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Superior parathyroid blood supply safety in thyroid cancer surgery: A randomized controlled trial.
Kong, DD, Wang, W, Wang, MH
International journal of surgery (London, England). 2019;:33-39
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Abstract
BACKGROUND To evaluate the clinical value of a technique protecting blood supply to the superior parathyroid during surgery for thyroid cancer. MATERIALS AND METHODS The observation group comprised 113 patients admitted to our hospital during the period from January 1, 2016 to December 31, 2016, who were diagnosed with thyroid cancer and treated by surgery using a technique protecting blood supply to the superior parathyroid. The control group comprised 113 patients diagnosed with thyroid cancer who were treated by surgery using the conventional technique. Postoperative parathyroid function damage and blood calcium levels were assessed in both groups. RESULTS The incidences of hypocalcemia and low parathyroid hormone in the observation and control groups were 10.6% and 31.9%, and 14.2% and 35.4%, respectively. The relative risk (RR) of the control group was increased (RR = 3.009 for control; RR = 2.493 for observation). Univariate logistic regression analysis showed that postoperative temporary hypoparathyroidism was associated with lymph node metastasis, use of the above protective technique, and tumor size [(odds ratio, OR = 1.936, 95%CI 1.029-3.643; P = 0.041), (OR = 0.301, 95%CI 0.156-0.579; P = 0.001) and (OR = 2.022, 95%CI 1.089-3.756; P = 0.026), respectively]. Postoperative temporary hypoparathyroidism was also associated with lymph node dissection (Bilateral vs. No, P = 0.003) and T classification (T3 vs. T1, P = 0.034). Multivariate logistic regression analysis showed that, after including significant independent variables of univariate logistic regression analysis (e.g., lymph node metastasis, lymph node resection, protective technique, tumor size, and T classification), the protective technique was a factor supporting reduced incidence of postoperative temporary hypoparathyroidism (OR = 0.325, 95% CI 0.163-0.648; P = 0.001). CONCLUSION Application of a technique protecting blood supply to the superior parathyroid during thyroid cancer surgery effectively reduced the incidence of postoperative temporary hypoparathyroidism. However, because of the imbalance in lymph node dissection between the two groups, confounding factors could not be completely eliminated, and matched pair analysis is needed to eliminate these factors.
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Executive summary of the SEORL CCC-SEEN consensus statement on post-thyroidectomy hypoparathyroidism.
Castro, A, Oleaga, A, Parente Arias, P, Paja, M, Gil Carcedo, E, Álvarez Escolá, C
Endocrinologia, diabetes y nutricion. 2019;(7):459-463
Abstract
Hypoparathyroidism is the most common complication after total or completion thyroidectomy. It is defined as the presence of hypocalcemia accompanied by low or inappropriately normal parathyroid hormone (PTH) levels. Acute hypocalcemia is a potential lethal complication. Hypocalcemia treatment is based on endovenous or oral calcium supplements as well as oral calcitriol, depending on the severity of the symptoms. The risk of clinical hypocalcemia after bilateral thyroidectomy is considered very low if postoperative intact PTH decrease less than 80% with respect to preoperative levels. These patients could be discharged home without treatment, although this threshold may vary between institutions, and we recommend close surveillance in cases with increased risk (Graves disease, large goiters, reinterventions or evidence of parathyroid gland removal). Long-term treatment objectives are to control the symptoms and to keep serum calcium levels at the lower limit of the normal range, while preserving the calcium phosphate product and avoiding hypercalciuria.
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Long-term outcome of hyperthyroidism diagnosed in childhood and adolescence: a single-centre experience.
Gill, DS, Greening, JE, Howlett, TA, Levy, MJ, Shenoy, SD
Journal of pediatric endocrinology & metabolism : JPEM. 2019;(2):151-157
Abstract
Background The objective of the study was to evaluate the long-term outcome of paediatric-onset hyperthyroidism with follow-up into adulthood and to identify any early predictors of a need for definitive therapy (DT). Methods In a retrospective analysis of patients diagnosed with hyperthyroidism under the age of 18 years and at follow-up, a comparison was made by categorising them into those who underwent definitive therapy (DT group), i.e. thyroidectomy/radioactive iodine (RAI), those who remained on antithyroid drugs (ATD) (CBZ group) and those who had complete remission (RE group). Results Sixty-one (49 females, 12 males) patients with a median age of 15.1 years (range: 3.6-18) at diagnosis were studied. The duration of the first course of ATD varied from <1 year (7%), 1-2 years (26%), >2 years (46%) and ATD never discontinued (21%). Disease relapsed in 69% of patients with <1 year of ATD vs. 79% with >2 years of ATD. At follow-up, the median duration since diagnosis was 8.75 years (range 2.0-20.7 years) and the median age at follow-up was 23.2 years (8-36 years). Thirty-three percent (20/61) had undergone DT (DT group) - with 16.5% (n=10) on RAI and 16.5% (n=10) on surgery, 36% (22/61) were on ATD (CBZ group), whilst 32% (19/61) had undergone full remission (RE group). The comparison did not identify any statistically significant difference for predictor factors at diagnosis including age, T4 and free T4 levels, thyroid peroxidise antibody levels (TPO) and the duration of the first course of carbimazole (CBZ) treatment. Conclusion Long-term complete remission of paediatric-onset hyperthyroidism in our study was 31%. There were no predictors identified that could help predict the long-term outcome, especially into adulthood.
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Discharging a Patient Treated With Parathyroid Allotransplantation After Having Been Hospitalized for 3.5 Years With Permanent Hypoparathyroidism: A Case Report.
Aysan, E, Yucesan, E, Idiz, UO, Goncu, B
Transplantation proceedings. 2019;(9):3186-3188
Abstract
INTRODUCTION Parathyroid allotransplantation is one of the methods used in the treatment of permanent hypoparathyroidism. We present a patient who underwent continuous intravenous (IV) calcium replacement therapy because of permanent hypoparathyroidism after total thyroidectomy. CASE PRESENTATION A 47-year-old woman who underwent a total thyroidectomy with a multinodular goiter developed hypoparathyroidism and hypocalcemia 1 week after discharge. The patient was started on daily oral calcitriol, magnesium effervescent, vitamin D, and IV calcium gluconate and was unable to be discharged because the IV calcium could not be stopped. After 3.5 years, 50×10⁶ parathyroid cells were transplanted by injecting the cells into the left deltoid muscle of the patient. The immunosuppression of the patient, who used 20-mg methylprednisolone for the first month, was completely discontinued. RESULTS No complications were observed in the patient after transplantation. The parenteral calcium replacement of the patient was progressively interrupted after transplantation. The patient's serum calcium level was 7.8 mg/dL and the PTH level was 6.9 pg/mL without IV calcium replacement at 12 weeks after transplantation, and the patient was discharged using oral ionized calcium. In the 10-week follow-up after discharge, the need for IV calcium was not observed in the patient. CONCLUSION Parathyroid allotransplantation is a simple, fast, and cost-effective method that should be tried in patients with persistent hypoparathyroidism, especially those who have to take IV calcium replacement, because its cost is much cheaper than standard medical care, its morbidity is much more limited, and it increases the patient's quality of life.
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Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study.
Castinetti, F, Waguespack, SG, Machens, A, Uchino, S, Hasse-Lazar, K, Sanso, G, Else, T, Dvorakova, S, Qi, XP, Elisei, R, et al
The lancet. Diabetes & endocrinology. 2019;(3):213-220
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BACKGROUND Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. METHODS This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. FINDINGS 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. INTERPRETATION Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. FUNDING None.
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Calcium, vitamin D or recombinant parathyroid hormone for managing post-thyroidectomy hypoparathyroidism.
Edafe, O, Mech, CE, Balasubramanian, SP
The Cochrane database of systematic reviews. 2019;(5):CD012845
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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.
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Role of oral calcium supplementation alone or with vitamin D in preventing post-thyroidectomy hypocalcaemia: A meta-analysis.
Xing, T, Hu, Y, Wang, B, Zhu, J
Medicine. 2019;(8):e14455
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BACKGROUND Thyroidectomy is the main intervention for thyroid malignancies and some benign thyroid diseases. Its most common complication is hypocalcaemia, which requires oral or intravenous calcium therapy. The aim of this meta-analysis was to assess the efficacy of routine calcium supplementation with or without vitamin D in preventing hypocalcaemia post-thyroidectomy. METHODS Systematic searches of the PubMed, EMBASE, and Cochrane Library databases were performed. The qualities of the included articles were assessed using the Cochrane risk of bias tool. The studies' qualities of outcomes and strengths of evidence were evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Data analysis was performed using Review Manager 5.3, and odds ratio (ORs) with their 95% confidence intervals (CIs) were computed for dichotomous data. RESULTS Ten randomized controlled trials (RCTs) were included. The combined study recruited 1620 patients (343 men and 1277 women) who underwent total thyroidectomy alone or with neck dissection. Calcium supplementation decreased the risk of transient postoperative hypocalcaemia (OR 0.48 [95% CI, 0.31-0.74]; P < .001) but did not decrease the demand for intravenous supplementation or the rate of permanent hypocalcaemia compared to no treatment. Calcium and vitamin D supplementation significantly reduced the rate of transient hypocalcaemia and the demand for intravenous supplementation compared to either no treatment (OR 0.21 [95% CI, 0.11-0.40]; P < .001 and OR 0.26 [95% CI, 0.10-0.69]; P = .007, respectively) or calcium alone (OR 0.39 [95% CI, 0.18-0.84]; P = .02 and OR 0.18 [95% CI, 0.07-0.47]; P < .001, respectively), but did not decrease the rate of permanent hypocalcaemia. GRADE-based confidence was moderate. CONCLUSION Postoperative calcium supplementation is effective for preventing post-thyroidectomy hypocalcaemia. Calcium plus vitamin D was more effective than calcium alone in preventing postoperative hypocalcaemia and decreasing the demand for intravenous calcium supplementation. Further, well-designed RCTs with larger sample sizes are required to validate our findings.
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Parathyroid autotransplantation at a novel site for better evaluation of the grafted gland function: study protocol for a prospective, randomized controlled trial.
Cui, Q, Kong, D, Li, Z, Wang, K, Zhang, D, Tang, J, Liao, X, Yuan, Q, Gong, Y, Wu, G
Trials. 2019;(1):96
Abstract
BACKGROUND Hypoparathyroidism is one of the most common complications encountered in thyroidectomy. In addition to parathyroid in-situ preservation, parathyroid autotransplantation (PA) is another important remedial method for patients whose parathyroid glands have been removed. However, an accurate evaluation method for the function of a transplanted parathyroid is lacking. Our preliminary study indicated that patients with PA at novel sites near antecubital veins had higher serum concentrations of parathyroid hormone (PTH). Therefore, the main hypothesis is that a grafted site closer to the cephalic vein is more useful for better evaluation of transplanted parathyroid function. This study aims to confirm the more efficient and accurate evaluation system through a prospective, randomized controlled trial. METHODS In total, 280 patients will be enrolled in this study and randomly divided into two groups: 140 patients with transplanted parathyroid glands in the traditional sites (group A) and the other 140 transplanted in the novel sites (group B), close to the antecubital veins. The serum concentration of PTH and calcium ion from both forearms will be measured and monitored regularly for 12 months. The primary outcome of this trial will be the survival of grafted glands, defined as the ratio of PTH between the grafted vs. the non-grafted forearms being no less than 1.5. The secondary outcome is hypoparathyroidism, defined as the PTH level from the non-grafted forearms being less than 15 pg/ml (normal range 15-65 pg/ml). DISCUSSION Our results from this study should provide a more accurate method to evaluate the function of transplanted parathyroid glands by comparing PTH concentrations in both the grafted and non-grafted forearms following PA at novel sites. A better PTH measurement is helpful not only for the management of postoperative patients, but also for further identification of factors affecting PA success. TRIAL REGISTRATION ClinicalTrials.gov, ID: NCT02906748 . Registered on 16 March 2016.
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Cost-effectiveness in transient hypocalcemia post-thyroidectomy.
Mercante, G, Anelli, A, Giannarelli, D, Giordano, D, Sinopoli, I, Ferreli, F, Digiesi, G, Appetecchia, ML, Barnabei, A, Cristalli, G, et al
Head & neck. 2019;(11):3940-3947
Abstract
BACKGROUND Three different strategies to manage transient hypocalcemia after total thyroidectomy were compared to evaluate cost-effectiveness. The reliability of total serum calcium (TSCa), ionized calcium (ICa), and intact parathyroid hormone (iPTH) were investigated to achieve this goal. METHODS A multicenter, prospective randomized study was carried out with 169 patients. The strategies were "preventive" (oral calcium + vitamin D supplementation), "reactive" (therapy in hypocalcemia), and "predictive" (therapy if iPTH <10 pg/mL). RESULTS TSCa had higher accuracy in identifying patients who developed hypocalcemia-related symptoms than ICa (84.6% vs 50.0%). TSCa 24 h after surgery showed 24.8% of patients with hypocalcemia, whereas TSCa 48 h after surgery identified a further 10.6% with hypocalcemia (only in the "reactive" and "predictive" groups). iPTH showed low sensitivity as a predictor of hypocalcemia. Between the 3 groups, there was no significant difference in hospitalization time or number of symptomatic hypocalcemic patients. Interestingly, the cost-per-patient was significantly different among the groups. CONCLUSIONS None of the discussed strategies allowed for early discharge of patients without any risk of transient hypocalcemia. The "preventive" strategy was the most cost-effective, despite overtreatment.
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Serum levels of intact parathyroid hormone on the first day after total thyroidectomy as predictor of permanent hypoparathyroidism.
Calvo Espino, P, Rivera Bautista, JÁ, Artés Caselles, M, Serrano González, J, García Pavía, A, García-Oria, MJ, Caravaca-Fontán, F, Lucena de la Poza, JL, Sánchez Turrión, V
Endocrinologia, diabetes y nutricion. 2019;(3):195-201
Abstract
BACKGROUND Permanent hypoparathyroidism is the most common long-term complication after total thyroidectomy, causing significant morbidity and requiring long-term replacement therapy. Our study objective was to assess whether intact parathyroid hormone (iPTH) levels on the first day after total thyroidectomy are a good predictor of permanent hypoparathyroidism. PATIENTS AND METHODS A retrospective observational study of all patients undergoing total thyroidectomy between January 2009 and December 2014. iPTH and calcium levels were measured the first day after surgery. Patients were followed up for at least one year after surgery. RESULTS The study group consisted of 481 patients with a mean age of 53±14 years, 82% of them females. The most common reason for thyroidectomy was multinodular goiter (75%), followed by papillary thyroid cancer (15%). Transient hypocalcemia was the most common early complication after total thyroidectomy (49%), and permanent hypoparathyroidism was the most common long-term complication (6%). ROC curve analysis showed that iPTH level on the first postoperative day was a good predictor of permanent hypoparathyroidism (area under the curve 0.87; 95% CI: 0.84-0.91). Cut-off iPTH levels of 5pg/mL had 95% sensitivity, 77% specificity, 21.6% positive predictive value, and 99.6% negative predictive value. CONCLUSIONS iPTH level on the first day after total thyroidectomy is a useful predictor of permanent hypoparathyroidism because of its high negative predictive value. Serum iPTH levels >5pg/mL virtually exclude presence of permanent hypoparathyroidism.