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.

E41K Mutation Activates Bruton's Tyrosine Kinase by Stabilizing an Inositol Hexakisphosphate dependent Invisible Dimer.

Bruton's tyrosine kinase (BTK) regulates diverse cellular signaling of the innate and adaptive immune system in response to microbial pathogens. Downregulation or constitutive activation of BTK is reported in patients with autoimmune diseases or various B-cell leukemias. BTK is a multidomain protein tyrosine kinase that adopts an Src-like autoinhibited conformation maintained by the interaction between the kinase and PH-TH domains. The PH-TH domain plays a central role in regulating BTK function. BTK is activated by binding to PIP3 at the plasma membrane upon stimulation by the B-cell receptor (BCR). The PIP3 binding allows dimerization of the PH-TH domain and subsequent transphosphorylation of the activation loop. Alternatively, a recent study shows that the multivalent T-cell-independent (TI) antigen induces BCR response by activating BTK independently of PIP3 binding. It was proposed that a transiently stable IP6-dependent PH-TH dimer may activate BTK during BCR activation by the TI antigens. However, no IP6-dependent PH-TH dimer has been identified yet. Here, we investigated a constitutively active PH-TH mutant (E41K) to determine if the elusive IP6-dependent PH-TH dimer exists. We showed that the constitutively active E41K mutation activates BTK by stabilizing the IP6-dependent PH-TH dimer. We observed that a downregulating mutation in the PH-TH domain (R28H) linked to X-linked agammaglobulinemia impairs BTK activation at the membrane and in the cytosol by preventing PH-TH dimerization. We conclude that the IP6 dynamically remodels the BTK active fraction between the membrane and cytoplasm. Stimulating with IP6 increases the cytosolic fraction of the activated BTK.

Common Hematological Reference Indices Among Healthy Reproductive Age Indian Women-Data Subset from Nationwide Study.

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.

Insulin Access Enhancement in India: Expert Views on Integrating Interchangeable Biosimilar Insulin Glargine.

Achieving and maintaining optimal glycemic targets is the fundamental goal of the management of diabetes. However, failure of oral antidiabetic drugs (OADs) to sustain the targeted glycemic levels in individuals with progressing disease often requires initiation of insulin therapy. This article consolidates the expert opinions of 377 doctors who participated in 34 advisory board meetings held digitally (n=23) and in person (n=11) across India. The present report underscores the need for readily available alternatives, such as biosimilar insulins, in the Indian healthcare market to make insulin accessible to every patient with diabetes. The introduction of biosimilar insulins in the Indian healthcare market is the key to making insulin accessible to every patient with diabetes. Biosimilars are biologic products that closely resemble reference/originator biologics and demonstrate no clinically meaningful differences in safety and effectiveness. The concept of interchangeability serves as a pivotal differentiator for biosimilars, underlining their reliability and safety, and plays a significant role in their broader acceptance and integration into healthcare systems. The 'interchangeability' designation by the United States Food and Drug Administration (USFDA) elevates the biosimilar concept, promoting faster and broader adoption of insulin biosimilars, especially benefiting patients prone to non-adherence to insulin therapy. Healthcare providers are encouraged to consider the option of initiating or transitioning to biosimilar insulin glargine to address the insulin accessibility challenges.

Etiology and Biochemical Profile of Rickets in Tertiary Care Centres in Eastern India: A Retrospective Cross-sectional Study.

Introduction: We aimed to describe the clinical, biochemical and etiological profile of patients referred with a provisional diagnosis of rickets in tertiary care centres. In addition, we tried to propose a diagnostic algorithm for the evaluation of such patients. Methods: This was a retrospective cross-sectional study conducted in two tertiary care centres of West Bengal. Data of patients were retrieved between 2014 and 2021. Results: Out of 101 children, 22 had conditions simulating rickets. Renal tubular acidosis (RTA) was the most common (53.2%) etiology of rickets, followed by phosphopenic rickets (PR) (22.8%) and calcipenic rickets (CR) (17.7%). The prevalence of true nutritional rickets (NR) was only 8.9%. Children with RTA had a significantly higher prevalence of chronic ill health (69%) and polyuria (95.2%). Weight standard deviation score (SDS) and body mass index (BMI) SDS scores were significantly lower in the RTA group compared to others. Around 90.5% of children with RTA, and none in the other groups, had hypokalemia. Biochemically, hypophosphatemia and elevated alkaline phosphatase (ALP) were present in all patients with PR and CR. Compared to CR, median serum phosphate was significantly lower in the PR group. A significant difference in ALP values was noticed in patients with hypophosphatemia (815 ± 627 IU/L) compared to those without (279 ± 204 IU/L). Plasma parathyroid hormone (PTH) of 100 pg/ml seemed useful to differentiate CR from other forms. Conclusion: NR is uncommon in tertiary care centres. Children with rickets should be approached systematically with the estimation of ALP, phosphorus, creatinine, calcium, PTH and 25-hydroxy vitamin D to reach an etiological diagnosis.

Variable presentation and outcomes of primary hyperparathyroidism in children and adolescents.

OBJECTIVES: Primary hyperparathyroidism (PHPT) in paediatric and adolescent age group presents with some unique challenges for clinicians. While the disease in the adult counterparts presents with symptoms which are described quite extensively in literature, children/adolescents have manifestations which are quite different and severe compared to the former. The present case series aimed to highlight the peculiarities of presentation of PHPT in children and adolescents. CASE PRESENTATION: In this case series, we present experience of 5 cases of PHPT in children and adolescents from our centre. We compared our data with the data already available in literature. We have also described salient presenting features of PHPT in individuals less than 19 years old previously reported in literature and pointed out the specificities of this disease at this age group. CONCLUSIONS: PHPT in children and adolescents should be considered as a separate entity compared to that in adults, given its unique features, such as rachitic features, and severity of different presenting phenotypes. Persistence of rachitic features despite vitamin D correction, pancreatitis, bilateral nephrolithiasis and otherwise unexplained psychiatric abnormalities of insidious onset require greater clinical vigilance and serum/urine calcium testing to rule out this uncommon yet possible entity.

Serum BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) levels in the first trimester may predict the future development of gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a prevalent condition with an unclear pathogenesis. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are potential key players in GDM. PARTICIPANTS, MATERIALS, AND METHODS: In a longitudinal observational study, we monitored women from the first trimester through 24-28 weeks of gestation, focusing on the development of GDM. Serum levels of BAFF and APRIL, as well as their mRNA expression, were evaluated in both the first and third trimesters. Furthermore, we assessed cytokines, adipokines, and placental hormones in the serum. RESULTS: In the first trimester, participants who later developed GDM exhibited elevated serum BAFF and reduced serum APRIL levels, although the mRNA expression of these molecules was similar to controls. Serum BAFF exhibited significant positive correlations with metabolic markers and placental hormones. Conversely, serum APRIL was negatively correlated with insulin resistance and inflammatory markers but positively correlated with adiponectin. In the early third trimester, GDM participants continued to display higher serum BAFF levels and lower serum APRIL levels than controls. There was no significant difference in mRNA expression of BAFF between GDM and control groups. Conversely, APRIL mRNA expression was significantly lower in the GDM group. The predictive potential of first-trimester BAFF and APRIL levels for future GDM development was explored, with both molecules demonstrating strong predictive capability. DISCUSSION AND CONCLUSION: This study suggests that elevated serum BAFF and reduced serum APRIL levels during pregnancy may be associated with the development of GDM. These biomarkers can serve as potential early predictors for GDM.

Heterophilic Interference of Rheumatoid Factor in TSH Immunometric Assay: A Cross-Sectional Observational Study.

Introduction: Considering the inherent vulnerability of immunoassays for heterophilic interference and the potential of Rheumatoid Factor (RF) to act as a heterophile-like antibody, we conducted this study to investigate if RF leads to any such heterophilic interference in seropositive rheumatoid arthritis (RA) patients. The study was done on the TSH assay as it is a noncompetitive, double antibody sandwich assay, which is known to be vulnerable to heterophilic interference. Methods: In this cross-sectional observational study, eighty-four consecutive newly diagnosed RF-positive RA patients underwent TSH, Free T4, and anti-TPO estimation using the chemiluminescence technique (CLIA) on Siemens Immulite 1000 platform. The samples were screened for TSH interference using four methods: 1) analysis on a different platform, 2) assessment of linearity using doubling dilutions, 3) polyethylene glycol (PEG) precipitation, and 4) addition of a commercial blocker. Results: Ten samples had a loss of linearity on serial dilution, indicating potential interference. After heterophile blocker treatment, five cases exhibited interference. One patient had diagnostic interpretation discordance on the second platform. No sample on PEG precipitation suggested the influence of antibodies. It is worth noting that even in cases where interference was suspected, the clinical interpretation was largely unaffected by the correction of TSH values based on mean dilution or measurement after heterophile blocker treatment. Conclusion: RF can cause heterophilic interference in TSH immunoassays used commercially. However, in most cases, this interference does not affect clinical decision-making.

Toe brachial index and not ankle brachial index is appropriate in initial evaluation of peripheral arterial disease in type 2 diabetes.

BACKGROUND: Non-invasive clinic-based tools for assessing PAD are not without limitations. Therefore, costly tests like Doppler study, CT angiography and MR angiography are often required to make a diagnosis. Ankle brachial index (ABI), commonly used for assessment of PAD, has high false positivity rates in sclerosed, calcified arteries which render them non-compressible. Toe brachial index (TBI) can be an alternative, as digital arteries are relatively unaffected by these changes. AIM: To compare the reliability of ABI and TBI in diagnosing PAD in type 2 diabetes using CT angiography (CTA) as the reference. METHODS: 175 adults with T2D were selected. ABI &TBI were measured with an automated vascular Doppler XT 6 ports bilaterally for all subjects. For any subject, the limb with lower ABI and TBI was included for analysis. ABI < 0.9 & TBI < 0.6 were taken as evidence of PAD. CTA showing > 50% narrowing was taken as evidence of PAD. RESULTS: 24% of our study subjects had CTA confirmed PAD. ABI has low sensitivity of 35.29% (95% CI 0.21-0.52) compared to TBI being 82.35% (95% CI 0.66-0.92). The specificity however was similar. ABI < 0.9 was able to detect CTA confirmed PAD, but ABI > 0.9, including the so-called normal ABI (0.9-1.3) was unable to detect PAD. ROC showed ABI at 1.005 has sensitivity 64.71% (95% CI 0.48- 0.79) and specificity 61.7% (95% CI 0.53-0.69) and TBI at 0.6 has sensitivity 82.35% (95% CI 0.66-0.92) & specificity 92% (95% CI 0.87-0.96). Utilizing Cohen's Kappa, the reliability of ABI with respect to CTA showed fair agreement (K = 0.225, p = 0.001), whereas the reliability of TBI with respect to CTA showed substantial agreement (K = 0.759, p < 0.0001). CONCLUSION: ABI < 0.9 detects PAD reliably, but presence of PAD in patients with ABI > 9.0 including the normal of ABI (0.9-1.3) can be confirmed with TBI, which correlated strongly with CTA. TBI is also non-inferior for PAD detection, when ABI < 0.9. TBI and not ABI can be utilized for initial assessment of PAD in subjects with T2D.

Association of common variants of TCF7L2 and PCSK2 with gestational diabetes mellitus in West Bengal, India.

The genetic etiology of gestational diabetes mellitus (GDM) was suggested to overlap with type-2 diabetes(T2D). Transcription factor 7-like 2 (TCF7L2) and Proprotein Convertase Subtilisin/Kexin type 2 (PCSK2) are T2D susceptibility genes of the insulin synthesis/processing pathway. We analyzed associations of TCF7L2 and PCSK2 variants with GDM risk and evaluated their potential impact on impaired insulin processing in an eastern Indian population. The study included 114 GDM (case) and 228 non-GDM pregnant women (control). rs7903146, rs4132670, rs12255372 of TCF7L2, and rs2269023 of PCSK2 were genotyped by PCR-RFLP, and genotype distributions were compared between case and control. Fasting serum proinsulin and C-peptide levels were measured by ELISA and the Proinsulin/C-peptide ratio was considered an indicator of proinsulin conversion. Significantly higher frequency of risk allele (T) of rs12255372 (p = 0.02, OR = 2.0, 95%CI = 1.11-3.64) and rs4132670 (p = 0.002, OR = 2.26, 95%CI = 1.32-3.87) of TCF7L2 was found in GDM cases than non-GDM controls; TT genotype was associated with significantly increased disease risk. In rs7903146 (TCF7L2) and rs2269023 (PCSK2), although the frequency of risk allele (T) was not significantly higher in cases than controls, an association of TT for both variants remained significant with higher GDM risk in the recessive model. Increased serum pro-insulin and proinsulin:c-peptide ratio was found in GDM than non-GDM women and the phenomenon showed significant association with careers of risk alleles for TCF7L2 variants. In conclusion, TCF7L2 and PCSK2 variants are related to GDM risk in the studied population and hence may serve as potential biomarkers for assessing the disease risk. TCF7L2 variants contribute to impaired insulin processing.

Growth hormone therapy is associated with improved uterine dimensions in girls with Turner syndrome prior to oestrogen replacement.

BACKGROUND: Adult women with Turner syndrome (TS) have high rates of miscarriage, presumably due to the abnormal size and shape of the uterus. There is a paucity of data regarding the determinants of uterine volume (UtVol) in young girls with TS before the initiation of oestrogen replacement therapy (ERT). METHODS: We performed a cross-sectional study on premenarchal girls with TS, aged 5-15 years, pubertal stage B1-B3, not having received ERT (n = 73) and 50 age-matched healthy controls. Anthropometric parameters and a history of growth hormone (GH) therapy (≥1 year) were noted. Uterine length (UtL), UtVol, and mean-ovarian-volume (MOV) standard-deviation scores (SDS) were determined from transabdominal ultrasonography data. RESULTS: Girls with TS had lower median UtVol-SDS (-1.07 vs. 0.86; p < .001), UtL-SDS (-3.72 vs. -0.41; p < .001) and MOV-SDS (-5.53 vs. 1.96; p < .001) compared to age-matched controls. Among TS girls, recipients of GH (n = 38) had higher UtVol-SDS (-0.63 vs. -1.39; p = .0001), UtL-SDS (-1.73 vs. -6.49; p < .0001) but similar MOV-SDS compared to nonrecipients (n = 35). Those with normal uterine volume for age (NUVA, n = 29) had earlier initiation (7.8 vs. 9.3 years; p = .03) and a longer duration of GH (3.71 vs. 2.14 years; p = .002) than those with low UtVol for age (n = 44). UtVol-SDS correlated with duration of GH (ρ = 0.411, p = .01) and negatively with age at GH initiation (ρ = -0.479, p = .003). In a model adjusted for pubertal status, karyotype and height-SDS, GH use could independently predict having NUVA (odds ratio: 5.09, confidence interval: 1.63-15.94, p = .005). CONCLUSION: GH therapy has a stimulatory effect on uterine dimensions in pre-and peripubertal girls with TS. Earlier initiation and longer duration of GH is important in TS girls before ERT.

Renal Dysfunction in Primary Hyperparathyroidism is associated with nephrolithiasis, elevated serum calcium-phosphate product and parathormone levels.

PURPOSE: Baseline renal dysfunction predicts mortality in primary hyperparathyroidism (PHPT). However, it remains controversial whether renal insufficiency in PHPT is due to disease severity alone or other risk factors. This study aimed to explore the association of clinico-biochemical variables with renal dysfunction [estimated glomerular filtration rate (eGFR) < 60 ml/min/m2] in PHPT. METHODS: A total of 112 patients of PHPT were selected and divided into following subgroups: renal dysfunction (n = 28) and normal renal function (n = 84). Demographic characteristics, traditional risk factors, phenotypes of PHPT based on target organ involvement, and biochemical parameters were compared between these subgroups. RESULTS: Patient subgroups of PHPT with and without renal dysfunction had similar age, frequency of diabetes, and hypertension. Renal dysfunction was more prevalent in males (p < 0.05). Compared to normal renal function subgroup, individuals with renal dysfunction had higher serum levels of calcium, phosphate, alkaline phosphatase, intact parathormone (all p < 0.05), while having lower hemoglobin levels (p < 0.05) and higher nephrolithiasis rates (p < 0.05). Multiple regression analysis revealed that nephrolithiasis, serum calcium-phosphorous product (CaxP), parathormone levels were positively associated with baseline renal dysfunction (all p < 0.01). A baseline PTH > 456 pg/mL and CaxP > 30.0 mg2/dl2 could discriminate renal dysfunction from normal renal function with sensitivity and specificity of 75% and 74.5% and 92.6% and 74.4%, respectively. CONCLUSION: Renal dysfunction was associated with presence of nephrolithiasis, elevated serum CaxP and PTH levels in our cohort with predominantly symptomatic PHPT, indicating an association with the underlying disease itself. Serum CaxP may additionally be appraised during risk assessment in PHPT.

Association of adipocyte size and SREBP-1c in visceral and subcutaneous adipose tissue in non-obese type 2 diabetes mellitus.

OBJECTIVE: Non-obese type 2 diabetes seems to be common in India; hence the current study tried to understand the pathogenesis of diabetes in this group focusing on the role of adipocytes especially abdominal fat compartment. Comparison was made between non-obese subjects with newly detected diabetes and those without diabetes, in relation to levels of adipogenic factor and adipokines in pre-adipocytes and mature adipocytes respectively. RESEARCH DESIGN METHODS: Non-obese subjects (BMI-18-25 Kg/m2) were consecutively selected of whom 15 had newly-detected, treatment naïve type 2 diabetes (HbA1% ≥6.5) while 25 were control (HbA1c% ≤5.6). We examined the expression of adipocyte differentiation factor - SREBP-1c from preadipocytes and adipocyte specific adipokines- HMW isoform and total adiponectin, leptin, FABP-4, TNF-α and IL-6 from adipocytesisolated from abdominal visceral and subcutaneous adipose tissues (VAT and SCAT) by RT-PCR and as well as from serum by ELISA. Size of cultured adipocytes was measured in a fully automated imaging system microscope. RESULT: Both in SCAT and VAT, SREBP-1c and adiponectin had significantly lower expression along with increased mRNA level of inflammatory adipokinesdiabetes.Average adipocyte size and frequency of large(hypertrophied) adipocytes were comparatively higher in T2DM subjects and had significant negative correlation with SREBP-1c. HMW adiponectin level significantly reduced in the secretion from VAT and SCAT of T2DM subjects compared to control. CONCLUSION: Reduced expression of SREBP-1c in preadipocytes may lead to increased number of hypertrophied adipocytes in T2DM. Therefore, these dysfunctional hypertrophied adipocytes could cause imbalanced expression of insulin resistant and insulin sensitive adipokines.

Cytological findings of phosphaturic mesenchymal tumor: Report of a case with summary of prior published cases.

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm causing tumor-induced osteomalacia (TIO) and is characterized by secretion of FGF23, renal phosphate wasting and hypophosphataemia. It can be completely cured by resection and therefore its diagnosis is of utmost importance. Although the histology is well described, there is sparse literature on cytology of PMT and only three cases have been described so far. A 45-year-old lady presented with a non-tender mass in hard palate for 2 years from which fine-needle aspiration was done. The smears were paucicellular and showed bland spindle cells embedded in osteoid-like stromal matrix in a hemorrhagic background. Here we take the opportunity to describe the cytological findings of PMT along with its cytological differentials and a summary of prior published cases.

Abnormal Body Composition Increases the Cardiometabolic Risk in Adolescents and Young Adults With Turner Syndrome.

OBJECTIVE: To determine the cardiometabolic risk of adolescents and adults with Turner syndrome (TS) and whether and how anthropometry and body composition predict this risk. METHODS: We compared the anthropometric, biochemical, and dual-energy x-ray absorptiometry-derived body composition parameters of 103 girls and women with TS aged 12 to 30 years and 103 controls of the same age and body mass index: (1) between TS with and without metabolic syndrome (MetS), (2) between the different karyotypes of TS, and (3) between growth hormone recipients and nonrecipients. RESULTS: Individuals with TS had higher prevalence rates of truncal obesity (57.2%), MetS (37.9%), prediabetes (20.4%), dyslipidemia (73.8%), hypertension (9.7%), and hepatic steatosis (15.5%) and a greater total body fat percentage (38.43% vs 34.26%) and fat mass index (9.15 vs 6.71 kg/m2) but a lower lean mass index (11.05 vs 12.49 kg/m2) than controls (P <.001). Individuals with TS and MetS (n = 39) had a higher total body fat percentage (41.74% vs 36.42%, P <.0001), truncal fat percentage (44.66% vs 36.09%, P <.0001), and visceral adipose tissue mass (495.57 vs 276 g, P <.0001) than those with TS but without MetS. Those with classic TS (45,X) had a higher prevalence of prediabetes (32.6% vs 10.5%, P =.01). Growth hormone recipients had a lower prevalence of MetS and lesser truncal obesity. Altered body composition was significantly correlated with metabolic risk. The truncal fat percentage independently predicted MetS (odds ratio, 1.12; 95% confidence interval, 1.003-1.24; P =.04). Waist circumference and waist-hip ratio predicted metabolic risk with good sensitivity and specificity. CONCLUSION: Adverse cardiometabolic risk and altered body composition start early in life in TS. Postpubertal women with TS should be routinely assessed for truncal obesity, dysglycemia, dyslipidemia, and liver steatosis, irrespective of body mass index and karyotype.

Marked increase in bone mineral density with oral phosphate and calcitriol in tumour-induced osteomalacia.

Patients with osteomalacia have a low bone mineral density (BMD) and are often misdiagnosed as osteoporosis. A marked increase in BMD is noticed following successful treatment of osteomalacia. The biochemical hallmark of tumour-induced osteomalacia (TIO) is hypophosphatemia. Patients with TIO often have severe hypophosphatemic osteomalacia and dual-energy X-ray absorptiometry may demonstrate low BMD. Surgical removal of the phosphatonin-secreting lesion restores serum phosphate, corrects osteomalacia and is associated with a dramatic increase in BMD. We report two patients with TIO and low BMD, who were treated with oral phosphate and calcitriol supplementation. The percentage increase in BMD at 33 months was as high as 94.3% in areas with the lowest BMD at baseline. The BMD at 33 months was higher than the +2SD of the population-specific reference ranges, a finding not reported in surgically treated patients with TIO. An intermittent rise in parathyroid hormone following oral phosphate supplementation might have resulted in such findings.

Prevalence and Predictors of Prediabetes in Adolescents and Young Adults with Turner Syndrome: A Cross-Sectional Study from Eastern India.

Background: Individuals with Turner syndrome (TS) have a high risk for prediabetes/type 2 Diabetes Mellitus (T2DM). There is scarce data regarding risk factors for prediabetes in TS, specially from South Asia. Methods: We conducted a cross-sectional study on girls with TS aged 12-30 years who had achieved pubertal stage B3 and above-spontaneously or with oestrogen. Anthropometric measurements and biochemical tests were conducted, and medical records were reviewed for details about pubertal onset and progression, growth hormone (GH) and oestrogen therapy. Results: Out of 129 patients with TS in our database, 99 met the criteria for inclusion, mean age 18.33+/-3.78 years and mean BMI 20.57+/- 3.71 kg/m2. Prevalence of prediabetes was 23.23%. Plasma-glucose measured after 75 g-oral-anhydrous-glucose-load (OGTT-PPG) identified five additional prediabetes cases, who had normal fasting plasma glucose (FPG) or HbA1c%. Compared to those without prediabetes, TS with prediabetes (n = 23) had higher mean body weight, BMI, waist circumference (WC) [42.02+/- 5.83 vs 36.22+/-8.07, 22.77+/-2.78 vs 19.91+/- 3.72, 85.26+/- 3.52 vs 81.08+/- 4.59, pall < 0.03 ], higher median WC-to-height ratio (WHtR) and WC-to-hip ratio (WHR)((0.64 [0.6-0.69] vs 0.59[0.56- 0.66], 0.9[0.84-1.12] vs 0.85[0.75-1.01], pboth < 0.02), and higher LDL-cholesterol, triglycerides, and greater prevalence of hepatosteatosis (47.1% vs 21.1%, P < 0.01). Among GH recipients (n = 36), those with prediabetes had delayed initiation and shorter duration of GH therapy. There were no differences in cardiometabolic parameters or the prevalence of diabetes between different karyotypic variants of TS. BMI, WC and WHR had significant positive correlation with FBG, OGTT-PPG and HbA1c% (pall < 0.004). Delay in oestrogen initiation had a significant correlation with OGTT-PPG (Spearman's-rho = 0.69, P < 0.004). BMI, WHR and pubertal status were independent predictors for prediabetes (OR: 1.27 [1.03-1.57]), 1.18 [1.04-1.34]) and 0.09[0.02-0.38], respectively, pall < 0.02), but karyotype was not. BMI had the highest sensitivity [cut-off: 21.04 kg/m2 (sensitivity: 82.6%, specificity: 62.2%) and WHR had the highest specificity [cut-off: 0.89 (sensitivity: 73.9%, specificity 78.4%)] for predicting prediabetes. Conclusion: Indian girls with TS have a high risk for prediabetes, irrespective of underlying karyotype and should be screened with oral glucose challenge to identify prediabetes. Timely intervention against central obesity and early initiation of GH and oestrogen should be ensured in TS. Late presenting girls should be closely monitored for dysglycaemia before and during treatment with GH and/or oestrogen.