Primary hyperparathyroidism in pregnancy: experience of a tertiary centre.

BACKGROUND AND PURPOSE: The management of primary hyperparathyroidism (PHPT) during pregnancy is challenging and there is no clear consensus on whether it increases the risk of complications in pregnancy. We conducted this study to review the maternal and fetal outcomes of pregnant women treated for PHPT in a single centre. METHODS: Data on relevant clinical parameters, demographics, management strategies, maternal and fetal outcomes were collected from the medical records of pregnant patients with PHPT diagnosed between 2012 and 2019. RESULTS: Of 15 pregnant women with PHPT, 6 were managed medically and 9 underwent surgery. The median age at their index pregnancy was 28 years [range 19-42]. The median highest adjusted calcium level in the medical group was 2.90 [range 2.61-3.25] mmol/L vs. 3.11 [2.78-4.95] mmol/L in the surgical group. There was one miscarriage and the stillbirth of twins in the medical group, but no such outcomes in the surgical group. The median gestational ages were 39 + 3 weeks [range 24 + 2-41 + 2 weeks] and 39 + 4 weeks [range 37 + 1-39 + 5 weeks] in the medical and surgical groups, respectively. No birth was complicated by neonatal tetany or convulsions. CONCLUSION: More complications developed in the pregnant PHPT patients who were managed medically than in those who underwent surgery. Surgery performed during the second trimester resulted in good outcomes. Multi-centre prospective studies are required to ascertain the risk of various complications in women with PHPT during pregnancy.

The influence of incidental detection of thyroid nodule on thyroid cancer risk and prognosis-A systematic review.

BACKGROUND: Clinically inapparent thyroid nodules discovered serendipitously on imaging for nonthyroid indications are termed as thyroid incidentalomas. It is unclear whether these incidentalomas have a lower prevalence of malignancy or slower tumour progression compared to symptomatic nodules. The aims of this systematic review were to determine the impact of incidental detection of thyroid nodules on both the risk of malignancy and on prognosis in patients with thyroid cancer. METHOD: PubMed and MEDLINE® on Web of Science databases were searched from inception to March 2020 for English language articles reporting on human studies of thyroid cancer risk and/or prognosis in incidental and nonincidental nodules. RESULTS: Eighteen observational studies published between 1998 and 2020 were eligible for analysis; four studies reported on risk, nine on prognosis and five studies reported on both risk and prognosis. When comparing the incidental and nonincidental groups in the risk study, the odds of incidental detection in the cancer and benign groups ranged from 0.16 to 0.5 and 0.06 to 0.38, respectively (odds ratio [OR] = 0.64-2.86) in case-control studies (n = 6); the risk of malignancy for thyroid nodules ranged from 4% to 23.5% in the incidental and 3.8% to 28.7% in the nonincidental groups (relative risk = 0.13-6.27) in the cohort studies (n = 3). A meta-analysis of the eligible case-control studies (n = 3) showed a nonsignificant summated OR of 1.04 (95% confidence interval = 0.63-1.70; p = .88). In the prognosis study, five direct and thirteen indirect markers of prognosis were compared between the incidental and nonincidental groups. A meta-analysis was not possible but incidentally detected thyroid cancer had better progression-free and overall survival. CONCLUSION: Current evidence suggests that investigation and management of thyroid nodules should not be influenced by the mode of detection.

Quality of Life in Post-Surgical Hypoparathyroidism (PoSH) in Thyroid and Parathyroid Surgery.

BACKGROUND: Post-surgical hypoparathyroidism (PoSH) is often long term, with significant associated morbidity and ongoing treatment. A recent systematic review found impaired quality of life (QoL) in patients with PoSH, despite stable treatment. Most studies did not include an appropriate control arm and further studies were recommended, taking into account underlying disease and comorbidities. This study aims to compare QoL in patients with PoSH with appropriate control groups. METHODS: This was a cross-sectional observational study using the general quality of life SF-36 tool and a hypocalcaemia symptom score (HcSS) to assess QoL in patients with PoSH and controls (who had similar surgery but without PoSH). Participants were identified from two patient groups (the Butterfly Thyroid Cancer Trust and the Association for Multiple Endocrine Neoplasia Disorders) and a single tertiary centre in the UK. RESULTS: Four hundred and thirty-nine responses (female n = 379, PoSH n = 89) were included with a median (range) age of 52 (19-92) years. Reported dates of surgery ranged from 1973 to 2019. HcSS scores showed significantly more associated symptoms in patients with PoSH than those without (p < 0.001). Although there was no overall difference in QoL between groups, patients with PoSH consistently had lower scores (p = 0.008) in the energy/fatigue subdomain of the SF-36. CONCLUSION: Patients with PoSH reported significantly more fatigue and loss of energy compared to appropriately matched controls, but overall QoL was not significantly different. Standardised QoL measures may not be sensitive enough to highlight the impact on QoL in these patients. A disease-specific tool may be required.

Parathyroid cancer: A systematic review of diagnostic biomarkers.

INTRODUCTION: Parathyroid cancers are rare and difficult to distinguish from benign parathyroid tumours. Prediction of malignancy often relies on intraoperative assessment of invasion. Standard histology is also inadequate; especially in the absence of local invasion, lymph nodal disease and metastasis. The aim of this project was to systematically review published literature on potential bio-markers used for the diagnosis of parathyroid cancer. METHODS: Pubmed, Web of Science and Medline databases were searched. Inclusion criteria included English language papers published after 1985 and reporting on biomarkers in human studies of parathyroid cancer and benign disease. RESULTS: 118 relevant papers were appraised; all were observational studies. At least 2 papers studied 8 serum, 4 urine and 27 tissue biomarkers on the diagnosis of parathyroid cancer. Of these, 5 serum and 13 tissue markers have been demonstrated in at least one study to be statistically different in benign and malignant disease. We present a synthesis of data for each biomarker and measures of diagnostic accuracy where possible. CONCLUSIONS: Consideration should be given to the use of a panel of biomarkers to review patients with suspected parathyroid cancer. A profile including serum calcium and PTH levels and tissue expression of APC, Parafibromin, PGP9.5, Galectin 3 and Ki67 is proposed. Systematic Review Registration Number - CRD42019127833.

Use of Electrical Impedance Spectroscopy for Intraoperative Tissue Differentiation During Thyroid and Parathyroid Surgery.

BACKGROUND: Electrical impedance (EI) measures tissue resistance to alternating current across several frequencies and may help identify tissue type. A recent rabbit model demonstrated that electrical impedance spectroscopy (EIS) may facilitate identification of parathyroid glands and potentially improve outcomes following surgery. This study looks at the EI patterns of soft tissues in the human neck to determine whether parathyroid tissue can be accurately identified. METHODS: This was a phase 1, single-arm interventional study involving 56 patients undergoing thyroid and/or parathyroid surgery. Up to 12 EI readings were taken from in vivo and ex vivo thyroid and parathyroid glands, adipose tissue and muscle of each patient. Each reading consists of a series of measurements over 14 frequencies from each tissue. EI patterns were analysed. Two patients were excluded due to data loss due to device malfunction. RESULTS: The median age of participants was 53.5 (range 20-85) years. Thirty-five participants had surgery for thyroid pathology, 17 for parathyroid pathology and four for both. Six hundred and six EIS spectra were reviewed for suitability. One hundred and eighty-four spectra were rejected leaving 422 spectra for analysis. The impedance patterns of the soft tissues differed by histological type. The EI ratio of low (152 Hz) to high (312 kHz) frequencies demonstrated a significant difference between the soft tissues (p = 0.006). Using appropriate thresholds, parathyroid tissue can be distinguished from thyroid tissue with a sensitivity of 76% and specificity of 60%. CONCLUSIONS: This study demonstrates the feasibility of using EIS to aid parathyroid identification and preservation. Further changes to the device and modelling of the EI patterns across the range of frequencies may improve accuracy and facilitate intraoperative use. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02901873).

The role of multimedia in surgical skills training and assessment.

INTRODUCTION: Multimedia is an educational resource that can be used to supplement surgical skills training. The aim of this review was to determine the role of multimedia in surgical training and assessment by performing a systematic review of the literature. METHODS: A systematic review for published articles was conducted on the following databases: PubMed/MEDLINE (1992 to November 2014), SCOPUS (1992 to November 2014) and EMBASE (1992 to November 2014). For each study the educational content, study design, surgical skill assessed and outcomes were recorded. A standard data extraction form was created to ensure systematic retrieval of relevant information. RESULTS: 21 studies were included; 14 randomized controlled trials (RCTs) and 7 non-randomized controlled trials (Non-RCTs). Technical skills were assessed in 7 RCTs and 3 non-RCTs; cognitive skills were assessed in 9 RCTs and 4 non-RCTs. In controlled studies, multimedia was associated with significant improvement in technical skills (4 studies; 4 RCTs) and cognitive skills (7 studies; 6 RCTs). In two studies multimedia was inferior in comparison to conventional teaching. Evaluation of multimedia (9 studies) demonstrated strongly favourable results. CONCLUSIONS: This review suggests that multimedia effectively facilitates both technical and cognitive skills acquisition and is well accepted as an educational resource.

Near infrared fluorescence imaging of rabbit thyroid and parathyroid glands.

BACKGROUND: Near infrared fluorescence imaging using intravenous methylene blue (MB) is a novel technique that has potential to aid the parathyroid gland (PG) localization during thyroid and parathyroid surgery. The aim of this study was to examine MB fluorescence in the rabbit neck and determine the influence of MB dose and time following administration on fluorescence from thyroid and PGs. METHODS: Thyroid and external PGs were exposed in six New Zealand white rabbits under anesthesia. Varying doses of MB (0.025-3 mg/kg) were injected through the marginal ear vein. Near infrared fluorescence from exposed tissues was recorded at different time intervals (10-74 min) using Fluobeam 700. Specimens of identified glands were then resected for histologic assessment. RESULTS: Histology confirmed accurate identification of all excised thyroid and PGs; these were the only neck structures to demonstrate significant fluorescence. The parathyroid demonstrated lower fluorescence intensities and reduced washout times at all MB doses compared with the thyroid gland. A dose of 0.1 mg/kg MB was adequate to identify fluorescence; this also delineated the blood supply of the external PGs. CONCLUSIONS: The study demonstrates that near infrared fluorescence with intravenous MB helps differentiate between thyroid and PGs in the rabbit. This has potential to improve outcomes in thyroid and parathyroid surgery by increasing the accuracy of parathyroid identification; however, the findings require replication in human surgery. The use of low doses of MB may also avoid the side effects associated with currently used doses in humans (3-7 mg/kg).

Findings of pilot study following the implementation of point of care intraoperative PTH assay using whole blood during surgery for primary hyperparathyroidism.

Objective: To report findings of pilot study using a novel point of care (POC) intraoperative parathyroid hormone (IOPTH) assay for parathyroid hormone (PTH) using whole blood during surgery for primary hyperparathyroidism (PHPT). Methods: Patients undergoing surgery for primary hyperparathyroidism from March to November 2022 where intraoperative PTH assay was performed using the NBCL CONNECT IOPTH and the laboratory PTH assay were included (group 1). The biochemistry results were reviewed to determine concordance between NBCL and lab PTH values and diagnostic test parameters of the NBCL CONNECT assay. 'In-theatre' times were then compared with a historical cohort (group 2) where the lab-based IOPTH assay alone was used. Results: Of the 141 paired samples in group I, correlation between NBCL and the lab assay was high (rho=0.82; p<0.001). PTH levels using the NBCL assay dropped satisfactorily (>50% of the basal or 0 min sample; whichever was lower - i.e. positive test) in 23 patients; giving a positive predictive value of 100%. Of the 9 patients that did not demonstrate a drop, two were true negative (negative predictive value of 22%) leading to cure after excision of another gland. Group 1 (150 mins) had a significantly shorter 'in-theatre' time compared to group 2 (167 mins) (p=0.007); despite much higher use of near infra-red autofluorescence (NIRAF) (72% vs 11.6% in group I and 2 respectively). Conclusion: The NBCL CONNECT POC IOPTH assay gives comparable results to lab based PTH assays and can be performed without need for a centrifuge or qualified technicians. Surgeons, however, need to be aware of the potential for false-negative results.

Abnormal Calcium Levels are Associated With Worse Maternal and Fetal Outcomes; Results From an Exploratory Study.

CONTEXT: Precise estimates of the incidence of hyper- and hypocalcemia in pregnancy are unknown. Abnormal calcium levels have been associated with unfavorable pregnancy-related outcomes. OBJECTIVE: Determine frequency of hypercalcemia and hypocalcemia in pregnancy when tested and their associations with maternal and fetal outcomes. DESIGN: Exploratory retrospective cohort study. SETTING: Single tertiary care maternity unit. PATIENTS: Pregnant women with expected delivery date between 2017 and 2019 and a second additional cohort of pregnant women with hypercalcemia between 2014 and 2016 and 2020 and 2021. INTERVENTIONS: Observational. MAIN OUTCOMES MEASURED: (1) Incidence of hyper- and hypocalcemia when calcium tested; (2) maternal outcomes: incidence of preterm delivery, emergency cesarean section, and blood loss during delivery; and (3) fetal outcomes: fetal loss (miscarriage/stillbirth), neonatal intensive care unit admission, and fetal birth weight (for term deliveries). RESULTS: Total number of gestations and livebirths recorded were 33 118 and 20 969, respectively, with median [interquartile range] age of 30.1 [25.6-34.3] years. A total of 15.7% (n = 5197) of all gestations had albumin-adjusted calcium tested, and incidence of hypercalcemia and hypocalcemia when tested was 0.8% (n = 42) and 9.5% (n = 495), respectively. Both hypercalcemia (including additional cohort n = 89) and hypocalcemia were associated with increased incidence of preterm delivery (P < .001), emergency cesarean section (P < .001 and .019), blood loss (P < .001), and neonatal intensive care unit admission (P < .001). A total of 27% in the hypercalcemic group had an established diagnosis of primary hyperparathyroidism. CONCLUSIONS: Abnormal calcium levels during pregnancy are common and associated with worse pregnancy-related outcomes, which raises the possible need for routine calcium testing. Prospective studies to confirm the incidence, etiology, and effects of abnormal calcium in pregnancy are recommended.

Near-infrared fluorescent imaging for parathyroid identification and/or preservation in surgery for primary hyperparathyroidism.

Introduction: Near infrared autofluorescence (NIRAF) is a novel intraoperative technology that has shown promising results in the localisation of parathyroid glands (PGs) over the last decade. This study aimed to assess the potential utility of NIRAF in first time surgery for primary hyperparathyroidism (PHPT). Methods: An observational study over a period of 3 years in patients who underwent surgery for PHPT was designed. Data on the use of NIRAF and fluorescent patterns in different organs (thyroid and parathyroid) and parathyroid pathology (single versus multi-gland disease) were explored. In addition, cure rates and operating times were compared between the NIRAF and no-NIRAF groups to determine the potential value of NIRAF in this cohort. Results: In 230 patients undergoing first time surgery for PHPT, NIRAF was used in 50 patients. Of these 50 patients, NIRAF was considered to aid parathyroid identification in 9 patients (18%). The overall cure rate at 6 months of follow-up was 96.5% (98% in NIRAF and 96.1% without NIRAF; p=1.0). The median (interquartile range) operating time was longer in the NIRAF arm at 102 minutes (74-120 minutes) compared to the no-NIRAF arm at 75 minutes (75-109 minutes); however, this difference was not statistically significant (p=0.542). Although the median parathyroid to thyroid (P/T) auto-fluorescence (AF) ratio was similar between single gland and multi gland disease (2.5 vs to 2.76; p=1.0), the P/T AF ratio correlated negatively with increasing gland weight (p=0.038). Conclusion: The use of NIRAF resulted in some potential "surgeon-perceived" benefit but did not lead to improvements in cure rates. The negative correlation between fluorescent intensity and gland weight suggests loss of fluorescence with pathology, which needs further investigation. Further studies on larger cohorts of patients, in depth analysis of fluorescence patterns between normal, adenomatous, and hyperplastic glands and evaluation of user experience are needed. Primary hyperparathyroidism, hyperparathyroidism, autofluorescence, near-infrared fluorescence, parathyroid glands, endocrine, surgery.

Evaluating the performance of artificial intelligence software for lung nodule detection on chest radiographs in a retrospective real-world UK population.

OBJECTIVES: Early identification of lung cancer on chest radiographs improves patient outcomes. Artificial intelligence (AI) tools may increase diagnostic accuracy and streamline this pathway. This study evaluated the performance of commercially available AI-based software trained to identify cancerous lung nodules on chest radiographs. DESIGN: This retrospective study included primary care chest radiographs acquired in a UK centre. The software evaluated each radiograph independently and outputs were compared with two reference standards: (1) the radiologist report and (2) the diagnosis of cancer by multidisciplinary team decision. Failure analysis was performed by interrogating the software marker locations on radiographs. PARTICIPANTS: 5722 consecutive chest radiographs were included from 5592 patients (median age 59 years, 53.8% women, 1.6% prevalence of cancer). RESULTS: Compared with radiologist reports for nodule detection, the software demonstrated sensitivity 54.5% (95% CI 44.2% to 64.4%), specificity 83.2% (82.2% to 84.1%), positive predictive value (PPV) 5.5% (4.6% to 6.6%) and negative predictive value (NPV) 99.0% (98.8% to 99.2%). Compared with cancer diagnosis, the software demonstrated sensitivity 60.9% (50.1% to 70.9%), specificity 83.3% (82.3% to 84.2%), PPV 5.6% (4.8% to 6.6%) and NPV 99.2% (99.0% to 99.4%). Normal or variant anatomy was misidentified as an abnormality in 69.9% of the 943 false positive cases. CONCLUSIONS: The software demonstrated considerable underperformance in this real-world patient cohort. Failure analysis suggested a lack of generalisability in the training and testing datasets as a potential factor. The low PPV carries the risk of over-investigation and limits the translation of the software to clinical practice. Our findings highlight the importance of training and testing software in representative datasets, with broader implications for the implementation of AI tools in imaging.

Post-parathyroidectomy parathyroid hormone levels: the impact on patient survival - a single-centre study in a stage 5 chronic kidney disease population.

BACKGROUND/AIMS: Both severe, uncontrolled and low parathyroid hormone (iPTH) levels are associated with adverse outcomes in stage 5 chronic kidney disease (CKD) patients; however, the impact of iPTH levels following parathyroidectomy (PTX) is unexplored. METHODS: A total of 235 stage 5 CKD patients who underwent PTX between 1990 and 2007 were identified, and iPTH levels following surgery were used to divide patients according to the quartile of maximum iPTH recovery during the 5 years following PTX. Survival, biochemistry and pharmacotherapy were analysed. RESULTS: The maximum iPTH level in each quartile during the follow-up period was <46, 47-139, 140-420 and >420 pg/ml. The overall 5-year survival for the group was 81%. Adjusting for age, time on renal replacement therapy and the presence of diabetes identified an increased hazard for mortality of 2.459 in the quartile of lowest iPTH recovery (p = 0.035). The median 1-alfacalcidol dose during the follow-up period was higher (0.5 µg/day) in the lower iPTH group compared to the 3 quartiles of higher iPTH recovery (0.25 µg/day). CONCLUSION: An association between the lowest quartile of iPTH recovery in the 5 years following PTX and poorer patient survival was found. This finding should be tested in larger datasets.