Development and Validation of an Explainable Machine Learning Model for Identification of Hyper-Functioning Parathyroid Glands from High-Frequency Ultrasonographic Images.

OBJECTIVE: To develop and validate a machine learning (ML) model based on high-frequency ultrasound (HFUS) images with the aim to identify the functional status of parathyroid glands (PTGs) in secondary hyper-parathyroidism (SHPT) patients. METHODS: This retrospective study enrolled 60 SHPT patients (27 female, 33 male; mean age: 51.2 years) with 184 PTGs detected from February 2016 to June 2022. All enrollments underwent single-photon emission computed tomography/computed tomography and contrast-enhanced ultrasound examinations. The PTGs were randomly divided into training (n = 147) and testing datasets (n = 37). Four effective ML classifiers were used and combined models incorporating multi-modal HFUS visual signs and radiomics features was constructed based on the optimal classifier. Model performance was compared in terms of discrimination, calibration and clinical utility. The Shapley additive explanation method was used to explain and visualize the main predictors of the optimal model. RESULTS: This model, using a random forest classifier algorithm, outperformed other classifiers. Based on optimal classifier features, the model constructed from ultrasound visual and ML features achieved a favorable performance in the prediction of hyper-functioning PTGs. Compared with the traditional visual model, the ultrasound-based ML model achieved significant (p = 0.03) improvement (area under the curve: 0.859 vs. 0.629) and higher sensitivity (100.0% vs. 94.1%) and accuracy (86.5% vs. 67.6%). Among the predictors attributed to model development, large size and high echogenic heterogeneity of PTGs in ultrasonographic images were more often associated with high risk of hyper-functioning PTGs. CONCLUSION: The ultrasound-based ML model for identifying hyper-functioning PTGs in SHPT patients showed good performance and interpretability using high-frequency ultrasonographic images, which may facilitate clinical management.

Thyroid and parathyroid function disorders induced by short-term exposure of microplastics and nanoplastics: Exploration of toxic mechanisms and early warning biomarkers.

Human exposure to micro- and nano-plastics (MNPs) primarily occurs through respiration and diet in the environment. However, the early effects and warning signs of MNPs exposure on vertebrates are unclear. Here we used intratracheal instillation and intragastric infusion to establish mouse models for MNPs exposure to systematically investigate the toxic mechanisms of MNPs on endocrine organs. Results showed that MNPs induced endocrine disruptions in short-term exposure by both dietary and respiratory pathways. Microplastics (MPs) exposed through dietary route were more toxic to thyroid gland, whereas nanoplastics (NPs) exhibited the highest level of toxicity to parathyroid gland through respiration. The transcriptome and validation of related functional genes revealed that MNPs affected the synthesis of thyroglobulin by interfering with the expressions of PAX8 and CREB. MNPs also impacted the levels of thyroid stimulating hormone, further mediating the secretion of thyroid hormones. Moreover, MNPs modulate the expression of Mafb, thereby exerting regulatory effects on parathyroid hormone (PTH) synthesis and growth development in parathyroid cells. Meanwhile, MNPs interfered with the expression of IP3R in the calcium signaling pathway, indirectly affecting the secretion of PTH. This study reveals the effects and mechanisms of MNPs on thyroid and parathyroid and highlights the significance of early warning of MNPs exposure.

Update in imaging tests used for the localization of parathyroid pathology.

Preoperative localization of parathyroid pathology, generally a parathyroid adenoma, can be difficult in some cases due to the anatomical variants that these glands present. The objective of this review is to analyse the different imaging techniques used for preoperative localization of parathyroid pathology (scintigraphy, ultrasound, CT, MRI and PET). There is great variability between the different tests for the preoperative localization of parathyroid pathology. The importance of knowing the different diagnostic options lies in the need to choose the most suitable test at each moment and for each patient for an adequate management of primary hyperparathyroidism (PHP) with surgical criteria.

Challenges in genetic screening for inherited endocrinopathy affecting the thyroid, parathyroid and adrenal glands in Singapore.

Significant progress has been made in the understand-ing of many human diseases, especially cancers, which has contributed to improved and increased survival. The Human Genome Project and The Cancer Genome Atlas project brought about a new era, with an understanding of inherited diseases at a molecular level, which subsequently facilitated the option of precision medicine. Precision medicine has helped tailor treatment decisions at an individual level, for instance in terms of surgical treatments or targeted therapies in advanced diseases. Despite the increasing advances in genetic-lead precision medicine, this has not translated into increasing uptake among patients. Reasons for this may be potential knowledge gaps among clinicians; on reasons for poor uptake of genetic testing such as for cultural, religious or personal beliefs; and on financial implications such as lack of support from insurance companies. In this review, we look at the current scenario of genetic screening for common inherited endocrine conditions affecting the thyroid, parathyroid and adrenal glands in Singapore, and the implications associated with it.

Molecular imaging of thyroid and parathyroid diseases.

INTRODUCTION: Molecular imaging of thyroid and parathyroid diseases has changed in recent years due to the introduction of new radiopharmaceuticals and new imaging techniques. Accordingly, we provided an clinicians-oriented overview of such techniques and their indications. AREAS COVERED: A review of the literature was performed in the PubMed, Web of Science, and Scopus without time or language restrictions through the use of one or more fitting search criteria and terms as well as through screening of references in relevant selected papers. Literature up to and including December 2023 was included. Screening of titles/abstracts and removal of duplicates was performed and the full texts of the remaining potentially relevant articles were retrieved and reviewed. EXPERT OPINION: Thyroid and parathyroid scintigraphy remains integral in patients with thyrotoxicosis, thyroid nodules, differentiated thyroid cancer and, respectively, hyperparathyroidism. In the last years positron-emission tomography with different tracers emerged as a more accurate alternative in evaluating indeterminate thyroid nodules [18F-fluorodeoxyglucose (FDG)], differentiated thyroid cancer [124I-iodide, 18F-tetrafluoroborate, 18F-FDG] and hyperparathyroidism [18F-fluorocholine]. Other PET tracers are useful in evaluating relapsing/advanced forms of medullary thyroid cancer (18F-FDOPA) and selecting patients with advanced follicular and medullary thyroid cancers for theranostic treatments (68Ga/177Ga-somatostatin analogues).

Captación patológica con 18-Fluorocolina frente a 99mTc-MIBI en la localización de las glándulas paratiroides en el hiperparatiroidismo. Revisión sistemática y metanálisis / Pathological uptake with 18-Fluorocholine versus 99mTc-MIBI in the location of the parathyroid glands in hyperparathyroidism. Systematic review and meta-analysis

Introduction: The location of the pathological parathyroid glands in hyperparathyroidism is usually carried out by means of 99mTc-sestamibi scintigraphy, which increases its precision by adding the ultrasound examination. The non-localization of the parathyroid glands increases the difficulties for surgical removal. To increase the detection of pathological glands, other radioactive tracers are used, such as methionine, fluorocholine or 18F-flurpiridaz. Objective: To establish if PET / CT with 18-Fluorocholine in patients with hyperparathyroidism increases the number of uptakes compared to the 99mTc-sestamibi scan. Method: Systematic review and meta-analysis. Two subgroups were analyzed. Subgroup 1: trials comparing both techniques as an initial exploration. Thirteen studies including 1131 examinations were selected (596 PET / CT with 18-Fluorocholine vs. 535 scintigraphy with 99mTc-sestamibi). Meta-analysis was performed following the random effects model and the odds ratio was calculated. Subgroup 2: studies that include 18-Fluorocholine as a rescue examination in patients with a previous negative study with a 99mTc-sestamibi scan. 17 articles including 412 examinations with 359 patients in which there was at least one uptake were selected. Meta-analysis of the prevalence of the number of patients in whom there was at least one uptake was performed using the random effects model. Results: Subgroup 1: The number of patients in which at least one uptake occurs is significantly higher with the 18-Fluorocholine examinations (OR 4.264, 95% CI 2.400-7.577). The prevalence of uptake with 18-Fluorocholine is 0.91 [0.86, 0.95] and with sestamibi 0.68 [0.56, 0.80]. Subgroup 2: the prevalence of uptake among patients with previous negative MIBI studies was 0.90 [0.87, 0.94]. The probability of detection of both techniques in this group reaches 0.98. Publication bias in the meta-analyzes is low. ... (AU)

Introducción: La localización de las glándulas paratiroides patológicas en el hiperparatiroidismo usualmente se realiza mediante gammagrafía con 99mTc-sestamibi que incrementa su precisión al añadir la exploración ecográfica. La no localización de las glándulas paratiroides incrementa las dificultades para la extirpación quirúrgica. Para incrementar la detección de glándulas patológicas se utilizan otros trazadores radiactivos como la metionina, la fluorocolina o el 18F-flurpiridaz.Objetivo: Establecer si el PET/TC con 18-Fluorocolina en pacientes con hiperparatiroidismo incrementa el número captaciones comparada con la gammagrafía con 99mTc-sestamibi.Método: Revisión sistemática y metanálisis. Se analizaron dos subgrupos. Subgrupo 1: ensayos que comparan ambas técnicas como exploración inicial. Se seleccionaron 13 estudios que incluyen 1131 exploraciones (596 PET/TC con 18-Fluorocolina vs. 535 gammagrafía con 99mTc-sestamibi). Se realizó metanálisis siguiendo el modelo de efectos aleatorios y se calculó la odds ratio. Subgrupo 2: estudios que incluyen la 18-Fluorocolina como exploración de rescate en pacientes con estudio previo negativo con gammagrafía con 99mTc-sestamibi. Se seleccionaron 17 artículos que incluyen 412 exploraciones con 359 pacientes en los que al menos hubo una captación. Se realizó metanálisis de la prevalencia del número de pacientes en los que hubo al menos una captación aplicando el modelo de efectos aleatorios.Resultados: Subgrupo 1: El número de pacientes en los que se presenta al menos una captación es significativamente superior con las exploraciones con 18-Fluorocolina (OR 4.264, IC 95% 2.400-7.577). La prevalencia de captaciones con 18-Fluorocolina es de 0.91 [0.86, 0.95] y con sestamibi de 0.68 [0.56, 0.80]. Subgrupo 2: la prevalencia de captaciones entre pacientes con estudios MIBI negativos previos fue de 0.90 [0.87, 0.94]. ... (AU)

[Non-functioning parathyroid cysts]. / Nefunktsional'nye kisty okoloshchitovidnykh zhelez.

OBJECTIVE: To study the features of clinical course, diagnosis and treatment of true non-functioning parathyroid cysts. MATERIAL AND METHODS: We retrospectively analyzed 18 patients with non-functioning true parathyroid cysts. Inclusion criteria: US-confirmed anechoic lesion of the neck without tissue component, cytological data on cystic lesion, high cystic parathyroid hormone and no laboratory signs of hyperparathyroidism. RESULTS: Non-functioning parathyroid cysts were asymptomatic and diagnosed accidentally after ultrasound of the neck. All patients were women aged 35-77 years. Four patients had cysts near the upper parathyroid glands, 14 patients - near the lower parathyroid glands. Of these, 2 ones had cysts below the level of the clavicle. Cyst volume was 4.3-110.3 cm3 (24.1±26.2 cm3). High cystic parathyroid hormone (2012.5±946.7 pg/ml) was observed in all patients. Simple aspiration was performed in 5 patients, aspiration with sclerotherapy - in 10 patients, cystectomy - in 3 patients. Recurrence was diagnosed in 1 patient after aspiration and 2 patients after sclerotherapy. CONCLUSION: No pathognomonic clinical and ultrasonic symptoms, as well as specific cytological data lead to misdiagnosis. Analysis of PTH in non-functioning parathyroid cysts is essential for diagnosis. Minimally invasive treatment is preferable for true parathyroid cysts. However, these approaches are not radical.

Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder.

OBJECTIVES: Although potential adverse effects of lithium treatment on renal and endocrine systems have been extensively investigated, most prior studies are limited by selected populations and short follow-up. METHODS: Within the Psychiatric Services of the Central Denmark Region, we identified all patients with bipolar disorder and ≥1 serum-lithium (se-Li) measurements between January 1, 2013, and July 20, 2022, and reference patients with bipolar disorder matched on age, sex, and baseline creatinine. Outcomes were diagnoses of renal, thyroid and parathyroid disease, and blood tests measuring creatinine, estimated glomerular filtration rate (eGFR), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium. Analyses included unadjusted multilevel regression to describe changes in biochemical markers, and adjusted Cox regression to compare rates of disease/biochemical outcomes between lithium users and reference patients. RESULTS: Among 1646 lithium users (median age 36 years, 63% women) and 5013 reference patients, lithium users had decreasing TSH and eGFR, stable PTH, and increasing calcium levels over time. Lithium use was associated with increased rates of renal, thyroid and parathyroid disease, and levels of biochemical markers outside normal ranges (hazard rate ratios: 1.07-11.22), but the absolute number of severe outcomes was low (e.g., chronic kidney disease: N = 10, 0.6%). Notably, the rate of blood testing was substantially higher among lithium users than among reference patients (e.g., mean number of creatinine tests during the second year of follow-up: lithium users = 2.5, reference patients = 1.4). CONCLUSIONS: Severely adverse renal and endocrine outcomes are rare during lithium treatment. Observational studies of long-term lithium treatment are prone to detection bias.

Overview of Thyroid and Parathyroid Disease-The Endocrinology Perspective.

Thyroid and parathyroid disorders are quite common in the population and range from benign to malignant conditions that may be hormonally active or inactive. Select disorders of the thyroid and parathyroid can be managed medically, although there are a variety of circumstances that may require definitive management with surgery. Surgical intervention may be required for hormonal control, compressive symptoms, or for the removal and/or control of malignancy. The endocrinologist's perspective of the preoperative and postoperative management regarding thyroid and parathyroid surgeries will be discussed.

Overview of Thyroid and Parathyroid Disease: The Otolaryngology Perspective.

The management of thyroid and parathyroid pathology varies widely, with unifying goals of symptomatic control and mitigating patient morbidity. In general, surgery is indicated when addressing malignancy or when medical management is insufficient. Over the last few decades, treatment paradigms for patients with head and neck endocrine disease have shifted significantly as our understanding of disease processes has expanded and with the advent of numerous relevant technologies. Here we provide a general overview of thyroid and parathyroid disease that may be managed by the otolaryngologist, with attention to emerging strategies in diagnosis and treatment.

A contemporary analysis of the pre- and intraoperative recognition of multigland parathyroid disease.

BACKGROUND: Despite advances in biochemical and radiological identification of parathyroid gland enlargement, primary hyperparathyroidism (PHPT) due to sporadic multigland parathyroid disease (MGPD) remains a perioperative diagnostic dilemma. Failure to recognise MGPD pre- or intraoperatively may negatively impact surgical cure rates and result in persistent PHPT and ongoing patient morbidity. METHODS: We have conducted a comprehensive review of published literature in attempt to determine factors that could aid in reliably diagnosing sporadic MGPD pre- or intraoperatively. We discuss preoperative clinical features and examine pre- and intraoperative biochemical and imaging findings concentrating on those areas that give practicing surgeons and the wider multi-disciplinary endocrine team indications that a patient has MGDP. This could alter surgical strategy. CONCLUSION: Biochemistry can provide diagnosis of PHPT but cannot reliably discriminate parathyroid pathology. Histopathology can aid diagnosis between MGPD and adenoma, but histological appearance can overlap. Multiple negative imaging modalities indicate that MGPD may be more likely than a single parathyroid adenoma, but the gold standard for diagnosis is still intraoperative identification during BNE. MGPD remains a difficult disease to both diagnose and treat.

[The role of calcium sensitive and vitamin D receptors in the pathogenesis of sporadic multiple parathyroid gland disease].

BACKGROUND: Sporadic multiple parathyroid gland disease is » cases of primary hyperparathyroidism (PHPT). However, a single tactic for diagnosing and operating volume in patients with this variant of PHPT has not yet been developed. One of the possible directions in the search for pathogenetically substantiated methods of diagnosis and treatment is the study of the molecular genetic features of the disease and associated clinical and laboratory factors. AIM: To study the features of the expression of calcium sensitive (CaSR) and vitamin D (VDR) receptors on the surface of parathyroid cells in primary hyperparathyroidism with solitary and multiple lesions of the parathyroid glands, as well as its changes under the influence of a decrease in the filtration function of the kidneys. MATERIALS AND METHODS: In a single center observational prospective study with retrospective data collection, there were patients who during 2019-2021. operated on for PHPT, secondary hyperparathyroidism (SHPT) and all cases of tertiary hyperparathyroidism (THPT) operated during 2014-2021. The expression of CaSR, VDR and its relationship with the main laboratory parameters, the clinical variant of hyperparathyroidism, and the morphological substrate were studied. RESULTS: The study included 69 patients: 19 with multiple and 25 with solitary PTG near PHPT, 15 with SHPT, 10 with THPT. A statistically significant decrease in the frequency of detection of normal expression of CaSR and VDR receptors occurs in any morphological variant of hyperparathyroidism and is observed in 93-60% of drugs. A decrease in the normal expression of CaSR in hyperplasia is detected statistically significantly less frequently than in adenoma (p≤0.01). The median expression intensity in adenoma was 2.5 (2:3), in hyperplasia 3.5 (3-4) (p≤0.01). The difference in the molecular mechanisms of the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma (PHPT with solitary adenoma) or hyperplasia (SHPT and PHPT with multiple PTG lesions) is realized in the frequency of maintaining normal CaSR expression in the PTG tissue. These mechanisms are implemented at the local level, their variability does not change under the influence of RRT. A common molecular genetic mechanism for the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma or hyperplasia has been found to reduce the frequency of maintaining normal VDR expression in PTG (up to 7-13%), p<0.01. This mechanism is implemented at the local level, its variability changes under the influence of RRT, reaching statistically significant differences in patients with THPT. CONCLUSION: The study demonstrates the features of changes in the expression of CaSR and VDR in PHPT with multiple lesions of the parathyroid glands. The relationship between the expression of these receptors and the clinical variant of hyperparathyroidism, the morphological substrate, the main laboratory parameters, and renal function was shown.

[Ultrasound-guided anhydrous ethanol and microwave ablation for functional parathyroid cyst: a case report].

We report a case of functional parathyroid cyst treated by ultrasound-guided anhydrous ethanol sclerotherapy and microwave ablation. The 63-year-old female patient was diagnosed to have functional parathyroid cyst with hypercalcemia, high PTH and cystic space-occupying lesions in the neck by ultrasound, radionuclide scanning and PTH measurement of the cystic fluid. The patient refused to receive cyst resection, and anhydrous ethanol sclerotherapy with microwave ablation was performed under ultrasound guidance. The procedure was completed smoothly without any complications either during or after the operation. Follow-up examination of the patient at 18 months after the operation showed a significant reduction of the mass and normal blood calcium and iPTH levels, demonstrating a clinical cure of the patient. Ablative treatment of functional parathyroid cyst has not been documented so far. This approach provides a minimally invasive treatment modality for such cases where surgical resection is not an option, but its efficacy and safety need to be evaluated in more cases with longer follow-up time.

Imaging Features of Ectopic Tissues and Their Complications: Embryologic and Anatomic Approach.

Ectopic tissue is an anatomic abnormality in which tissue develops in an area outside its normal location. It is primarily caused by abnormalities during the process of embryologic development. Although the majority of individuals with ectopic tissues remain asymptomatic, various symptoms and associated complications can occur. Failure in normal embryologic development leads to loss of normal physiologic function or may result in harmful functions such as ectopic hormonal secretion in the ectopic pituitary adenoma. Ectopic tissues may also frequently mimic tumors. For example, developmental abnormalities in the pharyngeal pouches may result in an ectopic parathyroid gland and ectopic thymus, both of which are frequently misdiagnosed as tumors. Adequate knowledge of embryology is essential for understanding the differential diagnoses of ectopic tissues and facilitating appropriate management. The authors summarize the embryologic development and pathogenesis of ectopic tissues by using illustrations to facilitate a deeper understanding of embryologic development and anatomy. Characteristic imaging findings (US, CT, MRI, and scintigraphy) are described for ectopic tissues of the brain, head, neck, thorax, abdomen, and pelvis by focusing on common conditions that radiologists may encounter in daily practice and their differential diagnoses. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.