Rabson-Mendenhall Syndrome: Analysis of the Clinical Characteristics and Gene Mutations in 42 Patients.

Aims: Rabson-Mendenhall syndrome (RMS) is a rare autosomal, recessive disorder characterized by severe insulin resistance due to mutations in the insulin receptor (INSR) gene. This study aims to analyze the clinical features and gene mutations in RMS, which have not been extensively studied. Methods: PubMed, Embase, the China National Knowledge Infrastructure, and Wanfang were searched for "Rabson-Mendenhall syndrome" or "Black acanthosis hirsutism insulin resistance syndrome." Results: A total of 42 cases from 33 articles were included. The body mass index ranged from 18.50 to 20.00 kg/m2 with an average of 16.00 kg/m2. There were no overweight (25.00∼29.90 kg/m2) or obese (≥30.00 kg/m2) patients. Acanthosis was present in 29 cases (29/42, 69.05%); growth retardation in 25 cases (25/42, 59.52%); dental anomalies including absence of teeth, crowding, and malocclusion in 23 cases (23/42, 54.76%); and hirsutism in 17 cases (17/42, 40.48%). The average glycosylated hemoglobin was 9.35%, and the average fasting blood-glucose was 8.44 mmol/L; the mean fasting insulin was 349.96 µIU/mL, and the average fasting C-peptide was 6.00 ng/mL. Diabetes was reported in 25 cases (25/33, 75.76%) all of which were diagnosed before 23 years old. All 42 patients had recorded gene mutations, with 22 patients (22/42, 52.38%) having ≥ 2 mutations and 20 cases (20/42, 47.62%) having only 1 mutation. No statistical differences were found in clinical features and laboratory parameters between patients with different mutations. Conclusion: The study indicates that RMS should be considered in young patients with hyperinsulinemia, hyperglycemia with low weight, acanthosis nigricans, growth retardation, dental anomalies, and hirsutism.

Comparison of metformin, myoinositol and metformin-myoinositol combined treatments for polycystic ovary syndrome.

Objective: The objective of this study was to assess the effectiveness of myoinositol (4 g myoinositol + 400 mcg folic acid/day) compared with metformin (average 1700 mg/day), as well as the combined efficacy of both treatments in managing insulin-resistant polycystic ovary syndrome (PCOS) among women. Materials and Methods: We retrospectively analyzed the records of 68 reproductive-age PCOS patients with insulin resistance over a 3-month period. Oral glucose tolerance tests (OGTT) (75 gr) were conducted to measure glucose levels at 0 and 120 min. Moreover, changes in prolactin, thyroid stimulating hormone, high-density lipoprotein, low-density lipoprotein, triglyceride levels, total cholesterol, follicle-stimulating hormone, luteinizing hormone, total testosterone, free testosterone, and dehydroepiandrosterone sulfate (DHEA-S) levels were evaluated pre- and post-treatment over a 3-month period. Results: Statistically significant improvements were observed in menstrual regularity, body mass index (BMI), modified Ferriman Gallwey scores, OGTT glucose levels at 0 and 120 min, total testosterone, free testosterone, and DHEA-S levels across all groups (p<0.005). Conclusion: No significant variances were observed in terms of BMI, modified Ferriman Gallwey scores, or androgen levels across the three treatment cohorts. The combination of myoinositol and metformin did not confer additional benefits compared with either treatment alone.

Impact of Laser Therapy on the Quality of Life in Women Living With Polycystic Ovary Syndrome-Associated Hirsutism: An Observational Study.

INTRODUCTION: This study aimed to observe the impact of laser-assisted hair removal (LAHR) on the quality of life in women with polycystic ovary syndrome (PCOS)-associated hirsutism. METHODOLOGY: An observational study was conducted on 172 women living with PCOS at a specialized clinic. The Dermatology Life Quality Index (DLQI) and Ferriman-Gallwey (FG) score were employed to assess the quality of life and severity of hirsutism, respectively. Laser therapy was administered using ruby diode or alexandrite lasers. Follow-up on the DLQI and FG score assessment was done at 12-, 18-, and 24-week post-treatment. RESULTS: The number of cases that reported stress, anxiety, and depression reduced over time. However, there was no correlation between the patient-reported decrease and DLQI scores. The FG score was significantly related to mental health. The severity of the hirsutism impacted mental health. The regrowth of hair at six months indicated limited long-term efficacy LAHR. CONCLUSION:  LAHR significantly improves the quality of life in the short term for women living with PCOS. However, the short-term benefit of the therapy indicates a need for research to find new treatment strategies.

A Narrative Review of Herbal Remedies for Managing Hirsutism.

Hirsutism is a condition that can have medical, social, and psychological implications, affecting 5% to 10% of women worldwide. Management options include cosmetic procedures and pharmacological interventions. However, medications used to treat hirsutism can have side effects, ranging from mild symptoms like nausea and headaches to more serious complications such as vascular clots, heart attacks, hepatotoxicity, osteoporosis, and effeminization of a male fetus. Therefore, this study aims to investigate the potential benefits of medicinal plants on hirsutism as a complementary approach, specifically whether they can be used as adjuvants to cosmetic procedures. Databases including Google Scholar, PubMed, Scopus, Embase, ISI, SID, and Mag Iran have been checked with related keywords from 2000 to 2023. Moreover, related articles were isolated. In total, ten trials were identified in the search. The results suggested that various herbs, including fennel, licorice, spearmint, saw palmetto, green tea, combination of Zingiber and neem, curcumin, and teupolioside have the potential as herbal remedies for hirsutism. However, further extensive well-designed studies involving a large sample size on the most promising herbs are necessary to determine their efficacy.

Social anxiety and psychological distress among polycystic ovarian syndrome patient's in Pakistan.

OBJECTIVE: To examine the fear of negative evaluation as a predictor, and to explore the association of social anxiety with psychological correlates among women with polycystic ovaries. Methods: The cross-sectional study was conducted from August 2020 to November 2021 after approval form the University of Central Punjab, Lahore, Pakistan, and comprised unmarried women aged 18-26 diagnosed with polycystic ovary syndrome. The sample was raised from different clinics and hospitals based in Lahore and Gujranwala cities. The sample was divided into obese, hirsutism and acne vulgaris groups. Data was collected using a demographic proforma along with standardised Derriford Appearance Scale, Brief Fear of Negative Evaluation Scale, University of California, Los Angeles, Loneliness Scale and the Social Interaction Anxiety Scale. Data was analysed using SPSS 24. RESULTS: Of the 180 patients, 60(33.3%) were in each of the 3 groups. The overall mean age was 21.4+/-2.27 years. A significant association of fear of negative evaluation was found with appearance distress, social anxiety and loneliness (p<0.05). The fear of negative evaluation and appearance distress also significantly predicted loneliness in the subjects (p<0.01). The obese group scored significantly higher in terms of fear of negative evaluation and social anxiety compared to the other groups (p<0.05). Conclusion: Women with polycystic ovaries were found to be suffering from adverse psychological outcomes and social anxiety.

Identifying the First Val281L Mutation Causing Nonclassic Congenital Adrenal Hyperplasia in the Central-East Region of Tunisia.

Nonclassic congenital adrenal hyperplasia (NCAH) is a genetic disorder characterized by mutations in the genes encoding enzymes involved in cortisol production, most commonly the 21-hydroxylase enzyme. Unlike classic congenital adrenal hyperplasia (CAH), NCAH typically presents later in life with milder symptoms. The diagnosis of NCAH can be challenging due to its nonspecific symptoms and variable presentation. Early detection is crucial for timely intervention and management, particularly in families with a history of the condition. We report a case of NCAH in a patient from the Central-East Region of Tunisia, in whom the subsequent genetic testing revealed a Val281Leu (V281L) mutation in the CYP21A2 gene. A 26-year-old female presented with facial hirsutism and irregular menstrual cycles. Physical examination revealed mild hirsutism and laboratory tests showed elevated levels of testosterone and 17-hydroxyprogesterone (17-OHP). A provisional diagnosis of NCAH was made, subsequently confirmed by an adrenocorticotropic hormone (ACTH) stimulation test demonstrating an exaggerated 17-OHP response. Genetic testing revealed heterozygosity for the V281L mutation. Family testing showed the patient's mother to be homozygous and the father heterozygous for the mutation. This report highlights the importance of recognizing subtle symptoms of NCAH for early diagnosis and management. Genetic testing aids in confirming the diagnosis and identifying carriers within families. Treatment with glucocorticoids aims to suppress adrenal androgen production and manage symptoms. Regular follow-up is essential to monitor treatment response and adjust medication as needed. NCAH can present with subtle symptoms, necessitating a high index of suspicion for a proper diagnosis. Genetic testing plays a crucial role in confirming the diagnosis and identifying carriers within families. Early intervention and regular follow-up improve outcomes in affected individuals. This report also underscores the significance of genetic testing in the management of NCAH and highlights the need for increased awareness about this condition among healthcare providers.

Phenotypic Characterization of Patients with Polycystic Ovary Syndrome in a Population from the Ecuadorian Andes: A Cross-Sectional Study.

Background: Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder in women of reproductive age. Diagnosis is based on the evidence-based international guideline 2018 and the Rotterdam Consensus to classify PCOS phenotypes. This study aims to characterize the biodemographic, clinical, metabolic, and reproductive variables and their relationship with PCOS phenotypes in a population from the Ecuadorian Andes. Methodology: A cross-sectional study was conducted with a non-random consecutive sample of 92 women who attended the outpatient gynecology and endocrinology clinic at the Hospital of the Technical University of Loja (UTPL)-Santa Inés, Loja, Ecuador, between January 2022 and July 2023. Descriptive statistics, mean calculations, standard deviation, parametric and nonparametric tests, odds ratios (OR), confidence intervals (CI), and p-values were employed. Results: The average age was 22 ± 3.4 years, with a predominantly mestizo, urban, single, highly educated, and medium-high socioeconomic level population. It was identified that phenotypes A + B are at a higher risk of developing oligomenorrhea and hypertriglyceridemia compared to phenotypes C + D, with statistically significant differences (p < 0.05). Furthermore, in terms of reproductive variables, phenotypes A + B exhibit a significantly higher frequency of elevated anti-Müllerian hormone (AMH) compared to phenotypes C + D, also with statistical significance (p < 0.05). Conclusions: The classical phenotypes A and B of PCOS are the most common in Ecuadorian Andean women and carry a higher risk of insulin resistance, anovulation, metabolic disorders, and elevated triglyceride levels compared to phenotypes C and D. Ethnic diversity and sociocultural habits influence the prevalence and clinical manifestations of these phenotypes.

Unveiling the spectrum: A cross-sectional exploration of hirsutism causes in women.

Background and Objective: Hirsutism is a common endocrine disorder and its etiology varies from benign and idiopathic disorders to serious malignant diseases. Hirsutism creates negative impact on quality of life and considerable effects on fertility. Our objective was to determine the various causes of hirsutism in women presenting at two endocrine clinics. Method: This cross-sectional study was conducted at Baqai Institute of Diabetology and Endocrinology, Karachi and at Jinnah hospital, Lahore from August 2020 to December 2021 women between 12-45 years of age with complains of hirsutism were included in the study. Severity of Hirsutism was evaluated using modified Ferriman-Gallwey score (FG). Patients with modified FG score of 8 or more were considered having hirsutism. Results: The study had 113 patients with a mean age of 15.50+7.29 years with 89% having moderate hirsutism (FG score 16-25). Polycystic ovaries was the most common cause of hirsutism. Common sites for hirsutism included back (83%), arms (74%), buttocks (70%), and upper abdomen (47%). High BMI (p-value <0.01) and high Dehydroepiandrosterone levels were positively associated with the severity of hirsutism (p-value of 0.006.). Conclusion: The various causes of hirsutism identified were polycystic ovaries, followed by idiopathic, thyroid dysfunction, congenital adrenal hyperplasia, and hyperprolactinemia; therefore, all women presenting with hirsutism should be evaluated for potential serious and curable etiologies, before embarking on a treatment plan.

Prevalence and Clinical Management of Adrenal Tumour-Related Hyperandrogenism: A Narrative Review.

Hyperandrogenism is a condition in which the levels of androgen hormones in the blood are significantly increased and could be of an adrenal or ovarian origin. The adrenal androgens, normally secreted by the zona reticularis, are steroid hormones with weak androgen activity. The causes of hyperandrogenism are diverse and could be endogenous and exogenous. Androgen excess affecting different tissues and organs results in clinical features such as acne, hirsutism, virilization, and reproductive dysfunction such as oligomenorrhoea/amenorrhoea. Although androgen excess is rarely associated with adrenal tumours, it is important as it could be predictive of malignancy. A careful evaluation of the androgen pattern, also in patients with clear signs of hyperandrogenism, could be useful. Laboratory evaluation should focus on measuring total testosterone levels, followed by the estimation of other androgens such as dehydroepiandrosterone and androstenedione, and using visualisation procedures in the further management. The treatment of adrenal hyperandrogenism is eminently surgical, in consideration of the frequent malignant origin. The aim of this review is to elaborate and summarize the prevalence and clinical management of hyperandrogenism of an adrenal origin by describing the physiological mechanisms of adrenal androgen steroidogenesis, the clinical manifestations of hyperandrogenism with a special reference to hyperandrogenism in adrenal adenomas and carcinomas, and the diagnostic methods that will lead us to establishing the correct diagnosis and different treatment options to manage this condition according to the clinical presentation of the patient.

Imaging features of intra-abdominal and intra-pelvic causes of hirsutism.

Hirsutism is a relatively common disorder which affects approximately 5% to 15% of women. It is defined by excessive growth of terminal hair in women, which primarily affects areas dependent on androgens, such as the face, abdomen, buttocks, and thighs. Hirsutism can be caused by a variety of etiologies, which are most often not lifethreatening. However, in some cases, hirsutism can be an indicator of more serious underlying pathology, such as a neoplasm, which may require further elucidation with imaging. Within the abdomen and pelvis, adrenal and ovarian pathologies are the primary consideration. The goal of this manuscript is to review the etiologies and imaging features of various intra-abdominal and intra-pelvic causes of hirsutism.

The Search for the Causes of Common Hyperandrogenism, 1965 to Circa 2015.

From 1965 to 2015, immense strides were made into understanding the mechanisms underlying the common androgen excess disorders, premature adrenarche and polycystic ovary syndrome (PCOS). The author reviews the critical discoveries of this era from his perspective investigating these disorders, commencing with his early discoveries of the unique pattern of plasma androgens in premature adrenarche and the elevation of an index of the plasma free testosterone concentration in most hirsute women. The molecular genetic basis, though not the developmental biologic basis, for adrenarche is now known and 11-oxytestosterones shown to be major bioactive adrenal androgens. The evolution of the lines of research into the pathogenesis of PCOS is historically traced: research milestones are cited in the areas of neuroendocrinology, insulin resistance, hyperinsulinism, type 2 diabetes mellitus, folliculogenesis, androgen secretion, obesity, phenotyping, prenatal androgenization, epigenetics, and complex genetics. Large-scale genome-wide association studies led to the 2014 discovery of an unsuspected steroidogenic regulator DENND1A (differentially expressed in normal and neoplastic development). The splice variant DENND1A.V2 is constitutively overexpressed in PCOS theca cells in long-term culture and accounts for their PCOS-like phenotype. The genetics are complex, however: DENND1A intronic variant copy number is related to phenotype severity, and recent data indicate that rare variants in a DENND1A regulatory network and other genes are related to PCOS. Obesity exacerbates PCOS manifestations via insulin resistance and proinflammatory cytokine excess; excess adipose tissue also forms testosterone. Polycystic ovaries in 40 percent of apparently normal women lie on the PCOS functional spectrum. Much remains to be learned.

Exploring the unusual: a testosterone-secreting ovarian tumor.

Ovarian steroid cell tumors are rare, representing less than 0.1% of all ovarian neoplasms. Among the myriad causes of hirsutism, ovarian tumors account for 1% of the reported cases. We present the case of a 49-year-old parous postmenopausal woman who sought medical attention for hirsutism for 2 years. This case illustrates the unusual and interesting connection between rare ovarian pathology and the clinical manifestation of hirsutism in a postmenopausal patient. Her ultrasonography and MRI showed a right adnexal mass of solid-cystic consistency with thin septations. Her laboratory workup revealed high levels of total testosterone of 256 ng/ml (8.4-48.1ng/ml) and free testosterone of 7.36 pg/ml (0.2-4.1 pg/ml), while DHEAS - 234 µg/dl (35.4-256 µg/dl) and CA125 - 15.8U/L (0.0-35 U/L) were in the normal range. She underwent exploratory laparotomy with a total abdominal hysterectomy and oophorectomy. Histopathological examination and immunohistochemistry conclusively established the presence of a steroid cell tumor, specifically classified as "Not Otherwise Specified"(NOS), in the right ovary.

Intervenciones dietéticas en el tratamiento del síndrome del ovario poliquístico. Una revisión bibliográfica / Dietary interventions in the treatment of polycystic ovary syndrome: A bibliographic review

El síndrome del ovario poliquístico (SOP), es una endocrinopatía femenina reconocida como un trastorno heterogéneo caracterizado por un hiperandrogenismo y una disfunción ovulatoria que conlleva problemas de fertilidad. Además, las pacientes suelen presentar una sintomatología asociada como la resistencia a la insulina, la intolerancia a la glucosa, la obesidad central y/o el síndrome metabólico que pueden inducir a un aumento del riesgo de enfermedad cardiovascular. Dado que uno de los principales objetivos del tratamiento del SOP es reducir las consecuencias metabólicas relacionadas con la obesidad, la resistencia a la insulina y el síndrome metabólico, las intervenciones dietéticas dirigidas a este propósito pueden resultar eficaces en el tratamiento de este padecimiento. Se ha llevado a cabo una búsqueda bibliográfica en diferentes bases de datos como Web of Science (WOS), PubMed y Google Académico estableciendo unos criterios de búsqueda previamente definidos. Se han elegido 11 trabajos para su revisión completa y análisis crítico. Entre las diferentes intervenciones que se han utilizado, se han seguido estrategias dietéticas como la Dietary Approaches to Stop Hypertension (DASH), modificaciones en los hidratos de carbono (HC), la inclusión de algún alimento determinado en el patrón dietético habitual y/o los cambios en el estilo de vida. De los resultados obtenidos, destacan las mejoras propiciadas en los marcadores corporales con un régimen DASH, los beneficios promovidos por dietas con modificaciones en los HC, en la resistencia insulínica (IR) y los marcadores hormonales, así como los efectos favorables en las manifestaciones clínicas relacionadas con el hiperandrogenismo, fomentados por el consumo de soja y las modificaciones en el estilo de vida (LSM).(AU)

Polycystic ovary syndrome (PCOS) is a female endocrinopathy recognized as a heterogeneous disorder characterized by hyperandrogenism and ovulatory dysfunction that leads to fertility problems. In addition, patients usually present with associated symptoms such as insulin resistance, glucose intolerance, central obesity and/or metabolic syndrome that can induce an increased risk of cardiovascular disease. Since one of the main goals of PCOS is to reduce the metabolic consequences related to obesity, insulin resistance, and the metabolic syndrome, targeted dietary interventions may be effective in treating PCOS.A bibliographic search has been carried out in different databases such as Web of Science, Pubmed and Google Scholar, establishing previously defined search criteria. Eleven have been chosen for full review and critical analysis. Among the different interventions that have been used, dietary strategies have been followed such as the dietary approaches to stop hypertension (DASH), modifications in carbohydrates, the inclusion of a certain food in the usual dietary pattern and/or lifestyle modifications. Of the results obtained, we highlight the improvements in body markers with a DASH diet, the benefits promoted by diets with modifications in carbohydrates, in insulin resistance and hormonal markers and favorable effects on clinical manifestations related to hyperandrogenism, fostered by soy consumption and lifestyle modifications.(AU)

Fifteen-Year History of Virilization in a 17th-Century Woman.

The Spanish artist, Jusepe de Ribera, painted a portrait of a virilized woman in 1631. He provided a brief clinical history on stone tablets, which indicates that the woman most likely harbored a benign, androgen-secreting ovarian tumor for 15 years.

Understanding hirsutism in PCOS.

INTRODUCTION: Hirsutism is a prevalent condition among women and represents a primary clinical feature of polycystic ovary syndrome (PCOS). AREAS COVERED: Our study aims to address the principal challenges associated with this hyperandrogenic manifestation in PCOS women. Our narrative review based on the available indexed literature explored the complexities of establishing mFG cutoff values for various ethnic groups, investigated hirsutism during peri- and postmenopausal stages, and examined the role of oxyandrogens. EXPERT OPINION: Hirsutism may have a negative impact on the quality of life and on the mental health, being associated with anxiety and depression. Future perspectives for its diagnosis include the use of artificial intelligence and the consideration of the distress caused by excessive hair growth.

Quality of Life of Women with Polycystic Ovary Syndrome.

Background and Objectives: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by multiple hormonal and metabolic abnormalities, including insulin resistance, hyperandrogenism, and disturbances in lipid and carbohydrate metabolism. The objective of this study is to assess the quality of life of women diagnosed with polycystic ovary syndrome (PCOS) and to identify any factors within the study group that may impact the scores related to quality of life. Materials and Methods: This research was carried out among women diagnosed with PCOS. An original questionnaire, developed through an online Google Forms survey, was utilized as the research instrument and distributed through social networks and support groups to women facing PCOS. This study encompassed a participant pool of 200 women with PCOS, aged 24 years or older. For the analytical component, Pearson's χ2 test was employed-a nonparametric test designed to assess the relationship between two variables measured on a qualitative scale. The chosen level of statistical significance was set at p < 0.05. Results: The analysis revealed that the quality of life of the women under study was not linked to the duration of the disease or comorbidities. However, a significant association was observed with the inconvenience caused by PCOS symptoms. Women experiencing very bothersome symptoms of PCOS reported a lower quality of life compared to those with symptoms rated as not very bothersome. Despite the majority of women with PCOS rating their quality of life as good or very good, they often find the associated symptoms of PCOS bothersome. Women reporting lower quality of life tend to acknowledge the impact of PCOS on their lives, experience a sense of lack of control over the disease, struggle with depression, and do not accept their physical appearance. Conclusions: Hence, the support from specialists like endocrinologists, gynecologists, and nutritionists becomes crucial for many women dealing with PCOS. Adopting a healthy lifestyle, incorporating a balanced diet, and engaging in regular physical activity can assist in managing the troublesome symptoms of PCOS, thereby enhancing overall quality of life. In instances of emotional difficulties, seeking psychological support is equally important, and the significance of support and acceptance from loved ones should not be overlooked.