Determinants and clinical significance of negative scintigraphic findings in primary hyperparathyroidism: a retrospective observational study

Abstract

Aim In patients with recurrent primary hyperparathyroidism (pHPT) or preceding thyroid operation, scintigraphic localization of the pathological parathyroid gland is sometimes unsuccessful. Reason for diagnostic failure, and its clinical relevance is poorly understood.

Methods This retrospective observational study in patients suffering from a pHPT evaluated independent predictors of a negative preoperative scintigraphy (SC) result, and its relevance for intraoperative outcome using logistic regression analysis.

Results Among 86 pHPT patients scheduled for parathyroid operation, 63 (73%) had a history of a preceding thyroid or parathyroid operation. Preoperative SC could not identify an adenoma in 30 patients (34.9%), and in 12 patients (14.0%), the surgeon was subsequently unable to localize abnormal parathyroid tissue. Preoperative parathyroid hormone concentration was the only significant independent predictor of a negative SC finding (non-linear and indirect association). Independent from surgical history, an unsuccessful intraoperative focus localization was exclusively predicted by preoperative ultrasonographic (US) and SC findings (OR per diagnostic category 2.98; 95%-CI 1.03–8.58, p=0.043, and OR 2.26; 95%-CI: 1.10–4.63, p=0.027, respectively). Compared to exclusive US, however, the combination of SC and US significantly increased the sensitivity and predictive power to identify patients at a high risk for a complicated surgical procedure.

Conclusion In patients before parathyroidectomy, a low preoperative parathyroid hormone concentration is significantly associated with a high likelihood for a negative SC finding. Combining US with SC before operation significantly increases the chance to identify patients prone to negative intraoperative findings.

Zusammenfassung

Ziel Bei Patienten mit rezidivierendem primärem Hyperparathyreoidismus (pHPT) oder vorangegangenen Schilddrüsenoperationen ist die szintigrafische (SZ) Lokalisierung der pathologischen Nebenschilddrüse manchmal erfolglos. Die Gründe dafür und die klinische Relevanz dieses Befundes sind nur unzureichend bekannt.

Methoden In dieser retrospektiven Beobachtungsstudie wurden unabhängige Prädiktoren für ein negatives präoperatives SZ Ergebnis und dessen Bedeutung für das intraoperative Ergebnis anhand von logistischen Regressionsanalysen untersucht.

Ergebnisse Bei 30 (34,9%) von 86 pHPT Patienten konnte präoperativ mittels SZ kein Adenom festgestellt werden, und bei 12 Patienten (14,0%) gelang es intraoperativ nicht, abnormales Nebenschilddrüsengewebe zu lokalisieren. Die präoperative Parathormonkonzentration war der einzige signifikante unabhängige Prädiktor für einen negativen SZ Befund (nicht-linearer indirekter Zusammenhang). Eine erfolglose intraoperative Fokuslokalisation wurde ausschließlich durch präoperativen Ultraschall (US)- und SZ-Befunde vorhergesagt (OR pro diagnostische Kategorie 2.98; 95%-CI 1.03–8.58, p=0.043 bzw. OR 2.26; 95%-CI: 1.10 4.63, p=0.027). Im Vergleich zum ausschließlichen US erhöhte der kombinierte Einsatz von SZ und US jedoch die Chance signifikant, Patienten mit hohem Risiko für einen negativen intraoperativen Befund zu identifizieren.

Schlussfolgerung Bei Patienten vor Parathyreoidektomie ist eine niedrige präoperative Parathormonkonzentration signifikant mit einer hohen Wahrscheinlichkeit für einen negativen SZ Befund assoziiert. Die präoperative Kombination von US und SZ erhöht die Wahrscheinlichkeit, Patienten zu identifizieren, bei denen ein negativer intraoperativer Befund zu erwarten ist, erheblich.

Schlüsselwörter

primärer Hyperparathyreoidismus - Nebenschilddrüsenszintigrafie - Parathyreoidektomie - Nebenschilddrüsenultraschall - Parathormon - Nebenschilddrüsenadenom

Keywords

primary hyperparathyroidism - parathyroid scintigraphy - parathyroidectomy - parathyroid ultrasonography - parathyroid hormone - parathyroid adenoma

Publication History

Received: 27 January 2022

Accepted after revision: 01 June 2022

Article published online:
29 July 2022

• References

• 1 Chirurgische Arbeitsgemeinschaft Endokrinologie (CAEK) der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). S2k-Leitlinie: Operative Therapie des primären und renalen Hyperparathyreoidismus. AWMF LL-Nr. 088–009. https://www.awmf.org/uploads/tx_szleitlinien/088–009l_S2k_Operative-Therapie-des-primaeren-und-renalen-Hyperparathyreoidismus_2021–02.pdf 2020
• 2 Ruda JM, Hollenbeak CS, Stack BC. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg 2005; 132: 359-372
• 3 Haciyanli M, Lal G, Morita E. et al. Accuracy of preoperative localization studies and intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism and double adenoma. J Am Coll Surg 2003; 197: 739-746
• 4 Erbil Y, Barbaros U, Yanik BT. et al. Impact of gland morphology and concomitant thyroid nodules on preoperative localization of parathyroid adenomas. Laryngoscope 2006; 116: 580-585
• 5 Siperstein A, Berber E, Barbosa GF. et al. Predicting the success of limited exploration for primary hyperparathyroidism using ultrasound, sestamibi, and intraoperative parathyroid hormone: analysis of 1158 cases. Ann Surg 2008; 248: 420-428
• 6 Treglia G, Trimboli P, Huellner M. et al. Imaging in primary hyperparathyroidism: focus on the evidence-based diagnostic performance of different methods. Minerva Endocrinol 2018; 43: 133-143
• 7 Mehta NY, Ruda JM, Kapadia S. et al. Relationship of technetium Tc 99m sestamibi scans to histopathological features of hyperfunctioning parathyroid tissue. Arch Otolaryngol Head Neck Surg 2005; 131: 493-498
• 8 Lumachi F, Marzola MC, Zucchetta P. et al. Hyperfunctioning parathyroid tumours in patients with thyroid nodules. Sensitivity and positive predictive value of high-resolution ultrasonography and 99mTc-sestamibi scintigraphy. Endocr Relat Cancer 2003; 10: 419-423
• 9 Pinero A, Rodriguez JM, Ortiz S. et al. Relation of biochemical, cytologic, and morphologic parameters to the result of gammagraphy with technetium 99m sestamibi in primary hyperparathyroidism. Otolaryngol Head Neck Surg 2000; 122: 851-855
• 10 Krausz Y, Lebensart PD, Klein M. et al. Preoperative localization of parathyroid adenoma in patients with concomitant thyroid nodular disease. World J Surg 2000; 24: 1573-1578
• 11 Beus KS, Stack BC. Synchronous thyroid pathology in patients presenting with primary hyperparathyroidism. Am J Otolaryngol 2004; 25: 308-312
• 12 Peduzzi P, Concato J, Kemper E. et al. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 1996; 49: 1373-1379
• 13 Rao D, Bhadada S, Parfitt A. Parathyroid growth: normal and abnormal. In: Bilezikian JP, Marcus R, MA L. The Parathyroids. 3rd. Aufl. San Diego CA: Academic Press (Elsevier); 2016: 255-272
• 14 Caveny SA, Klingensmith WC, Martin WE. et al. Parathyroid imaging: the importance of dual-radiopharmaceutical simultaneous acquisition with 99mTc-sestamibi and 123I. J Nucl Med Technol 2012; 40: 104-110
• 15 Uludag M, Aygun N, Isgor A. Main Surgical Principles and Methods in Surgical Treatment of Primary Hyperparathyroidism. Sisli Etfal Hastan Tip Bul 2019; 53: 337-352
• 16 Bhangu JS, Riss P. The role of intraoperative parathyroid hormone (IOPTH) determination for identification and surgical strategy of sporadic multiglandular disease in primary hyperparathyroidism (pHPT). Best Pract Res Clin Endocrinol Metab 2019; 33: 101310
• 17 Hosmer DW, David W, Hosmer SL. et al. Applied Survival Analysis: Time-to-Event. Wiley; 1999
• 18 Hosmer DW, Lemeshow S. Applied logistic regression. New York: Wiley; 1989
• 19 Scott-Coombes DM, Rees J, Jones G. et al. Is Unilateral Neck Surgery Feasible in Patients with Sporadic Primary Hyperparathyroidism and Double Negative Localisation?. World J Surg 2017; 41: 1494-1499
• 20 Udelsman R, Donovan PI. Remedial parathyroid surgery: changing trends in 130 consecutive cases. Ann Surg 2006; 244: 471-479
• 21 Hessman O, Stalberg P, Sundin A. et al. High success rate of parathyroid reoperation may be achieved with improved localization diagnosis. World J Surg 2008; 32: 774-781
• 22 Bagul A, Patel HP, Chadwick D. et al. Primary hyperparathyroidism: an analysis of failure of parathyroidectomy. World J Surg 2014; 38: 534-541
• 23 Allendorf J, Kim L, Chabot J. et al. The impact of sestamibi scanning on the outcome of parathyroid surgery. J Clin Endocrinol Metab 2003; 88: 3015-3018
• 24 Bergenfelz AO, Wallin G, Jansson S. et al. Results of surgery for sporadic primary hyperparathyroidism in patients with preoperatively negative sestamibi scintigraphy and ultrasound. Langenbecks Arch Surg 2011; 396: 83-90
• 25 Cron DC, Kapeles SR, Andraska EA. et al. Predictors of operative failure in parathyroidectomy for primary hyperparathyroidism. Am J Surg 2017; 214: 509-514
• 26 Ozdemir E, Genc M, Aydos U. et al. Comparison of (99m)Tc-MIBI planar scintigraphy, SPET/CT and ultrasonography in detection of parathyroid adenoma in patients with primary hyperparathyroidism. Hell J Nucl Med 2020; 23: 21-26