The utility of parathyroid autofluorescence as an adjunct in thyroid and parathyroid surgery 2023.

Thyroid and parathyroid surgery requires careful dissection around the vascular pedicle of the parathyroid glands to avoid excessive manipulation of the tissues. If the blood supply to the parathyroid glands is disrupted, or the glands are inadvertently removed, temporary and/or permanent hypocalcemia can occur, requiring post-operative exogenous calcium and vitamin D analogues to maintain stable levels. This can have a significant impact on the quality of life of patients, particularly if it results in permanent hypocalcemia. For over a decade, parathyroid tissue has been noted to have unique intrinsic properties known as "fluorophores," which fluoresce when excited by an external light source. As a result, parathyroid autofluorescence has emerged as an intra-operative technique to help with identification of parathyroid glands and to supplement direct visualization during thyroidectomy and parathyroidectomy. Due to the growing body of literature surrounding Near Infrared Autofluorescence (NIRAF), we sought to review the value of using autofluorescence technology for parathyroid detection during thyroid and parathyroid surgery. A literature review of parathyroid autofluorescence was performed using PubMED. Based on the reviewed literature and expert surgeons' opinions who have used this technology, recommendations were made. We discuss the current available technologies (image vs. probe approach) as well as their limitations. We also capture the opinions and recommendations of international high-volume endocrine surgeons and whether this technology is of value as an intraoperative adjunct. The utility and value of this technology seems promising and needs to be further defined in different scenarios involving surgeon experience and different patient populations and conditions.

The impact of near-infrared autofluorescence on postoperative hypoparathyroidism during total thyroidectomy: a case-control study.

PURPOSE: Near-infrared autofluorescence is a new technology in thyroid surgery to better localize and preserve parathyroid glands. The purpose of this study is to assess if the adoption of NIR-AF can improve in short-, medium-, and long-term post-operative calcium and PTH levels compared to conventional "naked eye" surgery in patients undergoing TT for benign or malignant conditions. METHODS: 134 patients undergone total thyroidectomy between January 2020 and June 2022; 67 were treated with conventional thyroidectomy, the other 67 underwent surgery adopting an autofluorescence detecting device. RESULTS: Significant differences were found between the two groups in percentage of patients with short-term hypocalcemia (p = 0.04) and short-term hypoparathyroidism (p = 0.011). Median short-term (p = 0.01) and medium-term (p = 0.03) PTH levels were significantly higher in autofluorescence group, while, short- (p = 0.001), medium- (p < 0.001) and long-term (p = 0.019) percentage variation of PTH levels from baseline were significantly higher in the standard-care group. Finally, the prescription of oral calcium (p < 0.01) after surgery were significantly lower in the autofluorescence group. CONCLUSION: The adoption of near-infrared autofluorescence during total thyroidectomy is related to lower short-term hypocalcemia and hypoparathyroidism rates, decreased variation of post-operative PTH levels in short- and medium- and long-term, reducing the necessity of supplementation therapy with oral calcium compared to conventional surgery.

Usefulness of ICG Angiography-Guided Thyroidectomy for Preserving Parathyroid Function.

INTRODUCTION: Hypoparathyroidism is the most frequent complication after total thyroidectomy and, when permanent, it becomes a severe chronic disease. We assessed the usefulness of indocyanine green (ICG) angiography-guided thyroidectomy to reduce the postoperative hypocalcemia. METHODS: Prospective study with two consecutive cohorts of patients who underwent total thyroidectomy: historical control group (CG) and angiography-guided thyroidectomy group (AG). In all patients, ICG-angiography was performed at the end of the surgery to predict immediate parathyroid gland (PG) function. In the AG, ICG-angiography was also done after PG identification to show their vascular supply. We compared the rate of postoperative hypocalcemia (calcium supplementation needed due to hypocalcemia symptoms or calcium levels < 1.8 mmol/L on the first postoperative day) and permanent hypocalcemia (need of calcium ± vitamin D supplementation 12 months after thyroidectomy). RESULTS: We included 120 consecutive patients (84 CG; 36 AG). Thyroid cancer was the most common diagnostic (63.1% CG-69.4% AG; p = 0.646) and central neck dissection was also frequent (54.8% CG-64.3% AG; p = 0.468). The AG developed a lower rate of postoperative (26.2-5.6%; p = 0.011) and permanent hypocalcemia (11.9-0%; p = 0.032). The OR for permanent hypocalcemia was 0.673 (95% CI 0.591-0.766). A significant higher rate of well vascularized PG at the end of the surgery (score 2) in the AG (39.2-52.9%; p = 0.018) was also seen. CONCLUSION: ICG angiography-guided thyroidectomy is a useful tool to identify PG vascularization, allowing a better PG preservation and a significant decrease in hypocalcemia rates.

Near-infrared autofluorescence of the parathyroid glands during thyroidectomy for the prevention of hypoparathyroidism: a prospective randomized clinical trial.

PURPOSE: Postoperative hypoparathyroidism remains the most often complication in thyroid surgery. Near-infrared autofluorescence (NIR-AF) is a modality to identify parathyroid glands (PG) in vivo with high accuracy, but its use in daily routine surgery is unclear so far. In this randomized controlled trial, we evaluate the ability of NIR-AF to prevent postoperative hypoparathyroidism following total thyroidectomy. METHODS: Patients undergoing total thyroidectomy were allocated in two groups with the use of NIR-AF in the intervention group or according to standard practice in the control group. The aim was to identify the PGs in an early most stage of the operation to prevent their devascularization or removal. Parathyroid hormone was measured pre- and postoperatively and on postoperative day (POD) 1. Serum calcium was measured on POD 1 and 2. Possible symptoms and calcium/calcitriol supplement were recorded. RESULTS: A total of 60 patients were randomized, of whom 30 underwent NIR-AF-based PG identification. Hypoparathyroidism at skin closure occurred in 7 out of 30 patients using NIR-AF, respectively, in 14 out of 30 patients in the control group (p=0.058). There was no significant difference in serum calcium and parathyroid hormone levels between both groups. Likewise, NIR-AF could not detect PGs at a higher rate. CONCLUSION: The use of NIR-AF may help surgeons identify and preserve PGs but did not significantly reduce the incidence of postoperative hypoparathyroidism in this trial. Larger case series have to clarify whether there is a benefit in routine thyroidectomy. TRIAL REGISTRATION NUMBER: DRKS00009242 (German Clinical Trial Register). Registration date: 03.09.2015.

Preoperative imaging in primary hyperparathyroidism: Are 11 C-Choline PET/CT and 99m Tc-MIBI/123 Iodide subtraction SPECT/CT interchangeable or do they supplement each other?

OBJECTIVE: Preoperative location of hyperfunctioning parathyroid glands (HPGs) is vital when planning minimally invasive surgery in patients with primary hyperparathyroidism (PHPT). Dual-isotope subtraction scintigraphy with 99m Tc-MIBI/123 Iodide using SPECT/CT and planar pinhole imaging (Di-SPECT) has shown high sensitivity, but is challenged by high radiation dose, time consumption and cost. 11 C-Choline PET/CT (faster with a lower radiation dose) is non-inferior to Di-SPECT. We aim to clarify to what extent the two are interchangeable and how often there are discrepancies. DESIGN: This is a prospective, GCP-controlled cohort study. PATIENTS AND MEASUREMENTS: One hundred patients diagnosed with PHPT were included and underwent both imaging modalities before parathyroidectomy. Clinical implications of differences between imaging findings and negative imaging results were assessed. Surgical findings confirmed by biochemistry and pathology served as reference standard. RESULTS: Among the 90 patients cured by parathyroidectomy, sensitivity was 82% (95% confidence interval [CI]: 74%-88%) and 87% (95% CI: 79%-92%) for Choline PET and Di-SPECT, respectively, p = .88. In seven cases at least one imaging modality found no HPG. Of these, neither modality found any true HPGs and only two were cured by surgery. When a positive finding in one modality was incorrect, the alternative modality was correct in approximately half of the cases. CONCLUSION: Choline PET and Di-SPECT performed equally well and are both appropriate as first-line imaging modalities for preoperative imaging of PHPT. When the first-line modality fails to locate an HPG, additional preoperative imaging with the alternate modality offers no benefit. However, if parathyroidectomy is unsuccessful, additional imaging with the alternate modality has merit before repeat surgery.

The value of clinical-ultrasonographic feature model to predict the severity of secondary hyperparathyroidism.

OBJECTIVES: To analyze conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in patients with secondary hyperparathyroidism (SHPT) and to evaluate the clinical-ultrasonographic feature based model for predicting the severity of SHPT. METHODS: From February 2016 to March 2021, a total of 59 patients (age 51.3 ± 11.7 years, seCr 797.8 ± 431.7 µmol/L, iPTH 1535.1 ± 1063.9 ng/L) with SHPT (including 181 parathyroid glands (PTGs)) without the history of intact parathyroid hormone (iPTH)-reducing drugs using were enrolled. The patients were divided into the mild SHPT group (mSHPT, iPTH <800 ng/L) and the severe SHPT group (sSHPT, iPTH ≥ 800 ng/L) according to the serum iPTH level. The clinical test data of patients were collected and CUS and CEUS examinations were performed for every patient. Multivariable logistic regression model according to clinical-ultrasonographic features was adopted to establish a nomogram. We performed K-fold cross-validation on this nomogram model and nomogram performance was determined by its discrimination, calibration, and clinical usefulness. RESULTS: There were 19 patients in the mSHPT group and 40 patients in the sSHPT group. Multivariable logistic regression indicated serum calcium, serum phosphorus and total volume of PTGs were independent predictors related with serum iPTH level. Even though CEUS score of wash-in and wash-out were showed related to severity of SHPT in univariate logistic regression analysis, they were not predictors of SHPT severity (p = 0.539, 0.474 respectively). The nomogram developed by clinical and ultrasonographic features showed good calibration and discrimination. The accuracy and the area under the curve (AUC), positive predictive value (PPV), negative predictive value (NPV) and accuracy of this model were 0.888, 92.5%, 63.2% and 83.1%, respectively. When applied to internal validation, the score revealed good discrimination with stratified fivefold cross-validation in the cohort (mean AUC = 0.833). CONCLUSIONS: The clinical-ultrasonographic features model has good performance for predicting the severity of SHPT.

Intraoperative Indocyanine Green Angiography of Parathyroid Glands and the Prevention of Post-Thyroidectomy Hypocalcemia.

BACKGROUND: We compared the reliability of indocyanine green (ICG) angiography and intraoperative PTH levels for predicting early post-thyroidectomy hypocalcemia. METHODS: Prospective study of 94 patients (71% women, mean age 53.7 years) undergoing total thyroidectomy. An ICG score of 2 (white) indicated a well-vascularized gland. PTH preoperative levels-PTH postresection levels divided by preoperative PTH × 100 was used to determine the PTH decline percentage. A decrease of at least 62.5% or <17.1 pg/mL in ioPTH was the criterion for predicting hypocalcemia. RESULTS: At surgery, the four parathyroid glands were identified in 50 (53.2%) patients and <4 glands in 44. Calcium supplements were needed by 22 patients (23.4%) postoperatively, 11 patients in each group of 4 and <4 parathyroid glands identified. The diagnostic accuracy of ICG angiography (0.883, 95% confidence interval [CI] 0.800-0.940) and ioPTH (0.862, 95% CI 0.775-0.92) was similar. When all four parathyroid glands were identified, ICG angiography showed a slightly higher diagnostic accuracy, specificity and positive predictive than ioPTH levels, but when < 4 glands were identified, the ioPTH showed a slightly higher diagnostic accuracy, specificity and positive predictive value. Differences were not statistically significant for any of the comparisons. CONCLUSIONS: The presence of one well-perfused parathyroid gland (ICG score 2) using ICG angiography or ioPTH decline, measured before and after completion of thyroid surgery, is both reliable methods in prediction of early post-thyroidectomy hypocalcemia independently of the number of glands identified intraoperatively.

Usefulness of PET/CT with Carbon-11-Labeled Methionine in the Diagnosis of Tertiary Hyperparathyroidism.

Introduction: Tertiary hyperparathyroidism (tHP) may develop in patients treated with hemodialysis or peritoneal dialysis. Parathyroidectomy may result in a significant reduction in the severity of symptoms. For the effective surgical treatment of hyperparathyroidism, proper localization of the parathyroid glands prior to surgery is essential. The sensitivity of scintigraphy in the diagnosis of tHP is lower than in the diagnosis of primary hyperparathyroidism. In recent years, positron emission tomography (PET/CT) has been gaining importance, usually as a complementary technique. Aim: The aim of this study was to determine the usefulness of PET/CT with [11C]MET in the preoperative localization diagnosis of patients with tertiary hyperparathyroidism caused by chronic kidney disease, in whom first-line diagnostic methods did not allow the localization of pathologically parathyroid glands. Material and methods: The study was conducted in a group of 19 adult patients with severe tHP who were resistant or intolerant to non-invasive treatment, with negative results of scintigraphy and ultrasonography of the neck. The study protocol included measurement of the concentration of calcium, phosphorus, and PTH in the blood serum and performing PET/CT with [11C]MET. Results: A positive result of PET/CT was obtained in 89.5% of the patients (17/19). Parathyroidectomy was performed in 52.9% of the patients (9/17) with positive results of PET/CT with [11C]MET, which were fully consistent with the results of the histopathological examinations of the removed parathyroid glands. On this basis, the sensitivity of PET/CT with [11C]MET in the preoperative localization diagnosis of patients with tHP was found to be 100%. Multiple lesions were visualized in 57.9% of the patients (11/19). Ectopic lesions were visualized in 21.1% of the patients (4/19). Conclusions: PET/CT with [11C]MET is a sensitive technique for the second-line preoperative imaging of parathyroid glands in patients with tertiary hyperparathyroidism in whom first-line examinations, such as ultrasound and scintigraphy, has failed.

Sestamibi Single-Positron Emission Computed Tomography/Diagnostic-quality Computed Tomography for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism: What clinicopathologic factors affect its accuracy?

PURPOSE: Sestamibi Single-Positron Emission Computed Tomography/Diagnostic-quality Computed Tomography (MIBI-SPECT/CT) is a common technology used for primary hyperparathyroidism (PHPT) localization in clinical practice. However, the clinicopathologic factors affecting the accuracy of MIBI-SPECT/CT and the potential limitations remain unclear. METHODS: Retrospectively enrolled PHPT patients (n = 280) were analyzed from August 2017 to December 2019. RESULTS: Of 96 patients with PHPT (mean age, 54 years; 63 females), 17 had discordance between MIBI-SPECT/CT and intraoperative findings. Among the 17 patients with discordance, 58.8% had major discordance, which occurred in most patients with multigland disease (MGD). Compared with concordant patients, discordant patients exhibited increased frequencies of autoimmune thyroid disease (29.4% vs 10.1%, p = 0.035), MDG (41.2% vs 3.8%, p = 0.035), higher PTH (296 pg/mL vs 146 pg/mL; p = 0.012),and lower phosphorus levels (0.77 mmol/L vs 0.90 mmol/L; p = 0.024). MDG (odds ratio [OR], 16.95; 95% CI 2.10-142.86), parathyroid lesion size of 12 mm or less (OR, 6.93; 95% CI 1.41-34.10), and a PTH level higher than 192.5 pg/mL (OR, 12.66; 95% CI 2.17-71.43) were independently associated with discordant MIBI-SPECT/CT results. CONCLUSION: MGD was most strongly associated with discordance between MIBI-SPECT/CT and intraoperative findings followed by a PTH level higher than 192.5 pg/mL and parathyroid lesion size of 12 mm or less. Surgeons should recognize these potential limitations, which may improve the preoperative procedure by encouraging further localization imaging and promptly facilitate intraoperative troubleshooting.

Misleading localization by 18F-fluorocholine PET/CT in familial hypocalciuric hypercalcemia type-3: a case report.

BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) is a heterogeneous autosomal-dominant disorder of calcium hemostasis that may be difficult to distinguish clinically from mild primary hyperparathyroidism. Loss-of-function mutations mainly involving Arg15 residue of the adaptor-related protein complex 2, sigma subunit 1 (AP2S1) cause a rarer, more recently recognized form of FHH, FFH type-3. Recently, 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) showed superior sensitivity to conventional imaging in localizing parathyroid adenomas. We report a new FFH type-3 patient who underwent unnecessary parathyroidectomy in association with misleading FCH-PET/CT imaging. CASE PRESENTATION: A 29-year old woman was initially evaluated for parathyroid hormone (PTH)-dependent hypercalcemia in 2013. Medical history was positive only for chronic constipation and malaise with no personal or family history of hypercalcemia, kidney stones, or neck surgery. Over seven years, serum calcium level was 2.51-2.89 mmol/L with concomitant PTH level of 58.7-94.8 mmol/L. Serum phosphate levels were in the low/low normal range. Serum creatinine and magnesium levels were normal. 25-hydroxy vitamin D level was 13 nmol/L. 24-hour urine calcium level was 1.92 mmol/day but increased to 6.99 mmol/day after treatment with cholecalciferol 1000 IU daily. Bone mineral density and renal ultrasound were normal. Parathyroid ultrasound showed two hypoechoic nodules inferior to the left and right thyroid lobes; however, 99mtechnitium-sestamibi scans (2013, 2016, 2018) were negative. FCH-PET/CT (2019) showed focal uptake co-localizing with the nodule inferior to the left thyroid lobe. The patient underwent left inferior parathyroidectomy and pathology was consistent with parathyroid hyperplasia. However, postoperatively, serum calcium and PTH levels remained elevated and FCH-PET/CT and ultrasound showed persistence of the uptake/nodule. Whole exome sequencing showed Arg15Cys mutation in the AP2S1 gene characteristic of FHH type-3. CONCLUSIONS: In this new case of FHH type-3, FCH-PET/CT failed to localize to the hyperplastic parathyroid glands and localized instead to apparently a lymph node. This, together with increased urinary calcium after vitamin D supplementation, led to unnecessary parathyroidectomy. Given the increasingly lower cost of genetic testing and the cost of follow up and unnecessary surgery, it may prudent to include genetic testing for FHH early on in patients with mild PTH-dependent hypercalcemia.

Microsatellite instability driven metastatic parathyroid carcinoma managed with the anti-PD1 immunotherapy, pembrolizumab.

The present case report describes a 65-year-old man with Lynch syndrome and hypercalcaemia associated with hyperparathyroidism. Parathyroid surgery confirmed the diagnosis of parathyroid carcinoma. Serum calcium and parathyroid hormone (PTH) concentrations serially increased after initial surgery. Imaging study and subsequent biopsy confirmed lung metastases with mismatch repair deficiency. Pembrolizumab was initiated achieving 60% reduction in tumour burden.

Research on Intra-Operative Indocyanine Green Angiography of the Parathyroid for Predicting Postoperative Hypoparathyroidism: A Noninferior Randomized Controlled Trial.

OBJECTIVE: A noninferiority randomized controlled trial was undertaken to clarify whether the postoperative measurements of serum calcium and parathyroid hormone and oral supplementation of calcium and calcitriol could be omitted if patients had at least one well-perfused parathyroid gland evaluated by intra-operative indocyanine green (ICG) angiography. METHODS: Patients with at least one parathyroid gland well-perfused by ICG angiography (ICG score >2) were randomized to the control group or test group. For the control group, oral calcium and calcitriol were systematically supplemented. For the test group, no oral calcium or calcitriol was supplemented to the patients. Levels of serum calcium and parathyroid hormone of patients on the first and 30th postoperative day were compared between the two groups. RESULTS: Among all 68 selected patients, 56 patients had at least one well-perfused parathyroid gland evaluated by intra-operative ICG angiography. The 56 patients were randomized to the control group or test group. There were no statistically significant differences in the levels of serum calcium and parathyroid hormone between test group and control group on the first or 30th postoperative day. CONCLUSION: The postoperative measurements of serum calcium and parathyroid hormone and oral supplementation of calcium and calcitriol were evaluated as redundant, if patients had at least one well-perfused parathyroid gland evaluated by intra-operative ICG angiography. ABBREVIATIONS: ICG = indocyanine green; NIR = near infrared; POD = postoperative day; PTH = parathyroid hormone; SBR = signal background ratio.

Correlation Between the Parathyroid Glands Size and Parathormones Value in Patients with Hyperparathyroidism.

INTRODUCTION: Hyperparathyroidism is a common endocrine disorder with potential complications of bone, renal, neurocognitive and cardiovascular system. AIM: To determine the correlation between the size of parathyroid glands and parathormone values in the patients with hyperparathyroidism. METHODS: We analyzed a retrospective-prospective database of 79 consecutive patients who underwent parathyroidectomy for hyperparathyroidism at our institution between January 2011 and February 2018. The values of parathormone, calcium and phosphorus were determined in all patients before and after surgery. Ultrasonography were performed before surgery. Imaging results were confirmed by pathology. We analyzed the correlation between the sizes parathyroid glands obtained trough ultrasonography and pathology with parathormone values. RESULTS: The median age of the patients were 51 age (range 20-73) and 67,1% of the patients were female. Our study demonstrated that between actual glands sizes (volumes), expresses in millimeters, measured on pathohistological analysis and ultrasound examination and size value of parathormone its increased value does not affect the size of the gland. We investigate the correlation between the size of glands measured according to the pathohistological finding and the value of parathormone we obtained the correlation results close to the statistical features. The correlation value of parathormone and glands sizes according to the pathohistological finding measured trough the determined assessment scale we determined the statistically important of medium value. CONCLUSION: One of the important factors for parathyroidectomy is the value of parathormone. Serum parathormone level might be predictable by a total size of parathyroid glands and could be an effective the predictor of gland localisation.

Randomized clinical trial of intraoperative parathyroid gland angiography with indocyanine green fluorescence predicting parathyroid function after thyroid surgery.

BACKGROUND: Hypoparathyroidism, the most common complication after thyroid surgery, leads to hypocalcaemia and significant medical problems. An RCT was undertaken to determine whether intraoperative parathyroid gland angiography with indocyanine green (ICG) could predict postoperative hypoparathyroidism, and obviate the need for systematic blood tests and oral calcium supplementation. METHODS: Between September 2014 and February 2016, patients who had at least one well perfused parathyroid gland on ICG angiography were randomized to receive standard follow-up (measurement of calcium and parathyroid hormone (PTH) on postoperative day (POD) 1 and systematic supplementation with calcium and vitamin D; control group) or no supplementation and no blood test on POD 1 (intervention group). In all patients, calcium and PTH levels were measured 10-15 days after thyroidectomy. The primary endpoint was hypocalcaemia on POD 10-15. RESULTS: A total of 196 patients underwent ICG angiography during thyroid surgery, of whom 146 had at least one well perfused parathyroid gland on ICG angiography and were randomized. None of these patients presented with hypoparathyroidism, including those who did not receive calcium supplementation. The intervention group was statistically non-inferior to the control group (exact 95 per cent c.i. of the difference in proportion of patients with hypocalcaemia -0·053 to 0·053; P = 0·012). Eleven of the 50 excluded patients, in whom no well perfused parathyroid gland could be identified by angiography, presented with hypoparathyroidism on POD 1, and six on POD 10-15, which was significantly different from the findings in randomized patients (P = 0·007). CONCLUSION: ICG angiography reliably predicts the vascularization of the parathyroid glands and obviates the need for postoperative measurement of calcium and PTH, and supplementation with calcium in patients with at least one well perfused parathyroid gland. Registration number: NCT02249780 (http://www.clinicaltrials.gov).

Pilot study of parathyroid glands in adult and pediatric subjects exposed to ionizing radiation after the ChNPP accident, methodology of parathyroid diagnostic ultrasound. / PILOTNE DOSLIDZhENNIa STANU PRYShchYTOPODIBNYKh ZALOZ OSIB, OPROMINENYKh VNASLIDOK AVARIÏ NA ChAES DOROSLOGO TA DYTIaChOGO VIKU, METODOLOGIIa ÏKh UL'TRAZVUKOVOGO DOSLIDZhENNIa.

OBJECTIVE: Estimation of the parathyroid hyperplasia prevalence after the ChNPP accident in adults exposed to ion izing radiation and their descendants using the diagnostic ultrasound and its methodology elaboration. MATERIALS AND METHODS: The pilot prospective study of the prevalence of parathyroid hyperplasia among the Chornobyl Nuclear Power Plant (ChNPP) accident adult survivors (n=686) and their descendants (54 children) was performed using diagnostic ultrasound examination of thyroid and parathyroids. Among the study subjects there were 339 ChNPP accident clean up workers (ACUW), 32 persons were evacuated from the 30 km exclusion zone and 224 ones were included to the control group. Diagnostic ultrasound of thyroid and parathyroids was performed according to the standard method. Additionally, in children with parathyroid hyperplasia an additional assay of 25 hydroxyvitamin D levels in serum was performed. In calculating the statistical significance, its level p < 0.05 was considered statistically significant. RESULTS: Parathyroids are a few small but critically important endocrine glands that synthesize parathyroid hormone, regulating mainly phosphoric calcium metabolism. Insufficient (hypoparathyroidism) or excessive (hyperparathy roidism) function of parathyroids is harmful to the patients affecting the state of nervous and cardiovascular sys tem. Parathyroidss can accumulate isotopes of cesium, strontium and radioactive iodine. The available data testify to an increased incidence of clinically significant hyperplasia of parthyroids (more than 9 mm in adults and more than 5 mm in children) among persons exposed toionizng radiation as a result of the accident at the ChNPP (28.64%) and their descendants (23.8-70.6%). First of all are concerned those adults who live in contaminated areas in comparison with the control group (24.15% in not irradiated). Evacuees from the 30 km exclusion zone being the category of people who were exposed to the absorbed iodine isotopes in the first days of the Chernobyl accident are the another risk group. These data demonstrate sensitivity of parathyroidss to the impact of incorpo rated isotopes (iodine, cesium and strontium), which in the long term exposure create conditions for structural and functional changes in regulation of phosphorous calcium metabolism being the basis for a significant prevalence of osteopenia and osteoporosis in irradiated individuals and their descendants. A number of further studies are required to clarify the findings and to disclose the hormonal mechanisms of radiation effects on parathyroids. CONCLUSIONS: Parathyroid glands are radiosensitive and susceptible to effects of strontium, cesium and iodine iso topes, which cause parathyroid irradiation and subsequent structural and functional changes, being a prerequisite for development of osteopenia and osteoporosis in the ChNPP accident survivors and their descendants. High inci dence of parathyroid hypertrophy is found in the inhabitants of the radiation contaminated territories (long term irradiation by cesium isotopes), as well as in evacuated from the 30 km exclusion zone (irradiation by iodine iso topes in the early days of the accident).

Minimally invasive radioguided parathyroid surgery using low-dose Tc-99m-MIBI - comparison with standard high dose.

INTRODUCTION: Surgery remains the most effective treatment for primary hyperparathyroidism (PHPT). Minimally invasive radioguided parathyroidectomy (MIRP) is a common technique for detecting and excising abnormal parathyroid glands. The aim of this study was to compare injections of low-dose and high-dose (99m) Tc methoxy isobutyl isonitrile (MIBI) for intraoperative localisation of parathyroid adenomas by means of a gamma probe in patients with primary hyperparathyroidism (PHPT). MATERIAL AND METHODS: Thirty patients with PHPT and a preoperative diagnosis of parathyroid adenoma were enrolled between 2010 and 2012. They were considered as Group B and underwent MIRP using 5 mCi Tc-99m MIBI, and their perioperative data were compared with twenty patients treated with conventional 20 mCi Tc-99m MIBI previously (Group A). RESULTS: Group A was made up of 20 patients (mean age, 41.55 years; 14 women and 6 men), and group B included 30 patients (mean age, 40.43 years; 19 women and 11 men). The mean serum parathyroid hormone (PTH) and calcium values were recorded pre- and postoperatively. The mean follow-up period for the patients in the two groups was 18.4 and 16.5 months, respectively. Pre-operative evaluation demonstrated that the groups were statistically similar. Intraoperative data and success rate of surgery showed no difference between the two groups. No significant complication was detected after surgeries and no recurrence happened in either of the two groups during the follow-up period. CONCLUSIONS: A new protocol of MIRP using low doses of Tc-99m-MIBI resulted in an excellent success rate. Comparing results of the study, we conclude that low-dose Tc-99m-MIBI may be preferred for identification of parathyroid adenomas intraoperatively by means of a gamma probe in PHPT patients because it appears to be as effective as high-dose Tc-99m-MIBI.

A case report of mediastinal ectopic parathyroid adenoma presented as parathyroid crisis localized by SPECT/CT.

INTRODUCTION: Parathyroid crisis due to ectopic parathyroid adenomas can pose diagnostic and management challenges, since it is quite rare in clinical practice. CLINICAL FINDINGS/PATIENT CONCERNS: A 67-year-old Chinese male presented as a parathyroid crisis due to an ectopic mediastinal parathyroid adenoma with his serum calcium and PTH markedly increased in short time. An ultrasonography and computed tomography (CT) scan of the neck did not reveal any parathyroid adenoma. Thoracic CT detected a contrast-enhanced mass in the mediastinum. Although the ectopic location is difficult to appreciate on anterior planar technetium-99m-sestamibi scintigraphy views but has been accurately localized with single photon-emission computed tomography/computed tomography. After fluid resuscitation, loop diuretic, and calcitonin treatment, a thoracoscope surgery was performed. The histopathology of the mediastinal nodule was consistent with a parathyroid adenoma. Hypocalcemia due to hungry bone syndrome occurred after surgery and was resolved quickly with large-dose calcium and calcitriol supplementation. He is asymptomatic and has normal serum calcium and PTH levels on regular follow-up. DIAGNOSES: The ultrasonography, CT, sestamibi, and single photon-emission computed tomography/computed tomography provide limited sensitivity in the detecting ectopic parathyroid adenomas alone. The combination of these techniques has incremental value in localizing ectopic parathyroid adenomas over either technique alone. CONCLUSION: Any parathyroid crisis without parathyroid adenoma in the neck should alert physicians to search for ectopic locations through combination of imaging techniques.

Intraoperative Near-infrared Imaging for Parathyroid Gland Identification by Auto-fluorescence: A Feasibility Study.

BACKGROUND: Parathyroid glands (PGs) can be particularly hard to distinguish from surrounding tissue and thus can be damaged or removed during thyroidectomy. Postoperative hypoparathyroidism is the most common complication after thyroidectomy. Very recently, it has been found that the parathyroid tissue shows near-infrared (NIR) auto-fluorescence which could be used for intraoperative detection, without any use of contrast agents. The work described here presents a histological validation ex vivo of the NIR imaging procedure and evaluates intraoperative PG detection by NIR auto-fluorescence using for the first time to our knowledge a commercially available clinical NIR imaging device. METHODS: Ex vivo study on resected operative specimens combined with a prospective in vivo study of consecutive patients who underwent total or partial thyroid, or parathyroid surgery at a comprehensive cancer center. During surgery, any tissue suspected to be a potential PG by the surgeon was imaged with the Fluobeam 800 (®) system. NIR imaging was compared to conventional histology (ex vivo) and/or visual identification by the surgeon (in vivo). RESULTS: We have validated NIR auto-fluorescence with an ex vivo study including 28 specimens. Sensitivity and specificity were 94.1 and 80 %, respectively. Intraoperative NIR imaging was performed in 35 patients and 81 parathyroids were identified. In 80/81 cases, the fluorescence signal was subjectively obvious on real-time visualization. We determined that PG fluorescence is 2.93 ± 1.59 times greater than thyroid fluorescence in vivo. CONCLUSIONS: Real-time NIR imaging based on parathyroid auto-fluorescence is fast, safe, and non-invasive and shows very encouraging results, for intraoperative parathyroid identification.

Effects of Denosumab and Calcitriol on Severe Secondary Hyperparathyroidism in Dialysis Patients With Low Bone Mass.

CONTEXT: Secondary hyperparathyroidism (SHPT) may worsen with administration of denosumab in chronic renal failure patients with low bone mass. OBJECTIVE: This study aimed to evaluate the short-term effect of coadministration of calcitriol and denosumab on PTH secretion and parathyroid structure and the incidence of adverse effects in patients with SHPT and low bone mass. DESIGN AND SETTING: This was a 24-week, open-label study at Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan. PATIENTS: Dialysis patients with SHPT (intact parathyroid hormone [iPTH] > 800 pg/mL) and low bone mass (T score < -2.5) were enrolled. INTERVENTION: Patients received denosumab (60 mg) and doses of calcitriol adjusted to achieve iPTH < 300 pg/mL. MAIN OUTCOME MEASURES: Parathyroid gland volume was assessed upon study initiation and completion. Serum calcium, phosphate, alkaline phosphatase, iPTH, and adverse effects were assessed at each visit (Day 7, 14, and 21, and every month thereafter). RESULTS: iPTH significantly decreased (mean decrease, 58.28 ± 6.12%) with denosumab/calcitriol administration (P < .01) but not in the controls (patients not receiving denosumab). Parathyroid gland volume decreased (mean decrease, 21.98 ± 5.54%) with denosumab/calcitriol administration (P < .01) and progressively increased (20.58 ± 4.48%) in the controls (P < .05). Serum alkaline phosphatase and iPTH levels were significantly correlated to decreased iPTH and regression of parathyroid hyperplasia (P < .05). The most common adverse events were hypocalcemia (33.33%) and respiratory tract infection (4.17%). Hypocalcemia rapidly resolved with calcium and calcitriol supplements. CONCLUSIONS: Denosumab allows for supra-physiologic doses of calcitriol resulting in decreased parathyroid secretion and parathyroid hyperplasia. Supervised administration and weekly laboratory and clinical monitoring of serum calcium are recommended during the first month to prevent hypocalcemia.

11C-methionine PET/CT imaging of 99mTc-MIBI-SPECT/CT-negative patients with primary hyperparathyroidism and previous neck surgery.

CONTEXT: (99m)Tc-Methoxy-isobutyl-isonitrile (MIBI) scintigraphy is a standard preoperative localization imaging modality in patients with primary hyperparathyroidism (pHPT). Its accuracy in localizing a hyperactive parathyroid gland after previous cervical surgery is limited. Recently, (11)C-methionine has been introduced as a promising radiotracer for pHPT imaging. Yet, few data exist for this technique in patients with persisting or recurrent pHPT before reoperation. OBJECTIVES: We aimed to investigate the ability of (11)C-methionine positron emission tomography (PET)/computed tomography (CT) to localize a parathyroid disorder after cervical surgery and negative postsurgical (99m)Tc-MIBI single-photon emission CT (SPECT)/CT. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients (6 males, 9 females; age range, 36-85 years) with pHPT and negative (99m)Tc-MIBI SPECT/CT who had undergone earlier neck surgery because of pHPT and/or thyroid disorder were recruited. Twelve of the 15 patients had thyroidectomy for goiter or differentiated thyroid carcinoma. Ten patients had previous parathyroid surgery for pHPT, and 2 patients had a history of parathyroid carcinoma. Thirteen of 15 patients showed elevated levels of intact PTH at the time of PET/CT imaging, whereas all patients had elevated serum calcium values. MAIN OUTCOME MEASUREMENTS: Pathological results of contrast-enhanced (11)C-methionine PET/CT and surgical results were evaluated. RESULTS: In 6 of 15 patients (11)C-methionine PET/CT showed a hypermetabolic focus in the upper mediastinum in 2 patients, in the thoracic outlet in 1 patient, and in the cervical region in 3 patients. In 9 of the 15 patients, no hyperactive parathyroid gland could be visualized. Reoperation was performed in 5 of 6 patients without surgical complications. One patient refused surgery. In 2 of the 5 patients, a transsternal procedure was performed. Correlating with the (11)C-methionine PET/CT results, a single parathyroid adenoma was found in 4 patients and parathyroid carcinoma metastasis in 1 patient. CONCLUSION: (11)C-Methionine PET/CT is a useful complementary imaging technique to localize parathyroid adenoma or carcinoma in (99m)Tc-MIBI SPECT/CT-negative patients.