Acanthosis Nigricans Research Articles

Unveiling the Silent Danger of Childhood Obesity: Non-Invasive Biomarkers Such as Carotid Intima-Media Thickness, Arterial Stiffness Surrogate Markers, and Blood Pressure Are Useful in Detecting Early Vascular Alterations in Obese Children.

Obese children present a higher cardio-metabolic risk. Measuring vascular biomarkers that assess the evolution of arterial stiffness, subclinical atherosclerosis, and hypertension in such patients could be helpful in the long term. We studied 84 children, aged from 6 to 18 years: 50 obese subjects, versus 34 of normal weight. Clinical examination involved: BMI, waist circumference, waist-to-height ratio, and detection of the presence of acanthosis nigricans and irregular menstrual cycles (the latter in adolescent girls). The carotid intima-media thickness (CIMT) was measured with the Aixplorer MACH 30 echography device. The pulse wave velocity (PWV), augmentation index (AIx), and peripheral and central blood pressures (i.e., SBP, DBP, cSBP, cDBP, and cPP) were acquired through a Mobil-O-Graph device. Obese subjects underwent body composition analysis with a Tanita BC-418. Blood tests were: HOMA-IR, lipid panel, uric acid, and 25-OH vitamin D. All vascular biomarkers presented increased values in obese subjects versus controls. The following cut-off values were significant in detecting obesity: for PWV > 4.6 m/s, cSBP > 106 mmHg for the <12-year-olds, PWV > 4.5 m/s and cSBP > 115 mmHg for the 12-15-year-olds, and PWV > 5 m/s, cSBP > 123 mmHg for the >15-year-olds. AIx is higher in obese children, regardless of their insulin resistance status. Waist circumference and waist-to-height ratio correlate to all vascular parameters. HOMA-IR is an independent predictor for all vascular parameters except CIMT. Cut-off values for PWV of >4.8 m/s, SBP > 125 mmHg, and a cSBP > 117 mmHg predicted the presence of acanthosis nigricans. Obese girls with irregular menses displayed significantly higher PWV, SBP, and DPB. Elevated levels of uric acid, LDL-c, non-LDL-c, triglycerides, and transaminases, and low levels of HDL-c and 25-OH vitamin D correlated with higher arterial stiffness and CIMT values. We conclude that CIMT and the markers of arterial stiffness are useful in the early detection of vascular damage in obese children.

Improved Insulin Secretion Response and Beta-cell Function Correlated with Increased Prolactin Levels After Laparoscopic Sleeve Gastrectomy in Morbidly Obese Patients with Acanthosis Nigricans.

To explore insulin secretion patterns, β-cell function, and serum prolactin (PRL) concentrations in Chinese morbidly obese patients with Acanthosis nigricans (AN) and their alterations after laparoscopic sleeve gastrectomy (LSG). A total of 138 morbidly obese subjects undergoing LSG were categorized as simple obesity without AN (OB group, n = 55) and obesity with AN (AN group, n = 83). Oral glucose tolerance test (OGTT), PRL, and related metabolic indices were performed pre- and 12 months post-LSG. Insulin secretion patterns were derived from insulin secretion peak time during OGTT: type I (peak at 30 or 60 min) and type II (peak at 120 or 180 min). Preoperatively, AN group showed significantly higher proportions of type II insulin secretion pattern, fasting insulin (FINS), and homeostatic model assessment of insulin resistance (HOMA-IR) whereas lower oral glucose insulin sensitivity (OGIS), insulinogenic index (IGI), and disposition index (DI) than OB group, which were improved significantly at 12 months postoperatively in both groups, more pronounced in AN group. Intriguingly, serum PRL declined substantially in AN group than OB group at baseline whereas elevated only in the AN group post-LSG. After adjusting for confounding factors, elevated PRL correlated significantly with increased IGI and DI, and decreased HOMA-IR in both genders, as well as increased OGIS in females, which was detected only in the AN group CONCLUSION: Morbidly obese patients with AN presented delayed insulin secretion response, impaired insulin secretion, and β-cell dysfunction, which were significantly improved by LSG and might benefit from elevated PRL.

1136-P: Type A Insulin Resistance Masquerading as Type 1 Diabetes Mellitus

More than 150 mutations in the INSR gene encoding the insulin receptor have been identified causing a spectrum of insulin resistance syndromes from mild (type A insulin resistance) to more severe (Rabson-Mendenhall syndrome, Donahue syndrome). Type A insulin resistance typically presents in childhood or early adulthood. We describe a 19-year-old male with type A insulin resistance due to heterozygous INSR gene mutation, c.3470A&amp;gt;G (His1157Arg). This mutation has previously been identified in female patients with hyperglycemia, insulin resistance. The patient presented at age 14 with polyuria, polydipsia, hyperglycemia (glucose 200s) without acidosis, and normal BMI (50th%) and was presumed to have type 1 diabetes. He was treated with insulin though required escalating doses to 2-2.5 units/kg/day and was started on metformin to improve insulin sensitivity which had a minor effect on total daily insulin requirements. HbA1c was typically 7-9% for several years with this treatment plan and BMI remained near 50th%. The patient was subsequently lost to follow-up and after self-discontinuing insulin for approximately 1 year, re-presented with hyperglycemia, the absence of ketonuria or acidosis, elevated insulin level (92.2 μIU/ml), negative islet cell antibodies, HbA1c 10.9%. Notably, he did not have acanthosis nigricans. Subsequent genetic testing revealed a mutation in the INSR gene consistent with type A insulin resistance. This case highlights the importance of considering monogenic forms of diabetes and insulin resistance syndromes in lean patients who require higher-than-expected insulin doses with presumed type 1 diabetes. Disclosure E.A.Los: Other Relationship; Medtronic. K.Wirthwein: None.

Unravelling the pathogenesis of foramen magnum stenosis in patients with severe achondroplasia: a CT-based comparison with age-matched controls and FGFR3 craniosynostosis syndromes.

Foramen magnum(FM) stenosis can be responsible for acute and chronic damage to the cervicomedullary junction in children with achondroplasia. The bony anatomy and patterns of suture fusion of the FM in this context are incompletely understood, yet becoming increasingly important in the light of novel medical therapies for achondroplasia. The objective of this study was to describe and quantify bony anatomy and fusion patterns of FM stenosis in patients with achondroplasia using CT scans, comparing them to age-matched controls and other FGFR3 craniosynostosis patients. Patients with achondroplasia and severe FM stenosis, classified as achondroplasia foramen magnum score(AFMS) grades 3 and 4, were identified from a departmental operative database. All had pre-operative CT scans of the craniocervical junction. Measurements obtained comprised sagittal diameter (SD), transverse diameter (TD), foramen magnum area, and opisthion thickness. Anterior and posterior interoccipital synchondroses (AIOS and PIOS) were graded by the extent of fusion. These measurements were then compared with CT scans from 3 age-matched groups: the normal control group, children with Muenke syndrome, and children with Crouzon syndrome with acanthosis nigricans (CSAN). CT scans were reviewed in 23 cases of patients with achondroplasia, 23 normal controls, 20 Muenke, and 15 CSAN. Children with achondroplasia had significantly smaller sagittal diameter (mean 16.2 ± 2.4mm) compared to other groups (control 31.7 ± 2.4mm, p < 0.0001; Muenke 31.7 ± 3.5mm, p < 0.0001; and CSAN 23.1 ± 3.4mm, p < 0.0001) and transverse diameters (mean 14.3 ± 1.8mm) compared with other groups (control 26.5 ± 3.2mm, p < 0.0001; Muenke 24.1 ± 2.6mm, p < 0.0001; CSAN 19.1 ± 2.6mm, p < 0.0001). This translated into a surface area which was 3.4 times smaller in the achondroplasia group compared with the control group. The median grade of the AIOS fusion achondroplasia group was 3.0 (IQR 3.0-5.0), which was significantly higher compared with the control group (1.0, IQR 1.0-1.0, p < 0.0001), Muenke group (1.0, IQR 1.0-1.0, p < 0.0001), and CSAN (2.0, IQR 1.0-2.0, p < 0.0002). Median PIOS fusion grade was also highest in the achondroplasia group (5.0, IQR 4.0-5.0) compared with control (1.0, IQR 1.0-1.0, p < 0.0001), Muenke (2.5, IQR 1.3-3.0, p < 0.0001), and CSAN (4.0, IQR 4.0-4.0, p = 0.2). Distinct bony opisthion spurs projecting into the foramen magnum were seen in achondroplasia patients but not others, resulting in characteristic crescent and cloverleaf shapes. Patients with AFMS stages 3 and 4 have significantly reduced FM diameters, with surface area 3.4 times smaller than age-matched controls. This is associated with premature fusion of the AIOS and PIOS in comparison with controls and other FGFR3-related conditions. The presence of thickened opisthion bony spurs contributes to stenosis in achondroplasia. Understanding and quantifying bony changes at the FM of patients with achondroplasia will be important in the future quantitative evaluation of emerging medical therapies.

Diet and Acanthosis Nigricans over a Two-Year Period in Children of the Pacific Region.

The impact that dietary carbohydrates have on children developing type 2 diabetes remains controversial. Furthermore, there are limited pediatric longitudinal studies on changes in body mass index (BMI) and diet related to the development of acanthosis nigricans (AN), a risk factor associated with type 2 diabetes. Two 24 h dietary records were collected for 558 children, 2-8 years of age, at baseline and at a 2-year follow-up. Data on age, sex, BMI, and the presence of AN were also collected at each time point from the Children's Healthy Living Program. Logistic regression was used to determine factors associated with the presence of AN at follow-up. Multinominal regression was used to determine factors associated with changes in AN status. Linear regression was used to measure the associations between changes in dietary intake and in the Burke Score for AN. AN was present in 28 children at baseline and 34 children at follow-up. Adjusting for the presence of AN at baseline, age, sex, study group, baseline BMI, change in BMI z-score, time between assessments, and baseline intake, an increase from baseline for each teaspoon of sugar and serving of carbohydrate-rich food increased the risk for having AN at follow-up by 9% and 8%, respectively (p ≤ 0.05). An increased intake of added sugar (teaspoons) increased the risk of developing AN by 13% (p ≤ 0.01) and an increase in servings of foods rich in starch increased the risk of developing AN by 12% (p ≤ 0.01) compared to children who never had AN. Increasing the intake of fruit was also associated with decreased Burke Scores using multiple regression. However, the intake of energy and macronutrients were not associated with AN. Added sugar and foods rich in starch were independently associated with the occurrence of AN, suggesting the type of carbohydrates consumed is a factor in AN occurrence.

A Deep Dive into Polycystic Ovary Syndrome

Introduction: Polycystic ovary syndrome (PCOS) is a common disorder found in women of reproductive age in India. It has multigenic etiology, including genetic, lifestyle, stress, diet, exercise, and obesity. Methods: We have searched various databases such as PubMed and Google Scholar including the relevant literature on “PCOS.” Results: Some of the most common clinical features observed are oligomenorrhea/amenorrhea, hyperandrogenemia, hyperinsulinemia, polycystic ovaries in ultrasonography, hirsutism, alopecia, acne, and acanthosis nigricans. Several studies have shown an association between PCOS and heart disease because of varied causes, including altered lipid/glucose metabolism, hypertension, systemic inflammatory conditions, vascular injuries, obesity, and hyperandrogenism. PCOS and hyperprolactinemia are the two most common etiologies of anovulation in women, although evidence linking them suggests independent origins of these conditions. Hence, PCOS influences the quality of life as its clinical manifestations may lead to fear of sexual unattractiveness, poor self-esteem, discontent with one’s physical appearance, social anxiety, emotional changes, and mood swings, causing huge psychological distress. Conclusion: It is essential to focus on managing the patients’ primary needs and reducing the impact of long-term risk factors when treating a patient with PCOS. The symptoms of a PCOS patient could be well managed when a variety of specialists work together, catering to a multidisciplinary approach.

Clinical Phenotypes of PCOS: a Cross-Sectional Study.

This cross-sectional study examines the Doi-Alshoumer PCOS clinical phenotype classification in relation to measured clinical and biochemical characteristics of women with polycystic ovary syndrome (PCOS). Two cohorts of women (Kuwait and Rotterdam) diagnosed with PCOS (FAI > 4.5%) were examined. These phenotypes were created using neuroendocrine dysfunction (IRMA LH/FSH ratio > 1 or LH > 6 IU/L) and menstrual cycle status (oligo/amenorrhea) to create three phenotypes: (A) neuroendocrine dysfunction and oligo/amenorrhea, (B) without neuroendocrine dysfunction but with oligo/amenorrhea, and (C) without neuroendocrine dysfunction and with regular cycles. These phenotypes were compared in terms of hormonal, biochemical, and anthropometric measures. The three suggested phenotypes (A, B, and C) were shown to be sufficiently distinct in terms of hormonal, biochemical, and anthropometric measures. Patients who were classified as phenotype A had neuroendocrine dysfunction, excess LH (and LH/FSH ratio), irregular cycles, excess A4, infertility, excess T, highest FAI and E2, and excess 17αOHPG when compared to the other phenotypes. Patients classified as phenotype B had irregular cycles, no neuroendocrine dysfunction, obesity, acanthosis nigricans, and insulin resistance. Lastly, patients classified as phenotype C had regular cycles, acne, hirsutism, excess P4, and the highest P4 to E2 molar ratio. The differences across phenotypes suggested distinct phenotypic expression of this syndrome, and the biochemical and clinical correlates of each phenotype are likely to be useful in the management of women with PCOS. These phenotypic criteria are distinct from criteria used for diagnosis.

CD36−SREBP1 Axis Mediates TSLP Production in Obesity-Exacerbated Atopic Dermatitis

Obesity is associated with an increased risk of atopic dermatitis (AD) and may accelerate its development. Keratinocyte dysfunction has been observed in obesity-related skin diseases, including psoriasis and acanthosis nigricans, but is not fully understood in AD. In this study, we found that high-fat diet-induced obesity exacerbated AD-like dermatitis in mice, with elevated inflammatory molecules and increased CD36-SREBP1-related fatty acid accumulation in the lesional skin. Blocking CD36 or SREBP1 with chemical inhibitors effectively alleviated AD-like inflammation, decreased fatty acid accumulation, and downregulated TSLP expression in obese calcipotriol (MC903)-treated mice. Moreover, palmitic acid treatment induced TSLP overexpression in keratinocytes through the activation of the CD36-SREBP1 signaling pathway. The chromatin immunoprecipitation assay further revealed increased binding of SREBP1 to the TSLP promoter region. Our findings provide compelling evidence that obesity triggers the activation of the CD36-SREBP1-TSLP axis in keratinocytes, leading to epidermal lipid disorders and the aggravation of AD-like inflammation. By targeting CD36 or SREBP1, future combination therapies or modified treatment strategies could be developed to help manage patients with both obesity and AD.

Dermatoses in overweight and obese children and their relationship with insulin and skin color.

The aim of the present study was to investigate the prevalence of obesity-related dermatoses in obese children, and the association between these dermatoses and insulin resistance as well as skin color. Obese, overweight, and normal weight children according to body mass index who were followed up and treated in the outpatient clinics were included in the study. Dermatological examinations of the participants were performed, and fasting insulin and glucose levels were checked. The obese and overweight children were evaluated as the patient group (70 girls, 41 boys, mean age: 12.37 ± 3.14 years). One hundred one healthy children with normal weight were determined as the control group (59 girls, 42 boys, mean age: 12.15 ± 2.43). The first five common dermatoses in the patient group when compared with the control group were keratosis pilaris (KP), striae distensae, hyperhidrosis, acanthosis nigricans (AN), and plantar hyperkeratosis. The first five dermatoses which were positively correlated with formation and insulin resistance were KP, striae distensae, AN, hyperhidrosis, and plantar hyperkeratosis. According to the Fitzpatrick skin scale, we found that the darker the skin color, the higher the probability of ANand KP(OR, 0.298; 95% CI, 0.106-0.834, p = 0.021; OR, 0.306; 95% CI, 0.117-0.796, p = 0.015, respectively). Some dermatoses associated with obesity and insulin resistance were not found in obese children, or there was no significant association. These results indicate that many skin morbidities may be prevented by preventing and treating obesity and insulin resistance in the early period.

Clinical profiling of Acanthosis nigricans in Emirati patients and its association with sex-specific differences in insulin secretion and insulin resistance: a case-control study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Association of polycystic ovary syndrome with multiple health factors and adverse pregnancy outcomes

Polycystic ovary syndrome (PCOS), an endocrine and metabolic disorder in women of reproductive age, is characterized by high androgen levels, irregular periods, and small cysts in the ovaries. PCOS affects approximately 10% of reproductive age women of all races and ethnicities. PCOS has been recognized to affect women of reproductive age since antiquity and in the 21st century, it emerges as the most widespread and serious reproductive metabolic disorder in the world. PCOS is a multifactorial disorder that affects both the reproductive and metabolic health of women. In addition, PCOS is a leading symptom of infertility in women. Nevertheless, women with PCOS who become pregnant unfortunately have an increased risk of complications, such as gestational diabetes mellitus (GDM), preterm birth. Many people believe GDM disappears after childbirth, despite the fact that GDM is a warning symptom of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. According to growing evidence, GDM complicates 40% of PCOS pregnancies, suggesting that PCOS is a risk factor for GDM. Hence, PCOS is a lifelong disorder that can eventually lead to various long-term health complications, including chronic menstrual irregularity, infertility, endometrial hyperplasia, and endometrial cancer. Thus, it’s a scientific fact that both PCOS and GDM are significantly associated with each other. However, most studies on the risk of GDM in PCOS patients are retrospective. Therefore, there is no strong evidence whether PCOS is a risk factor for GDM or any other related factor. PCOS, a polygenic endocrinopathy, is in a true sense a set of diseases that worsen the state of the body. Reproductive and metabolic disorders associated with PCOS cause several clinical symptoms, such as irregular and painful periods, hirsutism, acanthosis nigricans, acne, psoriasis, anxiety, mood swings, patterned baldness, cardiovascular problems, type 2 diabetes, infertility, pelvic pain, low libido, low self-esteem, etc. Further studies are needed to understand the genetic and epigenetic contributions of PCOS, PCOS-related comorbidities, the role of placenta in nutrient availability, and influence of medications that may affect the long-term offspring health.

Cardiometabolic risk factors among children who are affected by overweight, obesity and severe obesity.

The increasing severity of obesity is expected to lead to more serious health effects. However, there is limited information on the prevalence and clinical characteristics of cardiometabolic risk factors in severely children affected by obesity in Malaysia. This baseline study aimed to investigate the prevalence of these factors and their association with obesity status among young children. In this study, a cross-sectional design was employed using the baseline data obtained from the My Body Is Fit and Fabulous at school (MyBFF@school) intervention program involving obese school children. Obesity status was defined using the body mass index (BMI) z-score from the World Health Organization (WHO) growth chart. Cardiometabolic risk factors presented in this study included fasting plasma glucose (FPG), triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood pressure, acanthosis nigricans, insulin resistance (IR), and MetS. MetS was defined using the International Diabetes Federation (IDF) 2007 criteria. Descriptive data were presented accordingly. The association between cardiometabolic risk factors, such as obesity status, and acanthosis nigricans with MetS was measured using multivariate logistic regression, which was adjusted for gender, ethnicity, and strata. Out of 924 children, 38.4% (n = 355) were overweight, 43.6% (n = 403) were obese, and 18% (n = 166) were severely obese. The overall mean age was 9.9 ± 0.8 years. The prevalence of hypertension, high FPG, hypertriglyceridemia, low HDL-C, and the presence of acanthosis nigricans among severely children affected by obesity was 1.8%, 5.4%, 10.2%, 42.8%, and 83.7%, respectively. The prevalence of children affected by obesity who were at risk of MetS in <10-year-old and MetS >10-year-old was observed to be similar at 4.8%. Severely children affected by obesity had higher odds of high FPG [odds ratio (OR) = 3.27; 95% confdence interval (CI) 1.12, 9.55], hypertriglyceridemia (OR = 3.50; 95%CI 1.61, 7.64), low HDL-C (OR = 2.65; 95%CI 1.77, 3.98), acanthosis nigricans (OR = 13.49; 95%CI 8.26, 22.04), IR (OR = 14.35; 95%CI 8.84, 23.30), and MetS (OR = 14.03; 95%CI 3.97, 49.54) compared to overweight and children affected by obesity. The BMI z-score, waist circumference (WC), and percentage body fat showed a significant correlation with triglycerides, HDL-C, the TG: HDL-C ratio, and the homeostatic model assessment for IR (HOMA-IR) index. Severely children affected by obesity exhibit a higher prevalence of and are more likely to develop cardiometabolic risk factors compared to overweight and children affected by obesity. This group of children should be monitored closely and screened periodically for obesity-related health problems to institute early and comprehensive intervention.

The Roles of Fibroblast Growth Factor Receptor 3 (FGFR3) in the Spectrum of Skeletal Dysplasia

The fibroblast growth factor receptor 3 (FGFR3) gene mutations were identified to be involved in the pathogenesis of most chondropathies. The FGFR3 gene encodes the FGFR3 receptor and is involved in the regulation of bone growth by limiting the ossification of long bones. Mutations of the FGFR3 gene result in abnormal cell proliferation and improper cartilage development. We aim to provide an overview of the roles of FGFR3 in skeletal dysplasia by highlighting the pathogenesis, clinical variants of skeletal dysplasia, diagnosis, and their management.&#x0D; Achondroplasia is the most common form of chondropathies, occurring in approximately 1 in 20,000-30,000 live births, and it is the most common form of genetic dwarfism. In over 80% of cases of achondroplasia, the mutation is sporadic, and only 20% are inherited autosomal dominant. Achondroplasia results from a point mutation in the gene encoding the transmembrane portion of FGFR3. Two viable base substitutions are identified in achondroplasia, including a point mutation of guanine substituted for adenine (c.1138G&gt;A); this is identified in approximately 98% of the affected individuals, and transversion of guanine to cytosine (c.1138G&gt;C).&#x0D; Hypochondroplasia is a milder form of chondropathies with an incidence between 1 in 33,000 and 1 in 47,000 live births. Missense mutations of FGFR3 (p.Asn540Lys) are isolated in tyrosine kinase domain I occurring in approximately 60% of cases, and missense mutation of FGFR3 (p.Lys650Asn) identified in the tyrosine kinase domain II of FGFR3. Thanatophoric dysplasia is the most lethal form of chondropathies, with neonatal fetal death secondary to pulmonary hypoplasia. In thanatophoric dysplasia, there is Lys650Met substitution in FGFR3 (Type I) with impairment of endochondral bone growth and a pathogenic variant of p.Lys650Glu substitution in FGFR3 (Type II). In addition, specific amino acid substitution in the FGFR3 gene (G380R) was identified to be associated with severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN).&#x0D; The diagnosis of achondroplasias is routinely made from clinical presentations and radiological findings. FGFR3 molecular genetic testing is performed in children with atypical presentations. In addition, a pre-implantation genetic diagnosis should be available for parents pursuing in-vitro fertilization and embryo implantation procedures. Management of chondropathies includes symptomatic treatment with drugs, surgical intervention, and lifelong follow-up care. Different pharmacological options have been used, including those that directly block FGFR3 activation or regulate signalling pathways controlling chondrocyte proliferation and differentiation.

Clinico-Metabolic Profile in Lean Versus Obese Polycystic Ovarian Syndrome Women.

Background Polycystic ovarian syndrome (PCOS), which affects women of reproductive age, is the most prevalent endocrine disorder. Signs of excessive androgen, irregular menses, prolonged anovulation, and infertility are characteristics of the clinical phenotype. Women with PCOS are more likely to have diabetes, obesity, dyslipidemia, hypertension, anxiety, and depression. PCOS affects women's health starting before conception and continuing through their post-menopausal years. Methods Ninety-six study subjects were recruited from women visiting the gynaecology clinic according to the Rotterdam criteria for PCOS. Study subjects were then divided into lean and obese groups according to their body mass index (BMI). Demographic data, and obstetrical and gynaecological history were obtained including marital status, menstrual cycle regularity, recent abnormal weight gain (in the preceding six months), and subfertility. To identify any clinical signs of hyperandrogenismsuch as acne, acanthosis nigricans, or hirsutism, a general and systemic examination was conducted. Data were analyzed after the clinico-metabolic profile was assessed, compared, and contrasted between the two groups. Results The findings showed a significant correlation between obese women with PCOS and the clinical profile of PCOS i.e. menstrual irregularities, acne vulgaris, acanthosis nigricans and hirsutism; the waist-hip ratio was higher in both groups. Higher levels of fasting insulin, fasting glucose: insulin ratio, postprandial sugars, homeostasis model assessment of insulin resistance (HOMA-IR) index, total testosterone, free testosterone, and luteinizing hormone/follicle-stimulating hormone (LH: FSH) ratio were seen in obese women with PCOS, whereas the levels of fasting glucose, serum triglycerides, serum high-density lipoprotein cholesterol (HDL) were higher in all the study subjects irrespective of BMI. Conclusion The study showed that women with PCOS have a deranged metabolic profile like abnormal blood sugar, insulin resistance (IR), and hyperandrogenemia with clinical derangements like irregular menses, subfertility, and recent weight gain more frequently with higher BMI.

Prevalence, Predictors and Morphological Patterns of Acanthosis Nigricans Between Obese Non-diabetic Patients on Second Generation Antipsychotics Versus Non-obese Insulin Dependent Diabetes mellitus: A Nested Case-Control Study

INTRODUCTION: There is no study in literature for analyzing acanthosis nigricans (AN) in psychotropic induced obesity or hypercholesterolemia.&#x0D; AIM: To assess the prevalence and explore the predictors and morphological patterns in AN in patients on antipsychotics induced hypercholesterolemia versus those with diabetes mellitus.&#x0D; MATERIALS AND METHODS: 491 schizophrenia patients on second generation antipsychotics were screened. 26 out of 491 patients have AN and cholesterol 200 mg/dl but non-diabetic. We used MannWhitney U-test, Pearsons 2 test, Fischer Exact and Spearmans correlation coefficient.&#x0D; RESULTS: In the group of antipsychotics induced hypercholesterolemia having developed AN in 5.29% (26 out of 491) of individuals, we observed significance of Burkes knuckle (p 0.001), knee (p = 0.002), elbow (p = 0.042) compared to patients without hypercholesterolemia. Interestingly Burkes neck severity (p 0.001), neck texture (p = 0.001) and axilla (p = 0.007) index also showed marked differences on MannWhitney U-test and Wilcoxson W-test. On Spearmans correlation coefficient antipsychotics induced hypercholesterolemia was found to affect most positively and significantly as the emergence of AN specifically for neck texture ( = 0.413, p = 0.003) compared to other bodily regions.&#x0D; CONCLUSION: About 5.29% prevalence of AN in the group having obesity secondary to psychotropic drugs which was significantly less than what even non-obese, insulin dependent diabetic patients who almost had 13.55% prevalence, close to three times. This suggests that diabetes is strongly linked with occurrence of AN lesions and might reflect the continuity in the paradigm of metabolic syndrome as its definitive predictor of severity while obesity is the initiation of phase shift in the process.

Hypochondroplasia with Acanthosis Nigricans and Moyamoya Disease

Hypochondroplasia with Acanthosis Nigricans and Moyamoya Disease

Clinical and dermatoscopic correlation in facial melanosis: A cross-sectional study at a tertiary hospital

Background: Facial pigmentary disorders are a group of heterogeneous entities, sharing a common clinical feature of altered pigmentation of the face. The overlapping features among the different clinical entities of facial hyperpigmentation may be differentiated by dermatoscopy. Objective: The objective was to evaluate the different types of facial melanosis and their dermatoscopic findings. Methods: This non-interventional, cross-sectional study was conducted at our dermatology department over a period of one year. All clinically diagnosed cases of facial melanosis were included in our study and their dermatoscopic evaluation was performed. Results: We included 500 patients with facial melanosis. While 370 patients were female, 130 were males. Three hundred patients had melasma, 59 (lichen planus pigmentosus) had LPP, 40 had Riehl’s melanosis, while 35 had frictional melanosis. Other dermatoses included acanthosis nigricans, ashy dermatosis, and poikiloderma of Civatte, to name a few. The most common dermatoscopic finding in our study evident in almost all cases of facial melanosis was exaggerated pseudo-reticular hyperpigmentation. The unique observation in our study, the reticulo-globular pattern seen in melasma, was thin and in the shade of brown pigmentation, whereas in LPP and ashy dermatosis, it was comparatively thicker and grayish-brown in color. The other specific finding observed was telangiectasia due to topical steroids, more prominent and enlarged than telangiectasia due to sun exposure in melasma and poikiloderma of Civatte. Conclusion: This study highlights the clinical and dermatoscopic features of facial melanosis. Further research is required in this field of dermatoscopic evaluation of facial melanosis to define more accurate diagnostic features as a facial biopsy is mostly refused by the patients, yet meanwhile, clinical evaluation should not be neglected. Study Limitations: The limitations of our study were the lack of direct histopathological correlation and the inclusion of both therapy-naive patients and patients on therapy. Key words: Facial melanosis; Dermatoscope; Melasma

A family with type A insulin resistance syndrome caused by a novel insulin receptor mutation.

A 17-year-old boy was referred to our endocrinology clinic for a clinical investigation of hyperinsulinemia. An oral glucose tolerance test showed plasma glucose concentrations in the normal range. However, insulin concentrations were considerably elevated (0 min: 71 μU/mL; 60 min: 953 μU/mL), suggesting severe insulin resistance. An insulin tolerance test confirmed that he had insulin resistance. There was no apparent hormonal or metabolic cause, including obesity. The patient had no outward features of hyperinsulinemia, including acanthosis nigricans or hirsutism. However, his mother and grandfather also had hyperinsulinemia. Genetic testing showed that the patient (proband), his mother, and his grandfather had a novel p.Val1086del heterozygous mutation in exon 17 of the insulin receptor gene (INSR). Although all three family members have the same mutation, their clinical courses have been different. The onset of the mother's diabetes was estimated at 50 years, whereas the grandfather developed diabetes at 77 years. Type A insulin resistance syndrome is caused by mutations in the insulin receptor (INSR) gene and results in severe insulin resistance. Genetic evaluation should be considered in adolescents or young adults with dysglycemia when an atypical phenotype, such as severe insulin resistance, or a relevant family history is observed. Clinical courses may differ even if the same genetic mutation is found in a family.

Acanthosis Nigricans in Adolescents versus Adults; Association with Obesity, Diabetes and Hypertension

Objectives: Acanthosis nigricans presents as black velvety plaques on flexural surfaces which is associated with obesity, T2DM and HTN. To study sites and types of AN (Acanthosis Nigricans) in adolescents Vs. adults and its associations. Study design &amp; setting: This cross sectional study was conducted from IstMar-31stAug 2021 at RIHS Islamabad after ethical approval. Methodology: Adolescents and adult cases of both the genders with AN were included by convenience sampling. Critically ill cases, endocrine disorders, pregnancy and malignancy were excluded.57 adolescents and 57 gender matched adults were included. After the detailed clinical evaluation, BMI, waist circumference, sites and types of AN were documented. Blood sugars and workup for PCO’s, suggested. Data was analyzed by SPSS 21. Chi-square test and Mann-Whitney-U test applied. Results: Out of 114 cases,77(67.5%) were females. The mean age was 17.99+14.18 years and mean BMI was 31.63+6.92 kg/m2.Obesity was observed in 75(65.8%); 44(77.2%) adolescents Vs. 31(54.4%) adults (p=0.010). Mean waist circumference was 37.03+3.74 inches.AN at Neck 113(99.1%) and benign AN 111(97.4 %) were the most frequent. The types of AN were associated with obesity, DM 31(27.2%) and HTN 27(23.7%) (p&lt;0.05). Conclusions: Benign and HAIR-AN were most frequent. Adolescents with AN have significantly higher obesity than adults. HTN was significantly higher in adults. DM in AN was observed regardless of age group. It is suggested to screen all AN cases regardless of age or gender for obesity, HTN and DM. Early diagnosis may contribute to improve quality of life, prevent morbidity of systemic diseases and improve outcome in AN cases.

Congenital adrenal hyperplasia in adolescence - a gynecological perspective.

Analysis of congenital adrenal hyperplasia (CAH) cases, gynaecological implications, referral reasons to gynaecologist and treatment. Retrospective, longitudinal, single-centre study with female CAH paediatric patients ≥ 10 years-old, followed between 1998-2018 in gynaecology and endocrinology departments at a public university tertiary hospital. 47 patients, 34.0% (n = 16) with classic, 66.0% (n = 31) with non-classic forms (NCAH), CYP21 deficit and 46,XX karyotype. We found a normal median menarche age (11.5 IQR 2 [6-15] years-old), but significantly earlier in NCAH (p = 0.003). Precocious puberty occurred in 48.9%, n = 23. Primary amenorrhea occurred in salt-wasting form (21.4%, n = 3). Oligomenorrhea and hirsutism were significantly more prevalent in NCAH (p = 0.018, p = 0.014 respectively) and acanthosis nigricans and virilization signs in classic forms (p = 0.05, p = 0.000 respectively). Sixteen patients (34.0%) were referred to gynaecology, mostly due to menstrual irregularities (50.0%, n = 8). Medical treatment with isolated or combined corticoids, oestrogen and progestogen were chosen in all but one case. Gonadotropin-releasing hormone analogues were used in 19.0% (n = 9). Surgery was performed in 34.0% (n = 16) patients, median age 2.0 IQR 2.5 (0.6-90) years-old. This paper highlights the importance of a multidisciplinary approach. Early treatment contributes to a phenotypical feminine differentiation and normalization of the hypothalamus-pituitary-ovarian axis, which is essential given the gynaecologic and obstetric consequences of untreated cases.