The Natural History of Primary Hyperparathyroidism with or without Parathyroid Surgery after 15 Years

Journal of Clinical Endocrinology and Metabolism - Tập 93 Số 9 - Trang 3462-3470 - 2008
Mishaela R. Rubin1, John P. Bilezikian1,2, Donald J. McMahon1, Thomas P. Jacobs1, Elizabeth Shane1, Ethel S. Siris1, Julia Udesky1, Shonni J. Silverberg1
1Departments of Medicine (M.R.R., J.P.B., D.J.M., T.J., E.Sh., E.Si., J.U., S.J.S.), Columbia University, College of Physicians and Surgeons, New York, New York 10032
2Pharmacology (J.P.B.), Columbia University, College of Physicians and Surgeons, New York, New York 10032

Tóm tắt

Context: Primary hyperparathyroidism (PHPT) often presents without classical symptoms such as overt skeletal disease or nephrolithiasis. We previously reported that calciotropic indices and bone mineral density (BMD) are stable in untreated patients for up to a decade, whereas after parathyroidectomy, normalization of biochemistries and increases in BMD ensue. Objective: The objective of the study was to provide additional insights in patients with and without surgery for up to 15 yr. Design: The study had an observational design. Setting: The setting was a referral center. Patients: Patients included 116 patients (25 men, 91 women); 99 (85%) were asymptomatic. Intervention: Fifty-nine patients (51%) underwent parathyroidectomy and 57 patients were followed up without surgery. Main Outcome Measure: BMD was measured. Results: Lumbar spine BMD remained stable for 15 yr. However, BMD started to fall at cortical sites even before 10 yr, ultimately decreasing by 10 ± 3% (mean ± sem; P < 0.05) at the femoral neck, and 35 ± 5%; P < 0.05 at the distal radius, in the few patients observed for 15 yr. Thirty-seven percent of asymptomatic patients showed disease progression (one or more new guidelines for surgery) at any time point over the 15 yr. Meeting surgical criteria at baseline did not predict who would have progressive disease. BMD increases in patients who underwent surgery were sustained for the entire 15 yr. Conclusions: Parathyroidectomy led to normalization of biochemical indices and sustained increases in BMD. Without surgery, PHPT progressed in one third of individuals over 15 yr; meeting surgical criteria at the outset did not predict this progression. Cortical bone density decreased in the majority of subjects with additional observation time points and long-term follow-up. These results raise questions regarding how long patients with PHPT should be followed up without intervention.

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Tài liệu tham khảo

Albright, 1948

Heath 3rd, 1980, Primary hyperparathyroidism. Incidence, morbidity, and potential economic impact in a community., N Engl J Med, 302, 189, 10.1056/NEJM198001243020402

Silverberg, 1999, A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery., N Engl J Med, 341, 1249, 10.1056/NEJM199910213411701

NIH conference, 1991, Diagnosis and management of asymptomatic primary hyperparathyroidism: consensus development conference statement., Ann Intern Med, 114, 593, 10.7326/0003-4819-114-7-593

Locker, 1997, Optimal dietary calcium intake in primary hyperparathyroidism., Am J Med, 102, 543, 10.1016/S0002-9343(97)00053-3

Nussbaum, 1987, Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia., Clin Chem, 33, 1364, 10.1093/clinchem/33.8.1364

Silverberg, 1989, Skeletal disease in primary hyperparathyroidism., J Bone Miner Res, 4, 283, 10.1002/jbmr.5650040302

Parfitt, 1990, Interpretation of bone densitometry measurements: disadvantages of a percentage scale and a discussion of some alternatives., J Bone Miner Res, 5, 537, 10.1002/jbmr.5650050602

Fang, 2002, Retrospective evaluation and adjustment of dual energy X-ray absorptiometry measurements for bone mineral density research studies., J Clin Densitom, 5, 421, 10.1385/JCD:5:4:421

Faulkner, 1995, Quality control of DXA instruments in multicenter trials., Osteoporos Int, 5, 218, 10.1007/BF01774010

Liang, 1986, Longitudinal data analysis using generalized linear models., Biometrika, 73, 13, 10.1093/biomet/73.1.13

Kenward, 1997, Small sample inference for fixed effects from restricted maximum likelihood., Biometrics, 53, 983, 10.2307/2533558

Eriksen, 1986, Trabecular bone remodeling and balance in primary hyperparathyroidism., Bone, 7, 213, 10.1016/8756-3282(86)90020-7

Dempster, 1999, On the mechanism of cancellous bone preservation in postmenopausal women with mild primary hyperparathyroidism., J Clin Endocrinol Metab, 84, 1562

Parisien, 1992, Maintenance of cancellous bone connectivity in primary hyperparathyroidism: trabecular strut analysis., J Bone Miner Res, 7, 913, 10.1002/jbmr.5650070808

Parisien, 1990, The histomorphometry of bone in primary hyperparathyroidism: preservation of cancellous bone structure., J Clin Endocrinol Metab, 70, 930, 10.1210/jcem-70-4-930

Parfitt, 1986, Accelerated cortical loss: primary and secondary hyperparathyroidism, In: Uhthoff H, Stahl E, eds. Current concepts of bone fragility. Berlin: Springer-Verlag;, 279, 10.1007/978-3-642-70709-4_25

Rao, 2003, Forearm bone density in primary hyperparathyroidism: long-term follow-up with and without parathyroidectomy., Clin Endocrinol (Oxf), 58, 348, 10.1046/j.1365-2265.2003.01722.x

Leppla, 1982, Sequential changes in bone density before and after parathyroidectomy in primary hyperparathyroidism., Invest Radiol, 17, 604, 10.1097/00004424-198211000-00013

Parfitt, 1991, Asymptomatic primary hyperparathyroidism discovered by multichannel biochemical screening: clinical course and considerations bearing on the need for surgical intervention, J Bone Miner Res, 6, S97

Elvius, 1995, Seventeen year follow-up study of bone mass in patients with mild asymptomatic hyperparathyroidism some of whom were operated on, Eur J, Surg161, 863

Rao, 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, 1294, 10.1210/jcem-67-6-1294

Silverberg, 2003, “Incipient” primary hyperparathyroidism: a “forme fruste” of an old disease., J Clin Endocrinol Metab, 88, 5348, 10.1210/jc.2003-031014

Bilezikian, 2004, Clinical practice. Asymptomatic primary hyperparathyroidism., N Engl J Med, 350, 1746, 10.1056/NEJMcp032200

Bilezikian, 2002, Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century., J Clin Endocrinol Metab, 87, 5353, 10.1210/jc.2002-021370

Christiansen, 1990, Primary hyperparathyroidism: changes in trabecular bone remodeling following surgical treatment–evaluated by histomorphometric methods., Bone, 11, 75, 10.1016/8756-3282(90)90053-2

Christiansen, 1999, Primary hyperparathyroidism: short-term changes in bone remodeling and bone mineral density following parathyroidectomy., Bone, 25, 237, 10.1016/S8756-3282(99)00150-7

Dalen, 1974, Bone mineral content in patients with primary hyperparathyroidism without radiological evidence of skeletal changes., Acta Endocrinol (Copenh), 75, 297, 10.1530/acta.0.0750297

Almqvist, 2004, Early parathyroidectomy increases bone mineral density in patients with mild primary hyperparathyroidism: a prospective and randomized study., Surgery, 136, 1281, 10.1016/j.surg.2004.06.059

Rao, 2004, Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic primary hyperparathyroidism., J Clin Endocrinol Metab, 89, 5415, 10.1210/jc.2004-0028

Ambrogini, 2007, Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial., J Clin Endocrinol Metab, 92, 3114, 10.1210/jc.2007-0219

Bollerslev, 2007, Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial., J Clin Endocrinol Metab, 92, 1687, 10.1210/jc.2006-1836

Bilezikian, 2003, Bone strength in primary hyperparathyroidism, Osteoporos Int, 14, 113, 10.1007/s00198-003-1482-4

Ahlborg, 2003, Bone loss and bone size after menopause., N Engl J Med, 349, 327, 10.1056/NEJMoa022464

Charopoulos, 2006, Effect of primary hyperparathyroidism on volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in postmenopausal women., J Clin Endocrinol Metab, 91, 1748, 10.1210/jc.2005-2102

Roschger, 2007, New observations on bone quality in mild primary hyperparathyroidism as determined by quantitative backscattered electron imaging., J Bone Miner Res, 22, 717, 10.1359/jbmr.070120

Vestergaard, 2000, Cohort study of risk of fracture before and after surgery for primary hyperparathyroidism., BMJ, 321, 598, 10.1136/bmj.321.7261.598

Khosla, 1999, Primary hyperparathyroidism and the risk of fracture: a population-based study., J Bone Miner Res, 14, 1700, 10.1359/jbmr.1999.14.10.1700

Nilsson, 2002, Clinical presentation of primary hyperparathyroidism in Europe-nationwide cohort analysis on mortality from nonmalignant causes, J Bone Miner Res, 17, N68

Wermers, 1998, Survival after the diagnosis of hyperparathyroidism: a population-based study., Am J Med, 104, 115, 10.1016/S0002-9343(97)00270-2