OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

Introduction: Steroid cell tumors are rare sex cord-stromal tumors, accounting for <0.1% of ovarian neoplasms. Extraovarian steroid cell tumors are exceptionally rare, often androgensecreting, and pose significant diagnostic challenges. Early recognition is essential to prevent prolonged morbidity from hyperandrogenism. Case: A 60-year-old female, 15 years after total hysterectomy and bilateral salpingo-oophorectomy for a large ovarian mass with massive ascites, presented with deranged liver function tests on routine follow-up. Ultrasonography and computed tomography imaging revealed multiple hypervascular lesions in the liver, retroperitoneum, and peritoneum, suggestive of metastatic disease, with normal-appearing adrenal glands. Biopsy of a liver lesion demonstrated a metastatic neoplasm with morphology and immunoprofile favoring a steroid cell tumor. However, metastasis from the adrenal cortex or an ovarian primary could not be excluded. Given the prior bilateral oophorectomy, metastatic adrenocortical carcinoma was initially suspected, prompting endocrine evaluation. Further history revealed a 1-year history of progressive virilization, including increased facial hair and frontal balding. Hormonal studies demonstrated elevated testosterone (12.2 mmol/L and reference range 0.1–1.42) and dehydroepiandrosterone sulfate (15.9 µmol/L and reference range 0.510–5.560) and the adrenocorticotropic hormone level of 11.7 pmol/L (reference range 1.60–13.9) with suppressed gonadotrophins. Additional workup for catecholamine, cortisol, and aldosterone excess was unremarkable. The discordance between androgen excess and normal adrenal imaging, despite absent ovarian tissue, suggested an extraadrenal androgen-secreting steroid cell tumor. A second histopathology review and multidisciplinary discussion with radiology, gynecologic oncology, and pathology teams were undertaken. As the disease was deemed inoperable, repeat retroperitoneal lesion biopsy confirmed metastatic steroid cell tumor and guided palliative chemotherapy. She was subsequently referred to gynecologic oncology for systemic chemotherapy. Conclusion Extra-adrenal steroid cell tumors, though rare, should be considered in patients with hyperandrogenism long after bilateral oophorectomy, especially when adrenal imaging is normal. Multidisciplinary evaluation and repeat biopsy are often crucial for establishing the diagnosis and guiding treatment.
Hyperandrogenism ; Ovariectomy ; Steroids ; Neoplasms

Introduction: Polycystic ovary syndrome (PCOS) is the most common cause of hyperandrogenism in women of reproductive age. However, several endocrine disorders, particularly Cushing disease (CD), can closely mimic the clinical, biochemical, and radiological features of PCOS. This overlap may lead to misdiagnosis and delayed recognition of hypercortisolism, with significant metabolic and reproductive consequences. Case: We report a 24-year-old female with young-onset diabetes mellitus who was referred for endocrine co-management during admission for recurrent mons pubis and labial abscesses with poorly controlled glycemia. She had a 5-year history of progressive hirsutism, oligomenorrhoea, scalp hair loss, significant weight gain, and insulin resistance, and had previously been labelled as having PCOS during adolescence, with subsequent default of follow-up. On examination, she was obese (body mass index 33 kg/ m²) with plethoric facies, acanthosis nigricans, proximal myopathy, and hirsutism (Ferriman–Gallwey score 10), without overt virilization or acromegalic features. Biochemical evaluation demonstrated severe hyperandrogenism with markedly elevated total testosterone (7.05 nmol/L), suppressed gonadotropins, and adrenocorticotropic hormone (ACTH)-dependent hypercortisolism. Cortisol failed to suppress on low-dose dexamethasone testing, and 24-hour urinary free cortisol was markedly elevated (>4,900 nmol/24 h). Pelvic ultrasonography and computed tomography imaging showed polycystic ovarian morphology without evidence of an ovarian mass. Pituitary magnetic resonance imaging revealed a small right-sided pituitary microadenoma measuring 2.6 × 3.7 mm. Inferior petrosal sinus sampling demonstrated a central-to-peripheral ACTH gradient with adequate prolactin ratios, confirming pituitary CD. Conclusion This case highlights how Cushing disease can closely mimic PCOS, including polycystic ovarian morphology and hyperandrogenism. Progressive symptoms, severe biochemical androgen excess, and marked insulin resistance should prompt evaluation for secondary causes of hyperandrogenism, particularly hypercortisolism, to avoid delayed diagnosis and prolonged morbidity.
Female ; Hyperandrogenism ; Pituitary ACTH Hypersecretion ; Polycystic Ovary Syndrome

BACKGROUND

Polycystic ovarian syndrome (PCOS) is a common gynecologic endocrine disorder affecting between 2.2% and 26% of the population. It is typically characterized by hirsutism and signs of ovulatory dysfunction. Hirsutism is defined as the presence of excess body or facial terminal hair growth in females, following a male-like pattern. It is diagnosed using visual assessment methods, such as the modified Ferriman–Gallwey (mFG) scoring system, and biochemical tests, including measurements of total testosterone (tT) and the free androgen index (FAI).

OBJECTIVES

The general objective of the study is to identify the correlation of visual scoring with the biochemical evaluation of hirsutism. Specific objectives include (1) to describe the visual and biochemical scores of hirsutism in PCOS patients and (2) to determine a cutoff score for the visual scoring of hirsutism among Filipinos.

METHODOLOGY

This is a cross-sectional study done in a tertiary hospital. Ethical approval was obtained for this study. Patients who satisfied the inclusion criteria were included in the study. Age, height, weight, body mass index (BMI), and OB score were noted. Visual scoring for hirsutism using the mFG scoring system was performed. Blood extraction was done for testosterone and sex hormone-binding globulin tests. FAI was then computed and correlated with the mFG scores.

RESULTS

A total of 52 patients were identified. A positive correlation is noted between the mFG with testosterone and FAI. A positive correlation was also noted between the BMI with testosterone and FAI. An mFG value of >4 is an acceptable cutoff for Filipinos.

CONCLUSION

The study showed as the mFG score increases, FAI and tT levels also increase. It was also noted that as BMI increases, the FAI and tT levels are also expected to increase. It can also be concluded that a lower mFG cutoff value, >4, is applicable for Filipinos.

Human ; Female ; Hirsutism ; Hyperandrogenism ; Polycystic Ovary Syndrome

OBJECTIVE: To investigate the clinical therapeutic effect of Rendu Tongtiao acupuncture (acupuncture for regulating and improving the circulation of the conception and governor vessels) on hyperandrogenism (HA) in polycystic ovary syndrome (PCOS) with kidney-yin deficiency induced fire hyperactivity. METHODS: A total of 80 PCOS-HA patients were selected and randomly divided into an observation group and a control group, 40 cases in each group. In the control group, ethinylestradiol and cyproterone acetate tablets were administered orally,2 mg each time, once daily and for 21 consecutive days as one menstrual cycle. In the observation group, Rendu Tongtiao acupuncture was delivered at Qihai (CV6), Zhongwan (CV12), Guanyuan (CV4), Zhongji (CV3), Mingmen (GV4), Yaoyangguan (GV3), etc. once daily till ovulation, which was taken as the treatment session of one menstrual cycle. The treatment was completed after 3 menstrual cycles in each group. Before and after treatment, the serum levels of testosterone (T), dihydrotestosterone (DHT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), sex hormone-binding globulin (SHBG), and the scores of acne and hirsutism were compared in the two groups; besides, menstrual recovery rate, ovulation recovery rate, basic body temperature (BBT) biphasic rate and clinical effect were compared between the two groups. RESULTS: Compared with those before treatment, the levels of T, DHT, LH and PRL, as well as the scores of acne and hirsutism were reduced in the two groups after treatment (P<0.05), and the levels of FSH and SHBG were increased (P<0.05). After treatment, the levels of T, DHT, LH and PRL, as well as the scores of acne and hirsutism in the observation group were lower than those in the control group (P<0.05); and FSH and SHBG were higher (P<0.05). After treatment, the menstrual recovery rate and ovulation recovery rate, as well as BBT biphasic rate in the observation group increased in comparison with the control group (P<0.05). The total effective rate was 97.5% (39/40) in the observation group, which was higher than 82.4% (33/40) of the control group (P<0.05). CONCLUSION Rendu Tongtiao acupuncture can effectively regulate the secretion of hormones, alleviate the clinical symptoms of HA, and accelerate the recovery of menstruation and natural ovulation in patients with PCOS-HA of kidney-yin deficiency induced fire hyperactivity .
Humans ; Female ; Polycystic Ovary Syndrome/complications* ; Acupuncture Therapy ; Adult ; Young Adult ; Hyperandrogenism/blood* ; Yin Deficiency/therapy* ; Kidney/physiopathology* ; Acupuncture Points ; Testosterone/blood* ; Luteinizing Hormone/blood* ; Follicle Stimulating Hormone/blood* ; Adolescent

Aromatase deficiency (AD) is a rare autosomal recessive genetic disease caused by loss-of-function mutations in aromatase gene (CYP19A1), leading to congenital estrogen deficiency syndrome. Both mothers of AD patients during pregnancy and female AD fetus show virilization, while male patients are usually diagnosed in adulthood due to continued height increase and metabolic abnormalities. In 2019, a patient with AD was admitted in the Second Xiangya Hospital. The patient was a 37-year-old adult male who continued to grow linearly after adulthood. His estradiol was below the measurable line, the follicle-stimulating hormone (FSH) increased, bone age delayed, epiphysis unfused, and the bone mass reduced. CYP19A1 gene detection showed that c.1093C>T, p.R365W was homozygous mutation. This disease is rare in clinic. Clinicians need to raise awareness of the disease for early diagnosis and treatment to improve the long-term prognosis of patients.
46, XX Disorders of Sex Development/genetics* ; Adult ; Aromatase/metabolism* ; Female ; Gynecomastia/genetics* ; Humans ; Infertility, Male ; Male ; Metabolism, Inborn Errors ; Mutation ; Pregnancy

OBJECTIVE: To explore the effect of curcumin on the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/endometrial expression of glucose 4 (GLUT4) signalling pathway and its regulator, phosphatase and tensin homolog (PTEN), in a rat model of polycystic ovarian syndrome (PCOS). METHODS: PCOS model was induced by letrozole intragastric administration. Sprague-Dawley rats were randomized into 4 groups according to a random number table: (1) control group; (2) PCOS group, which was subjected to PCOS and received vehicle; (3) curcumin group, which was subjected to PCOS and treated with curcumin (200 mg/kg for 2 weeks); and (4) curcumin+LY294002 group, which was subjected to PCOS, and treated with curcumin and LY294002 (a specific PI3K inhibitor). Serum hormone levels (17 β-estradiol, follicle stimulating hormone, luteinizing hormone, progesterone, and testosterone) were measured by enzyme linked immunosorbent assay, and insulin resistance (IR) was assessed using the homeostasis model assessment of IR. Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination. Expression levels of key transcriptional regulators and downstream targets, including IRS1, PI3K, protein kinase B (AKT), GLUT4, and PTEN, were measured via reverse transcription polymerase chain reaction and Western blot, respectively. RESULTS: The PCOS group showed impaired ovarian morphology and function. Compared with the PCOS group, curcumin treatment exerted ovarioprotective effects, down-regulated serum testosterone, restored IR, inhibited inflammatory cell infiltration in ovarian tissues, decreased IRS1, PI3K, and AKT expressions, and up-regulated GLUT4 and PTEN expressions in PCOS rats (P<0.05 or P<0.01). In contrast, IRS1, PI3K, AKT, and PTEN expression levels were not significantly different between PCOS and curcumin+LY294002 groups (P>0.05). CONCLUSION The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions, in which, PTEN, a new target, may play a role in regulating the IRS1/PI3K/GLUT4 pathway.
Animals ; Female ; Humans ; Rats ; Cell Proliferation ; Curcumin/therapeutic use* ; Follicle Stimulating Hormone ; Glucose ; Hyperandrogenism ; Insulin Receptor Substrate Proteins/metabolism* ; Insulin Resistance ; Ovarian Cysts ; Ovarian Neoplasms ; Phosphatidylinositol 3-Kinase/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Polycystic Ovary Syndrome/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Testosterone

OBJECTIVE: To explore the clinical, neuropathological and genetic characteristics of a patient with Perrault syndrome caused by TWNK mutation. METHODS: Potential variation of the TWNK gene was detected by next-generation sequencing (NGS) and verified by Sanger sequencing. RESULTS: The patient has featured primary amenorrhoea and progressive sensorineural hearing loss since childhood. She also had gait anormaly, distal limb atrophy and weakness, and nystagmus. Further study confirmed sensory neuronopathy accompanied with upper and lower motor neuron involvement as well as cerebellum atrophy. NGS has identified two heterozygous variants of the TWNK gene, namely c.794G>A (p.Arg265His) and c.1181G>A (p.Arg394His). Sanger sequencing confirmed that c.1181G>A (p.Arg394His), a known pathogenic variant, was derived from her farther, while c.794G>A(p.Arg265His), a novel variant, was derived from her mother and likely pathogenic according to the ACMG guidelines. CONCLUSION Perrault syndrome is a group of disorders with a high phenotypic heterogeneity. The compound heterozygous variation of c.794G>A (p.Arg265His) and c.1181G>A(p.Arg394His) of the TWNK gene may underlie Perrault syndrome in the patient.
Child ; Female ; Genetic Testing ; Gonadal Dysgenesis, 46,XX ; Hearing Loss, Sensorineural ; Humans ; Pedigree

BACKGROUND: The modified Ferriman-Gallwey (mFG) score is the gold standard for the clinical evaluation of hirsutism. However, racial variations in terminal hair growth limit this tool. This study aimed to determine the mFG cut-off score among Filipino women and its association with biochemical hyperandrogenism.METHODS: A total of 128 Filipino women were included in this prospective cross-sectional study and were divided into two groups: a polycystic ovary syndrome (PCOS) group (n=28) and a non-PCOS group (n=100). The participants underwent mFG score determination, ovarian ultrasound conducted by a single sonographer, and hormone testing. The mFG cut-off score was determined based on the 95th percentile of the non-PCOS group. Logistic regression was used to analyze the relationship between mFG score and biochemical hyperandrogenism.RESULTS: Although the mFG score was generally low in both the PCOS and non-PCOS groups, the former exhibited a higher mean score than the latter (4.3±3.0 vs. 2.0±2.2, P<0.001). Normal values for the total mFG score ranged from 0 to 7. Using a cut-off score of 7, a higher proportion of hirsute women (mFG score ≥7) was observed in the PCOS group versus the non-PCOS group (17.9% vs. 5.0%, P=0.025). Elevated calculated free testosterone (FT) was also found to be significantly associated with hirsutism (odds ratio, 6.2; 95% confidence interval, 1.2 to 32.4 pmol/L; P=0.030).CONCLUSION: A score of 7 and above constitutes hirsutism in this population of Filipino women. Hirsute women are more likely than non-hirsute women to have elevated calculated FT.
Cross-Sectional Studies ; Female ; Gonadal Disorders ; Hair ; Hirsutism ; Humans ; Hyperandrogenism ; Logistic Models ; Polycystic Ovary Syndrome ; Prospective Studies ; Reference Values ; Testosterone ; Ultrasonography

ObjectiveTo identify the etiology of chromosome abnormality in an infertile man and analyze the correlation between the genotype and phenotype.

METHODSWe analyzed the karyotype of an infertile male using the routine G-banding technique and then the chromosome abnormality of the patient by Illumina Human CytoSNP-12 Beadchip array.

RESULTSNegative results were found in the examination of the sex-determining region Y (SRY) gene and the STR locus in the AZF zone of the patient. The karyotype of the patient was 46, XX. SNP array showed a 1.05 Mb 19p12 duplication and a 0.93 Mb Xq27.1 duplication.

CONCLUSIONSThe patient was confirmed as a case of 46,XX male syndrome. The increased copies of the FGF13 gene may be the major causes of abnormal sex determination and testis development.

46, XX Testicular Disorders of Sex Development ; diagnosis ; genetics ; Chromosome Aberrations ; Chromosome Banding ; Genetic Testing ; Humans ; Infertility, Male ; genetics ; Karyotype ; Karyotyping ; Male ; Phenotype ; Sex-Determining Region Y Protein ; genetics