Evidence - Heterotopic parathyroid autotransplantation in total parathyroidectomy

  1. Literature summary

    Since the initial publication (Mandl, Vienna) in the 1930s, bilateral cervical exploration has become the procedure of choice. With sufficient experience the healing rate in primary procedures is more than 95%, with only minimum morbidity.

    The treatment aims to normalize, completely and long-term, the serum calcium in one operation and without any morbidity.

    Once the thyroid has been exposed, the first goal is to expose the recurrent laryngeal nerve and the inferior thyroid artery. The nerve is best exposed inferior to the artery and then followed to where the former terminates in the larynx. In most cases, the nerve is situated anterior to the artery. In bilateral cervical exploration, parathyroid excision before the nerve has been exposed is not permitted.

    The systematic search for the parathyroids should start with the superior glands. Most superior parathyroids are almost always superior to the inferior thyroid artery and posterior to the recurrent laryngeal nerve. If this is not the case, then check whether it is situated posteriorly on the spine next to the esophagus and in the direction of the posterior mediastinum. The location of the inferior parathyroids is more varied. The inferior parathyroids are located inferior to the inferior thyroid artery and anterior to the recurrent laryngeal nerve.

    If 4 parathyroids have been exposed, with only one gland being enlarged, the latter is excised and the diagnosis confirmed by fresh frozen section. The presence of two adenomas is rare (2-6%). If three or more parathyroids are enlarged, the excision of 3½ glands is recommended, once familial hyperparathyroidism and MEN syndrome have been ruled out for certain. The residual parathyroid tissue is marked with a metal clip.

    Improved results of preoperative diagnostic procedures for adenoma location and the option of intraoperative PTH measurements (Quick PTH assay) allow for minimally invasive surgery; however, the significance of the intraoperative Quick PTH assay has not been established for certain and in trials improves surgical success only by 1%.

    In many cases, revision operations for persistent or recurrent hyperparathyroidism are extremely difficult, time-consuming and should only be performed by surgeons experienced in parathyroid surgery. To document the success of the procedure, determine the serum calcium level on postoperative day 1 and verify the function of the vocal cords.

    Parathyroid scintiscan studies further substantiating the ultrasound findings are indicated primarily in persistent or recurrent hyperparathyroidism, suspected ectopia or planned minimally invasive surgery.

    In some trials, MRI and CT studies have demonstrated mostly good results, but are considered supplementary modalities for special cases.

    Most parathyroid adenomas may be located by imaging modalities. Problems arise whenever there are hypoechoic thyroid masses as well, because quite often these cannot be differentiated from the parathyroid adenomas. Standard imaging modalities often cannot locate such adenomas.

    In these cases, the parathyroid adenomas may be located by parathyroid scintiscanning.

    This modality combines Tc pertechnetate thyroid scintiscanning with a TL-chlorite scintiscan immediate before or after. The application of optimized SPECT allows the detection of very small masses (0.3-1 grams) of parathyroid adenoma with a sensitivity of 95%.

    The standard procedure for hyperparathyroidism comprises bilateral cervical exploration, identification of all four parathyroids and the excision of all pathologic parathyroid tissue. New localization modalities such as Tc sestamibi scintiscanning, combined high-resolution and color duplex ultrasonography, and intraoperative study of the intact PTH allow selective surgery without having to explore all parathyroid glands.

    Up until the 1980s the standard procedure was open bilateral cervical exploration, exposing all four parathyroids via a Kocher/collar incision. This resulted in healing rates of 92%-99%, surgical morbidity of 1%-3% and a late recurrence rate of less than 3%. Very few mortalities have been reported in the literature. Despite these outstanding results, progress in preoperative location work-up by high-resolution ultrasonography and Tc methoxyisobutylisonitrile scintiscanning has triggered attempts to minimize the procedure by specific unilateral exploration via various access routes, which improves the results even further. Shorter operating time, shorter length of stay in the hospital and therefore lower costs are arguments favoring specific, and possibly minimally invasive, exploration.

    However, since 10%-20% of patients with disorders of more than one gland suffer from hyperplasia of all four parathyroids or two adenomas, which are only detected inadequately in the preoperative location work-up, specific limited exploration mandates optimum preoperative location work-up and functional intraoperative verification of success. Preoperative diagnostic work-up usually comprises high-resolution ultrasonography and MIBI scintiscanning. While these modalities can correctly locate a solitary parathyroid adenoma in 60% and 90% of cases respectively, multiple adenomas as such are detected in less than 20% of patients. PTH monitoring permits specific unilateral exploration in primary hyperparathyroidism with the same success rates as in bilateral exploration and is the foundation for minimally invasive surgery.

  2. Current trials

  3. References on this topic

    Niederle BE, Schmidt G, Organ CH,et al. Albert J and his surgeon: a historical reevaluation of the first parathyroidectomy. J Am coll Surg. 2006;202(1):181–90

    Lundgren E, et al. Population-based screening for primary hyperparathyroidism with serum calcium and parathyroid homone values in menopausal women. Surgery. 1997;121:287–94

    Chan AK, Duh QY, Katz MH, et al. Clinical manifestations of primary hyperparathyreoidism before and after parathyroidectomy. A case-control study. Ann Sur. 1995;222:402–12

    Weber T, Dotzenrath C, Dralle H, et al. Management of primary and renal hyperparathyroidism: guidelines from  the German Association of Endocrine Surgeons (CAEK). Langenbecks Arch Surg. 2021 May; 406(3):571–585.

    Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016 Oct 1;151(10):959–68.

    Khan AA, Hanley DA, Rizzoli R, et al. Primary Hyperparathyroidism: review and recommendations on evaluation, diagnosis and management. A Canadian and international consensus. Osteoporos Int. 2017 Jan; 28(1):1–19

    Walker MD, Silverberg SJ. Primary Hyperparathyroidism. Nat Rev Endocrinol. 2018; 14(2):115–25.

    Udelsman R, Akerström G, Biagini C, et al. The surgical management of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014 Oct;99(10):3595–606.

    Yu N, Donnan PT, Leese GP. A record linkage study of outcomes in patients with mild primary hyperthyroidism: The Parathyroid Epidemiology and Research Study (PEARS). Clin Endocrinol (Oxf) 2011 Aug; 75(2):169–76.

    Yu N, Leese GP. What predicts adverse outcomes in untreated primary hyperparathyroidism? The Parathyroid Epidemiology and Research Study (PEARS). Clin Endocrinol (Oxf) 2013 Jul;79(1):27–34

    Zanocco K, Angelos P, Sturgeon C. Cost-effectiveness analysis of parathyroidectomy for asymptomatic primary hyperparathyroidism. Surgery. 2006;140(6):874–81.

    Scott-Coombes DM, Rees J, Jones G, et al. Is unilateral neck surgery feasible in patients with sporadic primary hyperparathyroidism and double negative localization? World J Surg. 2017 Jun;41(6):1494–9.

    Cheung K, Wang TS, Farrokhyar F, et al. A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism. Ann Surg Oncol. 2012;19(2):577–83.

    Treglia G, Piccardo A, Imperiale A, et al. Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):751–65.

    Abdulla AG, Iduarte PH, Hariri A, et al.Trends in the frequency and quality of parathyroid surgery: analysis of 17,082 cases over 10 years. Ann Surg. 2015;261(4):746–750.

    McCoy KL, Chen NH, Armstrong NJ, et al. The small abnormal parathyroid gland is increasingly common and heralds operative complexity. World J Surg 2014;38(6):1274–1281.

    Kebebew E, Hwang J, Reiff E, et al. Predictors of single-gland vs. Multigland parathyroid disease in primary hyperparathyroidism: a simple and accurate scoring model. Arch Surg. 2006;141(8):777–82

    Spartalis E, Ntokos G, Georgiou K, et al. Intraoperative Indocyanine Green (ICG) Angiography for the Identification of the Parathyroid Glands: Current Evidence and Future Perspectives. In Vivo. 2020;34:23–32

    Kovatcheva R, Vlahov J, Stoinov J, et al. US-guided, high-frequency ultrasound as a promising non-invasive method for treatment of primary hyperparathyroidism. Eur Radiol. 2014 Sep;24(9):2052–8.

    Imbus Jr, Randle RW, Pitt SC, et al. Machine learning to identify multigland disease in primary hyperparathyroidism. J Surg Res. 2017 Nov;219:173–9.

Reviews

Ahmadieh H, Kreidieh O, Akl EA, El-Hajj Fuleihan G. Minimally invasive parathyroidectomy guided by

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