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.

The American Thyroid Association risk stratification and long-term outcomes of differentiated thyroid cancer: a 20-year follow-up of patients in Saudi Arabia.

Background: Studies have reported differing factors associated with poor outcomes in patients with differentiated thyroid cancer (DTC). We aimed to describe our 20 years of experience in the management of thyroid cancer (TC) and identify predictors of treatment outcomes. Methods: We conducted a retrospective review of medical records of patients with TC seen in the Thyroid Center at King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia, between the years 2000 and 2020. Demographic and clinical data including pathological characteristics were collected. The American Thyroid Association (ATA) risk stratification was determined for all patients at the postoperative period as well as the response to therapy at the final follow-up visit. Results: A total of 674 patients (mean age: 47.21 years) with TC, 571 (84.7%) of which were women, were included. There were 404 (60.0%) patients with ATA low risk, 127 (18.8%) with intermediate risk, and 143 (21.2%) with high-risk histology. Overall, 461 patients (68.4%) had an excellent response to treatment, 65 (9.6%) had an indeterminate response, 83 (12.3%) had a biochemical incomplete response, and 65 (9.6%) had a structural incomplete response. Patients who had an excellent response were mostly ATA low risk (n = 318 of 431, 68.1%), whereas 40 of 65 patients (61.5%) of those with ATA high-risk histology had a structural incomplete response to treatment. There were significantly more women who had an excellent response compared with men. Obesity, lymphovascular invasion, and size of the tumor were significant predictors of worse outcomes to therapy. Conclusion: Tumor size, lymphovascular invasion, and obesity are strong predictors of a worse response to therapy among patients with TC. Patients with obesity should be carefully followed up regardless of their risk stratification in light of the recent compelling evidence associating obesity with thyroid cancer and its higher risk of a worse disease outcome. ATA risk stratification is well correlated with patient long-term outcomes.

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.

Optimal Timing of Thyroid Hormone Replacement During Ramadan Fasting: A Randomized Controlled Trial in Patients with Prior Total Thyroidectomy.

Background: Fasting during Ramadan may be challenging for patients on levothyroxine (LT4), as the drug has a narrow therapeutic index and is administered on an empty stomach. The majority of Muslims who fast in Ramadan have two meals per day, iftar immediately after sunset and suhoor just before dawn. This study aimed at evaluating the impact of LT4 timing during Ramadan on thyrotropin (TSH) levels in patients who underwent total thyroidectomy to determine the best timing for intake and identify the predictors of TSH level changes. Methods: We conducted a parallel, double-blind, randomized controlled trial on Saudi patients diagnosed with hypothyroidism who underwent total thyroidectomy. Patients were required to have stable thyroid function for 6 months before the study period and fast ≥20 days of Ramadan. Participants were randomized to one of three times for LT4 administration: Group A, 30 minutes pre-iftar (n = 48); Group B, 3 hours post-iftar (n = 47); or Group C, 1 hour pre-suhoor (n = 47). The number of participants in the final analysis (excluding patients who dropped out) was as follows: Group A, (n = 31); Group B, (n = 34); and Group C, (n = 22). The changes in TSH and free thyroxine (fT4) levels two weeks before and after Ramadan were compared. Factors associated with a change in TSH levels were examined through multivariable analysis. Results: The TSH levels significantly increased in Group B (1.7 ± 1.8 mU/L vs. 3.1 ± 3.9 mU/L, p = 0.003) and Group C (2 ± 1.7 mU/L vs. 5.5 ± 10 mU/L, p = 0.011), but not Group A (1.8 ± 1.6 mU/L vs. 3.3 ± 4.2 mU/L, p = 0.158). The change in fT4 levels was comparable among the groups: Group A, 16.5 ± 2.7 mcg/dL vs. 15.9 ± 3.2 mcg/dL, p = 0.144; Group B, 15.8 ± 3.8 mcg/dL vs. 16.3 ± 3.6 mcg/dL, p = 0.620; and Group C, 17.5 ± 2.8 mcg/dL vs. 17.3 ± 3.9 mcg/dL, p = 0.770. In multivariable linear regression analysis, the following variables were significantly independently associated with TSH level change: age, weight gain, and the number of nonadherence days to LT4, where ß = -0.2, p = 0.026; ß = + 0.2, p = 0.026; and ß = + 0.5, p < 0.0001, respectively. Conclusions: Fasting patients who took LT4 pre-iftar did not experience significant changes in TSH, whereas those who took LT4 post-iftar or pre-suhoor did. The TSH changes during Ramadan may be associated with age (inverse association), weight gain, and the number of non-adherence to LT4 days. Trial Registration: SCTR Application no. 21122002.

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.

Predictors of use and improvement in glycemic indices after initiating continuous glucose monitoring in real world: Data from Saudi Arabia.

BACKGROUND AND AIMS: To identify predictors of use and benefit from continuous glucose monitoring (CGM) in people with type 1 diabetes (T1D). METHODS: Predictors of CGM use and changes in glycemic indices and other clinical parameters after initiating intermittently-scanned CGMs were examined in 116 individuals with T1D living in Saudi Arabia. Participants were categorized based on frequency of CGM sensor scanning at month 6 into: Frequent users (≥10 scans/day) and infrequent users (<10 scans/day). RESULTS: Frequent CGM users had an improvement in time in range (TIR) and time above range (TAR) at months 6 and 12; whereas infrequent users had comparable improvements but only at month 12. Individuals with baseline TIR <50% had a significant improvement in TIR and TAR; whereas those with baseline TIR ≥50% had a significant improvement only in time below range (TBR). Baseline TIR <50% and higher frequency of scans were predictive of improvement in TIR at month 6 (OR: 4.84, p <0.01, 1.05, p= 0.04; respectively); whereas baseline TBR was the only predictor of improvement in TBR (OR:1.24,p < 0.01). Being a woman, higher number of scans/day during the first 2 weeks of CGM use, and having a lower A1C at baseline predict being a frequent scanner at month 6 (OR: 2.81, p=0.04; 1.12, p <0.01; and 0.73, p <0.01; respectively). CONCLUSIONS: Improvement in glycemic control with CGM use can be predicted by: number of scans per day and baseline TIR and TBR in people with T1D.

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.

Severe vitamin D deficiency is not related to SARS-CoV-2 infection but may increase mortality risk in hospitalized adults: a retrospective case-control study in an Arab Gulf country.

PURPOSE: As the world continues to cautiously navigate its way through the coronavirus disease 2019 (COVID-19) pandemic, several breakthroughs in therapies and vaccines are currently being developed and scrutinized. Consequently, alternative therapies for severe acute respiratory coronavirus 2 (SARS-CoV-2) prevention, such as vitamin D supplementation, while hypothetically promising, require substantial evidence from countries affected by COVID-19. The present retrospective case-control study aims to identify differences in vitamin D status and clinical characteristics of hospitalized patients screened for SARS-CoV-2, and determine associations of vitamin D levels with increased COVID-19 risk and mortality. METHODS: A total of 222 [SARS-CoV-2 (+) N = 150 (97 males; 53 females); SARS-CoV-2 (-) N = 72 (38 males, 34 females)] out of 550 hospitalized adult patients screened for SARS-CoV-2 and admitted at King Saud University Medical City-King Khalid University Hospital (KSUMC-KKUH) in Riyadh, Saudi Arabia from May-July 2020 were included. Clinical, radiologic and serologic data, including 25(OH)D levels were analyzed. RESULTS: Vitamin D deficiency (25(OH)D < 50 nmol/l) was present in 75% of all patients. Serum 25(OH)D levels were significantly lower among SARS-CoV-2 (+) than SARS-CoV-2 (-) patients after adjusting for age, sex and body mass index (BMI) (35.8 ± 1.5 nmol/l vs. 42.5 ± 3.0 nmol/l; p = 0.037). Multivariate regression analysis revealed that significant predictors for SARS-CoV-2 include age > 60 years and pre-existing conditions (p < 0.05). Statistically significant predictors for mortality adjusted for covariates include male sex [Odds ratio, OR 3.3 (95% confidence interval, CI 1.2-9.2); p = 0.02], chronic kidney disease [OR 3.5 (95% CI 1.4-8.7); p = 0.008] and severe 25(OH)D deficiency (< 12.5 nmol/l), but at borderline significance [OR 4.9 (95% CI (0.9-25.8); p = 0.06]. CONCLUSION: In hospital settings, 25(OH)D deficiency is not associated with SARS-CoV-2 infection, but may increase risk for mortality in severely deficient cases. Clinical trials are warranted to determine whether vitamin D status correction provides protective effects against worse COVID-19 outcomes.

The impact of a prolonged lockdown and use of telemedicine on glycemic control in people with type 1 diabetes during the COVID-19 outbreak in Saudi Arabia.

BACKGROUND: To minimize the spread of Coronavirus Disease-2019, Saudi Arabia imposed a nationwide lockdown for over 6 weeks. We examined the impact of lockdown on glycemic control in individuals with type 1 diabetes (T1D) using continuous glucose monitoring (CGM); and assessed whether changes in glycemic control differ between those who attended a telemedicine visit during lockdown versus those who did not. MATERIALS AND METHODS: Flash CGM data from 101 individuals with T1D were retrospectively evaluated. Participants were categorized into two groups: Attended a telemedicine visit during lockdown (n = 61) or did not attend (n = 40). Changes in CGM metrics from the last 2 weeks pre-lockdown period (Feb 25 - March 9, 2020) to the last 2 weeks of complete lockdown period (April 7-20, 2020) were examined in the two groups. RESULTS: Those who attended a telemedicine visit during the lockdown period had a significant improvement in the following CGM metrics by the end of lockdown: Average glucose (from 180 to 159 mg/dl, p < 0.01), glycemic management indicator (from 7.7 to 7.2%, p = 0.03), time in range (from 46 to 55%, p < 0.01), and time above range (from 48 to 35%, p < 0.01) without significant changes in time below range, number of daily scans or hypoglycemic events, and other indices. In contrast, there were no significant changes in any of the CGM metrics during lockdown in those who did not attend telemedicine. CONCLUSIONS: A six-week lockdown did not worsen, nor improve, glycemic control in individuals with T1D who did not attend a telemedicine visit. Whereas those who attended a telemedicine visit had a significant improvement in glycemic metrics; supporting the clinical effectiveness of telemedicine in diabetes care.

Rapid Implementation of a Diabetes Telemedicine Clinic During the Coronavirus Disease 2019 Outbreak: Our Protocol, Experience, and Satisfaction Reports in Saudi Arabia.

BACKGROUND: The importance of telemedicine in diabetes care became more evident during the coronavirus disease 2019 (COVID-19) pandemic as many people with diabetes, especially those in areas without well-established telemedicine, lost access to their health care providers (HCPs) during this pandemic. SUBJECTS AND METHODS: We describe a simplified protocol of a Diabetes Telemedicine Clinic that utilizes technological tools readily available to most people with diabetes and clinics around the world. We report the satisfaction of 145 patients and 14 HCPs who participated in the virtual clinic and 210 patients who attended the virtual educational sessions about "Diabetes and Ramadan." RESULTS: The majority of patients agreed or strongly agreed that the use of telemedicine was essential in maintaining a good glucose control during the pandemic (97%) and they would use the clinic again in the future (86%). A similar high satisfaction was reported by patients who attended the "Diabetes and Ramadan" virtual educational session and 88% of them recommended continuing this activity as a virtual session every year. Majority of the HCPs (93%) thought the clinic protocol was simple and did not require a dedicated orientation session prior to implementing. CONCLUSIONS: The simplicity of our Diabetes Telemedicine Clinic protocol and the high satisfaction reported by patients and HCPs make it a suitable model to be adopted by clinics, especially during pandemics or disasters in resource-limited settings. This clinic model can be quickly implemented and does not require technological tools other than those widely available to most people with diabetes, nowadays. We were able to successfully reduce the number of patients, HCPs, and staff physically present in the clinics during the COVID-19 pandemic without negatively impacting the patients' nor the HCPs' satisfaction with the visits.