MYRF mutation leads to a single manifestation of sexual development and mimics partial androgen insensitivity syndrome: a case report and literature review.

OBJECTIVE: To highlight the challenges in diagnosing 46, XY disorder of sex development related to MYRF mutation. METHODS: We present an unusual case of a 12-year-old female child came for enlargement of clitoris and initially diagnosed as partial androgen insensitivity syndrome (AIS). RESULTS: On examination, the patient's vulva was found virilized with 3cm-long clitoris. Her peripheral blood karyotype was 46, XY. The ultrasound showed an empty pelvis and hormone results confirmed hyperandrogenism. Therefore, the partial AIS was suspected, but the following whole exon sequencing indicates a pathological missense mutation in MYRF. Further investigation and surgery did not reveal any brain, heart, lung or diaphragm lesions related to MYRF, but only maldeveloped internal genitalia and a persistent urachus. Her serum testosterone dropped to normal after surgical removal of the remaining ipsilateral testis and epididymitis without spermatogenesis as shown by pathology. CONCLUSION: Due to the karyotype, hyperandrogenism, empty pelvis but a virilism after puberty, the patient was initially diagnosed as partial AIS. This misleading clinical diagnose will not be verified as the MYRF mutation if without the whole exon sequencing, particularly in the absence of obvious brain, heart, lung and diaphragm lesions as in this case.

Practice guideline on ovarian tissue cryopreservation and transplantation in the prevention and treatment of iatrogenic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.

Diagnostic challenges and management advances in cytochrome P450 oxidoreductase deficiency, a rare form of congenital adrenal hyperplasia, with 46, XX karyotype.

Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of congenital adrenal hyperplasia that can manifest with skeletal malformations, ambiguous genitalia, and menstrual disorders caused by cytochrome P450 oxidoreductase (POR) mutations affecting electron transfer to all microsomal cytochrome P450 and some non-P450 enzymes involved in cholesterol, sterol, and drug metabolism. With the advancement of molecular biology and medical genetics, increasing numbers of PORD cases were reported, and the clinical spectrum of PORD was extended with studies on underlying mechanisms of phenotype-genotype correlations and optimum treatment. However, diagnostic challenges and management dilemma still exists because of unawareness of the condition, the overlapping manifestations with other disorders, and no clear guidelines for treatment. Delayed diagnosis and management may result in improper sex assignment, loss of reproductive capacity because of surgical removal of ruptured ovarian macro-cysts, and life-threatening conditions such as airway obstruction and adrenal crisis. The clinical outcomes and prognosis, which are influenced by specific POR mutations, the presence of additional genetic or environmental factors, and management, include early death due to developmental malformations or adrenal crisis, bilateral oophorectomies after spontaneous rupture of ovarian macro-cysts, genital ambiguity, abnormal pubertal development, and nearly normal phenotype with successful pregnancy outcomes by assisted reproduction. Thus, timely diagnosis including prenatal diagnosis with invasive and non-invasive techniques and appropriate management is essential to improve patients' outcomes. However, even in cases with conclusive diagnosis, comprehensive assessment is needed to avoid severe complications, such as chromosomal test to help sex assignment and evaluation of adrenal function to detect partial adrenal insufficiency. In recent years, it has been noted that proper hormone replacement therapy can lead to decrease or resolve of ovarian macro-cysts, and healthy babies can be delivered by in vitro fertilization and frozen embryo transfer following adequate control of multiple hormonal imbalances. Treatment may be complicated with adverse effects on drug metabolism caused by POR mutations. Unique challenges occur in female PORD patients such as ovarian macro-cysts prone to spontaneous rupture, masculinized genitalia without progression after birth, more frequently affected pubertal development, and impaired fertility. Thus, this review focuses only on 46, XX PORD patients to summarize the potential molecular pathogenesis, differential diagnosis of classic and non-classic PORD, and tailoring therapy to maintain health, avoid severe complications, and promote fertility.

A deletion variant Arg616 of androgen receptor in a Chinese family with complete androgen insensitivity syndrome.

Background: Complete androgen insensitivity syndrome (CAIS, OMIM; 300068) is a disorder of sex development with X-linked recessive inheritance. Cases of CAIS usually present as female phenotype, with primary amenorrhea and/or inguinal hernia. Family aggregation is a rare scenario. Methods: This study is a retrospective analysis of CAIS cases in a three-generation pedigree. The patients' genomes were determined by sequencing the androgen receptor (AR) gene. The clinical data of the patients, including manifestations, hormone levels, and AR variants, were analyzed. Results: Sixteen people in this family were involved. A deletion variant (c.1847_1849del; p. Arg616del) was identified in exon 3 of AR, which encodes the DNA binding domain. Until now, four patients and four carriers have been identified in three generations of this family. All the patients live as female, and one has developed gonadal malignancy. Conclusion: The present study identified a deletion variant in three generations of a family with CAIS, including four carriers and four patients. This study verified the genetic pattern and the corresponding clinical characteristics of CAIS. Furthermore, a case with gonadal malignancy was discovered. The information on diagnosis and treatment in this pedigree is useful for prenatal diagnosis and genetic counseling of similar families.

Genotype-Phenotype Correlation Analysis and Identification of a Novel SRD5A2 Mutation in Four Unrelated Chinese Patients with 5α-Reductase Deficiency.

Objective: The 5α-reductase type 2 deficiency is mainly caused by mutations in the SRD5A2 gene. Our study aims to investigate the SRD5A2 gene mutations and their corresponding manifestations. Methods: Four unrelated Chinese patients with 46, XY ambiguous genitalia were studied. Molecular genetic alterations and clinical presentations were analyzed. Results: Five variants in the SRD5A2 gene were identified, all highly conserved in vertebrate orthologs. The p.P251A was a novel variant, predicted to "Affect protein function" and to be "probably damaging". Combining patients' gene mutations with their external genitalia and male sexual characteristics, we found that three variants, p.Q6X, p.N193S, and p.H90Y, were associated with severe undervirilization of external genitalia, and the other two, p.G203S and p.P251A, probably retained part of the enzyme activity. Conclusion: Mutation analysis of SRD5A2 gene is crucial for differential diagnosis in patients with 5α-reductase type 2 deficiency. Patients' variable manifestations depend on the mutation type and residual enzyme activity. The novel variant p.P251A enlarges the spectrum of SRD5A2 mutations.

Ovarian gonadoblastoma with dysgerminoma in a girl with 46,XX karyotype 17a-hydroxylase/17, 20-lyase deficiency: A case report and literature review.

17α-hydroxylase/17,20-lyase deficiency (17-OHD), caused by mutations in the gene of the cytochrome P450 family 17 subfamily A member 1 (CYP17A1), is a rare type of congenital adrenal hyperplasia (CAH), usually characterized by cortisol and sex steroid deficiency combined with excessive mineralocorticoid. Gonadoblastoma is a relatively rare ovarian tumor that is frequently seen among patients with 46,XY gonadal dysgenesis. Rarely have they been reported in female patients with normal 46,XX karyotype. Here, we report an interesting case of an 11-year-old Chinese girl who presented acute abdominal pain that was later attributed to tumor rupture of right ovarian gonadoblastoma with dysgerminoma. Further evaluations revealed hypertension and hypokalemia. Hormonal findings showed increased progesterone, hypergonadotropic hypogonadism, and low cortisol levels. Her chromosome karyotype was 46,XX without Y chromosome material detected. Genetic analysis revealed that the patient had a homozygous pathogenic variant c.985_987delTACinsAA (p.Y329Kfs*90) in exon 6 of the CYP17A1 gene and that her parents were all heterozygous carriers of this pathogenic variant. Due to the variable clinical manifestations of 17-OHD, meticulous assessment including genetic analysis is necessary. Further study is warranted to unravel the mechanism of gonadoblastoma in a patient with normal karyotypes.

Clinical characteristics and molecular etiology of partial 17α-hydroxylase deficiency diagnosed in 46,XX patients.

Introduction: Complete 17α-hydroxylase deficiency (17OHD) is relatively common, with typical juvenile female genitalia, severe hypertension, hypokalemia, and the absence of sexual development, but partial (or non-classical) 17OHD (p17OHD) is extremely rare. The p17OHD patients can present with a broad spectrum of symptoms in 46,XX karyotype including various degree of spontaneous breast development after puberty, recurrent ovarian cysts, oligomenorrhea and infertility depending on specific gene mutations and other influencing factors. Methods: This paper is a retrospective analysis of p17OHD cases from 1997 to 2021 in a Chinese tertiary hospital. Eight patients were recruited from unrelated families according to clinical data. Genotypes of patients were determined by sequencing the CYP17A1 genes. Clinical characteristics were summarized based on manifestations, hormone profiles, and responses to treatments. Results: All seven post-pubertal patients had abnormal menses. All patients had enlarged multilocular ovaries, and six (6/8) had a history of ovarian cystectomy prior to a definite diagnosis of p17OHD. All eight patients' sex hormone levels were in accord to hypogonadism with mildly elevated follicle-stimulating hormone levels, and oral contraceptives effectively suppressed the ovarian cysts. Of the four patients who underwent plasma renin activity tests, all showed results below the reference range. Fourteen alleles with a CYP17A1 mutation were found. Exon 6 was the most frequent mutation site (5/14), and four out of these five mutations were c.985_987delTACinsAA, being the most common one. In Case 2, c.1220dupA was a newly reported mutation of CYP17A1. Conclusions: 46,XX p17OHD patients were born with highly fragile ovarian reserve due to diverse mutations of CYP17A1. However, their multi-ovarian cysts can be managed conservatively for fertility preservation. This study focuses on p17OHD in 46,XX by locating the complex genetic causes in novel mutations, summarizing the puzzling spectrum of clinical manifestations, and illustrating the significance of fertility preservation in these scarce cases.

Clinical characteristics and management of Turner patients with a small supernumerary marker chromosome.

OBJECTIVE: To summarize the clinical characteristics of Turner syndrome (TS) with a small supernumerary marker chromosome (sSMC) and discuss the clinical significance and management of TS patients with sSMC. METHODS: A retrospective analysis was conducted on the clinical data of 244 patients with disorders of sexual development admitted to Peking Union Medical College Hospital from February 1984 to July 2020. RESULTS: Among the 244 patients with a disorder of sexual development, 69 cases of TS were identified in which 13 patients had sSMC. Their ages ranged from 3 to 28 years old with an average of 14.31 ± 6.40 years. All 13 sSMC-positive patients had typical clinical manifestations of TS except ambiguous genitalia in four cases. SRY gene testing was performed in 11sSMC-positive patients and 10 patients were positive for SRY and one was negative. Among the 10 SRY-positive patients, two cases had hirsutism and clitoral enlargement and two cases had clitoral enlargement only. Nine sSMC and SRY-positive patients underwent gonadectomy and one had left gonadal gonadoblastoma with seminoma in situ and right gonadal seminoma in situ. CONCLUSIONS: Although the sSMC positive detection rate in DSD patients is uncommon (5.33% in our sample), the positive SRY detection rate in sSMC-positive TS patients was extremely high in our TS patients. And TS patients with sSMC and SRY positive had a significantly increased risk of gonadal germ cell tumors. Routine SRY screening should be performed in TS patients with sSMC, and a gonadectomy should be performed in TS patients with sSMC and SRY positive to prevent the occurrence of tumors.

Clinical characteristics and molecular genetics of complete androgen insensitivity syndrome patients: a series study of 30 cases from a Chinese tertiary medical center.

OBJECTIVE: To study the clinical characteristics and genetic basis of complete androgen insensitivity syndrome (CAIS) in patients from the People's Republic of China. CAIS patients with 46 XY karyotype produce male levels of androgens but present with female external genitalia and secondary sex characteristics. The majority of affected individuals have androgen receptor (AR) gene mutations. This case series explored clinical and molecular characteristics of CAIS patients from the People's Republic of China. DESIGN: Genomic DNA from peripheral blood of clinically diagnosed CAIS patients was sequenced for mutation in the androgen receptor (AR) gene and steroid 5α-reductase type 2 gene (SRD5A2). SETTING: Participants were recruited from Peking Union Medical College Hospital when they came in for consultation. PATIENTS: Thirty patients from unrelated families were recruited. INTERVENTIONS: Data from medical documents recording diagnosis and treatment of these patients were retrospectively collected. MAIN OUTCOME MEASURES: Patient genotypes were determined by sequencing the AR and SRD5A2 genes. Their clinical characteristics were summarized based on symptoms, hormone profiles, operative findings, and pathological results. RESULTS: Twenty-one patients diagnosed with CAIS had mutations in AR exons. Analysis of AR exons revealed the presence of seven novel mutations (c.58C>T, c.645_652delGGGGGCTC, c.910G>T, c.1078C>T, c.1786T>A, c.2230G>T, and c.2522G>C); of these mutations, 47.6% (10/21) were located in the ligand-binding domain. Gonadal insufficiency was found in one case of CAIS. Among the remaining nine patients, three had SRD5A2 mutations and therefore a steroid 5α-reductase deficiency. No AR or SRD5A2 mutations were detected in the other six patients. CONCLUSION: This study broadens the spectrum of known AR gene mutations responsible for CAIS, and implies that there can be more complex underlying causes of CAIS.

Evaluation and Management of Unexpected Functional Rudimentary Uteri in Mayer-Rokitansky-Küster-Hauser Syndrome of Chinese Women.

OBJECTIVE: To elucidate the characteristics of symptomatic attack of rudimentary uteri in MRKH syndrome and highlight the rare and unexpected possibilities. METHODS: A cohort of 202 Chinese MRKH syndrome patients admitted to the Peking Union Medical College Hospital from Jan 2009 to Dec 2016 was analyzed retrospectively. Based on the symptoms of abdominal pain before vaginoplasty, the patients were categorized into the asymptomatic and symptomatic groups. RESULTS: Totally, 21 patients had their uteri removed due to obstructive bleeding, 19 of them had symptoms of abdominal pain before vaginoplasty, the mean duration of abdominal pain before artificial vaginoplasty was 5.0 years (range, 0.5-10 years), and the mean age at first onset of recurrent abdominal pain was 14.3 years old (range 11-18). Two special cases showed unusual long incubation periods up to 23 years. Ultrasound detected endometrioid echo in four asymptomatic patients. Among the symptomatic group, 7 patients had no imaging evidence for endometrial cavities despite clinical pain. Two of them developed severe symptoms over the next two or four years and eventually had their uteri removed. Two patients reported persistent abdominal pain with a visual analog scale (VAS) score of 4-5, still under observation. Three patients were lost to follow-up. CONCLUSION: More than 10% of the patients with MRKH syndrome had surgical indication to remove the rudimentary uteri. The discrepancy between clinical symptoms and imaging calls for the vigilance for prophylactic surgery or prolonged follow-up.

Heavy menstrual bleeding among women aged 18-50 years living in Beijing, China: prevalence, risk factors, and impact on daily life.

BACKGROUND: Heavy menstrual bleeding (HMB) has been shown to have a profound negative impact on women's quality of life and lead to increases in health care costs; however, data on HMB among Chinese population is still rather limited. The present study therefore aimed to determine the current prevalence and risk factors of subjectively experienced HMB in a community sample of Chinese reproductive-age women, and to evaluate its effect on daily life. METHODS: We conducted a questionnaire survey in 2356 women aged 18-50 years living in Beijing, China, from October 2014-July 2015. A multivariate logistic regression model was used to identify risk factors for HMB. RESULTS: Overall, 429 women experienced HMB, giving a prevalence of 18.2%. Risk factors associated with HMB included uterine fibroids (adjusted odds ratio [OR] =2.12, 95% confidence interval [CI] = 1.42-3.16, P < 0.001) and multiple abortions (≥3) (adjusted OR = 3.44, 95% CI = 1.82-6.49, P < 0.001). Moreover, women in the younger age groups (≤24 and 25-29 years) showed higher risks for HMB, and those who drink regularly were more likely to report heavy periods compared with never drinkers (adjusted OR = 2.78, 95% CI = 1.20-6.46, P = 0.017). In general, women experiencing HMB felt more practical discomforts and limited life activities while only 81 (18.9%) of them had sought health care for their heavy bleeding. CONCLUSIONS: HMB was highly prevalent among Chinese women and those reporting heavy periods suffered from greater menstrual interference with daily lives. More information and health education programs are urgently needed to raise awareness of the consequences of HMB, encourage women to seek medical assistance and thus improve their quality of life.

Gonadal Dominance and Internal Genitalia Phenotypes of Patients with Ovotesticular Disorders of Sex Development: Report of 22 Cases and Literature Review.

This study aimed to delineate internal genitalia phenotypes in patients with ovotesticular disorders of sex development (OT-DSD). Therefore, a cohort of 22 OT-DSD patients admitted to the Peking Union Medical College Hospital from March 1977 to August 2019 was analyzed retrospectively. The characteristics of karyotype, gonad type and location, and internal genital organs were reviewed and compared to 242 pooled cases from the Chinese literature. As a result, the most common karyotype was 46,XX (68.2% in 22 cases of our hospital, 60.8% in the domestic literature). The combination of gonads was separated (ovary-testis, 45.1%), unilateral (ovotestis-ovary, 17.4%; ovotestis-testis, 13.0%), and bilateral (ovotestis-ovotestis, 24.5%). All the cases in our hospital had a uterus on the side of the ovary or ovotestis. Among the 19 female patients, 5 had a hysterectomy due to genital tract obstruction, 9 had vaginal dysplasia, 3 had premature ovarian failure, and only 2 women gave birth to a child. In conclusion, OT-DSD is a typical model of unilateral gonadal determinism: the uterus is present on the side of the ovotestis and ovary and the internal genital organs predominantly exhibit female characteristics. However, combined reproductive tract malformation and ovarian function of premature failure are not uncommon.

Persistent megalocystic ovaries after ovarian hyperstimulation syndrome in a postpartum patient with polycystic ovarian syndrome: a case report.

BACKGROUND: Ovary enlargement is common in controlled ovarian stimulation, which could continue several months during a successful pregnancy. However, persistent megalocystic ovaries 3 years after ovarian hyperstimulation syndrome (OHSS) were rare. Here we will present you the case and treatment as well as discuss the probable etiology. CASE PRESENTATION: A 34-year-old woman with polycystic ovarian syndrome (PCOS) and a history of infertility presented to the Department of Obstetrics and Gynecology at Peking Union Medical College Hospital with abdominal pain and persistently enlarged ovaries 36 months after OHSS. Enlarged ovaries were evaluated with ultrasonography and serum tests. Diagnostic laparoscopic surgery with detorsion and drainage followed by GnRHa treatment was performed. Symptoms and ovarian size evaluated by vaginal ultrasound were the main outcome measures. The patient was discharged from the hospital 5 days after surgery without any remarkable complications. Both ovaries recovered to almost normal after a monthly injection of GnRHa for 3 months. CONCLUSIONS: Ovarian enlargement may persist for a long time in patients with severe OHSS even after sex hormone levels and ovarian functions return to normal. Long term follow-up is necessary and ovarian torsion should be suspected when accompanied by abdominal pain. Acupuncture plus GnRHa treatment may be an effective way for these cases.

Gonadal tumour risk in 292 phenotypic female patients with disorders of sex development containing Y chromosome or Y-derived sequence.

OBJECTIVE: Phenotypic female disorders of sex development (DSD) patients with Y chromosome or Y-derived sequence have an increased risk of gonadal germ cell tumours (GCTs). The objective of the study was to evaluate tumour risk of DSD, summarize the clinical characteristics of patients with GCTs and propose management suggestions. METHODS: Medical records of 292 patients diagnosed DSD and undergoing bilateral gonadectomy at Peking Union Medical College Hospital from January 1996 to March 2016 were retrospectively reviewed. Tumour histopathological types, risks and clinical characteristics were evaluated. RESULTS: The tumours in DSD included gonadoblastoma, seminoma, dysgerminoma, Sertoli cell tumour, yolk sac tumour and choriocarcinoma. The overall GCTs risk was 15·41% and 46, XY pure gonadal dysgenesis (46, XY PGD) carried the highest risk up to 23·33%, followed by complete androgen insensitivity syndrome (CAIS). The risk of mixed gonadal dysgenesis (GD) or 46, XY 17 alpha-hydroxylase/17, 20-lyase deficiency (46, XY 17 OHD) was <10%, and no tumour was found in five testis regression patients. The ages (years) of tumour diagnosed ranged from 11 to 29 [18 (15, 21) years]. The median age of androgen insensitivity syndrome (AIS) with tumours was comparatively late [19 (18, 24) years], while GCTs occurred during adolescence in 46, XY PGD [17 (15, 20) years] and mixed GD [15 (15, 17) years]. Sex hormone levels were generally unaffected by gonadal GCTs. The positive tumour marker rate before surgery was 58·82% (10/17). Elevated lactate dehydrogenase (LDH) was observed in six cases with dysgerminoma/seminoma. Remarkably elevated α-fetoprotein (AFP) or human chorionic gonadotropin (hCG) was seen in cases with yolk sac tumour or choriocarcinoma, respectively. Mild hyperandrogenism was observed in seven cases with GCTs. Fourteen of 17 pelvic masses found before operation was later proved malignant. CONCLUSION: Disorders of sex development patients with Y chromosome materials have a significantly increased risk of GCTs. Gonadoblastoma and dysgerminoma/seminoma are the most prevalent GCTs and 46, XY PGD carries the highest tumour presence and malignancy risk. AIS could postpone bilateral gonadectomy until or after adolescence, while others with streak gonads should undergo surgery as soon as diagnosis. Specific serum tumour markers could be used in predicting GCTs and monitoring. Optimal care and close follow-up are required.

Surgical Therapy of 17α-hydroxylase Deficiency in 30 Patients.

Objective To analyze the clinical features of 17α-hydroxylase deficiency and explore the appropriate timing and methods of surgical treatment. Methods We retrospectively analyzed the clinical data of patients with complete 17α-hydroxylase deficiency,containing Y chromosome material in their karyotype,adimitted to Peking Union Medical College Hospital from January 2004 to December 2014. Results Thirty patients with complete 17α-hydroxylase deficiency were included. Their social gender were all female and the mean age at diagnosis was (16.1±2.7) years. Twenty-six patients (86.7%) presented with primary amenorrhea and hypertension. The development of secondary sexual characteristics was poor and their uterus was absent. The levels of gonadotropin,progesterone,and adrenocorticotropic hormone were elevated in all patients and the levels of estradiol,testosterone,and cortisol were decreased. All patients had undergone laparoscopic gonadectomy. Most (86.7%) of the gonads were located in abdomen,while 13.3% were in inguinal canal. Histopathology confirmed that gonadal malignancy was obsetved in two patients (6.7%): one with leydig cell tumor and the other with sertoli cell tumor. Conclusions Patients with complete 17α-hydroxylase deficiency have specific clinical features. Early diagnosis and timely laparoscopic gonadectomy are critical to prevent gonadal malignancy.

Primary amenorrhea after bone marrow transplantation and adjuvant chemotherapy misdiagnosed as disorder of sex development: A case report.

INTRODUCTION: Disorders of sex development (DSD) is a congenital condition in which the development of chromosomal, gonadal or genital sex is atypical. Majority of patients present clinical characteristics of primary amenorrhea, absent secondary sex characters, and abnormal hormone level. A female appearance patient with primary amenorrhea and 46 XY karyotype seems to be solid evidences to diagnose Y-chromosome-related DSD diseases, while it is not necessarily the accurate diagnosis. We report the case of an 18-year-old girl with primary amenorrhea and 46 XY karyotype misdiagnosed as Y-chromosome-related DSD. CLINICAL FINDINGS: The patient has normal female reproductive organs and a disrupted pubertal development after the treatment for acute myeloid leukemia (AML). We consider that her gonads were probably functional and later impaired after AML. The clinical manifestations were not consistent with DSD. With doubts, we found that she received bone marrow transplantation (BMT) from her brother and adjuvant chemotherapy 6 years ago. Her karyotype changed from normal female to a karyotype of donor (her brother) origin after BMT.Adjuvant chemotherapy for AML may impair her ovarian function and finally bring about disrupted puberty or primary ovarian insufficiency (POI). INTERVENTIONS: We provided close follow-up. OUTCOMES: During the second visit, the patient had her menarche lasting 4 days without any medication. CONCLUSION: The present case serves as a reminder that a correct diagnosis depends on the comprehensive collection of present and past medical history, complete physical examination, and careful evaluation of related adjuvant tests. Do not presumptively judge a test and mislead reasoning. In addition, ovarian function protection should be considered for young girls having chemotherapy.

Utility of T-cell interferon-γ release assays for the diagnosis of female genital tuberculosis in a tertiary referral hospital in Beijing, China.

Diagnosis of female genital tuberculosis (FGTB) remains a challenge. The aim of this study was to evaluate the diagnostic value of T-SPOT.TB on peripheral blood mononuclear cells (PBMCs) for diagnosing FGTB in an area with high TB burden.Patients with suspected FGTB were enrolled consecutively between August 2010 and August 2015. T-SPOT.TB on PBMCs and histopathology were performed in all patients. T-SPOT.TB results were evaluated against patients' final diagnosis of FGTB which was made based on clinical manifestations, radiology, microbiological and histopathological evaluation, and response to anti-TB treatment. The sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB were analyzed.Among the 66 patients enrolled, 32 were diagnosed with confirmed FGTB, 33 with non-TB including ovarian tumor in 10 patients (30%), pelvic inflammatory diseases in 8 patients (24%), endometriosis in 7 patients (21%), endometrial polyps in 3 patients (9%), abscess of fallopian tube in 2 patients (6%), cyst of fallopian tube in 2 patients (6%), and endometrial carcinoma in 1 patient (3%). One patient with clinically indeterminate diagnosis was not included in the final analysis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio, and negative likelihood ratio of T-SPOT.TB on PBMCs for diagnosis of FGTB were 94%, 70%, 75%, 92%, 3.09, and 0.09, respectively. Frequencies of spot forming cells (SFCs) of T-SPOT.TB were 430 (interquartile range [IQR] 155-706) SFCs/10 PBMCs and 124 (IQR 61-313) SFCs/10 PBMCs in FGTB and non-TB patients, respectively, and the difference was statistically significant (P = 2.14 × 10). By receiver operating characteristic curve analysis, a cutoff value of 40 SFCs/10 PBMCs of T-SPOT.TB had a sensitivity of 94% and specificity of 76% for the diagnosis of FGTB.T-SPOT.TB on PBMCs appeared to be a valuable and rapid diagnostic method for FGTB in TB endemic settings with high sensitivity and NPV.

Clinical Features of 32 Patients with XO/XY Gonadal Dysgenesis.

Objective To summarize the clinical features of XO/XY gonadal dysgenesis. Method We retrospectively analyzed the clinical data of patients with XO/XY gonadal dysgenesis admitted to Peking Union Medical College Hospital from January 2008 to May 2015. Results Totally 32 patients with XO/XY gonadal dysgenesis were included. The social gender was female in all subjects and the age 6 to 33 years. Patients presented mainly with primary amenorrhea or short stature,and usually had specific somatic signs of Turner's syndrome. The breast development of 27 patients (84.38%) was less than level 3. The armpit hair was sparse or absent in 28 patients (87.5%) and the pubic hair was sparse or absent in 26 patients (81.25%).Other findings include naive vulva (n=18,56.25%)) and enlarged clitoris (n=5,15.63%). The average level of follicle stimulating hormone was (78.56±35.62) mIU/ml,the luteinizing hormone level was (20.23±11.35) mIU/ml,the estradiol level was (9.94±8.21) pg/ml,and the testosterone level was (0.24±0.18) ng/ml. All patients received prophylactic gonadectomy. The histopathology results showed a variety of gonads,and gonadal malignancy were observed in 4 patients.Conclusions Patients with XO/XY gonadal dysgenesis manifest primary amenorrhea or short stature,poorly developed secondary sexual characteristics,and elevated gonadotropin level. The gonads have increased risk of gonadal malignancy.

Clinical features and management of 33 patients with 46,XX pure gonadal dysgenesis.

The objective of the study is to summarize the clinical characteristics of 33 patients' cohort (46,XX pure gonadal dysgenesis, 46,XX PGD), discuss the management, and propose treatment suggestions. Patients' information, medical history, and medical records were obtained. All patients were closely followed up. At the time of diagnosis, the patients presented 19.53 ± 3.60 years old, 165 ± 6.49 cm height, breast development of Tanner stage I, and infantile female genitalia. High level of follicle-stimulating hormone (87.41 ± 21.50 mIU/mL) and LH (27.10 ± 8.47 mIU/mL) and low level of E2 (8.85 ± 6.13 pg/mL) were observed. Individualized hormone replacement therapy (HRT) was initiated after diagnosis. After 2 years of treatment, all patients had obvious breast development; the uterus showed (2.38 ± 0.60) × (1.38 ± 0.70) × (1.38 ± 0.55) cm growth. The incidence of osteopenia changed from 69.70% to 22.22% and that of osteoporosis changed from 18.18% to 0. Dysgeminoma was found in one patient. We concluded that gonadal dysgenesis in 46,XX PGD causes secondary sexual characteristic absence, tendency of taller, osteoporosis, infertility, and sexual health problems. There is minor chance of tumor occurrence for the patients. Optimal care including HRT and close follow-up are required.