Postpartum glycemic and cardiometabolic profile of women testing positive for gestational diabetes mellitus by International Association of Diabetes and Pregnancy Study Groups (IADPSG) but negative by alternate criteria: Insights from CHIP-F study.

OBJECTIVE: To evaluate burden of postpartum diabetes and other cardiometabolic risk factors among women who test positive for gestational diabetes mellitus (GDM) by International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria, but negative by alternate criteria. METHODS: This prospective cross-sectional study was conducted from 2019 to 2022 and is a sub-study of the CHIP-F cohort (Cohort Study of Indian Women with Hyperglycemia in Pregnancy and their Families). RESULTS: Study participants (n = 826; 183 with normoglycemia and 643 with GDM using IADPSG criteria) were evaluated at a median (IQR) postpartum interval of 31 (21-45) months. Using the United Kingdom National Institute of Health and Care Excellence (UK NICE), Canadian Diabetes Association (CDA), and Diabetes in Pregnancy Study Group India (DIPSI) criteria, 251 (39.0 %), 148 (23.0 %) and 384 (59.7 %) women who tested positive for GDM by IADPSG criteria, would have tested negative. The incidence of postpartum diabetes among such women was 30.4, 34.3, and 48.2 per 1000 women-years, respectively, which was significantly higher than those testing negative by both IADPSG and UK NICE (5.0 per 1000 women-years), IADPSG and CDA (9.2/1000 women-years) and IADPSG and DIPSI criteria (5.0/1000 women-years). The burden of obesity and metabolic syndrome was also significantly higher in such women. CONCLUSIONS: We found a significant burden of postpartum diabetes and cardiometabolic risk factors among women who tested positive for GDM by IADPSG, but negative by alternate criteria. There are potential clinical implications of a "failed" diagnosis for future cardiometabolic diseases that need to be carefully examined.

Pragmatic Evaluation of Growth Hormone Stimulation Tests in Short Stature.

Introduction: To assess the performance of growth hormone stimulation tests (GHSTs) in the evaluation of short stature. Methods: It was a single-centre retrospective study carried out in children evaluated for short stature between January 2005 to March 2020. The clonidine stimulation test (CST) and glucagon stimulation test (GST) were used to assess growth hormone (GH) reserve (GST was performed only when peak GH levels were between 5 to ≤10 ng/mL on CST). A GH level of <5 ng/mL on CST or ≤10 ng/ml on both was used to corroborate GH deficiency. Results: A total of 556 children were eligible for this study. The mean (SD) age was 12.9 (3.5) years, and 66.3% were male. The peak GH level [median (IQR)] was 5.50 ng/ml (1.90 - 7.50) on CST (at 60 minutes) and 7.45 ng/ml (2.15 - 10.77) on GST (at 120 minutes). On restricting sampling to two time points, the false positive rate was 13.6% on CST (60, 90 minutes) and 11.5% on GST (120, 150 minutes). Similarly, restricting to three time points was associated with a false positive rate of 8.5% on CST (60, 90, 120 minutes) and 3.8% on GST (90, 120, 150 minutes). Using the treating clinician-determined diagnosis of GHD as a reference standard, the optimal cut-off of peak GH on CST was 7.79 ng/ml (sensitivity: 83.8%; specificity: 89.4%). Conclusion: Restricting the GH sampling to fewer time points is associated with an increase in the false positivity rate (FPR).

Bone mass, microarchitecture and turnover among young Indian women with non-alcoholic fatty liver disease.

PURPOSE: To evaluate comprehensive bone health among young Indian women, including bone mass, microarchitecture, and turnover, in relation to their non-alcoholic fatty liver disease (NAFLD) status. METHODS: This cross-sectional study (May 2018-November 2019) recruited women with a history of gestational diabetes mellitus (GDM) and normoglycemia in their index pregnancy, who were at least 6 months postpartum. All participants underwent abdominal ultrasonography for determination of NAFLD status (grades 2 and 3: severe NAFLD) and transient elastography (FibroScan) for hepatic fibrosis (LSM >6 kPa). Bone mass was assessed by DXA, bone microarchitecture with trabecular bone score {TBS} (low TBS ≤ 1.310) and bone turnover with markers of bone formation (osteocalcin and P1NP), and resorption (CTX). RESULTS: Bone mineral density (BMD) at femoral neck (p = 0.026) and total hip (p = 0.007) was significantly higher among women with NAFLD (n = 170) compared to those without (n = 124). There was no significant difference in bone turnover markers between the two groups. The presence of NAFLD [adjusted OR: 1.82 (1.07, 3.11)] was associated with low TBS, with a greater strength of association among women with severe NAFLD [adjusted OR: 2.97 (1.12, 7.88)]. However, these associations were attenuated and no longer significant after additionally adjusting for BMI. Women with NAFLD and hepatic fibrosis manifested significantly higher BMD at lumbar spine, femoral neck, and total hip (p < 0.001 for all) and significantly lower bone turnover markers (osteocalcin, p = 0.009 and CTX, p = 0.029), however, the association with low TBS was not observed. CONCLUSION: Among young Indian women, NAFLD is associated with increased bone mass and impaired bone microarchitecture, and hepatic fibrosis with increased bone mass and reduced bone turnover.

Postpartum diabetes and cardiometabolic outcomes among Indian (South Asian) women with early Gestational diabetes mellitus: Insights from the CHIP-F study.

Early GDM is associated with adverse pregnancy outcomes, however data on other outcomes are scarce. We evaluated women with early (n = 117) and classical (n = 412) GDM for long-term postpartum (median 32 months) glycemic and cardiometabolic outcomes and found a significantly higher prevalence of diabetes in the former [22.2 % vs. 12.6 %, p = 0.010].

Validity of Montreal Cognitive Assessment to Detect Cognitive Impairment in Individuals with Type 2 Diabetes.

INTRODUCTION: Guidelines recommend screening older people (> 60-65 years) with type 2 diabetes (T2D) for cognitive impairment, as it has implications in the management of diabetes. The Montreal Cognitive Assessment (MoCA) is a sensitive test for the detection of mild cognitive impairment (MCI) in the general population, but its validity in T2D has not been established. METHODS: We administered MoCA to patients with T2D (age ≥ 60 years) and controls (no T2D), along with a culturally validated neuropsychological battery and functional activity questionnaire. MCI was defined as performance in one or more cognitive domains ≥ 1.0 SD below the control group (on two tests representing a cognitive domain), with preserved functional activities. The discriminant validity of MoCA for the diagnosis of MCI at different cut-offs was ascertained. RESULTS: We enrolled 267 patients with T2D and 120 controls; 39% of the participants with T2D met the diagnostic criteria for MCI on detailed neuropsychological testing. At the recommended cut-off on MoCA (< 26), the sensitivity (94.2%) was high, but the specificity was quite low (29.5%). The cut-off score of < 23 showed an optimal trade-off between sensitivity (69.2%), specificity (71.8%), and diagnostic accuracy (70.8%). The cut-off of < 21 exhibited the highest diagnostic accuracy (74.9%) with an excellent specificity (91.4%), a good positive and negative predictive value (78.5% and 73.7%, respectively). CONCLUSIONS: The recommended screening cut-off point on MoCA of < 26 has a suboptimal specificity and may increase the referral burden in memory clinics. A lower cut-off of < 21 on MoCA maximizes the diagnostic accuracy. Interactive Visual Abstract available for this article.

Type 2 diabetes (T2D) is a risk factor for cognitive dysfunction which potentially impacts diabetes self-management skills. Guidelines recommend screening older adults with diabetes for early detection of cognitive impairment. For screening cognitive impairment in busy endocrine clinics, we need a test that is easy and rapid to administer, sensitive enough to pick the cognitive deficits of T2D and at the same time gives less false-positive outcomes. The Montreal Cognitive Assessment (MoCA) scale is a widely available cognitive screening tool, but there are no studies evaluating its discriminant properties in people with diabetes. We evaluated the performance metrics of MoCA in this population. We found mild cognitive impairment in four out of ten participants with T2D at or above 60 years of age. At the recommended cut-off on MoCA (< 26), the sensitivity was high, but the specificity quite low. We found better diagnostic accuracy at lower cut-offs (20/21), with high specificity but a lower sensitivity. At this cut-off, approximately one out of five people screened using MoCA would require detailed neuropsychological testing, and four out of five who undergo detailed evaluation would have true cognitive impairment.

Burosumab: Current status and future prospects.

Hypophosphatemic rickets/osteomalacia caused by FGF23 excess is conventionally treated with multiple doses of inorganic phosphate salts and active vitamin D analogs. However, conventional therapy targets the consequences of elevated FGF23 and not the elevated FGF23 itself and is associated with poor adherence and long-term complications such as nephrocalcinosis and secondary/tertiary hyperparathyroidism. Burosumab is a fully human IgG1 monoclonal antibody that binds to and neutralises FGF-23, thereby leading to improvement in phosphate homeostasis and healing of rickets and osteomalacia. Data from phase 2 and 3 trials report overall safety and efficacy and Burosumab is now FDA approved for treatment of XLH and TIO in children and adults. Cost and absence of long-term data are major issues with Burosumab which should be addressed in near future. At present, experts recommend Burosumab use in patients with severe disease or those with mild-moderate disease and a failed response to a trial of conventional therapy.

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

Incidence of Prediabetes/Diabetes among Women with Prior Gestational Diabetes and Non-Alcoholic Fatty Liver Disease: A Prospective Observational Study.

Background and Objectives: This prospective longitudinal study aims to evaluate and compare the incidence of prediabetes/diabetes among women stratified at the baseline postpartum visit according to the prior GDM and NAFLD status. Methods: Of the 309 women with baseline postpartum assessment at a median of 16 months following the index delivery, 200 (64.7%) [GDM: 137 (68.5%), normoglycaemia: 63 (31.5%)] were available for the follow-up analysis (performed at median of 54 months following the index delivery) and were participants for this study. We obtained relevant demographic, medical and obstetric details and performed a 75 g OGTT with glucose estimation at 0 and 120 min. NAFLD status was defined by ultrasonography at the baseline visit. Participants were divided into four groups: no NAFLD and no prior GDM (group 1), NAFLD but no prior GDM (group 2), prior GDM but no NAFLD (group 3), and NAFLD and prior GDM (group 4). Results: The mean age of study participants (n = 200) was 32.2 ± 5.1 years, and the mean interval between the two visits was 34.8 ± 5.5 months. A total of 74 (37%) women had progression to prediabetes/diabetes [incidence rate of 12.8/100 woman-years]. The incidence rates (per 100 woman-years) were 8.6, 8.9, 13.4 and 15.3 in groups 1, 2, 3 and 4, respectively. The adjusted hazard ratio for incident (new-onset) prediabetes/diabetes in group 4 (reference: group 1) was 1.99 (95% CI 0.80, 4.96, P = 0.140). Among women with baseline NAFLD (irrespective of GDM status), the risk of incident prediabetes/diabetes increased with an increase in the duration of follow-up (3.03-fold higher per year of follow-up, P = 0.029) and was significantly higher in women who were not employed (6.43, 95% CI 1.74, 23.7, P = 0.005) and in women with GDM requiring insulin/metformin during pregnancy (4.46, 95% CI 1.27, 15.64, P = 0.019). Conclusion: NAFLD and GDM increased the risk for glycaemic deterioration in young Indian women. Future studies should focus on evaluating the effectiveness of lifestyle and behavioural interventions in such high-risk women.

Current insights and emerging trends in early-onset type 2 diabetes.

Type 2 diabetes diagnosed in childhood or early adulthood is termed early-onset type 2 diabetes. Cases of early-onset type 2 diabetes are increasing rapidly globally, alongside rising obesity. Compared with a diagnosis later in life, an earlier-onset diagnosis carries an unexplained excess risk of microvascular complications, adverse cardiovascular outcomes, and earlier death. Women with early-onset type 2 diabetes also have a higher risk of adverse pregnancy outcomes. The high burden of complications renders individuals with early-onset type 2 diabetes at future risk of multimorbidity and interventions to reverse these concerning trends should be a priority. Within the early-onset cohort, disease pathophysiology and interventions have been better studied in paediatric-onset (<19 years) type 2 diabetes compared to adults; however, young adults aged 19-39 years (a larger number proportionally) are not well characterised and are also invisible in the current evidence base supporting management, which is derived from trials in later-onset type 2 diabetes. Young adults with type 2 diabetes face challenges in self-management that older individuals are less likely to experience (being in education or of working age, higher diabetes distress, and possible obesity-related stigma and diabetes-related stigma). There is a major research gap as to the optimal strategies to deploy in managing type 2 diabetes in adolescents and young adults, given that current models of care appear to not work as well in this age group. In the face of manifold risk factors (obesity, female sex, social deprivation, non-White European ethnicity, and genetic risk factors) prevention strategies with tailored lifestyle interventions, where needed, are likely to have greater success, but more evidence is needed. In this Review, we draw on evidence from both adolescents and young adults to provide a contemporary update on the current insights and emerging trends in early-onset type 2 diabetes.

68Ga-DOTANOC PET/CT for Screening and Surveillance of Von Hippel-Lindau (VHL) disease.

Purpose: Hereditary tumor syndrome Von Hippel-Lindau (VHL) disease is characterized by various benign and malignant tumors that are known to express somatostatin receptors (SSTR). We evaluated the role of 68Ga-DOTANOC PET/CT scan in patients with positive germline mutation of the VHL gene, presented initially or on follow-up, for the detection of recurrent or synchronous/metachronous lesions. Methods: Fourteen patients (8 males; 6 females) with mean age 30 ± 9.86 years were retrospectively analyzed, were tested positive for VHL on gene dosage analysis, and underwent 68 Ga-DOTANOC PET/CT scan for disease evaluation. The number and site of lesions were determined. The tracer uptake was analyzed semi-quantitatively by calculating the maximum standardized uptake values (SUVmax) of lesion. Results: Four of the 14 patients underwent scan for initial diagnosis as baseline, 6 patients for post-therapy disease status, and 4 patients for initial diagnosis as well as follow-up evaluation of the disease. A total of 67 lesions were detected in 14 patients. The sites of lesions were cerebellar/vertebral/spinal (17; mean SUVmax = 7.85); pancreatic neuroendocrine tumor (NET) (11; mean SUVmax = 20.64); retina (3; mean SUVmax = 10.46); pheochromocytoma (10; mean SUVmax = 16.32); paragangliomas (3; mean SUVmax = 10.65); pancreatic cyst (9; mean SUVmax = 2.54); and renal cyst (8; mean SUVmax = 1.56) and miscellaneous lesions constituted 6 lesions. Conclusion: Our results show that 68 Ga-DOTANOC PET/CT may be a useful modality for screening and follow-up of associated tumors in patients with germline gene mutation for VHL. It can be used as a one-stop imaging modality for VHL patients and may substitute for separate radiological investigations, making it more convenient for patients in terms of time and cost.

Cardiometabolic profile of women with a history of overt diabetes compared to gestational diabetes and normoglycemia in index pregnancy: Results from CHIP-F study.

PURPOSE: We aimed to evaluate the prevalence of postpartum diabetes among women with a history of overt diabetes in pregnancy (ODiP) and compare with women having a history of gestational diabetes mellitus (GDM) and normoglycemia in pregnancy. METHODS: We have an established longitudinal cohort of postpartum women with a history of hyperglycemia (preexisting diabetes [PED] [n = 101], ODiP [n = 92], GDM [n = 643]), and normoglycemia (n = 183) in pregnancy. For this study, we excluded women with PED and invited other eligible women in a fasting state for clinical and biochemical evaluation. RESULTS: We evaluated 918 women with a mean (SD) age of 33.6 (5.0) years and at a median (interquartile range) postpartum interval of 31 (20-45) months. Diabetes was diagnosed in 65 (70.7%) women in ODiP compared to 99 (15.4%) in GDM (p < .001) and 4 (2.2%) in normoglycemia group (p < .001). In the ODiP group, the prevalence of diabetes was 47.4% among women tested in the first year postpartum, increasing to 86.8% among women tested at >3 years postpartum. Diabetes was more common when ODiP was diagnosed in the first (27/29, 93.1%) compared to the second trimester of pregnancy (35/57, 61.4%). The adjusted odds ratio for diabetes in ODiP was 14.82 (95% confidence interval, 8.49-25.87; p < .001; reference category: GDM). CONCLUSIONS: The prevalence of postpartum diabetes was significantly higher in women with ODiP compared to GDM. Nearly 50% of women with ODiP did not develop diabetes in the first year of follow-up, especially when ODiP was diagnosed after the first trimester of pregnancy and on the basis of a 2-h oral glucose tolerance test value. Such women are amenable to prevention strategies.

Clinical profile and treatment outcomes among patients with sporadic and multiple endocrine neoplasia syndrome-related primary hyperparathyroidism.

OBJECTIVE: Accurate demarcation between multiple endocrine neoplasia, type 1 (MEN1)- related primary hyperparathyroidism (MPHPT) and sporadic PHPT (SPHPT) is important to plan the management of primary parathyroid disease and surveillance for other endocrine and nonendocrine tumours. The objective of this study is to compare the clinical, biochemical and radiological features and surgical outcomes in patients with MPHPT versus SPHPT and to identify the predictors of MEN1 syndrome in PHPT. DESIGN, PATIENTS AND MEASUREMENTS: This was an ambispective observationalstudy involving 251 patients with SPHPT and 23 patients with MPHPT evaluated at the endocrine clinic of All India Institute of Medical Sciences, New Delhi, India between January 2015 and December 2021. RESULTS: The prevalence of MEN1 syndrome among patients with PHPT was 8.2% and a genetic mutation was identified by Sanger sequencing in 26.1% of patients with MPHPT. Patients with MPHPT were younger (p < .001), had lower mean serum calcium (p = .01) and alkaline phosphatase (ALP; p = .03) levels and lower bone mineral density (BMD) Z score at lumbar spine (p < .001) and femoral neck (p = .007). The prevalence of renal stones (p = .03) and their complications (p = .006) was significantly higher in MPHPT group. On multivariable analysis, factors predictive of MPHPT were hyperplasia on histopathology [OR 40.1, p < .001], ALP levels within reference range [OR 5.6, p = .02] and lumbar spine BMD [OR 0.39 per unit increase in Z score, p < .001]. CONCLUSIONS: Patients with MPHPT have more severe, frequent and early onset of bone and renal involvement despite milder biochemical features. A normal serum ALP, low BMD for age and gender at lumbar spine and histopathology evidence of hyperplasia are predictive factors for MEN1 syndrome in PHPT.

Comparison of Accuracy of Freestyle Libre Pro and Medtronic iPro2 Continuous Glucose Monitoring Systems in Pregnancy.

There are limited data on head-to-head performance of Freestyle Libre Pro (FSL-Pro) and blinded Medtronic iPro2 continuous glucose monitoring system in pregnancy. In this prospective observational study, women with hyperglycemia in pregnancy (n = 42) underwent simultaneous FSL-Pro and Medtronic iPro2 sensor insertion and self-monitoring of blood glucose using Contour Plus meter (reference). The overall mean absolute relative difference (MARD) for iPro2 and FSL-Pro systems were 8.0% ± 9.2% and 19.0% ± 12.7%, respectively. At hypoglycemic range, both sensors performed less accurately (MARD: 18.0% and 16.8%, respectively), whereas iPro2 showed higher accuracy at euglycemic (8.2% and 19.3%, respectively) and hyperglycemic (6.8% and 18.0%, respectively) ranges. On Bland-Altman analysis, iPro2 and FSL-Pro underestimated glucose by 0.01 and 1.09 mmol/L, respectively. The ISO criteria were fulfilled for 88.5% and 44.9% of all values, respectively. To conclude, iPro2 was more accurate; however, both sensors demonstrated inaccuracy at hypoglycemic range, highlighting the need for refinements in the current generation of sensors to address this problem.

Metabolic syndrome in patients with type 1 diabetes mellitus at a tertiary centre in North India: A five year follow up study.

BACKGROUND AND AIMS: Metabolic syndrome (MS) is prevalent in the Indian population and has been traditionally linked to Type 2 diabetes mellitus (T2DM). Its presence is now being increasingly recognized in patients with Type 1 diabetes mellitus (T1DM). Presence of MS may increase the risk of diabetes related complications. This study was designed to determine the prevalence of MS in a cohort of patients with T1DM at baseline and at 5 years of follow up. METHODS: Longitudinal cohort study in a tertiary care center in North India. Patients with T1DM attending the Diabetes of the Young (DOY) Clinic from January 2015 to March 2016 included. Microvascular and macrovascular complications assessed. The cohort was followed after a period of 5 years. RESULTS: We included 161 patients (males, 49.4%) with a median (IQR) age of 23 (18-34) years and median (IQR) diabetes duration of 12 (7, 17) years. At baseline, 31 (19.2%) patients had MS. Patients with MS were more likely to have microvascular complications: retinopathy (p = 0.003), neuropathy (p = 0.02) and nephropathy (p = 0.04). Independent predictors of MS: insulin sensitivity (IS) (adjusted OR (aOR) 0.02 [95% CI, 0.003-0.118]), body weight (aOR 1.05 [95% CI, 1.007-1.108]), diastolic blood pressure (aOR 1.08 [95% CI, 1.01-1.15]) and duration of diabetes (aOR 1.09 [95% CI, 1.02-1.16]). On follow-up (n = 100), 13 (13%) had MS. CONCLUSIONS: One in 5 patients with T1DM suffers from MS, and is therefore predisposed to its attendant risks, calling for early identification and targeted interventions.

Late-night salivary cortisol cut-offs for diagnosis of Cushing syndrome using second-generation electrochemiluminescence immunoassay kits.

CONTEXT: Late-night salivary cortisol (LNSC) is a simple and reliable screening test for Cushing syndrome (CS). With improved analytical performance of the current second-generation electrochemiluminescence immunoassay (ECLIA; Elecsys Cortisol-II; Roche Diagnostics), there is a need to revisit the LNSC cut-offs, especially in a South-Asian population. OBJECTIVE: To derive LNSC cut-offs for diagnosis of CS using second-generation ECLIA kits. DESIGN: Diagnostic accuracy study. METHODS: We prospectively recruited 155 controls aged 18-60 years, including, normal-weight (body mass index [BMI] < 25 kg/m2 and no hypertension or diabetes [n = 53]) and overweight/obese (BMI 25-30 kg/m2 and hypertension and/or diabetes [n = 52] or BMI ≥ 30 kg/m2 with/without comorbidities [n = 50]) participants. All participants submitted LNSC samples collected at home; overweight/obese controls additionally underwent dexamethasone suppression test to exclude CS. We also reviewed records of adults with endogenous CS (cases, n = 92) and a valid LNSC result using the same method. RESULTS: The 95th percentile for LNSC in controls was 6.76 nmol/L. The mean ± SD LNSC levels were 40.47 ± 49.63 nmol/L in cases and 3.37 ± 1.18 nmol/L in controls (p < 0.001). Receiver operating characteristic (ROC) analysis showed excellent diagnostic performance of LNSC for CS, with area under curves (AUCs) of 0.994 (cases vs. all controls) and 0.993 (cases vs. overweight/obese controls), respectively. The best diagnostic performance was achieved at cut-offs ≥6.73 nmol/L (sensitivity: 97.8%, specificity: 94.8%) and ≥7.26 nmol/L (sensitivity: 97.8%, specificity: 95.1%), respectively. CONCLUSIONS: LNSC measured using second-generation ECLIA demonstrated high diagnostic accuracy for CS. Based on this study, we propose a LNSC cutoff ≥6.73 nmol/L to diagnose CS.

Imaging characteristics of phosphaturic mesenchymal tumors.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome associated with phosphaturic mesenchymal tumors (PMTs). Localization of the causative tumor in these cases is an arduous task since the culprit lesions are usually small, slow-growing, and can be located almost anywhere from head to toe. PURPOSE: To describe the morphological characteristics of histologically proven PMTs on various radiological modalities. MATERIAL AND METHODS: After institutional ethical approval, this retrospective study analyzed 20 cases with a histopathological evidence of PMT. Various imaging characteristics of the tumors on available computed tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated. Descriptive statistical analyses were conducted. RESULTS: The tumors were located in diverse locations: lower extremities (n = 10); head and neck (n = 5); vertebral column (n = 3); pelvis (n = 1); and upper extremities (n = 1). Bone lesions seen on CT had variable morphology: sclerotic (n = 3/8, 37.5%); lytic (n = 3/8, 37.5%), and both lytic and sclerotic (n = 2/8, 25%) with presence of narrow zone of transition in all cases (n = 8/8) and amorphous internal matrix calcifications in 25% of cases (n = 2/8). Of the tumors, 68.4% (n = 13/19) were hypointense on T1 and all of them showed hyperintense signal on T2-weighted and STIR images (n = 19/19) and contrast enhancement (n = 16/16). Of the tumors, 66.7% (n = 6/9) showed restricted diffusion. DOTANOC PET/CT showed tumor uptake in all cases (n = 8/8). CONCLUSION: PMTs may have variable and non-specific tumor appearances on various imaging modalities. However, in an appropriate clinical scenario and a background of suggestive biochemical work-up, the radiologist should keep a high index of suspicion.

Clinical profile and treatment outcomes of patients with ectopic ACTH syndrome compared to Cushing disease: a single-center experience.

PURPOSE: We aimed to evaluate and compare the clinical, biochemical and radiological profile and outcomes of patients with ectopic ACTH syndrome (EAS) and Cushing disease (CD) treated over a period of 10 years (2013-2022). METHODS: In this ambispective observational study, we collected data for 146 patients with ACTH-dependent CS (EAS, n = 23; CD, n = 94; occult ACTH source, n = 29). Relevant details were filled in a predesigned proforma and outcomes were ascertained at the most recent visit. RESULTS: EAS was more common in males (65.2 vs. 27.6%, p < 0.001). Patients with EAS had a shorter duration of symptoms [12 (6-12) vs. 31.5 (15-48) months, p < 0.001] and were more likely to have hypokalemia (82.6 vs. 21.0%, p = 0.001), pedal edema (65.2 vs. 34.2%, p = 0.015), weight loss (34.8 vs. 4.0%, p < 0.001) and systemic infection (30.4 vs. 6.5%, p = 0.006). They also had significantly higher 8 a.m. serum cortisol, midnight serum and salivary cortisol and 8 a.m. plasma ACTH levels. Bronchial carcinoid (n = 10, 43.5%) was the most common etiology of EAS. Bilateral adrenalectomy was performed in 11 (47.8%) patients with EAS. Eight patients (34.8%) with EAS died at the last follow-up, of whom 7 (87.5%) had metastatic disease. In CD group, overall remission rate was 69.4% (56.1%, early and 13.3%, delayed) and 26.3% of patients with an initial remission had recurrence. CONCLUSIONS: Bronchial carcinoid was the most common cause of EAS in our cohort. Bilateral adrenalectomy was performed in approximately every 1 in 2 patients with EAS and approximately every 1 in 3 patients expired till the last follow-up.