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Primary Hyperparathyroidism in the Geriatric Population

Primary Hyperparathyroidism in the Geriatric Population. Nahid Rianon, M.D., Dr.Ph . The University of Texas Health Science Center at Houston (UTHealth). Learning Objectives. Attendees will have the understanding of the changing epidemiology of primary hyperparathyroidism in older adults.

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Primary Hyperparathyroidism in the Geriatric Population

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  1. Primary Hyperparathyroidism in the Geriatric Population Nahid Rianon, M.D., Dr.Ph. The University of Texas Health Science Center at Houston (UTHealth)

  2. Learning Objectives • Attendees will have the understanding of the changing epidemiology of primary hyperparathyroidism in older adults. • Attendees will be able to recognize clinical presentation and indication for surgery in older patients with primary hyperparathyroidism. • Attendees will be able to determine fracture risk in older patients with primary hyperparathyroidism.

  3. Primary Hyperparathyroidism (PHPT) Primary hyperparathyroidism is the unregulated overproduction of parathyroid hormone (PTH) resulting in abnormal calcium homeostasis1. (1) http://emedicine.medscape.com/article/127351-overview#aw2aab6b4 Image from UTHealth’s Multimedia Scriptoriu (www.uth.tmc.edu/scriptorium)

  4. Why Geriatric Population? • Risk of PHPT increases with age – often dx in 6th or 7th decade of life. • Prevalence of PHPT • General: 1-4/1000 • Elderly: 1/100 • By 2030, ~1/5 people ≥65 years in the USA • Presenting symptoms • May often be confusing with other age related disease presentations. • Presenting symptoms may be different in older patients. Adami et al., JBMR 2002; Siilin et al., World J Surg 2011; Shin et al., J Am CollSurg, 2009

  5. Epidemiology • Very few studies with somewhat varied range • Few studies in the US and most others in Europe • Most studies done in Caucasian population • Ethnic/racial variation? • Women: Men = 3-5: 1 • Rising numbers in older adults • Most studies in countries with high life expectancy

  6. Changing Rates of Incidence in the USA: Before and After 1974 1965 - June 1974 = 7.8/100,000 person-years Introduction of auto-analyzer in the 70’s & start of routine serum calcium testing July 1974-June 1975 = 51/100,000 person-yrs 1975 = 112/100,000person-yrs 1992 = 4/100,000 person-yrs Wermers et al., 1997, Ann Int Med

  7. Incidence of PHPT in the USA Age & sex-adjusted definite & possible cases, Rochester, MN 1965-1992 1970 1965 1975 1980 1990 1985 Melton III., JBMR, 2002

  8. Change in Prevalence: Asymptomatic Patients Heath et al., 1980 N Eng J Med

  9. Mortality & Hospitalization for HPT • In 1999, 83 deaths from HPT (0.3/million- crude) • Total death = 2.4 million (from all causes) • No change in survival after diagnosis • Observed = expected • Reason for hospitalization as a first dx • 4.7/100,000 in 1977 & 2.9/100,000 in 1986 • Diagnose & treat to improve quality of life Melton III., JBMR, 2002

  10. A Case • RW is a 70 year old AA man with PMHx of HTN, HLD, COPD (on steroid inhaler- former smoker) recurrent abdominal pain which was diagnosed as diverticulitis, chronic constipation for several years that he treated on his own with OTC meds and PRN use of lactulose in the past - was being seen in August, 2011 in the outpatient clinic for constipation with no BM for past 5 days and abdominal discomfort - he ran out of lactulose, wanted refill. He was not taking any multivitamin, or any calcium/vitamin D supplements. He lives alone, independent with ADL and IADL. • Mild cognitive decline; hypercalcemia in May with 11.1 mg/dl (nl range 8.5-10.5), in August 10.4 and in Sept 10.4; 25 Hydroxy vitamin D 17 ng/ml (was replaced); Mg and Phos were within normal range; PTH in Aug 149 and in Sept 147 pg/ml (nl range 11.1 – 79.5); GFR >60. • Not taking medications known to alter serum calcium, e.g., HCTZ, Lithium, bisphosphonates (no DXA done in the past).

  11. Clinical Presentation of PHPT

  12. Signs and Symptoms • Fragility fracture (osteoporosis) • Pain due to kidney stones • Excessive urination • Abdominal pain • Tiring easily/weakness/fatigue • Depression or forgetfulness • Bone and joint pain • Frequent complaints of illness with no apparent cause • Nausea, vomiting or loss of appetite In the geriatric population: these symptoms may be confusing in the setting of dementia, depression, infection

  13. Biochemical Indices in PHPT: Data from Prospective Observational Study In mild PHPT patients – baseline data of a 15 yr follow up study 85% of patients with PHPT usually have single adenoma. Bilezikian, 2011

  14. Presentation in the Elderly • 50% patients present with mental disturbance • Personality change, depression, psychosis • Sudden fast decline in health/becoming frail Presenting symptoms by age group in Swedish study Tibblin S et al., Ann Surg 1983

  15. Normocalcemic PHPT • Asymptomatic PHPT • “Consistently normal calcium with persistently abnormal PTH in the absence of recognizable underlying cause of elevated PTH” • Vitamin D >30 ng/ml • GFR >60 ml/min/1.73m2 • Observational study of 37 post-menopausal women with follow up for a mean of 3 years • 19% became hypercalcemic • 40% symptomatic with renal stones and fractures • 10% marked decline in BMD Lowe et al., 2007; Bilezikian, 2011

  16. Risk Factors & Complications • Complications: • Osteoporosis • Kidney stones • Cardiovascular disease: HTN, LVH, carotid plaque thickness • Risk factors: • Post-menopausal women • Prolonged, severe calcium or vitamin D deficiency • Rare, inherited disorder, such as multiple endocrine neoplasia-type I - usually affects multiple glands • Radiation exposure to head and neck regions • Medications, e.g., lithium, a drug most often used to treat bipolar disorder

  17. Guidelines for Surgery in PHPT • All biochemically confirmed PHPT with signs/symptoms • Asymptomatic patient with one of the following criteria • Age < 50 • Serum calcium >1 mg/dl (0.25 mmol/L) above normal range • GFR <60 ml/min/1.73m2 • T score <-2.5 SD at spine, hip (total or femoral neck) or radius (distal 1/3 site) or presence of fragility fracture Bilezikian et al., 2009; NIH workshop report, 2008

  18. Surgery in the Elderly? • Improved symptoms, e.g., ↑BMD, ↓renal stones, neurocognitive function, support PTX • Higher quality imaging • Advances in effectiveness & safety of surgical techniques • Out-patient minimally invasive PTX in the elderly • Age criteria needs to be revisited. Bilezikian et al., 2009; Bilezikian, 2011; Shin et al., 2009

  19. Bone Loss in PHPT • PHPT associated with “high bone turnover & accelerated bone remodeling” • PTH catabolic to cortical & anabolic to cancellous bone • In PHPT patients - highest loss in distal radius BMD & least or no change in lumbar spine BMD • Deficit in distal radius often persists even after PTX Highest  to  lowest BMD loss Bilezikian et al., 2009; Bilezikian, 2011; Silverberg et al., 1989; Vestergaard & Mosekilde 2003; Siilin et al., 2011

  20. Differences in Hip BMD: Mr. Os Sweden Study N in PHPT = 22 & Control = 2213; Age range for 2235 men 69-81 years; Mean±SD age in PHPT = 74.8±3.5 & Control = 74.9±3.1 years Siilin et al., 2011

  21. Fracture Risk in PHPT • Monitoring BMD - traditional way of determining fracture risk in PHPT. • Significant ↓in BMD often leads to fracture before diagnosing PHPT or parathyroidectomy. • Older patients are at risk of bone loss due to age. • Discussion about FRAX (future research) • PHPT is not a listed 2ndary risk of osteoporosis • NIH recognizes PHPT as 2ndary risk of osteoporosis. • Bone marker monitoring (ongoing research) Bilezikian et al., 2009; Sankaran S et al., 2010

  22. Summary • Changing epidemiology of PHPT • Routine screening for S-calcium, vitamin D & osteoporosis • Clinical presentation in older patients • May be confusing with other age related complications in older patients. • Presentations may be different in older patients. • Indication for surgery • Age criteria needs to be revisited. • Fracture risk in older patients • Future research with FRAX and bone markers

  23. References • Primary hyperparathyroidism diagram. Retrieved from: http://emedicine.medscape.com/article/127351-overview#aw2aab6b4 • Adami S, Marcocci C, Gatti D. Epidemiology of primary hyperparathyroidism in Europe. J Bone Miner Res 2002;17 Suppl2:N18-23. • Siilin H, Lundgren E, Mallmin H, Mellström D, Ohlsson C, Karlsson M, Orwoll E, Ljunggren O. Prevalence of primary hyperparathyroidism and impact on bone mineral density in elderly men: MrOs Sweden. World J Surg 2011;35:1266-72. • Shin SH, Holmes H, Bao R, et al. Outpatient minimally invasive parathyroidectomy is safe in elderly patients. J Am CollSurg2009;208:1071-1076. • Wermers RA, Khosla S, Atkinson EJ, Hodgson SF, O'Fallon WM, Melton III LJ. The Rise and Fall of Primary Hyperparathyroidism: A Population-Based Study in Rochester, Minnesota, 1965-1992. Ann Int Med 1997;126:433-440. • Melton III LJ. The epidemiology of primary hyperparathyroidism in North America. Journal of bone and mineral research. JBMR 2002;17 Supp 2:N12-N17 • Heath III H, Hodgson SF, Kennedy MA. Primary Hyperparathyroidism — Incidence, Morbidity, and Potential Economic Impact in a Community. N Engl J Med 1980;302:189-193 • Bilezikian JP, Khan A, Potts JT, et al. Hypoparathyroidismin the adult: Epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J Bone Miner Res 2011;26:2317–2337. • Tibblin S, Pålsson N, Rydberg J. Hyperparathyroidism in the elderly. Ann Surg 1983;197:135–138. • Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, et al. Normocalcemic Primary Hyperparathyroidism: Further Characterization of a New Clinical Phenotype. J ClinEndocrinolMetab 2007;92:3001–3005 • Bilezikian JP, Khan A, Potts JT. Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Third International Workshop. J ClinEndocrinolMetab 2009;94:335–339 • Silverberg SJ, Shane E, de la Cruz L, Dempster DW, et al. Skeletal disease in primary hyperparathyroidism. J Bone Miner Res 1989;4:283–291. • Vestergaard P, Mosekilde L. Cohort study on effects of parathyroid surgery on multiple outcomes in primary hyperparathyroidism. BMJ 2003;327:530-535 • Sankaran S, Gamble G, Bolland M, et al. Skeletal Effects of Interventions in Mild Primary Hyperparathyroidism: A Meta-Analysis. J ClinEndocrinolMetab2009;95: 1653-1662 • Photographs used for the cover slide are allowed by the MorgueFile free photo agreement and the Royalty Free usage agreement at Stock.xchng. They appear on the cover slide in this order: Wallyir at morguefile.com/archive/display/221205 Mokra at www.sxc.hu/photo/572286 Clarita at morguefile.com/archive/display/33743

  24. The Training Excellence in Aging Studies (TEXAS) program promotes geriatric training from medical school through the practicing physician level. This project is funded by the Donald W. Reynolds Foundation to the division of Geriatrics and Palliative Medicine within the department of Internal Medicine at The University of Texas Health Science Center at Houston (UTHealth). • TEXAS would also like to recognize the following for contributions: • Houston Geriatric Education Center • Harris County Hospital District • Memorial Hermann Foundation • The TEXAS Advisory Board • Othello "Bud" and Newlyn Hare • UTHealth Medical School Office of the Dean • UTHealth Medical School Office of Educational Programs • UTHealth School of Nursing • UTHealth Consortium on Aging

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