Use of Calcium and Parathyroid Hormone Nomogram to Distinguish Between Atypical Primary Hyperparathyroidism and Normal Patients

Abstract

Background

The diagnosis of primary hyperparathyroidism (1°HP) has become more complex, as fewer patients present with classic phenotype of concomitant elevation of calcium and parathyroid hormone (PTH). In addition, the distinction between normal versus abnormal patients is challenging, with an increasing number of patients with 1°HP, who have calcium and/or PTH values within the “reference” range. Patients with “inappropriately” elevated PTH values relative to their serum calcium are considered to have 1°HP.

Methods

The study population consisted of 1753 patients with pathologically proven 1°HP and 74 healthy control patients. Nomograms were created by plotting PTH versus calcium of the two groups. The 95 % confidence zone of calcium and PTH for normal individuals was plotted and compared to patients with 1°HP.

Results

The comparison of control and disease groups showed a clear demarcation zone on the plots of calcium versus PTH. In the group of 1°HP, 70 % had classic 1°HP presentation with the concomitant elevation of both calcium (≥10.5 mg/dL) and PTH (≥65 pg/dL). 21 % had “normocalcemic” HP with calcium ≤10.5 mg/dL and PTH ≥65 pg/dL. 6 % had “normohormonal” HP with calcium ≥10.5 mg/dL and PTH ≤65 pg/dL. 3 % had both calcium and PTH within the reference range. 68.5 % of patients had single adenoma, 16 % double adenoma, and 15.5 % hyperplasia.

Conclusion

This nomogram serves as a diagnostic tool to distinguish normal patients from those with 1°HP, particularly those with atypical presentations. This recognition would permit previously observed patients to benefit from curative surgery.

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References

  1. 1.

    Nauck MA, Meier JJ (2012) Diagnostic accuracy of an “amended” insulin-glucose ratio for the biochemical diagnosis of insulinomas. Ann Intern Med 157(11):767–775

    Article  PubMed  Google Scholar 

  2. 2.

    AACE/AAES Task Force on Primary Hyperparathyroidism (2005) The american association of clinical endocrinologists and the american association of endocrine surgeons position statement on the diagnosis and management of primary hyperparathyroidism. Endocr Pract 11(1):49–54

    Article  Google Scholar 

  3. 3.

    Siperstein A, Berber E, Barbosa GF et al (2008) Predicting the success of limited exploration for primary hyperparathyroidism using ultrasound, sestamibi, and intraoperative parathyroid hormone: Analysis of 1158 cases. Ann Surg 248(3):420–428

    PubMed  Google Scholar 

  4. 4.

    Press DM, Siperstein AE, Berber E et al (2013) The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record. Surgery 154(6):1232–1237 (discussion 1237–8)

    Article  PubMed  Google Scholar 

  5. 5.

    Barczynski M, Branstrom R, Dionigi G, Mihai R (2015) Sporadic multiple parathyroid gland disease-a consensus report of the european society of endocrine surgeons (ESES). Langenbecks Arch Surg 400(8):887–905

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Jin J, Mitchell J, Shin J, Berber E, Siperstein AE, Milas M (2012) Calculating an individual maxPTH to aid diagnosis of normocalemic primary hyperparathyroidism. Surgery 152(6):1184–1192

    Article  PubMed  Google Scholar 

  7. 7.

    Wallace LB, Parikh RT, Ross LV et al (2011) The phenotype of primary hyperparathyroidism with normal parathyroid hormone levels: How low can parathyroid hormone go? Surgery 150(6):1102–1112

    Article  PubMed  Google Scholar 

  8. 8.

    Dalemo S, Hjerpe P, Bostrom Bengtsson K (2006) Diagnosis of patients with raised serum calcium level in primary care, Sweden. Scand J Prim Health Care 24(3):160–165

    Article  PubMed  Google Scholar 

  9. 9.

    Harvey A, Hu M, Gupta M et al (2012) A new, vitamin D-based, multidimensional nomogram for the diagnosis of primary hyperparathyroidism. Endocr Pract. 18(2):124–131

    Article  PubMed  Google Scholar 

  10. 10.

    Mayer GP, Hurst JG (1978) Sigmoidal relationship between parathyroid hormone secretion rate and plasma calcium concentration in calves. Endocrinology 102(4):1036–1042

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    O’Neill SS, Gordon CJ, Guo R, Zhu H, McCudden CR (2011) Multivariate analysis of clinical, demographic, and laboratory data for classification of disorders of calcium homeostasis. Am J Clin Pathol 135(1):100–107

    Article  PubMed  Google Scholar 

  12. 12.

    Norman J, Goodman A, Politz D (2011) Calcium, parathyroid hormone, and vitamin D in patients with primary hyperparathyroidism: normograms developed from 10,000 cases. Endocr Pract. 17(3):384–394

    Article  PubMed  Google Scholar 

  13. 13.

    Milas M, Wagner K, Easley KA, Siperstein A, Weber CJ (2003) Double adenomas revisited: nonuniform distribution favors enlarged superior parathyroids (fourth pouch disease). Surgery 134(6):995–1003 (discussion 1003-4)

    Article  PubMed  Google Scholar 

  14. 14.

    Thier M, Nordenstrom E, Bergenfelz A, Almquist M (2015) Presentation and outcomes after surgery for primary hyperparathyroidism during an 18-year period. World J Surg 40(2):356–364

    Article  Google Scholar 

  15. 15.

    Almquist M, Bergenfelz A, Martensson H, Thier M, Nordenstrom E (2010) Changing biochemical presentation of primary hyperparathyroidism. Langenbecks Arch Surg. 395(7):925–928

    Article  PubMed  Google Scholar 

  16. 16.

    Aloia JF, Feuerman M, Yeh JK (2006) Reference range for serum parathyroid hormone. Endocr Pract 12(2):137–144

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Rolighed L, Rejnmark L, Sikjaer T et al (2014) Vitamin D treatment in primary hyperparathyroidism: A randomized placebo controlled trial. J Clin Endocrinol Metab 99(3):1072–1080

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Allan E. Siperstein.

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Lavryk, O.A., Siperstein, A.E. Use of Calcium and Parathyroid Hormone Nomogram to Distinguish Between Atypical Primary Hyperparathyroidism and Normal Patients. World J Surg 41, 122–128 (2017). https://doi.org/10.1007/s00268-016-3716-6

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Keywords

  • Reference Range
  • Primary Hyperparathyroidism
  • Bilateral Neck Exploration
  • Single Adenoma
  • Parathyroid Disease