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Gene expression profile in functioning and non-functioning nodules of autonomous multinodular goiter from an area of iodine deficiency: unexpected common characteristics between the two entities.
Agretti, P, De Marco, G, Ferrarini, E, Di Cosmo, C, Montanelli, L, Bagattini, B, Chiovato, L, Tonacchera, M
Journal of endocrinological investigation. 2022;(2):399-411
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PURPOSE Toxic multinodular goiter is a heterogeneous disease associated with hyperthyroidism frequently detected in areas with deficient iodine intake, and functioning and non-functioning nodules, characterized by increased proliferation but opposite functional activity, may coexist in the same gland. To understand the distinct molecular pathology of each entity present in the same gland, the gene expression profile was evaluated by using the Affymetrix technology. METHODS Total RNA was extracted from nodular and healthy tissues of two patients and double-strand cDNA was synthesized. Biotinylated cRNA was obtained and, after chemical fragmentation, was hybridized on U133A and B arrays. Each array was stained and the acquired images were analyzed to obtain the expression levels of the transcripts. Both functioning and non-functioning nodules were compared versus healthy tissue of the corresponding patient. RESULTS About 16% of genes were modulated in functioning nodules, while in non-functioning nodules only 9% of genes were modulated with respect to the healthy tissue. In functioning nodules of both patients and up-regulation of cyclin D1 and cyclin-dependent kinase inhibitor 1 was observed, suggesting the presence of a possible feedback control of proliferation. Complement components C1s, C7 and C3 were down-regulated in both types of nodules, suggesting a silencing of the innate immune response. Cellular fibronectin precursor was up-regulated in both functioning nodules suggesting a possible increase of endothelial cells. Finally, Frizzled-1 was down-regulated only in functioning nodules, suggesting a role of Wnt signaling pathway in the proliferation and differentiation of these tumors. None of the thyroid-specific gene was deregulated in microarray analysis. CONCLUSION In conclusion, the main finding from our data is a similar modulation for both kinds of nodules in genes possibly implicated in thyroid growth.
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Duration of Parathyroid Function Recovery in Patients With Protracted Hypoparathyroidism After Total Thyroidectomy for Papillary Thyroid Carcinoma.
Qiu, Y, Xing, Z, Xiang, Q, Yang, Q, Su, A, Luo, Y
Frontiers in endocrinology. 2021;:665190
Abstract
PURPOSE The aim of the present study is to investigate the time to recovery of parathyroid function in patients with protracted hypoparathyroidism at 1 month after total thyroidectomy of papillary thyroid carcinoma. MATERIALS AND METHODS Adult patients who underwent total thyroidectomy for papillary thyroid cancer were included. Cases of long-term hypoparathyroidism were studied for recovery of parathyroid function during the follow-up. The duration of recovery and associated variables were recorded. RESULTS Out of the 964 patients, 128 (13.28%) developed protracted hypoparathyroidism and of these, 23 (2.39%) developed permanent hypoparathyroidism and 105 (10.89%) recovered: 86 (8.92%) before 6 months, 11 (1.14%) within 6 and 12 months and 8 (0.83%) after 1 year follow-up. Variables significantly associated with the time to parathyroid function recovery were number of autotransplanted parathyroid glands (HR, 1.399; 95% CI, 1.060 - 1.846; P = 0.018), serum calcium concentration >2.07 mmol/L (Hazard ratio [HR], 1.628; 95% confidence interval [CI], 1.009 - 2.628; P = 0.046) and PTH level > 1.2 pmol/L (HR, 1.702; 95% CI, 1.083 - 2.628; P = 0.021) at 1 month postoperatively. CONCLUSION Permanent hypoparathyroidism should not be diagnosed easily by time, since up to one-fifth of the patients will experience recovery after a period of 6 months and a few patients even beyond one year. The number of autotransplanted parathyroid glands is positively associated with the time to parathyroid function recovery.
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Beneficial effect of low-dose radioiodine ablation for Graves' orbitopathy: results of a retrospective study.
Lanzolla, G, Menconi, F, Nicolì, F, Posarelli, C, Maglionico, MN, Figus, M, Nardi, M, Marcocci, C, Marinò, M
Journal of endocrinological investigation. 2021;(12):2575-2579
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OBJECTIVE Graves' orbitopathy (GO) reflects an autoimmune response against antigens expressed by the thyroid and orbital tissues. Elimination of thyroid antigens may be beneficial for GO. Total thyroid ablation (TTA) [thyroidectomy (Tx), followed by 30 mCi of radioiodine] was shown to exert a beneficial effect on GO following intravenous glucocorticoids (ivGC) compared with Tx alone. Here, we investigated retrospectively whether TTA performed with a 15 mCi of radioiodine still maintains advantages over Tx. METHODS Thirty-two subjects, 13 treated with TTA (performed with 15 mCi of radioiodine) and 19 with Tx alone, all with moderately severe, active GO, treated with ivGC, were studied. The primary objective was the outcome of GO at 24 weeks based on a composite evaluation. RESULTS The two groups did not differ at baseline in terms of sex, age, smoking habits, TSH, anti-TSH receptor autoantibodies, GO duration and eye features. The proportion of GO responders at 24 weeks was greater in the TTA (61.5%) than in the Tx group (26.3%, P = 0.046). In contrast, GO outcome at 48 weeks did not differ between the two groups (69.2% vs 52.6% of responder in TTA and Tx group, respectively). The outcome of the individual GO features did not differ between the two groups both a 24 and 48 months. CONCLUSIONS The advantage of total thyroid ablation seems to be a more rapid response for GO to ivGC treatment. Prospective, randomized studies in a larger number of subjects are needed to confirm our findings.
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MANAGEMENT OF ENDOCRINE DISEASE: Postsurgical hypoparathyroidism: current treatments and future prospects for parathyroid allotransplantation.
Mihai, R, Thakker, RV
European journal of endocrinology. 2021;(5):R165-R175
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BACKGROUND Permanent postsurgical hypoparathyroidism (POSH) is a major complication of anterior neck surgery in general and of thyroid surgery in particular. Depending on diagnostic criteria, up to 10% of patients undergoing bilateral thyroid surgery develop POSH. This leads to a multitude of symptoms that decrease the quality of life and burden the healthcare provision through complex needs for medication and treatment of specific complications, such as seizures and laryngospasm. METHODS Narrative review of current medical treatments for POSH and of the experience accumulated with parathyroid allotransplantation. RESULTS In most patients, POSH is controlled with regular use of calcium supplements and active vitamin D analogues but a significant proportion of patients continue to experience severe symptoms requiring repeated emergency admissions. Replacement therapy with synthetic PTH compounds (PTH1-34, Natpara® and PTH1-84, teriparatide, Forsteo®) has been assessed in multicentre trials, but the use of this medication is restricted by costs and concerns related to the risk of development of osteosarcoma. Based on recent case reports of successful allotransplantation of parathyroid tissue between siblings, there is renewed interest in this technique. Data on selection of donors, parathyroid cell preparation before allotransplantation, site and timing of transplantation, need for immunosuppression and long-term outcomes are reviewed. CONCLUSION A prospective trial to assess the efficacy of parathyroid allotransplantation in patients with severely symptomatic protracted post-surgical hypoparathyroidism is warranted.
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Utility of Stimulated Thyroglobulin in Reclassifying Low Risk Thyroid Cancer Patients' Following Thyroidectomy and Radioactive Iodine Ablation: A 7-Year Prospective Trial.
Jammah, AA, Masood, A, Akkielah, LA, Alhaddad, S, Alhaddad, MA, Alharbi, M, Alguwaihes, A, Alzahrani, S
Frontiers in endocrinology. 2020;:603432
Abstract
CONTEXT Following total thyroidectomy and radioactive iodine (RAI) ablation, serum thyroglobulin levels should be undetectable to assure that patients are excellent responders and at very low risk of recurrence. OBJECTIVE To assess the utility of stimulated (sTg) and non-stimulated (nsTg) thyroglobulin levels in prediction of patients outcomes with differentiated thyroid cancer (DTC) following total thyroidectomy and RAI ablation. METHOD A prospective observational study conducted at a University Hospital in Saudi Arabia. Patients diagnosed with differentiated thyroid cancer and were post total thyroidectomy and RAI ablation. Thyroglobulin levels (nsTg and sTg) were estimated 3-6 months post-RAI. Patients with nsTg <2 ng/ml were stratified based on their levels and were followed-up for 5 years and clinical responses were measured. RESULTS Of 196 patients, nsTg levels were <0.1 ng/ml in 122 (62%) patients and 0.1-2.0 ng/ml in 74 (38%). Of 122 patients with nsTg <0.1 ng/ml, 120 (98%) had sTg levels <1 ng/ml, with no structural or functional disease. sTg levels >1 occurred in 26 (35%) of patients with nsTg 0.1-2.0 ng/ml, 11 (15%) had structural incomplete response. None of the patients with sTg levels <1 ng/ml developed structural or functional disease over the follow-up period. CONCLUSION Suppressed thyroglobulin (nsTg < 0.1 ng/ml) indicates a very low risk of recurrence that does not require stimulation. Stimulated thyroglobulin is beneficial with nsTg 0.1-2 ng/ml for re-classifying patients and estimating their risk for incomplete responses over a 7 years follow-up period.
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The Afirma Xpression Atlas for thyroid nodules and thyroid cancer metastases: Insights to inform clinical decision-making from a fine-needle aspiration sample.
Krane, JF, Cibas, ES, Endo, M, Marqusee, E, Hu, MI, Nasr, CE, Waguespack, SG, Wirth, LJ, Kloos, RT
Cancer cytopathology. 2020;(7):452-459
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Recent analytical and clinical validation of the Afirma Xpression Atlas (XA) demonstrates test reliability and the identification of genomic alterations that may inform patient management. The updated Afirma Genomic Sequencing Classifier and XA reports aim to optimize the understanding of these contributions, including decisions about observation versus surgery, the need for disease‐specific preoperative testing, associated neoplasm types, prognostics, the identification of molecular targets for systemic therapy, and the recognition of potential hereditary syndromes.
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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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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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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.