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Medicine Dec 2023Disorders/differences of sex development (DSD) include a diverse group of congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is... (Review)
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.
Topics: Male; Humans; Female; Child; Testis; Disorder of Sex Development, 46,XY; Hirsutism; Mutation; Gonadal Dysgenesis; Steroidogenic Factor 1; Gonadal Dysgenesis, 46,XY
PubMed: 38206718
DOI: 10.1097/MD.0000000000036725 -
Expert Review of Endocrinology &... Mar 2024Hyperandrogenism is a clinical state consequent to excess androgen production by the ovary, adrenals, or increased peripheral conversion of androgens. The varied... (Review)
Review
An updated clinico-investigative approach to diagnosis of cutaneous hyperandrogenism in relation to adult female acne, female pattern alopecia & hirsutism a primer for dermatologists.
INTRODUCTION
Hyperandrogenism is a clinical state consequent to excess androgen production by the ovary, adrenals, or increased peripheral conversion of androgens. The varied manifestations of hyperandrogenism include seborrhea, acne, infertility, hirsutism, or overt virilization of which adult female acne, hirsutism, and female pattern hair loss are of clinical relevance to dermatologists.
AREAS COVERED
We limited our narrative review to literature published during period from 1 January 1985 to Dec 2022 and searched PubMed/MEDLINE, Web of Science (WOS), Scopus, and Embase databases with main search keywords were 'Hyperandrogenism,' 'Female,' 'Biochemical,' 'Dermatological', and 'Dermatology.' We detail the common etiological causes, nuances in interpretation of biochemical tests and imaging tools, followed by an algorithmic approach which can help avoid extensive tests and diagnose the common causes of hyperandrogenism.
EXPERT OPINION
Based on current data, total testosterone, sex hormone binding globulin, DHEAS, prolactin, free androgen index, and peripheral androgenic metabolites like 3-alpha diol and androsterone glucuronide are ideal tests though not all are required in all patients. Abnormalities in these biochemical investigations may require radiological examination for further clarification. Total testosterone levels can help delineate broadly the varied causes of hyperandrogenism. Serum AMH could be used for defining PCOM in adults.
Topics: Adult; Humans; Female; Hirsutism; Hyperandrogenism; Androgens; Dermatologists; Testosterone; Alopecia; Acne Vulgaris
PubMed: 38205927
DOI: 10.1080/17446651.2023.2299400 -
Journal of Pediatric and Adolescent... Jun 2024The complex correlation between ethnicity and race, clinical hyperandrogenism as signified by hirsutism, and biochemical androgen concentrations in polycystic ovary...
BACKGROUND
The complex correlation between ethnicity and race, clinical hyperandrogenism as signified by hirsutism, and biochemical androgen concentrations in polycystic ovary syndrome (PCOS) is poorly understood.
STUDY OBJECTIVE
The aim of this study was to define the correlation between ethnicity/race and hirsutism score in patients with PCOS.
METHODS
We conducted a retrospective chart review of a total of 251 patients with PCOS at the time of diagnosis. Patients were categorized by their ethnicity and race into 5 main groups: Asian (n = 19, 7.6%), Black or African American (n = 11, 4.4%), Hispanic or Latino (n = 26, 10.3%), White (n = 177, 70.5), and others (n = 18, 7.2%). A general linear model was applied using BlueSky software.
RESULTS
For the entire study population, the mean age at diagnosis was 15.6 ± 1.7, the mean body mass index (BMI) was 30.6 ± 9.8, the mean hirsutism score using the modified Ferriman-Gallwey score chart was 6.2 ± 3.8, and the mean total testosterone was 40.1 ± 20. The hirsutism score was the highest in the Asian population (mean = 9.1, P = .002) and Hispanic or Latino population (mean = 7.8, P = .02), followed by others (mean = 7.4, P = .04) and the Black or African American population (mean = 7.1, P = .2), compared with the White population (mean = 5.4). This correlation remained significant despite accounting for BMI and androgen levels (P < .001).
CONCLUSION
There are factors likely related to hair follicle sensitivity or endogenous response to circulating free androgens that differ between ethnicities and races, such that similar biochemical concentrations lead to differing severity of hirsutism, despite accounting for differences in BMI and androgen levels. More research is needed in this realm to understand the pathophysiologic basis of this interaction.
Topics: Humans; Polycystic Ovary Syndrome; Hirsutism; Female; Retrospective Studies; Adolescent; Testosterone; Body Mass Index; Hispanic or Latino; Black or African American; White People; Ethnicity; Hyperandrogenism
PubMed: 38151058
DOI: 10.1016/j.jpag.2023.12.008 -
Journal of the European Academy of... Jul 2024
Topics: Humans; Turkey; Prevalence; Female; Hirsutism; Adult; Male; Adolescent; Middle Aged; Young Adult
PubMed: 38147489
DOI: 10.1111/jdv.19763 -
Clinical Endocrinology Mar 2024Spironolactone (SPL) has been used to manage hyperandrogenic manifestations in women with polycystic ovary syndrome (PCOS), but data on the risk of hyperkalemia in this...
OBJECTIVE
Spironolactone (SPL) has been used to manage hyperandrogenic manifestations in women with polycystic ovary syndrome (PCOS), but data on the risk of hyperkalemia in this population are scarce. The aim of this study was to evaluate the incidence of hyperkalemia in women with PCOS using SPL in the long term.
DESIGN
Single-centre retrospective study.
PATIENTS
Inclusion and analysis of 98 treatment periods in 78 women with PCOS (20 of whom were duplicates, returning after treatment interruption for a mean of 38 months) who received SPL for a minimum of 12 months and had at least three measurements of potassium levels over time.
MEASUREMENTS
Clinical and hormonal profiles before and during SPL treatment.
RESULTS
Mean age was 29.1 (SD: 9.6) years, and body mass index was 32.2 (SD: 8.1) kg/m². Nine patients had diabetes, and 22 had prediabetes. SPL was used in combination with combined oral contraceptive pills in 55 participants and progestin-only pills/long-acting reversible contraception in 28; metformin was added in 35, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in 15. Median SPL dose was 100 (range: 50-150) mg. A total of 327 serum potassium measurements were obtained (84 pre-exposure and 243 postexposure). Four potassium measurements were above the reference range before exposure and 19 during exposure. All potassium measurements above the reference range during follow-up were classified as mild hyperkalemia (5.1-5.5 mEq/L).
CONCLUSIONS
The present findings suggest that women with PCOS, without kidney or heart disease, using SPL combined with hormonal contraception for managing clinical hyperandrogenism have a low incidence of hyperkalemia and well-tolerated minor adverse effects.
Topics: Adult; Female; Humans; Hirsutism; Hyperkalemia; Polycystic Ovary Syndrome; Potassium; Retrospective Studies; Spironolactone
PubMed: 38127445
DOI: 10.1111/cen.15008 -
Journal of Pediatric and Adolescent... Apr 2024Ovarian tumors are rare in children; however, their incidence increases with age. Of these ovarian tumors, Leydig cell tumors are some of the rarest, accounting for less...
Ovarian tumors are rare in children; however, their incidence increases with age. Of these ovarian tumors, Leydig cell tumors are some of the rarest, accounting for less than 0.1% of all ovarian tumors across all ages. Leydig cell tumors predominantly occur in postmenopausal women and are characterized by nodular proliferation of Leydig cells in the ovarian hilum with intracytoplasmic Reinke crystals. These tumors secrete androgens, which can disrupt ovarian function, clinically presenting with abnormal uterine bleeding and virilization. Although they are generally benign, current recommendations are for treatment with a unilateral salpingo-oophorectomy. In adolescents, hyperandrogenism is most commonly caused by polycystic ovarian syndrome (PCOS); however, the differential for hyperandrogenism is broad. We present a case of a 15-year-old girl with a history of primary amenorrhea who presented with a Leydig cell tumor associated with recurrent ovarian torsion and virilization. This case reviews the challenges with diagnosis, management, and future implications of a rare androgen-secreting tumor in young patients.
Topics: Child; Humans; Female; Adolescent; Leydig Cell Tumor; Hyperandrogenism; Virilism; Ovarian Neoplasms; Androgens
PubMed: 38110028
DOI: 10.1016/j.jpag.2023.11.014 -
Journal of Obstetrics and Gynaecology... Dec 2023This guideline reviews the etiology, diagnosis, evaluation, and treatment of hirsutism.
OBJECTIVE
This guideline reviews the etiology, diagnosis, evaluation, and treatment of hirsutism.
TARGET POPULATION
Women with hirsutism.
OPTIONS
Three approaches to management include: 1) mechanical hair removal; 2) suppression of androgen production; and 3) androgen receptor blockade.
OUTCOMES
The main limitations of the management options include the adverse effects, costs, and duration of treatment.
BENEFITS, HARMS, AND COSTS
Implementation of the recommendations in this guideline may improve the management of hirsutism in women with this condition. Adverse effects and a potential long duration of treatment are the main drawbacks to initiating treatment, as is the possibility of significant financial costs for certain treatments.
EVIDENCE
A comprehensive literature review was updated to April 2022, following the same methods as for the prior Society of Obstetricians and Gynaecologists of Canada (SOGC) Hirsutism guidelines. Results were restricted to systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies. There were no date limits, but results were limited to English- or French-language materials.
VALIDATION METHODS
The authors rated the quality of evidence and strength of recommendations using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, along with the option of designating a recommendation as a "good practice point." See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations).
INTENDED AUDIENCE
Primary care providers, family medicine physicians, obstetricians and gynaecologists, reproductive endocrinologists and others who manage the care of patients with hirsutism.
TWEETABLE ABSTRACT
Management of hirsutism involves a 3-pronged approach of mechanical hair removal, suppression of androgen production, and androgen receptor blockade.
SUMMARY STATEMENTS
RECOMMENDATIONS.
Topics: Female; Humans; Androgens; Canada; Hirsutism; Receptors, Androgen
PubMed: 38049282
DOI: 10.1016/j.jogc.2023.102272 -
Pediatric Endocrinology, Diabetes, and... 2023Adrenocortical carcinoma (ACC) accounts for 0.2% of childhood malignancies. The most common symptom in children is rapidly progressive androgenization. Herein, we report... (Review)
Review
BACKGROUND
Adrenocortical carcinoma (ACC) accounts for 0.2% of childhood malignancies. The most common symptom in children is rapidly progressive androgenization. Herein, we report a case of a patient with symptoms of hypercortisolaemia and androgenization, who was diagnosed with ACC.
CASE PRESENTATION
In a 10-year-old patient with ACC the course of the disease was complicated by 3 recurrences. She was treated with surgery, chemo-, and radiotherapy. Currently, 8 years after the end of treatment, there have been no signs of recurrence.
CONCLUSIONS
A patient after ACC treatment requires regular check-ups and long-term observation. Constant supervision enables early diagnosis of disease recurrence, and the use of treatment improves the prognosis.
Topics: Child; Female; Humans; Adrenocortical Carcinoma; Adrenal Cortex Neoplasms; Virilism
PubMed: 38031835
DOI: 10.5114/pedm.2023.132131 -
Epigenetics Dec 2023Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic...
Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic modifications. Therefore, we assessed the associations of PCOS traits with neonatal DNA methylation (DNAm) using two independent cohorts. DNAm was measured in both cohorts using the Infinium MethylationEPIC array. Multivariable robust linear regression was used to determine associations of maternal PCOS exposure or preconception testosterone with methylation β-values at each CpG probe and corrected for multiple testing by false-discovery rate (FDR). In the birth cohort, 12% (102/849) had a PCOS diagnosis (8.1% PCOS without hirsutism; 3.9% PCOS with hirsutism). Infants exposed to maternal PCOS with hirsutism compared to no PCOS had differential DNAm at cg02372539 [β(SE): -0.080 (0.010); FDR = 0.009], cg08471713 [β(SE):0.077 (0.014); FDR = 0.016] and cg17897916 [β(SE):0.050 (0.009); FDR = 0.009] with adjustment for maternal characteristics including pre-pregnancy BMI. PCOS with hirsutism was also associated with 8 differentially methylated regions (DMRs). PCOS without hirsutism was not associated with individual CpGs. In an independent preconception cohort, total testosterone concentrations were associated with 3 DMRs but not with individual CpGs, though the top quartile of testosterone compared to the lowest was marginally associated with increased DNAm at cg21472377 near an uncharacterized locus (FDR = 0.09). Examination of these probes and DMRs indicate they may be under foetal genetic control. Overall, we found several associations among newborns exposed to PCOS, specifically when hirsutism was reported, and among newborns of women with relatively higher testosterone around conception.
Topics: Pregnancy; Infant; Humans; Infant, Newborn; Female; Polycystic Ovary Syndrome; Hirsutism; DNA Methylation; Hyperandrogenism; Testosterone
PubMed: 37992405
DOI: 10.1080/15592294.2023.2282319 -
Archives of Medical Research Nov 2023Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. In Mexico, its prevalence in patients with type 1 diabetes...
BACKGROUND
Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. In Mexico, its prevalence in patients with type 1 diabetes (T1D) is unknown.
AIM
To evaluate the clinical and biochemical characteristics of patients with T1D with and without PCOS.
METHODS
A cross-sectional study was conducted to evaluate women of reproductive age with T1D for the diagnosis of PCOS using the criteria of the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine. Clinical information was obtained from clinical records, and we recorded anthropometric variables and performed a laboratory test during the follicular phase. The estimated glucose disposal rate and visceral adiposity index were also calculated to assess insulin resistance. Subsequently, participants were evaluated based on the presence or absence of PCOS.
RESULTS
Thirty-nine percent of patients with T1D had PCOS. The most frequent components of PCOS were polycystic ovary morphology (58.5%), clinical hyperandrogenism (41.5%), oligomenorrhea (29.2%), and biochemical hyperandrogenism (19.5%). Patients with PCOS used more insulin per day (1.04 ± 0.33 vs. 0.71 ± 0.29 IU/kg/d, p = 0.003), had lower fasting glucose (116.4 ± 59.79 vs. 161.16 ± 63.9 mg/dl, p = 0.029) and higher right ovarian volume (11.36 [8.64-15.89] vs. 6.9 [5.55-8.77] cm, p = 0.005) and Ferriman-Gallwey scores (9.06 ± 2.05 vs. 7.12 ± 3.15 points, p = 0.035) compared to patients without PCOS. The frequency of insulin resistance and metabolic syndrome in women with PCOS was 37.5 and 18.8%, respectively.
CONCLUSION
PCOS is a very heterogeneous entity, with a high frequency in women with T1D.
Topics: Humans; Female; Polycystic Ovary Syndrome; Hirsutism; Hyperandrogenism; Diabetes Mellitus, Type 1; Insulin Resistance; Cross-Sectional Studies; Glucose
PubMed: 37866088
DOI: 10.1016/j.arcmed.2023.102895