Occurrence of malignant neoplasia in patients with primary hyperparathyroidism

      Highlights

      • The risk of cancer in patients with primary hyperparathyroidism (1HPT) is discussed.
      • The cancer risk was evaluated in 163 patients with 1HPT and in 1443 controls.
      • During the 10 years before the study, the cancer risk was increased in 1HPT patients
      • Breast, kidney and skin cancer were the more frequent malignancies in 1HPT patients
      • The 1HPT diagnosis was associated with these cancers regardless for confounders.

      Abstract

      Introduction

      The association between primary hyperparathyroidism (1HPT) and cancer is debated. The present study was aimed to investigate the occurrence of neoplasia in 1HPT.

      Patients and methods

      All consecutive patients (n = 1750) referred to our “Osteoporosis and Metabolic Disease” outpatients clinic for osteoporosis or hypercalcemia were eligible for the study. The exclusion criteria were: the finding of osteoporosis and/or altered calcium-phosphorous metabolism in the context of investigations for malignancy, the presence of diseases known to influence the cancer risk and the heavy smoking habit. Eventually, 1606 patients (1407 females, 199 males) were enrolled. In all patients calcium-phosphorous metabolism, PTH and vitamin D levels were measured and the occurrence of cancer during the 10 years prior the study inclusion was recorded.

      Results

      One-hundred-sixty-three patients had 1HPT while 1443 had not. Patients with and without 1HPT were comparable for age and gender. In 1HPT patients the occurrence of all, breast, kidney and skin cancer was significantly higher (21.5%, 12.2%, 2.5%, 1.8%, respectively) than in patients without 1HPT (12.4%, 6.9%, 0.3%, 0.3%, p < 0.05 for all comparisons). The 1HPT presence was significantly associated with the occurrence of all neoplasia and of breast, skin and kidney neoplasia (odds ratio, 95% confidence interval, p value: 1.93, 1.27–2.92, 0.002; 1.93, 1.11–3.35, 0.002; 9.18, 2.16–38.8, 0.003; 8.23, 1.71–39.5, 0.008, respectively), after adjusting for age, gender (as appropriate), smoking habit and vitamin D levels.

      Conclusion

      During the 10 years prior the diagnosis of 1HPT, the occurrence of all, breast, skin and kidney neoplasia is increased.

      Keywords

      To read this article in full you will need to make a payment

      References

        • Marcocci C.
        • Cetani F.
        Clinical practice. Primary hyperparathyroidism.
        New Engl J Med. 2011; 365: 2389-2397
        • Fraser W.D.
        Hyperparathyroidism.
        Lancet. 2009; 374: 145-158
        • Bilezikian J.P.
        • Brandi M.L.
        • Eastell R.
        • Silverberg S.J.
        • Udelsman R.
        • Marcocci C.
        • et al.
        Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop.
        J Clin Endocrinol Metab. 2014; 99: 3561-3569
        • Silverberg S.J.
        • Clarke B.L.
        • Peacock M.
        • Bandeira F.
        • Boutroy S.
        • Cusano N.E.
        • et al.
        Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop.
        J Clin Endocrinol Metab. 2014; 99: 3580-3594
        • Goswami S.
        • Ghosh S.
        Hyperparathyroidism: cancer and mortality.
        Indian J Endocrinol Metab. 2012; 16: 217-220
        • Hedback G.
        • Tisell L.E.
        • Bengtsson B.A.
        • Hedman I.
        • Oden A.
        Premature death in patients operated on for primary hyperperathyroidism.
        World J Surg. 1990; 14: 829-836
        • Whitfield J.F.
        • MacManus J.P.
        • Youdale T.
        • Franks D.J.
        The roles of calcium and cyclic AMP in the stimulatory action of parathyroid hormone on thymic lymphocyte proliferation.
        J Cell Physiol. 1971; 78: 355-368
        • McCarty M.F.
        Parathyroid hormone may be a cancer promoter - an explanation for the decrease in cancer risk associated with ultraviolet light, calcium, and vitamin D.
        Med Hypoths. 2000; 54: 475-482
        • Pettway G.J.
        • Meganck J.A.
        • Koh A.J.
        • Keller E.T.
        • Goldstein S.A.
        • McCauley L.K.
        Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation.
        Bone. 2008; 42: 806-818
        • Palmér M.
        • Adami H.O.
        • Krusemo U.B.
        • Ljunghall S.
        Increased risk of malignant diseases after surgery for primary hyperparathyroidism – a nationwide cohort study.
        Am J Epidemiol. 1988; 127: 1031-1040
        • Pickard A.L.
        • Gridley G.
        • Mellemkjae L.
        • Johansen C.
        • Kofoed-Enevoldsen A.
        • Cantor K.P.
        • et al.
        Hyperparathyroidism and subsequent cancer risk in Denmark.
        Cancer. 2002; 95: 1611-1617
        • Øgard C.G1.
        • Engholm G.
        • Almdal T.P.
        • Vestergaard H.
        Increased mortality in patients hospitalised with primary hyperparathyroidism during the period 1977–1993 in Denmark.
        World J Surg. 2004; 28: 108-111
        • Nilsson I.L.
        • Zedenius J.
        • Yin L.
        • Ekbom A.
        The association between primary hyperparathyroidism and malignancy: nationwide cohort analysis on cancer incidence after parathyroidectomy.
        Endocr Relat Cancer. 2007; 14: 135-140
        • Palmér M.
        • Adami H.O.
        • Bergström R.
        • Akerström G.
        • Ljunghall S.
        Mortality after surgery for primary hyperparathyroidism: a follow-up of 441 patients operated on from 1956 to 1979.
        Surgery. 1987; 102: 1-7
        • Hedbäck G.
        • Odén A.
        • Tisell L.E.
        Parathyroid adenoma and the risk of death after treatment for primary hyperparathyroidism.
        Surgery. 1995; 117: 134-139
        • Cinamon U.
        • Levy D.
        • Marom T.
        Is primary hyperparathyroidism a risk factor for papillary thyroid cancer? An exemplar study and literature review.
        Int Arch Otorhinolaryngol. 2015; 19: 42-45
        • Söreide J.A.
        • van Heerden J.A.
        • Grant C.S.
        • Yau Lo C.
        • Schleck C.
        • Ilstrup D.M.
        Survival after surgical treatment for primary hyperparathyroidism.
        Surgery. 1997; 122: 1117-1123
        • Wermers R.A.
        • Khosla S.
        • Atkinson E.J.
        • Grant C.S.
        • Hodgson S.F.
        • O'Fallon W.M.
        • et al.
        Survival after the diagnosis of hyperparathyroidism: a population-based study.
        Am J Med. 1998; 104: 115-122
        • Eric P.
        • Cohen E.P.
        • Krzesinski J.M.
        • Launay-Vacher V.
        • Sprangers B.
        Onco-nephrology: core curriculum 2015.
        Am J Kidney Dis. 2015; 66: 869-883
        • Eller-Vainicher C.
        • Cairoli E.
        • Zhukouskaya V.V.
        • Morelli V.
        • Palmieri S.
        • Scillitani A.
        • et al.
        Prevalence of subclinical contributors to low bone mineral density and/or fragility fracture.
        Eur J Endocrinol. 2013; 169: 225-237
        • Vescini F.
        • Attanasio R.
        • Balestrieri A.
        • Bandeira F.
        • Bonadonna S.
        • Camozzi V.
        • et al.
        Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis.
        J Endocrinol Invest. 2016; 39: 807-834
        • Zeichner S.B.
        • Stanislaw C.
        • Meisel J.L.
        Prevention and screening in hereditary breast and ovarian cancer.
        Oncology (Williston Park). 2016; 30: 896-904
        • Klil-Drori A.J.
        • Azoulay L.
        • Pollak M.N.
        Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing?.
        Nat Rev Clin Oncol. 2016; 14: 85-99
        • Qian J.
        • Cai M.
        • Gao J.
        • Tang S.
        • Xu L.
        • Critchley J.A.
        Trends in smoking and quitting in China from 1993 to 2003: National Health Service Survey data.
        Bull World Health Organ. 2010; 88: 769-776
        • Jodkowska A.
        • Tupikowski K.
        • Szymczak J.
        • Bohdanowicz-Pawlak A.
        • Bolanowski M.
        • Bednarek-Tupikowska G.
        Interdisciplinary aspects of primary hyperparathyroidism: symptomatology in a series of 100 cases.
        Adv Clin Exp Med. 2016; 25: 285-293
      1. NIH Consens Statement. 2000; 17: 1-45
        • Ferrari S.
        • Bianchi M.L.
        • Eisman J.A.
        • Foldes A.J.
        • Adami S.
        • Wahl D.A.
        • et al.
        Osteoporosis in young adults: pathophysiology, diagnosis, and management.
        Osteoporos Int. 2012; 23: 2735-2748
        • Husten C.G.
        How should we define light or intermittent smoking? Does it matter?.
        Nicotine Tob Res. 2009; 11: 111-121
        • Rossini M.
        • Adami S.
        • Bertoldo F.
        • Diacinti D.
        • Gatti D.
        • Giannini S.
        • et al.
        Guidelines for the diagnosis, prevention and management of osteoporosis.
        Reumatismo. 2016; 68: 1-39
        • Eastell R.
        • Arnold A.
        • Brandi M.L.
        • Brown E.M.
        • D'Amour P.
        • Hanley D.A.
        • et al.
        Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Third International Workshop.
        J Clin Endocrinol Metab. 2009; 94: 340-350
        • Minisola S.
        • Pepe J.
        • Piemonte S.
        • Cipriani C.
        The diagnosis and management of hypercalcaemia.
        Br Med J. 2015; https://doi.org/10.1136/bmj.h2723
      2. UpToDate calculator. In Calcium correction in hypoalbuminemia, version 18.2. Waltham, MA: Wolters Kluwer-Health (available at: www.uptodate.com), 2010.

        • Genant H.K.
        • Wu C.Y.
        • van Kuijk C.
        • Nevitt M.C.
        Vertebral fracture assessment using a semi-quantitative technique.
        J Bone Miner Res. 1993; 8: 1137-1148
        • Cairoli E.
        • Eller-Vainicher C.
        • Ulivieri F.M.
        • Zhukouskaya V.V.
        • Palmieri S.
        • Morelli V.
        • et al.
        Factors associated with bisphosphonate treatment failure in postmenopausal women with primary osteoporosis.
        Osteoporos Int. 2014; 25: 1401-1410
        • Lin S.Y.
        • Lin W.M.
        • Lin C.L.
        • Yang T.Y.
        • Sung F.C.
        • Wang Y.H.
        • et al.
        The relationship between secondary hyperparathyroidism and thyroid cancer in end stage renal disease: a population based cohort study.
        Eur J Intern Med. 2014; 25: 276-280
        • Almquist M.
        • Manjer J.
        • Bondeson L.
        • Bondeson A.G.
        Serum calcium and breast cancer risk: results from a prospective cohort study of 7847 women.
        Cancer Causes Control. 2007; 18: 595-602
        • Li M.
        • Chen P.
        • Li J.
        • Chu R.
        • Xie D.
        • Wang H.
        Review: the impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: a systematic review and meta-analysis.
        J Clin Endocrinol Metab. 2014; 99: 2327-2336
        • Gandini S.
        • Gnagnarella P.
        • Serrano D.
        • Pasquali E.
        • Raimondi S.
        Vitamin D receptor polymorphisms and cancer.
        Adv Exp Med Biol. 2014; 810: 69-105