Context Female sex is a risk factor for differentiated thyroid carcinoma (DTC), potentially due to reproductive influences. However, data on the association between parity and DTC risk remain inconsistent. Objective To assess the association between parity and DTC risk in a high-multiparity population. Design Population-based case-control study (1982-2022). Setting A single tertiary medical center. Patients or Other Participants The study included 300 female patients with DTC and 900 controls, matched by birth year and ethnicity. The primary exposure was the number of deliveries before DTC diagnosis. Main Outcome Measure(s) Association between parity and DTC risk evaluated by logistic regression, adjusted for socioeconomic status, TSH levels, oral contraceptive use, and autoimmune thyroid diseases. Results The median age at DTC diagnosis was 39 years; 60% of participants were Jewish and 40% were Arab. Baseline characteristics were comparable, except for higher rates of autoimmune thyroid diseases in cases: Hashimoto thyroiditis (9.7% vs 1.8%, P < .001) and Graves’ disease (6.3% vs 2.7%, P = .005). Parity was associated with increased DTC risk starting at 4 deliveries (OR = 1.70, 95% CI: 1.051-2.741, P = .030), with the highest risk at 6 or more (odds ratio = 1.89; 95% CI, 1.052-3.393; P = .033). This association was largely driven by Arab women, who had significantly higher grand multiparity rates (62.6% vs 13.4%; median 5 vs 3 deliveries; P < .001). Conclusion High parity, primarily among Arab women, was associated with increased DTC risk, with significance observed at 4 or more deliveries.

BackgroundThe COVID-19 pandemic has been associated with various autoimmune manifestations. Several studies have suggested a potential association between COVID-19 and thyroid diseases (TDs); however, findings remain inconclusive and are primarily based on relatively small studies. Population-level data examining the differential impact of the pandemic on specific thyroid conditions are scarce.ObjectiveTo examine the incidence patterns of Hashimoto’s Thyroiditis (HT), Graves’ Disease (GD), and Subacute Thyroiditis (SAT) during the COVID-19 pandemic compared to the pre-pandemic period.MethodsWe conducted a population-based retrospective cohort study using interrupted time series analysis of adults (≥16 years) in the Clalit Health Services southern district of Israel from January 2018 to December 2022. New cases of TDs were identified using either ICD-9 codes, laboratory results, medication dispensing data or a combination of them. Monthly disease-specific incidence rates were compared between pre-pandemic (January 2018-February 2020) and pandemic (March 2020-December 2022) periods, with adjustment for seasonal variations.ResultsAmong 4,765 incident TD cases identified, 3,731 (78.3%) had HT, 698 (14.6%) had GD, and 336 (7.1%) had SAT. The mean age was similar across groups (43–45 years) with consistent female predominance (77%). Interrupted time series analysis revealed a significant 30% increase in HT incidence during the pandemic period (IRR 1.30, 95% CI 1.04-1.64, p=0.023), which began prior to the national vaccination campaign. GD showed a non-significant upward trend suggestive of a possible increased incidence (IRR 1.66, 95% CI 0.99-2.79, p=0.054). Conversely, SAT demonstrated a significant 54% reduction in incidence (IRR 0.46, 95% CI 0.21-0.99, p=0.049).ConclusionsThe COVID-19 pandemic was associated with a significant increase in HT incidence and an unexpected decrease in SAT. These findings highlight the heterogeneous impact of the pandemic on different TDs.

Metastatic cervical lymph nodes (LN) are detected in 20-30% of patients with differentiated thyroid cancer (DTC). Current guidelines recommend that once a cervical LN is suspected to be DTC metastasis during a neck ultrasound (US) procedure, it should be investigated via a fine needle aspiration (FNA) biopsy for cytological evaluation and saline washout of the needle for thyroglobulin (Tg) measurement (FNA-Tg). Since Tg is a protein produced exclusively by thyroid follicular cells, a positive FNA-Tg result establishes the diagnosis of metastatic DTC irrespective of cytology. The conventional, immunoassay-based, FNA-Tg washout requires a laboratory and skilled personnel. We developed a semi-quantitative, lateral flow-based method which was shown to detect at the point-of-care (POC), within 10 minutes, positive Tg samples in needle washouts of a suspicious LN at the site of FNA biopsy. In the pre-clinical phase, the POC-Tg limit of detection was determined to be at a concentration equal to 5 ng/mL, after a 1 mL dilution with normal saline. Our prototype was optimized by evaluating different components: types of membranes, pads, antibodies, and gold conjugates. We evaluated our POC-Tg kits on thirty clinical samples: 16 were found positive while the other 14 were seen as negative. All the negative and positive results were further validated by the attending clinical labs, resulting in 100% compatibility compared to the standard procedure. The proof-of-value of our POC-Tg test lies in its ability to significantly reduce the time to results, thus enhancing clinical decision-making, and saving time and valuable resources. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Israel Innovation Authority [Kmin grant, number 64994], and the Israel Cancer Association [grant number 20230021]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for this study was obtained by the Helsinki committee of Soroka University Medical Center (SUMC), approval number 190-17-SOR. All patients provided written informed consent before the FNA procedure was initiated. Patients 18-year-old and older, able to understand and sign the informed consent form, who were evaluated for cervical LN suspected as DTC metastases, were offered to participate. Pregnant women were excluded. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Background/Objective:We present the case of a patient whose initial biochemical results suggested an ectopic adrenocorticotropic hormone (ACTH)-secreting tumor, with markedly increased serum ACTH levels, increased 24-hour urinary free cortisol levels, and hypokalemia. Although these features are more commonly associated with ectopic ACTH secretion, the patient was ultimately diagnosed with Cushing disease. Case Report:A 46-year-old man presented with recurrent headaches and progressive skin darkening. He had hypertension and a body mass index of 28.4 kg/m2. Initial blood work revealed hypokalemia at 3.2 mEq/L (normal reference range, 3.5-5.1 mEq/L), and screening tests for Cushing syndrome were pathologic including a highly increased urinary free cortisol level (605 μg/24 h; normal reference range, 20.9-292 μg/24 h). The serum ACTH level was high (89 pg/mL; normal reference range, 0-45.4 pg/mL), and pituitary magnetic resonance imaging showed an 8-mm lesion in the pituitary gland. Transsphenoidal pituitary surgery was performed with subsequent postsurgical remission. Discussion:Higher urinary and plasma cortisol levels are typical of ectopic ACTH-secreting tumors and likely cause hypokalemia and hypertension, which are encountered more frequently in patients with ectopic ACTH-secreting tumors. In the absence of a pituitary mass 1 cm or more in size, further testing to differentiate Cushing disease from an ectopic source is required. Conclusion:Highly increased serum ACTH and cortisol levels, hypokalemia, and hypertension occur more frequently in patients with ectopic ACTH-secreting tumors. However, we show that they may occur in Cushing disease, and therefore, it would be wrong to assume a diagnosis of an ectopic ACTH-secreting tumor based on these findings alone.

Background/Objectives: Overt hypothyroidism during pregnancy has been linked to adverse outcomes, including preterm birth, low birth weight, and impaired fetal neurocognitive development. This study aimed to evaluate pregnancy complications in women with overt hypothyroidism (TSH ≥ 10) through a cross-sectional study. Methods: Data from 259,897 live-birth pregnancies (2013-2022) from Clalit Health Services (CHS) were analyzed. The study included all CHS-insured women aged ≥ 18 years with available TSH results during pregnancy. Overt hypothyroidism was defined as a mean TSH ≥ 10 mIU/L, while the euthyroid reference group had TSH levels < 4 mIU/L and no history of hypothyroidism or levothyroxine use. Cases of overt hypothyroidism were matched with 15 controls using propensity score-based matching. Covariates included maternal age, ethnicity, socioeconomic status, IVF use, recurrent pregnancy loss, and smoking. Pregnancy complications were compared between groups using descriptive statistics and univariate analysis. A quasi-Poisson regression model was used to assess complication risk in overt hypothyroidism versus matched controls. Results: The final analysis included 9125 euthyroid and 611 overt hypothyroid pregnancies, with comparable baseline characteristics between groups. No significant differences were found in maternal age, ethnicity, socioeconomic scores, IVF rates, recurrent pregnancy loss, diabetes, smoking, gestational age at delivery, or rates of preterm birth, pre-eclampsia, gestational diabetes, cesarean section, and intrauterine growth restriction. Overall, overt hypothyroidism was not associated with increased complications. Sensitivity analyses using maximum TSH levels during pregnancy showed a slightly elevated risk for pregnancy complications (IRR 1.1, CI 1.04-1.18; p = 0.002). Conclusions: Overt hypothyroidism was not associated with an increased risk of adverse pregnancy outcomes when adjusted for confounding factors, suggesting that treatment decisions should be made on an individual basis.

BACKGROUND: Surgical decompression is the recommended treatment for patients with nonfunctioning pituitary macroadenomas (NFPMAs) with associated visual impairment. Other relative indications for surgery include endocrinopathies, craniopathies, and headaches. Nevertheless, patients without these classical indications who would otherwise be considered asymptomatic with regard to the NFPMA and treated conservatively with clinical radiological surveillance may experience higher rates of other morbidities related to the NFPMA. We aimed to evaluate the prevalence of newly diagnosed comorbidities in conservatively treated patients with NFPMAs. METHODS: We reviewed the medical records of 55 patients with NFPMAs from 2012 to 2022 who lacked classical indications for surgery at diagnosis. During the follow-up period, we searched for any of the following potentially associated newly reported symptoms and signs: headache, dizziness, syncope, gastrointestinal symptoms, hyponatremia, falls, weakness and general deterioration, cerebrovascular accident-related symptoms, and endocrine-related symptoms including type 2 diabetes mellitus. Patients were compared with a matched control group. Cohort patients were further analyzed to detect specific endocrine axis deficiencies, and tumor volumes were measured using magnetic resonance imaging at diagnosis. RESULTS: The final cohort included 55 patients. NFPMAs were associated with the development of newly diagnosed headaches, hypertension, and hypopituitarism. Other symptoms associated with NFPMAs included dizziness, syncope/ presyncope, gastrointestinal-related symptoms, hyponatremia, general weakness and falls, and infection-related in this group were higher compared with the control group. CONCLUSIONS: These results may suggest the advantages of early surgical intervention for NFPMAs to mitigate comorbidities and improve health-related quality of life.

Purpose: To assess the safety of zoledronic acid (ZOL) and denosumab (Dmab) administered following hip fracture in a hospital setting. Methods: Patients older than 65 years were treated by a fracture liaison service following hip fracture. Generally, patients who had a glomerular filtration rate (eGFR) > 35 mL/min were treated with ZOL, whereas patients who had previously received bisphosphonates or had a eGFR between 20 and 35 mL/min were treated with Dmab. Adverse events included hypocalcemia (calcium corrected for albumin less than 8.5 mg/day), renal functional impairment (0.5 mg/dL or more increase in serum creatinine) within 30 days of treatment, or a fever (>38 degrees C) within 48 hours of drug administration. Results: Two hundred twenty-eight and 134 patients were treated with ZOL and Dmab, respectively. Mean body temperature was elevated following ZOL administration (0.18 degrees C P < .001) but remained below 38 degrees C. Hypocalcemia occurred in 18% and 29% of the ZOL and Dmab groups, respectively (P = .009). Renal functional impairment was observed in 9 and 6 patients (4% and 5%) in the ZOL and Dmab groups, respectively (P = .8). Pretreatment calcium above 9.3 mg/dL was associated with a lower risk of posttreatment hypocalcemia (odds ratio 0.30, 95% confidence interval 0.13-0.68, P = .004). While the absolute risk of hypocalcemia was higher in the Dmab group, multivariate analysis did not find that the choice of drug was predictive of hypocalcemia. Conclusion: In-hospital parenteral osteoporosis treatment was rarely associated with fever or renal function impairment but was associated with hypocalcemia. Posttreatment hypocalcemia risk did not vary significantly between patients receiving ZOL or Dmab.

Obesity is a risk factor for differentiated thyroid cancer (DTC), but the association with DTC aggressiveness is controversial. To evaluate the association between preoperative body mass index (BMI)/other metabolic parameters and DTC aggressiveness in our surgical cohort, we retrospectively evaluated patients following thyroid surgery who were diagnosed with DTC between December 2013 and January 2021. Baseline characteristics, histopathological features, treatment modalities, and follow-up data were studied. We conducted logistic regression to analyze the association between BMI/other metabolic parameters and adverse DTC features. The final study cohort included 211 patients (79.6% women; mean age± standard deviation 48.7 ± 15.9 years): 66 (31.3%) with normal weight, 81 (38.4%) with overweight, and 64 (30.3%) with obesity. The median follow-up was 51 months (range 7–93). Complete versus partial thyroidectomy was more common among patients living with overweight or obesity than in normal weight patients (79.7% versus 61.7%, p = 0.017, respectively). Logistic regression demonstrated that higher BMI was associated with mildly increased risk for lymph nodes metastases (odds ratio [OR] 1.077, 95% CI: 1.013–1.145), and higher triglycerides/high-density lipoprotein–cholesterol (TG/HDL-C) ratio was associated with aggressive histological variants of DTC (OR 1.269, 95% CI 1.001–1.61). To conclude, specific adverse clinical and histopathological DTC features were indeed associated with higher BMI and higher TG/HDL-C ratio.

The implementation of an in-hospital fracture liaison service facilitated prompt initiation of anti-osteoporosis treatment following a hip fracture (HF), increasing follow-up and treatment rates. This led to a 48

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Familial non-medullary thyroid cancer (FNMTC) is a well-differentiated thyroid cancer (DTC) of follicular cell origin in two or more first-degree relatives. Patients typically demonstrate an autosomal dominant inheritance pattern with incomplete penetrance. While known genes and chromosomal loci account for some FNMTC, the molecular basis for most FNMTC remains elusive. To identify the variation(s) causing FNMTC in an extended consanguineous family consisting of 16 papillary thyroid carcinoma (PTC) cases, we performed whole exome sequence (WES) analysis of six family patients. We demonstrated an association of ARHGEF28, FBXW10, and SLC47A1 genes with FNMTC. The variations in these genes may affect the structures of their encoded proteins and, thus, their function. The most promising causative gene is ARHGEF28, which has high expression in the thyroid, and its protein-protein interactions (PPIs) suggest predisposition of PTC through ARHGEF28-SQSTM1-TP53 or ARHGEF28-PTCSC2-FOXE1-TP53 associations. Using DNA from a patient's thyroid malignant tissue, we analyzed the possible cooperation of somatic variations with these genes. We revealed two somatic heterozygote variations in XRCC1 and HRAS genes known to implicate thyroid cancer. Thus, the predisposition by the germline variations and a second hit by somatic variations could lead to the progression to PTC.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)