New Onset Diabetes After COVID 19 (NODAC) is predominantly due to exacerbated Insulin Resistance (IR) rather than beta cell dysfunction: Lessons from tertiary care hospital data during confluence of two epidemics.

PURPOSE: To investigate determinants of new onset diabetes after COVID-19 (NODAC) and its recovery at 6 months. METHODS: This was an observational follow up study conducted from August, 2020 to July, 2023, recruiting patients with preexisting DM and COVID 19 patients with no history of DM. Multivariate regression analysis was used to determine the factors responsible for severity of COVID 19 infection in preexisting DM group. Clinical, laboratory and glycometabolic parameters were estimated at baseline and 6 months in NODAC and euglycemic group to determine the factors responsible for NODAC and its persistence at 6 months. RESULTS: Of 1310 patients, 855 (65.3%) COVID 19 patients were further divided based on their glycemic status: preexisting DM (19%), NODAC (8.5%) and euglycemia (72.5%). Older age and male gender were independent risk factors for severe COVID 19 disease in patients with preexisting diabetes. Prevalence of NODAC in present study was 8.5%. Patients with NODAC had higher mean fasting blood glucose (FBG), random blood glucose (RBG) and HbA1c at baseline as compared to COVID with euglycemic group with no difference in serum C-peptide levels. Female gender, family history of DM, signs of insulin resistance, higher BMI, WHR, HbA1c, serum insulin levels, FBG and RBG predicted persistence of NODAC at 6 months. CONCLUSION: Preexisting DM is a risk factor for severe COVID 19 disease. Patients with NODAC have evidence of persistence insulin resistance on follow up, underscoring the need for long term glycemic monitoring.

Spondyloocular Syndrome: First Case of Rare Osseous and Ocular Syndrome from India with Novel Mutation and Expanded Phenotypic Spectrum.

Spondyloocular syndrome (SOS) is a rare autosomal recessive skeletal and ocular disorder with variable phenotypes. It is caused by pathogenic mutation in the XYLT2 gene, which encodes the enzyme xylo-transferase, necessary for the synthesis of proteoglycan. It is characterized by generalized osteoporosis, short stature, hearing impairment, eye abnormalities, and cardiac defects. Till date only 24 cases have been reported worldwide with no cases documented from India. We subjected the patient to relevant biochemical investigations and Dual Energy X-ray Absorptiometry (DEXA) scan along with Next Generation Clinical Exome Sequencing (NGCES). We report a case of 23-year-old male who presented with recurrent long bone fractures, congenital heart defects, eye abnormalities (bilateral corneal opacities and atrophic bulbi), and short stature. In addition, our patient also had genu valgum and right-sided hydrocele which have never been reported in SOS till date. On genetic analysis, NGCES revealed a novel pathogenic frameshift variant c.191_192 delCA, p.(Thr64fs*22) in the XYLT2 gene. The patient is doing well on six monthly zoledronic acid infusions.

Clinical, Biochemical and Surgical Outcomes of Primary Hyperparathyroidism in the Present Era: A Prospective Study From a Tertiary Care Hospital.

Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic. This is the first large study from North India to study the clinical and biochemical features and surgical outcomes in the present era. Study design This is a cross-sectional study that was conducted in the Department of Endocrinology (SKIMS) from February 2021 to December 2022, in which 103 patients diagnosed with PHPT were included. Evaluation included measurement of total calcium, phosphorus, alkaline phosphate, intact parathyroid hormone, 25-hydroxy vitamin, 24-hour urinary calcium, radiological survey of hands and skull, Dual Energy X-ray absorptiometry, and ultrasonography (USG) of the abdomen. USG neck and technetium-99m sestamibi scans were used for preoperative localization; however, in cases of discordance between these investigations or suspicions of multi-glandular disease, four-dimensional computerized tomography of the neck was used. Patients were subjected to surgery according to the guidelines and monitored post-surgery for complications like hypocalcemia and hungry bone syndrome and to document the cure. Results The mean age of patients was 42.8±14.73 years, with a female-to-male ratio of 4.4:1. The mean eGFR of patients was 99.1±30.87 ml/min, with 55 (53.4%) of them having renal disease. Osteoporosis and fractures were present in 41 (39.8%) and 5 (4.8%) patients, respectively. Cholelithiasis and pancreatitis were present in 25 (24.3%) and 5 (4.9%) patients, respectively. Hypertension (HTN) and diabetes mellitus (DM) were the commonest comorbidities, which were present in 34 (33.1%) and 15 (14.5%) patients, respectively. Mean preoperative levels of calcium, phosphorus (PO4), alkaline phosphate (ALP), intact parathyroid hormone (iPTH), 25(OH)vitamin D, and 24-hour urinary calcium were 12.1 mg/dl, 2.35 mg/dl, 210.2 U/L, 332.9 pg/ml, 25.7 ng/ml, and 452.1 mg/day, respectively. The most common type was right inferior parathyroid adenoma, present in 45 cases (43.7%), followed by left inferior parathyroid adenoma in 31 cases (30.1%). A total of 75 patients (72.8%) underwent minimally invasive parathyroidectomy, with 68 patients (90.7%) achieving a biochemical cure. The mean adenoma weight was 3.19±2.25 g. There was no statistically significant correlation (r) between preoperative biochemical parameters and adenoma weight. Conclusion Despite improvements in imaging and the easy availability of immunoassays for early diagnosis, renal disease continued to be the most common presentation, followed by skeletal involvement in our population. In developing countries like India, any patient presenting with nephrolithiasis or nephrocalcinosis, low bone mass, or fragility fractures should be evaluated for PHPT.

Pituitary stalk interruption syndrome due to novel ROBO1 mutation presenting as combined pituitary hormone deficiency and central diabetes insipidus.

OBJECTIVES: The genetic causes of pituitary stalk interruption syndrome (PSIS) remain elusive in 95 % of cases. The roundabout receptor-1 gene (ROBO1) plays critical roles in axonal guidance and cell migration. Recently, mutations in the ROBO1 gene have been reported patients with PSIS. CASE PRESENTATION: We report a 2.9-year-old boy with PSIS who presented with combined pituitary hormone deficiency, central diabetes insipidus, and the classical triad of MRI findings. Through clinical exome sequencing using next-generation sequencing techniques, a previously unidentified novel heterozygous frame shift mutation in the ROBO1 gene was identified. This is the first report of ROBO1 mutation associated with posterior pituitary dysfunction. CONCLUSIONS: We conclude and emphasize that ROBO1 should be investigated in patients with PSIS. Our case is unique in the published literature in that we are first time reporting posterior pituitary dysfunction as manifestation of ROBO1 mutation. The full clinical spectrum of the mutations may not be fully known.

Subacute Thyroiditis in Active COVID-19 Infection: A Report of Two Cases With a Systematic Review of the Literature.

Subacute thyroiditis (SAT) is a self-limiting inflammatory condition of the thyroid gland with distinct symptoms and a predictable outcome. During the current COVID-19 pandemic, there have been multiple isolated reports of SAT either during the active viral illness or following recovery. Here, we report two such cases of COVID-19 infection presenting with SAT. A 65-year-old male presented with a two-week history of anterior neck pain, odynophagia, high-grade fever (38.9°C), sweating, palpitations, and tremulousness. At physical examination, the patient presented with a slightly increased heart rate and a tender and enlarged thyroid on palpation. Laboratory examination showed high C-reactive protein levels, with elevated erythrocyte sedimentation rate, and thyroid function tests were suggestive of thyrotoxicosis. Ultrasonography showed a heterogeneous thyroid gland with ill-defined hypoechoic areas, and thyroid scintigraphy showed reduced uptake, confirming the diagnosis of SAT. In another case, a 52-year-old male presented with fever, cough, and myalgias, and was diagnosed with mild COVID-19 pneumonia, and managed conservatively. After two weeks, the patient had a recurrence of high-grade fever, odynophagia, palpitations, and tremors. Examination revealed tachycardia, hyperhidrosis, and a tender and enlarged thyroid on palpation. Thyroid function tests revealed low thyroid-stimulating hormone, with normal total T4 and total T3. Ultrasonography examination showed a heterogeneous thyroid gland with bilateral ill-defined hypoechoic areas. In our systematic review, including 103 SAT cases, it has been suggested that SAT should be recognized as an uncommon extra-pulmonary clinical manifestation of COVID-19 infection and clinicians need to be aware of the association. Pending larger multicentric studies, management of the condition has to be on a case-by-case basis.

Spectrum of EGFR mutation and its relation with high-risk predictors in thyroid cancer in Kashmiri population: 2 years prospective study at a tertiary care hospital.

BACKGROUND: EGFR mutation has not been extensively studied in thyroid cancer. This study was conducted to study spectrum of EGFR mutation in thyroid cancer in Kashmiri population for possible therapeutic purpose. METHODS: It was 2 years prospective cross-sectional study conducted at a tertiary care center in which histologically confirmed, untreated thyroid cancers were included. These specimens were subjected to EGFR mutation analysis by AS-PCR method. RESULTS: There were a total 60 patients with preponderance of females [44(73%) vs 16(27%)]. Most were in the age group of less than 45 years (75%). Most of these patients were non-smokers [50(83.3%) vs 10 (17.3%)]. Papillary thyroid carcinoma (PTC) was the commonest type 48(80%), rest was follicular type (FTC) 12(20%). Well-differentiated carcinoma (WDC) was common than poorly differentiated (PDC) [41(68.4%) vs 19 (31.6%)]. Lymph node metastasis and vascular invasion were present in 32 (53.4%) and 17 (28.4%) respectively. Thirty-two (53.3%) patients were having 15 bp deletion in exon 19 of EGFR. These deletions were common in PTC than FTC, 29(60.5%) vs 3(25%) which was statistically significant (p = 0.04, CI = 0.2). The total mutational rate of T790M in EGFR tyrosine kinase domain (exon 20) was found to be only 8.4% (5 of 60). Only 4 (8.3%) of these mutations were detected in PTC and rest in FTC (1 of 12). Twenty-six (43.3%) of exon 21 were positive for L858R mutation in EGFR tyrosine kinase domain. Married persons and PDC were significant predictors of L858R mutation in EGFR tyrosine kinase domain in thyroid cancer as this was statistically significant in them with p = 0.04, 0.03 respectively. CONCLUSION: In our population, PTC is common in females with half of population harboring EGFR mutation and it is statistically significant in poorly differentiated carcinoma and in married individuals. It implies that EGFR may be used in thyroid cancer as a possible therapeutic agent in our set of population.