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PURPOSE: To investigate determinants of new onset diabetes after COVID-19 (NODAC) and its recovery at 6 months. METHODS: This was an observational follow up study conducted from August, 2020 to July, 2023, recruiting patients with preexisting DM and COVID 19 patients with no history of DM. Multivariate regression analysis was used to determine the factors responsible for severity of COVID 19 infection in preexisting DM group. Clinical, laboratory and glycometabolic parameters were estimated at baseline and 6 months in NODAC and euglycemic group to determine the factors responsible for NODAC and its persistence at 6 months. RESULTS: Of 1310 patients, 855 (65.3%) COVID 19 patients were further divided based on their glycemic status: preexisting DM (19%), NODAC (8.5%) and euglycemia (72.5%). Older age and male gender were independent risk factors for severe COVID 19 disease in patients with preexisting diabetes. Prevalence of NODAC in present study was 8.5%. Patients with NODAC had higher mean fasting blood glucose (FBG), random blood glucose (RBG) and HbA1c at baseline as compared to COVID with euglycemic group with no difference in serum C-peptide levels. Female gender, family history of DM, signs of insulin resistance, higher BMI, WHR, HbA1c, serum insulin levels, FBG and RBG predicted persistence of NODAC at 6 months. CONCLUSION: Preexisting DM is a risk factor for severe COVID 19 disease. Patients with NODAC have evidence of persistence insulin resistance on follow up, underscoring the need for long term glycemic monitoring.
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Polycystic ovary syndrome (PCOS) and type-2 diabetes mellitus (T2DM) share common genetic features. Transcription factor 7-like-2 (TCF7L2) is consistently studied T2DM susceptibility locus. However, limited studies on TCF7L2 have failed to demonstrate any link with the PCOS risk. Therefore, we investigated the association of TCF7L2 polymorphic variant (rs12255372) with the PCOS risk. We recruited 120 PCOS cases, diagnosed as per Rotterdam 2003 criteria, and an equal number of age-matched controls. Besides a detailed clinical assessment, subjects underwent biochemical and hormonal profiling. Genotyping for rs12255372 was done by PCR-RFLP. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of genotype-phenotype correlations. The PCOS cases reported fewer menstrual cycles per year and exhibited signs of hyperandrogenism. The heterozygous genotype of rs12255372 was strongly associated with the PCOS risk (OR = 2.00; 95%CI: 1.07-3.76). Unlike controls, only 3 cases harbored TT genotype, and the PCOS risk persisted in the dominant model (GT + TT) as well. Moreover, we found a synergistic effect modification by the variant genotype in the subjects who had family histories of T2DM, hirsutism, or menstrual irregularities. We report a significant association of the TCF7L2 polymorphic variant rs12255372 with the PCOS risk.
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BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders largely affecting women of reproductive age group. OBJECTIVES: This study aimed to understand the Indian public health-care systems' preparedness in addressing PCOS. MATERIALS AND METHODS: A multicentric rapid assessment cross-sectional study was undertaken among 173 health-care providers serving across various public health-care facilities in India. This study was a component of a larger task force study that aimed to estimate the community-based prevalence of PCOS in India. Information on PCOS cases reported that knowledge about PCOS diagnosis, management practices, availability of diagnostic facilities, and drugs was explored. RESULTS: Irregular menstrual cycle was the most commonly reported PCOS symptom. Most of the health-care providers (HCPs) lacked correct knowledge about diagnostic criteria and investigation needed for the diagnosis of PCOS. Diagnostic facilities and drugs were inadequate. However, some facilities had access to investigations through public-private partnerships. Awareness programs on PCOS in the community were negligible, and PCOS cases were not documented. Training HCPs on PCOS along with the availability of specialists and strengthening diagnostic facilities were some major demands from the HCPs. CONCLUSION: Results suggest the need for training HCPs, strengthening infrastructure with good referral linkages, and adequate supply of drugs to help improve PCOS management at public health-care facilities in India. There is a need to develop national technical and operational guidelines to address PCOS using a multidisciplinary approach across all levels of care. Creating demand for services and advocating healthy lifestyles through community awareness can help early diagnosis and prevention of complications.
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Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Síndrome del Ovario Poliquístico , Humanos , Síndrome del Ovario Poliquístico/terapia , Síndrome del Ovario Poliquístico/epidemiología , Femenino , India/epidemiología , Estudios Transversales , Personal de Salud/educación , Adulto , MasculinoRESUMEN
Despite the negative implications on women's health, pregnancy, and fetal outcomes, population-based studies on hematological indices among reproductive age women in India have received inadequate attention. This study aimed to generate normative ranges for various hematological parameters among these women. After ethics approval, apparently healthy (n = 5884) women (aged 18-40 years) were recruited from six eco-geographic zones of India. After various exclusions (n = 5412), including women having anemia, data of clinically, and biochemically healthy women (n = 472) was analysed to generate centiles (2.5 and 97.5th) and correlations. The mean age and mean BMI of women was 29.3 ± 6.5 years and 23.25 ± 3.26 kg/m2 with BP of 112.26 ± 8.9/74.04 ± 6.7 mmHg. The reference intervals for hemoglobin (12-15.1 gm/dl), RBC (3.68-5.55 millions/µl), WBC (4.1-11.26*109/L), platelet count (1.32-4.42*105/µl), and erythrocyte sedimentation rate (4.35-41.65 mm/hr) were different from currently used reference values (p < 0.05). However, these haematological indices did not vary among various age categories, geographical zones, ethnicities and rural or urban origins. Pearson's correlation revealed a statistically significant association between ESR, WBC, monocytes, and platelets with homeostasis model assessment of insulin resistance (HOMA-IR). Women with HOMA-IR > 2 displayed a statistically significant differences in parameters like MCV, ESR, eosinophil and platelet counts as compared to the women with HOMA-IR < 2. This study provides a pioneering reference data of hematological indices among women of reproductive age in India. Despite the small sample size results can be extrapolated to the national population given the representative sampling of various geographical zones. This may pave way for future comprehensive large-scale studies on the subject. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01714-6.
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BACKGROUND AND PURPOSE: Despite thiamine deficiency being a lesser-known entity in modern times, beriberi in various forms, including thiamine deficiency-related neuropathy, remains endemic in Kashmir due to the consumption of polished rice as a staple food. This observational study investigates cases of peripheral neuropathy of unknown etiology and their potential responsiveness to thiamine administration. METHODS: This prospective study enrolled adult patients presenting to the emergency department with weakness consistent with thiamine deficiency-related neuropathy and conducted a therapeutic challenge with thiamine on 41 patients. Response to thiamine therapy was monitored based on subjective and objective improvements in weakness and power. Patients were divided into thiamine responders (n = 25) and nonresponders (n = 16) based on their response to thiamine therapy and nerve conduction studies. RESULTS: Most of the baseline characteristics were similar between responders and nonresponders, except the responders exhibited lower thiamine levels and higher partial pressure of oxygen and lactate levels compared to nonresponders. All patients had a history of consuming polished rice and traditional salt tea. Although weakness in the lower limbs was present in both groups, nonresponders were more likely to exhibit weakness in all four limbs. Clinical improvement was observed within 24 h, but proximal muscle weakness persisted for an extended period of time. CONCLUSIONS: Thiamine deficiency-related neuropathy presents with predominant lower limb weakness, exacerbated by vomiting, poor food intake, psychiatric illness, and pregnancy. Thiamine challenge should be followed by observation of clinical and biochemical response.
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Beriberi , Enfermedades del Sistema Nervioso Periférico , Deficiencia de Tiamina , Adulto , Femenino , Embarazo , Humanos , Beriberi/complicaciones , Beriberi/tratamiento farmacológico , Estudios Prospectivos , Deficiencia de Tiamina/complicaciones , Deficiencia de Tiamina/tratamiento farmacológico , Tiamina/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/complicaciones , Debilidad Muscular/etiologíaRESUMEN
Anti-mullerian hormone (AMH) has been proposed to add significance to diagnosis of PCOS in case of ambiguity. However, variable cutoffs of AHM among PCOS women have been reported. Using case-control design, this study investigated the diagnostic threshold of serum AMH levels among age matched 113 PCOS and 75 normo-ovulatory women and its correlation with clinical, hormonal and ultrasonographic parameters.PCOS was defined as per Rotterdam criteria 2003. Results depicted the mean serum AMH level to be significantly higher in PCOS group (7.84 ± 3.67vs. 3.23 ± 1.56 ng/mL) than controls. The AMH levels were positively(p = 0.001) associated with ovarian volume (r = 0.521) as well as number of ovarian follicles(r = 0.461). Further, serum AMH levels showed a positive correlation with luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (r = 0.206, p = 0.02), but no correlation significant with age, BMI,FG score and testosterone levels. As per receiver operating characteristic (ROC) curve, cut-off was worked out to be 3.76 ng/ml with 86.7% sensitivity and 62.7% specificity. The mean level of AMH were highest among PCOS women with phenotype A (12.67 ± 3.46 ng/ml) with least among PCOS women displaying phenotype B(7.28 ± 1.60 ng/ml) where there is absence of PCOM. In conclusion, serum AMH levels are highly predictive of PCOM and high LH/FSH ratio among PCOS women and may be a potent diagnostic marker of ovarian dysfunction either alone or in conjunction with other tools. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01058-4.
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Introduction: Polycystic Ovary syndrome (PCOS) affects the health of many women around theworld. Apart from fundamental metabolic problems connected to PCOS, focus of our study is on the role of quercetin on genes relevant to steroidogenesis and folliculogenesis. Methods: Eighteen mature parkes strain mice (4-5 weeks old) weighing18-21 g were randomly divided into three groups of six each as follows: Group I serves as the control and was given water and a regular chow diet ad lib for 66 days; group II was given oral gavage administration of letrozole (LETZ) (6 mg/kgbw) for 21 days to induce PCOS and was left untreated for 45 days; For three weeks, Group III received oral gavage dose of LETZ (6 mg/kg), after which it received Quercetin (QUER) (125 mg/kg bw orally daily) for 45 days. Results: In our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH ratio, decreased estrogen level and decline in expression of Kitl, Bmp1, Cyp11a1, Cyp19a1, Ar, lhr, Fshr and Esr1 in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in cholesterol, triglycerides, testosterone, vascular endothelial growth factor VEGF and insulin levels. All these changes were reversed after the administration of quercetin in PCOS mice. Discussion: Quercetin treatment reversed the molecular, functional and morphological abnormalities brought on due to letrozole in pathological and physiological setting, particularly the issues of reproduction connected to PCOS. Quercetin doesn't act locally only but it acts systematically as it works on Pituitary (LH/FSH)- Ovary (gonad hormones) axis. the Side effects of Quercetin have to be targeted in future researches. Quercetin may act as a promising candidate for medical management of human PCOS.
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Síndrome del Ovario Poliquístico , Femenino , Humanos , Animales , Ratones , Quercetina , Letrozol , Factor A de Crecimiento Endotelial Vascular , Hormona Folículo EstimulanteRESUMEN
BACKGROUND: A clear understanding of the anthropometric and sociodemographic risk factors related to BMI and hypertension categories is essential for more effective disease prevention, particularly in India. There is a paucity of nationally representative data on the dynamics of these risk factors, which have not been assessed among healthy reproductive-age Indian women. OBJECTIVE: This cross-sectional polycystic ovary syndrome (PCOS) task force study aimed to assess the anthropometric and sociodemographic characteristics of healthy reproductive-age Indian women and explore the association of these characteristics with various noncommunicable diseases. METHODS: We conducted a nationwide cross-sectional survey from 2018 to 2022 as part of the Indian Council of Medical Research-PCOS National Task Force study, with the primary aim of estimating the national prevalence of PCOS and regional phenotypic variations among women with PCOS. A multistage random sampling technique was adopted, and 7107 healthy women (aged 18-40 years) from 6 representative geographical zones of India were included in the study. The anthropometric indices and sociodemographic characteristics of these women were analyzed. Statistical analysis was performed to assess the association between exposure and outcome variables. RESULTS: Of the 7107 study participants, 3585 (50.44%) were from rural areas and 3522 (49.56%) were from urban areas. The prevalence of obesity increased from 8.1% using World Health Organization criteria to 40% using the revised consensus guidelines for Asian Indian populations. Women from urban areas showed higher proportions of overweight (524/1908, 27.46%), obesity (775/1908, 40.62%), and prehypertension (1008/1908, 52.83%) categories. A rising trend of obesity was observed with an increase in age. Women aged 18 to 23 years were healthy (314/724, 43.4%) and overweight (140/724, 19.3%) compared with women aged 36 to 40 years with obesity (448/911, 49.2%) and overweight (216/911, 23.7%). The proportion of obesity was high among South Indian women, with 49.53% (531/1072) and 66.14% (709/1072), using both World Health Organization criteria and the revised Indian guidelines for BMI, respectively. BMI with waist circumference and waist-to-height ratio had a statistically significant linear relationship (r=0.417; P<.001 and r=0.422; P<.001, respectively). However, the magnitude, or strength, of the association was relatively weak (0.3<|r|<0.5). Statistical analysis showed that the strongest predictors of being overweight or obese were older age, level of education, wealth quintile, and area of residence. CONCLUSIONS: Anthropometric and sociodemographic characteristics are useful predictors of overweight- and obesity-related syndromes, including prehypertension, among healthy Indian women. Increased attention to the health of Indian women from public health experts and policy makers is warranted. The findings of this study can be leveraged to offer valuable insights, informing health decision-making and targeted interventions that mitigate risk factors of overweight, obesity, and hypertension. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/23437.
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Síndrome del Ovario Poliquístico , Prehipertensión , Femenino , Humanos , Sobrepeso , Estudios Transversales , Prevalencia , ObesidadRESUMEN
OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex disorder with diverse metabolic implications. Diagnosis typically relies on oligo-amenorrhoea (OA), hyperandrogenism (HA), and polycystic ovarian morphology (PCOM). However, the role of polymenorrhoea in PCOS remains understudied. Additionally, limited information exists regarding metabolic disturbances in women with partial PCOS phenotypes that do not meet diagnostic criteria. This extensive database aims to provide substantial evidence on the metabolic implications of polymenorrhoea and partial PCOS phenotypes. DESIGN: Prospective observational study. PATIENTS AND MEASUREMENTS: In this single-centre study, 6463 women with PCOS-like characteristics and 3142 age-matched healthy women were included. The study compared clinical (anthropometry, modified Ferriman Gallwey [mFG] score), hormonal (serum testosterone), and metabolic (plasma glucose, serum lipids, insulin) characteristics between women diagnosed with PCOS, those with partial PCOS phenotypes, and the healthy control group RESULTS: In all, 5174 women met Rotterdam criteria for PCOS diagnosis, while 737 were classified as Pre-PCOS, including HA (n = 538), OA (n = 121), or PCOM (n = 78). Common clinical features included oligomenorrhoea (75.5%), hirsutism (82.9%), obesity (27.2%), hypertension (1.6%), metabolic syndrome (19.6%), and diabetes mellitus (5.6%). Women diagnosed with PCOS, HA only, and OA only exhibited higher average body mass index, plasma glucose levels (both fasting and 2 h after the oral glucose tolerance test), and lipid fractions in comparison to those with PCOM and the healthy controls. However, indices of insulin resistance were similar among women with PCOS, HA, PCOM, and OA, albeit higher than in the healthy controls. The polymenorrhoea subgroup (5.9%) had lower BMI and serum testosterone, but similar mFG score, plasma glucose, insulin, and lipid levels as the oligomenorrhoea subgroup. CONCLUSION: The metabolic disturbances observed in Pre-PCOS women highlight the need to reassess diagnostic criteria. Including the polymenorrhoea subcategory in PCOS criteria is recommended due to similar metabolic dysfunctions as the oligomenorrhoea group.
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Hiperandrogenismo , Síndrome del Ovario Poliquístico , Femenino , Humanos , Oligomenorrea , Glucemia , Insulina , Testosterona , LípidosRESUMEN
Background: The hormonal profile varies considerably with age, gender, ethnicity, diet or physiological state of an individual. Limited population-specific studies have studied the variations in hormonal parameters among apparently healthy women. We aimed to analyse the biological reference interval for various hormonal parameters in the reproductive-aged healthy Indian women. Methods: Out of 3877 participants that were clinically evaluated, 1441 subjects were subjected to laboratory investigations. All participants underwent a detailed clinical, biochemical and hormonal profiling. The hormone analysis was carried out at a single centre using a uniform methodology. Among the participants evaluated for biochemical and hormonal parameters, subjects that presented any abnormal profile or had incomplete investigations (n = 593) were excluded for further analysis. Findings: The mean age (±SD) of the subjects retained in the final analysis (n = 848) was 29.9 (±6.3) years. In the present study, the biological reference interval (2.5th-97.5th centile) observed were: serum T4: µg/dL (5.23-12.31), TSH: µg/mL (0.52-4.16) and serum prolactin: ng/mL (5.13-37.35), LH: mIU/mL (2.75-20.68), FSH: mIU/mL 2.59-15.12), serum total testosterone: ng/mL (0.06-0.68), fasting insulin: mIU/mL (1.92-39.72), morning cortisol: µg/dL (4.71-19.64), DHEAS:µg/dL (50.61-342.6) and SHBG: nmol/L (21.37-117.54). Unlike T4, TSH, LH, and E2, the biological reference interval for prolactin, FSH, testosterone, C-peptide insulin and DHEAS varied when the subjects were stratified by age (p < 0.05). The comparative analysis showed marginal differences in the normative ranges for the hormones analysed among different populations. Interpretation: Our first large composite data on hormonal measures will benefit future endeavours to define biological reference intervals in reproductive-aged Indian women. Funding: The study was financially supported by the grant-in-aid from ICMR vide file No:5/7/13337/2015-RBMH.
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Multiple parallel factors are frequently interrogated with various toxic radicals which are abundantly generated in the liver, heart, and pancreas in stress conditions. They are actively involved in the development of diabetes and metabolic aberrations. However, whether over-activation of GDF-15mRNA and influxes of iron-by-iron trafficking genes are directly suppressing the Nrf-2 gene in patients with diabetes and metabolic aberrations in context with undiagnosed individuals with diabetes and metabolic aberrations? Therefore, we have investigated inter and intra- related Zip8/14 mRNA, GDF-15mRNA, and Nrf-2 mRNA expressions in diabetes and metabolic syndrome as it is expected to be up to 134 million by 2045 in India. We recruited 120 subjects from the Department of Medicine, Endocrinology and Metabolic Clinic, All India Institute of Medical Sciences, New Delhi, India. Various investigations related to anthropometry, nutritional, hematological, biochemical, cytokine, and oxidative stress were measured in diabetes, metabolic syndrome, diabetes with metabolic aberration, and healthy controls. Relative expression of GDF-15, ZIP8, ZIP14, Nrf-2, and housekeeping genes was done in all subjects. Stress-responsive cytokines are highly expressed in patients with metabolic aberration with respect to body weight, IR, waist circumference, and fat mass. IL-1ß, TNF-α, and IL-6 levels were significantly higher in metabolic syndrome, whereas Adiponectin levels were profoundly lower side. MDA levels were significantly raised in diabetes with metabolic syndrome while SOD activities were lowered (p = 0.001). GDF-15 mRNA expression was 1.79-fold upregulated in group III as compared with Group I while 2-threefold down-regulation of Nrf-2 expression was observed in diabetes with metabolic aberration groups. Zip 8 mRNA expressions were downregulated (p = 0.014), and Zip 14 mRNA expressions were upregulated (p = 0.06) in diabetes and metabolic aberrations. The association of GDF-15 and Nrf-2 mRNA expression was found contradictory and highly interlinked with ROS. Zip 8/14mRNA expressions were also dysregulated in diabetes and metabolic-associated complications.
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OBJECTIVES: Clinical biochemistry reference intervals (RIs) play a crucial role in interpreting patient test results and making informed clinical decisions. Using data from an ongoing Indian Council of Medical Research-National task force study on healthy women, normative ranges for commonly analyzed biochemical analytes were established. MATERIALS AND METHODS: A.total of 13,181 women of reproductive age (18-40 years) were recruited from different urban and rural regions of the country, of which 9898 women signed an informed consent were included. Among these, women having features of hyperandrogenism, menstrual cycle irregularities, and comorbidities were excluded. RIs of 22 analytes were computed in the remaining 938 women controls. To estimate the 95% range of the reference distribution, the limits of the 2.5th percentile and the 97.5th percentile were used in the study. RESULTS: Mean ± standard deviation of age and body mass index of participants was 30.12 ± 6.32 years and 22.8 ± 3.36 kg/m2 respectively. Centiles (2.5th-97.5th) of liver function parameters, lipid parameters, glycaemic parameters, and renal parameters are presented. No significant difference in analytes was observed in relation to the area of residence, and age groups except in albumin (P = 0.03). The distribution of most of the parameters was consistent with the various RI studies conducted in India as well as other countries. CONCLUSION: This is the first study generating biochemical RIs data among a large representative sample of healthy reproductive-age women recruited using a robust design across the country. The resource may serve as a reference range for common biochemical analytes for future in this age group.
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Investigación Biomédica , Síndrome del Ovario Poliquístico , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , India , Consentimiento Informado , RiñónRESUMEN
The hypoglycemia induced by insulin hypersecretion in congenital hyperinsulinemia (CHI), a rare life-threatening condition can lead to irreversible brain damage in neonates. Inactivating mutations in the genes encoding KATP channel (ABCC8 and KCNJ11) as well as HNF4A, HNF1A, HADH, UCP2, and activating mutations in GLUD1, GCK, and SLC16A1 have been identified as causal. A 3-month-old male infant presenting tonic-clonic seizures and hyperinsulinemia was clinically assessed and subjected to genetic analysis. Besides the index patient, his parents were clinically investigated, and a detailed family history was also recorded. The laboratory investigations and the genetic test results of the parents were compared with the index patient. The biochemical and hormonal profile of the patient confirmed his suffering from CHI and did not respond to diazoxide treatment. The genetic testing revealed that the subject harbored a novel homozygous missense mutation in the KCNJ11 gene, (c.107T>A, p.Val36Glu.). The bioinformatic analysis revealed that valine is highly conserved and predicted that the variant allele (p.Val36Glu) is likely pathogenic and causal for CHI. Parents were heterozygous carriers and did not report any abnormal metabolic profile. Identification of such mutations is critical and likely to change the therapeutic interventions for such patients in the future.
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Hiperinsulinismo Congénito , Humanos , Lactante , Masculino , Hiperinsulinismo Congénito/genética , Hiperinsulinismo Congénito/tratamiento farmacológico , Diazóxido/uso terapéutico , Heterocigoto , Insulina/genética , Mutación , Receptores de Sulfonilureas/genéticaRESUMEN
Thiamine deficiency, commonly presenting as dry and wet beriberi, a lesser-known entity in the present era, is increasingly being reported from Kashmir, a north Indian state. The present study aims to present the clinical profile of patients presenting with high-output heart failure (HOHF). Subjects with a primary diagnosis of denovo heart failure and features suggestive of HOHF were recruited; those who responded to intravenous administration of thiamine alone (responders) were adults with no co-morbidities and those who required other medications particularly diuretics (non-responders) were elderly with co-morbidities and underlying heart disease. Responders showed considerably lower mean thiamine pyrophosphate (TPP) levels and higher mean lactate and venous oxygen saturation than non-responders. More importantly, the mean drop in lactate and SVO2 following thiamine therapy was more in responders. In a setting of high risk for thiamine deficiency, features suggestive of HOHF along with elevated lactate and higher venous oxygen saturation, a response to thiamine challenge may serve as surrogate marker of thiamine deficiency.
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Beriberi , Insuficiencia Cardíaca , Deficiencia de Tiamina , Humanos , Adulto , Anciano , Tiamina/uso terapéutico , Deficiencia de Tiamina/tratamiento farmacológico , Beriberi/tratamiento farmacológico , Beriberi/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Tiamina Pirofosfato/uso terapéuticoRESUMEN
BACKGROUND: Spironolactone use as a treatment for hirsutism and other dermatological conditions among polycystic ovary syndrome (PCOS) and idiopathic hirsutism shows varied results. OBJECTIVE: This study thus summarizes the entire evidence to better define its impact on Ferriman-Gallwey (FG) score in addition to other derangements associated with PCOS. METHODS: PubMed, Embase, Scopus and bibliographies of relevant articles were searched. Randomized controlled trails (RCTs) investigating the efficacy of spironolactone in PCOS and idiopathic hirsutism were included. Pooled mean difference (MD) was calculated using random effects model and relevant subgroup analysis was done. Potential heterogeneity and publication bias was assessed. RESULTS: Of 1041 retrieved studies, 24 RCTs were included. Spironolactone (100 mg/daily) exhibited a significant reduction in FG score in idiopathic hirsutism compared to finasteride (MD: -2.43; 95% C.I: -3.29, -1.57) and cyproterone acetate (MD: -1.18; 95% C.I: -2.10, -0.26), however, no significant difference was found among PCOS subjects in comparison to flutamide and finasteride. A lower dose of spironolactone (50 mg/day) exhibited no significant difference relative to metformin on FG Score (MD: -0.61; 95% C.I: -1.76, 0.54, I2 = 57%), serum total testosterone (MD: -0.61; 95% C.I: -1.76, 0.54), I2 = 57% and HOMA-IR (MD: 1.03; 95% C.I: -1.22, 3.29), I2 = 60% among PCOS women. The main side effects reported by the studies were menstrual irregularity, mild nausea, vomiting and diarrhea. CONCLUSION: Spironolactone is well tolerated among idiopathic hirsute and PCOS women. The drug significantly improved hirsutism in the former group and shows a positive trend in the latter women, however, displays no effect on FSH, LH, menstrual cyclicity, BMI, and HOMA-IR in PCOS women.
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Síndrome del Ovario Poliquístico , Femenino , Humanos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Espironolactona/uso terapéutico , Hirsutismo/tratamiento farmacológico , Finasterida/uso terapéutico , Antagonistas de Andrógenos/uso terapéuticoRESUMEN
Polycystic ovary syndrome (PCOS) is a common multifaceted endocrine disorder among reproductive-aged women. Deranged luteinizing hormone levels and associated downstream signaling cascade mediated by its receptor luteinizing hormone chorionic gonadotropin receptor (LHCGR) are pivotal in the etiopathogenesis of PCOS. Genetic variations in the LHCGR have been associated with PCOS risk. However, the results are mixed and inconclusive. We evaluated the association of the LHCGR rs2293275 polymorphic variant with PCOS risk and its association with clinico-biochemical features of PCOS. 120 confirmed PCOS cases and an equal number of age-matched controls were subjected to clinical, biochemical, and hormonal investigations. Genotyping for rs2293275 was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models were used to calculate odds ratios (ORs) at 95% confidence intervals (95% CIs). In the current study, PCOS cases reported a lower number of menstrual cycles per year than respective controls. A significantly higher BMI, Ferriman Galway score, levels of serum testosterone, insulin, TSH, FSH, and fasting glucose were observed in cases than in controls (p < 0.01). Compared to GG carriers, we observed a higher risk of developing PCOS in the subjects who harbored GA (OR 10.4, p < 0.0001) or AA (OR 7.73, p = 0.02) genotype. The risk persisted in the dominant model (GA + AA) as well (OR 10.29, p = 0.01). On stratification, a higher risk of developing PCOS was observed in variant genotype carriers who had a family history of either type two diabetes mellitus (OR 117; p < 0.0001) or hirsutism (OR 79; p < 0.0001). We also found significantly elevated levels of serum LH levels in the subject harboring GA and AA genotypes when compared to GG carriers. In the present study, we report a significant association of the LHCGR rs2293275 variant with the PCOS risk.
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Síndrome del Ovario Poliquístico , Receptores de HL , Humanos , Femenino , Adulto , Receptores de HL/genética , Síndrome del Ovario Poliquístico/genética , Predisposición Genética a la Enfermedad , Estudios de Casos y Controles , Frecuencia de los Genes , Hormona Luteinizante/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Vitamin D (VD) deficiency (serum 25 hydroxy vitamin D (25(OH)D) concentration of < 20 ng/ml), in endemic proportions, demands a supplementation strategy with optimal dosing regimens. A randomised parallel-group, active-controlled trial was conducted among apparently healthy, VD-deficient subjects, aged 18-60 years who received 600 µg/d (Group A), 1000 µg/d (Group B), 2000 µg/d (Group C) and 60 000 µg/month (Group D) of oral cholecalciferol. The intervention was carried in two phases (I and II) of 12 weeks each, with same dose, separated by a washout phase of 12 weeks. Serum 25(OH)D, intact parathyroid hormones (iPTH), Ca, phosphorous (PO4), alkaline phosphatase (ALP) and spot urine Ca/Cr were measured at baseline, 12, 24 and 36 weeks following the intervention, and adverse events were recorded at each occurrence and at 12, 24 and 36 weeks. A statistically significant time-group interaction was found in serum 25(OH)D concentration (P < 0·05). Serum 25(OH)D concentration increased significantly from baseline to 12 weeks (P < 0·05) in all the groups with no change at 24 weeks but further increase at 36 weeks (P < 0·05). At the end of the study, Group C had maximum increment in serum 25(OH)D concentration, while as Groups C and D (95 %, and 90 %) had higher proportion of subjects VD sufficient than Groups A and B (65 % and 78 %) (P < 0·05). No significant time-dose interactions were observed in serum iPTH, Ca, PO4 and ALP or urine Ca/Cr ratio. Three subjects (two in Group C and one in Group D) developed transient hypercalciuria. Supplementation with daily 2000 µg or monthly 60 000 µg of oral cholecalciferol among adults seems optimal and safe.
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Colecalciferol , Deficiencia de Vitamina D , Adulto , Humanos , Colecalciferol/efectos adversos , Calcio , Vitamina D , Deficiencia de Vitamina D/tratamiento farmacológico , Hormona Paratiroidea , Fosfatasa Alcalina , Suplementos DietéticosRESUMEN
Background/Objective. We present a case of Langerhans cell histiocytosis (LCH) with gastrointestinal involvement masquerading as inflammatory bowel disease (IBD) in a patient who initially had features of central diabetes insipidus (CDI). Case Report. A 19-year-old male presented at 14 years of age with central diabetes insipidus. He subsequently developed panhypopituitarism and sellar-suprasellar mass, the biopsy of which was inconclusive. Secondary causes for hypophysitis were ruled out. Five years later, he developed perianal pus discharging sinuses, positive ASCA, and sacroiliitis. Rectal ulcer biopsy showed nonspecific inflammation and necrosis. Hence, he was managed as inflammatory bowel disease (IBD). Due to nonresponsiveness of symptoms, doubt about diagnosis was invoked and rectal ulcer biopsy was repeated, which then showed infiltration by Langerhans cells. Hence, he was diagnosed with LCH and showed resolution of symptoms on initiating steroids and vinblastine. Discussion. Gastrointestinal involvement by LCH is unusual and only rarely has represented a prominent clinical manifestation. In most cases, such involvement suggests widespread multisystem disease. Its distinctive morphologic and immunohistochemical features allow LCH to be distinguished from other inflammatory infiltrations found in mucosal biopsy specimens. Conclusion. Preceding CDI and hypopituitarism may predict LCH in patients with IBD-like diseases.
RESUMEN
OBJECTIVES: Although beriberi is considered a forgotten disease in the West, Kashmir has a rice-eating population that has beriberi in endemic proportions. Patients with a thiamine deficiency (TD) occasionally present with gastrointestinal (GI) symptoms, including nausea, recurrent vomiting, loss of appetite, and abdominal discomfort. Together these often respond to thiamine, which points to gastric beriberi. METHODS: Patients with GI symptoms suggestive of TD were recruited from the Department of Medicine at the Government Medical College and its associated hospital, SMHS, in Srinagar, India. Patients were evaluated for serum thiamine levels, serum lactate, biochemical parameters, and transabdominal ultrasonography after ruling out the usual causes of acute abdominal pain and vomiting. RESULTS: A total of 27 patients were recruited with a mean age of 47.28 ± 20.84 y. The mean lactate of patients at the time of admission was 6.43 ± 5.22 mmol/L, and the mean lactate at the time of discharge was 1.23 ± 0.50 mmol/L. All patients had a history of consuming polished rice, washed two to three times before cooking, as the staple diet. The most common GI symptoms were recurrent vomiting, nausea, and loss of appetite. All of the patients responded to the thiamine treatment, and showed improvement in their GI symptoms and decreased serum lactate levels within 2 to 6 h of their hospital stay. CONCLUSIONS: Gastric beriberi is a rare presentation of TD that can lead to severe GI symptoms and lactic acidosis. Given the rapid response to thiamine, it is the standard-of-care treatment in such cases. Thus, clinicians should suspect TD when patients present with either mild or moderate-to-severe GI symptoms and raised blood lactate.
Asunto(s)
Beriberi , Enfermedades Gastrointestinales , Deficiencia de Tiamina , Adulto , Anciano , Beriberi/diagnóstico , Beriberi/tratamiento farmacológico , Beriberi/etiología , Enfermedades Gastrointestinales/tratamiento farmacológico , Enfermedades Gastrointestinales/etiología , Humanos , Ácido Láctico , Persona de Mediana Edad , Náusea/etiología , Tiamina/uso terapéutico , Deficiencia de Tiamina/complicaciones , Deficiencia de Tiamina/tratamiento farmacológico , Vómitos/etiologíaRESUMEN
Purpose: TCF7L2 mediated Wnt signaling cascade regulates glucose homeostasis by orchestrating expression, processing, and hepatic clearance of insulin. Type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome (PCOS) significantly overlap in pathophysiological features with insulin resistance as a central driver. While TCF7L2 is the most potent T2DM locus, studies on the association of TCF7L2 with PCOS are limited and inconclusive. Therefore, in addition to expression profiling, the association of TCF7L2 polymorphic variant rs7903146 with PCOS was evaluated. Methods: Using Rotterdam-2003 criteria for the diagnosis, 120 PCOS cases, and 120 age-matched controls were recruited. Subjects underwent clinical, biochemical, and hormonal assessment, followed by genotyping for rs7903146, carried out by PCR-RFLP and TCFL2 expression profiling by qRT-PCR. Genotype-phenotype correlation analysis was performed to evaluate any such associations. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were computed by conditional logistic regression. Results: Higher odds of developing PCOS were observed in the women having a family history (FH) of either T2DM (OR = 3.86, 95% CI:1.90 - 7.83), hirsutism (OR = 4.74. 95%CI: 1.91 - 17.21) or menstrual irregularities (MI) (OR = 3.07, 95%CI: 1.61 - 8.54). The genotypes of rs7903146 did not confer any risk for developing PCOS (OR = 0.46;95%CI: 0.15 - 2.03). However, the elevated risk was seen in the subjects who harbored the variant allele and had FH of either T2DM (OR = 6.71; 95%CI: 1.89 - 23.78) or MI (OR = 9.71; 95% CI:1.89 - 23.78). Conclusion: TCF7L2 polymorphic variant rs7903146 is not independently linked to PCOS risk, but modulates the risk in the subjects having a family history of either T2DM or MI. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01050-y.