Background:Metabolic syndrome is typically polygenic; however, rare monogenic forms such as DYRK1B-associated abdominal obesity-metabolic syndrome 3 (AOMS 3) exist. We report a case with an AOMS 3-like phenotype and highlight novel features and treatment response. Case Report:A 21-year-old woman with metabolic syndrome was initially misdiagnosed as polycystic ovarian syndrome. She had abdominal obesity, hyperglycemia, hypertriglyceridemia, and hyperandrogenism. Genetic analysis revealed a heterozygous DYRK1B c.755G>A (p.R252H) variant. She lacked prominent adipogenesis. Due to inadequate control with conventional oral antidiabetic therapy, sodium glucose co-transporter 2 (SGLT2) inhibitor was initiated, leading to metabolic improvement over 6 months. Discussion:This case expands the phenotypic spectrum of DYRK1B-associated AOMS 3 by demonstrating hyperandrogenism, severe hypertriglyceridemia, and absence of marked adipogenesis. It also suggests a potential therapeutic role of SGLT2 inhibitors in such patients. Conclusion:DYRK1B variants should be considered in young patients with atypical metabolic syndrome. SGLT2 inhibitors may provide benefit when conventional therapy is inadequate.

Sindbis virus (SINV), belonging to the genus Alphavirus, is the causative agent of Pogosta disease in humans. The clinical infection is characterized by fever, malaise, rash, myalgia, and arthralgia, which is generally self-limiting. Chronic infection with SINV triggers autoimmune conditions that lead to persistent arthritis. Despite its clinical relevance, no licensed vaccine is currently available for the prevention of SINV infection. To the best of our knowledge, this study presents the first in silico design and evaluation of a multi-epitope vaccine candidate against SINV. Using an integrated immunoinformatics framework, the SINV structural polyprotein was systematically screened, leading to the identification of twelve highly antigenic immunological hotspots, derived from both experimentally validated and computationally predicted B-cell and T-cell epitopes. These epitopes were rationally assembled into a 317-amino acid multi-epitope vaccine construct using suitable linkers and the human β-defensin 2 as an immunostimulatory adjuvant. The designed construct exhibited favorable antigenicity, non-toxicity, stability, and physicochemical properties. Molecular docking and molecular dynamics simulations demonstrated encouraging interactions between the vaccine construct and innate immune receptors TLR-2 and TLR-4, highlighting its potential to trigger immune responses. Immune simulation predicted robust humoral and cell-mediated immune responses, while codon optimization and in silico cloning into the pETite vector indicated expression feasibility in Escherichia coli K12. This work proposes a novel immunoinformatics and molecular dynamics-based vaccine design pipeline for Sindbis virus and presents a computationally validated multi-epitope vaccine candidate, providing a foundation for future experimental validation toward effective vaccine development.

Background Pancreatic cancer (PC) has a high fatality rate and is often diagnosed late. Obesity is a significant risk factor for PC, leading to inflammation and altered gut microbiota that may contribute to its development. Non-alcoholic fatty liver disease (NAFLD) is linked to obesity but its association with PC risk remains unclear. Both PC and NAFLD may share genetic factors, and research is ongoing to understand their underlying mechanisms through comprehensive sequencing data analysis. Method The study utilized bioinformatics tools and databases to analyze gene expression data from PC and obese NAFLD. Differential gene expression, enrichment analysis, and protein-protein interaction analysis identified potential biomarkers and therapeutic targets. Survival analysis validated hub genes, and correlation analysis was used to evaluate the relationships between immune cells and PC. Prognostic miRNA analysis and drug sensitivity assessment revealed predictive biomarkers for drug efficacy. Statistical methods were applied to evaluate significance. Results The study compared gene expression profiles between PC and NAFLD, revealing 58 common genes. Important pathways such as tyrosine metabolism, fatty acid degradation, and glycolysis/gluconeogenesis were revealed by enrichment analysis to be connected to the common genes in both diseases. Notably, five hub genes (MARCO, COL11A1, CDCP1, CLEC5A, COL6A6) emerged as potential players in PC and NAFLD. Survival analysis confirmed their significance in PC prognosis. The study also identified hsa-miR-29c-3p as a promising prognostic biomarker targeting COL11A1 in PC, along with the long non-coding RNA (IncRNA) taurine-upregulated gene 1 (TUG1) axis, which was associated with poor survival of PC patients. The clinical significance of hsa-miR-29c-3p was highlighted by Receiver Operating Characteristic (ROC) curve analysis, which also provided insight into the relationships between chemo-resistance, particularly with regard to Capecitabine. Conclusion The study identified the shared genetic factor COL11A1 as a possible biomarker in PC and NAFLD. Notably, hsa-miR-29c-3p emerged as a promising prognostic biomarker targeting COL11A1 in PC, with implications for patient survival. These findings contribute to our understanding of the underlying mechanisms and may offer clinical significance in predicting outcomes and guiding therapeutic approaches for these challenging diseases.

The ongoing global threat posed by the influenza A virus, exacerbated by antigenic drift and the emergence of antiviral resistance, accentuates the urgent need for innovative therapeutic strategies. Through molecular docking, this study revealed that mangiferin has a strong binding affinity for the active site of the neuraminidase (NA) protein of influenza virus A(H1N1)pdm09, with a binding energy of −8.1 kcal/mol. In vitro assays confirmed a dose-dependent inhibition of NA, with an IC50 of 88.65 μM, and minimal cytotoxicity, as indicated by a CC50 of 328.1 μM in MDCK cells. In murine models, the administration of mangiferin at a dosage of 25 mg/kg significantly mitigated weight loss, decreased viral loads in nasal turbinates and lungs by over 1 log10 TCID50, and enhanced survival rates from 0% in control groups to 20% in mangiferin-treated group at 14 days post-infection. In addition, mangiferin was found to modulate host immune responses by simultaneously inhibiting pro-inflammatory cytokines, IL-6 and TNF-α, and upregulating the expression of anti-inflammatory IL-10 and antiviral IFN-γ, thus mitigating infection-induced inflammation. Our findings elucidate the dual mechanism of mangiferin involving the direct inhibition of NA and immunomodulation, thereby providing experimental evidence for exploring dual-mechanism-based anti-influenza strategies against resistant strains of influenza.

Type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC) have a strong bidirectional relationship. T2DM increases the risk of developing HCC, mainly through the nonalcoholic steatohepatitis pathway, but a significant proportion of patients develop HCC without developing cirrhosis. The identification of HCC in T2DM patients is difficult considering the low incidence of HCC and the high prevalence of T2DM. However, considering the alarming increase in the incidence of diabetes mellitus in the global population, effective strategies are urgently needed to identify patients at high risk. Nonetheless, various classes of drugs, such as sodium-glucose cotransporter-2 inhibitors and incretin analogs, may be promising for reducing the risk of nonalcoholic steatohepatitis and HCC development in T2DM patients in the future. In this review, we discuss all these facets of the relationship between HCC and T2DM, and we summarize future directions.

Context Pachydermoperiostosis (primary hypertrophic osteoarthropathy, PHO), usually due to biallelic loss of function variants in HPGD and SLCO2A1, has some features overlapping with acromegaly and is often referred to endocrinologists. A detailed endocrine assessment is not available for these patients.Objective To assess the genetic and endocrine characteristics of patients with PHO referred to endocrine centers with a possible diagnosis of acromegaly.Methods Seventeen patients from 14 families in which acromegaly was excluded based on lack of elevated insulin-like growth factor (IGF)-1 levels and/or growth hormone suppression on an oral glucose tolerance test were assessed for HPGD and SLCO2A1 variants.Results Age at diagnosis was 26.2 +/- 9.0 years (mean +/- SD, range 9-43). Digital clubbing was present in all patients. Periostosis (94%), arthralgia (88%), periarticular edema (77%), pachydermia (82%), and coarsened facial features resembling acromegaly (71%) were present in the vast majority of the patients, while eyelash trichomegaly, blepharoptosis, high-arched palate, gingival hypertrophy, gastrointestinal symptoms, and marfanoid habitus were seen in some. Nine patients (53%) had low IGF-1 levels; the rest of the patients had IGF-1 levels in the lowest quartile of the reference range. Estradiol concentration was increased above the normal range in 8 male patients (62%) with normal testosterone and prolactin levels. Biallelic HPGD (2/14 kindreds) or SLCO2A1 (8 novel) variants (12/14 kindreds) were found. Two patients had no identifiable pathogenic/likely pathogenic variant in HPGD or SLCO2A1. Their phenotype was not different from the other patients.Conclusion We establish that low IGF-1 and elevated estradiol levels are frequent features of PHO. Nine novel and 5 known pathogenic/likely pathogenic genetic variants were identified.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Recent global outbreak of monkeypox virus (MPXV) infections has challenged global public health. Infection cases have been reported from various countries such as North Africa, Middle East, Australia, the Americas, and Europe. Monkeypox virus is zoonotic in the genus Orthopoxvirus that can infect animals as well as human beings. The apprehensions over available therapeutics and vaccines necessitates an immediate need for exploring effective antivirals targeted specifically against MPXV infections. Our study employs extensive molecular docking and molecular dynamics simulations to explore the therapeutic potential of cyanobacterial proteins targeted against envelope proteins of MPXV. AutoDock tools were used to prepare the proteins under study. Molecular docking was executed using PATCHDOCK server. High-score compound was then confirmed using the molecular dynamics simulation for 120 ns using GROMACS ver. 2019 with GROMOS96 43a1 force field parameters. PRODIGY HADDOCK server was used to calculate the binding energies. Dimplot software were used to analyze the protein–protein complexes with lowest binding score and the interactive residues were studied using Ligplot. Our data establish cyanovirin as a promising inhibitor of MPXV envelope proteins A26, A27, D8L, and H3, and generates scope for future in vitro and in vivo studies towards therapeutic development.

Objectives: Captopril is a commonly used therapeutic agent in the management of renovascular hypertension (high blood pressure), congestive heart failure, left ventricular dysfunction following myocardial infarction, and nephropathy. Captopril has been found to interact with proteins that are significantly associated with bladder cancer (BLCA), suggesting that it could be a potential medication for BLCA patients with concurrent hypertension. Methods: DrugBank 5.0 was utilized to identify the direct protein targets (DPTs) of captopril. STRING was used to analyze the multiple protein interactions. TNMPlot was used for comparing gene expression in normal, tumor, and metastatic tissue. Then, docking with target proteins was done using Autodock. Molecular dynamics simulations were applied for estimate the diffusion coefficients and mean-square displacements in materials. Results: Among all these proteins, MMP9 is observed to be an overexpressed gene in BLCA and its increased expression is linked to reduced survival in patients. Our findings indicate that captopril effectively inhibits both the wild type and common mutated forms of MMP9 in BLCA. Furthermore, the LCN2 gene, which is also overexpressed in BLCA, interacts with captopril-associated proteins. The overexpression of LCN2 is similarly associated with reduced survival in BLCA. Through molecular docking analysis, we have identified specific amino acid residues (Tyr179, Pro421, Tyr423, and Lys603) at the active pocket of MMP9, as well as Tyr78, Tyr106, Phe145, Lys147, and Lys156 at the active pocket of LCN2, with which captopril interacts. Thus, our data provide compelling evidence for the inhibitory potential of captopril against human proteins MMP9 and LCN2, both of which play crucial roles in BLCA. Conclusion: These discoveries present promising prospects for conducting subsequent validation studies both in vitro and in vivo, with the aim of assessing the suitability of captopril for treating BLCA patients, irrespective of their hypertension status, who exhibit elevated levels of MMP9 and LCN2 expression.

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic dysfunction characterized by hyperglycemia. T2DM is a growing global epidemic with diffuse complications, including a high mortality rate. High blood sugar can be lowered by impeding the activities of pancreatic alpha-amylase and intestinal alpha-glucosidase enzymes. Although there are a number of orthodox medications used in the management of hyperglycemia, medicinal plants remain a veritable option in many cultures of the world owing to their overall efficacy and affordability. This study was designed to investigate the hypoglycemic potential of Syzygium cordatum leaf extract fractions in the retardation of pancreatic alpha-amylase and intestinal alpha-glucosidase enzymes in vitro. The bioactive components of the active fractions were identified using the Gas Chromatography-Mass Spectrometry (GC-MS) and their potential hypoglycemic properties were assessed using the molecular in silico modelling approach. The in vitro alpha-amylase and alpha-glucosidase inhibitory activities of S. cordatum revealed that the organic solvent fractions retarded the digestive enzymes considerably although the standard drug (acarbose) had the least half-maximal inhibitory concentration (IC50) value. Analytical and computational analysis identified the potential of cubenol, to interact with important residues of alpha-glucosidase and alpha-amylase emphasizing its hypoglycemic potential. The result of this study revealed that S. cordatum is a rich source of pharmacologically important bioactive compounds with a remarkable capacity to retard alpha-amylase and alpha-glucosidase enzymes. Cubenol was identified as an efficient and safe hypoglycemic agent of S. cordatum. (c) 2024 SAAB. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Introduction: The aim of this study was to compare insulin sensitivity, islet cell function, and incretin axes in pregnant subjects with GDM and normal healthy controls. Methods: Pregnant women at 24 to 28 weeks of gestation were subjected to a 75 g oral glucose tolerance test (OGTT). Samples for glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were collected at 0, 30, 60, and 120 min during the OGTT. The Matsuda index (MI) and insulin secretion and sensitivity index-2 (ISSI-2) were assessed. The glucagon suppression index (GSI) was calculated along with the area under the curve (AUC) for glucose, insulin, glucagon, GLP-1, and GIP. Results: A total of 48 pregnant women (25 GDM and 23 controls) were finally analysed. The MI and ISSI-2 were low in the GDM group [4.31 vs. 5.42; P = 0.04], [1.99 vs. 3.18, P ≤ 0.01] respectively). Total AUCglucagon was higher in the GDM group (7411.7 vs. 6320.1, P = 0.02). GSI30 was significantly lower in the GDM group (-62.6 vs. -24.7, P = 0.03). Fasting GLP-1 levels were low in GDM women (17.3 vs. 22.2, P = 0.04). The total AUCGLP-1 positively correlated with total GSI in the GDM group. Conclusion: Asian-Indian GDM women have high insulin insensitivity, islet cell dysfunction, and low fasting GLP-1. Incretin axis dysfunction plays a potential role in their islet cell dysfunction.

Hypophosphatemic osteomalacia in an adult often gives clinical diagnostic challenges. Usually, they are caused by either tumor-induced osteomalacia or due to genetically mediated hypophosphatemia, particularly X-linked hypophosphatemia. However, heavy metal toxicity, leading to global proximal renal tubular dysfunction, is a rare cause, and in particular, cadmium toxicity is rarely encountered in clinical practice. The presence of bony pain and neurological deficit, along with a classical exposure history, provides the diagnostic clue. In this background, here we present a middle-aged man who had severe bony pains all over his body and lower back stiffness for five years. He underwent an initial workup as a suspected spondyloarthropathy but was later on, found to have hypophosphatemic osteomalacia and severe proximal renal tubular dysfunction. Further, the workup revealed elevated FGF-23. His occupational history revealed prolonged exposure to cadmium fumes in the silverware industry. He improved moderately with treatment; however, significant renal damage is still present. This case highlights the importance of considering cadmium toxicity in proper clinical and occupational contexts in the evaluation of hypophosphatemic osteomalacia in an adult.

The majority of patients with congenital adrenal hyperplasia (CAH) present with a deficiency of 21-hydroxylase or 11-beta-hydroxylase, which account for 90% and 7% of cases, respectively. However, CAH due to 17α-hydroxylase deficiency (17OHD) is an extremely rare form of CAH (<1% of all CAH cases) that leads to a deficiency of cortisol and sex steroids, along with features of aldosterone excess. This is a case of a 51-year-old single female who was referred to us for the evaluation of new-onset hypertension and hypokalaemia of one-year duration. She was born out of a second-degree consanguineous marriage and reared as a female. She was diagnosed to have testicular feminization syndrome when she presented with a history of primary amenorrhea, absence of secondary sexual characteristics, and bilateral labial swellings at pubertal age. Subsequently, she underwent gonadectomy at the age of 16. Due to the presence of hypertension, metabolic alkalosis and bilaterally enlarged adrenals on CT scan, 46, XY disorders of sexual development (DSD) was considered. A karyotype confirmed the presence of 46, XY chromosomal sex, and genetic analysis revealed a mutation in the CYP17A1 gene, thus confirming the diagnosis of 17α-hydroxylase deficiency.

The discovery of prenatal and neonatal molecular biomarkers has the potential to yield insights into autism spectrum disorder (ASD) and facilitate early diagnosis. We characterized metabolomic profiles in ASD using plasma samples collected in the Norwegian Autism Birth Cohort from mothers at weeks 17–21 gestation (maternal mid-gestation, MMG, n = 408) and from children on the day of birth (cord blood, CB, n = 418). We analyzed associations using sex-stratified adjusted logistic regression models with Bayesian analyses. Chemical enrichment analyses (ChemRICH) were performed to determine altered chemical clusters. We also employed machine learning algorithms to assess the utility of metabolomics as ASD biomarkers. We identified ASD associations with a variety of chemical compounds including arachidonic acid, glutamate, and glutamine, and metabolite clusters including hydroxy eicospentaenoic acids, phosphatidylcholines, and ceramides in MMG and CB plasma that are consistent with inflammation, disruption of membrane integrity, and impaired neurotransmission and neurotoxicity. Girls with ASD have disruption of ether/non-ether phospholipid balance in the MMG plasma that is similar to that found in other neurodevelopmental disorders. ASD boys in the CB analyses had the highest number of dysregulated chemical clusters. Machine learning classifiers distinguished ASD cases from controls with area under the receiver operating characteristic (AUROC) values ranging from 0.710 to 0.853. Predictive performance was better in CB analyses than in MMG. These findings may provide new insights into the sex-specific differences in ASD and have implications for discovery of biomarkers that may enable early detection and intervention.

The objectives were to study the effect of a single dose of intravenous (IV) zoledronic acid (ZA) on changes in bone mineral density (BMD) (lumbar spine (LS), hip, distal forearm), trabecular bone score (TBS) and bone turnover markers (BTMs) in postmenopausal osteoporotic women with and without diabetes over 12 months. Patients were divided into two groups: type 2 diabetes mellitus (T2DM) (n = 40) and non-DM (n = 40). Both groups received a single dose of 4 mg IV ZA at baseline. The BMD with TBS and BTMs (β-CTX, sclerostin, P1NP) were measured at baseline, six months, and 12 months. At baseline, BMD in all three sites was similar in both groups. T2DM patients were older and had lower BTMs than non-DM patients. The mean increase in LS-BMD (gram/cm2) at 12 months in T2DM and the non-DM group was 3.6 ± 4.7

Objective:The aim of this study was to evaluate the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs, the association between hypovitaminosis D and migraine, and the effects of oral vitamin D supplementation on migraine-related symptoms as compared to placebo. Methods:Relevant databases were searched for observational studies and randomized-controlled trials (RCTs) which evaluated the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs; the association between hypovitaminosis D and migraine; and the effects of vitamin D supplementation on migraine-frequency, duration, and severity. Pooled mean difference and odds ratio were calculated (random-effects model, RevMan version 5.3). Results:Ten observational studies and two RCTs were included. The serum 25-hydroxy vitamin D level in the migraineurs was significantly lower than that in the nonmigraineurs [mean difference - 4.44 ng/mL (95% CI: -6.11, -2.77)] (low-GRADE evidence). Hypovitaminosis D was found to be significantly associated with migraine [OR: 1.95 (95% CI: 1.07, 3.58)] (low-GRADE evidence). As compared to placebo, oral vitamin D supplementation significantly reduced the monthly migraine-frequency [mean difference: -2.20 (95% CI: -3.04, -1.36)]. ,:although it did not reduce the migraine-duration [mean difference: -16.00 hours per month (95% CI: -42.77, 10.76)] and migraine-severity score [standardized mean difference: -0.23 (95% CI: -0.79, 0.32)] (moderate-GRADE evidence). Conclusion:Serum 25-hydroxy vitamin D level was significantly lower in the migraineurs than that in the nonmigraineurs, and hypovitaminosis D was significantly associated with migraine. Oral vitamin D supplementation significantly reduced migraine-frequency, but not its duration and severity.

Metabolic bone disease in chronic neurological disorders remains an active area of research now. Parkinson’s disease (PD) is one of the commonest neurological disorders, characterized by tremors, rigidity, and slowness of movement and is associated with significant morbidity in the advanced stages. On the other hand, osteoporosis, which is characterized by low bone mineral density (BMD) (≤2.5 T-score and Z-score), a surrogate marker of decreased bone strength, is another chronic condition common among the elderly population. These two conditions can go hand in hand in the elderly population and confer a significant risk of fragility fracture and morbidity. PD is associated with a significant risk of lower BMD at all the sites (femoral neck, lumbar spine, and total hip region) in a recently performed meta-analysis.[1] PD patients have consistently increased fracture risk at different sites, such as vertebral and hip fractures, compared to controls.[2,3] Apart from low BMD, the propensity to repeated falls, decreased muscle strength, low vitamin D levels, and drugs like levodopa can play an important role in the fracture occurrence in PD.[4] All these factors often are present in tandem with PD patients, making them vulnerable to osteoporotic fractures. Moreover, PD by itself can increase fracture risk in a BMD-independent manner.[5] Thus, it is essential to look for additional factors beyond BMD. A study by Schini and colleagues also suggested to include PD as an independent factor in the Fracture risk assessment (FRAX) score calculations. The lowering of BMD in PD is often evident at an early stage of the disease,[3,6] but the outcomes are not conclusive to provide evidence-based recommendations on early screening for osteoporosis in all patients with PD. In this context, it is interesting to see if newer tools like trabecular bone score (TBS) adds to the diagnosis of osteoporosis in PD. TBS is a relatively new tool which uses pixel-to-pixel variation in the gray area level in the lumbar spine image derived from dual-energy X-ray absorptiometry. It gives a better idea about the skeletal textur, is an indirect indicator of bone microarchitectures, and improves the fracture prediction independent of BMD measurements.[7] In this issue of this journal, the study by Sooragonda BG, et al. has explored the difference in BMD, TBS along with hip structural analysis in male PD patients compared to healthy controls (ref, current study[8]). The interesting finding is lower TBS in PD patients despite no significant difference in BMD as compared to controls. This study also found a lower trend of TBS in severe PD but did not reach statistical significance, possibly due to a low sample size. Thus, the study explored a new tool (TBS) in a relatively understudied area of osteoporosis in men that too in a vulnerable group of PD patients. This study further consolidated the finding of low vitamin D in PD patients with severe disease. However, this certainly does not explain the finding of the low TBS in this population. BMD data in PD has always been conflicting and BMD seldom reflects the microarchitectural deterioration in neurological disease, for which TBS can be a useful adjunct. However, as discussed earlier, many factors other than bone-related parameters are involved in the pathogenesis of osteoporosis and fracture in PD; fracture data is certainly required. It would be very much interesting to see the fracture prevalence in the PD group as compared to controls and whether this correlates with low TBS. Moreover, a longitudinal follow-up of this cohort is warranted to gain further insight if low TBS can predict incident fracture in PD population. Moreover, if we want to provide good quality of life to PD patients, the fracture has to be prevented. Whether medications bisphosphonates will have any role? This remains an interesting point to ponder and whether low TBS at baseline can be a guide for therapeutic intervention? Possibly, we need multiprong strategies including strict fall prevention measure, improvement in muscle strength through structured exercise programs including adequate vitamin D supplementation. There is an ongoing randomized clinical trial going on the impact of bisphosphonates (zoledronic acid) in PD patients, which might provide evidence for therapeutic intervention in PD patients.[9] Having said that, bone strength and bone quality measurement should be considered in PD patients, preferably at an early stage to prevent fracture and ongoing search should continue to have a reasonable predictive tool or model for clinical use.

Abstract A 58 year old man presented to our hospital three years ago with history of upper abdominal pain, recurrent vomiting and dehydration. On evaluation, pancreatitis with mass in the head of pancreas was diagnosed. Fine needle aspiration from pancreatic head mass was suggestive of low-grade adenocarcinoma. Whipple's procedure was planned and the surgical gastroenterology team did open pylorus resecting pancreatoduodenectomy and feeding jejunostomy for him in October 2016. But the biopsy was reported as chronic calcific pancreatitis. On workup, hypercalcemia (12.5 mg/dl) was noted and hyperparathyroidism due to right inferior parathyroid adenoma was diagnosed as PTH levels were elevated (iPTH-474 pg/ml). He had a slippage of the jejunostomy tube and was readmitted. Right inferior parathyroidectomy was done by the surgical oncologist along with the repair of slipped feeding jejunostomy tube by the surgical gastroenterology team in the same sitting in March 2017. Biopsy was reported as right inferior parathyroid adenoma. Post-surgery, he had hungry bone syndrome which stabilized after one month. After 6 months, he started noticing a small nodule in the right side of the neck which progressively increased in size from a small nodule to a size of 1*1 cm over a duration of one year, associated with multiple small nodules superiorly. He also complained of weight loss, constipation, generalized weakness, and bone pains. Hypercalcemia was noted and iPTH level was again elevated (564.7 pg/ml). He was admitted for evaluation for recurrence of parathyroid adenoma/ parathyroid carcinoma/ parathyromatosis. Ultrasonography of the neck showed a 4*3 mm hypoechoic lesion with internal vascularity noted posterior to right lobe of thyroid and medial to great vessels, and multiple heterogenous hypoechoic well-defined lesions noted in the subcutaneous plane on the right side of the neck, few noted along surface of right strap muscle and sternocleidomastoid muscle. FNAC of the subcutaneous nodule was suggestive of parathyroid adenoma. Parathyroid scan showed multiple MIBI-avid nodule seen anterior and lateral to inferior pole of thyroid gland. He was operated in February 2019 and five nodules were removed. Biopsy was suggestive of parathyroid carcinoma. After the surgery, his symptoms improved but Calcium(13mg/dl) and iPTH (453 pg/ml) levels were elevated at 3 months follow up. Biopsy was suggestive of parathyroid carcinoma. But in view of the previous surgery, earlier biopsy report of adenoma and no metastasis, he was diagnosed to have parathyromatosis. A follow up CT revealed residual nodules in the neck. A repeat surgery was done in August 2019 to remove the nodules as the patient complained of persistent generalized malaise and bone pains. Following surgery, his iPTH levels remained elevated (iPTH pre-op-492.4 pg/ml; post-op- 444.4 pg/ml). His symptoms improved mildly. He was started on medical management for hypercalcemia with Cinacalcet. Figure 1. Image of the neck of the patient showing multiple nodules.

Diabetes mellitus (DM) is characterized by persistently elevated blood glucose concentration that lead to multisystem complications. There are about 400 medicinal plants cited to have a beneficial effect on DM. We must choose products wisely based on data derived from scientific studies. However, a major obstacle in the amalgamation of herbal medicine in modern medical practices is the lack of clinical data on its safety, efficacy and drug interaction. Trials of these herbal products often underreport the side effects and other crucial intervention steps deviating from the standards set by Consolidated Standards of Reporting Trials. Due to a lack of knowledge of the active compounds present in most herbal medicines, product standardization is difficult. Cost-effectiveness is another issue that needs to be kept in mind. In this mini-review, we focus on the anti-hyperglycemic effect of herbal products that are commonly used, along with the concerns stated above.