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      MANAGEMENT OF ENDOCRINE DISEASE: Postsurgical hypoparathyroidism: current treatments and future prospects for parathyroid allotransplantation

      review-article
      1 , 2
      European Journal of Endocrinology
      Bioscientifica Ltd

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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.

          Related collections

          Most cited references52

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          European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults.

          Hypoparathyroidism (HypoPT) is a rare (orphan) endocrine disease with low calcium and inappropriately low (insufficient) circulating parathyroid hormone levels, most often in adults secondary to thyroid surgery. Standard treatment is activated vitamin D analogues and calcium supplementation and not replacement of the lacking hormone, as in other hormonal deficiency states. The purpose of this guideline is to provide clinicians with guidance on the treatment and monitoring of chronic HypoPT in adults who do not have end-stage renal disease. We intend to draft a practical guideline, focusing on operationalized recommendations deemed to be useful in the daily management of patients. This guideline was developed and solely sponsored by The European Society of Endocrinology, supported by CBO (Dutch Institute for Health Care Improvement) and based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) principles as a methodological base. The clinical question on which the systematic literature search was based and for which available evidence was synthesized was: what is the best treatment for adult patients with chronic HypoPT? This systematic search found 1100 articles, which was reduced to 312 based on title and abstract. The working group assessed these for eligibility in more detail, and 32 full-text articles were assessed. For the final recommendations, other literature was also taken into account. Little evidence is available on how best to treat HypoPT. Data on quality of life and the risk of complications have just started to emerge, and clinical trials on how to optimize therapy are essentially non-existent. Most studies are of limited sample size, hampering firm conclusions. No studies are available relating target calcium levels with clinically relevant endpoints. Hence it is not possible to formulate recommendations based on strict evidence. This guideline is therefore mainly based on how patients are managed in clinical practice, as reported in small case series and based on the experiences of the authors.
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            Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia.

            Hypocalcaemia is common after thyroidectomy. Accurate prediction and appropriate management may help reduce morbidity and hospital stay. The aim of this study was to perform a systematic literature review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia.
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              The impact of surgical technique on postoperative hypoparathyroidism in bilateral thyroid surgery: a multivariate analysis of 5846 consecutive patients.

              Limited information exists about risk factors for postoperative hypoparathyroidism after bilateral thyroid surgery. Between January 1 and December 31, 1998, bilateral thyroid surgery was performed on 5846 patients for benign and malignant thyroid disease. Data were prospectively collected by questionnaires from 45 hospitals. A logistic regression model was used to determine independent risk factors. The overall incidence of transient and permanent hypoparathyroidism was 7.3% and 1.5%, respectively. On logistic regression analysis, total thyroidectomy (odds ratio [OR], 4.7), female gender (OR, 1.9), Graves' disease (OR, 1.9), recurrent goiter (OR, 1.7), and bilateral central ligation of the inferior thyroid artery (OR, 1.7) constituted independent risk factors for transient hypoparathyroidism. When the multivariate analysis was confined to permanent hypoparathyroidism, total thyroidectomy (OR, 11.4), bilateral central (OR, 5.0) and peripheral (OR, 2.0) ligation of the inferior thyroid artery, identification and preservation of no or only a single parathyroid gland (OR, 4.1), and Graves' disease (OR, 2.4) emerged as independent risk factors. Extent of resection and surgical technique had a greater impact on the rates of permanent postoperative hypoparathyroidism than thyroid pathologic condition. In bilateral thyroid surgery, peripheral ligation of the inferior thyroid artery at the thyroid capsule should be favored over central ligation, and at least 2 parathyroid glands should be identified and preserved. High-risk procedures, such as total thyroidectomy and Graves' disease, require special surgical training and expertise.

                Author and article information

                Journal
                Eur J Endocrinol
                Eur J Endocrinol
                EJE
                European Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                0804-4643
                1479-683X
                May 2021
                17 February 2021
                : 184
                : 5
                : R165-R175
                Affiliations
                [1 ]Department of Endocrine Surgery , Churchill Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK
                [2 ]Academic Endocrine Unit , Radcliffe Department of Medicine, University of Oxford, Oxford, UK
                Author notes
                Correspondence should be addressed to R Mihai; Email: radumihai@ 123456doctors.org.uk
                Author information
                http://orcid.org/0000-0001-6153-1970
                Article
                EJE-20-1367
                10.1530/EJE-20-1367
                8052514
                33599211
                3bb630ee-e231-4ae6-ad81-e5452a16f97f
                © 2021 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 27 November 2020
                : 17 February 2021
                Categories
                Review

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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