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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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Abstract
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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Calcitonin Stimulation Tests: Rationale, Technical Issues and Side Effects: A Review.
Băetu, M, Olariu, CA, Moldoveanu, G, Corneci, C, Badiu, C
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2021;(6):355-363
Abstract
Calcitonin (CT) stimulation tests have great value and could help to: differentiate thyroid causes of elevated CT apart from non-thyroid sources, determine whether the patients with slightly elevated basal CT could/could not be candidates for surgery, and indicate the right moment for prophylactic thyroidectomy in children with MEN syndromes when with normal basal CT. This triggered the requests for development of CT stimulation tests, taking into consideration their safety and aimed us to write a systematic review of literature regarding the rationale, technical issues, and side effects of CT stimulating tests used for diagnosis of MTC. After a thorough review of the literature, we classified the reported side effects by severity, as defined by United States Food and Drug Administration. A statistical analysis was performed using IBM SPSS Statistics version 20. Various side effects were noticed during stimulation tests that differ by intensity, duration and severity, depending on types of substances and protocols used. The side effects after pentagastrin test were significantly more severe than those reported after calcium stimulation test (p=0.0396). There are also significant gender-specific differences in side effects induced by stimulation tests. In conclusion, we recommend performing Ca CT stimulation test when needed, considering preventive evaluation of some clinical, instrumental, and biochemical aspects of each patient. Precise instructions should be followed before a stimulation test and furthermore continuous cardiac monitoring is essential during and after the test to minimize the possibility of a serious event.
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Impact of Permanent Post-thyroidectomy Hypoparathyroidism on Self-evaluation of Quality of Life and Voice: Results From the National QoL-Hypopara Study.
Frey, S, Figueres, L, Pattou, F, Le Bras, M, Caillard, C, Mathonnet, M, Hamy, A, Brunaud, L, Lifante, JC, Trésallet, C, et al
Annals of surgery. 2021;(5):851-858
Abstract
OBJECTIVE The aim of this study was to compare the quality of life (mental health) and voice in patients with or without permanent hypoparathyroidism after total thyroidectomy. SUMMARY BACKGROUND DATA Permanent hypoparathyroidism is an underestimated complication of thyroid surgery owing to suppression of parathormone secretion. Few studies have evaluated the consequences of hypoparathyroidism on quality of life and none has studied its effects on voice. METHODS The QoL-hypopara study (ClinicalTrial.gov NCT04053647) was a national observational study. Adult thyroidectomized patients were included between January and June 2020. A serum parathormone level <15 pg/mL >6 months after surgery defined permanent hypoparathyroidism. Patients answered the MOS-36-item short-form health (SF-36), the Voice Handicap Index (VHI) surveys, and a list of questions regarding their symptoms. RESULTS A total of 141 patients were included, 45 with permanent hypoparathyroidism. The median period between thyroid surgery and the questionnaire was 6 (Q1-Q3 4-11) and 4 (4-5) years in hypoparathyroid patients and controls respectively. Hypoparathyroid patients presented a reduced median mental score ratio (SF-36) [0.88 (Q1-Q3 0.63-1.01) vs 1.04 (0.82-1.13), P = 0.003] and a lower voice quality (incidence rate ratio for total VHI 1.83-fold higher, P < 0.001). In multivariable analysis, hypoparathyroidism [-0.17 (95% confidence interval -0.28 to -0.07), P = 0.002], but not age, female sex, thyroid cancer, or abnormal TSH level, was associated with the reduced mental score ratio. Myalgia, joint pain, paresthesia, tetany, anxiety attack, and exhaustion were the most common symptoms among hypoparathyroid patients (>50%). CONCLUSIONS Hypoparathyroid patients present significantly impaired quality of life, lower voice quality, and frequent symptoms. These results reinforce the importance of preventing this complication.
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What is the impact of continuous neuromonitoring on the incidence of injury to the recurrent laryngeal nerve during total thyroidectomy?
Bihain, F, Nomine-Criqui, C, Demarquet, L, Blanchard, C, Gallet, P, Nguyen, PL, Mirallie, E, Brunaud, L
Surgery. 2021;(1):63-69
Abstract
BACKGROUND Continuous intraoperative neuromonitoring may facilitate reversal of intraoperative injurious operative maneuvers in comparison with intermittent intraoperative neuromonitoring. The aim of this study was to evaluate the impact of the routine use of continuous intraoperative neuromonitoring on intraoperative injuries to the recurrent laryngeal nerve. METHOD This study was a prospective case series with retrospective analysis of consecutive patients undergoing total thyroidectomy from August 2013 to August 2019. During this period, intermittent intraoperative neuromonitoring (before Mar 2016) and continuous intraoperative neuromonitoring (after Mar 2016) were used in all patients. RESULTS We reviewed the outcomes of 603 patients (466 female patients) comprising 236 who underwent intermittent intraoperative neuromonitoring and 367 who underwent continuous intraoperative neuromonitoring. Intraoperative adverse electromyography events (>50% decrease in amplitude between VN1 and VN2) were observed in 87 patients (14.5%) and were less frequent in the continuous intraoperative neuromonitoring group (10.6 vs 20.3%, P = .001). Intraoperative loss of signal (electromyography events with VN2 ≤100μV) were observed in 35 patients (5.8%) without any difference between the 2 groups of patients (5.2 vs 6.8%, P = .415). Postoperative recurrent laryngeal nerve palsies were observed in 36 patients (5.9%) without any difference between the 2 groups of patients (4.9 vs 7.6%, P = .168). CONCLUSION The routine use of continuous intraoperative neuromonitoring improves the rate of intraoperative adverse electromyography events but does not impact significantly the rates of loss of signal and recurrent laryngeal nerve palsy.
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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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Abstract
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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Abstract
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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Use of pre-operative calcium and vitamin D supplementation to prevent post-operative hypocalcaemia in patients undergoing thyroidectomy: a systematic review.
Khatiwada, AS, Harris, AS
The Journal of laryngology and otology. 2021;(7):568-573
Abstract
OBJECTIVE This systematic review aimed to establish the evidence behind the use of pre-operative calcium, vitamin D or both calcium and vitamin D to prevent post-operative hypocalcaemia in patients undergoing thyroidectomy. METHOD This review included prospective clinical trials on adult human patients that were published in English and which studied the effects of pre-operative supplementation with calcium, vitamin D or both calcium and vitamin D on the rate of post-operative hypocalcaemia following total thyroidectomy. RESULTS Seven out of the nine trials included reported statistically significantly reduced rates of post-operative laboratory hypocalcaemia (absolute risk reduction, 13-59 per cent) and symptomatic hypocalcaemia (absolute reduction, 11-40 per cent) following pre-operative supplementation. CONCLUSION Pre-operative treatment with calcium, vitamin D or both calcium and vitamin D reduces the risk of post-operative hypocalcaemia and should be considered in patients undergoing total thyroidectomy.
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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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Potential Impact of BMI on the Aggressiveness of Presentation and Clinical Outcome of Differentiated Thyroid Cancer.
Matrone, A, Ceccarini, G, Beghini, M, Ferrari, F, Gambale, C, D'Aqui, M, Piaggi, P, Torregrossa, L, Molinaro, E, Basolo, F, et al
The Journal of clinical endocrinology and metabolism. 2020;(4)
Abstract
BACKGROUND Obesity is a risk factor for several cancers, including differentiated thyroid cancer (DTC). Moreover, it has also been investigated as a potential risk factor for aggressiveness of DTC, but the data gathered so far are conflicting. The aim of our study was to evaluate the relationship between body mass index (BMI), aggressiveness of DTC at diagnosis, and clinical outcome. METHODS We evaluated 1058 consecutive DTC patients treated with total thyroidectomy and enrolled at the time of first radioactive iodine (131I) treatment. Patients were divided into 4 groups based on their BMI: underweight (< 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥ 30 kg/m2). Histological aggressiveness of DTC at the time of diagnosis and clinical outcome according to 2015 American Thyroid Association (ATA) guidelines were evaluated. RESULTS No differences in histological features, ATA risk of recurrence, activity of 131I administered and prevalence of 131I avid metastatic disease after first131I treatment, have been demonstrated among the groups. Furthermore, at the end of follow up (median = 5.7 years), no differences were evident in the number of further treatments performed as well as in the clinical response. CONCLUSIONS In our study group of Caucasian subjects, we could not demonstrate any association between BMI and aggressiveness of DTC, neither at the time of diagnosis nor during follow-up. These data indicate that postsurgical assessment and therapeutic attitude for treatment and follow-up of DTC should be based on the class of risk applied to the general population, with no concern for BMI.