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Evidence - Exstirpation of a solitary parathyroid adenoma

  1. Summary of the Literature

    In approximately 75 - 90 % of cases, primary hyperparathyroidism (pHPT) is due to a solitary parathyroid adenoma (PT adenoma). While double adenomas are rather rare, hyperplasias of all four PTs are somewhat more common. The latter are predominantly genetically determined and occur with familial clustering. In < 1 % of cases, a PT carcinoma is present. With a prevalence of 0.2 - 0.4% in those over 60 years of age, pHPT is one of the three most common hormonally induced diseases in the population [1, 2, 3].

    Localization Diagnostics of PT Adenomas

    While bilateral neck exploration was common until about 20 years ago [4], focused surgical techniques are now in the foreground. Once the biochemical diagnosis of pHPT has been made, localization diagnostics follow.

    Ultrasound is the localization diagnostic tool of first choice, with which about 70 % of PT adenomas can be visualized [5]. Similarly good results can be achieved with Tc-99m-Methoxyisobutyl-Isonitrile(MIBI)-Scintigraphy. The informative value of scintigraphy can be further improved by using SPECT technology [6]. SPECT (Single Photon Emission Computed Tomography) combines gamma camera and computed tomography and enables three-dimensional imaging of the compartment to be examined. In contrast to ultrasound, scintigraphy can also visualize mediastinally located adenomas.

    The sensitivity of computed and magnetic resonance tomography is reported in the literature as 30 – 80 % and is thus below that of ultrasound and scintigraphy.

    With 11C-Methionine-Positron Emission Tomography(PET)-CT, a portion of PT adenomas can be localized that cannot be visualized with other imaging methods [7]. However, the procedure cannot be performed at the expense of statutory health insurance (as of: 2017).

    In selective venous blood sampling from the jugular veins, the brachiocephalic vein, and the superior vena cava, the determination of PTH concentration in the blood samples can contribute to narrowing down the adenoma localization if values are elevated. The procedure is not indicated for primary operations.

    Focused surgical techniques require ultrasound and, if necessary, scintigraphy; further examinations for adenoma localization must be viewed critically. Before a primary operation, the surgical indication for PT adenoma should not be made dependent on successful localization diagnostics. Exceptions are previous thyroid surgeries due to the increased surgical risk.

     

    Surgical Indication

    The surgical indication is given for all patients with classic symptoms and secondary diseases of pHPT. In supposedly asymptomatic patients, the indication is discussed controversially [8, 9]. According to the recommendations, asymptomatic patients should be operated on if

    • they are younger than 50 years or
    • have a calcium level of more than 0.25mmol/l above the upper normal value or
    • a creatinine clearance of less than 60ml/min or
    • a calcium excretion in the urine of more than 10mmol/day.

    The surgical indication should also be considered if

    • the bone density measurement yields a T-score of <  - 2.5,
    • a vertebral body fracture is present,
    • imaging diagnostics show asymptomatic kidney stones or nephrocalcinosis.

    In many supposedly asymptomatic patients, an improvement in quality of life is also observed after successful surgery [10]. If no surgery is performed, annual follow-up examinations are recommended (calcium level, bone density measurement, imaging diagnostics of the kidneys).

    Focused Surgical Technique

    This term encompasses various surgical techniques with which a preoperatively localized PT tumor is specifically sought and removed [11, 12, 13]. Preparation on the contralateral side with corresponding surgical risks and postoperative scarring is thus avoided.

    The previously common bilateral neck exploration with visualization of all four PTs is indicated in patients who likely have multigland disease, or if no PT adenoma could be localized preoperatively or there is no possibility to perform intraoperative PTH level measurement.

    Intraoperative PTH Determination

    To monitor the success of focused surgical techniques, intraoperative PTH determination is required. If no further adenoma is present, the PTH level drops within a few minutes after adenoma removal due to the short half-life of PTH. The procedure can be ended in these cases. If the PTH level does not drop, the contralateral side must be explored. According to the European Society of Endocrine Surgeons, intraoperative PTH determination can be dispensed with if the adenoma was localized preoperatively both with ultrasound and scintigraphy [14].

    Various recommendations exist for the interpretation of intraoperatively obtained PTH values [15], which relate to the timing of blood draws and the required PTH drop. In the USA, the “soft” Miami criteria are common (drop in PTH level after adenoma removal to < 50 % of the baseline value), in Germany, however, the “hard” Halle criteria (drop in PTH level < 35 pg/ml). With the Miami criteria, there is a risk of overlooking multigland disease, with the Halle criteria, the risk is greater of unnecessarily exploring the contralateral side.

  2. Currently ongoing studies on this topic

  3. Literature on this topic

    1. Jorde, R.; Bonaa, K.H.; Sundsfjord, J.: Primary hyperparathyroidism detected in a Health screening. The Tromso study. J Clin Epidemiol 53 (2000) 1164 - 1169

    2. Moalem, J.; Guerrero, M.; Kebebew, E.: Bilateral neck exploration in primary  hyperparathyroidism - When is it selected and how is it performed? World J Surg 33 (2009) 2282 - 2291 

    3. Wermers, R.A.; Khosla, S.; Atkinson, E.J.; Hodgson, S.F.; O'Fallon, W.M.; Melton,  L.J.: The rise and fall of primary hyperparathyroidism: a population-based study in Rochester, Minnesota, 1965 - 1992.  Ann Intern Med 126 (1997) 433 – 440

    4. Funke M, Kim M, Hasse Cetal (1997) Results of a standardized therapy concept in primary hyperparathyroidism. Dtsch MedWochenschr 122:1475–1481

    5. Cheung K, Wang TS, Farrokhyar F et al (2012) A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism. Ann Surg Oncol 19:577–583

    6. Thomas DL, Bartel T, Menda Y et al (2009) Single photon emission computed tomography (SPECT) should be routinely performed for the detection of parathyroid abnormalities utilizing technetium 99m-sestamibi parathyroid scintigraphy. ClinNucl Med 34:651–655

    7. Weber T, Gottstein M, Schwenzer S et al (2017) Is C-11 Methionine PET/CT able to localise sesta-mibi negative parathyroid adenomas. WorldJSurg41:980–981

    8. Third International Workshop on the Management of asymptomatic primary hyperparathyroidism, Bilezikian JO, Khan AA, Potts JT Jr (2009) Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop. J Clin EndocrinolMetab94:335–339

    9. Udelsman R, Akerström G, Biagini C et al (2014) the surgical management of asmptomatic primary hyperparathyroidism: proceedings of the fourth international workshop. J Clin Endocrinol Metab 99:3595–3606

    10. Dulfer R, Geilvoet W, Morks A et al (2016) Impact of parathyroidectomy for primary hyperparathyroidism on quality of life: a case-control study using short form health. Survey36. HeadNeck 38:1213–1220

    11. Miccoli P, Pinchera A, Cecchini G et al (1997) Minimally invasive, video-assisted parathyroid surgery for primary hyperparathyroidism. J Endocrinol Invest 20:429–430

    12. Henry JF, Defechereux T, Gramatica L, de Boissezon C (1999) Minimally invasive videoscopic parathyroidectomy by lateral approach. Langenbecks Arch Surg 384:298–301

    13. Bergenfelz A, Kanngiesser V, Zielke A et al (2005) Conventional bilateral cervical exploration versus open minimally invasive parathyroidectomy under local anaesthesia for primary hyperparathyroidism. BrJ Surg 92:190–197

    14. Barczynski M, Bränström R, Dionigi G, Mihai R (2015) Sporadic multiple gland disease –a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg 400:887–905

    15. Lorenz K, Dralle H (2010) Intraoperative parathyroid hormone determination in primary hyperparathyroidism. Chirurg 81:636–642

  4. Reviews

    Gosnell HL, Sadow PM. Preoperative, Intraoperative, and Postoperative Parathyroid Pathology: Clinical Pathologic Collaboration for Optimal Patient Management. Surg Pathol Clin. 2023 Mar;16(1):87-96. doi: 10.1016/j.path.2022.10.001. Epub 2022 Dec 9. Review.

    Patel DD, Bhattacharjee S, Pandey AK, Kopp CR, Ashwathanarayana AG, Patel HV, Barnabas R, Bhadada SK, Dodamani MH. Comparison of 4D computed tomography and F-18 fluorocholine PET for localisation of parathyroid lesions in primary hyperparathyroidism: A systematic review and meta-analysis. Clin Endocrinol (Oxf). 2023 Jan 2

    St Amour TC, Demarchi MS, Thomas G, Triponez F, Kiernan CM, Solόrzano CC. Educational Review: Intraoperative Parathyroid Fluorescence Detection Technology  in Thyroid and Parathyroid Surgery. Ann Surg Oncol. 2023 Feb;30(2):973-993.

    Lui MS, Shirali AS, Huang BL, Fisher SB, Perrier ND. Advances in Endocrine Surgery. Surg Oncol Clin N Am. 2023 Jan;32(1):199-220

    das Neves MC, Santos RO, Ohe MN. Surgery for primary hyperparathyroidism. Arch Endocrinol Metab. 2022 Nov 11;66(5):678-688. 

    Bandeira F, de Moura Nóbrega J, de Oliveira LB, Bilezikian J. Medical management of primary hyperparathyroidism. Arch Endocrinol Metab. 2022 Nov 11;66(5):689-693.

    Park HS, Hong N, Jeong JJ, Yun M, Rhee Y. Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism. Endocrinol Metab (Seoul). 2022Oct;37(5):744-755. 

  5. Guidelines

  6. literature search

    Literature search on the pages of pubmed.