primary hyperparathyroidism in the geriatric population
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
Primary Hyperparathyroidism in the Geriatric Population
Nahid Rianon, M.D., Dr.Ph.The University of Texas Health Science Center at Houston (UTHealth)
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.
Learning Objectives
Primary hyperparathyroidism is the unregulated overproduction of parathyroid hormone (PTH) resulting in abnormal calcium homeostasis1.
Primary Hyperparathyroidism (PHPT)
(1) http://emedicine.medscape.com/article/127351-overview#aw2aab6b4 Image from UTHealth’s Multimedia Scriptoriu (www.uth.tmc.edu/scriptorium)
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.
4 Adami et al., JBMR 2002; Siilin et al., World J Surg 2011; Shin et al., J Am Coll Surg, 2009
Why Geriatric Population?
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
5
Epidemiology
6
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
Changing Rates of Incidence in the USA: Before and After 1974
7
1965 1970 1975 1980 1985 1990
Melton III., JBMR, 2002
Age & sex-adjusteddefinite & possible cases, Rochester, MN 1965-1992
Incidence of PHPT in the USA
8
Before June 1974 = 18%
After July 1974 = 52%
Heath et al., 1980 N Eng J Med
Change in Prevalence: Asymptomatic Patients
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
9Melton III., JBMR, 2002
Mortality & Hospitalization for HPT
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).
A Case
Clinical Presentation of PHPT
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
Signs and Symptoms
In the geriatric population: these symptoms may be confusing in the setting of dementia, depression, infection
Biochemical tests Patient Normal rangeCalcium (mg/dl) 10.7± 0.1 8.4 -10.2
Phosphorus (mg/dl) 2.9 ± 0.1 2.5 - 4.5
Alk Phos (IU/I) 114 ± 4 <100
PTH (pg/ml) 121 ± 7 10-65
25-OH Vit D (ng/ml) 21 ± 1 9-52
Urinary calcium (mg) 248 ± 12 100-300
DPD (nmol/mmol Cr) 17 ± 6 4-21
In mild PHPT patients – baseline data of a 15 yr follow up study
Bilezikian, 2011
85% of patients with PHPT usually have single adenoma.
Biochemical Indices in PHPT: Data from Prospective Observational Study
50% patients present with mental disturbance Personality change, depression, psychosis
Sudden fast decline in health/becoming frail
Signs/Symptoms < 60 years (N = 74) ≥ 60 years (N = 112)
Neuromuscular 16% 31%
Renal 41% 19%
Hypercalcemic crisis 4% 4%
Gastrointestinal 1% 1%
Skeletal abnormality 2% 1%
Presenting symptoms by age group in Swedish study
Tibblin S et al., Ann Surg 1983
Presentation in the Elderly
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
Normocalcemic PHPT
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
Risk Factors & Complications
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
17Bilezikian et al., 2009; NIH workshop report, 2008
Guidelines for Surgery in PHPT
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.
Surgery in the Elderly?
Bilezikian et al., 2009; Bilezikian, 2011; Shin et al., 2009
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
Bone Loss in PHPT
PHPT control PHPT Control PHPT ControlL total hip L femoral neck Lumbar Spine
0200400600800
1000120014001600
BM
D m
g/c
m2
p = NS
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
Differences in Hip BMD: Mr. Os Sweden Study
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
Fracture Risk in PHPT
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
Summary
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 Suppl 2: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 Coll Surg 2009;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. Hypoparathyroidism in 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 Clin Endocrinol Metab 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 Clin Endocrinol Metab 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 Clin
Endocrinol Metab 2009;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
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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