Public Health System's Preparedness to Address Polycystic Ovarian Syndrome: A Rapid Assessment Survey of Health-care Providers in India.

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.

Prevalence, Regional Variations, and Predictors of Overweight, Obesity, and Hypertension Among Healthy Reproductive-Age Indian Women: Nationwide Cross-Sectional Polycystic Ovary Syndrome Task Force Study.

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.

Normative range of various serum hormonal parameters among Indian women of reproductive age: ICMR-PCOS task force study outcome.

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.

Evaluation of the Prevalence, Regional Phenotypic Variation, Comorbidities, Risk Factors, and Variations in Response to Different Therapeutic Modalities Among Indian Women: Proposal for the Indian Council of Medical Research-Polycystic Ovary Syndrome (ICMR-PCOS) Study.

BACKGROUND: There is scanty data in India on polycystic ovary syndrome (PCOS) from several small, undersized, convenience-based studies employing differing diagnostic criteria and reporting varied regional prevalence. It is difficult to draw clear-cut conclusions from these studies; therefore, the present multicentric, well-designed, large-scale representative countrywide epidemiological study on PCOS across India was conceived with the aim to generate the actual prevalence rates of PCOS in India with a total sample size of approximately 9000 individuals. OBJECTIVE: The primary objectives of the study are to estimate the national prevalence of PCOS in India and the burden of comorbidities and to compare the variation in efficacy of standard therapeutic modalities for metabolic dysfunction in women with PCOS. METHODS: This multicentric umbrella study consists of three different substudies. Substudy 1 will involve recruitment of women aged 18-40 years using a multistage sampling technique from randomly selected polling booths across urban and rural areas to estimate national prevalence, phenotypic variation, and risk factors among regions. Substudy 2 involves recruitment of subjects from the community pool of substudy 1 and the institutional pool for quantitation of comorbidities among women with PCOS. Substudy 3, an interventional part of the study, aims for comparison of variation in efficacies of common treatment modalities and will be conducted only at 2 centers. The eligible consenting women will be randomized in a 1:1 ratio into 2 arms through a blinding procedure. All these women will undergo clinical, biochemical, and hormonal assessment at baseline and at 3 and 6 months. The data generated will be analyzed using the reliable statistical software SPSS (version 26). RESULTS: The study is ongoing and is likely to be completed by April 2022. The data will be compiled and analyzed, and the results of the study will be disseminated through publications. CONCLUSIONS: The Indian Council of Medical Research-PCOS study is the first of its kind attempting to provide accurate and comprehensive data on prevalence of PCOS in India. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2018/11/016252; ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=26366. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23437.

Lipid Profile in Indian Patients With Type 2 Diabetes: The Scope for Atherosclerotic Cardiovascular Disease Risk Reduction.

OBJECTIVE: Reduction of atherosclerotic cardiovascular disease (ASCVD) risk in patients with diabetes requires proper management of lipid parameters. This study aimed to find the pattern of dyslipidemia and scope of ASCVD risk reduction in patients with diabetes by lipid management. METHODS: Clinical, biochemical, and medication profiles of all patients with diabetes attending a tertiary diabetes care hospital over a 2-year period were collected. The prevalence of various lipid abnormalities was determined after excluding patients with thyroid dysfunction and those on lipid-lowering medications. Patients were stratified according to LDL cholesterol, HDL cholesterol, and triglyceride levels, and other clinical parameters were compared among the groups. The adequacy of statin treatment was assessed based on American Diabetes Association guidelines. RESULTS: Nine hundred and seventy-one patients were included. The prevalence of hyperlipidemia was 40.0%, of whom 14.6% were newly diagnosed. The most common lipid abnormality was elevated LDL cholesterol. Higher A1C and fasting blood glucose values were found to be associated with higher LDL cholesterol levels. Twenty-seven percent of patients with indications for treatment with statins were receiving them. Of those being treated with statins, 42.6% had an LDL cholesterol level ≥100 mg/dL. CONCLUSION: In South Indian patients with type 2 diabetes and fair glycemic control, high LDL cholesterol is the predominant lipid abnormality. There remains a huge potential for ASCVD risk reduction in this population if the knowledge practice gap is addressed.

Long-acting porcine ACTH stimulated salivary cortisol in the diagnosis of adrenal insufficiency.

BACKGROUND: Synacthen stimulated salivary cortisol has been previously evaluated and found beneficial in the diagnosis of adrenal insufficiency (AI), especially in situations with altered cortisol-binding protein (CBG) levels. Unfortunately, Synacthen is not marketed in many parts of the world whereas porcine sequence corticotrophin (Acton Prolongatum) is readily available. This study aimed to find the diagnostic accuracy of Acton prolongatum stimulated salivary cortisol test (APSST) compared to the short synacthen test (SST). METHODS: Consecutive outpatients with suspected AI underwent SST initially, followed by APSST after 3 days. For APSST, saliva was collected at 0, 60 and 120 minutes after administering 30 units Acton Prolongatum intramuscularly. Serum and salivary cortisol were estimated using electrochemiluminescence assay. (Cobas e 411, Elecsys Cortisol II kits) RESULTS: Sixty-seven patients with clinically suspected AI were enrolled for the study. Based on SST, 35 patients were classified as having AI [primary AI (n=19) and secondary AI (n=16)] whereas 32 had normal glucocorticoid reserve. The area under receiver operator curve of 0.99 and 0.98 was observed for salivary cortisol values at 60 and 120 minutes, respectively, for APSST. A cut-off value of 18.5 nmol/L (0.67 µg/dL) and 29.3 nmol/L (1.06 µg/dL) at 60 and 120 minutes, respectively, had a sensitivity as well as specificity of 93%-100% in diagnosing AI. CONCLUSION: Salivary cortisol estimation following stimulation using intramuscular porcine ACTH (Adrenocorticotrophic hormone) (30 units) is an economical and accurate alternative to SST in the diagnosis of AI, m and its level of 30 nmol/L or more at 2 hours confirms adrenal sufficiency.

Late-Night Salivary Cortisol in Healthy, Community-Dwelling Asian Indians Assessed by Second-Generation ECLIA.

BACKGROUND: Late-night salivary cortisol (LNSC) is used as a screening test for Cushing syndrome (CS), but there is no community-derived normative data for the normal upper limit in the South Asian population. This study aimed to determine the upper limit of normal (97.5th percentile) for LNSC in an Asian Indian population using a commercially available second-generation electrochemiluminiscence immunoassay (ECLIA). METHODS: LNSC in apparently healthy community-dwelling individuals was assessed by multistage cluster sampling. Healthy individuals age 18 to 60 years from 8 urban and 8 rural clusters of Thiruvananthapuram district were studied. Thirty people from an approximate population of 1000 individuals from each cluster participated in the study. A saliva sample was collected between 11 PM and 12 midnight and analyzed using Roche COBAS-e-411 and ultrasensitive Cortisol II kits the next day. RESULTS: Cortisol values from 474 salivary samples were available for final analysis after exclusion of improperly collected samples. The 97.5th percentile of the LNSC concentrations was 0.25 µg/dL (6.89 nmol/L) (90% CI, 0.23-0.27 µg/dL; ie, 6.34-7.45 nmol/L). In postmenopausal women, median LNSC was significantly higher but the 90% CI for the upper limit of their LNSC (0.28µg/dL or 7.72 nmol/L) overlapped with that of premenopausal women. CONCLUSIONS: This study establishes the normal value of LNSC estimated by second-generation ECLIA in healthy community-dwelling Asian Indian individuals for the first time. Salivary cortisol at 11 pm to 12 am is less than 0.25µg/dL (6.89 nmol/L) in the general Asian Indian population. Menopause causes a significant increase in LNSC and may lead to overdiagnosis of CS if not interpreted carefully.

Slipped Capital Femoral Epiphysis in Primary Hyperparathyroidism - Case Report with Literature Review.

Primary hyperparathyroidism is not common in children and adolescents. Association of slipped capital femoral epiphysis and hyperparathyroidism is rare. We report the case of a 15-year-old boy who presented with pain in both hips and limping. He was diagnosed to have bilateral slipped capital femoral epiphysis (SCFE) and underwent cancellous screw fixation of both hips. He had proximal myopathy and pain at multiple points over the chest. Examination revealed an emaciated patient with genu valgum, rachitic rosary, Harrison's sulcus, and bony tenderness over the ribs. Investigations showed PTH-dependent hypercalcemia with serum calcium levels reaching >17 mg/dL and electrocardiography showing QTc shortening. Imaging revealed parathyroid adenoma. The work up for multiple endocrine neoplasia syndromes (MEN) was negative. Serum calcium was controlled by medical management and patient underwent expedited surgery. Postoperatively serum calcium levels normalized and patient became better biochemically and clinically including resolution of skeletal changes on follow-up. Only 12 cases of SCFE associated with primary hyperparathyroidism have been reported worldwide till date including the current case. The literature has been reviewed and it indicates that SCFE is associated with late adolescent age and severe hyperparathyroidism (severe bone disease, higher parathormone, serum calcium, and alkaline phosphatase levels).

Long acting porcine sequence ACTH in the diagnosis of adrenal insufficiency.

OBJECTIVES: Injectable tetracosactide hexa-acetate, ACTH 1-24 (Synacthen), is not marketed in many countries including India, whereas Injectable long acting porcine sequence, ACTH 1-39 (Acton Prolongatum®) is easily available and much cheaper. This study aimed to find the diagnostic accuracy of ACTH stimulation test using i.m. Acton Prolongatum® (acton prolongatum stimulation test, APST) in comparison with Synacthen (short synacthen test, SST) for the diagnosis of glucocorticoid insufficiency. METHODS: Subjects with a suspicion of adrenal insufficiency based on clinical features underwent a SST with 250 µg Synacthen followed by APST using 30 units of Acton Prolongatum®. Serum cortisol levels were measured at 60 and 120 min following injection of Acton Prolongatum®. Stimulated peak cortisol of less than 18 µg/dL on SST was considered as adrenal insufficiency. RESULTS: Forty seven patients with mean age of 36.7 ± 14.4 years were enrolled for the study. Based on SST, twenty (n = 20) persons were classified as having adrenal insufficiency, whereas twenty-seven (n = 27) were found to be normal. Area under the curve of APST (at 120 min) was 0.986 when compared to SST, thus proving its high accuracy. A serum cortisol cut off value of 19.5 µg/dL at 120-min following stimulation with Acton Prolongatum® showed a sensitivity of 100% and specificity of 88%. CONCLUSION: ACTH stimulation test using Acton Prolongatum® is an economical and accurate alternative to the short Synacthen test.

Peptide Receptor Radionuclide and Octreotide: A Novel Approach for Metastatic Tumor-Induced Osteomalacia.

KEY MESSAGES: Octreotide can be used as an adjunctive therapy to increase phosphorus levels in patients with tumor-induced osteomalacia. Malignant phosphaturic mesenchymal tumor (PMT) may benefit from treatment with peptide receptor radionucleotide therapy. CONTEXT: The success of treatment modalities for malignant PMT is limited. Octreotide has been used to treat hypophosphatemia in patients with tumor-induced osteomalacia with equivocal results. To our knowledge, there are no reports of octreotide or peptide receptor radionuclide therapy use for malignant PMT. CASE DESCRIPTION: We report a 40-year-old man having hypophosphatemia, phosphaturia (tubular maximum of phosphorus corrected for glomerular filtration rate of <2.5 mg/dL), and somatostatin avid lesions in the right foot region with metastasis to both lungs. The patient had been subjected to resection of the primary tumor from the foot with thoracoscopic removal of the lung secondaries. Histology from all three lesions showed a spindle cell soft tissue tumor with a high mitotic index and somatostatin receptor 2 and 5 positivity. A trial of subcutaneous octreotide therapy at a dose of 100 µg thrice daily resulted in an increase in serum phosphorus levels from an average of 1.44 mg/dL to an average of 2.3 mg/dL. Finally, the affected limb was amputated, and the hypophosphatemia persisted postoperatively. In view of persistent hypophosphatemia and transient response to octreotide, the patient was administered four cycles of peptide receptor radionuclide therapy using 177Lutetium, which showed moderate improvement of serum phosphorus levels. CONCLUSION: Although octreotide use has been reported in four patients with benign PMT, to our knowledge, this is the first case of malignant PMT that has used peptide receptor radionuclide therapy in the treatment of malignant PMT. This moderately beneficial evidence is likely to guide the future use of radionuclide treatments in such tumors.