Langenbeck's Archives of Surgery

, Volume 403, Issue 3, pp 317–323 | Cite as

Is parathyroidectomy safe and effective in patients with normocalcemic primary hyperparathyroidism?

  • Emanuela Traini
  • Rocco Bellantone
  • Serena Elisa Tempera
  • Salvatore Russo
  • Carmela De Crea
  • Celestino Pio Lombardi
  • Marco Raffaelli



Indications and advantages of parathyroidectomy in patients with normocalcemic primary hyperparathyroidism (NHPT) are still matter of debate. We aimed to compare clinical presentation and surgical outcome between normocalcemic and hypercalcemic forms in a consecutive series of patients who underwent parathyroidectomy for primary hyperparathyroidism.


Data of 731 consecutive patients were reviewed and retrospectively compared according to normocalcemic (group A) and hypercalcemic (group B) phenotypes.


No significant differences were found between the two groups concerning demographics and symptomatic onset. Mean preoperative PTH levels were significantly higher in group B (252.0 ± 320.7 pg/ml vs 151.7 ± 112.0; p < 0.001). Mean PTH levels in first postoperative day were significantly lower in group B (30.9 ± 26.2 vs 22.7 ± 20.7; p < 0.001). No significant difference in overall accuracy of preoperative imaging studies was found. Significantly more patients in group A underwent bilateral explorations (83 vs 255; p < 0.05). The rate of multigland disease was significantly higher in group A (13.0 vs 6.8%; p < 0.05). At a mean follow-up period of 72.9 ± 46.8 months, all but three patients, among the 96 of group A who completed follow-up evaluation, were biochemically cured. The remaining patients had persistent high PTH values. Among NHPT patients who had target organ disease before parathyroidectomy, improvement in bone density and in kidney stones was observed in 41.7 and 40.0%, and stability in 50.0 and 60.0% respectively.


In normocalcemic patients, parathyroidectomy is as safe and effective as in hypercalcemic patients. In the presence of symptoms and/or target organ disease, parathyroidectomy may have a positive effect on the outcome of NHPT patients.


Hyperparathyroidism Normocalcemic Parathyroidectomy Outcome 


Authors’ contribution

Study conception and design: E Traini, M Raffaelli, CP Lombardi, and R Bellantone. Acquisition of the data: SE Tempera and S Russo. Analysis and interpretation of data: E Traini, M Raffaelli, C De Crea, and SE Tempera. Drafting of manuscript: E Traini, M Raffaelli, SE Tempera, and S Russo. Critical revision of manuscript: R Bellantone, CP Lombardi, and C De Crea.


The present study was in part supported by financial research contributions from the Università Cattolica del Sacro Cuore (Linea D1-2017, code R4124500587).

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Monchik JM (1995) Normocalcemic hyperparathyroidism. Surgery 118(6):917–923. CrossRefPubMedGoogle Scholar
  2. 2.
    Siperstein AE, Shen W, Chan AK, Duh QY, Clark OH (1992) Normocalcemic hyperparathyroidism biochemical and symptom profiles before and after surgery. Arch Surg 127(10):1157–1156 discussion 1161-1153 CrossRefPubMedGoogle Scholar
  3. 3.
    Lundgren E, Rastad J, Thrufjell E, Akerstrom G, Ljunghall S (1997) Population-based screening for primary hyperparathyroidism with serum calcium and parathyroid hormone values in menopausal women. Surgery 121(3):287–294. CrossRefPubMedGoogle Scholar
  4. 4.
    Cusano NE, Silverberg SJ, Bilezikian JP (2013) Normocalcemic primary hyperparathyroidism. J Clin Densitom 16(1):33–39. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kontogeorgos G, Trimpou P, Laine CM, Olerod G, Lindahl A, Landin-Wilhelmsen K (2015) Normocalcaemic, vitamin D-sufficient hyperparathyroidism - high prevalence and low morbidity in the general population: a long-term follow-up study, the WHO MONICA project, Gothenburg, Sweden. Clin Endocrinol 83(2):277–284. CrossRefGoogle Scholar
  6. 6.
    Berger C, Almohareb O, Langsetmo L, Hanley DA, Kovacs CS, Josse RG, Adachi JD, Prior JC, Towheed T, Davison KS, Kaiser SM, Brown JP, Goltzman D (2015) Characteristics of hyperparathyroid states in the Canadian multicentre osteoporosis study (CaMos) and relationship to skeletal markers. Clin Endocrinol 82(3):359–368. CrossRefGoogle Scholar
  7. 7.
    Bilezikian JP, Khan AA, Potts JT Jr (2009) Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop. J Clin Endocrinol Metab 94(2):335–339. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wilhelm SM, Wang TS, Ruan DT, Lee JA, Asa SL, Duh QY, Doherty GM, Herrera MF, Pasieka JL, Perrier ND, Silverberg SJ, Solorzano CC, Sturgeon C, Tublin ME, Udelsman R, Carty SE (2016) The American Association of Endocrine Surgeons Guidelines for definitive management of primary hyperparathyroidism. JAMA Surg 151(10):959–968. CrossRefPubMedGoogle Scholar
  9. 9.
    Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, Potts JT Jr (2014) Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab 99(10):3561–3569. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Khan AA, Hanley DA, Rizzoli R, Bollerslev J, Young JE, Rejnmark L, Thakker R, D'Amour P, Paul T, Van Uum S, Shrayyef MZ, Goltzman D, Kaiser S, Cusano NE, Bouillon R, Mosekilde L, Kung AW, Rao SD, Bhadada SK, Clarke BL, Liu J, Duh Q, Lewiecki EM, Bandeira F, Eastell R, Marcocci C, Silverberg SJ, Udelsman R, Davison KS, Potts JT Jr, Brandi ML, Bilezikian JP (2017) Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus. Osteoporos Int 28(1):1–19. CrossRefPubMedGoogle Scholar
  11. 11.
    Koumakis E, Souberbielle JC, Sarfati E, Meunier M, Maury E, Gallimard E, Borderie D, Kahan A, Cormier C (2013) Bone mineral density evolution after successful parathyroidectomy in patients with normocalcemic primary hyperparathyroidism. J Clin Endocrinol Metab 98(8):3213–3220. CrossRefPubMedGoogle Scholar
  12. 12.
    Wade TJ, Yen TW, Amin AL, Wang TS (2012) Surgical management of normocalcemic primary hyperparathyroidism. World J Surg 36(4):761–766. CrossRefPubMedGoogle Scholar
  13. 13.
    Amaral LM, Queiroz DC, Marques TF, Mendes M, Bandeira F (2012) Normocalcemic versus hypercalcemic primary hyperparathyroidism: more stone than bone? J Osteoporos 2012:128352–128354. PubMedPubMedCentralGoogle Scholar
  14. 14.
    Lombardi CP, Raffaelli M, Traini E, De Crea C, Corsello SM, Bellantone R (2009) Video-assisted minimally invasive parathyroidectomy: benefits and long-term results. World J Surg 33(11):2266–2281. CrossRefPubMedGoogle Scholar
  15. 15.
    Lombardi CP, Raffaelli M, Traini E, Di Stasio E, Carrozza C, De Crea C, Zuppi C, Bellantone R (2008) Intraoperative PTH monitoring during parathyroidectomy: the need for stricter criteria to detect multiglandular disease. Langenbeck's Arch Surg 393(5):639–645. CrossRefGoogle Scholar
  16. 16.
    Cusano NE, Maalouf NM, Wang PY, Zhang C, Cremers SC, Haney EM, Bauer DC, Orwoll ES, Bilezikian JP (2013) Normocalcemic hyperparathyroidism and hypoparathyroidism in two community-based nonreferral populations. J Clin Endocrinol Metab 98(7):2734–2741. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Garcia-Martin A, Reyes-Garcia R, Munoz-Torres M (2012) Normocalcemic primary hyperparathyroidism: one-year follow-up in one hundred postmenopausal women. Endocrine 42(3):764–766. CrossRefPubMedGoogle Scholar
  18. 18.
    Marques TF, Vasconcelos R, Diniz E, Rego D, Griz L, Bandeira F (2011) Normocalcemic primary hyperparathyroidism in clinical practice: an indolent condition or a silent threat? Arq Bras Endocrinol Metabol 55(5):314–317. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Vignali E, Cetani F, Chiavistelli S, Meola A, Saponaro F, Centoni R, Cianferotti L, Marcocci C (2015) Normocalcemic primary hyperparathyroidism: a survey in a small village of Southern Italy. Endocr Connect 4(3):172–178. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Berger C, Langsetmo L, Hanley, D, Hadachi J, Kovacs C, Brown J, Josse R, Goltzman D (2011) Relative prevalence of normocalcemic and hypercalcemic hyperparathyroidism in a community-dwelling cohort. Paper presented at the 33rd Annual Meeting of the American Society of Bone and Mineral Research, San Diego, CaliforniaGoogle Scholar
  21. 21.
    Maruani G, Hertig A, Paillard M, Houillier P (2003) Normocalcemic primary hyperparathyroidism: evidence for a generalized target-tissue resistance to parathyroid hormone. J Clin Endocrinol Metab 88(10):4641–4648. CrossRefPubMedGoogle Scholar
  22. 22.
    Chen G, Xue Y, Zhang Q, Xue T, Yao J, Huang H, Liang J, Li L, Lin W, Lin L, Shi L, Cai L, Wen J (2015) Is normocalcemic primary hyperparathyroidism harmful or harmless? J Clin Endocrinol Metab 100:2420–2424. CrossRefPubMedGoogle Scholar
  23. 23.
    Pawloska M, Cusano NE (2015) An overview of normocalcemic primary hyperparathyroidism. Diabetes Curr Opin Endocrinol Diabetes Obes 22(6):413–421. CrossRefGoogle Scholar
  24. 24.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911–1300. CrossRefPubMedGoogle Scholar
  25. 25.
    Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ (2007) Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype. J Clin Endocrinol Metab 92(8):3001–3005. CrossRefPubMedGoogle Scholar
  26. 26.
    Rao DS, Wilson RJ, Kleerekoper M, Parfitt AM (1988) Lack of biochemical progression or continuation of accelerated bone loss in mild asymptomatic primary hyperparathyroidism: evidence for biphasic disease course. J Clin Endocrinol Metab 67(6):1294–1298. CrossRefPubMedGoogle Scholar
  27. 27.
    De Crea C, Raffaelli M, Traini E, Giustozzi E, Oragano L, Bellantone R, Lombardi CP (2013) Is there a role for video-assisted parathyroidectomy in regions with high prevalence of goitre? Acta Otorhinolaryngol Ital 33(6):388–392PubMedGoogle Scholar
  28. 28.
    de la Plaza LR, Ramia Ángel JM, Arteaga Peralta V, García Amador C, López Marcano AJ, Medina Velasco AA, González Sierra B, Manuel Vázquez A, Latorre Fragua RA (2017) Elevated parathyroid hormone levels after successful parathyroidectomy for primary hyperparathyroidism: a clinical review. Eur Arch Otorhinolaryngol.
  29. 29.
    Rejnmark L, Vestergaard P, Mosekilde L (2011) Nephrolithiasis and renal calcifications in primary hyperparathyroidism. J Clin Endocrinol Metab 96(8):2377–2385. CrossRefPubMedGoogle Scholar
  30. 30.
    Suh JM, Cronan JJ, Monchik JM (2008) Primary hyperparathyroidism: is there an increased prevalence of renal stone disease? AJR Am J Roentgenol 191(3):908–911. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Endocrine and Metabolic Surgery, Fondazione Policlinico Universitario “A. Gemelli”Università Cattolica del Sacro CuoreRomeItaly

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