particularly to the lungs and lymph nodes. Biopsy of the tumor was performed in 12 patients. Tumor rupture occurred in 11 patients. Preoperative biopsy and/or experienced tumor rupture were associated with poorer OS rate. R2 resection only was achievable in 5 patients, and surgery was not feasible in 3 patients.In conclusion, since most of the pediatric ACC are hormone active and can be diagnosed clinically, the need of a tumor biopsy has to be discussed critically. Thorough pre- and perioperative management is essential for oncosurgical success.

Mature teratoma, a rare cause of virilization in adolescence.

Virilization in an adolescent patient can occur for multiple reasons (ovarian, suprarenal or exogenous reasons). We describe a 14-year-old patient with 1-year secondary amenorrhea, who had an ovarian mature teratoma as a cause of her clinical history.

Virilizing ovarian Krukenberg tumor in a 27-year-old pregnant woman. A case report and literature review.

A case is reported of a 27-year-old pregnant woman with ovarian tumors, measuring 12 cm and 11.5 cm in the greatest diameter, discovered during investigation for virilization symptoms. Termination of the pregnancy at the 22nd week of gestation and tumorectomy with both adnexa were performed, with the provisional diagnosis of arrhenoblastoma. Pathological examination of the tumors showed typical Krukenberg neoplasms and subsequent upper GI tract endoscopy revealed a gastric cancer that was excised. The pathological examination revealed a diffuse type gastric adenocarcinoma with signet ring morphology, similar to ovarian tumors. In any case of ovarian tumor with unusual hormonal manifestations, in addition to hormonally active sex cord-stromal neoplasms, metastatic ovarian tumors must be considered as well, especially in cases of bilateral tumors.

A case study of virilizing adrenal tumor in an adolescent female elite tennis player--insight into the use of anabolic steroids in young athletes.

A 14-year-old Caucasian girl was referred to the endocrine clinic for evaluation of voice deepening, facial hirsutism, and acne starting 2 years previously. She had been a competitive tennis player since age 7 years, practicing for 4-6 hours daily. On physical examination she was noticed to have a masculine appearance with mild facial acne and moderate hirsutism. Tanner stage was 1 for breast tissue and 5 for pubic hair. Her androgen levels (testosterone, androstenedione, dehydroepiandrosterone sulfate) were extremely elevated. Adrenal ultrasonography revealed a round left 4.6 × 5.3-cm adrenal mass. Laparoscopic left adrenalectomy was performed. The histologic findings were compatible with a benign adrenocortical tumor. Postoperatively, androgen levels dropped to within the normal range. Breast development proceeded normally, menarche occurred 2 months after tumor resection, and menses has been regular since then. Muscle strength of the dominant and nondominant upper and lower extremities was measured 1 month before surgery and 1 year later, using an isokinetic dynamometer (Biodex Systems II, Biodex, Shirley, NY, USA). There was no significant decrease in overall muscle strength after removal of the virilizing tumor and the marked drop in circulating androgens. In addition, the patient maintained her age category, number 1, national tennis ranking. The results suggest that even extremely high levels of tumor-related circulating androgens had no evident effect on muscle strength and competitive performance in a female adolescent tennis player. The lack of beneficial effect on performance in adolescents, combined with the potentially hazardous side effects of anabolic steroids, suggests that teenage athletes should avoid their use.

Virilizing adrenocortical oncocytoma in a child: a case report.

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

[Bilateral ovarian luteinized thecoma associated with pregnancy--a case report]. / Ciaza powiklana obustronnym zluteinizowanym otoczkowiakiem--opis przypadku.

Hormonally active, associated with pregnancy ovarian tumors can cause some diagnostic and therapeutic problems. In the following work we present a 28-year-old primigravida in the 21st week of pregnancy who was admitted to hospital with acute abdominal pain and virilizing symptoms. Bilateral luteinized thecoma of a considerable size, secreting testosterone, was diagnosed and the woman received surgical treatment. During the operation a rupture of the left tumor was discovered. Bilateral adnexectomy was performed. After the operation the symptoms subsided. The pregnancy continued until 38 weeks gestation. A normal female fetus without virilizing symptoms was delivered by caesarean section.

Successful laparoscopic resection of virilizing ovarian steroid cell tumor, not otherwise specified, in a 22-year-old woman: a case report and evaluation of the steroidogenic pathway.

OBJECTIVE: Ovarian steroid cell tumor (SCT) is a rare tumor with steroid-producing ability. We report a 22-year-old woman with secondary amenorrhea and hirsutism caused by an ovarian SCT-not otherwise specified (NOS), who underwent successfully laparoscopic resection of the tumor. CASE REPORT: A 22-year-old null gravida woman presented to a hospital, having amenorrhea for 18 months and increasing facial hair. Physical examination revealed obesity (body mass index, 37.3 kg/m2) with evident facial and trunk hair. Total and free serum testosterone, and dehydroepiandrosterone sulfate levels were found to be elevated. Levels of serum adrenocorticotropic hormone, gonadotropins, cortisol, aldosterone, and ovarian steroids were observed to be within reference intervals. Although polycystic ovaries were not found, a hyperechogenic solid tumor (3 cm) was detected on transvaginal ultrasonography. Laparoscopic resection of the tumor was performed. One month post-surgery, total and free testosterone levels were observed to have decreased, and menstruation resumed two months thereafter. The patient was histologically diagnosed with ovarian SCT-NOS. Expression of ovarian steroidogenic enzymes, which are related to hyperandrogenism, was observed. No disease recurrence has been reported for more than 5 years post-surgery.

Laparoscopic resection of a virilizing adrenocortical tumor.

Virilizing adrenocortical tumors are rare. Laparoscopic unilateral adrenalectomy with serum androgen surveillance may provide curative treatment for benign, functional adenomas. Herein, we describe a case of laparoscopic resection of a testosterone-producing adrenal tumor in a sixteen-year-old female.

Steroid responsive hypertension secondary to 11-beta hydroxylase deficiency--a case report.

BACKGROUND: Congenital adrenal hyperplasia (CAH), due to deficiency in 11â hydroxylase enzyme is rare a cause of virilization associated with glucocorticoid responsive hypertension. OBJECTIVE: To present a rare cause of CAH and secondary hypertension responsive to glucocorticoid therapy. METHODS: Clinical and laboratory evaluation of a young woman with a "phallus" and hypertension. Investigations carried out included serum biochemistry, bone age determination, sex chromatin evaluation and serum levels of androgens and 17-OH progesterone, as well as pelvic ultrasonography. RESULTS: There was a history of cliteromegaly, first noticed at age 14 years, but menstrual periods were said to be regular. Physical findings included male type hairline and musculature with a blood pressure of 160/110mmHg. Breast development was Tanner Grade 3 while the public hair was male in pattern. The clitoris was 5cm long. Serum electrolytes were normal but levels of testosterone, dehydroepiandosterone sulphate and 17-OH progesterone were elevated. Features were compatible with a diagnosis of congenital adrenal hyperplasia (CAH) due to Il-beta-hydroxylase defficiency. Hypertension responded to glucocorticoid therapy, recurred on default and was corrected again on re-starting hydrocortisone. CONCLUSION: Congenital adrenal hyperplasia due to 11â-hydroxylase deficiency though rare, should be considered in the differential diagnosis of hypertension with virilization in young females.

[Maternal virilization due to mucinous ovarian tumour: a case report]. / Tumeur ovarienne mucineuse virilisante et grossesse: à propos d'un cas.

Virilization in pregnancy is rare and mostly due to luteoma or to hyper-reactio luteinalis. We present a rare case of a virilization borderline mucinous ovarian tumour on a gravida 1 patient. The tumour was responsible for a clinical hyperandrogenism and for an increased level of testosterone. This patient was treated by ovariectomy at 31 weeks of gestation. The surgery was completed one month after delivery. There was no fetal consequence and the clinical and biological signs of virilization totally disappeared after surgery.

The Role of Patient Advocacy and the Declining Rate of Clitoroplasty in 46,XX Patients With Congenital Adrenal Hyperplasia.

Prior to the 1990s, most 46,XX infants with clitoromegaly secondary to congenital adrenal hyperplasia were treated with feminizing genitoplasty to make their cosmetic appearance congruent with their genotypic sex. A 2006 consensus statement for the management of intersex disorders accepted input from patient advocates and did not support purely cosmetic surgery for clitoromegaly. This study examined the extent to which the desired change was implemented in practice. Retrospective chart review was performed at a single Midwestern tertiary care medical center for patients born between 1979 and 2013. Of 45 virilized patients, 40 had clitoromegaly and 39 had urogenital sinus or posterior labial fusion. Twenty-seven (67.5%) patients underwent clitoroplasty and 33 (84.6%) underwent perineoplasty, including vaginoplasty, urethroplasty, imperforate vagina repair, and/or posterior labial fusion repair. There was a linear decline in the rate of clitoroplasty over time for the patient cohort. This study demonstrates the power of patient advocacy to improve medical practice.

Update on diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

PURPOSE OF REVIEW: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a relatively common inherited disorder of cortisol biosynthesis that can be fatal if untreated. RECENT FINDINGS: The basic biochemistry and genetics of CAH have been known for decades but continue to be refined by the discoveries of an alternative 'backdoor' metabolic pathway for adrenal androgen synthesis and the secretion of 11-hydroxy and 11-keto analogs of known androgens, by the elucidation of hundreds of new mutations, and by the application of high-throughput sequencing techniques to noninvasive prenatal diagnosis. Although hydrocortisone is a mainstay of treatment, overtreatment may have adverse effects on growth, risk of obesity, and cardiovascular disease; conversely, undertreatment may increase risk of testicular adrenal rest tumors in affected men. SUMMARY: Refinements to screening techniques may improve the positive predictive value of newborn screening programs. Alternative dosing forms of hydrocortisone and additional therapeutic modalities are under study. Although surgical treatment of virilized female genitalia is widely accepted by families and patients, it is not without complications or controversy, and some families choose to defer it.

Surgical outcomes and complications of reconstructive surgery in the female congenital adrenal hyperplasia patient: What every endocrinologist should know.

Surgical management of classical congenital adrenal hyperplasia (CAH) in 46, XX females has evolved significantly. Virilization of the genitalia of 46, XX females with CAH begins prenatally as a result of excess fetal androgen production. Improved understanding of anatomy and surgical outcomes has driven changes in surgical techniques as well as the timing of surgery. For endocrinologists treating these patients, it is important to understand the outcome of genitoplasty, identify patients who need further treatment and direct these patients to experienced surgeons. We performed a literature search on PubMed of publications addressing CAH and genital reconstruction published in the English language from 1990 to the present. In accordance with our institutional review board, we performed a retrospective analysis of clitoroplasty and/or vaginoplasty procedures performed by a single surgeon at our institution from 1996 to 2015. We found that genital reconstruction in 46, XX CAH patients is associated with few immediate post-operative, infectious, and urinary complications. Vaginal stenosis is a common complication of vaginal reconstruction and requires evaluation by an experienced surgeon. Clitoral pain or decreased sensation can be associated with clitoral recession and clitorectomy. Outcomes in sexual satisfaction and gender identity can also be impacted by surgical technique and success. Long term follow up and patient reported feedback are crucial to our understanding and management of this special group of patients. Improved awareness and understanding of the complications of genital surgery will allow endocrinologists to know what to ask patients and be ready to provide them with a resource with the understanding and experience to help them improve their quality of life.

Postmenopausal hyperandrogenism: the under-recognized value of inhibins.

We report a 70-year-old female presenting with increased libido and mild but rapid onset virilism. Investigations showed markedly elevated androstenedione and 17 hydroxyprogesterone misdirecting to possible late-onset congenital adrenal hyperplasia. High serum testosterone and oestrogens with suppressed gonadotrophins, however, indicated an androgen-secreting tumour. A normal dehydroepiandrosterone sulphate and elevated inhibins A and B indicated the tumour was ovarian in origin, which was confirmed on pelvic examination and imaging. At laparotomy, a right ovarian sertoliform endometrioid carcinoma was removed, following which the patient developed menopausal vasomotor symptoms and improvement of her virilism. Serum testosterone, oestradiol, inhibins A and B became undetectable, gonadotrophins appropriately increased and 17 hydroxyprogesterone and androstenedione normalized. We propose that inhibins may be of diagnostic value and should be included in investigative algorithms of females with virilization and hyperandrogenaemia, especially if postmenopausal. Androgen-secreting tumours must be excluded before raised 17 hydroxyprogesterone concentrations are used to diagnose late-onset congenital adrenal hyperplasia in females with new-onset virilization.