ObjectiveRestoration of euthyroidism in patients with thyrotoxicosis prior to thyroidectomy is recommended to decrease perioperative morbidity and thyroid storm risk. This is challenging when conventional anti-thyroid medication is contraindicated or ineffective. Iopanoic acid (IOPA), an iodinated contrast medium formerly used as an oral cholecystographic agent, may facilitate treatment of thyrotoxicosis, but limited manufacture precludes its use in the UK. We investigated the effectiveness and safety of IOPA for optimizing thyroid status in treatment-resistant thyrotoxicosis prior to thyroidectomy at a referral centre. MethodsWith prior permission of our Drug and Therapeutics Committee, we sourced laboratory-grade (>98% pure) IOPA and administered this orally to control ongoing, severe thyrotoxicosis prior to thyroidectomy in 12 patients with inadequate response to standard therapies. Underlying aetiologies included Graves’ disease, amiodarone-induced thyrotoxicosis, toxic multinodular goitre and resistance to thyroid hormone beta. Medical case notes were reviewed retrospectively to analyse clinical and biochemical outcomes. ResultsAll patients exhibited a decline and normalization/near-normalization of free T3 (FT3) levels (mean 55% decrease, SEM 4.5%), with minimal changes in FT4 levels. Eleven patients proceeded to uneventful thyroidectomy, and IOPA was well tolerated with no directly attributable side effects. ConclusionIOPA is a safe and effective agent for controlling biochemical thyrotoxicosis in preparation for thyroidectomy, including disease refractory to conventional medication. Highly pure, laboratory-grade iopanoic acid that is approved for human use is now available in the UK; consideration should be given to more widespread use for emergency treatment of life-threatening hyperthyroidism.

Radiation therapy (RT) plays a vital role in managing thoracic cancers, though it can lead to adverse effects, including significant cardiotoxicity. Understanding the risk factors like hypertension in RT is important for patient prognosis and management. A Dahl salt-sensitive (SS) female rat model was used to study hypertension effect on RT-induced cardiotoxicity. Rats were fed a high-salt diet to induce hypertension and then divided into RT and sham groups. The RT group received 24 Gy of whole-heart irradiation. Cardiac function was evaluated using MRI and blood pressure measurements at baseline, 8 weeks and 12 weeks post-RT. Histological examination was performed after the last timepoint or animal death. The hypertensive RT rats demonstrated significant decreases in left-ventricular ejection fraction (EF) (45 ± 7.2%) compared to sham (68 ± 7.3%). Furthermore, circumferential (Ecc) and radial (Err) myocardial strains were significantly reduced (Ecc: -7.4 ± 2.0% RT rats vs. -11 ± 2.4% sham; Err: 15 ± 6.5% RT rats vs. 23 ± 8.9% sham). Histological analysis revealed significant pathophysiological remodeling post-RT, including nuclear size, interstitial fibrosis, necrosis, and the presence of inflammatory cells. This study provides valuable insights into the cardiotoxic effects of RT in the context of hypertension, highlighting the potential of using MRI for improved risk assessment with potential for future clinical translation.

AIMS:To determine in patients with clinical and radiological N0 necks in primary parotid carcinoma: (1) Rate of occult node positivity post-neck dissection. (2) Outcomes following elective neck dissection ± radiotherapy. (3) Factors predicting recurrence and mortality following treatment. METHODS:A retrospective study on patients diagnosed with malignant neoplasm of the parotid between January 2007 and December 2018 from three UK tertiary centres. RESULTS:One hundred and thirty-four patients were identified. 6% (4/62) of patients who underwent neck dissection for radiologically N0 neck had positive lymph nodes. There was no statistically significant feature associated with recurrence and disease-related mortality, but recurrence was associated with an increased risk of mortality (HR 1.444). CONCLUSION:This study has demonstrated a low rate of occult nodal disease in N0 parotid malignancy and suggests that high-grade disease has a higher risk of nodal disease and recurrence. These patients may benefit from elective neck treatment, but more prospective data is required.

Purpose: Dr. Richard Hill performed pioneering work in the field of radiation-induced normal tissue injury to the lung including noninvasive imaging studies aimed at identifying imaging biomarkers of radiation-induced lung injury (RILI). RILI is a life-threatening toxicity of radiation exposure relevant to both cancer patients undergoing thoracic radiation therapy (RT) and victims of accidental radiation exposure. The ability to detect RILI noninvasively has the potential to guide treatment planning for RT and, in the case of victims of acute radiation exposures, inform the decision to start mitigative therapies. As part of this special issue of IJRB honoring Dr. Hill's many contributions to the field of radiation biology, this article reviews current advances in noninvasive imaging of RILI including computed tomography (CT), magnetic resonance (MR), hyperpolarized MR, nuclear medicine (PET and SPECT), and optical imaging with near-infrared (NIR) probes. Conclusion: The imaging modalities reviewed have potential to not only provide early identification of RILI but may also provide mechanistic insights into the progression of RILI via noninvasive detection of characteristic RILI mechanisms including: inflammation, vascular damage, cell death, oxidative stress, and fibrosis.

Parathyroid disease consists of benign and malignant pathology. This chapter will focus on benign parathyroid diseases relevant to the ear, nose, and throat surgeon: primary, secondary, and tertiary hyperparathyroidism. Parathyroid cancer is a very rare entity and will not be discussed. Primary hyperparathyroidism is a condition characterized by hypercalcaemia driven by excess parathyroid hormone secretion. Secondary hyperparathyroidism occurs when there is a deficiency of vitamin D in the blood causing the parathyroid glands to produce more than normal amounts of parathyroid hormone to rectify this. Tertiary hyperparathyroidism occurs following prolonged secondary hyperparathyroidism, when the parathyroid glands autonomously overproduce parathyroid hormone in the absence of ongoing hypocalcaemia.

A young male patient presented with an incidental finding of a large supraglottic vascular lesion. The lesion was initially noted during intubation 4 years ago. Although originally listed for elective excision, there was a significant delay and at the time of surgery, the lesion proved too large to remove and a significant threat to the patient's airway. An emergency tracheostomy was performed, followed by two consecutive treatments with sclerotherapy agents to reduce the size of the lesion. It was then successfully excised using a Thunderbeat ultrasound and bipolar dissection and cautery device.

IntroductionRadiation therapy for head and neck squamous cell carcinoma is constrained by radiotoxicity to normal tissue. We demonstrate 100 nm theranostic nanoparticles for image-guided radiation therapy planning and enhancement in rat head and neck squamous cell carcinoma models. MethodsPEG conjugated theranostic nanoparticles comprising of Au nanorods coated with Gadolinium oxide layers were tested for radiation therapy enhancement in 2D cultures of OSC-19-GFP-luc cells, and orthotopic tongue xenografts in male immunocompromised Salt sensitive or SS rats via both intratumoral and intravenous delivery. The radiation therapy enhancement mechanism was investigated. ResultsTheranostic nanoparticles demonstrated both X-ray/magnetic resonance contrast in a dose-dependent manner. Magnetic resonance images depicted optimal tumor-to-background uptake at 4 h post injection. Theranostic nanoparticle + Radiation treated rats experienced reduced tumor growth compared to controls, and reduction in lung metastasis. ConclusionsTheranostic nanoparticles enable preprocedure radiotherapy planning, as well as enhance radiation treatment efficacy for head and neck tumors.

OBJECTIVE:Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45).DESIGN:Retrospective single-center cohort study.PATIENTS AND MEASUREMENTS:The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery.RESULTS:In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas.CONCLUSIONS:This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach.

Introduction: In experimental animal models, biological sex-differences in the manifestation and severity of normal tissue radiation injury have been well-documented. Previously we demonstrated male and female rats have differential and highly reproducible responses to high-dose partial body irradiation (PBI) with male rats having greater susceptibility to both gastrointestinal acute radiation syndrome (GI-ARS) and radiation pneumonitis than female rats.Methods: In the current study, we have investigated whether differential expression of the renin-angiotensin system (RAS) enzymes angiotensin converting enzyme (ACE) and ACE2 contribute to the observed sex-related differences in radiation response.Results: During the period of symptomatic pneumonitis, the relative ratio of ACE to ACE2 (ACE/ACE2) protein in the whole lung was significantly increased by radiation in male rats alone. Systemic treatment with small molecule ACE2 agonist diminazene aceturate (DIZE) increased lung ACE2 activity and reduced morbidity during radiation pneumonitis in both sexes. Notably DIZE treatment also abrogated morbidity in male rats during GI-ARS. We then evaluated the contribution of the irradiated bone marrow (BM) compartment on lung immune cell infiltration and ACE imbalance during pneumonitis. Transplantation of bone marrow from irradiated donors increased both ACE-expressing myeloid cell infiltration and immune ACE activity in the lung during pneumonitis compared to non-irradiated donors.Discussion: Together, these data demonstrate radiation induces a sex-dependent imbalance in the renin-angiotensin system enzymes ACE and ACE2. Additionally, these data suggest a role for ACE-expressing myeloid cells in the pathogenesis of radiation pneumonitis. Finally, the observed sex-differences underscore the need for consideration of sex as a biological variable in the development of medical countermeasures for radiation exposure.

Though angiogenesis has been investigated in depth, vascular regression and rarefaction remain poorly understood. Regression of renal vasculature accompanies many pathological states such as diabetes, hypertension, atherosclerosis, and radiotherapy. Radiation decreases microvessel density in multiple organs, though the mechanism is not known. By using a whole animal (rat) model with a single dose of partial body irradiation to the kidney, changes in the volume of renal vasculature were recorded at two time points, 60 and 90 days after exposure. Next, a novel vascular and metabolic imaging (VMI) technique was used to computationally assess 3D vessel diameter, volume, branch depth, and density over multiple levels of branching down to 70 µm. Four groups of rats were studied, of which two groups received a single dose of 12.5 Gy X-rays. The kidneys were harvested after 60 or 90 days from one irradiated and one non-irradiated group at each time point. Measurements of the 3D vasculature showed that by day-90 post-radiation, when renal function is known to deteriorate, total vessel volume, vessel density, maximum branch depth, and the number of terminal points in the kidneys decreased by 55%, 57%, 28%, and 53%, respectively. Decreases in the same parameters were not statistically significant at 60 days post-irradiation. Smaller vessels with internal diameters of 70-450 µm as well as large vessels of diameter 451-850 µm, both decreased by 90 days post-radiation. Vascular regression in the lungs of the same strain of irradiated rats has been reported to occur before 60 days supporting the hypothesis that this process is regulated in an organ-specific manner and occurs by a concurrent decrease in luminal diameters of small as well as large blood vessels.

Intrathyroidal parathyroid adenomas (IPAs) are a rare cause of primary hyperparathyroidism. They are often difficult to localize preoperatively and intraoperatively, making diagnosis and treatment challenging. Current data on IPAs are sparse and fragmented in the literature. This makes it difficult to compare the effectiveness of different imaging and surgical techniques. To address this issue, this scoping review maps the literature on IPAs, focusing on four domains: clinical presentation, current localization methods, different surgical techniques, and histopathological features. A search of MEDLINE, Embase, and the Cochrane Library was conducted, with 19 studies meeting the inclusion criteria. The characteristics of IPAs on ultrasound, fine-needle aspiration, CT, MRI, sestamibi-based techniques, and selective venous sampling are summarized. Emerging imaging modalities, including autofluorescence, are introduced. Surgical methods and intraoperative factors that correlate with high success rates for removal are highlighted. This review also identifies gaps in knowledge to guide further research into this area.

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

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia driven by excess parathyroid hormone (PTH) secretion. PHPT is a common endocrine condition with a prevalence of 1 to 7 cases per 1000 adults. PHPT typically presents in the fifth or sixth decade and shows significant female preponderance. Solitary hyperfunctioning parathyroid adenomas account for 85% to 90% of PHPT cases. The remaining 10% to 15% include cases of multiglandular disease (multiple adenomas or hyperplasia) and, rarely, parathyroid carcinoma (1%). Ectopic parathyroid adenomas may arise due to abnormal embryological migration of the parathyroid glands and can be difficult to localize preoperatively, making surgical cure challenging on the first attempt. The potential existence of multiglandular disease should be considered in all patients in whom preoperative localization fails to identify a target adenoma or following unsuccessful parathyroidectomy. Risk factors for multiglandular disease include underlying genetic syndromes (eg, MEN1/2A), lithium therapy, or previous radiotherapy. In addition to multifocal disease, the possibility of an ectopic parathyroid gland should also be considered in patients requiring repeat parathyroid surgery. In this article, we use illustrative clinical vignettes to discuss the approach to a patient with primary hyperparathyroidism (PHPT) and a suspected ectopic parathyroid adenoma.

Abstract Aim The Covid-19 pandemic encouraged prompt modification to clinical practice to minimise hospital attendances in an aim to minimize exposure and protection of the NHS whilst maintaining the standards of patient care. Current literature advocates that Four-Dimensional Computerised Tomography (4DCT) has equal diagnostic value as ultrasound alone or a combination of ultrasound and Sestamibi scan in the identification of abnormal parathyroid glands in the work up for surgical management of hyperparathyroidism. In response to the evolving pandemic at Addenbrookes we modified our practice and escalated 4DCT as our first line imaging. In light of this we had a unique opportunity to evaluate the diagnostic value of the currently used imaging modalities. Methods This is a retrospective study of 270 parathyroidectomies who underwent pre-operative 4DCT (n=270), ultrasound (n= 254) and sestamibi scan (n=253). Subsequently, we assessed the accuracy of these three modalities with the of intra-operative findings, histology, post-operative calcium and PTH. Results The sensitivity of the 4DCT was 77% in comparison to 43% sensitivity of the ultrasound alone. (p>0.05). The combined sensitivity of ultrasound and Sestamibi scan was found to be 69%. Conclusion The implementation of 4DCT as a single modality diagnostic imaging can be considered equally effective and accurate in the diagnosis of parathyroid abnormality. Implementing this would reduce the number of diagnostic tests improving the likelihood of successful operative planning and reduce financial cost.

Primary hyperparathyroidism (pHPT) is a common endocrine disorder that can be cured by parathyroidectomy; patients unsuitable for surgery can be treated with cinacalcet. Availability of surgery may be reduced during COVID-19, and cinacalcet can be used as bridging therapy. In this single-centre retrospective analysis, we investigated the utility and safety of cinacalcet in patients with pHPT receiving cinacalcet between March 2019 and July 2020, including pre-parathyroidectomy bridging. We reviewed and summarised the published literature. Cinacalcet dosages were adjusted by endocrinologists to achieve target calcium < 2.70 mmol/L. Eighty-six patients were identified, with the most achieving target calcium (79.1%) with a mean dose of 39.4 mg/day (±17.1 mg/day) for a median duration of 35 weeks (1–178 weeks). Calcium was normalised in a median time of 5 weeks. The majority of patients commenced cinacalcet of 30 mg/day (78 patients) with the remainder at 60 mg/day (8 patients). Forty-seven patients commencing lower dose cinacalcet (30 mg/day) achieved target calcium without requiring 60 mg/day. Baseline PTH was significantly higher in patients requiring higher doses of cinacalcet. 18.6% of patients reported adverse reactions and 4.7% discontinued cinacalcet. Patients treated with cinacalcet pre-parathyroidectomy required a higher dose and fewer achieved target calcium compared to medical treatment with cinacalcet alone. Post-operative calcium was similar to patients who were not given pre-parathyroidectomy cinacalcet. In summary, cinacalcet at an initial dose of 30 mg/day is safe and useful for achieving target calcium in patients with symptomatic or severe hypercalcaemia in pHPT, including those treated for pre-parathyroidectomy. We propose a PTH threshold of >30 pmol/L to initiate at a higher dose of 60 mg/day.

SIGNIFICANCE:Three-dimensional (3D) vascular and metabolic imaging (VMI) of whole organs in rodents provides critical and important (patho)physiological information in studying animal models of vascular network.AIM:Autofluorescence metabolic imaging has been used to evaluate mitochondrial metabolites such as nicotinamide adenine dinucleotide (NADH) and flavine adenine dinucleotide (FAD). Leveraging these autofluorescence images of whole organs of rodents, we have developed a 3D vascular segmentation technique to delineate the anatomy of the vasculature as well as mitochondrial metabolic distribution.APPROACH:By measuring fluorescence from naturally occurring mitochondrial metabolites combined with light-absorbing properties of hemoglobin, we detected the 3D structure of the vascular tree of rodent lungs, kidneys, hearts, and livers using VMI. For lung VMI, an exogenous fluorescent dye was injected into the trachea for inflation and to separate the airways, confirming no overlap between the segmented vessels and airways.RESULTS:The kidney vasculature from genetically engineered rats expressing endothelial-specific red fluorescent protein TdTomato confirmed a significant overlap with VMI. This approach abided by the "minimum work" hypothesis of the vascular network fitting to Murray's law. Finally, the vascular segmentation approach confirmed the vascular regression in rats, induced by ionizing radiation.CONCLUSIONS:Simultaneous vascular and metabolic information extracted from the VMI provides quantitative diagnostic markers without the confounding effects of vascular stains, fillers, or contrast agents.

3D vasculature of non-irradiated and irradiated lungs was extracted, 60 and 90 days after radiation using optical Cryo-imaging. Quantitative measurements show that the number of terminal points and vessel diameter, volume, and terminal points decreases.