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Introduction: Pituitary apoplexy (PA) is a rare clinical syndrome due to acute/subacute pituitary hemorrhage and/or infarction; data on PA in functioning pituitary adenoma (FPA) is scarce., Methods: A retrospective record-review of details of PA in non-functioning (NFPA) and FPA managed at tertiary endocrine center., Results: 93 patients [56 males; 33.3% FPA: 5 acromegaly, 14 prolactinoma, and 12 Cushing's Disease (CD)] diagnosed with PA were included. Median age was 40 years, with younger age of presentation in FPA. Type A (acute) [49.5%] and headache (78.5%) were the commonest presentations, with PA being the initial manifestation in 98.4% of NFPA. Median (range) Pituitary Apoplexy Score (PAS) was 2 (0-8). Median tumor diameter was 2.5 cm, with larger tumors in FPA (3.2 cm vs. 2.3 cm). 29 (46.7%) NFPA-PA and 14 (45.2%) FPA-PA patients [71% prolactinoma, 33% in CD, and none in acromegaly] were conservatively managed. In the NFPA cohort, those managed surgically had significantly higher PAS (4 vs. 1) and larger tumor size (2.6 vs. 1.8 cm); however, both arms had comparable recovery of neuro-visual, radiological, and hormonal outcomes. In FPA cohort, CD and acromegaly required definitive treatment, whereas prolactinomas were effectively managed (clinical and biochemical recovery) with oral cabergoline and glucocorticoids. Matching PAS cohorts (to overcome allocation bias for management approach) in macroadenomas (excluding prolactinoma) showed comparable neuro-deficit and hormonal recovery between surgical and conservative approaches., Conclusion: PA in FPA has distinct features and management issues. Carefully selected patients (PAS guided) in NFPA with PA for conservative management have comparable outcomes to surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Pituitary apoplexy (PA) in Cushing's disease (CD) is rare with data limited to case reports/series., Methods: We retrospectively reviewed case records of PA in CD managed at our center from 1987 to 2023 and performed a systematic literature review., Results: We identified 58 patients (44 females), including twelve from our center (12/315 CD, yielding a PA prevalence in CD of 3.8%) and forty six from systematic review. The median age at PA diagnosis was 35 years. The most common presentation was type A (79.3%) and symptom was headache (89.6%), with a median Pituitary Apoplexy Score (PAS) of 2. Median cortisol and ACTH levels were 24.9 µg/dl and 94.1 pg/ml, respectively. Apoplexy was the first manifestation of underlying CD in 55.2% of cases, with 31.1% (14/45) presenting with hypocortisolemia (serum cortisol ≤ 5.0 µg/dl), underscoring the importance of recognizing clinical signs/symptoms of hypercortisolism. The median largest tumor dimension was 1.7 cm (53/58 were macroadenomas). PA was managed surgically in 57.8% of cases, with the remainder conservatively managed. All five PA cases in CD with microadenoma achieved remission through conservative management, though two later relapsed. Among treatment-naïve CD patients with macroadenoma, PA-related neuro-deficit improvement was comparable between surgical and conservative groups. However, a greater proportion of surgically managed patients remained in remission longer (70% vs. 38.5%; p = 0.07), for an average of 31 vs. 10.5 months., Conclusion: PA in CD is more commonly associated with macroadenomas, may present with hypocortisolemia, and surgical treatment tends towards higher and longer-lasting remission rates., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Fanconi renotubular syndromes (FRTS) are a rare group of inherited phosphaturic disorders with limited Indian as well as global data on this condition. Here, we describe the experience of a single Endocrinology center from Western India on FRTS., Materials and Methods: Comprehensive clinical, biochemical, radiological, management, and genetic details of FRTS patients managed between 2010 and 2023 were collected and analyzed., Results: FRTS probands had mutations (eight novel) in six genes [CLCN5 (n = 4), SLC2A2 (n = 2), GATM, EHHADH, HNF4A, and OCRL (1 each)]. Among 15 FRTS patients (11 families), rickets/osteomalacia was the most common (n = 14) presentation with wide inter- and intra-familial phenotypic variability. Delayed diagnosis (median: 8.8 years), initial misdiagnosis (8/11 probands), and syndrome-specific discriminatory features (8/11 probands) were commonly seen. Hypophosphatemia, elevated alkaline phosphatase, normal parathyroid hormone (median: 36 pg/ml), high-normal/elevated 1,25(OH) 2 D (median: 152 pg/ml), hypercalciuria (median spot urinary calcium to creatinine ratio: 0.32), and variable proximal tubular dysfunction(s) were observed. Elevated C-terminal fibroblast growth factor 23 in two probands was misleading, till the genetic diagnosis was reached. Novel observations in our FRTS cohort were preserved renal function (till sixth decade) and enthesopathy in FRTS1 and FRTS3 families, respectively., Conclusion: Our findings underscore frequent under- and misdiagnosis of FRTS; hence, a high index of suspicion for FRTS in phosphopenic rickets/osteomalacia, with early consideration of genetic testing is essential to ensure timely diagnosis of FRTS. The novel variants and phenotypic manifestations described here expand the disease spectrum of FRTS., (© 2024. The Japanese Society Bone and Mineral Research.)

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare disorder of phosphate homeostasis. We describe a single-center experience of genetically proven HHRH families and perform systematic review phenotype-genotype correlation in reported biallelic probands and their monoallelic relatives. Detailed clinical, biochemical, radiological, and genetic data were retrieved from our center and a systematic review of Pub-Med and Embase databases for patients and relatives who were genetically proven. Total of nine subjects (probands:5) carrying biallelic SLC34A3 mutations (novel:2) from our center had a spectrum from rickets/osteomalacia to normal BMD, with hypophosphatemia and hypercalciuria in all. We describe the first case of genetically proven HHRH with enthesopathy. Elevated FGF23 in another patient with hypophosphatemia, iron deficiency anemia, and noncirrhotic periportal fibrosis led to initial misdiagnosis as tumoral osteomalacia. On systematic review of 58 probands (with biallelic SLC34A3 mutations; 35 males), early-onset HHRH and renal calcification were present in ~ 70% and late-onset HHRH in 10%. c.575C > T p.(Ser192Leu) variant occurred in 53% of probands without skeletal involvement. Among 110 relatives harboring monoallelic SLC34A3 mutation at median age 38 years, renal calcification, hypophosphatemia, high 1,25(OH) 2 D, and hypercalciuria were observed in ~30%, 22.3%, 40%, and 38.8%, respectively. Renal calcifications correlated with age but were similar across truncating and non-truncating variants. Although most relatives were asymptomatic for bone involvement, 6/12(50%) had low bone mineral density. We describe the first monocentric HHRH case series from India with varied phenotypes. In a systematic review, frequent renal calcifications and low BMD in relatives with monoallelic variants (HHRH trait) merit identification., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: India has the highest number of prevalent type-1 diabetes (T1D) cases in the under-20-year age population. Data on the anthropometry of underprivileged Indian children with T1D are scarce. In economically disadvantaged countries like India, poor growth in patients with T1D is a major concern due to limited accessibility and affordability. Besides, due to the double burden of malnutrition, the prevalence of obesity is increasing mirroring the global trends, which may lead to the development of insulin resistance., Objectives: This study aims to assess the prevalence of malnutrition in Indian children and youth with T1D and to identify the determinants of short stature., Methods: A registry-based cross-sectional analysis of data collected from various centres across India enrolled in the Changing Diabetes in Children (CDiC) programme., Results: We observed that 6.4% were undernourished (3.4% severe undernutrition) and 17.7% (overweight 13.2%) had combined overweight/obesity. 21.2% of participants had short stature (adjusted for mid-parental height) with 7.4% cases of familial short stature. Longer duration of illness and insulin requirement were significant positive predictors of short stature while glycaemic control, insulin regimen and mid-parental height did not have a significant relationship with short stature. Participants on basal-bolus regimen had significantly higher insulin requirements and better glycaemic control than the ones on mixed-split regimen., Conclusion: We report that around one-fifth of children and youth with T1D were overweight/obese and around a fourth were stunted, especially those with longer duration of diabetes and higher insulin requirements. Close monitoring of anthropometric parameters is necessary for all children with T1D to optimize growth and nutrition., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Endocrinology and Metabolism.)

Alopecia in hereditary vitamin D resistant rickets (HVDRR) has some correlation with severe rickets and poor overall response. However, these observations are based on small series. Hence, we aim to assess the genotypic spectrum of HVDRR and its correlation with alopecia and clinical response. Seven genetically-proven HVDDR patients from five unrelated families and 119 probands from systematic review were analysed retrospectively for phenotypic and genotypic data and overall response to therapy. In our cohort mean age at rickets onset was 12 (± 3.4) months. Alopecia was present in all patients but one. All patients had poor overall response to oral high-dose calcium and calcitriol and most required intravenous calcium. Genetic analyses revealed four novel variants. On systematic review, alopecia was present in majority (81.5%) and preceded the onset of rickets. Patients with alopecia had higher serum calcium (7.6 vs.6.9 mg/dl, p = 0.008), lower 1, 25(OH) 2 D (200 vs.320 pg/ml, p = 0.03) and similar overall response to oral therapy (28.7% vs. 35.3%, p = 0.56). Alopecia was present in 51.4% of non-truncating (NT) ligand-binding domain (LBD) variants, whereas it was universal in truncating LBD and all DNA binding-domain (DBD) variants. Overall response to oral therapy was highest in LBD-NT (46.4%) as compared to 7.6% in LBD-truncating and 19% in DBD-NT variants. Among LBD-NT variants, those affecting RXR heterodimerization, but not those affecting ligand affinity, were associated with alopecia. Both alopecia and overall response have genotypic correlation. Age at diagnosis and overall response to oral therapy were similar between patients with and without alopecia in genetically proven HVDRR., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear., Design: We reviewed literature for first-line glucocorticoid treatment in PAH until December 2021 and performed an individual patient data meta-analysis to analyze clinical, hormonal, and radiological outcomes with respect to route, dose, and duration (<6.5 vs 6.5-12 vs >12 weeks) of glucocorticoid treatment according to disease severity., Results: A total of 153 PAH patients from 83 publications were included. The median age at presentation was 41 (32.5-48) years with a female preponderance (70.3%). Visual field recovery was significantly better with i.v. (91.7%) as compared to oral (54.5%) route and high dose (100%) and very high dose (90.9%) as compared to medium dose (20%) of glucocorticoids. Corticotroph axis recovery was greater in i.v. (54.8% vs 28.1% oral, P = 0.033) route and increasing glucocorticoid dose group (0% vs 38.1% vs 57.1%), attaining statistical significance (P = 0.012) with very high-dose. A longer duration of treatment (>6.5 weeks) was associated with better corticotroph and thyrotroph recovery. The need for rescue therapy was lower with i.v. route (38% vs 17.5%, P = 0.012) and with increasing glucocorticoid doses (53.3% vs 34.3% vs 17.3%, P = 0.016). In severe disease, visual field and corticotroph axis recovery were significantly higher with i.v. route and very high-dose steroids. The adverse effects of glucocorticoids were independent of dose and duration of treatment., Conclusions: Very high-dose glucocorticoids by i.v. route and cumulative longer duration (>6.5 weeks) lead to better outcomes and could be considered as first-line treatment of severe PAH cases.

Background  This study aimed to compare the sensitivity of 68 Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) with other imaging modalities in the detection of head and neck paraganglioma (HNPGL). Methods  The data of consecutive HNPGL patients ( n  = 34) who had undergone at least 68 Ga-DOTATATE PET/CT and anatomical imaging (contrast-enhanced computed tomography/magnetic resonance imaging [CECT/MRI]) were retrospectively reviewed. The diagnosis of HNPGL (the primary tumor) was confirmed either by histopathology ( n  = 10) or was based on clinical follow-up and correlation of anatomical with functional imaging in whom histopathology was not available ( n  = 24). The sensitivities of 68 Ga DOTATATE PET/CT, 18F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT), 131 I-metaiodobenzylguanidine ( 131 I-MIBG) scintigraphy, and CECT/MRI for primary HNPGL, associated primary pheochromocytoma + sympathetic paraganglioma (PCC + sPGL), and metastatic lesions were analyzed. Results  Thirty-four patients (males: 15) [isolated HNPGL: 26, HNPGL + PCC: 04, HNPGL+ sPGL: 03, HNPGL + PCC + sPGL: 01] harboring 50 primary lesions were included. For total lesions, 68 Ga-DOTATATE PET/CT (99.3%) had significantly higher lesion-wise sensitivity than 18 F-FDG PET/CT (81.6%, p  = 0.0164), 131 I-MIBG (15.2%, p ≤0.0001), CECT (46.3%, p ≤ 0.0001) but similar sensitivity as MRI neck (97%, p  = 0.79). On head-to-head comparison (21 primary HNPGL and 39 metastatic lesions), 68 Ga DOTATATE PET/CT had significantly higher lesion-wise sensitivities for the detection of metastatic (100 vs. 71.9%, p  = 0.04) and total lesions (100 vs. 77.2%, p ≤ 0.0001). Conclusion   68 Ga-DOTATATE PET/CT was the most sensitive imaging modality for the detection of HNPGL and related lesions with significantly higher lesion-wise sensitivities than those of 18 F-FDG PET/CT, 131 I-MIBG, and CECT., Competing Interests: Conflict of Interest None declared., (World Association of Radiopharmaceutical and Molecular Therapy (WARMTH). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Abstract: A 48-year-old man, a case of metastatic insulinoma, who failed transarterial chemoembolization of liver metastases underwent multiple cycles of peptide receptor radionuclide therapy with 177Lu-DOTATATE, following which a complete morphologic and metabolic response was demonstrated on 68Ga-DOTATATE PET/CT. Patient had a remarkable improvement in his quality of life as intractable hypoglycemic episodes resolved after treatment. Peptide receptor radionuclide therapy is a promising targeted radionuclide therapy in patients of metastatic insulinomas that can result in reduced tumor burden and improved quality of life, particularly those who fail the conventional treatment modalities as seen in the present case., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The literature regarding gonadoblastoma risk in exonic Wilms' tumor suppressor gene (WT1) pathogenic variants is sparse. The aim of this study is to describe the phenotypic and genotypic characteristics of Asian-Indian patients with WT1 pathogenic variants and systematically review the literature on association of exonic WT1 pathogenic variants and gonadoblastoma., Design: Combined retrospective-prospective analysis., Methods: In this study, 46,XY DSD patients with WT1 pathogenic variants detected by clinical exome sequencing from a cohort of 150 index patients and their affected relatives were included. The PubMed database was searched for the literature on gonadoblastoma with exonic WT1 pathogenic variants., Results: The prevalence of WT1 pathogenic variants among 46,XY DSD index patients was 2.7% (4/150). All the four patients had atypical genitalia and cryptorchidism. None of them had Wilms' tumor till the last follow-up, whereas one patient had late-onset nephropathy. 11p13 deletion was present in one patient with aniridia. The family with p.Arg458Gln pathogenic variant had varied phenotypic spectrum of Frasier syndrome; two siblings had gonadoblastoma, one of them had growing teratoma syndrome (first to report with WT1). On literature review, of >100 exonic point pathogenic variants, only eight variants (p.Arg462Trp, p.Tyr177*, p.Arg434His, p.Met410Arg, p.Gln142*, p.Glu437Lys, p.Arg458*, and p.Arg458Gln) in WT1 were associated with gonadoblastoma in a total of 15 cases (including our two cases)., Conclusions: WT1 alterations account for 3% of 46,XY DSD patients in our cohort. 46,XY DSD patients harboring exonic WT1 pathogenic variants carry a small but definitive risk of gonadoblastoma; hence, these patients require a gonadoblastoma surveillance with a more stringent surveillance in those harboring a gonadoblastoma-associated variant.

Risk of metastatic disease in the cluster 2-related pheochromocytoma/paraganglioma (PPGL) is low. In MEN2 patients, identification of origin of metastases from pheochromocytoma (PCC) or medullary thyroid carcinoma (MTC) is challenging as both are of neuroendocrine origin. We aim to describe our experience and perform a systematic review to assess prevalence, demographics, biochemistry, diagnostic evaluation, management, and predictors of cluster 2-related metastatic PPGL. Retrospective analysis of 3 cases from our cohort and 43 cases from world literature was done. For calculation of prevalence, all reported patients (n = 3063) of cluster 2 were included. We found that the risk of metastasis in cluster 2-related PPGL was 2.6% (2% in RET, 5% in NF1, 4.8% in TMEM127 and 16.7% in MAX variation). In metastatic PCC in MEN2, median age was 39 years, bilateral tumors were present in 71% and median tumor size was 9.7 cm (range 4-19) with 43.5% mortality. All patients had a primary tumor size ≥4 cm. Origin of primary tumor was diagnosed by histopathology of metastatic lesion in 11 (57.9%), 131I-MIBG scan in 6 (31.6%), and selective venous sampling and CT in 1 (5.3%) patient each. In subgroup of neurofibromatosis 1 (NF1), median age was 46 years (range 14-59) with median tumor size 6 cm and 57% mortality. To conclude, the risk of metastatic disease in cluster 2-related PPGL is low, being especially high in tumors with size ≥4 cm and associated with high mortality. One-third patients of NF1 with metastatic PPGL had presented in second decade of life. Long-term studies are needed to formulate management recommendations.

Context: POU1F1 mutations are prevalent in Indian CPHD cohorts. Genotype-phenotype correlation is not well-studied., Aim: To describe phenotypic and genotypic spectrum of POU1F1 mutations in our CPHD cohort and present systematic review as well as genotype-phenotype analysis of all mutation-positive cases reported in world literature., Methods: Retrospective study of POU1F1 mutation-positive patients from a western-Indian center. PRISMA guidelines based pubmed search of published literature of all mutation-positive patients., Results: Our cohort had 15 POU1F1 mutation-positive patients (9 index, 6 relatives). All had severe GH, TSH and prolactin deficiencies (GHD, TSHD and PD). TSHD was diagnosed earliest followed by GHD (median ages: TSHD-6 months, GHD-3 years), while PD was more variable. Two sisters had central precocious puberty at 7 years of age. Pubic hair was deficient in all post-pubertal patients (females: P1-P2, males: P3-P4). Splice-site/intronic/frameshift mutations were most common, while missense/nonsense mutations were less frequent (33%). Review of world literature yielded 114 patients (82 index patients) from 58 studies. GHD was present in all patients. TSHD was spared in 12.5% and PD in 4.4% patients. Missense/nonsense mutations accounted for 75% of spectrum. Phenotype-genotype analysis revealed higher mean peak-GH levels (1.1 vs 0.2 ng/ml, p = 0.008) and lower prevalence of anterior-pituitary hypoplasia (63.6% vs 86.3%, p = 0.03) in patients with heterozygous than homozygous and compound heterozygous mutations., Conclusions: We present largest series of POU1F1 mutation-positive patients. Precocious puberty and defective pubarche are lesser-appreciated phenotypic features. Our mutation spectrum is different from that of world literature. Patients with heterozygous mutations have milder phenotype., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Vitamin D dependent rickets type 1 (VDDR1) is a rare disease due to pathogenic variants in 1- α hydroxylase gene. We describe our experience with systematic review of world literature to describe phenotype and genotype., Methods: Seven patients from six unrelated families with genetically proven VDDR1 from our cohort and 165 probands from systematic review were analyzed retrospectively. The clinical features, biochemistry, genetics, management, and long-term outcome were retrieved., Results: In our cohort, the median age at presentation and diagnosis was 11(4-18) and 40(30-240) months. The delayed diagnoses were due to misdiagnoses as renal tubular acidosis and hypophosphatemic rickets. Four had hypocalcemic seizures in infancy whereas all had rickets by 2 years. All patients had biochemical response to calcitriol, however two patients diagnosed post-puberty had persistent deformity. Genetic analysis revealed two novel (p.Met260Arg, p.Arg453Leu) and a recurring variant (p.Phe443Profs*24). Systematic review showed that seizures as most common presentation in infancy, whereas delayed motor milestones and deformities after infancy. Diagnosis was delayed in 27 patients. Patients with unsatisfactory response despite compliance were >12 years at treatment initiation. Inappropriately normal 1,25(OH)2D may be present, however suppressed ratio of 1,25(OH)2 D/25(OH)D may provide a clue to diagnosis. Various region specific and hot-spot recurrent variants are described. Patients with truncating variants had higher daily calcitriol requirement and greatly suppressed ratio of 1,25(OH)2D/25(OH)D., Conclusion: Delayed diagnosis may lead to permanent short stature and deformities. Truncating variants tend to have severe disease as compared to non-truncating variants. Diagnostic accuracy of 1,25(OH)2 D/25(OH)D ratio needs further validation., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Purpose of the Report: Prostate-specific membrane antigen (PSMA) is a member of superfamily of zinc-dependent exopeptidases that is robustly expressed in prostate cancer cells and nonprostatic solid tumor neovasculature including microvessels of thyroid tumors. Its expression in differentiated thyroid cancer (DTC) has been confirmed in many recent studies, but systematic studies exploring PSMA expression in patients with DTC with thyroglobulin elevation and negative iodine scintigraphy (TENIS) are lacking. The aim of the present study was to evaluate the role of PSMA scan in TENIS patients with DTC., Methods: Nine consecutive patients with DTC with proven TENIS syndrome (6 men and 3 women with age range 29-68 years and mean age of 48 years) underwent 18F-FDG PET/CT as per the institution protocol. Thereafter, they were subjected to 68Ga-PSMA-HBED-CC PET/CT as per the institution protocol within a week of FDG PET imaging. Prostate-specific membrane antigen expression (SUVmax) in the lesions was compared with 18F-FDG PET and CT scan findings., Results: In 5 of 9 patients with TENIS, the metastatic lesions showed PSMA expression. A total of 14 lesions were seen on the CT scan. Prostate-specific membrane antigen PET detected 9 of 14 lesions (64.28%) (SUVmax ranging from 10.1 to 45.67; median SUVmax of 16.31), whereas FDG PET was positive in 11 of 14 lesions (78.57%). The lesions that showed PSMA uptake was localized to bones (5 of 9) and lungs (4 of 9). Two lesions that were localized to iliac crest and acetabulum were missed on FDG PET but were seen on CT and PSMA PET scan., Conclusions: The results of this pilot study indicate that 68Ga-HBED-CC-PSMA PET/CT demonstrates PSMA expression in TENIS patients with lesions being localized to the bones and lungs. 68Ga-PSMA PET/CT could be useful for the identification of TENIS patients who might benefit from PSMA-targeted radionuclide therapy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Radionuclide therapy is a promising treatment modality in metastatic pheochromocytoma/paraganglioma (PPGL). There is scarce data on 131 I-metaiodobenzyl guanidine ( 131 I-MIBG) therapy from the Indian subcontinent. Hence, we aim to study the safety and effectiveness of low-dose, low-specific activity (LSA) 131 I-MIBG therapy in patients with symptomatic, metastatic PPGL., Methods: Clinical, hormonal, and radiological response parameters and side effects of LSA 131 I-MIBG therapy in patients with symptomatic, metastatic PPGL were retrospectively reviewed. World health organizations' (WHO) symptomatic, hormonal, and tumor response, and response evaluation criteria in solid tumors (RECIST1.1) criteria were used to assess the response., Results: Seventeen (PCC: 11, sympathetic PGL: 06) patients (15 with disease progression) received low-dose LSA 131 I-MIBG therapy. Complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) were 18% (3/17), 24% (4/17), 18% (3/17), and 41% (7/17), respectively, for WHO symptomatic response; 20% (2/10), 10% (1/10), 30% (3/10), and 40% (4/10), respectively, for WHO hormonal response; and 19% (3/16), 6% (1/16), 31% (5/16), and 44% (7/16), respectively for tumor response based on RECIST1.1. All patients with symptomatic PD and 50% (2/4) with hormonal PD had progression as per RECIST1.1 criteria. Side effects included thrombocytopenia, acute myeloid leukemia, mucoepidermoid carcinoma, and azoospermia in 6% (1/17) each., Conclusions: Our study reaffirms the modest efficacy and safety of low-dose, LSA 131 I-MIBG therapy in patients with symptomatic, metastatic PPGL. Symptomatic, but not hormonal, progression after 131 I-MIBG therapy correlates well with tumor progression and should be further evaluated with imaging. In resource-limited settings, anatomic imaging alone may be used to assess tumor response to 131 I-MIBG therapy., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Endocrinology and Metabolism.)

Context: Regional variation in prevalence of genetic mutations in growth hormone deficiency (GHD) is known., Aim: Study phenotype and prevalence of mutations in GH1, GHRHR, POU1F1, PROP1 genes in GHD cohort., Methods: One hundred and two patients {Isolated GHD (IGHD): 79; combined pituitary hormone deficiency (CPHD): 23} with orthotopic posterior pituitary were included. Auxologic, hormonal and radiological details were studied. All four genes were analysed in IGHD patients. POU1F1 and PROP1 were studied in CPHD patients., Results: Of 102, 19.6% were familial cases. Height SDS, mean (SD) was - 5.14 (1.63). Peak GH, median (range) was 0.47 ng/ml (0-6.59), 72.5% patients had anterior pituitary hypoplasia (APH). Twenty mutations (novel: 11) were found in 43.1% patients (n = 44, IGHD-36, CPHD-8). GHRHR mutations (n = 32, p.Glu72* = 24) were more common than GH1 mutations (n = 4) in IGHD cohort. POU1F1 mutations (n = 6) were more common than PROP1 mutations (n = 2) in CPHD cohort. With few exceptions, this prevalence pattern is contrary to most studies in world-literature. No patients with peak GH > 4 ng/ml had mutations, signifying it as negative predictor. While many parameters were significant on univariate analysis, only positive family history and lower median peak GH levels were significant predictors of mutations on multivariate analysis in IGHD patients., Conclusion: At variance with world literature, we found reverse predominance of GHRHR over GH1 mutations, POU1F1 over PROP1 mutations and predominance of GHRHR p.Glu72* mutations thus re-affirming the regional diversity in GHD genetics. We report positive and negative predictors of mutations in GHD.

Introduction: 177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) is a promising therapy for metastatic and/or inoperable pheochromocytoma and paraganglioma (PPGL). We aim to evaluate the efficacy and safety of and identify predictors of response to 177Lu-DOTATATE therapy in metastatic and/or inoperable PPGL., Methods: This retrospective study involved 15 patients of metastatic or unresectable PPGL, who received 177Lu-DOTATATE PRRT therapy. Clinical, biochemical (plasma-free normetanephrine), and radiological (anatomical and functional) responses were compared before and after the last therapy., Results: A total of 15 patients (4 PCC, 4 sPGL, 5 HNPGL, 1 PCC + sPGL, 1 HNPGL + sPGL) were included. The median duration of follow up was 27 (range: 11-62) months from the start of PRRT. Based on the RECIST (1.1) criteria, progressive disease was seen in three (20%), stable disease in eight (53%), partial response in one (7%), and minor response in three (20%) and controlled disease in 12 (80%). On linear regression analysis the presence of PGL (P= 0.044) and baseline SUVmax >21 (P < 0.0001) were significant positive predictors of early response to PRRT. Encouraging safety profiles were noted with no long term nephrotoxicity and hematotoxicity., Conclusion: 177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax < 21, baseline SUVmax >21 can be used to predict early response to PRRT.

The optimum imaging modality for the screening of multiple endocrine neoplasia type 1 (MEN1)-associated tumors is not well established. Here, we compare the performance of contrast-enhanced CT (CECT) versus 68 Ga DOTA-NOC/TATE PET/CT in MEN1 patients. The retrospective case record study is conducted at a tertiary health-care center. Thirty-four patients, who have undergone both CECT and 68 Ga DOTA-NOC/ TATE PET, were included in the analysis. CECT had higher per-lesion sensitivity than 68 Ga DOTA-NOC/TATE PET/CT for the detection of parathyroid lesions, (82.6% vs. 24.6%, P < 0.001). 68 Ga DOTA-NOC/TATE PET/CT had higher per-lesion sensitivity than CECT for the detection of metastases (85% vs. 47.5%, P < 0.001) and gastrinomas (90% vs. 10%, P = 0.003). When combined use of the two imaging modalities is compared to CECT alone (63.7% vs. 93.1%, P = 0.00012) and 68 Ga-DOTA-NOC/TATE PET/CT alone (74.1% vs. 93.1%, P = 0.0057), it provided significantly higher per-lesion sensitivity for the detection of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). 68 Ga-DOTA-NOC/ TATE PET was more sensitive for the detection of gastrinomas and metastases than CECT, whereas it was less sensitive for the detection of parathyroid lesions than CECT. The combined use of both the imaging modalities significantly increases the sensitivity for detection of GEP-NETs., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 World Journal of Nuclear Medicine.)

A 50-year-man presented with debilitating lower-limb proximal muscle weakness and hip pain since 3 years. Investigations (serum calcium (8.9 mg/dL), serum phosphorus (1.5 mg/dL), serum albumin (40 g/L), parathyroid hormone (116 pg/mL (12.30 pmol/L)), 25(OH)D3 (25.2 ng/mL (63 nmol/L)) 1,25(OH) 2 D3 (19 pg/mL (45.60 pmol/L)), tubular reabsorption of phosphate of 0.22 and elevated serum fibroblast growth factor 23 (FGF23) (387.7 RU/mL)) were consistent with tumour-induced osteomalacia (TIO). Localisation studies ( 68 Ga DOTATATE positron emission tomography (PET)/CT and 18 FDG-PET/CT) did not reveal any lesion. Re-evaluation after 2 and 5 years with 68 Ga-DOTANOC PET/CT showed 2×1.4 cm progressively increasing rounded soft tissue enhancing mass close to splenic hilum (SUV max: 26.4). Tumour was resected by laparotomy. Both FGF23 (120 RU/mL on day 3) and serum phosphorus (2.5 mg/dL on day 10) normalised with significant clinical improvement after surgery. Histopathology revealed phosphaturic mesenchymal tumour. Here, we report the first case of intra-abdominal mesenchymal tumour causing TIO diagnosed by serial functional imaging., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale and Introduction: To evaluate the computerised tomography (CT) characteristics of phaeochromocytoma (PCC) that differentiate them from other non-benign adrenal masses such as adrenocortical carcinoma (ACC), primary adrenal lymphoma (PAL) and adrenal metastases (AM)., Methods: This retrospective study was conducted at a tertiary health care institute from Western India. Patients presented between January 2013 and August 2016 with histological diagnosis of PCC or other non-benign adrenal mass having adequate reviewable imaging data comprising all four CECT phases were included., Results: The study cohort consisted of 72 adrenal masses from 66 patients (33 PCC, 22 ACC, 4 PAL, 13 AM). Unlike other masses, majority of PCC (25/33) showed peak enhancement in early arterial phase (EAP). PCC had significantly higher attenuation in EAP and early venous phase (EVP), and higher calculated percentage arterial enhancement (PAE) and percentage venous enhancement (PVE) than other adrenal masses (P < 0.001). For diagnosis of PCC with 100% specificity, PAE value ≥100% and EAP attenuation ≥100 HU had 78.8 and 63.6% sensitivity respectively. ACC were significantly larger in size as compared to PCC and metastasis. The adreniform shape was exclusively found in PAL (two out of four) and AM (4 out of 13). None of the enhancement, wash-in or washout characteristics were discriminatory among ACC, PAL and AM., Conclusion: Peak enhancement in EAP, PAE value ≥100% and EAP attenuation ≥100 HU differentiate PCC from other malignant adrenal masses with high specificity.

Background Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing's syndrome (CS) in childhood. We describe a case series of patients presenting at our centre along with a review of the literature. Methods A retrospective analysis of six index cases and one family were done for demographic features, hormonal profile, imaging findings, genetic mutation status, histopathologic findings and follow-up details. Diagnosis was based on biochemistry and confirmed with histopathology and or genetic mutation. All patients had suppressed 8 am adrenocorticotropic hormone (ACTH) (<10 pg/mL) despite evidence of hypercortisolism. Results The mean age in our cohort was 8.2 years (range 15 months to 20 years). All patients presented with overt CS, including one patient with cyclic Cushing's. Three patients had additional features of Carney complex (CNC). Imaging did not reveal any obvious mass lesions on computed tomography (CT), the classical beaded appearance was present in only two of the patients. Mutation analysis was positive in three patients. Five patients underwent bilateral adrenalectomy and had features of PPNAD on histopathology. Conclusions PPNAD is a rare cause of ACTH-independent CS in childhood and may signal underlying CNC. Patients with younger age of onset with overt CS may still have a mutation in the PRKAR1A gene and warrant genetic testing.

Background: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection., Methods: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features., Findings: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs., Interpretation: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Objective: Co existent pituitary adenoma and Rathke's cleft cyst (RCC) is a rare entity. Purpose of this study is to describe the clinical presentation, imaging findings, and management of patients with this combination., Methods: Retrospective review of records from a single tertiary care center for a period of three years [2009-2012]., Results: Out of the total 284 pituitary adenoma patients in the study period, there were four patients one each of Cushing's disease, acromegaly, prolactinoma and non-secretory pituitary adenoma with coexisting RCC in all. Three of these were diagnosed to have coexisting RCC in preoperative MRI. All of them underwent transphenoidal excision of the lesions. Histopathology confirmed the collision sellar lesions in all four., Conclusions: It is difficult to diagnose coexisting RCC preoperatively due to variable size, position and signal intensity. However when a nonenhancing cyst is incidentally detected by MRI in a patient with pituitary adenoma, the possibility of a coexisting RCC should be considered., (© Journal of the Association of Physicians of India 2011.)

Background: Radiation exposure to neck by four-dimensional computerized tomography (4DCT) is relatively high and limits its use as a first-line investigation in evaluation of primary hyperparathyroidism (PHPT). Radiation exposure can be reduced by restricting the number of CT phases. Our aim was to study the performance of 4DCT in cohort of surgery-naïve PHPT patients, and to evaluate percentage enhancement as an objective radiological index to discriminate parathyroid lesions (adenoma/hyperplasia) from thyroid tissue and lymph nodes., Materials and Method: Retrospective study of 49 PHPT patients {(44 single-gland diseases (SGD) and five multiple-gland disease (MGD)} who underwent 4DCT (unenhanced, early arterial, early venous and delayed venous phase) pre-operatively. Two radiologists who were blinded to surgical location of parathyroid lesions examined the scans. Attenuation values were recorded for parathyroid lesions (n=50), thyroid gland (n=50) and lymph nodes (n=12) in different phases. Percentage enhancement for different phases was calculated as "(HU in a specific enhanced phase-HU in unenhanced phase)/HU in unenhanced phase" ×100., Results: Inter-rater reliability between the two radiologists was 0.83 (Cohen's kappa). In SGD, sensitivity and PPV were 93.18% and 98.8% for lateralization, and 89.77% and 95.18% for quadrant localization, respectively. In MGD, 4DCT showed 50% sensitivity and 100% PPV. Percentage arterial enhancement showed highest area under curve (AUC=0.992) for differentiation of parathyroid lesions from thyroid tissue and lymph nodes. A cut-off value of 128.9% showed 95.8% sensitivity and 100% specificity for the identification of parathyroid lesions., Conclusions: We propose that percentage arterial enhancement can be used as an objective radiological index for accurate identification of parathyroid adenoma/hyperplasia., (© 2017 John Wiley & Sons Ltd.)

Objective: Limited data are available on pituitary gigantism, as it is a rare disorder. This study was carried out to assess the clinical, hormonal, and radiologic profiles and management outcomes of patients with pituitary gigantism., Methods: We conduced a retrospective analysis of 14 patients with pituitary gigantism who presented to a single tertiary care institute from 1990 to 2014., Results: Thirteen patients were male, and 1 was female. The mean age at diagnosis was 21.9 ± 6.1 years, with a mean lag period of 6.5 ± 5.6 years. The mean height SD score at the time of diagnosis was 3.2 ± 0.6. Symptoms of tumor mass effect were the chief presenting complaint in the majority (50%) of patients, while 2 patients were asymptomatic. Six patients had hyperprolactinemia. At presentation, the nadir PGGH (postglucose GH) and insulin-like growth factor (IGF 1)-ULN (× upper limit of normal) were 63.2 ± 94.9 ng/mL and 1.98 ± 0.5, respectively. All (except 1 with mild pituitary hyperplasia) had pituitary macroadenoma. Six patients had invasive pituitary adenoma. Transsphenoidal surgery (TSS) was the primary modality of treatment in 13/14 patients, and it achieved remission in 4/13 (30.76%) patients without recurrence over a median follow-up of 7 years. Post-TSS radiotherapy (RT) achieved remission in 3/5 (60%) patients over a median follow-up of 3.5 years. None of the patients received medical management at any point of time., Conclusion: Gigantism is more common in males, and remission can be achieved in the majority of the patients with the help of multimodality treatment (TSS and RT).

Objective: Our study aimed to establish a local reference range for late-night salivary cortisol (LNSC) using enzyme immunoassay (EIA) and to study the intra-individual reproducibility of LNSC., Methods: Prospective study involving 30 healthy subjects (HS) with body mass index (BMI) <25 kg/m2, 37 obese/overweight subjects (OS) with BMI >25 kg/m2 and 28 patients with Cushing disease (CD). Salivary sampling was performed on 2 consecutive nights and assayed by EIA. The reference range was established using LNSC values of HS, and receiver operating characteristic (ROC) curves were used to determine diagnostic cutoffs., Results: The mean LNSC level of CD was significantly higher than HS and OS (CD: 16.96 ± 9.11 nmol/L, HS: 1.30 ± 0.95 nmol/L, and OS 1.21 ± 0.78 nmol/L). A cutoff of 2.92 nmol/L differentiated CD from HS with 100% sensitivity and 96.7 % specificity, and a cutoff of 5.04 nmol/L yielded a specificity of 100% with a sensitivity of 96.4% to distinguish CD from OS. There was more intra-individual variability in HS (55%) than in CD (49%) and OS (22%). There was no difference in the sensitivity and specificity derived from the ROCs using day 1 values or the higher of the 2 LNSCs., Conclusions: In our cohort, we found that LNSC assayed by EIA showed good sensitivity and specificity to screen patients suspected to have CD. Although intra-individual variability was significant, it did not hamper the diagnostic performance of the test.

Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. He underwent second surgery and, postoperatively, hypercostisolism persisted even after 2 years of surgery. Repeat evaluations after 8 years of second surgery revealed persistent hypocortisolism despite residual tumour of same size and similar plasma adrenocorticotropic hormone (ACTH) levels. We have also shown that the paradoxical increase in serum cortisol was preceded by a paradoxical increase in ACTH. The paradoxical response persisted despite hypocortisolism. This patient with Cushing's disease had two very rare features: paradoxical response to dexamethasone and spontaneous development of hypocortisolism.

Catecholamine-induced vasculitis is a well known but rarely described entity. However, aortoarteritis as a manifestation of catecholamine-induced vasculitis is not described in the literature. We have reported two patients in whom pheochromocytoma coexisted with aortoarteritis. Both patients were young females with history of bilateral pheochromocytomas in more than one first-degree relative. Both patients also had bilateral adrenal pheochromocytomas (second patient also had paraganglioma at left renal hilum) with elevation of plasma free normetanephrine levels. We conclude that there may be an association between pheochromocytoma and aortoarteritis, and that catecholamine excess may have a role in the etiopathogenesis of aortoarteritis in these patients.

Objective: To establish pediatric reference ranges for plasma fractionated free metanephrines by enzyme immunoassay (EIA) and to evaluate its performance in the diagnosis of catecholamine-secreting tumors in the pediatric population., Methods: Normotensive children and children with suspected catecholamine-secreting tumors underwent measurement of plasma fractionated metanephrines by EIA to establish pediatric reference ranges. Children with suspected pheochromocytoma or paraganglioma also underwent magnetic resonance imaging or computed tomography from the neck to the pelvis and were followed up for a minimum of 1 year. Diagnosis of pheochromocytoma/paraganglioma was confirmed by histologic examination. Pheochromocytoma/paraganglioma was excluded in children who had a histologic diagnosis other than pheochromocytoma/paraganglioma and in those who had no imaging evidence of tumor and no progression on follow-up., Results: Plasma fractionated metanephrines were measured in 78 normotensive children (age range, 1.5-17 years) and in 38 children with suspected catecholamine-secreting tumors. Of the 38 children (age range, 6-17 years) with suspected pheochromocytoma/paraganglioma, 17 had a histopathologically proven catecholamine-secreting tumor. The newly derived pediatric upper reference limit for metanephrine (128 pg/mL) was higher than in adults (90 pg/mL), whereas the pediatric upper reference limit for normetanephrine (149 pg/mL) was lower than in adults (180 pg/mL). The manufacturer's reference range for plasma fractionated metanephrines yielded a sensitivity of 100% and a specificity of 85.7%. Use of newly established pediatric reference ranges increased the specificity to 95.2% without altering the sensitivity (100%)., Conclusions: Plasma fractionated metanephrines by EIA provide an accurate test with good sensitivity and specificity for the diagnosis of pheochromocytoma and paraganglioma in children. Use of pediatric reference ranges improves accuracy of the test.

Pregnancy occurs rarely in patients with Cushing syndrome (CS) due to hypercortisolism. So far, about 150 cases of CS in pregnancy have been reported in the literature. We describe a 22-year-old female who presented in pregnancy with clinical features of CS. She delivered at 34 weeks of gestation and baby had transient adrenal insufficiency in the neonatal period. Mother underwent transsphenoidal surgery 1 year postpartum and on follow up she is under remission. Neonatal hypoadrenalism should be anticipated in maternal CS.

Certain pituitary imaging abnormalities are a specific indicator of hypopituitarism. The objective of this study is to compare phenotypical features with radiological findings in patients with congenital growth hormone deficiency (GHD). Magnetic Resonance imaging (MRI) was performed in 103 patients [72 with Isolated GHD (IGHD) and 31 with Combined Pituitary Hormone Deficiency (CPHD)]. Images were assessed for the following abnormalities: (1) small/absent anterior pituitary, (2) thin or interrupted pituitary stalk (PSA), and (3) Ectopic posterior pituitary (EPP), and (4) others. Radiological findings were correlated with the clinical and biochemical parameters. MRI abnormalities were observed in 48.6% patients with IGHD, 93.5% with CPHD. Jaundice, hypoxia, hypoglycemia and breech deliveries were more common in EPP/PSA group. EPP/PSA was observed in 87.1% patients with severe GHD (peak GH < 3 μg/L) as compared to 12.9% with mild to moderate GHD (peak GH: 3-10 μg/L). Amongst CPHD, EPP/PSA was present in 80% of subjects with associated hypocortisolism ± hypothyroidism as compared to 18.2% of subjects with hypogonadism. Over a mean follow up period of 4.5 years, 5.4% of subjects with IGHD and abnormal MRI progressed to CPHD while none of those with normal MRI progressed. This study emphasizes a significant clinico-radiological correlation in Asian Indian GHD patients. MRI abnormalities in the hypothalamic pituitary area, especially EPP/PSA are more common in patients with CPHD and severe GHD. Among CPHD, EPP/PSA predicts association with hypothyroidism or hypocortisolism. IGHD with MRI abnormality may evolve into CPHD.

Unlabelled: Information on vitamin D status of Indian health care professionals is limited. Among 2,119 subjects studied, just 6 % were found to be sufficient in vitamin D status. There is urgent need of an integrated approach to detect and treat vitamin D deficiency among health care professionals to improve on-the-job productivity., Introduction: Vitamin D deficiency is prevalent worldwide. India has been reported to be one of the worst affected countries. Several single-center studies from India have shown high prevalence of vitamin D deficiency. Little is known regarding the vitamin D status of Indian health care professionals., Aim: This study aimed to determine prevalence of vitamin D deficiency among health care professionals in different regions of India., Method: In this cross-sectional, multicenter study, we enrolled 2,119 medical and paramedical personnel from 18 Indian cities. Blood samples were collected from December 2010 to March 2011 and analyzed in a central laboratory by radioimmunoassay. Vitamin D deficiency was defined as 25-hydroxyvitamin D [25(OH)D] <20 ng/mL or <50 nmol/L, insufficiency as 25(OH)D = 20-30 ng/mL or 50-75 nmol/L, and sufficiency as 25(OH)D >30 ng/mL or >75 nmol/L., Results: Mean (±SD) age of subjects was 42.71 ± 6.8 years. Mean (±SD) 25(OH)D level was 14.35 ± 10.62 ng/mL (median 11.93 ng/mL). Seventy-nine percent of subjects were deficient, 15 % were insufficient, and just 6 % were sufficient in vitamin D status. No significant difference was found between vitamin D status in southern (25(OH)D = 13.3 ± 6.4 ng/mL) and northern (25(OH)D = 14.4 ± 8.5 ng/mL) parts of India., Conclusion: Our study confirms the high prevalence of vitamin D deficiency all across India in apparently healthy, middle-aged health care professionals.

Objective: To study the performance of measuring plasma fractionated free metanephrines by enzyme immunoassay (EIA) in the diagnosis of pheochromocytoma and catecholamine-secreting paraganglioma., Methods: Consecutive patients attending the endocrine clinic at King Edward Memorial Hospital, Mumbai, India, for suspicion of catecholamine-secreting tumors were included. Plasma fractionated free metanephrines were measured by EIA, and computed tomography of the neck, chest, abdomen, and pelvis was performed. Those with tumor identified by imaging underwent 131I m-iodobenzylguanidine scintigraphy. All patients with adrenal masses larger than 3 cm and patients with secretory tumors, irrespective of their size, underwent tumor excision. The rest were followed up for 6 to 12 months., Results: One hundred patients with a clinical suspicion of pheochromocytoma or paraganglioma were included. Plasma free normetanephrine alone had a sensitivity of 94.1% (cutoff: 180 ng/mL), while plasma free metanephrine had a sensitivity of 14.7% (cutoff: 90 pg/mL). Both had 96.9% specificity. When combined (either test positive), the sensitivity was 94.1% with a specificity of 93.75%. Thirty-four patients had a histopathologically proven pheochromocytoma or paraganglioma. It was concluded that 66 patients did not harbor a pheochromocytoma or catecholamine-secreting paraganglioma., Conclusion: Plasma fractionated free metanephrines measured by EIA have good sensitivity and specificity in the diagnosis of pheochromocytoma and catecholamine-secreting paraganglioma.

Dyslipidaemia is one of the most important modifiable risk factors for coronary disease. Despite the availability of highly effective lipid-modifying agents, many patients still do not reach lipid targets established by national guidelines. This, in turn, has prompted a resurgence of the search for drugs and algorithms that favourably affect the lipid profile. The preventive efforts made so far have demonstrated that lowering low density lipoprotein-cholestrol is one action that individuals and populations can do with significant success in delaying the onset of clinical events, but at the same time one should not neglect high density lipoprotein and triglyceride levels as they also play a significant role in the risk of developing complications. Combination regimens should be considered for use in patients who fail to meet target values and are compliant with their current therapy. Although the use of combination therapy varies considerably across the globe, this treatment strategy is becoming increasingly more common as treatment guidelines recommend more aggressive therapy in order to achieve lower target cholesterol goals.

Objective: We describe a rare combination of pheochromocytoma and medullary thyroid carcinoma (MTC) during pregnancy., Methods: Twenty-three-years old lady, primigravida, was detected to be hypertensive at 12 weeks of gestation and was found to have left adrenal mass on routine obstetric scan. She had a goitre on examination which was proven to be MTC on fine needle aspiration cytology. Twenty-four hours urinary vanillyl mandelic acid and serum calcitonin levels were elevated. After adequate α and β blockade she underwent left adrenalectomy during second trimester of gestation with no significant perioperative complications. Twelve days later she underwent total thyroidectomy., Results: Adrenal mass was confirmed to be pheochromocytoma while MTC was confirmed in the thyroidectomy specimen. Post-operatively, she was normotensive and delivered a healthy female baby at term. Both mother and the baby tested positive for germline RET mutation (C634W) in exon 11., Conclusion: We describe a rare case of pregnant multiple endocrine neoplasia-2A patient with pheochromocytoma and MTC.

Aims: To study the prevalence of upper airway obstruction (UAO) in "apparently asymptomatic" patients with euthyroid multinodular goitre (MNG) and find correlation between clinical features, UAO on pulmonary function test (PFT) and tracheal narrowing on computerised tomography (CT)., Materials and Methods: Consecutive patients with apparently asymptomatic euthyroid MNG attending thyroid clinic in a tertiary centre underwent clinical examination to elicit features of UAO, PFT, and CT of neck and chest., Statistical Analysis Used: Statistical analysis was done with SPSS version 11.5 using paired t-test, Chi square test, and Fisher's exact test. P value of <0.05 was considered to be significant., Results: Fifty-six patients (52 females and four males) were studied. The prevalence of UAO (PFT) and significant tracheal narrowing (CT) was 14.3%. and 9.3%, respectively. Clinical features failed to predict UAO or significant tracheal narrowing. Tracheal narrowing (CT) did not correlate with UAO (PFT). Volume of goitre significantly correlated with degree of tracheal narrowing., Conclusions: Clinical features do not predict UAO on PFT or tracheal narrowing on CT in apparently asymptomatic patients with euthyroid MNG.