Associations of Obesity, Vitamin D, Adjusted Total Calcium, and Parathyroid Hormone in US from NHANES

Abstract

Evidence for obesity and vitamin D deficiency as components of a data phenotype for primary hyperparathyroidism (pHPT) is critical to understanding primary hyperparathyroidism. This study examined the association between vitamin D, body mass index (BMI), albumin total calcium, parathyroid hormone (PTH) and data from National Health and Nutrition Examination Survey (NHANES). Associations of 25-hydroxyvitamin D, albumin adjusted calcium, and BMI with elevated PTH were evaluated, with elevated PTH being defined as>9.02 pmol/l. Outcomes were PTH (pmol/l), 25-hydroxyvitamin D (nmol/l), albumin adjusted calcium (mmol/l), and BMI. A weighted multivariable logistic regression model estimated the associations. A total of 9740 survey respondents were included in the study, 3.5% had elevated PTH. Mean vitamin D level was 57.7 (SD=22.6) nmol/l and BMI was 28.6 (SD=6.5) kg/m2. A one unit increase in BMI was associated with higher odds of elevated PTH [adjusted odds ratio (aOR)=1.04; 95% confidence interval (CI): 1.02, 1.06] whereas a one unit increase in vitamin D (aOR=0.97; 95% CI: 0.96, 0.98) or calcium (aOR=0.51; 95% CI: 0.29, 0.89) had decreased odds of elevated PTH. Higher BMI and lower levels of 25-hydroxyvitamin D are components of the primary hyperparathyroidism data phenotype. A refined data phenotype may improve detection/management of pHPT.

Keywords

National Health and Nutrition Examination Survey (NHANES) - primary hyperparathyroidism - vitamin D deficiency - obesity - parathyroid hormone (PTH) - album adjusted total calcium

Publikationsverlauf

Eingereicht: 03. März 2025

Angenommen nach Revision: 11. Juni 2025

Artikel online veröffentlicht:
27. Juni 2025

• References

• 1 Yeh MW, Ituarte PH, Zhou HC. et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab 2013; 98: 1122-1129
• 2 Ljunghall S, Hellman P, Rastad J. et al. Primary hyperparathyroidism: epidemiology, diagnosis and clinical picture. World J Surg 1991; 15: 681-687
• 3 Kanis JA, Harvey NC, Liu E. et al. Primary hyperparathyroidism and fracture probability. Osteoporos Int 2023; 34: 489-499
• 4 Soto-Pedre E, Newey PJ, Leese GP. Stable incidence and increasing prevalence of primary hyperparathyroidism in a population-based study in Scotland. J Clin Endocrinol Metab 2023; 108: e1117-e1124
• 5 Griebeler ML, Kearns AE, Ryu E. et al. Secular trends in the incidence of primary hyperparathyroidism over five decades (1965–2010). Bone 2015; 73: 1-7
• 6 Ruda JM, Hollenbeak CS, Stack BC. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg 2005; 132: 359-372
• 7 Hollowoa BR, Spencer HJ, Stack BC. Normocalcemic and normohormonal primary hyperparathyroidism: laboratory values and end-organ effects. Otolaryngol Head Neck Surg 2021; 165: 387-397
• 8 Quilao RJ, Greer M, Stack BC. Investigating the potential underdiagnosis of primary hyperparathyroidism at the University of Arkansas for Medical Sciences. Laryngoscope Investig Otolaryngol 2020; 5: 773-777
• 9 Duh QY, Suh I, Stoller ML. Underdiagnosis of primary hyperparathyroidism –the need for a system-level fix. JAMA Surg 2020; 155: 868-869
• 10 Alore EA, Suliburk JW, Ramsey DJ. et al. Diagnosis and management of primary hyperparathyroidism across the veterans affairs health care system. JAMA Intern Med 2019; 179: 1220-1227
• 11 Asban A, Dombrowsky A, Mallick R. et al. Failure to diagnose and treat hyperparathyroidism among patients with hypercalcemia: opportunities for intervention at the patient and physician level to increase surgical referral. Oncologist 2019; 24: e828-e834
• 12 Balentine CJ, Xie R, Kirklin JK. et al. Failure to diagnose hyperparathyroidism in 10 432 patients with hypercalcemia: opportunities for system-level intervention to increase surgical referrals and cure. Ann Surg 2017; 266: 632-640
• 13 Press DM, Siperstein AE, Berber E. et al. The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record. Surgery 2013; 154: 1232-1237 discussion 1237–1238
• 14 Dawood NB, Tseng CH, Nguyen DT. et al. Systems-level opportunities in the management of primary hyperparathyroidism: an informatics-based assessment. J Clin Endocrinol Metab 2021; 106: e4993-e5000
• 15 Greer ML, Davis K, Stack BC. Machine learning can identify patients at risk of hyperparathyroidism without known calcium and intact parathyroid hormone. Head Neck 2022; 44: 817-822
• 16 Bolland MJ, Grey AB, Gamble GD. et al. Association between primary hyperparathyroidism and increased body weight: a meta-analysis. J Clin Endocrinol Metab 2005; 90: 1525-1530
• 17 Center for Disease Control and Prevention: National Center for Health Statistics. NHANES Response Rates and Population Totals. Accessed 9/8/2023 https://wwwn.cdc.gov/nchs/nhanes/ResponseRates.aspx
• 18 Center for Disease Control and Prevention: National Center for Health Statistics. NHANES Survey Methods and Analytic Guidelines. Accessed 9/8/2023 https://wwwn.cdc.gov/nchs/nhanes/analyticguidelines.aspx
• 19 La’ulu SL, Roberts WL. Performance characteristics of six intact parathyroid hormone assays. Am J Clin Pathol 2010; 134: 930-938
• 20 Center for Disease Control and Prevention. Adult BMI Categories. Accessed 11/4/2024 https://www.cdc.gov/bmi/adult-calculator/bmi-categories.html
• 21 Suneja M. Hypocalcemia Differential Diagnoses. Accessed 12/03/2023 https://emedicine.medscape.com/article/241893-differential?form=fpf
• 22 Institute of Medicine Committee to Review Dietary Reference Intakes for Vitamin D, Calcium. The National Academies Collection: Reports funded by National Institutes of Health. In: Ross AC, Taylor CL, Yaktine AL et al. (eds). Dietary reference intakes for calcium and vitamin D. National Academy of Sciences. 2011. National Academic Press (US); Washington, D. C:
• 23 https://documentation.sas.com/doc/es/statcdc/14.2/statug/statug_surveyfreq_details58.htm
• 24 Belcher R, Metrailer AM, Bodenner DL. et al. Characterization of hyperparathyroidism in youth and adolescents: a literature review. Int J Pediatr Otorhinolaryngol 2013; 77: 318-322
• 25 Hedbäck G, Odén A. Increased risk of death from primary hyperparathyroidism--an update. Eur J Clin Invest 1998; 28: 271-276
• 26 Middleton L, Stack BC, Riggs AT. et al. Vitamin D deficiency: a simple algorithm employing weekly administration of 50 000 IU of vitamin D. Am J Otolaryngol 2014; 35: 85-88
• 27 Hinson AM, Wilkerson BM, Rothman-Fitts I. et al. Hyperparathyroidism associated with long-term proton pump inhibitors independent of concurrent bisphosphonate therapy in elderly adults. J Am Geriatr Soc 2015; 63: 2070-2073
• 28 Hollowoa BR, Spencer HJ, Stack BC. Normocalcemic and normohormonal primary hyperparathyroidism: laboratory values and end-organ effects. Otolaryngol Head Neck Surg 2021; 165: 387-397
• 29 Rutledge J, Siegel E, Belcher R. et al. Barriers to same-day discharge of patients undergoing total and completion thyroidectomy. Otolaryngol Head Neck Surg 2014; 150: 770-774
• 30 Hu L, Qian B, Bing K. et al. Association between tobacco smoke exposure and serum parathyroid hormone levels among US adults (NHANES 2003-2006). Sci Rep 2024; 14: 15781