Elsevier

Bone

Volume 73, April 2015, Pages 1-7
Bone

Original Full Length Article
Secular trends in the incidence of primary hyperparathyroidism over five decades (1965–2010)

https://doi.org/10.1016/j.bone.2014.12.003Get rights and content

Highlights

  • A second sharp increase in the incidence rate of primary hyperparathyroidism has occurred since 1998.

  • The greatest increase in primary hyperparathyroidism incidence was seen in women ≥ 65 and men ≥ 75 years.

  • Since 1998, patients with primary hyperparathyroidism are older and more likely to undergo parathyroidectomy.

  • Ascertainment bias associated with osteoporosis-related testing is the most likely cause of the increased incidence of primary hyperparathyroidism since 1998.

Abstract

Introduction of automated serum calcium measurements in the 1970s resulted in a sharp rise in primary hyperparathyroidism (PHPT) incidence. However, recent investigations suggest a significant rise in PHPT incidence for unclear reasons. Our objective was to update our population-based secular trends in PHPT incidence, to determine if there has been a significant rise in PHPT incidence as suggested by others, and, if possible, to identify changes in clinical practice that might be responsible. Rochester, Minnesota, residents who met the criteria for PHPT from 2002 through 2010 were identified through the medical records-linkage system of the Rochester Epidemiology Project and added to the historical cohort beginning in 1965. Incidence rates were adjusted to the 2010 US white population. Altogether, 1142 Rochester residents have been diagnosed with PHPT since 1965, including 341 in 2002–2010. Over time, two periods of increased PHPT incidence occurred, one beginning in 1974 (121.7 per 100,000 person-years) and a second peak (86.2 per 100,000 person-years) starting in 1998. The median age of PHPT subjects has increased significantly from 55 years in 1985–1997 to 60 years of age in 1998–2010 and more patients (36%) had a parathyroidectomy in 1998–2010. Although serum calcium measurement has declined since 1996, there was a progressive increase in parathyroid hormone testing between 1994 and 2008. There was also a rise in orders for bone mineral density measurements in women since 1998, which peaked in 2003–2004. A second sharp rise in PHPT incidence occurred in our community in 1998, simultaneously with the introduction of national osteoporosis screening guidelines, Medicare coverage for bone density measurement, and new medications for the treatment of osteoporosis. Case ascertainment bias from targeted PHPT screening in patients being evaluated for osteoporosis is the most likely explanation.

Introduction

Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder and the most common cause of hypercalcemia in the outpatient setting [1], [2]. We observed a significant increase in PHPT incidence among Rochester, Minnesota residents in 1974 that was associated with the introduction of automated serum chemistry panels and attributed to the identification of previously unrecognized prevalent cases of PHPT with asymptomatic hypercalcemia [3]. After the initial rise in PHPT diagnoses, the incidence fell to 27.7 per 100,000 person-years, which was thought to represent the true rate in an environment of automated measurement of serum calcium [3]. PHPT clinical characteristics also changed in the era of routine calcium measurement, from symptomatic disease with more severe hypercalcemia to asymptomatic PHPT with mild hypercalcemia that was more common in older women who are also at risk for osteoporosis [1], [2], [3], [4], [5], [6], [7].

Throughout the 1980s, the incidence of PHPT in Rochester steadily decreased, and this lower rate persisted throughout most of the 1990s [7], [8]. However, a second sharp increase in PHPT incidence was noted in 1998, which suggested that another important change in the epidemiology of PHPT might be occurring. Furthermore, three recent studies have suggested that the incidence of PHPT was higher than previously reported [4], [5], [9]. The goal of the current study was to update our population-based secular trends in PHPT incidence, to determine if there has been a significant rise in PHPT incidence as suggested by recent investigations, and, if possible, to identify changes in clinical practice that might be responsible. Availability of the population-based medical records-linkage system of the Rochester Epidemiology Project offered a unique opportunity to address this issue [10], [11].

Section snippets

Methods

Most endocrinologic care in this community is provided by the Mayo Clinic, which has maintained a common medical record with its two hospitals for over 100 years. The diagnoses and surgical procedures recorded in these records are indexed, as are the medical records of the other providers who serve the local population [11]. After the approval from the Institutional Review Boards of Mayo Clinic and the Olmsted Medical Center, we used this comprehensive medical records-linkage system (the

Results

Altogether, 341 Rochester residents (269 females, 72 males) were newly diagnosed with PHPT in 2002 through 2010 for a cohort total of 1142 PHPT patients from 1965 through 2010, of whom the majority had definite PHPT (94%). As shown in Fig. 1, however, two periods of increased PHPT incidence occurred, one beginning in 1974 (121.7 per 100,000 person-years, 95% CI: 88.4–154.9, re-adjusted to the 2010 U.S. white population) associated with the introduction of automated serum calcium measurement

Discussion

We have identified a second sharp rise in the incidence of PHPT in Rochester in 1998 similar to that observed in 1974 after the introduction of automated chemistry panels [3]. The first peak in PHPT incidence was attributed to “sweeping” the population for previously unrecognized PHPT cases through routine serum calcium testing. However, the most recent increase occurred despite a reduction in serum calcium measurements (Fig. 2) that accompanied a regulatory change on June 13, 1996, that

Conclusions

The epidemiology of PHPT has exhibited significant changes over the last 5 decades, which appear to largely reflect alterations in medical practice. Clinical medicine is dynamic, with constant innovations in patient care, introduction of new medications and treatment guidelines, and variations in reimbursement paradigms. The clinical spectrum of PHPT first shifted from a symptomatic disease with multiple complications to uncomplicated, asymptomatic PHPT in older individuals with the advent of

Conflict of interest

All authors state that they have no conflicts of interest.

The following are the supplementary data related to this article

. Utilization (per 100,000 person-years) of serum calcium measurements at Mayo Clinic Rochester for all Olmsted County, Minnesota, residents, 1994–2010, stratified by age.

. Utilization (per 100,000 person-years) of serum PTH measurements at Mayo Clinic Rochester for all Olmsted County, Minnesota, residents, 1994–2010, stratified by age.

Acknowledgments

The authors thank Mary G. Roberts for the help in preparing the manuscript as well as Philip I. Haigh, MD, MSc, FRCSC, FACS from Kaiser Permanente Los Angeles Medical Center and Dr. Ning Yu from Population Heath Sciences at the University of Dundee for providing the summary data from their respective cohorts to allow comparison of their incidence rates to Rochester, Minnesota.

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    This study was made possible using the resources of the Rochester Epidemiology Project, which is supported by the National Institute on Aging (R01AG034676). The content is solely the responsibility of the authors and does not necessarily represent official views of the National Institutes of Health.

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