Glycemic variability in chronic calcific pancreatitis with diabetes mellitus and its possible determinants.

AIMS: To study glycemic patterns and variability in patients with pancreatic diabetes or type 3c Diabetes mellitus (DM) due to chronic pancreatitis and its subtypes and assess the role of pancreatic enzyme replacement therapy (ERT) in modulating glycemic variability. METHODS: Patients having type 3c DM due to chronic pancreatitis, and on insulin underwent Flash continuous-glucose-monitoring (CGM) for 14 days. Parameters were compared between patients with fibrocalculous pancreatic diabetes (FCPD) and non-FCPD-chronic calcific pancreatitis (non-FCPD) and between the recipients and non-recipients of pancreatic enzyme-replacement-therapy (ERT). RESULTS: Out of 54 patients with pancreatic diabetes, 35 patients had chronic calcific pancreatitis. They underwent CGM, median HbA1c 9.20 % (77 mmol/mol) and mean Time-In-Range (TIR) being 41.21 % (23.48). Only 5 (15.2 %) patients achieved target TIR>70 % while 16 (48.5 %) patients had high glycemic-variability [Coefficient-of-variation (CV) > 36 %]. Patients with FCPD (n = 14) had higher hypoglycemia-indices like Time-Below-Range (18.92 % vs 8.20 %; p = 0.03) and Low-Blood-Glucose-Index (18.14 % vs 6.04 %; p = 0.02) compared to non-FCPD (n = 21). HbA1c% and hyperglycemic excursions were similar in both groups. Recipients of ERT (n = 20) had lower glycemic-variability [Standard Deviation (SD) 52.15 % vs 68.14 % and CV 32.59 % vs 41.79 %, p < 0.05 for both) than non-recipients. ERT-recipients had no serious hypoglycemia within the 14 days. On subgroup analysis, lower glycemic-variability and hypoglycemia with ERT were seen only in FCPD but not in non-FCPD subgroup (50.13 vs 77.91, 30.09 vs 48.36 for SD and CV respectively, p < 0.05). CONCLUSION: Patients with type 3c DM due to chronic pancreatitis have high frequency of hyperglycemic and hypoglycemic excursions, with those with FCPD having a particularly higher risk of hypoglycemia and glycemic-variability. Those receiving pancreatic ERT had lesser glycemic variability and hypoglycemia. The small sample size and lack of objective markers of documentation of exocrine pancreatic insufficiency like fecal elastase highlight the need for further larger studies in this field.

Type 2 diabetes in children and adolescents: Exploring the disease heterogeneity and research gaps to optimum management.

Over the past 20 years, the incidence and prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents have increased, particularly in racial and ethnic minorities. Despite the rise in T2DM in children and adolescents, the pathophysiology and progression of disease in this population are not clearly understood. Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM. Furthermore, the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients, mostly due to the challenges of implementing clinical trials. A better understanding of the mechanisms underlying the de-velopment and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies. This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.

Transient Neonatal Hypocortisolism in Neonates with Hypoglycemia - Coexistence or Cause?

Introduction: Infants born preterm, with low birth weight (LBW), or with perinatal stress are at high risk for neonatal hypoglycemia. Low cortisol levels have also been demonstrated in this group of neonates, which is often transient. We report a series of neonates with transient hypocortisolism who had neonatal hypoglycemia. Methods: A descriptive study on clinic-biochemical parameters of a group of five neonates who had persistent neonatal hypoglycemia and had demonstrated low cortisol on critical sample testing. Results: All five neonates had birth weights below normal and four were born preterm. A history of perinatal asphyxia was seen in four cases and neonatal sepsis in two. During critical sample testing (when blood glucose [BG] was <50 mg/dl), hyperinsulinism (Insulin >2 mIU/ml) was seen in three infants whereas insulin was undetectable in two. The median cortisol during critical sample testing was 1.9 mcg/dl (0.88 - 3.7). Critical GH was normal in all, and ACTH ranged from 7.2 pg/ml to 41.3 pg/ml. None of the infants had overt clinical features of panhypopituitarism or primary adrenal insufficiency. USG brain revealed germinal matrix hemorrhage in two infants, which resolved on follow-up. USG adrenals and electrolytes were normal in all. Four of the five babies were started on oral hydrocortisone, to which they responded well with the resolution of hypoglycemia. No adverse events were noted. On follow-up, the median time to recover of serum cortisol to normal was 4 months. Conclusion: The contribution of transient hypocortisolism to hypoglycemia in infants at risk, including preterm, LBW, or those with perinatal stress, in the presence or absence of hyperinsulinism, is not well known. While the non-specific use of glucocorticoids is not advocated, the role of therapeutic glucocorticoids among at-risk neonates with documented hypocortisolism during hypoglycemia should be an area for research. Close follow-up of these neonates for spontaneous recovery of cortisol levels is warranted.

Clinical, Hormonal, and Genetic Spectrum of 46 XY Disorders of Sexual Development (DSD) Patients.

OBJECTIVES: To evaluate the clinical, hormonal and genetic characteristics of 46XY disorders of sexual development (DSD) patients from South India. METHODS: 46XY DSD patients with a provisional diagnosis of 17ß-hydroxysteroid dehydrogenase 3 (17BHSD3) deficiency, 5 alpha-reductase type 2 deficiency (5ARD2) or partial androgen insensitivity syndrome (PAIS) based on clinical and hormonal analysis were included in this study. All the patients underwent detailed clinical and hormonal evaluations. Targeted next-generation sequencing for all three genes (AR, HSD17B3, and SRD5A2) in parallel was carried out for all the included patients and their parents. RESULTS: Based upon the clinical and hormonal analysis, among the 37 children with 46XY DSD in the present study, 21 children were diagnosed with 5ARD2, 10 with PAIS, and six with 17BHSD3 deficiency. However, genetic analysis revealed pathogenic mutations in nine patients - six in the AR gene, two in the SRD5A2 gene, and one in the HSD17B3 gene. The concordance rate between provisional hormonal and genetic diagnosis was only 22.2%. Two out of six subjects with AR gene variants were positive for somatic mosaicism. CONCLUSIONS: In the present study, a positive genetic diagnosis was detected in nine patients (24%), including five novel variants. In this study, mutations in the AR gene was the most reported. The authors did not find the testosterone: dihydrotestosterone (T: DHT) ratio to be an accurate hormonal diagnostic tool.

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.

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.

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.

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.

Timing of osteoporosis therapies following fracture: the current status.

In most patients, osteoporosis is diagnosed only after the occurrence of the first fragility fracture. It is of utmost importance to start osteoporosis medications immediately in these patients to prevent future fractures and also to reduce associated mortality and morbidity. There remains a hesitancy over initiating osteoporotic medications, specifically for antiresorptive agents like bisphosphonates following an acute fracture due to concern over their effect on fracture healing. The purpose of this review is to study the effect of the timing of initiation of different osteoporosis medications on healing after an acute fracture. Most of the human studies, including randomized control trials (RCTs), did not find any significant negative effect on fracture healing with early use of bisphosphonate after an acute fracture. Anabolic agents like teriparatide have shown either neutral or beneficial effects on fracture healing and thus can be started very early following any osteoporotic fracture. Although human studies on the early use of other osteoporosis medications like denosumab or strontium ranelate are very sparse in the literature, none of these medications have shown any evidence of delay in fracture healing. To summarize, among the commonly used anti-osteoporosis agents, both bisphosphonates and teriparatide are safe to be initiated in the early acute post-fracture period. Moreover, teriparatide has shown some evidence in favor of reducing fracture healing time.

Heterogeneity of non-alcoholic fatty liver disease: Implications for clinical practice and research activity.

Non-alcoholic fatty liver disease (NAFLD) is a heterogeneous condition with a wide spectrum of clinical presentations and natural history and disease severity. There is also substantial inter-individual variation and variable response to a different therapy. This heterogeneity of NAFLD is in turn influenced by various factors primarily demographic/dietary factors, metabolic status, gut microbiome, genetic predisposition together with epigenetic factors. The differential impact of these factors over a variable period of time influences the clinical phenotype and natural history. Failure to address heterogeneity partly explains the sub-optimal response to current and emerging therapies for fatty liver disease. Consequently, leading experts across the globe have recently suggested a change in nomenclature of NAFLD to metabolic-associated fatty liver disease (MAFLD) which can better reflect current knowledge of heterogeneity and does not exclude concomitant factors for fatty liver disease (e.g. alcohol, viral hepatitis, etc.). Precise identification of disease phenotypes is likely to facilitate clinical trial recruitment and expedite translational research for the development of novel and effective therapies for NAFLD/MAFLD.

Effect of 2 mg Versus 4 mg of Intravenous Zoledronic Acid on Bone Mineral Density at the Lumbar Spine in Indian Postmenopausal Women with Osteoporosis: A Double-blind Parallel-arm Randomized Controlled Trial.

OBJECTIVE: The primary purpose was to compare the effect of 2 mg and 4 mg of intravenous zoledronic acid (ZA) on change in the lumbar spine (LS) bone mineral density (BMD) at the end of 1 year in postmenopausal women with osteoporosis. The secondary objectives were changes in BMD at the total hip and femoral neck, change in bone turnover markers (BTMs), and the incidence of new fractures. METHODS: This was a double-blind, parallel-arm, randomized control trial with an allocation ratio of 1:1 done in 70 postmenopausal women with osteoporosis. FINDINGS: The mean (±standard deviation) percentage increase in LS BMD at the end of 1 year was 4.86% ± 3.05% and 5.35% ± 3.73% in the 2 mg and 4 mg group, respectively. The dose of 2 mg ZA proved to be inferior to 4 mg with a noninferiority margin of 0.5%. There was no difference in BMD change at hip and BTMs between the two groups at the end of 1 year. Only one patient in 4 mg group developed two new vertebral fractures during a 12-month follow-up. Acute-phase reactions were the most common (43%) side-effects noted without any difference between the two groups (P = 0.63). CONCLUSION: This study failed to show the noninferiority of 2 mg ZA compared to 4 mg ZA for change in LS BMD at the end of 1 year.

Critical review of bone health, fracture risk and management of bone fragility in diabetes mellitus.

The risk of fracture is increased in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, in contrast to the former, patients with T2DM usually possess higher bone mineral density. Thus, there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes. Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk. Moreover, some antidiabetic medications further enhance the fragility of the bone. On the other hand, antiosteoporosis medications can affect the glucose homeostasis in these patients. It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk. Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature. With the advancement in imaging technology, newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes. The purpose of this review is to explore the pathophysiology behind poor bone health in diabetic patients. Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.

The Risk of Fractures in Primary Hyperparathyroidism: A Meta-Analysis.

Primary hyperparathyroidism (PHPT) is a common metabolic bone disease affecting 1% of the adult population. Patients with PHPT have reduced BMD, especially at the cortical bone. However, studies evaluating its impact on fracture risk have shown contradictory results. In an effort to further inform fracture risk for this patient population, a meta-analysis of studies of fracture in patients with PHPT compared with a control population was undertaken. Articles were searched in PubMed/MEDLINE, Excerpta Medica, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Health Sciences Literature, and Web of Science bibliographic databases. The meta-analysis included 17 studies involving 3807 PHPT cases and 11,908 controls. The primary outcome was to determine the risk of vertebral fracture (VF), nonvertebral fracture, hip fracture, distal radius fracture, and total fracture (TF) among patients with PHPT in comparison with a control population. BMD (lumbar spine, femoral neck, total hip, and distal radius) and serum 25-hydroxy vitamin D level, as well as possible predictors of VF as secondary outcomes were assessed. From this meta-analysis, it was found that there was a significantly increased risk of VF (risk ratio [RR], 2.57; 95% CI, 1.3-5.09; p = 0.007) and TF (RR, 1.71; 95% CI, 1.48-1.97; p < 0.00001) in patients with PHPT. There was a significant decrease in BMD in patients with PHPT versus controls at all four sites. Older age, longer duration since menopause, and lower BMD at lumbar spine and distal radius were predictors for VF. To conclude, patients with PHPT had a significantly higher risk for VF and TF in comparison with controls. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Diagnosis and treatment outcomes of Cushing's disease during pregnancy.

PURPOSE: We report a case of a pregnant woman with Cushing's disease (CD) and performed a systematic review of literature on diagnosis, treatment, maternal and fetal outcomes of CD in pregnancy. METHODS: A PubMed search was performed for manuscripts in English language from inception till June 2020. Cases of CD with hypercortisolism during pregnancy were included and categorized into three groups based on treatment received. Data on diagnostic modalities, CD remission, materno-fetal outcomes were analysed. RESULTS: Fifty-five patients of CD with 62 pregnancies were analysed. 24-h urinary free cortisol(UFC) was elevated by a mean of 5.4 ± 4.2 fold upper limit of normal non-pregnant level. 12/19 (63.1%) CD patients had more than threefold elevation of UFC measured during pregnancy. Mean midnight serum cortisol was 753.7 ± 270.5 nmol/l. At a midnight serum cortisol cut off of 440 nmol/l, 15/16 patients were correctly identified as CD. 23.2% underwent trans-sphenoidal surgery (group 1), 16.1% received only medical treatment (group 2) while 60.7% received no treatment (group 3) during pregnancy. Remission rates for CD in groups 1 and 2 were 76.9% and 77.8%, respectively. Adverse maternal and fetal outcomes were seen in 53.9% and 59.3% of the patients, respectively and were not significantly different between groups, although, lesser live births and greater pregnancy losses were seen in group 3. CONCLUSION: Midnight serum cortisol had better sensitivity than UFC for diagnosing hypercortisolism due to CD during pregnancy. In general, CD should be treated during pregnancy in order to optimize maternal and fetal outcomes as a trend towards increased live births is seen in treated subjects.

Parathyroid Hormone Replacement versus Oral Calcium and Active Vitamin D Supplementation in Hypoparathyroidism: A Meta-analysis.

OBJECTIVES: Chronic hypoparathyroidism is treated conventionally with active vitamin D and high doses of calcium. Recombinant human parathyroid hormone (PTH) replacement is an attractive option for treating patients with hypoparathyroidism since it can replace the physiological action of native PTH. The aim of our study was to perform a comprehensive evaluation of the effects of PTH replacement on calcium homeostasis, bone metabolism, and daily requirement of calcium and active vitamin D. MATERIALS AND METHODS: Randomized controlled trials done in chronic hypoparathyroid patients were included in this meta-analysis. The PTH group included subjects receiving a subcutaneous injection of either PTH (1-84) or PTH (1-34) with oral calcium and/or active vitamin D. The control group included those receiving oral calcium and active vitamin D with/without subcutaneous placebo injection. The primary outcome of this meta-analysis was to compare serum calcium, 24-h urinary calcium, and severe adverse effects among PTH and control groups. RESULTS: In this meta-analysis, we did not find any difference in serum calcium level between PTH and control groups [mean difference (MD) - 0.01; 95% confidence interval (CI) - 0.09, 0.06; P = 0.71]. Although there was a trend towards low 24-h urinary calcium in the PTH group, the difference was not statistically significant (MD - 1.43; 95% CI - 2.89, 0.03; P = 0.06). The incidence of serious adverse events was also similar in both groups (RR 1.35; 95% CI 0.58, 3.16; P = 0.49). CONCLUSION: Both PTH and active vitamin D therapies are associated with comparable serum and urine calcium levels with a similar incidence of serious adverse events in patients with chronic hypoparathyroidism.

Dome-Shaped Pituitary Enlargement in Primary Hypothyroidism: Avoiding Neurosurgical Interventions.

We describe three cases of primary hypothyroidism which presented initially to neurosurgery department with pituitary hyperplasia. We have found a novel pattern of 'dome-shaped' enlargement of pituitary in MRI of these patients. Out of these 3 patients, in two of them, the planned surgery was deferred when endocrinologists were consulted and the pituitary hyperplasia completely resolved with levothyroxine treatment. In the third case, pituitary surgery was already performed before endocrinology consultation and histopathology revealed thyrotroph hyperplasia. The hyperplastic lesions described typically have a homogenous symmetrical 'dome' shaped architecture unlike the non-functioning pituitary adenoma (NFPA), which usually might often be of varying shapes and homogeneity. Analysis of pituitary images from similar case reports published in literature, also showed this typical 'dome' shaped pituitary enlargement. This imaging characteristic can be a clue to look for underlying hormone deficiency, especially in primary hypothyroidism. Therefore, a thorough endocrine evaluation especially looking for primary hypothyroidism in such dome-shaped pituitary lesions are mandatory to prevent unwarranted neuro-surgical intervention as treatment of primary hypothyroidism may result in resolution of the abnormal enlargement.

Change in insulin resistance, beta cell function, glucagon-like peptide-1 and calcitonin levels two weeks after bariatric surgery.

AIM OF THE STUDY: Bariatric surgery causes profound improvement in metabolic parameters by increasing plasma glucagon like peptide - 1 (GLP-1) level even few weeks after surgery. GLP-1 analogues can cause calcitonin secreting medullary thyroid carcinoma in animals. The studies relating to the mechanisms that underlie these changes are few. The objectives of the study were to measure the change in insulin resistance, beta cell function, GLP-1 and calcitonin levels before and 2 weeks after bariatric surgery. METHODS: Patients above 18 years of age who underwent either laparoscopic sleeve gastrectomy or Roux-en Y gastric bypass were recruited into the study. Measured indices were homeostatic model assessment 2 for insulin resistance (HOMA2-IR), an index for hepatic insulin resistance; Matsuda index, an index of whole body insulin sensitivity; and insulin secretion and sensitivity index (ISSI-2), a marker of beta cell secretion. RESULTS: Twenty eight patients completed the study. HOMA2-IR was lower (2.72 ±â€¯1.28 vs. 2.04 ±â€¯0.9; P = 0.001) and ISSI-2 was higher (0.80 (0.51-1.26) vs. 1.04 (0.56-1.38); P = 0.019) at 2 weeks after surgery compared to baseline. Matsuda index also improved after surgery but was not statistically significant (2.02 (1.1-2.94) vs. 2.84 (1.56-4.12); P = 0.078). Fasting GLP-1 and calcitonin levels did not change while both peak GLP-1, and area under curve for GLP-1 were higher after surgery. CONCLUSIONS: At 2 weeks following bariatric surgery, hepatic insulin resistance decreased while beta cell function improved due to increase in postprandial GLP-1 level without any change in fasting calcitonin levels.

Response to Zoledronic Acid in Patients with Active Paget's Disease of Bone: A Retrospective Study.

BACKGROUND: Traditionally, bisphosphonates are used to treat active Paget's disease of bone (PDB). Intravenous zoledronic acid (ZA) is the most effective treatment option leading to sustained remission. OBJECTIVE: The primary objective of this study was to analyze the effect of intravenous ZA in patients with active PDB in a tertiary care center of India. MATERIALS AND METHODS: Retrospective data of 13 patients with active PDB who received a single dose of 4 mg intravenous ZA at our institute from January 2011 to June 2017 were reviewed. Response to therapy was monitored clinically, biochemically by serum alkaline phosphatase (ALP), and scintigraphically by 99m-Technetium methylene diphosphonate bone scan. RESULTS: All of our patients reported relief of bone pain. The mean duration of follow-up in our study was 35.2 ± 16.8 months. Serum ALP levels reduced significantly from 1190.9 ± 666.1 IU/L (n = 13) at baseline to 200.5 ± 68.4 IU/L (n = 13) at 6 months (P < 0.001). ALP level at 1 year was 174 ± 33.6 IU/L (n = 12), which remained stable till 36 months at 176.5 ± 50 IU/L (n = 8). This indicates that remission achieved by 6 months post ZA is sustained for at least 3 years. Scintigraphic ratio reduced from 9.6 [interquartile range (IQR) 5.25-18.2] at baseline to 2.7 (IQR 1.20-4.05) at follow-up (P < 0.001). Similarly, scintigraphic index of involvement reduced from 9.9 (IQR 5.6-28.5) at baseline to 3 (IQR 2-4) at follow-up (P = 0.018). CONCLUSION: A 4 mg single dose of intravenous ZA results in clinical, biochemical, and scintigraphic response that is sustained for at least 3 years.

Adrenal adenoma in von Hippel-Lindau syndrome: A case report with review of literature.

A 29-year-old hypertensive male with von Hippel-Lindau (VHL) syndrome came to the Endocrinology department for evaluation. Contrast-enhanced computed tomography of the abdomen revealed an adrenal mass, bilateral renal cell carcinoma, and multiple pancreatic cysts. The hormonal investigations for adrenal mass were normal. He underwent left-sided adrenalectomy, and the histopathological report was suggestive of an adrenocortical adenoma. Genetic analysis of VHL gene in this patient revealed a heterogeneous 5' splice site variation of intron 1 of the VHL gene that affects splice site of exon 1 (c. 340 + 1G > A). Adrenocortical adenoma is very rare in VHL syndrome. Only two cases of adrenocortical adenoma in VHL have been reported in the literature, and both were associated with pheochromocytoma. This is probably the first reported case of adrenocortical adenoma in VHL syndrome without accompanying pheochromocytoma.