Poorly differentiated thyroid cancer: Clinical, pathological, mutational, and outcome analysis.

INTRODUCTION: Poorly differentiated thyroid cancer (PDTC) remains a challenge not only for pathologists and surgeons because of the difficulties associated with the diagnostic process and the compelling need for difficult thyroidectomy, but it is also of high clinical relevance because it is responsible for mortality in non-anaplastic follicular cell-derived thyroid cancer. MATERIALS AND METHODS: Cases of PDTC within a 30-year period were reviewed by two independent pathologists. Histological features like atypical mitosis, necrosis, capsular, and vascular invasion were studied. Mutation analysis was done for BRAF, RET/PTC, RAS, and PI3KCA, and P53 was performed using immunohistochemistry. RESULTS: There were 39 patients with a median age of 53 years; 14 patients were more than 55 years of age. At presentation, 38.4% had compressive features and the median tumor size was 9 cm. At presentation, 67.7% had an extrathyroidal extension (ETE). R0 resection was achieved in 41%, with 12 cases resulting in a difficult thyroidectomy. Necrosis was seen in 65.7% and mitosis in 73.3% with well-differentiated components in 41%. The commonest mutation was RAS (23.1%). Survival was higher in the operable group (54.26, 95% confidence interval [CI]: 30.83-77.70 vs. 20.25, 95% CI: 0-54.07) months, respectively; however, 10-year survival was only 5% and only the tumor size and presence of mitosis were independent risk factors. CONCLUSION: PDTC presents with worrisome features like large size, ETE, and rapid growth. Aggressive surgical resection with extended/radical thyroidectomy may result in better loco-regional control and improved survival. RAS was the frequent mutation detected. It is worthwhile to identify prognostic factors that can predict the course of PDTC.

Exome sequencing identified mutations in the WNT1 and COL1A2 genes in osteogenesis imperfecta cases.

BACKGROUND: Osteogenesis imperfecta (OI) is a heritable connective tissue disorder characterized by bone deformities, fractures and reduced bone mass. OI can be inherited as a dominant, recessive, or X-linked disorder. The mutational spectrum has shown that autosomal dominant mutations in the type I collagen-encoding genes are responsible for OI in 85% of the cases. Apart from collagen genes, mutations in more than 20 other genes, such as CRTAP, CREB3L1, MBTPS2, P4HB, SEC24D, SPARC, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, TMEM38B, and IFITM5 have been reported in OI. METHODS AND RESULTS: To understand the genetic cause of OI in four cases, we conducted whole exome sequencing, followed by Sanger sequencing. In case #1, we identified a novel c.506delG homozygous mutation in the WNT1 gene, resulting in a frameshift and early truncation of the protein at the 197th amino acid. In cases #2, 3 and 4, we identified a heterozygous c.838G > A mutation in the COL1A2 gene, resulting in a p.Gly280Ser substitution. The clinvar frequency of this mutation is 0.000008 (GnomAD-exomes). This mutation has been identified by other studies as well and appears to be a mutational hot spot. These pathogenic mutations were found to be absent in 96 control samples analyzed for these sites. The presence of these mutations in the cases, their absence in controls, their absence or very low frequency in general population, and their evaluation using various in silico prediction tools suggested their pathogenic nature. CONCLUSIONS: Mutations in the WNT1 and COL1A2 genes explain these cases of osteogenesis imperfecta.

Applications of Gas Discharge Visualization Imaging in Health and Disease: A Systematic Review.

Context: Gas discharge visualization (GDV) works on the principle of the Kirlian effect. It's a noninvasive, quick, and safe biometric tool to investigate the psychophysiological state of an individual, with the potential to identify deviations from the healthy functioning of humans at early stages. Objective: The study intended to systematically document the scientific evidence pertaining to the use of GDV devices in human health and disease conditions. Design: The research team performed a systematic search for studies on GDV on research databases such as Google Scholar, PubMed, and PsychINFO, using the following inclusion criteria: (1) experimental studies dealing with a GDV device, (2) studies dealing with human participants related to health and disease, and (3) studies published in the English language. The study excluded: (1) review articles, (2) case studies, (3) letter to editors, (4) studies with unclear methodology, and (5) studies published before the year 2000. Setting: The study took place in the Department of Integrative Medicine at the National Institute of Mental Health and Neurosciences (NIMHANS) in Bengaluru, India. Results: After filtering, the research team obtained 108 publications that dealt with the application of a GDV device in human participants. Based on the selection criteria, 42 studies were included in the review. These 42 studies included eight randomized controlled trials (RCTs), five nonrandomized controlled studies, 17 cross-sectional studies, 10 single-group pre-post studies, and two correlational studies. Conclusions: More studies with a robust methodology are needed to make definitive conclusions. The literature reveals that the GDV technique has the potential to provide early diagnosis and screening, especially in disorders of the endocrine and immune systems. It might also be used to assess wellness in healthy subjects and monitor the effects of interventions, such as yoga-including pranayama and meditation, acupuncture, qigong, music therapy, and massage on the human energy system. Future studies should focus on the validation of GDV imaging in clinical settings.

PHPT with Pancreatitis: Atypical Presentation of PHPT.

Background: Primary hyperparathyroidism (PHPT) is rarely associated with the occurrence of acute or chronic pancreatitis, requiring complex perioperative management. This study aimed to assess the prevalence and disease characteristics of pancreatitis in PHPT. Materials and Methods: This study is a clinicopathological analysis of the medical records of patients who were diagnosed with PHPT with pancreatitis between 1989 and 2021 in the Endocrine Surgery department, SGPGI, Lucknow. Results: Out of 548 PHPT cases, 44 (8.03%) were found to be associated with pancreatitis. The mean age was 33.57 years (15-65 years); 5 were ≤20 years, while 26 were ≤30 years of age. There were 27 males and 17 females. Twenty-one cases were of acute (11 acute, nine recurrent acute, one acute on chronic), whereas 23 were of chronic pancreatitis (six chronic calcific pancreatitis). The major clinical presentation of PHPT with pancreatitis was abdominal pain (65.91%). The mean number of attacks per patient in recurrent acute pancreatitis was two. Mean PTH levels were 68.19 pmol/L. The mean tumor size (in the largest dimension) was 2.79 ± 1.4 cm while the mean tumor weight was 4.91 g. Nephrolithiasis was associated with 25 cases. An association with multiple endocrine neoplasia type 1 syndrome was seen in one case. The final histopathological diagnosis was parathyroid carcinoma in two, hyperplasia in three, and parathyroid adenoma in 39 cases. Normocalcemia was seen in 27.2%, hypercalcemic crisis in 15.9%, and 25% of patients required semi-emergency parathyroidectomy. The outcome was favorable in all, as none had any further attacks of pancreatitis. Conclusion: In our study, the prevalence of pancreatitis in PHPT cases was 8.03%. The majority of patients were young. Normocalcemia was seen in 12 patients, so even if calcium levels are normal, PHPT should be suspected in young patients with pancreatitis. Parathyroidectomy resulted in the complete resolution of symptoms of pancreatitis in all 44 patients.

Clinical, Biochemical, Tumoural and Mutation Profile of VHL- and MEN2A-Associated Pheochromocytoma: A Comparative Study.

OBJECTIVE: To compare clinical, biochemical, tumoural and mutational characteristics of Von Hippel Lindau Syndrome (VHL)-associated pheochromocytoma (PCC) to multiple endocrine neoplasia 2A (MEN2A)-associated pheochromocytoma. DESIGN: Retrospective study design in a tertiary health care centre in Northern India. METHODS: A total of 47 patients with biochemical and histologically proven pheochromocytoma/paraganglioma (PCC/PGL): 29 associated with VHL and 18 with MEN2A, were divided in two cohorts, respectively. Analysis of their medical records along with a prospective follow-up was done. RESULTS: There were more children <19 years in VHL group (13 vs 1). Despite majority of VHL-PCC showing elevation of normetanephrine (NMN) (93%) as compared to MEN2A-PCC (22.2%), 75.8% presented with hypertension as compared to MEN2A (33.3%). The average size of VHL-PCC tumours was 5.66 cm. VHL-PCC as compared to MEN2A-PCC were multifocal (75% vs 61.1%), bilateral synchronous (72.4 vs 61.1%) and extra-adrenal (17.2% vs 0%). Both VHL (24%) and MEN2A-PCC (27.7%) showed multiple nodules, but more MEN2A PCC showed extra-tumoural hyperplasia (44.4% vs. 6.8%). In VHL, the commonest mutation (n = 17) was missense mutation with a hot spot on exon 3, while in MEN2A-PCC majority (66.6%) had 634 mutation in exon 11 and only 2 patients had the rare 611 mutation in exon 10. CONCLUSION: In contrast to world literature, our study suggests Indian VHL-PCC can be symptomatic in spite of noradrenergic phenotype, large in size and multifocal. Multiple nodules in VHL-PCC could increase risk of recurrence following subtotal adrenalectomy.

Calcium repletion to rats with calcipenic rickets fails to recover bone quality: A calcipenic "memory".

Calcipenic rickets is prevalent in underprivileged children in developing countries. Calcipenic rickets resulting from dietary calcium (Ca) deficiency decreases bone mass and deteriorates bone microstructure in humans. The effect of dietary Ca replenishment (CaR) on rachitic bones in animal models depends on the amount, critical period and duration of replenishment, however, the extent of recovery in various bone parameters including bone quality remains unclear. We investigated the effect of CaR in rat skeleton after inducing calcipenic rickets. Female SD rats (postnatal 28 days/P28) were rendered calcipenic by feeding calcium deficient (CaD) diet (0.1% Ca) till P70 while control SD rats were fed Ca sufficient diet (0.8% Ca). At P70, calcipenic rats were switched to 0.8% Ca diet till P150 for one group and P210 for another group (endpoint). The CaD groups received 0.1% Ca diet throughout the study (P210). In the CaD groups, serum Ca and phosphate, and bone mineral density (BMD) were significantly decreased whereas serum alkaline phosphatase (ALP), iPTH and CTX-1 were increased compared to age-matched controls. Moreover, at the endpoint, the CaD group had reduced bone mass, surface referent bone formation parameters, tissue mineralization and strength accompanied by the increased osteoid thickness and microarchitectural decay (measured by trabecular geometric parameters) with poor crystal packing. The CaR group showed complete recovery in serum Ca, iPTH, ALP and CTX-1, and BMD, however, the bone quality parameters including bone strength, microarchitectural decay, tissue mineralization, and crystallinity were incompletely restored. Decreased surface referent bone formation and increased unmineralized bones (osteoid) indicative of osteomalacia were also observed in the CaR group at P210 compared with control despite prolonged replenishment. We conclude that a prolonged Ca repletion following the induction of calcipenic rickets in rats although shows the recovery of biochemical measures of bone metabolism and bone mass, however, the bone quality remains compromised. This suggests that a "memory" of calcipenia occurring at the early growth stage persists in the skeleton of adult rats despite a prolonged Ca replenishment.

Endocrine Manifestations of Von Hippel-Landau Disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by various endocrine, nonendocrine, benign, and malignant tumors in various organs. VHL tumor suppressor gene, located on short arm of chromosome 3 is responsible for this. Pheochromocytoma (PCC) is one of the important endocrine manifestations that needs to be ruled out in case of VHL suspicion. In this review, we summarize the endocrine manifestations of VHL disease and their management while giving case history of five such cases.

Antifungal efficacy of herbs.

Candida carriage was reported to be common in oral cancer patients, with C. albicans being the predominant species. The prevalence of diseases caused by Candida species have been found to increase in recent years. AIM: The aim of our study was to find the antifungal activities at MIC of selected fifteen plant leaves extracts prepared in three different solutions (methanol and ethanol) against the opportunistic pathogen Candida albicans isolated from oral cavity infections. It may also help the clinician to treat the patient not only for the particular lesion that is present, but also to treat the infection by Candida albicans so as to reduce its potential to malignant transformation. Material n methods: Leaves extract of selected plant prepared in methanolic and eethanolic solution have been chosen for the investigation of in vitro antifungal activity which acts as expectorant and not having toxic properties on humans while for comparison or control, antifungal drugs have been taken. Results showed that Candida albicans shows most sensitivity towards the standard antibiotic cotrimoazol but very less towards other drugs like Fluconazole, minocycline, erythromycin respectively which indicated Candida albicans shows some resistance character towards drugs while the herbal extracts of Lawsonia inermis, Withania somnifer, Curcuma longa, Cymbopogon citrates and Zingiber officinale gives the best inhibitory effect and they have the potential to control growth of Candida albicans.

PHPT Masquerading as Rickets in Children and Presenting with Rare Skeletal Manifestations: Report of Three Cases and Review of Literature.

Primary hyperparathyroidism (PHPT) is an uncommon condition in children and adolescents. However, rapid growth spurt during puberty may result in unmasking and development of certain skeletal manifestations of PHPT. We present three cases of PHPT associated with rare skeletal manifestations of rickets. All three patients had radiological evidence of rickets with primary hyperparathyroidism. All the three patients had single gland adenoma. Literature is sparse regarding reversal of features of rickets following parathyroidectomy. In all three patients of our series, there was a complete resolution of bone/joint pain. However, in two children only the genu valgum persisted but their growth was normal and they had no proximal muscle weakness. In another child multiple corrective surgeries were done to correct the deformities.

Molecular Profiling of Follicular Variant of Papillary Thyroid Cancer Reveals Low-Risk Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Paradigm Shift to Reduce Aggressive Treatment of Indolent Tumors.

INTRODUCTION: Encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has been reclassified into noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and invasive EFVPTC. NIFTP is considered a low-risk neoplasm. Therefore, follicular variant of papillary thyroid cancer (FVPTC) presently has two distinct histopathological subtypes - invasive EFVPTC and infiltrative/diffuse FVPTC. Molecular characteristics of these groups remain unclear. METHODOLOGY: Thirty FVPTCs (10 NIFTPs, 12 invasive EFVPTCs, and 8 infiltrative/diffuse variants) were reviewed and screened for BRAF and RAS mutations by restriction fragment length morphism-polymerase chain reaction (PCR) and Sanger sequencing. The mRNA expression levels of iodine-metabolizing genes were analyzed using real-time PCR. The mutations status and mRNA expression levels were correlated with clinicopathological features. RESULTS: All 10 NIFTPs had predominant follicular pattern. One case showed NRAS mutation, whereas none showed BRAF mutation. All invasive EFVPTC had capsular and/or lymphovascular invasion and 4/12 showed lymph node metastasis. BRAF and NRAS were seen in three cases each of invasive FVPTC. All eight infiltrating/diffuse FVPTCs showed infiltration into adjacent thyroid parenchyma and lymph node metastasis. CONCLUSION: BRAF mutation was observed in 62.5% of cases; however, no NRAS mutation was found. Sodium iodide symporter (NIS) expressions in NIFTP were similar to that of normal thyroid tissue, whereas it was downregulated in invasive and infiltrative/diffuse FVPTC. Our study supports the argument that NIFTP can be considered as low-risk follicular thyroid neoplasm. Those tumors that harbor BRAF mutations may be offered a complete thyroidectomy because they show decreased expression of NIS gene which confers a tendency to lose radioactive iodine avidity and further recurrence of the tumor.

Mutational Profile of Papillary Thyroid Carcinoma in an Endemic Goiter Region of North India.

INTRODUCTION: Mitogen activated protein kinase (MAPK) pathway is regularly altered in papillary thyroid carcinomas (PTCs). Serine/threonine-protein kinase B-Raf (BRAF) V600E mutations were observed very frequently in PTC along with less frequent rat sarcoma (RAS) and rearranged during transfection (RET) gene, also known as RET/PTC translocation. The present study aimed to analyze the mutational profile of PTCs from an endemic Goiter area of North India. METHODOLOGY: Tissues from 109 PTC patients were used to isolate DNA and RNA. BRAF V600E was detected by restriction fragment length polymorphism-polymerase chain reaction (PCR). RAS mutations were screened by using Sanger's sequencing method. RET/PTC rearrangements were analyzed by real-time PCR. RESULTS: BRAF V600E mutation was detected in 51.38% (56/109) of PTCs, whereas RAS mutations were less frequent. No RET/PTC rearrangements were observed. BRAF V600E was found to be associated with the aggressive clinicopathological features such as lymph node metastasis, distant metastasis, higher tumor-node-metastasis stages, and high-risk groups. CONCLUSION: The prevalence of BRAF V600E is high in patients from Indian Subcontinent and found to be associated with aggressive features of PTC. Concomitant mutations of BRAF V600E and RAS mutations impart more aggressiveness to PTCs.

High Prevalence of Osteoporosis and Morphometric Vertebral Fractures in Indian Males Aged 60 Years and Above: Should Age for Screening Be Lowered?

Current guidelines recommend bone mineral density (BMD) measurement in asymptomatic men above age 70 years and vertebral fracture (VF) assessment above 80 years with T-score <-1.0 with risk factors. We studied the prevalence of osteoporosis and morphometric VF in asymptomatic males aged 60 years and above in North India. Free-living community-dwelling men (n = 241, age: mean ± standard deviation 68.0 ± 6.2 years) underwent a detailed history, physical examination, biochemical evaluation, and BMD measurements at 3 sites: lumbar spine, total hip (TH), and femoral neck (FN). Morphometric VF were assessed by instant vertebral assessment using Genant et al's semiquantitative method. We observed osteoporosis, osteopenia, and normal BMD in 19%, 56%, and 25% of subjects, respectively. The decade wise prevalence of osteoporosis in the age groups 60-70 years, 71-80 years, and >80 years was 16.9%, 17%, and 50%, respectively. Mean serum 25OHD levels were 17.2 ± 10.3 ng/mL. Vitamin D deficiency (<20 ng/mL) and secondary hyperparathyroidism (plasma intact parathyroid hormone >65 ng/mL) were present in 68.8% and 45.4%, respectively. VF were present in 29.6% subjects (grade I: 58%, grade II: 32.4%, and grade III: 8.8%). Age and iPTH had significant negative correlation with BMD at FN and TH. Serum 25OHD had no correlation with BMD at any site. The prevalence of VF was positively associated with age (p = 0.018) and negatively associated with BMD at FN (p = 0.002) and TH (p = 0.013). Osteoporosis and VF are common in asymptomatic Indian males aged 60 years and above. Screening for osteoporosis and instant vertebral assessment may be recommended earlier than currently existing guidelines.

Oncogenic osteomalacia: role of Ga-68 DOTANOC PET/CT scan in identifying the culprit lesion and its management.

OBJECTIVE: The aim of this study was to evaluate the role of 68Ga-DOTANOC positron emission tomography (PET)/CT scan in localization of culprit lesion for biopsy and required intervention [surgical excision/radiofrequency ablation (RFA)] in patients with long-standing oncogenic osteomalacia (OOM)/tumour-induced osteomalacia. METHODS: 17 patients (8 males and 9 females) underwent 68Ga-DOTANOC PET/CT scan. The patients referred with clinical and biochemical evidence of hypophosphatemia and raised fibroblast growth factor-23. Qualitative and semi-quantitative parameters were used to identify culprit lesions. RESULTS: 68Ga-DOTANOC PET/CT scan revealed 52 lesions in 17 patients, and 37/52 of these lesions were tracer avid. 26/37 lesions were non-specific focal tracer-avid skeletal lesions (fractures or degenerative changes). 11/37 tracer-avid skeletal lesions present in 9 patients (3 lesions in 1 patient and 1 each in rest of the 8 patients) were highly suspicious for culprit lesions in view of high maximum standardized uptake value (SUVmax) (range 1.5-15.4; mean 7.0 ± 4.6), lesion size (0.9-5.0 cm; mean 3.3 ± 1.5) and associated soft-tissue component. During subsequent imaging with CT/MRI, 7/9 patients showed concordant lesions which were excised or biopsied and histopathologically verified as phosphaturic mesenchymal tumours. Surgical excision was resorted to in most of the detected lesions, and RFA was performed in one patient. CONCLUSION: There is some overlap in SUVmax between fracture-/bone-associated lesions and culprit lesions with a tendency of most non-culprit lesions to have lower SUVmax and no associated soft-tissue component. In such scenario, intensely tracer-avid, larger non-fracture lesions with soft-tissue component may lead to identification of culprit lesion among multiple lesions. Following detection of culprit lesion, surgical removal is the best treatment. RFA is alternative to surgery in cases where surgery is not possible owing to osteopenia/poor bone health. Advances in knowledge: The main challenge in patients of long-standing OOM is the presence of multiple skeletal lesions (both tumour- or tracer-avid fractures), and it is confusing to identify culprit lesion. This was noted in our study with 68Ga-DOTANOC and has not been mentioned in studies performed with 68Ga-DOTATATE/TOC PET/CT. In such scenario, 68Ga-DOTANOC PET/CT needs to be reviewed and read thoroughly to localize the culprit lesion out of the multiple tracer-avid lesions.

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene.

A growing understanding of the bone remodeling process suggests that inflammation significantly contributes to the pathogenesis of osteoporosis. T cells and various cytokines contribute majorly to the estrogen deficiency-induced bone loss. Recent studies have identified the IL-12 cytokine family as consisting of pro-inflammatory IL-12 and IL-23 and the anti-inflammatory IL-27 and IL-35 cytokines. IL-27 exerts protective effects in autoimmune diseases like experimental autoimmune encephalomyelitis; however, its role in the pathogenesis of osteoporosis remains to be determined. In this report, we study the effect of IL-27 supplementation on ovariectomized estrogen-deficient mice on various immune and skeletal parameters. IL-27 treatment in ovariectomized mice suppressed Th17 cell differentiation by inhibiting transcription factor RORγt. Supplementation of IL-27 activates Egr-2 to induce IL-10 producing Tr1 cells. IL-27 treatment prevented the loss of trabecular micro-architecture and preserved cortical bone parameters. IL-27 also inhibited osteoblast apoptosis through increased Egr-2 expression, which induces anti-apoptotic factors like MCL-1. IL-27 suppressed osteoclastogenesis in an Egr-2-dependent manner that up-regulates Id2, the repressor of the receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis. Additionally, these results were corroborated in female osteoporotic subjects where we found decreased serum IL-27 levels along with reduced Egr-2 expression. Our study forms a strong basis for using humanized IL-27 toward the treatment of post-menopausal osteoporosis.

Utility of Osteoporosis Self-Assessment Tool as a Screening Tool for Predicting Osteoporosis in Indian Men.

The osteoporosis self-assessment tool (OSTA) predicts the risk of osteoporosis in an individual. It is a simple calculation-based tool [wt (kg) - age (yr)/5] and can be used for measuring bone mineral density (BMD). However, OSTA is influenced by ethnicity. We studied the performance of OSTA index as a screening tool for osteoporosis in 257 community-dwelling North Indian men above 50 yr age. Each subject underwent a detailed clinical, dietary, anthropometric, and biochemical assessment and bone density measurement using dual-energy X-ray absorptiometry. As per World Health Organization criteria, osteoporosis, osteopenia, and normal BMD were observed in 17.9%, 58.8%, and 23.3%, respectively. OSTA index ranged between -6.4 and 8.8. OST index ≤2 predicted osteoporosis with a sensitivity of 95.7% and a specificity of 33.6% and an area under the curve for a receiver operating characteristic curve of 0.702. The OSTA index is an effective screening tool for measuring BMD in elderly Indian men and can be used by primary care physicians.

Prevalence of colonic polyp and its predictors in patients with acromegaly.

BACKGROUND: There are conflicting data regarding the prevalence of colorectal polyp in patients with acromegaly. SUBJECTS AND METHODS: Consecutive forty-seven acromegalic patients (21 men, 26 women), with a mean age of (40 ± 12 years) attending endocrinology outpatient department underwent full colonoscopy. All the patients underwent clinical and biochemical evaluation (glucose suppressed growth hormone (GH), Insulin-like growth factor-1 [IGF-1], fasting insulin, and glucose). The control group (n = 120) for colonoscopy was adult subjects undergoing evaluation for symptoms of irritable bowel syndrome. Clinical and biochemical parameters in acromegalic patients with colonic polyp were compared to those without a polyp. RESULTS: Patients with acromegaly had significantly higher prevalence of colonic polyp as compared to control subjects (10.6% vs. 0.8%). None of the patients with polyp had skin tags. There was no significant difference between subjects with and without colonic polyp in duration of illness, basal, and glucose-suppressed GH and most recent IGF-1. Fasting blood sugar was significantly higher (P < 0.05) in adenoma group after adjusting for age, body mass index (BMI), and insulin levels. Patients in adenoma group showed a trend toward male gender and younger age as compared to those without adenoma. CONCLUSIONS: Subjects with acromegaly as compared to control have a higher prevalence of colonic polyps. There was no association of polyps seen with age, BMI, skin tags, homeostasis model assessment of insulin resistance index, duration of disease, and basal and glucose-suppressed GH and IGF-1 levels. There were no specific predictive factors detected. Screening full colonoscopy is recommended in all cases with acromegaly.

Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats.

The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug. When adult Sprague-Dawley rats were treated with theophylline, bone regeneration at fracture site was diminished compared with control. Theophylline treatment resulted in a time-dependent (at 4- and 8 weeks) bone loss. At 8 weeks, a significant loss of bone mass and deterioration of microarchitecture occurred and the severity was comparable to methylprednisone. Theophylline caused formation of hypomineralized osteoid and increased osteoclast number and surface. Serum bone resorption and formation marker were respectively higher and lower in the theophylline group compared with control. Bone strength was reduced by theophylline treatment. After 8 weeks, serum 25-D3 and liver 25-hydroxylases were decreased in theophylline group than control. Further, theophylline treatment reduced serum 1, 25-(OH)2 vitamin D3 (1,25-D3), and increased parathyroid hormone and fibroblast growth factor-23. Theophylline treated rats had normal serum calcium and phosphate but displayed calciuria and phosphaturia. Co-administration of 25-D3 with theophylline completely abrogated theophylline-induced osteopenia and alterations in calcium homeostasis. In addition, 1,25-D3 protected osteoblasts from theophylline-induced apoptosis and the attendant oxidative stress. We conclude that theophylline has detrimental effects in bone and prophylactic vitamin D supplementation to subjects taking theophylline could be osteoprotective.