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.

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.

Role of Ca²âº in Inhibiting Ischemia-Induced Apoptosis of Parathyroid Gland Cells in New Zealand White Rabbits.

BACKGROUND Hypoparathyroidism is a common complication after thyroidectomy. Calcium supplementation can relieve these symptoms, but it is not clear whether it can protect the parathyroid glands. This study aimed to verify whether Ca²âº inhibits the apoptosis of parathyroid cells following ischemic injury. MATERIAL AND METHODS A rabbit model of parathyroid gland ischemic injury was established. The blood calcium concentrations were measured by colorimetry. The parathyroid hormone (PTH) levels were measured by enzyme-linked immunosorbent assay (ELISA). The parathyroid tissues were observed by hematoxylin and eosin (H&E) staining and the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Western blotting was used to quantify the levels of the following proteins: caspase-3 and p38 MAP Kinase (p38 MAPK). RESULTS This study demonstrates that apoptosis can be a part of the pathological changes associated with parathyroid ischemic injury. Calcium supplementation inhibited the apoptosis of parathyroid cells following ischemic injury. There were no significant differences among the serum calcium levels from the Sham operation (Sham), the Control group (CG), or the Calcium supplementation group (CSG) after 24 h, 72 h, and 168 h of treatment. PTH levels in the CG were significantly higher than in the CSG at 24 h and 72 h after treatments. The apoptosis rate of parathyroid cells from rabbits in the CSG was significantly lower than that of those from rabbits in the CG at 24 h and 72 h after the treatment. Calcium supplementation inhibited p38 MAPK and caspase-3 expression. CONCLUSIONS This study demonstrates that calcium supplementation inhibited the apoptosis of parathyroid cells following ischemic injury.

Parathyroid score can predict the duration of required calcium supplementation after total thyroidectomy.

BACKGROUND: Postoperative hypoparathyroidism is the most common complication after total thyroidectomy, owing to unintentional injury or decreased blood flow to the parathyroid glands. Prediction of postoperative hypoparathyroidism would be helpful for surgeons to manage postoperative hypocalcemia. In this study, we scored the discoloration of the parathyroid glands using a new parathyroid scoring system and evaluated the correlation between the parathyroid score and duration of required calcium supplementation after total thyroidectomy. METHODS: A total of 316 patients undergoing total thyroidectomy between November 2009 and April 2010 were enrolled in this retrospective study. Parathyroid scoring was performed by one experienced surgeon. The status of each of the 4 parathyroid glands was classified as normal color (3 points), slightly discolored (2 points), dark discoloration (1 point), or loss of the gland (0 points), resulting in possible total scores of 0-12. Serum parathyroid hormone (PTH), serum calcium, and ionized calcium concentrations were measured at 2 hours, 2 weeks, 3 months, 6 months, and 1 year after surgery. Patients were also divided into three groups based on the duration of required calcium supplementation: no required supplementation (n = 260, 82.3%), required supplementation for <6 months (n = 38, 12%), and required supplementation for ≥6 months (n = 18, 5.75%). RESULTS: Parathyroid scores were positively correlated with ionized PTH concentrations at 2 hours (r = 0.053, p < 0.001), 2 weeks (r = 0.056, p < 0.001), 3 months (r = 0.032, p<0.001), 6 months (r = 0.072, p < 0.001), and 1 year (r = 0.071, p < 0.001) after thyroidectomy. Parathyroid scores were significantly and inversely associated with the duration of required calcium supplementation (p = 0.001). CONCLUSIONS: Parathyroid scores at the end of surgery might be helpful for predicting the degree of postoperative hypocalcemia after total thyroidetomy.

Preserving Parathyroid Gland Vasculature to Reduce Post-thyroidectomy Hypocalcemia.

BACKGROUND: The failure to preserve parathyroid function in patients who have undergone total thyroidectomy is of major concern, because hypocalcemia is difficult to prevent and remains a common postoperative complication. Here, we describe procedures designed to preserve the vasculature supplying the parathyroid glands and examine both recent outcomes and retrospective reports of results obtained prior to the application of these preservation techniques. METHODS: Our technique for preserving parathyroid function during thyroidectomy was adopted in 2009 and involves separating a relatively long segment of a vessel distally from the thyroid gland. We reviewed the medical records of 1,411 patients who underwent total thyroidectomy, with or without lateral neck dissection, at the Samsung Medical Center from January 2006 through June 2014 to determine outcomes. Patients were divided into three groups according to the time period during which the surgery took place: Group A, 2006-2008 (before the vasculature-preserving technique was applied); Group B, 2009-2011 (the time when the technique was first adopted); and Group C, 2012-2014 (more recent results of the technique). We analyzed the incidence of hypoparathyroidism in the three groups, as well as risk factors that influenced its development. RESULTS: The rates of transient and permanent hypoparathyroidism in Group A were 25.4 and 4.3 %, respectively. However, the incidence of hypoparathyroidism decreased significantly over time after the vasculature-preserving procedure was adopted. Transient hypoparathyroidism developed in 4.8 % of Group C patients, and only four (0.7 %) of the 565 patients in this group required calcium supplementation, despite the fact that a greater number of patients were included who underwent total thyroidectomy combined with lateral neck dissection. Although female sex and lateral neck dissection tended to increase the rate of transient hypoparathyroidism, multivariate analysis showed that the vasculature-preserving procedure was the only significant risk factor related to postoperative hypoparathyroidism. CONCLUSION: The blood flow of the final branch to the parathyroid gland is mostly in the lateral-to-medial direction; therefore, mobilization and preservation of the vessels lateral to the gland is essential to prevent devascularization of the parathyroid gland.

Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery.

BACKGROUND: Postoperative hypoparathyroidism remains the most common complication following thyroidectomy. The aim of this pilot study was to evaluate the use of intraoperative parathyroid gland angiography in predicting normal parathyroid gland function after thyroid surgery. METHODS: Angiography with the fluorescent dye indocyanine green (ICG) was performed in patients undergoing total thyroidectomy, to visualize vascularization of identified parathyroid glands. RESULTS: Some 36 patients underwent ICG angiography during thyroidectomy. All patients received standard calcium and vitamin D supplementation. At least one well vascularized parathyroid gland was demonstrated by ICG angiography in 30 patients. All 30 patients had parathyroid hormone (PTH) levels in the normal range on postoperative day (POD) 1 and 10, and only one patient exhibited asymptomatic hypocalcaemia on POD 1. Mean(s.d.) PTH and calcium levels in these patients were 3·3(1·4) pmol/l and 2·27(0·10) mmol/l respectively on POD 1, and 4·0(1.6) pmol/l and 2·32(0·08) mmol/l on POD 10. Two of the six patients in whom no well vascularized parathyroid gland could be demonstrated developed transient hypoparathyroidism. None of the 36 patients presented symptomatic hypocalcaemia, and none received treatment for hypoparathyroidism. CONCLUSION: PTH levels on POD 1 were normal in all patients who had at least one well vascularized parathyroid gland demonstrated during surgery by ICG angiography, and none required treatment for hypoparathyroidism.

Ultrasound in clinical setting of secondary hyperparathyroidism.

Secondary hyperparathyroidism (sHPT) is one of the most common and serious complications of chronic kidney disease (CKD) and maintenance hemodialysis (MHD). In sHPT, the biology of parathyroid cells changes significantly toward diffuse and nodular hyperplasia. Diagnosis and treatment of sHPT are based on intact parathyroid hormone (i-PTH) serum levels and on the parameters of mineral metabolism. The morphological diagnosis of sHPT relies on 2 complementary imaging techniques: high-resolution ultrasonography with color Doppler imaging (US/CD) and 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy. The main objective of this review is to stimulate nephrologists to use US/CD of the parathyroid glands during the progression of CKD in order to aid clinical, pharmacological and surgical strategies. The primary role of US/CD in sHPT should be to integrate the clinical diagnosis by defining the number and volume of hyperplastic glands, although the international guidelines do not state when and why to perform US/CD. This review also evaluates the role of US/CD in clinical follow-up and assessment of therapeutic response of sHPT, and it highlights how US/CD can evaluate the effect of therapy with phosphate binders, vitamin D or its analogues and calcimimetics, which are changing the natural history of sHPT and the frequency of parathyroidectomy. Evaluation of the morphological and vascular changes of hyperplastic parathyroids is useful to guide percutaneous ethanol injection therapy and to support clinical, pharmacological and surgical strategies. Epidemiological studies are needed to establish how US/CD could change the management of sHPT and why it should be repeated in patients with high levels of serum i-PTH.

Development and prevention of morphologic and ultrastructural changes in uremia-induced hyperplastic parathyroid gland.

The detailed ultrastructural changes of uremia-induced hyperplastic parathyroid gland and the effects of current medical treatments for secondary hyperparathyroidism were investigated. Marked enlargement of parathyroid cell with accumulation of mitochondria and lipids and a significant increase in the thickness of the pericapillary area with increased fibrosis and appearance of fibroblast like cells were noted in the hyperplastic gland caused by uremia and phosphate retention. These ultrastructural changes and biochemical findings indicating hyperparathyroidism were significantly suppressed by all of the treatment using phosphate restriction, calcitriol, and cinacalcet. The characteristic ultrastructural changes, including the morphologic evidence of nodule formation, were indicated.

Does truncal ligation of the inferior thyroid arteries during bilateral subtotal thyroidectomy affect serum calcium levels? A prospective, randomized, controlled study.

This study was designed to investigate the effect of truncal ligation of the inferior thyroid arteries on post-thyroidectomy serum calcium levels. This prospective, randomized study was carried out in 98 patients. In group 1, bilateral inferior thyroid arteries were ligated truncally during bilateral subtotal thyroidectomy procedure, whereas in group 2, ligation was not performed. In all patients, serum ionized calcium levels were measured preoperatively and on postoperative days 1, 2, 3 and 30. There were no statistically significant differences in serum ionized calcium values between group 1 and 2 on postoperative days 1, 2, 3, and 30 (P > 0.05). Laboratory hypocalcemia was found on postoperative days 1, 2, and 3 in 9 (9.2%), 15 (15.3%), and 2 (2.0%) patients, respectively. In all patients, laboratory hypocalcemia improved until postoperative day 5. It was thought that truncal ligation of the inferior thyroid arteries during bilateral subtotal thyroidectomy had no effect on post-thyroidectomy serum calcium levels.

Management of the neck in thyroid cancer.

The incidence of nodal metastasis in differentiated thyroid cancer ranges between 40% to 75%. Elective neck dissection is generally not advised in patients with differentiated thyroid cancer; however, if clinically apparent nodal disease is noted in the tracheoesophageal groove during surgery, central compartment clearance is advised. If clinically apparent nodal disease is present in the lateral compartment of the neck, modified neck dissection preserving the sternomastoid, accessory nerve, and jugular vein is advised. The "berry picking procedure" is generally not recommended because of the higher incidence of regional recurrence. Due consideration should be given for parathyroidal transplantation if the blood supply to the parathyroids is damaged during central compartment clearance. The incidence of lymph node metastasis is highest in young patients, however, lymph node metastasis has no bearing on long-term survival. There seems to be a higher incidence of regional recurrence in elderly individuals. If patients present with bulky nodal disease, consideration may be given for postoperative radioactive iodine dosimetry and ablation if necessary. Differentiated thyroid cancer represents a unique disease in the human body, where lymph node metastasis has no prognostic implication. Aggressive surgical clearance is advised in patients with medullary thyroid cancer in the central compartment and the jugular chain lymph nodes.

Rat parathyroid gland, with special reference to its blood vascular bed, pericapillary space and intercellular space.

The blood vascular bed, perivascular space and intercellular space of the rat parathyroid gland were studied using scanning electron microscopy of vascular casts, freeze-cracked tissue samples, and NaOH-digested tissue blocks. The findings were supplemented by transmission light and electron microscopy of iron colloid-treated or enzyme-digested tissue sections. The rat parathyroid gland contained a rich network of capillaries. These capillaries were surrounded by marked pericapillary spaces which were demarcated by basal lamina of both capillaries and parenchymal cells. The pericapillary spaces contained numerous collagen fibrils, and issued many crista-like projections which ran deep into the sheets of parenchymal cells. The intercellular spaces of parenchymal cells contained neither basal lamina nor collagen fibrils. The surfaces of the parenchymal cells showed strong negative charging, and maintained the intercellular spaces. The luminal surfaces of the capillary endothelium also showed strong negative charging, and maintained the capillary lumen.

Vascularized and nonvascularized parathyroid gland transfer: a comparative study.

There is currently no animal model available to study the results of vascularized parathyroid gland autotransfers and nonvascularized autotransfers in the same model. This study was undertaken to determine the technical feasibility of performing microvascular parathyroid gland autotransfers in the dog, and to compare the postoperative levels of calcium, phosphorous, and parathyroid hormone (PTH) levels to a group of dogs who underwent nonvascularized parathyroid gland transfers. Dogs in the nonvascularized group were unable to maintain normal calcium without supplements, whereas dogs in the vascularized group maintained levels in the normal range. Microsurgical techniques allow transplant of a precise amount of parathyroid gland with its vascular supply to another part of the body with almost immediate restoration of function.

[Parathyroid risk in thyroid surgery. Reality and prevention. 502 bilateral thyroidectomies]. / Le risque parathyroïdien en chirurgie thyroïdienne. Sa réalité et sa prévention. 502 exérèses bilatérales.

Prospective study of parathyroid risk in a bulk of 502 consecutive bilateral thyroidectomies. Early post-operative hypocalcemia has been documented in 8,8% of the patients, but persisted in only 1,6% one year later. Late parathyroid risk of total thyroidectomy is 3,3% but increases twofold if neck dissection is simultaneously performed. Methods of this study probably misdiagnose a number of mild hypoparathyroidism. Lack of early hyperphosphoremia seems to be an optimizing criteria for aftermath. In Grave's disease, early post-operative hypocalcemia is more common (6,9%) but often subsides (definitive risk: 0,4%). This acceptable morbidity is compared to the data of literature. To prevent post-operative hypoparathyroidism a painstaking dissection of parathyroid blood supply seems more promising and effective than routine autotransplantation of the glands.