Role of bisphosphonates in hypertrophic osteoarthropathy: a systematic review.

BACKGROUND: The role of bisphosphonates (BP) in hypertrophic osteoarthropathy (HPOA) is unclear. We presented a case of primary HPOA and performed a systematic review of literature on the effect of BP on treatment response in primary and secondary HPOA. METHODS: The study was prospectively registered in PROSPERO (CRD42022343786). We performed a PubMed literature search that restricted to the English language. We included patients diagnosed with primary or secondary HPOA who received BP. The primary endpoint assessed was the effectiveness of BP on response to pain or arthritis. Secondary outcomes included timing, degree, and duration of response, comparison to other HPOA therapies, impact of BP on radiology, bone scan, bone turnover markers, and adverse effects of BP. RESULTS: Literature search retrieved only case reports. Forty-five patients (21 primary, 24 secondary HPOA) had received BP. Majority(88.3%) experienced improvement in pain or arthritis. Response was gradual for primary HPOA and within a median of 3 to 7 days for secondary HPOA after treatment with BP. Most patients had reduced bone scan uptake after BP. When other HPOA therapies were tried, half responded to BP after not having previously responded to other therapies, while a third received the treatments concurrently, making it difficult to attribute treatment response to a drug. Reporting of other secondary outcomes was very heterogenous and qualitative to draw conclusions. No major adverse effects have been reported for BP in HPOA. CONCLUSION: Bisphosphonates provide an effective and safe treatment option for primary and secondary HPOA. However, there is a lack of randomized controlled trials.

Insulin Sensitivity, Islet Cell Function, and Incretin Axis in Pregnant Women With and Without Gestational Diabetes Mellitus.

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.

Male Hypogonadism After Recovery from Acute COVID-19 Infection: A Prospective Observational Study.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 can affect the hypothalamic-pituitary-gonadal axis (HPG) due to the expression of the angiotensin-converting enzyme 2 receptor. OBJECTIVES: To assess the prevalence of hypogonadism and Sertoli cell dysfunction in coronavirus disease 2019 (COVID-19) male survivors. METHOD: Male subjects recovered from acute COVID-19 infection were prospectively observed. The primary outcomes included the proportion of hypogonadism, defined biochemically as serum testosterone<230 ng/dL or CFT of<6.4 ng/mL if the total testosterone is between 230-320 ng/m. Sertoli cell dysfunction was defined as inhibin-B level<54.5 pg/mL. Subjects with hypogonadism were followed up at 12 months to assess the recovery of the HPG axis. RESULTS: Eighty-three subjects aged≥18 years were evaluated at a median of 120 (±35) days post-recovery. Their mean age was 49.50±12.73 years, and the mean BMI was 26.84±5.62 kg/m2. Low testosterone was detected in 21 (24.71%) and low inhibin-B was detected in 14 (19.71%) out of 71 subjects at 3 months. Subjects with low testosterone were younger, with a mean age of 43.29±12.03 years (P-0.08) and higher BMI (P-0.012). The severity of COVID-19 infection, duration of hospitalization, and other factors were not significantly associated with low testosterone. At 12 months, 18 out of 21 subjects came for follow-up, of which 9 (50%) showed persistently low testosterone, suggestive of hypogonadism. CONCLUSION: Following COVID-19 infection, testosterone levels recovered over time; however, a significant proportion of subjects had low levels at 12-month follow-up. These findings have long-term implications for the management of COVID-19 subjects.

Clinical Features of Unrecognized Congenital Adrenal Hyperplasia Due to 17α-hydroxylase Deficiency Since Adolescence: A Case Report.

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 Association of Dyslipidemia and Atherogenic Indices With Glycemic Control in Diabetic Dyslipidemia Patients: A Real-World Landscape.

BACKGROUND: Dyslipidemia is an important comorbid factor of type 2 diabetes mellitus (T2DM) that increases the risk of cardiovascular diseases. This study aimed to assess the pattern of dyslipidemia and atherogenic indices and determine its relation with glycemic control. METHODS: A cross-sectional study enrolled 382 patients with diabetic dyslipidemia. The socio-demographics data, clinical features, and laboratory parameters were collected. The baseline lipid parameters such as total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glycated hemoglobin (HbA1C) were measured. Atherogenic indices such as TC/HDL-C ratio, TG/HDL-C ratio, LDL-C/HDL-C ratio, non-HDL-C/HDL-C and atherogenic index of plasma (AIP) [log10 (TG/HDL-C)] were calculated. T2DM patients were classified into three groups based on the degree of glycemic control: Good glycemic control (HbA1C<7%), fair control (HbA1C 7-8%), and poor control (HbA1C>8%). RESULTS: The population's mean age was 48.60±6.15 years, with 145 (38%) males. We found mixed dyslipidemia as the most prevalent (36.1%) form of dyslipidemia in our patients. The most common pattern in atherogenic indices was AIP (94.2%). HbA1c was positively correlated with duration of diabetes (r=0.253, p<0.001). In multivariate logistic regression analysis, duration of diabetes (>10 years) was significantly associated with poor glycemic control with an odds ratio (OR) of 2.31(95% CI; 1.25-4.24, p=0.007). CONCLUSION: The present study indicated that neither the pattern of dyslipidemia nor the atherogenic indices were markers of poor glycemic control among South Indian patients attending our tertiary care institute. However, duration of diabetes was significantly associated with poor glycemic control.

Effects of Vitamin D on Migraine: A Meta-Analysis.

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 Preterm Neonates With Fetal Growth Restriction (FGR): A Prospective Cohort Study.

OBJECTIVE: To study the association of fetal growth restriction (FGR) with metabolic bone disease in preterm neonates. METHODOLOGY: This prospective cohort study included 94 preterm neonates with FGR as cases and an equal number of gestation-matched appropriate for gestational age (AGA) neonates without FGR as controls. The incidence of metabolic bone disease, and serum biochemical markers at various time intervals till 6 months corrected age were compared. The risk factors for metabolic bone disease and its association with stunting at 6 months of corrected age were studied. RESULTS: The incidence of metabolic bone disease, though higher in the FGR neonates (15.5%), was not significantly different from AGA neonates (6.7%) [RR (95%CI) 0.92-5.82; P=0.06]. Birth weight [aOR (95%CI) 0.8 (0.64-0.98); P=0.03] and time to reach full feeds [aOR (95%CI) 1.17 (1.01-1.36); P=0.03] were significantly associated with an increased risk of metabolic bone disease after adjusting for FGR status. Mean (SD) levels of calcium, phosphorus, alkaline phosphatase, parathormone (PTH), and vitamin D were similar in both groups. No significant association existed between metabolic bone disease and stunting at 6 months of corrected age [RR (95%CI) 2 (0.75-5.4); P=0.16]. CONCLUSION: FGR was not found to be significantly associated with metabolic bone disease in preterm neonates.

Effect of a single dose of zoledronic acid on bone mineral density and trabecular bone score in Indian postmenopausal osteoporotic women with and without type 2 diabetes mellitus - A prospective cohort pilot study.

PURPOSE: 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. METHODS: 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 (ß-CTX, sclerostin, P1NP) were measured at baseline, six months, and 12 months. RESULTS: 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% and 6.2 ± 4.7 %, respectively (P = 0.01). However, the age adjusted mean difference in LS BMD increment between two groups at one year was - 2.86 % (-5.02% to -0.69%), P = 0.01. There was a comparable change in BMD at other two sites, BTMs, and TBS in both the groups over one year follow-up. CONCLUSION: The gain in the LS-BMD was significantly lower in T2DM group compared to non-DM subjects over 12 months after a single IV infusion of 4 mg ZA. The explanation for this could be low bone turnover in diabetes subjects at baseline.

Peroxisome Proliferator-Activated Receptor α and γ Gene Polymorphisms among South Indian Patients with Diabetic Dyslipidaemia.

Background: Peroxisome proliferator-activated receptors (PPAR) α and γ genes play an important role in dyslipidaemia of T2DM. Aims: To estimate the frequency distribution of PPAR α and γ gene polymorphisms in South Indian T2DM patients with dyslipidaemia compared to healthy controls. Normative frequencies of SNPs were established and compared with data for 1000 genome populations. Methods: Eligible 382 cases and 336 age and sex-matched controls were enrolled. Six SNPs in PPARα [rs1800206 C>G (Leu162Val), rs4253778 G>C, rs135542 T>C] and PPARγ [rs3856806 (C>T), rs10865710 (C>G), rs1805192 C>G (Pro12Ala)] genes were selected for genotyping. Results: The allele and gene frequencies did not significantly differ between the diabetic dyslipidaemia cases and healthy controls. However, they were significantly different from that of 1000 genome populations except for rs1800206 C>G (Leu162Val) and rs1805192 C>G (Pro12Ala). Conclusion: The studied polymorphisms in PPARα and PPARγ genes are not associated with diabetic dyslipidaemia among South Indian patients.

Treatment on Nature's lap: Use of herbal products in the management of hyperglycemia.

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.

Deficiency of the mitochondrial ribosomal subunit, MRPL50, causes autosomal recessive syndromic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a common cause of infertility in women, characterised by amenorrhea and elevated FSH under the age of 40 years. In some cases, POI is syndromic in association with other features such as sensorineural hearing loss in Perrault syndrome. POI is a heterogeneous disease with over 80 causative genes known so far; however, these explain only a minority of cases. Using whole-exome sequencing (WES), we identified a MRPL50 homozygous missense variant (c.335T > A; p.Val112Asp) shared by twin sisters presenting with POI, bilateral high-frequency sensorineural hearing loss, kidney and heart dysfunction. MRPL50 encodes a component of the large subunit of the mitochondrial ribosome. Using quantitative proteomics and western blot analysis on patient fibroblasts, we demonstrated a loss of MRPL50 protein and an associated destabilisation of the large subunit of the mitochondrial ribosome whilst the small subunit was preserved. The mitochondrial ribosome is responsible for the translation of subunits of the mitochondrial oxidative phosphorylation machinery, and we found patient fibroblasts have a mild but significant decrease in the abundance of mitochondrial complex I. These data support a biochemical phenotype associated with MRPL50 variants. We validated the association of MRPL50 with the clinical phenotype by knockdown/knockout of mRpL50 in Drosophila, which resulted abnormal ovarian development. In conclusion, we have shown that a MRPL50 missense variant destabilises the mitochondrial ribosome, leading to oxidative phosphorylation deficiency and syndromic POI, highlighting the importance of mitochondrial support in ovarian development and function.

Clinicopathological Profile of Primary Hyperparathyroidism with Special Reference to Ki-67 Labelling Index.

Context: Primary hyperparathyroidism (PHPT) can occur due to a neoplastic process or hyperplasia. While the disease presentation is predominantly asymptomatic in developed countries, this is not the case yet in India. Differentiation of the type of lesion can only be done based on histomorphology but has its own challenges. Immunohistochemical markers like Ki-67 have been studied to aid in diagnosis but data on this is sparse from India. Aims: The aim of this study is to assess the clinical, biochemical and pathological profile of PHPT and to analyse the differences in immunohistochemical marker Ki-67 among the various lesions. Setting and Design: A descriptive study was carried out on 38 PHPT patients who were treated at our institute from January 2011 to March 2021. Materials and Methods: Post-surgery, the causative lesions were categorised as adenoma (31), hyperplasia (5) and carcinoma (2). Clinical, biochemical, radiological and histopathological features of all lesions were collected and analysed. Ki-67 proliferation index was calculated. The various parameters were compared across the three groups of lesions and correlated with Ki-67 index. Results: Out of 38 patients, 37 were symptomatic with skeletal symptoms being the most common followed by renal symptoms. There was no difference in clinical or biochemical parameters among the three types of lesions. Significant negative correlation was seen between serum iPTH and serum 25-OH Vitamin D levels (P0.006) The median Ki-67 index was found to be 0.40% in hyperplasia, 0.49% in adenoma and 5.84% in carcinoma. Conclusion: PHPT still presents as an overtly symptomatic disease in India. Diagnosis of the nature of lesion depends on the accurate application of morphological criteria. A high Ki-67 index was not found to be an absolute marker of carcinoma, as it was also seen in a small proportion of atypical adenomas.

Growth hormone and gastrointestinal malignancy: An intriguing link.

Growth hormone (GH) excess is associated with several systemic complications, one of which is the increased risk of neoplastic processes particularly of the gastrointestinal (GI) tract. Among the GI neoplasms, the most reported association is with benign and malignant neoplasms of the colon. In the majority of published literature, an increased incidence of GI neoplasms, both colonic adenomas as well as colorectal carcinoma is reported. However, the studies on colon cancer-specific mortality rate are conflicting with recent studies reporting similar cancer-specific mortality rates in comparison to controls. Many studies have reported an association of colorectal neoplasms with GH levels. Pathogenic mechanisms put forward to explain this association of GH excess and GI neoplasms primarily involve the increased GH-insulin-like growth factor 1 (IGF-1) signaling. Both GH and IGF-1 have proliferative, anti-apoptotic, and angiogenic effects on the systemic tissues leading to cellular proliferation. Other contributing factors to the increased risk of GI neoplasms include slow intestinal transit with a redundant large bowel, altered bile acids, deranged local immune response, shared genetic susceptibility factors and hyperinsulinemia. In view of the increased risk association, most guidelines for the care of acromegaly patients recommend an initial screening colonoscopy. Recommendations for further follow-up colonoscopy differ but broadly, the guidelines agree that it depends on the findings at first colonoscopy and state of remission of GH excess. Regarding the concern about the risk of colorectal cancers in patients receiving recombinant GH therapy, most cohort studies do not show an increased risk.

Thyroid Function Abnormalities and Outcomes in Hospitalized Patients with COVID-19 Infection: A Cross-Sectional Study.

Thyroid gland can be affected by the COVID-19 infection. The pattern of thyroid function abnormality reported in COVID-19 is variable; in addition, some drugs used in COVID-19 patients like glucocorticoids and heparin can affect the thyroid function tests (TFT). We conducted an observational, cross-sectional study of thyroid function abnormalities with thyroid autoimmune profile in COVID-19 patients with varying severity from November 2020 to June 2021. Serum FT4, FT3, TSH, anti-TPO, and anti-Tg antibodies were measured before the initiation of treatment with steroids and anti-coagulants. A total of 271 COVID-19 patients were included in the study, of which 27 were asymptomatic and remaining 158, 39, and 47 were classified to mild, moderate and severe categories, respectively, according to MoHFW, India criteria. Their mean age was 49±17 years and 64.9% were males. Abnormal TFT was present in 37.2% (101/271) patients. Low FT3, low FT4, and low TSH were present in 21.03%, 15.9% and 4.5% of patients, respectively. Pattern corresponding to sick euthyroid syndrome was the most common. Both mean FT3 and FT3/FT4 ratio decreased with increasing severity of COVID-19 illness (p=0.001). In multivariate analysis, low FT3 was associated with increased risk of mortality (OR 12.36, 95% CI: 1.23-124.19; p=0.033). Thyroid autoantibodies were positive in 58 (27.14%) patients; but it was not associated with any thyroid dysfunction. Thyroid function abnormality is common among COVID-19 patients. Both low FT3 and FT3/FT4 ratio are indicators of disease severity while low FT3 is a prognostic marker of COVID-19 associated mortality.

A Randomized Double-Blind Placebo-Controlled Trial Evaluating the Efficacy of Oral Cholecalciferol in Improving Renal and Vascular Functions in Vitamin D-Deficient Patients With Type 2 Diabetes Mellitus.

This study was performed to evaluate the efficacy of cholecalciferol in improving renal and vascular functions in vitamin D-deficient patients with type 2 diabetes mellitus (T2DM) along with chronic kidney disease (CKD). One hundred patients (18 - 65 years), having T2DM along with CKD (stage IIIA and IIIB) and hypovitaminosis D were randomized (1:1) to receive either oral cholecalciferol 60,000 IU (Group A) or placebo (Group B) weekly for 8 weeks along with standard background treatment. They were followed up for another 24 weeks. Various parameters of renal and vascular functions were compared. Except for serum calcium and phosphate levels which were significantly higher in Group A (p < 0.001), there was no significant difference in any of the biochemical or vascular parameters between the two groups at 8 weeks. There were comparable changes in urinary albumin-creatinine ratio and carotid-femoral pulse wave velocity in the two groups at 8 and 24 weeks. There was no improvement in any of the vascular parameters from the corresponding baseline values in the two groups at 8 and 32 weeks. No improvement in renal and vascular functions was observed following treatment with oral cholecalciferol in patients with T2DM and CKD.

Effect of Zoledronic Acid in Hepatic Osteodystrophy: A Double-Blinded Placebo-Controlled Trial.

Purpose: Literature on the treatment of pre-transplant hepatic osteodystrophy (HOD) is limited. The general treatment measures and their timing are currently adopted from the literature on postmenopausal osteoporosis. Therefore, we conducted this randomized study to investigate the effect of zoledronic acid (ZA) on HOD. Methods: We randomized 36 male patients with cirrhosis (Child-Pugh class A and B) into 19 to the ZA arm and 17 to the placebo arm, respectively. Patients in the ZA arm received a single infusion of 4 mg ZA dissolved in 100 mL of normal saline at baseline, while patients in the placebo arm received a similar infusion of normal saline at baseline. The primary outcome of the study was the change in lumbar spine bone mineral density (LS-BMD) at 12 months. Results: Of 36 patients, 28 completed the study (15 in the ZA arm and 13 in the placebo arm). The mean increase in LS-BMD (g/cm2) in the ZA and placebo arms was 5.11% (3.50) and 0.72% (4.63) [P = 0.008], respectively. The trabecular bone score (TBS) did not improve significantly in either arm. The incidence of vertebral fractures (VFs) was similar in both arms. There was a significant decrease in plasma beta-C-terminal telopeptide (ß-CTX) levels in the ZA arm compared to the placebo arm, while the change in plasma levels of procollagen 1 intact N-terminal propeptide (P1NP) was similar in both arms. Six patients (31.6%) in the ZA arm experienced adverse reactions such as fever and myalgia. Conclusion: ZA improved LS-BMD in male patients with HOD by decreasing bone resorption. However, it may not improve trabecular microarchitecture or prevent morphometric VFs in this population.

Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control.

Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.

Pituitary Dysfunction Following Snakebite Envenomation: A Clinico-Radiological Assessment of 15 Cases and Review of the Literature.

Background: Snakebite envenomation (SE) is an important tropical disease in India, causing significant morbidity and mortality among patients. The hormonal deficiencies due to the involvement of the pituitary in case of SE can present in either acute or delayed setting. Hypopituitarism (HP) is often an underrecognized and relatively rarely reported complication of this neglected disease. Methods: We present here the data of 15 patients diagnosed to have HP following systemic SE and are being currently followed-up in the Endocrinology outpatient department of a tertiary care hospital of South India. The study was approved by the Institute ethics committee, and informed onsent was taken from all the study patients. The study was a record-based retrospective analysis of the patients with HP following SE. Clinical data including lag time in diagnosis and type of snake were determined. Further, hormonal data including all the anterior pituitary functions (thyroid stimulating hormone, free T4, cortisol, insulin-like growth factor (IGF-1) luteinizing hormone, follicular-stimulating hormone, testosterone; prolactin) and water deprivation test to determine diabetes insipidus (DI) in patients with polyuria on follow-up were extracted from the records and the hospital information system. An experienced neuroradiologist examined the magnetic resonance imaging (MRI) findings of the pituitary. Results: The mean age of the patients was 43 ± 9 years and 80% were male. Around 90% of patients belonged to upper-lower socioeconomic status according to the modified Kuppuswamy scale. The commonest snake species reported was Russell's viper. Thirteen patients had delayed HP. The median duration from snakebite to onset of HP symptoms was 1 year (range 0.33-10 years). However, the median time from snakebite to the diagnosis of HP was 7 years (range 1-13 years). Central hypothyroidism and hypogonadism were present in all subjects. However, central hypocortisolism was noted in 93% of patients. Low IGF-1 was noted in all the six patients where data were available. One patient had partial central DI. Thirteen out of 15 patients had reduction of pituitary volume in MRI. Conclusion: HP in patients with SE can appear slowly and the diagnosis is frequently delayed for years. Following snakebite, multiple pituitary hormone deficiencies associated with radiological abnormalities like a significant reduction in the pituitary volume are common.

Primary hyperparathyroidism presenting as acute pancreatitis: An institutional experience with review of the literature.

BACKGROUND: Acute pancreatitis (AP) presenting as an initial manifestation of primary hyperparathyroidism (PHPT) is uncommon, and its timely diagnosis is crucial in preventing recurrent attacks of pancreatitis. AIM: To determine the clinical, biochemical, and radiological profile of PHPT patients presenting as AP. METHODS: This is a retrospective observational study, 51 consecutive patients admitted with the diagnosis of PHPT during January 2010 and October 2021 at a tertiary care hospital in Puducherry, India was included. The diagnosis of AP was established in the presence of at least two of the three following features: abdominal pain, levels of serum amylase or lipase greater than three times the normal, and characteristic features at abdominal imaging. RESULTS: Out of the 51 consecutive patients with PHPT, twelve (23.52%) had pancreatitis [5 (9.80%) AP, seven (13.72%) chronic pancreatitis (CP)]. PHPT with AP (PHPT-AP) was more common among males with the presentation at a younger age (35.20 ± 16.11 vs 49.23 ± 14.80 years, P = 0.05) and lower plasma intact parathyroid hormone (iPTH) levels [125 (80.55-178.65) vs 519.80 (149-1649.55, P = 0.01)] compared to PHPT without pancreatitis (PHPT-NP). The mean serum calcium levels were similar in both PHPT-AP and PHPT-NP groups [(11.66 ± 1.15 mg/dL) vs (12.46 ± 1.71 mg/dL), P = 0.32]. PHPT-AP also presented with more gastrointestinal symptoms like abdominal pain, nausea, and vomiting with lesser skeletal and renal manifestations as compared to patients with PHPT-NP. CONCLUSION: AP can be the only presenting feature of PHPT. Normal or higher serum calcium levels during AP should always draw attention towards endocrine causes like PHPT.

Incretin based therapy and pancreatic cancer: Realising the reality.

Incretin-based therapies like glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors help maintain the glycaemic control in patients with type 2 diabetes mellitus with additional systemic benefits and little risk of hypoglycaemia. These medications are associated with low-grade chronic pancreatitis in animal models inconsistently. The incidence of acute pancreatitis was also reported in some human studies. This inflammation provides fertile ground for developing pancreatic carcinoma (PC). Although the data from clinical trials and population-based studies have established safety regarding PC, the pathophysiological possibility that low-grade chronic pancreatitis leads to PC remains. We review the existing literature and describe the relationship between incretin-based therapies and PC.