Geographic variation in the association between Hashimoto's thyroiditis and Papillary thyroid carcinoma, a meta-analysis.

PURPOSE: The association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT) remains a matter of debate. Several genetic and environmental factors have been found to influence this association. Because of the variation in these factors among different populations, we conducted a country- and region-based meta-analysis to examine whether the geographic area influences this association. METHODS: We searched PubMed and Web of Science databases for original articles that investigated the association between HT and PTC from February 1955 to February 28, 2023. The included studies were stratified according to their country and region of origin. Various subgroup analyses were conducted. The primary outcome was the pooled relative risk (RR) and its 95% confidence interval (CI) for each region and country. RESULTS: Forty-six studies including a total of 93,970 participants met our inclusion criteria. They originated from 16 countries distributed in five regions. Significant variation was found among countries but not among regions. Upon analysis of all 46 included studies, countries were classified based on their RR and its 95% CI. Excluding countries with pooled sample sizes <500, Sri Lanka (RR 4.23, 95% CI 2.91-6.14), Poland (RR 3.16, 95% CI 2.79-3.57) and Japan (2.68, 2.14-3.36) showed the strongest association between HT and PTC while Greece (RR 1.06, 95% CI 1.00-1.13), Spain (RR 0.70, 95% CI 0.23-2.11), and Jordan (0.62, 0.32-1.32) showed no significant association. CONCLUSION: Our findings revealed a variation in the association between HT and PTC among countries but not among regions. The country-to-country variation could be due to certain genetic and/or environmental factors subject to geographic variation that influence this association. These findings may help guide health policies aiming to mitigate the risk of PTC in the HT population by helping identify high-risk and low-risk countries.

Prevalence of Depression in Patients with Type 1 Diabetes between 10 and 17 Years of Age in Jordan.

Methods: The study was conducted by distributing the Center for Epidemiological Studies Depression Scale for Children (CES-DC) to adolescents with T1D seen at Jordan University Hospital between February 2019 and February 2020. Demographic, clinical, and socioeconomic data were collected using electronic clinical charts. Possible predictors of depression were assessed using logistic regression analysis. Results: A total of 108 children were enrolled in the study with mean age of 13.7 ± 2.3 years. Fifty-eight children (53.7%) had a CES depression score less than 15, and 50 children (46.3%) had a depression score of 15 or more. The number of diabetes-related hospital admissions and the frequency of self-monitoring of blood glucose (SMBG) were significantly different between the two groups. In the multivariable analysis, both gender and SMBG frequency were statistically significant. Girls were more likely to have a depression score ≥ 15 (OR = 3.41, p = 0.025) than boys. Patients who were rarely testing blood glucose levels were more likely to have a depression score ≥ 15 compared to those who were testing regularly (OR = 36.57, p = 0.002). Conclusion: The prevalence of depressive symptoms is relatively high in adolescents with T1D, especially in those living in developing countries. Longer diabetes duration, higher glycated hemoglobin level, and less frequent blood glucose monitoring are associated with higher depression scores.

Serum IGF-1 to IGFBP-3 Molar Ratio: A Promising Diagnostic Tool for Growth Hormone Deficiency in Children.

BACKGROUND: The serum insulin-like growth factor-1 (IGF-1)/insulin-like growth factor binding protein-3 (IGFBP-3) ratio has various potential applications in growth hormone-related disorders. This study aimed to investigate the performance of the IGF-1/IGFBP-3 ratio, independently and in combination with serum IGF-1 and IGFBP-3, in the diagnosis of growth hormone deficiency (GHD) in children with short stature (SS). METHODS: A 7-year cross-sectional observational study was conducted on 235 children with SS. Participants with known disorders that may affect IGF-1 other than GHD were excluded. Participants were classified into GHD (n = 64) and non-GHD (n = 171) groups. GHD was defined as a slow growth rate (<25th percentile over 1 year) and suboptimal growth hormone (GH) response to 2 GH stimulation tests (peak GH < 6.25 ng/mL using the DiaSorin Liaison assay). The sensitivity and specificity of serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio, independently and in various combinations, were determined. RESULTS: GHD was diagnosed in 27.2% of participants. Among all studied variables, a low serum IGF-1/IGFBP-3 ratio demonstrated the greatest sensitivity for GHD (87.5%), with a comparable specificity (83.0%). The combination of low serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for GHD (97.7%), whereas the combination of normal serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for a non-GHD cause of SS (100.0%). CONCLUSION: Our data suggest that the serum IGF-1/IGFBP-3 ratio is a useful marker for the diagnosis of GHD in children who do not have other disorders that may affect serum IGF-1 levels. Further large studies are needed to confirm the diagnostic utility of the serum IGF-1/IGFBP-3 ratio.

SLC26A4 Phenotypic Variability Influences Intra- and Inter-Familial Diagnosis and Management.

SLC26A4 is one of the most common genes causing autosomal recessive non-syndromic sensorineural hearing loss (SNHL). It has been reported to cause Pendred Syndrome (PDS) and DFNB4 which is deafness with enlarged vestibular aqueduct (EVA). However, mutated SLC26A4 is not conclusive for having either DFNB4 or PDS. Three unrelated Jordanian families consisting of eight affected individuals with congenital bilateral hearing loss (HL) participated in this study. Whole-exome and Sanger sequencing were performed to investigate the underlying molecular etiology of HL. Further clinical investigations, including laboratory blood workup for the thyroid gland, CT scan for the temporal bone, and thyroid ultrasound were performed. Three disease-causing variants were identified in SLC26A4 in the three families, two of which were novel. Two families had a novel pathogenic homozygous splice-site accepter variant (c.165-1G>C), while the third family had compound heterozygous pathogenic variants (c.1446G>A; p.Trp482* and c.304G>A; p.Gly102Arg). Our approach helped in redirecting the diagnosis of several affected members of three different families from non-syndromic HL to syndromic HL. Two of the affected individuals had typical PDS, one had DFNB4, while the rest had atypical PDS. Our work emphasized the intra- and inter-familial variability of SLC26A4-related phenotypes. In addition, we highlighted the variable phenotypic impact of SLC26A4 on tailoring a personalized healthcare management.

Painful subacute thyroiditis occurring after the administration of influenza vaccine and hyaluronic acid dermal filler: A case report.

RATIONALE: The occurrence of subacute thyroiditis (SAT) after vaccines or after hyaluronic acid skin fillers is very rare and might be related to genetic susceptibility. We suggest that the co-administration of both products could potentially increase the possibility of development of SAT. PATIENT CONCERNS: A 58-year-old Caucasian healthy female initially presented with chills, myalgia, dysphagia, sore throat, dry cough, fatigue, and intermittent fever of 38.5°C orally after simultaneous injection of an influenza vaccine and a dermal filler containing hyaluronic acid. Ten days later the patient developed palpitations and neck pain radiating to the left jaw. DIAGNOSIS AND INTERVENTIONS: She was diagnosed with SAT on day 16 after her first visit and responded promptly to etoricoxib treatment. OUTCOMES: The patient progressed clinically from hyperthyroidism to euthyroid state and eventually to hypothyroidism and further testing showed she had HLA B-35 haplotype. LESSONS: Physicians should be aware that SAT might be associated with the administration an influenza vaccine and this possible association might increase if the vaccine was co-administered with a dermal filler.

Effect of Dosage Reduction of Hypoglycemic Multidrug Regimens on the Incidences of Acute Glycemic Complications in People With Type 2 Diabetes Who Fast During Ramadan: A Randomized Controlled Trial.

Objective: We aimed to investigate the effect of dosage reduction of four hypoglycemic multidrug regimens on the incidences of acute glycemic complications in people with type 2 diabetes who fast during Ramadan. Methods: We conducted an open-label, parallel-group, randomized controlled trial at a tertiary care center in Amman, Jordan. We recruited adults with type 2 diabetes who expressed an intention to fast during Ramadan and were adherent to one of four regimens-namely: metformin and glimepiride; metformin and vildagliptin; metformin and insulin glargine U100; or, metformin, insulin glargine U100, and human regular insulin. We randomly assigned participants in a 2:1 ratio to low- or regular-dosage therapy. The primary outcomes were the incidences of hypoglycemia and hyperglycemia during the 29 days of Ramadan 2017, and the secondary outcomes were the incidences of diabetic ketoacidosis and hyperosmolar hyperglycemic state during the same period. Results: We randomly assigned 687 participants to low-dosage therapy (n = 458) or regular-dosage therapy (n = 229) and included 678 (452 and 226, respectively) in the final analysis. The incidence of hypoglycemia was lower in the low-dosage group compared with the regular-dosage group (19 [4.2%] vs. 52 [23.0%], respectively; OR, 0.15 [95% CI, 0.08-0.26]; P < 0.001). The incidence of hyperglycemia did not differ between the low- and regular-dosage groups (319 [70.6%] vs. 154 [68.1%], respectively; OR, 1.12 [95% CI, 0.79-1.58]; P = 0.5). No participants experienced diabetic ketoacidosis or hyperosmolar hyperglycemic state. Each 1% decrease in the baseline HbA1c concentration was associated with a 19.9-fold (95% CI, 9.6-41.5; P < 0.001) increase in the odds of hypoglycemia, and each 1% increase in the baseline HbA1c concentration was associated with a 15.7-fold (95% CI, 10.0-24.6; P < 0.001) increase in the odds of hyperglycemia. Conclusion: Dosage reduction decreases the incidence of hypoglycemia without a concomitant increase in the incidences of hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic state in people with type 2 diabetes who fast during Ramadan. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04237493.

The prevalence of diabetic peripheral neuropathy among diabetic Palestinian refugees in the Nuzha area, Jordan: a cross-sectional study.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common type of diabetic neuropathy. It accounts for significant morbidity, including lower extremity amputations. There are few studies on the prevalence of DPN among Palestinian refugees in Jordan. This study aimed to determine the prevalence of DPN and its associated factors among Palestinian refugees with diabetes in the Nuzha area of Jordan, using the Michigan Neuropathy Screening Instrument (MNSI). METHODS: A cross-sectional study was conducted at the UNRWA Nuzha Health Centre, Amman, Jordan, during the first quarter of 2016 (Jan 2-Mar 31, 2016). The Nuzha Health Centre was randomly chosen from the UNRWA clinics in Jordan. Study participants were selected by systematic random sampling. The number of participants was decided with Cochran's formula and adjusting the sample size by use of the finite population correction equation. 343 patients with diabetes were assessed for DPN using the history and physical assessment sections of the MNSI. We generated descriptive statistics, and tested for associations between variables using univariate and multivariate logistic regression analysis to identify the best subset of predictors for the presence of DPN. We used SPSS version 22 to input and analyse data. This study was approved by the UNRWA Jordan Field Office and the Institutional Review Board at the University of Jordan, and by the Michigan Diabetes Research Centre, which gave its permission to use the MNSI. Written informed consent was obtained from each participant. FINDINGS: Prevalence of DPN was 11% (37 of 343) based on the history section and 36% (122 of 343) based on the physical assessment section of the MNSI. Multivariate logistic regression revealed that significant predictors for DPN based on the history section of the MNSI were education level and duration of diabetes. Compared with participants with no education, the odds ratio (OR) for DPN was 0·13 (95% CI 0·04-0·49, p=0·0023) for participants with elementary education, 0·11 (0·03-0·49, p=0·0035) for those with high school education, and 0·04 (0·01-0·41, p=0·0070) for those with a diploma. Compared with participants who had diabetes for less than 10 years, the OR for DPN was 7·69 (1·99-30·30, p=0·0031) for those who had diabetes for 10-19 years and 32·26 (6·76-142·86, p<0·0001) for those who had diabetes for 20 years or longer. However, the predictors for DPN based on the physical assessment part of MNSI were age, duration of diabetes, and type of treatment for diabetes. Compared with participants aged 70 years or older, the OR for DPN was 0·18 (0·04-0·89, p=0·036) for those aged 40-49 years and 0·22 (0·06-0·82, p=0·024) for those aged 50-59 years. Compared with participants who had diabetes for less than 10 years, the OR for DPN was 32·26 (13·70-76·92, p<0·0001) for those who had diabetes for 10-19 years and 200 (34·48-1000, p<0·0001) for those who had diabetes for 20 years or longer. The OR for DPN was 0·23 (0·08-0·70, p=0·0094) for participants who were treated with oral hypoglycemic agents alone, compared those who were treated with insulin and oral hypoglycaemic agents. INTERPRETATION: The prevalence of DPN is high among Palestinian refugees with diabetes in the Nuzha area, Jordan, consistent with the results of other studies of DPN in individuals with diabetes. There is a need for early detection and regular screening for DPN in patients with diabetes, with special attention given to patients with risk factors for DPN. FUNDING: None.

Association of Parental Consanguinity With Papillary Thyroid Carcinoma: A Case-Control Study.

CONTEXT: Papillary thyroid carcinoma (PTC) is the most common type of nonmedullary thyroid carcinoma. Uncommonly, PTC is associated with multiple genetic alterations and chromosomal abnormalities and displays familial patterns of inheritance. Parental consanguinity increases susceptibility to many genetic disorders. OBJECTIVE: This work aimed to investigate the association of parental consanguinity with PTC. METHODS: This case-control study of PTC patients compared with healthy controls took place in a tertiary referral hospital. We recruited 200 PTC patients who were managed at the endocrinology outpatient clinics of the Jordan University Hospital, and we recruited 515 healthy controls from a nonclinical setting. We interviewed all participants and collected sociodemographic data. We reviewed the family pedigrees of each participant four generations back and excluded any participant who was related. We established whether the parents of each participant were first cousins, first cousins once removed, second cousins, or unrelated. We then used binary logistic regression to assess the association of parental consanguinity with PTC adjusted for age, sex, smoking status, body mass index, and parental education. RESULTS: We recruited 715 participants. The numbers of PTC patients and healthy controls were 200 (28.0%) and 515 (72.0%), respectively. The rate of parental consanguinity was 25.5% in PTC patients and 12.2% in healthy controls. Parental consanguinity was significantly associated with PTC (adjusted odds ratio, 2.60; 95% CI, 1.63-4.17; P < .001). CONCLUSION: Parental consanguinity is a risk factor for PTC. Our findings should be considered during familial risk assessment and genetic counseling, especially in populations with high rates of consanguinity.

The Association between Apolipoprotein E Polymorphism and Response to Statins in Group of Hyperlipidemic Patients.

BACKGROUND AND OBJECTIVE: APOE has an important role in lipids metabolism, and in the variability in low density lipoprotein (LDL) response to statins treatment between individuals. In this study, we aim to investigate the association between APOE polymorphism and response to statins in Jordanian hyperlipidemic patients at the diabetic clinic of Jordan University Hospital. METHODS: One hundred and fifty two Jordanian Hyperlipidemic patients (52 males and 100 females) aged between 35-75 years were enrolled in this study. This study was approved by the Institutional Review Board (IRB) of Jordan University Hospital. The genotypes of the patients were identified by polymerase chain reaction followed by restriction fragment length polymorphism assay method (PCRRFLP). RESULTS AND CONCLUSION: The study showed that there is an association between APOE polymorphism and response to statin therapy. Patients who were APOE ε4 carriers had lower response to statins compared to ε3 and ε2 carriers (p=0.002). In addition, we found that there was no significant association between APOE polymorphism and LDL baseline (p=0.214). No significant differences were found in APOE genotypes distribution between males and females (p=0.06). No significant association was found between age and APOE genotypes (p=0.347). A genotype screening test for dyslipidemic Jordanian patients is recommended to choose the appropriate treatment decisions, dosage, and to recognize the potential side effects of statin therapy.

SLC30A8 gene polymorphism rs13266634 associated with increased risk for developing type 2 diabetes mellitus in Jordanian population.

BACKGROUND: Several genome-wide association studies (GWAS) have identified the single nucleotide polymorphism (SNP) rs13266634 in the Solute carrier family 30 member 8 (SLC30A8) gene as a risk factor to type 2 diabetes mellitus (T2DM). Nevertheless, other studies reported controversial findings of no significant association between the rs13266634 with T2DM. In this study, we aimed to investigate the association of this SNP with T2DM among Jordanian population in addition to define its corresponding allelic and genotypic frequencies. METHOD: This case-control study enrolled 358 T2DM patients and 326 healthy controls who fulfilled the inclusion criteria. Blood samples were collected from all participants and were used for the rs13266634 SNP genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: We demonstrated a significant association between the C/T rs13266634 SNP and T2DM among Jordanian population. A significant difference was found between the cases and controls regarding the allelic (P = 0.003) distribution. Compared to people having T allele, those with C allele had higher risk of T2DM (OR = 1.47 ; 95% CI: 1.14 - 1.89; P = 0.003). Having a CC genotype versus TT genotype was significantly associated with increased risk to T2DM (OR = 2.44; 95% CI: 1.16 - 5.12; P = 0.019) after adjusting for age, gender, and BMI. Under the recessive model, subjects with CC genotype were more likely to have T2DM compared to those with CT or TT genotypes, (OR = 1.64; 95% CI: 1.18 - 2.26; P = 0.003) after adjusting for age, gender and BMI. CONCLUSION: The rs13266634 SNP is significantly associated with T2DM susceptibility among Jordanian Population.

Esophageal 99mTc-pertechnetate uptake mimicking an autonomous thyroid adenoma in a patient with subacute thyroiditis: a case report.

Subacute thyroiditis (SAT) is one of the most common causes of thyrotoxicosis. Thyroid scans with radioiodine or technetium-99m pertechnetate (99mTc) are often performed in the workup of patients with thyrotoxicosis, particularly to differentiate between SAT and Graves's disease. Although very helpful, thyroid scans are prone to pitfalls that may occasionally lead to misdiagnosis. These pitfalls are largely related to physiologic uptake of radioiodine or 99mTc in non-thyroidal tissue, such as salivary gland and stomach that may result in false-positive findings. We present herein a very rare case of SAT misdiagnosed as an autonomous thyroid adenoma most likely due to focal 99mTc uptake in the esophagus. This case may have implications for the management of patients with suspected SAT, who undergo a radioiodine or 99mTc thyroid scan.

Contemporary considerations in adjuvant radioiodine treatment of adults with differentiated thyroid cancer.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy with a growing incidence worldwide. The initial conventional management is surgery, followed by consideration of 131 I treatment that includes three options. These are termed remnant ablation (targeting benign thyroid remnant), adjuvant (targeting presumed microscopic DTC) and known disease (targeting macroscopic DTC) treatments. Some experts mostly rely on clinicopathologic assessment for recurrence risk to select patients for the 131 I treatment. Others, in addition, apply radioiodine imaging to guide their treatment planning, termed theranostics (aka theragnostics or radiotheragnostics). In patients with low-risk DTC, remnant ablation rather than adjuvant treatment is generally recommended and, in this setting, the ATA recommends a low 131 I activity. 131 I adjuvant treatment is universally recommended in patients with high-risk DTC (a primary tumor of any size with gross extrathyroidal extension) and is generally recommended in intermediate-risk DTC (primary tumor >4 cm in diameter, locoregional metastases, microscopic extrathyroidal extension, aggressive histology or vascular invasion). The optimal amount of 131 I activity for adjuvant treatment is controversial, but experts reached a consensus that the 131 I activity should be greater than that for remnant ablation. The main obstacles to establishing timely evidence through randomized clinical trials for 131 I therapy include years-to-decades delay in recurrence and low disease-specific mortality. This mini-review is intended to update oncologists on the most recent clinical, pathologic, laboratory and imaging variables, as well as on the current 131 I therapy-related definitions and management paradigms, which should optimally equip them for individualized patient guidance and treatment.

EFFECT OF AGE AND GENDER ON FASTING AND FOOD-STIMULATED LEVELS OF CALCITONIN, PARATHYROID, AND GASTRIN HORMONES IN HEALTHY ADULTS.

Objective: To investigate the effect of age and gender on basal and food-stimulated serum calcitonin (CT), parathyroid hormone (PTH), and gastrin levels among healthy adults. Methods: Ninety-six healthy adults (76 men and 20 women) aged between 21 and 43 years were recruited. Serum CT, PTH, and gastrin levels were measured after a 9-hour overnight fast, and 1 and 3 hours postprandially. Results: PTH levels decreased early and increased late after feeding. This change was significant in men but not in women. CT levels increased in response to food intake in men but not in women. Gastrin levels were significantly increased after feeding in both men and women. Mean basal and food stimulated CT, PTH, and gastrin levels did not significantly differ between genders. Fasting and post-prandial PTH levels were higher while gastrin levels were lower in older subjects (>30 years old) compared to younger subjects (≤30 years old). Fasting and postprandial CT levels were not significantly different between age groups. Conclusion: Age had a significant effect on fasting and food-stimulated PTH and gastrin hormone levels. The effect of age on PTH levels was independent of baseline vitamin D levels. Men showed significant changes in CT and PTH levels in response to feeding compared to women, although the mean hormone levels were not significantly different between men and women. Abbreviations: CT = calcitonin; MTC = medullary thyroid carcinoma; PTH = parathyroid hormone; SD = standard deviation.