Effectiveness and safety of continuous subcutaneous hydrocortisone infusion in managing adrenocortical insufficiency in adult patients: a systematic review.

Oral hormone replacement therapy has been and continues to be the cornerstone of adrenocortical insufficiency management. However, the introduction of continuous subcutaneous hydrocortisone infusion (CSHI) shows great potential for advancing the management of adrenocortical insufficiency. It resembles the circadian rhythm of physiological cortisol secretion and was shown to have a promising outcome in terms of quality of life (QOL) and clinical outcomes in the literature. We conducted a systematic search strategy including MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and the online trials registers at ClinicalTrials.gov without geographic restrictions. Research investigations where self-reported quality of life (QOL) was assessed as a variable in adult individuals with confirmed adrenal disease, treated by CSHI, and results were presented in English. All articles included were published between 2014 and 2023, even though we had no timeframe limitations in our inclusion criteria. A total of six studies were included, with 63 subjects enrolled, and the average age was 40 years, a study showed a significant reduction in the average total daily dose of HC from 47.5 mg to 31.4 mg on CSHI, while other two studies estimated a reduction in the hospitalization rate due to adrenal crisis from 2.6 to 1.3 admissions per year on CSHI. Most of the studies on subjective well-being and quality of life have shown significant improvement. Overall, CSHI shows great potential as a treatment method for Adrenal insufficiency. It improves the quality of life and lowers hospitalization rates, resulting in increased patient satisfaction and acceptance. Additional comprehensive research is necessary to strengthen these discoveries, gain a deeper understanding of the effectiveness and safety of this treatment approach, and provide guidance for medical practitioners.

Ultrasonographic predictors of thyroid cancer in Bethesda III and IV thyroid nodules.

Background: Bethesda III and IV thyroid nodules continue to be difficult to manage. Although molecular testing may assist in decision-making, it is expensive, not widely available, and not without pitfalls. The objective of this study is to assess whether certain thyroid ultrasonographic features may predict the risk of thyroid cancer in patients with Bethesda III and IV thyroid nodules and be used as additional decision-making tools to complement cytopathological results in deciding on diagnostic thyroidectomy. Methods: We retrospectively evaluated the ultrasonographic features of Bethesda categories III and IV thyroid nodules in patients who underwent subsequent thyroidectomy. We used the final histopathological examination of the surgical specimens as the gold-standard test and analyzed individual preoperative ultrasonographic features as predictors of malignancy. Results: Of the 278 patients who were diagnosed with Bethesda III and IV thyroid nodules on fine needle aspiration cytology (FNAC), 111 (39.9%) had thyroid cancer, and 167 (59.9%) exhibited benign nodules. The malignancy rate was higher in patients with Bethesda IV nodules (28/50, 56%) than those with Bethesda III nodules (83/228, 36.4%; p=0.016). In univariate analysis, hypoechogenicity (55.6% in malignant vs. 35.3% in benign, p=0.006) and calcifications (54.5 in malignant vs. 35.4% in benign, p=0.008) were significantly different between the benign and malignant pathology groups, whereas the size of the dominant nodule, number of nodules, irregular borders, taller-than-wide shape, and the presence of lymph nodes were comparable between the two groups. These two ultrasonographic features (hypoechogenicity and calcifications) remained significantly associated with the risk of malignancy in multivariate logistic regression analysis (for hypoechogenicity, p=0.014, odds ratio: 2.1, 95% CI:1.0-3.7 and for calcifications, p=0.019, odds ratio: 1.98, 95% CI:1.12-3.50). The sensitivity, specificity, positive and negative predictive values, and accuracy were 31.5%, 83%, 55.6%,64.7%, and 62.6%, for hypoechogenicity, respectively and 32.4%, 82%, 54.5%, 67.8%, and 62%, for calcification, respectively. Conclusions: Hypoechogenicity and calcifications in Bethesda III and IV thyroid nodules are strong predictors of thyroid cancer and associated with a two-fold increased risk of malignancy.

Impulse control disorders in patients with dopamine agonist-treated pituitary adenomas: a cross-sectional multicenter study.

BACKGROUND: Impulse control disorders (ICDs) have been described as underrecognized side effects of dopamine agonists (DAs) in neurological disorders but are not sufficiently understood in endocrine conditions. OBJECTIVE: To identify the prevalence of DAs induced ICDs and determine potential risk factors related to these disorders in patients with prolactinoma and non-function pituitary adenomas (NFPAs). METHODS: This is a cross-sectional multicenter study involving 200 patients with prolactinoma and NFPAs, who received follow-ups in tertiary referral centers. DA-induced ICDs were assessed using ICD questionnaires modified from prior studies. RESULT: At least one ICD was reported by 52% of participants, among whom 28.5% mentioned compulsive shopping, 24.5% punding, and 24.5% hypersexuality. Furthermore, 33% of the patients reported the presence of one type of ICD behavior, while 12% specified two and 7% had three types of such behavior. The multivariable logistic regression showed that the significant risk factors of ICD were younger age (adjusted odds ratio [AOR]: 0.92, 95% confidence interval [CI]: 0.88-0.97, p 0.001), being single (AOR: 0.15, 95%CI: 0.03-0.84, p 0.03), and a positive history of psychiatric illness (AOR: 7.67, 95% CI: 1.37-42.97, p 0.021). CONCLUSION: ICDs with a broad range of psychiatric symptoms are common in individuals with DA-treated prolactinoma and NFPAs. Endocrinologists should be aware of this potential side effect, particularly in patients with a personal history of psychiatric disorder.

Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment.

Diabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear. Twelve male patients with T2DM (pre and post liraglutide treatment) and HbA1c between 8% and 11% were recruited. In the present study, a two-dimensional difference gel electrophoresis (2D-DIGE) matrix-assisted laser desorption/ionization-time of flight (MALDI TOF) mass spectrometric approach combined with bioinformatics and network pathway analysis was used to explore the urine proteomic profile. The mean age of the patients was 52.4 ± 7.5 years. After treatment with liraglutide, a statistically significant change (p < 0.006) was observed in HbA1c with no significant changes in body weight or markers of dyslipidemia. Two-dimensional difference gel electrophoresis identified significant changes (≥1.5-fold change, ANOVA, p ≤ 0.05) in 32 proteins (4 down- and 28 upregulated) in liraglutide post treatment compared to the pre-treatment state. Albumin, serotransferrin, metallothionein-2 (MT-2), and keratins K1 and K10 were found to be upregulated after liraglutide treatment. The patients showed significant improvement in glycemic control after the 12-week treatment with liraglutide. The renoprotective effect of liraglutide may be linked to the increased urinary abundance of MT-2 and the decreased abundance of zinc alpha 2-glycoprotein (ZAG) and Alpha-1 antitrypsin (α1-AT). More studies are needed to elucidate the molecular mechanisms behind the renoprotective effects of liraglutide.

Hybrid Nanoparticles of Manganese Oxide and Highly Reduced Graphene Oxide for Photodynamic Therapy.

BACKGROUND: Graphene-based nanomaterials possess unique optical, physicochemical and biomedical properties which make them potential tools for imaging and therapy. Manganese oxide nanoparticles are attractive candidates for contrast agents in magnetic resonance imagint (MRI). We used manganese oxide (Mn3O4) and highly reduced graphene oxide (HRG) to synthesize hybrid nanoparticles (HRG-Mn3O4) and tested their efficacy for photodynamic therapy (PDT) in breast cancer cells. METHODS: The newly synthesized nanoparticles were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, UV-visible spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetry, and X-ray diffraction (XRD) analyses. We used standard protocols of cytotoxicity and PDT after exposing A549 cells to various concentrations of hybrid nanoparticles (HRG-Mn3O4). We also performed fluorescence microscopy for live/dead cellular analysis. A549 cells were incubated with nanoparticles for 24 h and stained with fluorescein diacetate (green emission for live cells) and propidium iodide (red emission for dead cells) to visualize live and dead cells, respectively. RESULTS: The cell viability analysis showed that more than 98% of A549 cells survived even after the exposure of a high concentration (100 µg/mL) of nanomaterials. These results confirmed that the HRG-Mn3O4 nanoparticles are nontoxic and biocompatible at physiological conditions. When the cell viability analysis was performed after laser irradiation, we observed significant and concentration-dependent cytotoxicity of HRG-Mn3O4 as compared to Mn3O4 nanoparticles. Fluorescence microscopy showed that almost 100% cells were viable when treated with phosphate buffered saline or Mn3O4 while only few dead cells were detected after exposure of HRG-Mn3O4 nanoparticles. However, laser irradiation resulted in massive cellular damage by HRG-Mn3O4 nanoparticles which was directly related to the generation of reactive oxygen species (ROS). CONCLUSIONS: HRG-Mn3O4 hybrid nanoparticles are stable, biocompatible, nontoxic, and possess therapeutic potential for photodynamic therapy of cancer. Further studies are warranted to explore the MRI imaging ability of these nanomaterials using animal models of cancer.

Fasting Ramadan in patients with T1DM - Saudi Arabia versus other countries during the COVID-19 pandemic.

BACKGROUND AND AIMS: To compare Saudi Arabia with other countries regarding patient attitudes towards fasting Ramadan and complications related to fasting during the COVID-19 pandemic. METHODS: Data collected from Saudi Arabia and 12 other mostly Muslim majority countries, via physician administered questionnaire within post Ramadan 2020. RESULTS: 1485 Type1 diabetes (T1DM) patients analyzed; 705 (47.5%) from Saudi Arabia vs. 780 (52.5%) from other countries. 1056 (71.1%) fasted Ramadan; 636 (90.2%) of Saudi patients vs. 420 (53.8%) of other countries. Experiencing Ramadan during the COVID-19 pandemic did not affect the Saudi T1DM patients' decision to fast while it significantly influenced their decision in other countries (1.4 vs 9.9%, P < 0.001). More Saudi patients needed to break the fast due to a diabetes related complication compared to other countries (67.4% vs. 46.8%, p=<0.001). The mean number of days fasted in Saudi and other countries was 24 ± 7 and 23 ± 8 days respectively. Hypoglycemic events were more common among Saudi patients during Ramadan compared to other countries 72% and 43.6% (p < 0.001) respectively. There was a significant difference in timing; the largest peak for Saudi Arabia patients was after dawn (35% vs 7%, p < 0.001), while it was pre-sunset for the other countries (23 vs 54%, p = 0.595). Day time-hyperglycemia was also more common among Saudi patients (48.6% vs. 39%, p < 0.001), however it was a less likely cause to break the fast (25.6% vs 38.3%, p < 0.001). CONCLUSION: Observing the fast of Ramadan is extremely common among Saudi T1DM patients compared to other Muslim countries and was not affected by the COVID-19 pandemic. However, it was associated with higher frequency of hypoglycemic and hyperglycemic episodes.

Adoption of telemedicine care for osteoporotic patients during the COVID-19 pandemic: experience from a tertiary care center in Saudi Arabia.

The aim of this study was to examine the feasibility and effectiveness of telemedicine care provided to osteoporotic patients in Saudi Arabia. Our results show that this service was effective and feasible, and patients had a good rate of satisfaction with it. PURPOSE: To investigate the efficacy and feasibility of telemedicine care in osteoporotic patients during the COVID-19 lockdown period in Saudi Arabia compared to in-person patients, as well as their satisfaction with this service. METHODS: This observational retrospective study was conducted between March 2021 and September 2021 in King Saud University Medical City, Saudi Arabia. A survey was used to compare patients attending telemedicine clinics with in-person patients in terms of access and adherence to medications, occurrence of new fractures, and overall satisfaction with this service. RESULTS: 195 patients attended the telemedicine clinic, while 63 attended the in-person clinic. Exercise frequency was similar in both groups, although exercise intensity was greater in the in-person group. 25(OH)D levels were stable in both groups. The availability and delay of supply of osteoporosis medications were not statistically different between both groups while adherence to treatment did not differ significantly between the two groups. The majority of patients in the telemedicine group were satisfied. CONCLUSIONS: Telemedicine care was feasible and effective in managing osteoporotic patients during the COVID-19 epidemic. Such service could be considered in the future for managing disabled patients and those living in remote areas.

Nanocomposites of Nitrogen-Doped Graphene Oxide and Manganese Oxide for Photodynamic Therapy and Magnetic Resonance Imaging.

Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with Mn3O4 nanoparticles to produce NDG-Mn3O4 nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and Mn3O4, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn3O4 nanocomposites caused significant cell death under laser irradiation, while control and Mn3O4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn3O4 nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-Mn3O4 nanocomposites. In conclusion, NDG-Mn3O4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn3O4 nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-Mn3O4 nanocomposites using animal models of cancer.

Proportion and predictors of Hypogonadism Recovery in Men with Macroprolactinomas treated with dopamine agonists.

INTRODUCTION: Hypogonadism is the most common form of hypopituitarism in men with macroprolactinoma. However, evidence on factors related to hypogonadism recovery is limited. OBJECTIVES: We estimated the proportion of hypogonadism in men with macroprolactinoma exclusively treated with dopamine agonists, and we assessed the factors predicting hypogonadism recovery. PATIENTS AND METHODS: This was a multicenter retrospective study of men with macroprolactinoma identified using ICD 9 and 10 codes and treated between 2009 and 2019 in five centers in the United Arab Emirates and Saudi Arabia. We evaluated hypogonadism, defined as low total testosterone (TT) level with normal or low gonadotropins on presentation and during the last clinic visit. RESULTS: A total of 79 patients (median age 32 years) were included in the study. The most common symptoms at presentation were headache (73.7%), erectile dysfunction (55.4%), and low libido (54.3%). The median tumor size was 2.9 cm (1.0-9.7) at diagnosis. Sixty-three patients (79.7%) had hypogonadism at baseline. Growth hormone deficiency (GHD) and hypothyroidism were present in 34.4% and 32.9% of patients, respectively. The median serum prolactin (PRL) level was 20,175 (min-max 2254 - 500,000) mIU/l with a median serum TT of 4.5 (min-max 0.4-28.2) nmol/l. Most patients were treated with cabergoline (n = 77, 97.5%) with a median of 6 (min-max 0.6-22) years. At follow-up, 65% of patients recovered their pituitary-testicular axis. Patients with recovered hypogonadism had smaller median tumor size (2.4 [1-5.4] vs. 4.3 [1.6-9.7], p = 0.003), lower PRL level (18, 277 [2254 - 274, 250] vs. 63,703 [ 3,365-500,000], p = 0.008 ), higher TT level (4.6 [0.6-9.2] vs. 2.3 [0.5-7.3], p = 0.008), lower PRL normalization time on medical therapy (8 months (0.7-72) vs. 24 (3-120), p = 0.009) as well as lower frequency of GHD (17.1% vs. 60%, p = 0.006) and secondary hypothyroidism (17.9% vs. 57.1%, p = 0.003) compared with those with persistent hypogonadism respectively. Age at diagnosis, presenting symptoms and duration of medical therapy did not predict hypogonadism recovery. CONCLUSIONS: About two-thirds of men with macroprolactinoma recover from hypogonadism, mostly with 24 months of therapy. Smaller adenoma size, lower prolactin level, earlier prolactin normalization, and higher testosterone patients were related to testosterone normalization.

Graves' Ophthalmopathy in the Setting of Primary Hypothyroidism.

Graves' ophthalmopathy (GO) is commonly associated with hyperthyroidism secondary to Graves' disease (GD). Although rare, there have been case reports of it occurring in patients who are hypothyroid with underlying Hashimoto's thyroiditis (HT), as well as in euthyroid patients. Below, we describe a case of GO developing in a patient who has hypothyroidism secondary to HT successfully treated with high-dose steroids. We present a case of a 53-year-old female known to have primary hypothyroidism (Hashimoto's thyroiditis) diagnosed at the age of 39 years and has been on levothyroxine since diagnosis. She presented to our endocrine clinic complaining of new-onset diplopia and periorbital swelling for five months. There is no previous hyperthyroid state or radioactive iodine therapy. Examination showed left-sided upper and lower eyelid swelling, limited abduction with diplopia, and mild punctate keratopathy. Laboratory investigation revealed positive thyroid-stimulating immunoglobulin of 500 IU/mL (normal value: <140 IU/mL) with thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in the euthyroid range. She was found to have a small heterogeneous thyroid gland on ultrasound suggestive of atrophic thyroiditis, and magnetic resonance imaging (MRI) of the orbits demonstrated bilateral ocular proptosis with extraocular muscle enlargement. The patient was diagnosed with active moderate-severe isolated GO with a background of HT, clinically and biochemically euthyroid on levothyroxine. She was referred to an ophthalmologist and was started on a course of high-dose oral prednisone tapered over three months, which was followed by oral selenium and botox injections to both medial recti muscles. Graves' ophthalmopathy is an uncommon presentation in hypothyroid and euthyroid patients but should be considered in the differential diagnosis. The incidence varies between studies from 2% to 7.5%. Awareness of this clinical presentation is important, as early detection and treatment can prevent visual complications. To date, there are no clear guidelines on how to treat GO with underlying HT. Treating our patient with high-dose steroids extrapolated from treating GO secondary to GD showed significant improvement in her symptoms.

Thyroid Storm in a Patient With Alemtuzumab-Induced Graves' Disease: A Case Report.

Thyroid storm (TS) is a rare and life-threatening medical emergency, most commonly caused by Graves' disease (GD). GD can be induced by immune reconstitution therapy (IRT) such as alemtuzumab (ALZ), a humanized monoclonal antibody against CD52, which is shown to be effective in the treatment of relapsing-remitting multiple sclerosis (RRMS). Here, we present a rare case of TS developing in a 39-year-old female with ALZ-induced GD, managed with antithyroid medication followed by thyroidectomy. There is some evidence that ALZ-induced GD may behave less aggressively than conventional GD. However, physicians should be aware that severe thyrotoxicosis and thyroid storm can happen, which requires prompt recognition and aggressive therapy.

Plasma proteomics reveals an improved cardio-metabolic profile in patients with type 2 diabetes post-liraglutide treatment.

BACKGROUND: Diabetes mellitus is a chronic multisystem disease with a high global prevalence, including in Saudi Arabia. The Glucagon-like Peptide (GLP-1) receptor agonist liraglutide is known to lower glucose levels, reduce weight and improve cardiovascular outcome. However, mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear. METHODS: In the present study, a 2D-DIGE MALDI-TOF mass spectrometric approach combined with bioinformatics and network pathway analysis explore the plasma proteomic profile. The study involved 20 patients with T2DM with mean age of 54.4 ± 9.5 years and Hemoglobin A1c (HbA1c) between 8% and 11% (inclusive). RESULTS: A statistically significant change (p < .006) was observed in HbA1c with no significant changes in body weight, renal function, or markers of dyslipidemia post-treatment with liraglutide. 2 D-DIGE gel analysis identified significant changes (⩾1.5-fold change, Analysis of variance (ANOVA), p ⩽ 0.05) in 72 proteins, (62 down and 10 up) in liraglutide pre-treatment compared to the post-treatment state. Proteins identified in our study were found to regulate metabolic processes including acute phase response proteins, enzymes, apolipoproteins with involvement of the inflammatory signaling pathways, NF-κB, AKT, and p38 MAPK. CONCLUSION: Liraglutide treatment decreased levels of acute phase response that to reduce the systemic chronic inflammatory state and oxidative stress, and eventually improve the cardio-metabolic profile in these patients.

Fructosamine as an Index of Short-Term Glycemic Control in Pregnant Women with Diabetes: Before, During and After Ramadan.

Purpose: Impact of ramadan fasting on healthy and women with diabetes is already known. However, there is a scarcity of data on impact of fasting on pregnant women with diabetes. Moreover, religious and medical recommendations advise pregnant women against fasting as it is unsafe. Despite being exempted, many pregnant Muslim women with diabetes still choose to fast during ramadan. This study investigated different glycemic marker as an indicator for diabetes control in fasting pregnant women. Patients and Methods: This is a prospective observational study. A total of 89 pregnant diabetes women were recruited. Blood glucose was self-monitored in all the pregnant women using glucose monitoring device at home. We measure the fructosamine, HbA1c levels before, during and after ramadan. Results: Pregnant women with type 1 diabetes were 14 (25%), type 2 diabetes were 21 (37.5%), and gestational diabetes were 21 (37.5%). The mean fructosamine level decreased during and after ramadan in gestation diabetes pregnant women compared to type 2 diabetes and type 1 diabetes pregnant women subjects (p = 0.009). Conclusion: The present study indicates that pregnant women with diabetes were able to fast during ramadan and there fructosamine level reduced during fasting. Utilization of fructosamine for short-term monitoring of glycemic control in addition to home glucose monitoring in pregnant women with diabetes will provide a good index of glycemic control. Recommendation: Religious and medical recommendations advise pregnant women against fasting as it is unsafe, and they are under high risk. However, if they insist to do fast, they must do under strict medical supervision and fructosamine can be used as a glycemic control marker.

A Novel Mutation in a Gene Causes Sclerosteosis in a Family of Mediterranean Origin.

Background and Objectives: Sclerostin is an SOST gene product that inhibits osteoblast activity and prevents excessive bone formation by antagonizing the Wnt signaling pathway. Sclerosteosis has been linked to loss of function mutations in the SOST gene. It is a rare autosomal recessive disorder characterized by craniotubular hyperostosis and can lead to fatal cerebellar herniation. Our aim is to describe the clinical and radiological features and the new underlying SOST mutation in a patient with sclerosteosis. Case: A 25-year-old female who was referred to the endocrine clinic for suspected excess growth hormone. The patient complained of headaches, progressive blurred vision, hearing disturbances, increased size of feet, proptosis, and protrusion of the chin. She had normal antenatal history except for syndactyly. Images showed diffuse osseous thickening and high bone mineral density. Biochemical and hormonal tests were normal. Due to progressive compressive optic neuropathy, optic nerve fenestration with decompression hemicraniotomy was performed. Sclerosteosis was suspected due to the predominant craniotubular hyperostosis with syndactyly. Using peripheral leucocyte DNA, genomic sequencing of the SOST gene was performed. This identified a novel deletion homozygous mutation in the SOST gene (c.387delG, p.Asp131ThrfsTer116) which disrupts sclerostin function, causing sclerosteosis. Conclusions: Discovery of the molecular basis of sclerosteosis represents an important advance in the diagnosis and management of this fatal disease.

Phytochemicals reverse P-glycoprotein mediated multidrug resistance via signal transduction pathways.

P-glycoprotein, encoded by ATP-binding cassette transporters B1 gene (ABCB1), renders multidrug resistance (MDR) during cancer chemotherapy. Several synthetic small molecule inhibitors affect P-glycoprotein (P-gp) transport function in MDR tumor cells. However, inhibition of P-gp transport function adversely accumulates chemotherapeutic drugs in non-target normal tissues. Moreover, most small-molecule P-gp inhibitors failed in the clinical trials due to the low therapeutic window at the maximum tolerated dose. Therefore, downregulation of ABCB1-gene expression (P-gp) in tumor tissues seems to be a novel approach rather than inhibiting its transport function for the reversal of multidrug resistance (MDR). Several plant-derived phytochemicals modulate various signal transduction pathways and inhibit translocation of transcription factors, thereby reverses P-gp mediated MDR in tumor cells. Therefore, phytochemicals may be considered an alternative to synthetic small molecule P-gp inhibitors for the reversal of MDR in cancer cells. This review discussed the role of natural phytochemicals that modulate ABCB1 expression through various signal transduction pathways in MDR cancer cells. Therefore, modulating the cell signaling pathways by phytochemicals might play crucial roles in modulating ABCB1 gene expression and the reversal of MDR.

Radiofrequency Ablation as a Primary Therapy for Benign Functioning Insulinoma.

OBJECTIVE: Insulinomas are rare, life-threatening pancreatic neuroendocrine tumors. Surgical removal continues to be the treatment of choice, yet it is associated with considerable risk of morbidity. Here, we describe our patient with insulinoma who was successfully treated with radiofrequency ablation. METHODS: The patient was a 56-year-old man with no history of diabetes mellitus. He presented with recurrent episodes of transient ischemic attacks and stroke over the last 3 years. Some changes in his behavior and memory were noticed by family members. During his hospital stay for the second transient ischemic attack, frequent hypoglycemia was documented, which was asymptomatic. Insulinoma was confirmed biochemically. Radiological findings were also compatible with pancreatic neuroendocrine tumor. Treatment modalities were explained to the patient. However, he strongly refused surgery. Meanwhile, he was admitted because of a stroke and concurrent hypoglycemia again. In view of his refusal of the surgical treatment and due to his presentation with acute stroke and high-risk status for surgery, radiofrequency ablation was finalized. RESULTS: Radiofrequency ablation of the pancreatic tumor using 40.75 Gy over fractions was performed with a favorable outcome. The patient has achieved biochemical normalization and remained euglycemic during his follow- up. Computed tomography scan of the abdomen during follow-up showed a mild regression of the size of the tumor. CONCLUSION: This report shows a treatment challenge that required the use of an alternative treatment option other than the standard of care. It highlights the evolving evidence of radiofrequency as a therapeutic modality for patients with insulinoma.

Proteomics Profiling of the Urine of Patients with Hyperthyroidism after Anti-Thyroid Treatment.

Hyperthyroidism, which is characterized by increased circulating thyroid hormone levels, alters the body's metabolic and systemic hemodynamic balance and directly influences renal function. In this study, the urinary proteome of patients with hyperthyroidism was characterized using an untargeted proteomic approach with network analysis. Urine samples were collected from nine age-matched patients before and after carbimazole treatment. Differences in the abundance of urinary proteins between hyperthyroid and euthyroid states were determined using a 2D-DIGE coupled to MALDI-TOF mass spectrometry. Alterations in the abundance of urinary proteins, analyzed via Progenesis software, revealed a statistically significant difference in abundance in a total of 40 spots corresponding to 32 proteins, 25 up and 7 down (≥1.5-fold change, ANOVA, p ≤ 0.05). The proteins identified in the study are known to regulate processes associated with cellular metabolism, transport, and acute phase response. The notable upregulated urinary proteins were serotransferrin, transthyretin, serum albumin, ceruloplasmin, alpha-1B-glycoprotein, syntenin-1, and glutaminyl peptide cyclotransferase, whereas the three notable downregulated proteins were plasma kallikrein, protein glutamine gamma-glutamyl transferase, and serpin B3 (SERPINB3). Bioinformatic analysis using ingenuity pathway analysis (IPA) identified the dysregulation of pathways associated with cellular compromise, inflammatory response, cellular assembly, and organization and identified the involvement of the APP and AKT signaling pathways via their interactions with interleukins as the central nodes.

The Relationship Between Thyroid Function and Body Composition, Leptin, Adiponectin, and Insulin Sensitivity in Morbidly Obese Euthyroid Subjects Compared to Non-obese Subjects.

BACKGROUND/OBJECTIVES: Thyroid function tests (TFTs) changes in obese people have been studied with increasing interest, however, studies have been inconsistent hence it remains poorly understood. We compared the TFTs of morbidly obese euthyroid Saudi subjects with non-obese controls and then we examined the influence of leptin, adiponectin, and insulin resistance on TFTs. SUBJECTS/METHODS: Fifty-five euthyroid obese subjects attending bariatric surgery clinic and 52 non-obese age-and gender-matched controls were recruited. We measured body weight, BMI, body composition, thyroid-stimulating hormone (TSH), Free T4 (FT4), Free T3(FT3), thyroid antibodies, fasting leptin, adiponectin, and lipid profile. Insulin resistance was quantified by HOMA-IR. Data are presented as mean ± SEM. RESULTS: Mean BMI was 45.6 ± 1.5 and 23.2 ± 0.5 kg/m2, for the obese and non-obese controls, respectively, P value < 0.001. Mean TSH was 2.7 ± 0.18 mIU/L in obese subjects and 1.7 ± 0.13 mIU/L (0.27-4.2) in the non-obese controls, respectively, P value .014. Mean FT3 was 3.9 ± 0.1 pmol/L (3.1-6.8) in obese subjects compared to 5.0 ± 0.1 pmol/L in non-obese controls, respectively, P value 0.001, however, FT4 was similar in the 2 groups. In the whole group (N = 107), BMI correlated positively with TSH and negatively with FT3. Leptin correlated negatively with both FT4 and FT3 in the non-obese group only while none of the TFTs correlated with HOMA-IR or adiponectin in either group. Binary logistic regression showed that each 1 unit increase in TSH increased the odds of becoming obese by 12.7, P value 0.009, 95 C.I. (1.9-85.0). Conversely, each - unit increase in FT3 decreased the odds of becoming obese by 0.2, P value 0.023, 95% C.I. (0.05-0.80). CONCLUSIONS: We report a small increase in TSH and a small decrease in FT3 within the normal range in obese subjects compared to non-obese controls. We also report a positive correlation between TSH and BMI with increased odds ratio of becoming obese with the increase in TSH and decrease in FT3. These changes may be either causally related or adaptive to the obesity state. FT4 and FT3 seem to correlate with leptin (but not with adiponectin or HOMA-IR) in the non-obese controls only. Larger mechanistic studies are needed to further elucidate the interesting association between obesity and TFTs.

Identification of Protein Changes in the Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach.

The thyroid gland and thyroid hormones control a multitude of homeostatic functions including maintenance of fluid and electrolyte balance and normal functioning of the kidneys. Thyroid dysfunction alters the sytemic hemodynamic and metabolic balance, thereby affecting the kidney. In this study, we aimed to identify and characterize the urinary proteome of the patients with hypothyroidism. An untargeted proteomic approach with network analysis was used to identify changes in total urinary proteome in patients with newly diagnosed overt hypothyroidism. Urine samples were collected from nine age-matched patients' before and after l-thyroxine treatment. Differences in the abundance of urinary proteins between hypothyroid and euthyroid states were determined using a two-dimensional difference in gel electrophoresis (2D-DIGE) coupled to matrix-assisted laser desorption and ionization time-of-flight (MALDI TOF) mass spectrometry. Alterations in the abundance of urinary proteins, analyzed by Progenesis software, revealed statistically significant differential abundance in a total of 49 spots corresponding to 42 proteins, 28 up and 14 down (≥1.5-fold change, analysis of variance (ANOVA), p ≤ 0.05). The proteins identified in the study are known to regulate processes related to transport, acute phase response, oxidative stress, generation of reactive oxygen species, cellular proliferation, and endocytosis. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) identified dysregulation of pathways related to amino acid metabolism, molecular transport, and small-molecule biochemistry and involved the MAPK kinase, vascular endothelial growth factor (VEGF), PI3 kinase/Akt, protein kinase C (PKC), signaling pathways. The identified proteins were involved in the regulation of thyroglobulin (Tg) and thyrotropin (TSH) metabolism. Alterations in their levels indicate the presence of a compensatory mechanism aimed at increasing the regulation of Tg in the hypothyroid state.