Impact of adrenal surgeon volume on outcome: analysis of 4464 operations from the United Kingdom Registry of Endocrine and Thyroid Surgery (UKRETS).

BACKGROUND: There is a surgeon volume-outcome effect in adrenal surgery but the threshold for high-volume surgeon remains controversial. This study aimed to determine predictors of high-risk adrenal operations and to explore whether these should be restricted to high-volume surgeons. METHODS: Patients undergoing adrenal surgery and registered in the United Kingdom Registry of Endocrine and Thyroid Surgery between 2004 and 2021 were analysed. Outcomes included postoperative complications, duration of hospital stay, and mortality. Factors included in multivariable analysis were age, sex, diagnosis, surgical approach, laterality, and surgeon volume. Patients with missing data were excluded. RESULTS: A total of 4464 of 6174 patients (72.3%) were analysed. Postoperative complications occurred in 418 patients (9.4%) and 14 (0.3%) died. Median duration of hospital stay was 3 (i.q.r. 2-5) days. Co-variables significantly associated with an increase or decrease in postoperative complications (P < 0.050) were age (OR 1.02, 95% c.i. 1.01 to 1.03), adrenal cancer (OR 1.64, 1.14 to 2.36), minimally invasive approach (OR 0.317, 0.248 to 0.405), bilateral surgery (OR 1.66, 1.03 to 2.69), and surgeon volume (OR 0.98, 0.96 to 0.99). An increase or decrease in mortality was associated with patient age (OR 1.08, 1.03 to 1.13), minimally invasive approach (OR 0.08, 0.02 to 0.27), and bilateral surgery (OR 6.93, 1.40 to 34.34). The incidence of postoperative complications was significantly lower above a threshold of 12 operations per year (P = 0.034) and 20 per year (P < 0.001), but not six per year (P = 0.540). Median duration of hospital stay was 2 days for surgeons doing over 20 operations per year, compared with 3 days for those undertaking fewer than 20, fewer than 12 or fewer than 6 operations per year. CONCLUSION: Increasing surgical volume is associated with shorter hospital stay and fewer complications. This analysis supports the case for centralization of surgery for adrenal cancer and bilateral tumours to higher-volume surgeons performing a minimum of 12 operations per year.

The adrenal glands are found in the fatty tissue at the back of the abdomen above each kidney, and produce steroid and adrenaline hormones. Surgery on tumours of the adrenal gland is uncommon compared with surgery for other tumours such as those of the breast, bowel, kidney, and lung. Research has shown that the more adrenal operations a surgeon undertakes per year, the better the overall outcomes for patients undergoing that type of surgery. In this study, the outcomes from adrenal operations recorded over 18 years in the national adrenal surgical registry by members of the British Association of Endocrine and Thyroid Surgeons were analysed. The results confirmed previous findings showing that postoperative complications and length of hospital stay were reduced for patients operated by surgeons who did more adrenal operations per year. Operations done by keyhole surgery had better outcomes. Operations done either in older patients, or for the rare adrenal cancer tumours had worse outcomes, as did operations in which both adrenal glands were removed. The authors recommended that all surgeons performing adrenal surgery should monitor the outcomes of their operations, ideally in a national registry, and discuss these with patients before surgery; and undertake a minimum of 6 adrenal operations per year, but a minimum of 12 per year if doing surgery for adrenal cancer or surgery to remove both adrenal glands.

Consensus statement on the management of incidentally discovered FDG avid thyroid nodules in patients being investigated for other cancers.

With the widespread use of 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) in the investigation and staging of cancers, incidental discovery of FDG-avid thyroid nodules is becoming increasingly common, with a reported incidence in the range 1%-4% of FDG PET/CT scans. The risk of malignancy in an incidentally discovered FDG avid thyroid nodule is not clear due to selection bias in reported retrospective series but is likely to be less than 15%. Even in cases where the nodule is found to be malignant, the majority will be differentiated thyroid cancers with an excellent prognosis even without treatment. If, due to index cancer diagnosis, age and co-morbidities, it is unlikely that the patient will survive 5 years, further investigation of an incidental FDG avid thyroid nodule is unlikely to be warranted. We provide a consensus statement on the circumstances in which further investigation of FDG avid thyroid nodules with ultrasound and fine needle aspiration might be appropriate.

Urinary calcium indices in primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcaemia (FHH): which test performs best?

AIM: Primary hyperparathyroidism (PHPT) is much more common than familial hypocalciuric hypercalcaemia (FHH), but there is considerable overlap in biochemical features. Urine calcium indices help with the differential diagnosis, but their reliability in making this distinction is not clear. The aim of this study was to compare urinary calcium values in patients with PHPT and FHH. METHODS: This was a case-control study of patients with PHPT who had successful surgery and genetically proven FHH between 2011 and 2016. Due to low FHH numbers, patients from neighbouring hospitals and outside study period (2017-2019) were allowed to improve power. Data on demographics and urinary calcium were obtained from electronic records and compared between the two groups. RESULTS: During the study period, 250 patients underwent successful PHPT surgery, while in the FHH arm, 19 genetically proven cases were included. The median (IQR) 24-hour urine calcium excretion (UCE) in the PHPT group was 8.3 (5.6-11.2) mmol/24 hours compared with 3.2 (2.1-6.1) mmol/24 hour in the FHH group (p<0.001). Median (IQR) calcium to creatinine clearance ratio (CCCR) in the PHPT and FHH groups was 0.020 (0.013-0.026) and 0.01 (0.002-0.02), respectively (p=0.001). The sensitivity of urinary tests for PHPT was 96% for UCE (cut-off ≥2.5 mmol/24 hour) and 47% for CCCR (cut-off >0.02). The specificity of the urinary tests for FHH was 29.4% for UCE (cut-off <2.5 mmol/24 hour) and 93% for CCCR (cut-off <0.02). CONCLUSIONS: 24-hour UCE is more sensitive in diagnosing PHPT; however, it is less specific in ruling out FHH as compared with CCCR, when the cut-offs suggested by the International guidelines from the fourth international workshop are used. A significant proportion of patients with PHPT would have also required genetic studies if the guidelines were followed.

Systematic review of incidence, risk factors, prevention and treatment of post-laryngectomy hypoparathyroidism.

PURPOSE: Post-laryngectomy hypoparathyroidism is associated with significant short- and long-term morbidities. This systematic review aimed to determine incidence, risk factors, prevention and treatment of post-laryngectomy hypoparathyroidism. METHODS: Medline, EMBASE and the Cochrane library were searched for relevant articles on hypocalcaemia and/or hypoparathyroidism after laryngectomy or pharyngectomy. Two authors independently screened titles and abstracts from the search. Data from individual studies were collated and presented (without meta-analysis). Quality assessment of included studies was undertaken. The review protocol was registered in the PROSPERO database (CRD42019133879). RESULTS: Twenty-three observational studies were included. The rates of transient and long-term hypoparathyroidism following laryngectomy with concomitant hemi- or total thyroidectomy ranged from 5.6 to 57.1% (n = 13 studies) and 0 to 12.8% (n = 5 studies), respectively. Higher transient (62.1-100%) and long-term (12.5-91.6%) rates were reported in patients who had concomitant oesophagectomy and total thyroidectomy (n = 4 studies). Other risk factors included bilateral selective lateral neck dissection, salvage laryngectomy and total pharyngectomy. There is a lack of data on prevention and management. CONCLUSION: Hypoparathyroidism occurs in a significant number of patients after laryngectomy. Patients who underwent laryngectomy with concomitant hemithyroidectomy may still develop hypoparathyroidism. Research on prevention and treatment is lacking and needs to be encouraged.

Serum Magnesium Measurements After Parathyroidectomy for Primary Hyperparathyroidism: Should It be Routine?

BACKGROUND: Parathyroidectomy is the treatment of choice in primary hyperparathyroidism (PHPT). Following surgery, significant changes in bone and mineral metabolism may follow, but routine magnesium monitoring is not standard practice. The occurrence of significant clinical events linked to hypomagnesaemia in 3 patients after parathyroidectomy led to our evaluation of magnesium levels after surgery for PHPT. METHODS: Serum magnesium levels before and after parathyroidectomy for PHPT were prospectively evaluated in a single centre over a year. The incidence and severity of hypomagnesaemia and its correlation with other biochemical variables were assessed. RESULTS: A total of 138 patients underwent parathyroidectomy for PHPT. Pre-operative and day 1 post-operative serum magnesium levels were available in 57/138 (41.3%) and 99/138 (71.7%) patients, respectively. Serum magnesium decreased significantly after surgery (mean ± SD of 0.85 ± 0.08 and 0.75 ± 0.11 mmol/L, respectively, p < 0.001). On the day after parathyroidectomy, 31/99 (31.3%) patients had hypomagnesaemia (<0.70 mmol/L); in 3 of whom it was severe (<0.50 mmol/L). Patients with hypomagnesaemia had lower pre-operative magnesium (mean ± SD of 0.78 ± 0.06 and 0.87 ± 0.07 mmol/L, p < 0.001), higher pre-operative calcium [median (IQR) of 2.83 (2.71-2.99) and 2.71 (2.63-2.80) mmol/L, p = 0.001] and higher post-operative calcium [median (IQR) of 2.41 (2.30-2.51) and 2.35 (2.28-2.43) mmol/L, p = 0.046] compared to those with normomagnesaemia. In addition, these patients demonstrated higher drop in calcium levels after surgery (0.44 ± 0.20 and 0.35 ± 0.18 mmol/L, p = 0.033). Magnesium levels after surgery correlated positively with pre-operative magnesium (r = 0.561, p < 0.001) and post-operative PTH (r = 0.210, p = 0.037) and negatively with pre-operative adjusted calcium (r = - 0.389, p < 0.001). CONCLUSIONS: Serum magnesium decreased significantly following parathyroidectomy for PHPT and nearly a third of patients developed post-operative, mostly mild hypomagnesaemia. Whilst routine serum magnesium measurements could facilitate prompt recognition and treatment of this electrolyte disturbance, further research needs to establish the clinical importance of mild hypomagnesaemia in these clinical settings and, if indicated, to devise optimal treatment strategies.

Outcomes After Urgent Thyroidectomy Following Rapid Control of Thyrotoxicosis in Graves' Disease are Similar to Those After Elective Surgery in Well-Controlled Disease.

BACKGROUND: Surgery for Graves' disease (GD) is usually performed after adequate control with medical treatment. Occasionally, rapid pre-operative optimization is required. The primary objective was to compare the outcomes of patients undergoing elective surgery for well-controlled GD with those undergoing rapid pre-operative treatment. We also propose a formal treatment protocol for future use. METHODS: A retrospective cohort study in a tertiary referral centre included 247 patients with well-controlled GD undergoing elective surgery and 19 patients with poorly controlled disease undergoing surgery after rapid optimization. The latter group did not respond well to thionamides (carbimazole and/or propylthiouracil) or had intolerance or side effects to thionamides and were treated with a range of non-thionamide drugs, including Lugol's iodine, cholestyramine, beta blockers and steroids (with or without thionamides), and closely monitored for 1-2 weeks before surgery. Outcome measures included thyroid storm, hypoparathyroidism and recurrent laryngeal nerve palsy. RESULTS: In total, 266 patients with male-to-female ratio of 1:6 and median (interquartile range) age of 39 (31-51) were included. Overall, long-term recurrent laryngeal palsy and hypoparathyroidism occurred in 1 (0.38%) and 13 (4.9%) patients, respectively. No patient had thyroid storm. There was no significant difference in hypoparathyroidism (p = 1), vocal cord palsy (p = 0.803) and post-operative bleeding (p = 0.362), between elective surgery and rapid optimization groups. CONCLUSION: Rapid pre-operative treatment is effective, safe and is associated with similar outcomes compared to usual treatment. A rapid pre-operative optimization protocol is proposed.

Calcium, vitamin D or recombinant parathyroid hormone for managing post-thyroidectomy hypoparathyroidism.

BACKGROUND: Post-surgical hypoparathyroidism is a common complication after thyroid surgery. The incidence is likely to increase given the rising trend in the annual number of thyroid operations being performed. Measures to prevent post-thyroidectomy hypoparathyroidism including different surgical techniques and prophylactic calcium and vitamin D supplements have been extensively studied. The management of post-thyroidectomy hypoparathyroidism however has not been extensively evaluated. Routine use of calcium and vitamin D supplements in the postoperative period may reduce the risk of symptoms, temporary hypocalcaemia and hospital stay. However, this may lead to overtreatment and has no effect on long-term hypoparathyroidism. Current recommendations on the management of post-thyroidectomy hypoparathyroidism is based on low-quality evidence. Existing guidelines do not often distinguish between surgical and non-surgical hypoparathyroidism, and transient and long-term disease.The aim of this systematic review was to summarise evidence on the use of calcium, vitamin D and recombinant parathyroid hormone in the management of post-thyroidectomy hypoparathyroidism. In addition, we aimed to highlight deficiencies in the current literature and stimulate further work in this field. OBJECTIVES: The objective of this systematic review was to assess the effects of calcium, vitamin D and recombinant parathyroid hormone in managing post-thyroidectomy hypoparathyroidism. SEARCH METHODS: We searched CENTRAL, MEDLINE, PubMed, Embase as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search for all databases was 17 December 2018 (except Embase, which was last searched on 21 December 2017). No language restrictions were applied. SELECTION CRITERIA: We planned to include randomised control trials (RCTs) or controlled clinical trials (CCTs) examining the effects of calcium, vitamin D or recombinant parathyroid hormone in people with temporary and long-term post-thyroidectomy hypoparathyroidism. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full texts for relevance. MAIN RESULTS: Database searches yielded a total of 1751 records. We retrieved potentially relevant full texts and excluded articles on the following basis: not a RCT or CCT; intervention, comparator or both did not match prespecified criteria; non-surgical causes of hypoparathyroidism, and studies on prevention. None of the articles was eligible for inclusion in the systematic review. AUTHORS' CONCLUSIONS: This systematic review highlights a gap in the current literature and the lack of high-quality evidence in the management of post-thyroidectomy temporary and long-term hypoparathyroidism. Further research focusing on clinically relevant outcomes is needed to examine the effects of current treatments in the management of temporary and long-term post-thyroidectomy hypocalcaemia.

Is there a role for routine laryngoscopy before and after parathyroid surgery?

INTRODUCTION: Recurrent laryngeal nerve (RLN) palsy is a potential complication of parathyroid surgery with significant morbidity and a cause of medico-legal litigation. Peri-operative laryngoscopy to assess RLN function helps identify a vocal cord palsy and guide management. The value of its routine use in asymptomatic patients is however unclear. The low risk of permanent palsy, rarity of true asymptomatic palsy and costs, discomfort and inconvenience to patients are arguments against routine laryngoscopy. This study assessed the results of routine laryngoscopy in patients having parathyroid surgery for primary hyperparathyroidism (PHPT). METHODS: All patients having parathyroid surgery for PHPT (exclusion: re-do surgery and concurrent thyroidectomy) over a 3-year period were included from a tertiary endocrine surgical unit. Data on voice-related outcomes and pre- and post-operative laryngoscopy, including its local cost, were collected and analysed. RESULTS: Of 189 patients who underwent parathyroid surgery, 66 had a unilateral neck exploration. The incidence of vocal cord palsy was 0.5% (1 in 186 patients) and 1.7% (3 in 179 patients) for pre- and post-operative laryngoscopy respectively. The single patient with pre-operative cord palsy was asymptomatic. Of the three with post-operative cord palsy, two were temporary and symptomatic and one was asymptomatic. In the region, the clinical commissioning group was charged £127.00 per laryngoscopy, amounting to £46,736.00 for the whole cohort. CONCLUSIONS: The rare nature of vocal cord palsy suggests laryngoscopy is not necessary for patients having surgery for PHPT. It may be reserved for patients with voice change and those having re-operative or concomitant thyroid surgery.

Use of methylene blue and near-infrared fluorescence in thyroid and parathyroid surgery.

PURPOSE: Intraoperative localisation and preservation of parathyroid glands improves outcomes following thyroid and parathyroid surgery. This can be facilitated by fluorescent imaging and methylene blue; a fluorophore is thought to be taken up avidly by parathyroid glands. This preliminary study aims to identify the optimum dose of methylene blue (MB), fluorescent patterns of thyroid and parathyroid glands and develop a protocol for the use of intravenous MB emitted fluorescence to enable parathyroid identification. METHODS: This is a phase 1b, interventional study (NCT02089542) involving 41 patients undergoing thyroid and/or parathyroid surgery. After exposure of the thyroid and/or parathyroid gland(s), intravenous boluses of between 0.05 and 0.5 mg/kg of MB were injected. Fluobeam® (a hand held fluorescence real-time imager) was used to record fluorescence from the operating field prior and up to 10 min following administration. RESULTS: The optimum dose of MB to visualise thyroid and parathyroid glands was 0.4 mg/kg body weight. The median time to onset of fluorescence was 23 and 22 s and the median time to peak fluorescence was 41.5 and 40 s, respectively. The peak fluorescence for thyroid and parathyroid glands compared to muscle were 2.6 and 4.3, respectively. Parathyroid auto-fluorescence prior to methylene blue injection was commonly observed. CONCLUSIONS: A clinical protocol for detection of fluorescence from MB during thyroid and parathyroid surgery is presented. Parathyroids (especially enlarged glands) fluoresce more intensely than thyroid glands. Auto-fluorescence may aid parathyroid detection, but MB fluorescence is needed to demonstrate viability.

Patients' perceptions and views of surgery and radioiodine ablation in the definitive management of Graves' disease.

BACKGROUND: Patients' perceptions and preferences influence the choice of radioiodine ablation (RIA) or surgery in the definitive management of Graves' disease. This study aimed to evaluate their concerns, experiences and satisfaction following definitive treatment. METHODS: A postal survey of patients who had treatment with surgery or RIA between January 2011 and June 2013 for Graves' disease was conducted. RESULTS: Of 214 patients, 136 (64%) responded. The majority of patients felt actively involved in decision making (83.8%) and were satisfied (84.9%) with their treatment. Compared with RIA, patients who underwent surgery were more satisfied with their treatment (p=0.008). Discussion with the doctor was the most useful aid to decision making. Feeling involved in decision-making process was associated with improved satisfaction (p<0.001).Common reasons for not choosing surgery were need for general anaesthesia, scarring and voice change. Avoiding close contact, risk of persistent hyperthyroidism and worsening eye disease were common reasons for not choosing RIA. Ongoing concerns were hypothyroidism, scarring and eye problems after surgery and hypothyroidism and eye problems after RIA. CONCLUSIONS: This study provides insight into patients' experiences of surgery and RIA for Graves' disease and reinforces the importance of patient involvement in the decision-making process.

Variation in the use of definitive treatment options in the management of Graves' disease: a UK clinician survey.

BACKGROUND: Graves' disease can be treated with antithyroid drugs (ATDs), radioiodine or surgery. Use of definitive treatments (radioiodine or surgery) varies widely across centres. Specific clinical circumstances, local facilities, patient and clinician preferences and perceptions will affect the choice of treatment. Detailed understanding of UK clinicians' views and their rationale for different treatments is lacking. AIMS: To study the preferences and perceptions of UK clinicians on the role of surgery and radioiodine in the management of Graves' disease. METHODS: 'British Thyroid Association' (BTA), 'Society for Endocrinology' (SFE) and 'British Association of Endocrine and Thyroid Surgeons' (BAETS) members were invited to complete an online survey examining their management decisions in Graves' disease and factors that influenced their decisions. RESULTS: 158 responses from UK consultants were included. The ratio of physicians to surgeons was 11:5 and males to females was 12:4. Most clinicians would commence ATDs in uncomplicated first presentation of Graves' disease. A wide range of risk estimates on the effectiveness and risks of treatment was given by clinicians. Radioiodine was used most frequently in relapsed Graves' disease. However, severe eye disease and pregnancy strongly influenced choice in favour of surgery. Surgeons underestimated the success of radioiodine (p<0.01) and were more likely to recommend thyroidectomy than physicians. CONCLUSIONS: This survey demonstrates significant variation in clinicians' perceptions of risks of treatment and their choice of management options for relapsed Graves' disease. The variation appeared to be dependent on patient and disease-specific factors as well as physician experience, gender and specialty.

Electrical Impedance Spectroscopy to Aid Parathyroid Identification and Preservation in Central Compartment Neck Surgery: A Proof of Concept in a Rabbit Model.

BACKGROUND: Accurate identification of parathyroid glands during thyroid surgery is crucial to avoid postthyroidectomy hypocalcemia. Electrical impedance spectroscopy has the potential to differentiate between tissues of different morphology. The aim of this study was to determine the electrical impedance patterns of the thyroid, parathyroid, and other soft tissue structures in the rabbit neck. METHODS: The central compartments were exposed in 9 freshly culled New Zealand White rabbits. In situ and ex vivo electrical impedance was measured from thyroid lobes, external parathyroid glands, adipose tissue, and strap muscle using the APX100 device. Specimens of all identified glands were sent for histopathology examination. RESULTS: Histology confirmed correct identification of all excised thyroid and parathyroid glands. The impedance was higher for thyroid tissue at lower frequencies and for parathyroid tissue at higher frequencies. Ex vivo electrical impedance spectra were significantly higher compared with the in situ spectra across all frequencies for thyroid and parathyroid tissues (P < .001). The ratio of low to high frequency in situ impedance of thyroid, parathyroid, and muscle was significantly different (P < .001), allowing for differentiation between these tissues. CONCLUSION: The electrical impedance spectra of rabbit thyroid and parathyroid glands are distinct and different from each other and from skeletal muscle. If these results are replicated in human tissue, they have the potential to improve patient outcomes by achieving early identification and preservation of parathyroid glands.

A common coding variant in CASP8 is associated with breast cancer risk.

The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.

Thyroid incidentalomas on PET imaging--evaluation of management and clinical outcomes.

OBJECTIVES: 1. To determine the incidence of 'thyroid incidentaloma' in patients undergoing PET/CT in Sheffield. 2. To assess the distribution of cancer type, stage and short term outcomes of incidentally detected thyroid cancer in this cohort. METHODOLOGY: Patients with an unexpected thyroid radio-isotope uptake on reports of whole body nuclear imaging performed in Sheffield Teaching Hospitals NHS Foundation Trust for 'non-thyroid' indications from April 2008 to March 2011 were identified. Patients who have undergone PET imaging were then selected. The management, clinical and pathology details and short term 'thyroid-related' outcomes of patients with thyroid incidentaloma on PET scans were analysed. RESULTS: 1730 PET nuclear imaging studies were performed in this period. Thyroid incidentalomas were detected in 65 (3.8%)of these scans. Two thyroid cancers were detected in this cohort, both demonstrated focal uptake on the PET scan. Histology showed papillary thyroid cancer (TNM classification; pT1N1Mx and pT1bNxMx). CONCLUSION: The risk of cancer in PET detected thyroid incidentaloma in this series (3%) is low compared to published literature (5-50%). Potential reasons are discussed. The low rate of thyroid cancer in our incidentaloma cohort will influence decision making regarding management of these lesions. Only two thyroid cancers were detected in our cohort, limiting the narrative on type, stage of PET detected thyroid cancer and outcomes. Further observational research is required to study the natural history of these lesions in settings where there is a clear protocol for imaging, biopsy and treatment.