- Email: [email protected]
African Americans present with more severe primary hyperparathyroidism than non-African Americans
African Americans present with more severe primary hyperparathyroidism than non-African Americans Emad Kandil, MD,a,* Hua Ling Tsai,c Helina Somervell, MSN, CRNP,a Alan P. Dackiw, MD, PhD,a Ralph P. Tufano, MD,b Anthony P. Tufaro, MD, DDS,d Jeanne Kowalski, PhD,c and Martha A. Zeiger, MD,a Baltimore, Md
Background. Similar to other disease states, we postulated that African American patients present with more severe signs of primary hyperparathyroidism than non-African Americans. To test this hypothesis, we compared relevant preoperative laboratory values, sestamibi scan results, and intraoperative findings between African American and non-African American patients with primary hyperparathyroidism who underwent parathyroidectomy between January 2002 and May 2007. Methods. In all, 588 patients were included and 113 (19%) were African American. A linear model was used to examine the effect of race with respect to mean differences in serum calcium, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH), alkaline phosphatase (ALKP) levels, gland weight, presence of double adenomas and, sestamibi scan sensitivity. Results. Adjusted for age and gender, African Americans exhibited significantly higher median calcium (11.36 [SD = 0.91] vs 11.06 [SD = 0.72] mg/dL, P < .001), iPTH (138.5 [SD = 166.03] vs 117 [73.22] pg/mL, P < .01), and ALKP (101 [SD = 57.86] vs 90.5 [SD = 29.78] U/L, P < .01) levels compared with non- African Americans. They exhibited significantly lower median serum 25(OH)D (14 [SD = 9.36] vs 23 [SD = 12.160] ng/mL, P < .001), greater gland weight (P < .001), a higher probability of double adenomas (odds ratio = 2.83, 95% confidence interval [CI], 1.36–5.88), and a higher probability of presenting with a positive sestamibi scan (odds ratio = 4.99, 95% CI = 2.44–10.19) compared with non-African Americans. Conclusion. African Americans present with more advanced signs of primary hyperparathyroidism than non-African Americans. These results may reflect less access to health care, surgical consultations, or other unidentified factors. These highly significant findings, however, warrant additional investigation. (Surgery 2008;144:1023-7.) From the Endocrine Surgery Sectiona and Plastic Surgery Division,b Department of Surgery, Johns Hopkins Medical Institutions, Baltimore; the Department of Biostatisticsc and the Department of Otolaryngology-Head and Neck Surgery,d Johns Hopkins School of Public Health, Baltimore, Md
PRIMARY HYPERPARATHYROIDISM is a common disorder with an estimated incidence of 1 in every 500 women and 1 in every 2000 men older than 40 years of age.1 The most striking health discrepancies observed in the African American population include shorter life expectancy and higher rates of cancer, neonatal mortality, birth defects, cardiovascular disease, asthma, diabetes, and other obesity-related disorders.2 Based on our experience with other disease
*Affiliation at time of research. Accepted for publication October 13, 2008. Reprint requests: Martha A. Zeiger, MD, Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Carnegie 681, Baltimore, MD 21287. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2008 Mosby, Inc. All rights reserved. doi:10.1016/j.surg.2008.08.021
processes, we postulated that African American patients also present with more severe signs of primary hyperparathyroidism. To investigate this hypothesis, we compared preoperative laboratory values, sestamibi scan results, and intraoperative findings between African American and non-African American patients who underwent parathyroidectomy for primary hyperparathyroidism at our institution. SUBJECTS AND METHODS A retrospective database was created with Johns Hopkins Institutional Review Board approval and included patients who underwent parathyroid surgery from January 2002 to May 2007. Patients with familial hyperparathyroidism were excluded from the study. Among the 593 patients, 588 had information on race, 113 patients (19%) were reported as African American, and 475 patients (80%) as non-African American (440 Caucasians, SURGERY 1023
1024 Kandil et al
Surgery December 2008
Table. Descriptive of characteristics examined by race, African American vs non-African American Characteristic* Age (SD) Median (SD) vitamin D Median (SD) calcium Median (SD) iPTH Median (SD) gland weight in log scale Median (SD) alkaline phosphatase Sestamibi scan (%)y Number positive Number indeterminate or negative Double adenomas (%) Number present Number absent
African American (n = 113) 58.67 14 11.3 138.5 6.46 101
(14.40) (9.36) (0.91) (166.03) (1.17) (57.86)
Non-African American (n = 475) 60.13 23 11 117 6.18 90.5
(13.08) (12.16) (0.72) (73.22) (1.07) (29.78)
Pz NS <.001 .0001 .003 .004 .003
94 (91.3%) 9 (8.7%)
286 (67.3%) 137 (32.2%)
<.001
14 (12.4%) 99 (87.6%)
24 (5.1%) 451 (94.9%)
.008
iPTH, Intact parathyroid hormone. *Missing data: 31.8% for vitamin D, 10% for calcium, 10.2% for iPTH and sestamibi scan, 8.2% for adenoma and gland weight, and 43.7% for ALK. yn = 10; (50) patients had missing information on sestamibi scan among African Americans (non-African Americans). zComparisons of categorical characteristics between African Americans and non-African Americans were based on v2 tests; comparisons of continuous characteristics between the 2 groups were based on the Wilcoxon rank sum test.
16 Asians, and 19 others). Data compiled included age, gender, race, preoperative laboratory values for serum calcium, alkaline phosphatase, intact parathyroid hormone (PTH), 25-hydroxyvitamin D, sestamibi scan results, adenoma weight, and the presence of double adenomas. African Americans had a similar distribution of age (mean = 58.7 years, SD = 14.4) as non-African Americans (mean = 60.1 years, SD = 13.1). In all, 22 of 113 (19.46%) patients were males in the African American and 135 of 475 (28.42%) were males in the non-African American group. Almost all patients had outpatient parathyroid sestamibi single photon emission computed tomography scans performed preoperatively. A total of 526 patients had results from sestamibi scans available. Confidence for parathyroid adenoma location documented on sestamibi scan was assessed semiquantitatively with a 3-point scale (0 for no evidence of adenoma, 1 for intermediate, and 2 for confidently confirming evidence of an adenoma). Statistical analysis. A linear model was used to examine the effect of race with respect to mean differences in serum calcium, alkaline phosphatase, intact PTH, 25-hydroxyvitamin D levels, sestamibi scan results, adenoma weight in log scale, and the presence of double adenomas. Descriptive statistics were calculated for all variables. Reported results were adjusted for age and gender. For statistical analyses, all variables were summarized using medians and standard deviations (SD). Comparisons of categorical characteristics between African American and non-African American patients were based on v2 tests; comparisons of continuous characteristics between 2 groups were based on the
Wilcoxon rank sum test. A P value of less than .05 was considered statistically significant. RESULTS Our analysis revealed that African Americans in comparison with non-African Americans presented with more significantly abnormal laboratory signs of primary hyperparathyroidism (Table). African Americans exhibited significantly higher calcium levels (11.36 [SD = 0.91] vs 11.06 [SD = 0.72] mg/dL [normal, 8.4–10.5 mg/dL], P < .001). Furthermore, 19 (18%) patients were in the African American group, and only 29 (7%) patients were in the non-African American group with a calcium level above 12 mg/dL (P < .005). African Americans also exhibited significantly higher intact PTH levels (138.5 [SD = 166.03] vs 117 [SD = 73.22] pg/mL [normal, 10--65 pg/mL], P < .01) and higher alkaline phosphatase levels (101 [SD = 57.86] vs 90.5 [SD = 29.78] U/L, [normal, 30–120 U/L], P < .01) compared with non-African Americans. They also exhibited significantly lower serum 25-hydroxyvitamin D levels (14 [SD = 9.36] vs 23 [SD = 12.16] ng.mL [normal, 20–100 ng.mL], P < .001), a higher adenoma(s) weight in log scale (6.46 [SD = 1.17] vs 6.18 [SD = 1.07], P < .01], and a higher probability of double adenomas (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.36– 5.88). Of the 526 sestamibi scans, 419 were performed at Johns Hopkins Hospital and 107 were performed at an outside institution. African Americans exhibited a higher probability of presenting with a positive versus an indeterminate or negative sestamibi scan (OR = 4.99, 95% CI = 2.44–10.19). The
Surgery Volume 144, Number 6
significant association between scan results was irrespective of whether scans were conducted at Johns Hopkins or at an outside institution. In all, 5 (4.2%) African American patients and 20 (4.2%) non-African American patients had 4-gland disease. DISCUSSION This study represents the largest series to date documenting significant disparity in the severity of primary hyperparathyroidism among African Americans compared with non-African Americans. In this study, 113 African Americans were included and represented 19% of the 588 patients. A previous report documented that women in China presented with more advanced primary hyperparathyroidism disease compared with women in the United States.3 Furthermore, the incidence of primary hyperparathyroidism in African Americans is unknown, and only 2 population-based studies defining the incidence have been conducted in the United States. However, both of these studies only targeted residents of Rochester, Minnesota, who are predominately of Northern European descent.4,5 The features of primary hyperparathyroidism in developing countries have been examined recently. In India, patients with primary hyperparathyroidism not only present at an advanced stage, but also they have vitamin D deficiency.6-8 These patients present with severe skeletal, muscular, and renal manifestations as well as a young age. Furthermore, Indians have significantly larger parathyroid tumors compared with Americans.9 Barker et al10compared 36 African Americans with 36 Caucasian patients who had primary hyperparathyroidism and found no difference in serum calcium levels or symptoms related to hyperparathyroidism, but they did find higher PTH levels among the African American patients. Similar to other studies, our data also suggested that vitamin D levels are significantly lower in African Americans than in non-African Americans. Silverberg et al11 found a prevalence of 53% of serum 25-hydroxyvitamin D deficiency in 124 patients with primary hyperparathyroidism. However, they did not stratify their results according to race. Others have reported that African Americans are at greater risk for vitamin D deficiency for 2 reasons: greater skin melanin and a greater prevalence of obesity.12 The primary reasons for focusing on health disparities are 2-fold: (1) to prevent morbidity and mortality resulting from illnesses that are otherwise preventable or curable and (2) to reduce or eliminate strains on social systems that care for minorities. Both health systems and individual factors can
Kandil et al 1025
contribute to ongoing racial disparities; yet the relative contributions to health disparities remain poorly understood.13-15 Racial and ethnic disparities in health care delivery are associated with adverse health outcomes, and elimination of racial/ethnic disparities has become a national health goal.16 The etiology of the racial disparity with regard to the severity of primary hyperparathyroidism is uncertain but likely multifactorial. Possible explanations include variable access to health care, patient perceptions of a disease state, or differences in physician practice.13-15 Barriers to health care among minority groups may also include lower rates of insurance and a decreased availability to both primary-care physicians and clinics.16 The results of our study have several limitations that should be considered. First, the current study included only patients who underwent surgical intervention; in general this method selects the more severe cases with advanced disease than those who do not undergo operation. Future studies should evaluate the racial disparity in all patients who present with primary hyperparathyroidism, not only patients who underwent surgical intervention. Second, the study was retrospective, and therefore, whether certain clinical manifestations of the disease, such as osteopenia or nephrolithiasis, were present were unavailable. The bone densitometric profile and history of nephrolithiasis were not always addressed in the patient records by our surgeons during their preoperative consultation. Thus, these data were not included in the current study. Finally, some parathyroid scans were performed outside our inistitution and read by different radiologists. This shortcoming is a result of the retrospective nature of our study. However, African Americans exhibited a higher probability of presenting with a positive versus an indeterminate or negative sestamibi scan regardless of whether the scans were performed inside or outside our institution. In summary, our observations suggest that African Americans are at significantly greater risk of presenting with more abnormal laboratory findings associated with primary hyperparathyroidism and larger parathyroid adenomas as well as have a greater likelihood of having double adenomas and a positive sestamibi scan. Additional studies are needed to determine the reasons for these findings and whether these racial disparities result in worse health outcomes. The results of this study may reflect less access to health care, less likelihood of seeking surgical consultation, or other unidentified factors. These highly significant findings, however, warrant additional investigation to
1026 Kandil et al
delineate the reasons more accurately for these findings and to attempt to eliminate them.
REFERENCES 1. Akerstrom GLS, Lundren E. Natural history of untreated primary hyperparathyroidism. In: Clark OH, Duh QY, editors. Textbook of endocrine surgery. Philadelphia, PA: W.B. Saunders Company; 1997. 2. Murray CJL, Michaud C, McKenna MT, Marks JS. US county by county pattern of mortality by race, 1965–1994. Cambridge, MA: Harvard Center for Population and Development; 1997. 3. Bilezikian JP, Meng X, Shi Y, Silverberg SJ. Primary hyperparathyroidism in women: a tale of two cities—New York and Beijing. Int J Fertil Womens Med 2000;45:158-65. 4. Heath DA, Wright AD, Barnes AD, Oates GD, Dorricott NJ. Surgical treatment of primary hyperparathyroidism in the elderly. Br Med J 1980;280:1406-8. 5. Wermers RA, Khosla S, Atkinson EJ, Hodgson SF, O’Fallon VM, Melton LJ III. The rise and fall of primary hyperparathyroidism: a population-based study in Rochester, Minnesota, 1965–1992. Ann Intern Med 1997;126:433-40. 6. Mishra SK, Agarwal G, Kar DK, Gupta SK, Mithal A, Rastad J. Unique clinical characteristics of primary hyperparathyroidism in India. Br J Surg 2001;88:708-14. 7. Agarwal G, Prasad KK, Kar DK, Krishinani N, Pandey R, Mishra SK. Indian primary hyperparathyroidism patients with parathyroid carcinoma do not differ in clinicoinvestigative characteristics from those with benign parathyroid pathology. World J Surg 2006;30:732-42. 8. Pradeep PV, Mishra A, Agarwal G, Agarwal A, Verma AK, Mishra SK. Long-term outcome after parathyroidectomy in patients with advanced primary hyperparathyroidism and associated vitamin D deficiency. World J Surg 2008;32: 829-35. 9. Rao DS, Agarwal G, Talpos GB, Phillips ER, Bandeira F, Mishra SK, et al. Role of vitamin D and calcium nutrition in disease expression and parathyroid tumor growth in primary hyperparathyroidism: a global perspective. J Bone Miner Res 2002;17(Suppl 2):N75-80. 10. Barker H, Caldwell L, Lovato J, Woods KF, Perrier ND. Is there a racial difference in presentation of primary hyperparathyroidism? Am Surg 2004;70:504-6. 11. Silverberg SJ, Shane E, Jacobs TP, Siris E, Bilezikian JP. A 10year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med 1999;341: 1249-55. 12. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004; 291:2847-50. 13. Lieu TA, Newacheck PW, McManus MA. Race, ethnicity, and access to ambulatory care among US adolescents. Am J Public Health 1993;83:960-5. 14. Williams DR. Race and health: basic questions, emerging directions. Ann Epidemiol 1997;7:322-33. 15. Zuvekas SH, Taliaferro GS. Pathways to access: health insurance, the health care delivery system, and racial/ethnic disparities, 1996-1999. Health Aff 2003;22:139-53. 16. Smedley Bd SA, Nelson AR. Board on Health Sciences Policy. Unequal treatment: confronting racial and ethnic disparities in health care. Executive Summary. Washington, DC: Institute of Medicine, National Academy Press; 2002.
Surgery December 2008
DISCUSSION Dr Tracy Wang (New Haven, Conn): I was just wondering if in your study you separated the Hispanics into a separate population, and if you did, what your findings were, and if not, why not. Dr Emad Kandil (New Orleans, La): We had less than 20 patients of Hispanic origin in our study; too few to see a statistical difference among the groups. Dr Cord Sturgeon (Chicago, Ill): Last year we presented data on the utilization of thyroidectomy in the United States and showed that there is a difference in total thyroidectomy in racial groups. It kind of mirrors somewhat what you have shown us today, that African Americans may have lower access to health care. But what was interesting in our data was that Asians seemed to have greater access. So, I would like to ask 1 question. Did you notice any differences in that Asian group that you have up there? And my second question is not related, but do you have any data about the duration of hypercalcemia that would help us understand may be a cause for this higher severity? Dr Emad Kandil (New Orleans, La): To answer the first question, there were only 16 patients of Asian origin and so, not enough to draw any conclusions. To answer the second question: Our database was collected from the medical reports dictated by our surgeons. Unfortunately, many surgeons did not routinely report on the duration of disease prior to referral for surgical consultation. This question certainly warrants future prospective studies to better examine patient access to healthcare. One aspect of our findings, however, may reflect a longer duration of disease in the African American patients; approximately 18% of the African Americans, and only 7% of the non-African Americans had a calcium level above 12 mg/dL. Dr George L. Irvin III (Coral Gables, Fla): Just a quick question. What is your definition of a double adenoma? Was this based on size or histopathology or actual hypersecretion of those glands? Dr Emad Kandil (New Orleans, La): Patients were identified as having had double adenomas on the basis of surgical reports and pathology reports. The diagnosis of double adenomas was based on the surgeon’s clinical impression that both glands were enlarged, by pathologic confirmation that the glands were enlarged and hypercellular. We routinely measure intraoperative intact PTH during all procedures, and double adenomas are detected by an appropriate decrease in IOPTH after removal of both abnormal glands. Dr Gary B. Talpos (Detroit, Mich): Tremendous data, a lot of information. We looked up our results a couple of years ago, and it is interesting that we found that the incident of multiple gland disease was virtually identical between the African American population and the Caucasian population. We also have a group of HMO patients that should remove any access to medical care, and we found that those patients still came in a little bit later. And this was very similar to the breast cancer data that we reported years ago, that access to care,
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when you remove that as a barrier, it still does not account for the worst breast cancer stage that African American patients present with. So a lot of this has to do with outreach into the community and distrust of American medicine. Do you have any sense in the Hopkins population how many of your African American patients had traditional insurance, how many may have been indigent?
Kandil et al 1027
Dr Martha A. Zeiger (Baltimore, Md): We don’t have information about the insurance of these patients, but that would be interesting to examine. In general we operate on any patient who needs surgery if they do not have insurance. Generally, however, hyperparathyroidism is generally not life threatening; so these patients were all insured, or had medical assistance procured for them if they did not already have insurance.
Background. Similar to other disease states, we postulated that African American patients present with more severe signs of primary hyperparathyroidism than non-African Americans. To test this hypothesis, we compared relevant preoperative laboratory values, sestamibi scan results, and intraoperative findings between African American and non-African American patients with primary hyperparathyroidism who underwent parathyroidectomy between January 2002 and May 2007. Methods. In all, 588 patients were included and 113 (19%) were African American. A linear model was used to examine the effect of race with respect to mean differences in serum calcium, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH), alkaline phosphatase (ALKP) levels, gland weight, presence of double adenomas and, sestamibi scan sensitivity. Results. Adjusted for age and gender, African Americans exhibited significantly higher median calcium (11.36 [SD = 0.91] vs 11.06 [SD = 0.72] mg/dL, P < .001), iPTH (138.5 [SD = 166.03] vs 117 [73.22] pg/mL, P < .01), and ALKP (101 [SD = 57.86] vs 90.5 [SD = 29.78] U/L, P < .01) levels compared with non- African Americans. They exhibited significantly lower median serum 25(OH)D (14 [SD = 9.36] vs 23 [SD = 12.160] ng/mL, P < .001), greater gland weight (P < .001), a higher probability of double adenomas (odds ratio = 2.83, 95% confidence interval [CI], 1.36–5.88), and a higher probability of presenting with a positive sestamibi scan (odds ratio = 4.99, 95% CI = 2.44–10.19) compared with non-African Americans. Conclusion. African Americans present with more advanced signs of primary hyperparathyroidism than non-African Americans. These results may reflect less access to health care, surgical consultations, or other unidentified factors. These highly significant findings, however, warrant additional investigation. (Surgery 2008;144:1023-7.) From the Endocrine Surgery Sectiona and Plastic Surgery Division,b Department of Surgery, Johns Hopkins Medical Institutions, Baltimore; the Department of Biostatisticsc and the Department of Otolaryngology-Head and Neck Surgery,d Johns Hopkins School of Public Health, Baltimore, Md
PRIMARY HYPERPARATHYROIDISM is a common disorder with an estimated incidence of 1 in every 500 women and 1 in every 2000 men older than 40 years of age.1 The most striking health discrepancies observed in the African American population include shorter life expectancy and higher rates of cancer, neonatal mortality, birth defects, cardiovascular disease, asthma, diabetes, and other obesity-related disorders.2 Based on our experience with other disease
*Affiliation at time of research. Accepted for publication October 13, 2008. Reprint requests: Martha A. Zeiger, MD, Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Carnegie 681, Baltimore, MD 21287. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2008 Mosby, Inc. All rights reserved. doi:10.1016/j.surg.2008.08.021
processes, we postulated that African American patients also present with more severe signs of primary hyperparathyroidism. To investigate this hypothesis, we compared preoperative laboratory values, sestamibi scan results, and intraoperative findings between African American and non-African American patients who underwent parathyroidectomy for primary hyperparathyroidism at our institution. SUBJECTS AND METHODS A retrospective database was created with Johns Hopkins Institutional Review Board approval and included patients who underwent parathyroid surgery from January 2002 to May 2007. Patients with familial hyperparathyroidism were excluded from the study. Among the 593 patients, 588 had information on race, 113 patients (19%) were reported as African American, and 475 patients (80%) as non-African American (440 Caucasians, SURGERY 1023
1024 Kandil et al
Surgery December 2008
Table. Descriptive of characteristics examined by race, African American vs non-African American Characteristic* Age (SD) Median (SD) vitamin D Median (SD) calcium Median (SD) iPTH Median (SD) gland weight in log scale Median (SD) alkaline phosphatase Sestamibi scan (%)y Number positive Number indeterminate or negative Double adenomas (%) Number present Number absent
African American (n = 113) 58.67 14 11.3 138.5 6.46 101
(14.40) (9.36) (0.91) (166.03) (1.17) (57.86)
Non-African American (n = 475) 60.13 23 11 117 6.18 90.5
(13.08) (12.16) (0.72) (73.22) (1.07) (29.78)
Pz NS <.001 .0001 .003 .004 .003
94 (91.3%) 9 (8.7%)
286 (67.3%) 137 (32.2%)
<.001
14 (12.4%) 99 (87.6%)
24 (5.1%) 451 (94.9%)
.008
iPTH, Intact parathyroid hormone. *Missing data: 31.8% for vitamin D, 10% for calcium, 10.2% for iPTH and sestamibi scan, 8.2% for adenoma and gland weight, and 43.7% for ALK. yn = 10; (50) patients had missing information on sestamibi scan among African Americans (non-African Americans). zComparisons of categorical characteristics between African Americans and non-African Americans were based on v2 tests; comparisons of continuous characteristics between the 2 groups were based on the Wilcoxon rank sum test.
16 Asians, and 19 others). Data compiled included age, gender, race, preoperative laboratory values for serum calcium, alkaline phosphatase, intact parathyroid hormone (PTH), 25-hydroxyvitamin D, sestamibi scan results, adenoma weight, and the presence of double adenomas. African Americans had a similar distribution of age (mean = 58.7 years, SD = 14.4) as non-African Americans (mean = 60.1 years, SD = 13.1). In all, 22 of 113 (19.46%) patients were males in the African American and 135 of 475 (28.42%) were males in the non-African American group. Almost all patients had outpatient parathyroid sestamibi single photon emission computed tomography scans performed preoperatively. A total of 526 patients had results from sestamibi scans available. Confidence for parathyroid adenoma location documented on sestamibi scan was assessed semiquantitatively with a 3-point scale (0 for no evidence of adenoma, 1 for intermediate, and 2 for confidently confirming evidence of an adenoma). Statistical analysis. A linear model was used to examine the effect of race with respect to mean differences in serum calcium, alkaline phosphatase, intact PTH, 25-hydroxyvitamin D levels, sestamibi scan results, adenoma weight in log scale, and the presence of double adenomas. Descriptive statistics were calculated for all variables. Reported results were adjusted for age and gender. For statistical analyses, all variables were summarized using medians and standard deviations (SD). Comparisons of categorical characteristics between African American and non-African American patients were based on v2 tests; comparisons of continuous characteristics between 2 groups were based on the
Wilcoxon rank sum test. A P value of less than .05 was considered statistically significant. RESULTS Our analysis revealed that African Americans in comparison with non-African Americans presented with more significantly abnormal laboratory signs of primary hyperparathyroidism (Table). African Americans exhibited significantly higher calcium levels (11.36 [SD = 0.91] vs 11.06 [SD = 0.72] mg/dL [normal, 8.4–10.5 mg/dL], P < .001). Furthermore, 19 (18%) patients were in the African American group, and only 29 (7%) patients were in the non-African American group with a calcium level above 12 mg/dL (P < .005). African Americans also exhibited significantly higher intact PTH levels (138.5 [SD = 166.03] vs 117 [SD = 73.22] pg/mL [normal, 10--65 pg/mL], P < .01) and higher alkaline phosphatase levels (101 [SD = 57.86] vs 90.5 [SD = 29.78] U/L, [normal, 30–120 U/L], P < .01) compared with non-African Americans. They also exhibited significantly lower serum 25-hydroxyvitamin D levels (14 [SD = 9.36] vs 23 [SD = 12.16] ng.mL [normal, 20–100 ng.mL], P < .001), a higher adenoma(s) weight in log scale (6.46 [SD = 1.17] vs 6.18 [SD = 1.07], P < .01], and a higher probability of double adenomas (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.36– 5.88). Of the 526 sestamibi scans, 419 were performed at Johns Hopkins Hospital and 107 were performed at an outside institution. African Americans exhibited a higher probability of presenting with a positive versus an indeterminate or negative sestamibi scan (OR = 4.99, 95% CI = 2.44–10.19). The
Surgery Volume 144, Number 6
significant association between scan results was irrespective of whether scans were conducted at Johns Hopkins or at an outside institution. In all, 5 (4.2%) African American patients and 20 (4.2%) non-African American patients had 4-gland disease. DISCUSSION This study represents the largest series to date documenting significant disparity in the severity of primary hyperparathyroidism among African Americans compared with non-African Americans. In this study, 113 African Americans were included and represented 19% of the 588 patients. A previous report documented that women in China presented with more advanced primary hyperparathyroidism disease compared with women in the United States.3 Furthermore, the incidence of primary hyperparathyroidism in African Americans is unknown, and only 2 population-based studies defining the incidence have been conducted in the United States. However, both of these studies only targeted residents of Rochester, Minnesota, who are predominately of Northern European descent.4,5 The features of primary hyperparathyroidism in developing countries have been examined recently. In India, patients with primary hyperparathyroidism not only present at an advanced stage, but also they have vitamin D deficiency.6-8 These patients present with severe skeletal, muscular, and renal manifestations as well as a young age. Furthermore, Indians have significantly larger parathyroid tumors compared with Americans.9 Barker et al10compared 36 African Americans with 36 Caucasian patients who had primary hyperparathyroidism and found no difference in serum calcium levels or symptoms related to hyperparathyroidism, but they did find higher PTH levels among the African American patients. Similar to other studies, our data also suggested that vitamin D levels are significantly lower in African Americans than in non-African Americans. Silverberg et al11 found a prevalence of 53% of serum 25-hydroxyvitamin D deficiency in 124 patients with primary hyperparathyroidism. However, they did not stratify their results according to race. Others have reported that African Americans are at greater risk for vitamin D deficiency for 2 reasons: greater skin melanin and a greater prevalence of obesity.12 The primary reasons for focusing on health disparities are 2-fold: (1) to prevent morbidity and mortality resulting from illnesses that are otherwise preventable or curable and (2) to reduce or eliminate strains on social systems that care for minorities. Both health systems and individual factors can
Kandil et al 1025
contribute to ongoing racial disparities; yet the relative contributions to health disparities remain poorly understood.13-15 Racial and ethnic disparities in health care delivery are associated with adverse health outcomes, and elimination of racial/ethnic disparities has become a national health goal.16 The etiology of the racial disparity with regard to the severity of primary hyperparathyroidism is uncertain but likely multifactorial. Possible explanations include variable access to health care, patient perceptions of a disease state, or differences in physician practice.13-15 Barriers to health care among minority groups may also include lower rates of insurance and a decreased availability to both primary-care physicians and clinics.16 The results of our study have several limitations that should be considered. First, the current study included only patients who underwent surgical intervention; in general this method selects the more severe cases with advanced disease than those who do not undergo operation. Future studies should evaluate the racial disparity in all patients who present with primary hyperparathyroidism, not only patients who underwent surgical intervention. Second, the study was retrospective, and therefore, whether certain clinical manifestations of the disease, such as osteopenia or nephrolithiasis, were present were unavailable. The bone densitometric profile and history of nephrolithiasis were not always addressed in the patient records by our surgeons during their preoperative consultation. Thus, these data were not included in the current study. Finally, some parathyroid scans were performed outside our inistitution and read by different radiologists. This shortcoming is a result of the retrospective nature of our study. However, African Americans exhibited a higher probability of presenting with a positive versus an indeterminate or negative sestamibi scan regardless of whether the scans were performed inside or outside our institution. In summary, our observations suggest that African Americans are at significantly greater risk of presenting with more abnormal laboratory findings associated with primary hyperparathyroidism and larger parathyroid adenomas as well as have a greater likelihood of having double adenomas and a positive sestamibi scan. Additional studies are needed to determine the reasons for these findings and whether these racial disparities result in worse health outcomes. The results of this study may reflect less access to health care, less likelihood of seeking surgical consultation, or other unidentified factors. These highly significant findings, however, warrant additional investigation to
1026 Kandil et al
delineate the reasons more accurately for these findings and to attempt to eliminate them.
REFERENCES 1. Akerstrom GLS, Lundren E. Natural history of untreated primary hyperparathyroidism. In: Clark OH, Duh QY, editors. Textbook of endocrine surgery. Philadelphia, PA: W.B. Saunders Company; 1997. 2. Murray CJL, Michaud C, McKenna MT, Marks JS. US county by county pattern of mortality by race, 1965–1994. Cambridge, MA: Harvard Center for Population and Development; 1997. 3. Bilezikian JP, Meng X, Shi Y, Silverberg SJ. Primary hyperparathyroidism in women: a tale of two cities—New York and Beijing. Int J Fertil Womens Med 2000;45:158-65. 4. Heath DA, Wright AD, Barnes AD, Oates GD, Dorricott NJ. Surgical treatment of primary hyperparathyroidism in the elderly. Br Med J 1980;280:1406-8. 5. Wermers RA, Khosla S, Atkinson EJ, Hodgson SF, O’Fallon VM, Melton LJ III. The rise and fall of primary hyperparathyroidism: a population-based study in Rochester, Minnesota, 1965–1992. Ann Intern Med 1997;126:433-40. 6. Mishra SK, Agarwal G, Kar DK, Gupta SK, Mithal A, Rastad J. Unique clinical characteristics of primary hyperparathyroidism in India. Br J Surg 2001;88:708-14. 7. Agarwal G, Prasad KK, Kar DK, Krishinani N, Pandey R, Mishra SK. Indian primary hyperparathyroidism patients with parathyroid carcinoma do not differ in clinicoinvestigative characteristics from those with benign parathyroid pathology. World J Surg 2006;30:732-42. 8. Pradeep PV, Mishra A, Agarwal G, Agarwal A, Verma AK, Mishra SK. Long-term outcome after parathyroidectomy in patients with advanced primary hyperparathyroidism and associated vitamin D deficiency. World J Surg 2008;32: 829-35. 9. Rao DS, Agarwal G, Talpos GB, Phillips ER, Bandeira F, Mishra SK, et al. Role of vitamin D and calcium nutrition in disease expression and parathyroid tumor growth in primary hyperparathyroidism: a global perspective. J Bone Miner Res 2002;17(Suppl 2):N75-80. 10. Barker H, Caldwell L, Lovato J, Woods KF, Perrier ND. Is there a racial difference in presentation of primary hyperparathyroidism? Am Surg 2004;70:504-6. 11. Silverberg SJ, Shane E, Jacobs TP, Siris E, Bilezikian JP. A 10year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med 1999;341: 1249-55. 12. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004; 291:2847-50. 13. Lieu TA, Newacheck PW, McManus MA. Race, ethnicity, and access to ambulatory care among US adolescents. Am J Public Health 1993;83:960-5. 14. Williams DR. Race and health: basic questions, emerging directions. Ann Epidemiol 1997;7:322-33. 15. Zuvekas SH, Taliaferro GS. Pathways to access: health insurance, the health care delivery system, and racial/ethnic disparities, 1996-1999. Health Aff 2003;22:139-53. 16. Smedley Bd SA, Nelson AR. Board on Health Sciences Policy. Unequal treatment: confronting racial and ethnic disparities in health care. Executive Summary. Washington, DC: Institute of Medicine, National Academy Press; 2002.
Surgery December 2008
DISCUSSION Dr Tracy Wang (New Haven, Conn): I was just wondering if in your study you separated the Hispanics into a separate population, and if you did, what your findings were, and if not, why not. Dr Emad Kandil (New Orleans, La): We had less than 20 patients of Hispanic origin in our study; too few to see a statistical difference among the groups. Dr Cord Sturgeon (Chicago, Ill): Last year we presented data on the utilization of thyroidectomy in the United States and showed that there is a difference in total thyroidectomy in racial groups. It kind of mirrors somewhat what you have shown us today, that African Americans may have lower access to health care. But what was interesting in our data was that Asians seemed to have greater access. So, I would like to ask 1 question. Did you notice any differences in that Asian group that you have up there? And my second question is not related, but do you have any data about the duration of hypercalcemia that would help us understand may be a cause for this higher severity? Dr Emad Kandil (New Orleans, La): To answer the first question, there were only 16 patients of Asian origin and so, not enough to draw any conclusions. To answer the second question: Our database was collected from the medical reports dictated by our surgeons. Unfortunately, many surgeons did not routinely report on the duration of disease prior to referral for surgical consultation. This question certainly warrants future prospective studies to better examine patient access to healthcare. One aspect of our findings, however, may reflect a longer duration of disease in the African American patients; approximately 18% of the African Americans, and only 7% of the non-African Americans had a calcium level above 12 mg/dL. Dr George L. Irvin III (Coral Gables, Fla): Just a quick question. What is your definition of a double adenoma? Was this based on size or histopathology or actual hypersecretion of those glands? Dr Emad Kandil (New Orleans, La): Patients were identified as having had double adenomas on the basis of surgical reports and pathology reports. The diagnosis of double adenomas was based on the surgeon’s clinical impression that both glands were enlarged, by pathologic confirmation that the glands were enlarged and hypercellular. We routinely measure intraoperative intact PTH during all procedures, and double adenomas are detected by an appropriate decrease in IOPTH after removal of both abnormal glands. Dr Gary B. Talpos (Detroit, Mich): Tremendous data, a lot of information. We looked up our results a couple of years ago, and it is interesting that we found that the incident of multiple gland disease was virtually identical between the African American population and the Caucasian population. We also have a group of HMO patients that should remove any access to medical care, and we found that those patients still came in a little bit later. And this was very similar to the breast cancer data that we reported years ago, that access to care,
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when you remove that as a barrier, it still does not account for the worst breast cancer stage that African American patients present with. So a lot of this has to do with outreach into the community and distrust of American medicine. Do you have any sense in the Hopkins population how many of your African American patients had traditional insurance, how many may have been indigent?
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Dr Martha A. Zeiger (Baltimore, Md): We don’t have information about the insurance of these patients, but that would be interesting to examine. In general we operate on any patient who needs surgery if they do not have insurance. Generally, however, hyperparathyroidism is generally not life threatening; so these patients were all insured, or had medical assistance procured for them if they did not already have insurance.