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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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alyusuf, Alhmayin, Albasri, Enani, Altuwaijri, Alsomali, Arafah, Alyusuf, Jammah, Ekhzaimy and Alzahrani.)

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.

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., Competing Interests: Given his role as Guest Editor and member of Editorial Board, Haseeb Khan had no involvement in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Peter Brenneisen., (© 2023 The Author(s). Published by IMR Press.)

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., (Copyright © 2022 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). All rights reserved.)

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., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

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 Mn 3 O 4 nanoparticles to produce NDG-Mn 3 O 4 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 Mn 3 O 4 , rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn 3 O 4 nanocomposites caused significant cell death under laser irradiation, while control and Mn 3 O 4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn 3 O 4 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-Mn 3 O 4 nanocomposites. In conclusion, NDG-Mn 3 O 4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn 3 O 4 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-Mn 3 O 4 nanocomposites using animal models of cancer.

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

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., Competing Interests: The authors declare no conflict of interest in this work., (© 2022 Ekhzaimy et al.)

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., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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.

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/m 2 , 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., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

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., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: The Kingdom of Saudi Arabia (KSA) has the second highest prevalence of type 2 diabetes mellitus (T2DM) in the Middle East. There is a paucity of research on the experiences and treatment preferences of patients with T2DM in KSA. This study explored Saudi patients' health-related quality of life, eating habits, experiences during Ramadan, and preference between two glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatment devices., Methods: A cross-sectional, observational study was conducted in three cities in KSA. Participants completed sociodemographic and clinical forms, EQ-5D-5L, Impact of Weight on Self-Perceptions, and a diabetes treatment survey. Participants also viewed instructional videos on GLP-1 RA injection devices and indicated their device preference., Results: Of the 310 participants, 53% were male. The mean age was 43 years (range: 30.0-75.0), duration since diabetes diagnosis was 6.3 years (range: 0.2-27.1), the most commonly reported last HbA1c level was between ≥7.1% and 8% (45%). The mean EQ-5D-5L index score was 0.90, with some participants reporting problems with pain/discomfort (34.5%) and usual activities (33.2%). Patients reported a low-to-moderate impact of weight on self-perception. In preparation for Ramadan, participants sought physician advice on diabetes management (37%) and/or increased checks of their blood glucose (37%). After watching the videos, 89% (n=277) of participants indicated a device preference, with significantly more preferring the dulaglutide device (n=186, 67%) over the semaglutide device (n=91, 33%) (p<0.0001)., Conclusion: This study indicates that T2DM has a significant social, emotional, and behavioral impact on the lives of patients in KSA., Competing Interests: Heather L. Gelhorn, Louis S. Matza, Jessica B. Jordan, Savita B. Anand, and Huda Shalhoub are employees of Evidera, a company that received funding from Eli Lilly for time spent conducting this research. Alena A. Strizek, Kristina S. Boye, and Ali Alhammad are employees of and own stock in Eli Lilly and Company. Dr. Aishah A. Ekhzaimy is not an employee of Eli Lilly and Company and has no conflict of interest to disclose. The authors report no other potential conflicts of interest for this work., (© 2020 Gelhorn et al.)

Objective: The aim of this study was to evaluate physician attitudes and practices in the management of adult growth hormone deficiency (GHD) following pituitary surgery., Materials and Methods: An online questionnaire survey was sent to a sample group of physicians., Results: A total of 131 respondents provided usable responses. More than three quarters were senior physicians, with most practicing in tertiary care centers (73%). Four-fifths of the respondents see at least 1 to 5 patients with GHD following pituitary surgery per year. Seventy-four percent acknowledge the benefit in principle of growth hormone replacement therapy (GHRT) for patients with GHD after pituitary surgery. Most respondents (84%) would only consider GHRT for symptomatic patients. However, 16% stated that patients with GHD after pituitary surgery generally suffer from the side effects of GHRT. Forty-four percent said that the serum insulin-like growth factor-1 (IGF-1) level is the best screening test for assessing GHD after pituitary surgery but 57% of the respondents would use IGF-I levels, and 29% the insulin tolerance test (ITT), in patients with a documented deficiency in three pituitary axes. The main barriers to long-term GHRT use were that it requires injections (67%), and is costly with limited supply (61%). Other reasons not to use GHRT include an absence of GHD symptoms and apparent GHT ineffectiveness (44%), physician lack of familiarity with the medication (40%), and lack of adherence to available guidelines (38%)., Conclusion: This survey addressed physician attitudes and practices in recognizing and treating GHD in adult's post-pituitary surgery. Regional guidelines must be developed to help address/tackle these issues and assist physicians in understanding and treating this condition., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Avicenna Journal of Medicine.)

Background: Primary Empty Sella (PES) syndrome is an increasingly common disorder, mostly diagnosed as an incidental finding during brain imaging scans. We intended to review the clinical management and hormonal profile of patients with PES., Methods: The study included ten-year retrospective analysis of registry containing PES cases in the period 2007 to 2017, from a single tertiary care center. The keyword 'primary empty sella' was used to retrieve patient details from the radiology unit. The clinical and biochemical profile of PES patients was analyzed. Case management of PES patients and their rate of referral to endocrinologists was explored., Results: The registry had 765 cases with a male: female ratio of 1:3.8 suggesting female predominance by almost four times. Although not significant, the onset of disease was earlier for males [Mean ± standard deviation (SD) (46.7 years ±17.3 vs 48.8 years±14.1), p = 0.110]. Almost 79% of the cases were found as an incidental finding during Magnetic Resonance Imaging. Of the total PES cases, only 20% were referred to the endocrinologists and the rest were handled by general physicians. Only 1-2.5% of the cases were evaluated for gonadal, growth and adrenal hormones by the general physicians. The hormonal evaluation by the endocrinologists was also found to be sub-optimal. Headache and visual disturbances were the most common presenting complaints followed by menstrual abnormalities. Endocrine abnormalities like thyroid dysfunction, hyperprolactinemia, hypogonadism and hypocortisolism were highly prevalent among those assessed., Conclusion: There is a gross under-evaluation of hormonal assessment and minimal case-referral to Endocrinologists. PES is associated with varying degrees of hormonal dysfunction, and hence early assessment and management is needed. Establishing a standard protocol for diagnosis and case management is essential with the involvement of a multidisciplinary team consisting of endocrinologists, neurologists, primary care phys icians and ophthalmologists.

Thyroid hormones critically modulate body homeostasis and haemostasis by regulating energy and metabolism. Previous studies have focused on individual pathways or proteins that are affected by increases in thyroid hormone levels, while an overall plasma proteomic signature of this increased level is lacking. Herein, an integrated untargeted proteomic approach with network analysis was used to identify changes in circulating proteins in the plasma proteome between hyperthyroid and euthyroid states. Plasma from 10 age-matched subjects at baseline (hyperthyroid) and post treatment with carbimazole (euthyroid) was compared by difference gel electrophoresis (DIGE) and matrix-assisted laser desorption/ionization time of flight (MALDI TOF) mass spectrometry (MS). A total of 20 proteins were identified with significant difference in abundance (analysis of variance (ANOVA) test, p ≤ 0.05; fold-change ≥ 1.5) between the two states (12 increased and 8 decreased in abundance in the hyperthyroid state). Twelve protein spots corresponding to ten unique proteins were significantly more abundant in the hyperthyroid state compared with the euthyroid state. These increased proteins were haptoglobin (HP), hemopexin (HPX), clusterin (CLU), apolipoprotein L1 (APOL1), alpha-1-B glycoprotein (A1BG), fibrinogen gamma chain (FGG), Ig alpha-1 chain C region (IGHA1), complement C6 (C6), leucine rich alpha 2 glycoprotein (LRG1), and carboxypeptidase N catalytic chain (CPN1). Eight protein spots corresponding to six unique proteins were significantly decreased in abundance in the hyperthyroid samples compared with euthyroid samples. These decreased proteins were apolipoprotein A1 (APOA1), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), plasminogen (PLG), alpha-1 antitrypsin (SERPINA1), fibrinogen beta chain (FGB), and complement C1r subcomponent (C1R). The differentially abundant proteins were investigated by ingenuity pathway analysis (IPA). The network pathway identified related to infectious disease, inflammatory disease, organismal injury and abnormalities, and the connectivity map focused around two central nodes, namely the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways. The plasma proteome of patients with hyperthyroidism revealed differences in the abundance of proteins involved in acute phase response signaling, and development of a hypercoagulable and hypofibrinolytic state. Our findings enhance our existing knowledge of the altered proteins and associated biochemical pathways in hyperthyroidism.

Background: High prevalence of undiagnosed cases of diabetes mellitus (DM) has increased over the last two decades, most patients with DM only become aware of their condition once they develop a complication. Limited data are available regarding the knowledge and awareness about DM and the associated risk factors, complications and management in Saudi society. Aim: This study aimed to assess knowledge of DM in general Saudi society and among Saudi healthcare workers. Results: Only 37.3% of the participants were aware of the current DM prevalence. Obesity was the most frequently identified risk factor for DM. Most comparisons indicated better awareness among health workers. Conclusion: A significant lack of knowledge about DM in Saudi society was identified. Social media and educational curriculum can improve knowledge and awareness of DM.

Summary: Central diabetes insipidus (CDI) and several endocrine disorders previously classified as idiopathic are now considered to be of an autoimmune etiology. Dermatomyositis (DM), a rare autoimmune condition characterized by inflammatory myopathy and skin rashes, is also known to affect the gastrointestinal, pulmonary, and rarely the cardiac systems and the joints. The association of CDI and DM is extremely rare. After an extensive literature search and to the best of our knowledge this is the first reported case in literature, we report the case of a 36-year-old male with a history of CDI, who presented to the hospital's endocrine outpatient clinic for evaluation of a 3-week history of progressive facial rash accompanied by weakness and aching of the muscles., Learning Points: Accurate biochemical diagnosis should always be followed by etiological investigation. This clinical entity usually constitutes a therapeutic challenge, often requiring a multidisciplinary approach for optimal outcome. Dermatomyositis is an important differential diagnosis in patients presenting with proximal muscle weakness. Associated autoimmune conditions should be considered while evaluating patients with dermatomyositis. Dermatomyositis can relapse at any stage, even following a very long period of remission. Maintenance immunosuppressive therapy should be carefully considered in these patients.

Aim: To compare the effects of 5- and 50-nm naked and PEG-coated gold nanoparticles (AuNP) on proinflammatory cytokines (IL-1β, IL-6, TNF-α) expression and histopathological changes in liver and kidneys of rats. Materials & methods: Rats were injected with different nanoparticles and sacrificed after 24 h. Results: Both 5- and 50-nm AuNPs, and 50-nm PEG-AuNPs caused granular clumping of cytoplasm, edema and hydropic dystrophy in hepatic cells. Naked AuNPs of both sizes caused mild shrinkage, whereas 50-nm PEG-AuNPs enlarged the Bowman's space and capsule. Larger nanoparticles produced more profound mRNA expression of cytokines in both the organs. Conclusion: These findings suggest the roles of particle size and coating on immunological response and histopathological changes.

Periodontal disease is a chronic infectious disease, which is characterized by the damaged dental hard tissue by lactic acid generated by microorganisms after the fermentation of carbohydrates rich diet. The risk of periodontal disease is known to be higher in diabetic patients. We compared the diversity of five commonly occurring dental bacteria including Porphyromonas gingivalis , Tannerella forsythia , Capnocytophaga ochracea , Prevotella intermedia , and Aggregatibacter actinomycetemcomitans in 14 type-2 diabetic patients and equal numbers of healthy controls. The subgingival samples were collected using sterile paper points. We used 16S rRNA sequence specific primers for PCR-based identification of dental bacteria. Our results showed that A. actinomycetemcomitans was completely absent in control subjects but present in 43% of diabetic patients. C. ochracea was highly prevalent in diabetic patients (100%) as compared to controls (28.5%). The frequency of other three bacterial species was also higher in diabetic patients than control subjects. These findings indicate that dental bacteria are highly prevalent in subgingival pockets of diabetic patients. Therefore, proper monitoring of diabetic patients for dental care is important to prevent bacterial growth and its sequela in risky individuals. Further case-control studies using larger sample size would help in validating the association between oral diseases and diabetes., (© 2019 Published by Elsevier B.V. on behalf of King Saud University.)

Background: Coronavirus disease 2019 (COVID-19) has evolved into a devastating pandemic since December 2019. Saudi Arabia's first case was reported in March 2020. Subsequently, some 220,000 cases and 2000 deaths were recorded through July 2020. COVID-19 infection aggravates glycemic control and provokes acute hyperglycemic crises, according to some reports. We made the same observations in some of our patients diagnosed with COVID-19. However, we are unaware of any reported cases of diabetic ketoacidosis (DKA) among COVID-19 patients in Saudi Arabia., Objective: Highlighting the significance of hyperglycemia on COVID-19 patient outcomes., Methods: Five patients with DKA were admitted and diagnosed with COVID-19 based on real-time reverse transcription-polymerase chain reaction assays. Electronic medical records were reviewed and informed consent was obtained before reporting the index cases., Results: Five patients presenting with DKA complicating a concurrent COVID-19 infection were reported. Three were known to have preexisting diabetes and 2 had newly diagnosed diabetes based on significantly elevated glycated hemoglobin levels at admission. Four recovered and were discharged to their homes and 1 had a complicated course and died., Conclusions: Our cases demonstrate that COVID-19 infection can trigger DKA. DKA can occur among patients who are known to have diabetes mellitus or appears as a first presentation. Clinicians should be extremely careful in checking for admission hyperglycemia and closely monitor respiratory status during fluid resuscitation of COVID-19-related DKA. ( Curr Ther Res Clin Exp. 2020; 81:XXX-XXX)., (© 2020 The Authors.)

Background: The TBX1 gene encodes the T-box 1 protein that is a transcription factor involved in development. Haploinsufficiency of the TBX1 gene is reported to cause features similar to DiGeorge syndrome. The TBX1 gene is located within the DiGeorge syndrome region, and studies support that the TBX1gene is responsible for most of the features of the phenotype of hemizygous deletion of chromosome 22q11.2. In this study, we report a family of 4 (a father with 3 children) who presented with congenital hypoparathyroidism and hypocalcemia, facial asymmetry, deafness, normal intelligence, and no cardiac involvement., Methods: We performed whole genome sequencing, computational structural analysis of the mutants, and gene expression studies for all affected family members., Results: Whole genome sequencing revealed a paternal inherited novel heterozygous variant, c.1158&#95;1159delinsT p.(Gly387Alafs*73), in the exon 9 isoform C TBX1 gene, causing a loss of nuclear localization sequence (NLS) and transactivation domain (TAD) with no change in gene expression and resulted in a DiGeorge-like phenotype., Conclusion: A pathogenic variant in the TBX1 gene exon 9 C that predicted to cause a loss in the NLS region and most of TAD leads to variable features of hypoparathyroidism, distinctive facial features, deafness, and no cardiac involvement. In addition, our report and previous reports indicate the presence of a wide phenotypic spectrum of TBX1 genetic variants and the consistent absence of cardiac involvement in the case of pathogenic variants on exon 9 isoform C TBX1 gene., (© Endocrine Society 2019.)

Rationale, Aims, and Objectives: Clinical practice guidelines (CPGs) are significant tools for evidence-based health care quality improvement. The CPG program at King Saud University was launched as a quality improvement program to fulfil the international accreditation standards. This program was a collaboration between the Research Chair for Evidence-Based Healthcare and Knowledge Translation and the Quality Management Department. This study aims to develop a fast-track method for adaptation of evidence-based CPGs and describe results of the program., Methods: Twenty-two clinical departments participated in the program. Following a CPGs awareness week directed to all health care professionals (HCPs), 22 teams were trained to set priorities, search, screen, assess, select, and customize the best available CPGs. The teams were technically supported by the program's CPG advisors. To address the local health care context, a modified version of the ADAPTE was used where recommendations were either accepted or rejected but not changed. A strict peer-review process for clinical content and methodology was employed., Results: In addition to raising awareness and building capacity, 35 CPGs were approved for implementation by March 2018. These CPGs were integrated with other existing projects such as accreditation, electronic medical records, performance management, and training and education. Preliminary implementation audits suggest a positive impact on patient outcomes. Leadership commitment was a strength, but the high turnover of the team members required frequent and extensive training for HCPs., Conclusion: This model for CPG adaptation represents a quick, practical, economical method with a sense of ownership by staff. Using this modified version can be replicated in other countries to assess its validity., (© 2018 John Wiley & Sons, Ltd.)

Insulin resistance is a hallmark feature of type-2 diabetes mellitus (T2DM). We determined the homeostatic model assessment insulin resistance (HOMA-IR) and evaluated its association with C-peptide, insulin, fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) in T2DM patients and non-diabetic subjects. This study comprised a total of 47 T2DM patients and 38 non-diabetic controls. Venous blood samples from all the subjects were collected and sera were analyzed for FBG, HbA1c, insulin and C-peptide using an autoanalyzer. HOMA-IR was calculated using the following equation: HOMA-IR = fasting insulin (µU/ml) × fasting glucose (mmol/L)/22.5. There was a significant increase in the levels of FBG and HbA1c in diabetic patients. Although the levels of C-peptide and insulin did not differ significantly between the two groups, a significant increase in HOMA-IR was observed in T2DM patients. Both insulin and C-peptide were significantly correlated with HOMA-IR. In conclusion, C-peptide may serve as a simple and convenient predictor of HOMA-IR.

Thyroid hormone is a potent stimulator of metabolism, playing a critical role in regulating energy expenditure and in key physiological mechanisms, such as growth and development. Although administration of thyroid hormone in the form of levo thyroxine (l-thyroxine) has been used to treat hypothyroidism for many years, the precise molecular basis of its physiological actions remains uncertain. Our objective was to define the changes in circulating protein levels that characterize alterations in thyroid hormone status. To do this, an integrated untargeted proteomic approach with network analysis was used. This study included 10 age-matched subjects with newly diagnosed overt hypothyroidism. Blood was collected from subjects at baseline and at intervals post-treatment with l-thyroxine until they reached to euthyroid levels. Plasma protein levels were compared by two-dimensional difference in gel electrophoresis (2D-DIGE) pre- and post-treatment. Twenty differentially expressed protein spots were detected. Thirteen were identified, and were found to be unique protein sequences by MALDI-TOF mass spectrometry. Ten proteins were more abundant in the hypothyroid vs. euthyroid state: complement C2, serotransferrin, complement C3, Ig κ chain C region, α-1-antichymotrypsin, complement C4-A, haptoglobin, fibrinogen α chain, apolipoprotein A-I, and Ig α-1 chain C region. Three proteins were decreased in abundance in the hypothyroid vs. euthyroid state: complement factor H, paraneoplastic antigen-like protein 6A, and α-2-macroglobulin. The differentially abundant proteins were investigated by Ingenuity Pathway Analysis (IPA) to reveal their associations with known biological functions. Their connectivity map included interleukin-6 (IL-6) and tumour necrosis factor α (TNF-α) as central nodes and the pathway identified with the highest score was involved in neurological disease, psychological disorders, and cellular movement. The comparison of the plasma proteome between the hypothyroid vs euthyroid states revealed differences in the abundance of proteins involved in regulating the acute phase response., Competing Interests: The authors declare no conflict of interest.

Background: Osteopetrosis is a heterogeneous group of uncommon congenital disorders that causes bony sclerosis and remodeling. Patients who are symptomatic can show significant neurologic consequences with the involvement of cranial nerves and symptoms of increased intracranial pressure (ICP)., Case Description: We report an unusual case of a 26-year-old woman with an autosomal-dominant type of osteopetrosis who presented with headache and severe visual deterioration, both attributed to increased ICP. A hemicranioplasty was preformed, resulting in the resolution of her symptoms of ICP and stabilization of her vision. Postoperative imaging showed expansion of the ventricles and the subarachnoid spaces with an improvement of the associated cerebellar herniation., Conclusions: In conclusion, in patients with symptomatic osteopetrosis, cranioplasty can be considered as an option to treat high ICP-related symptoms., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Acute myocardial infarction (AMI), commonly known as heart attack, is a medical emergency that is potentially fatal if not promptly and properly managed. The early diagnosis of AMI is critically important for the timely institution of pharmacotherapy to prevent myocardial damage and preserve cardiac function. Ischemic insults during AMI cause myocardial tissue damage, releasing the cardiac muscle protein troponin T into the blood stream. Therefore, serum troponin T levels are used as a sensitive and specific indicator of myocardial injury for diagnosing AMI. However, there remains a requirement for developing technologies for more accurate biomarkers or signatures for AMI diagnosis or prognosis. Previous studies have implicated impaired lipid metabolism as a causative factor in AMI development. Lipoproteins are important constituents of lipid metabolism; their levels in the blood stream are a convenient biomarker tool for monitoring lipid metabolism. This review summarizes recent findings (data of studies from 2001 to 2016) regarding the biomarker potentials of various lipoproteins, including low-density lipoprotein, oxidized low-density lipoprotein, high-density lipoprotein, lipoprotein-a, and remnant lipoprotein, for the risk stratification of AMI.

Primary adrenal lymphoma is an extremely rare condition. We describe a case of bilateral adrenal lymphoma in a man aged 55 years who was admitted to our hospital. He had a 3-month history of left flank pain, nausea and vomiting with weight loss. A CT scan at a private hospital revealed bilateral large adrenal masses; the patient was referred to our centre based on these findings. He was evaluated for pheochromocytoma by an endocrinology team; however, all findings were negative. In addition, a cosyntropin stimulation test indicated adrenal insufficiency. A Trucut biopsy of the adrenal gland revealed diffuse large B-cell lymphoma of the adrenal glands, and the patient responded extremely well to chemotherapy., Competing Interests: Conflicts of Interest: None declared., (2016 BMJ Publishing Group Ltd.)

Diabetes is a global endemic with rapidly increasing prevalence in both developing and developed countries. The American Diabetes Association has recommended glycated hemoglobin (HbA1c) as a possible substitute to fasting blood glucose for diagnosis of diabetes. HbA1c is an important indicator of long-term glycemic control with the ability to reflect the cumulative glycemic history of the preceding two to three months. HbA1c not only provides a reliable measure of chronic hyperglycemia but also correlates well with the risk of long-term diabetes complications. Elevated HbA1c has also been regarded as an independent risk factor for coronary heart disease and stroke in subjects with or without diabetes. The valuable information provided by a single HbA1c test has rendered it as a reliable biomarker for the diagnosis and prognosis of diabetes. This review highlights the role of HbA1c in diagnosis and prognosis of diabetes patients.